THC Suppressed an Immune Defense Signal in Rats ↗
THC injection suppressed macrophage migration inhibition factor in immunized rats, with peak suppression at 15 hours, suggesting a mechanism for cannabis-related immune changes.
Neuroscience research
Explore published research on neuroscience, including study methods and limitations.
THC Suppressed Antibody-Producing Cells and Shrank Spleens in Mice ↗
THC suppressed antibody-producing spleen cells and reduced overall spleen cellularity in immunized mice, suggesting broad immune suppression effects.
An Opiate Blocker Also Blocked THC Effects in Rats, Suggesting Shared Brain Pathways ↗
An opiate receptor blocker inhibited THC-induced pain relief, temperature changes, tolerance, and dependence in rats, suggesting cannabis and opiates share brain pathways.
A Comprehensive Review Found THC and Synthetic Cannabinoids Outperformed Placebo for Chemotherapy Nausea ↗
A 1983 review found THC outperformed placebo and standard drugs for chemotherapy nausea, with effectiveness linked to the "high." Synthetic cannabinoids nabilone and levonantradol offered additional options.
CBD Improved Dystonia Symptoms by 20-50% but Worsened Parkinson's Features ↗
Five dystonia patients improved 20-50% on oral CBD up to 600 mg/day, but two with coexisting Parkinson's features experienced worsened tremor and slowed movement.
THC Suppressed Natural Killer Cell Activity That Normally Fights Tumor Cells ↗
THC suppressed human natural killer cell activity against tumor cells in lab tests at concentrations as low as 5 micrograms/mL. The effect was dose- and time-dependent.
The Orientation of a Single Chemical Group Determined Whether Cannabinoid Compounds Were Psychoactive ↗
Molecular modeling showed that the orientation of the C9 substituent relative to a hydroxyl oxygen determined whether cannabinoid compounds were psychoactive or inactive.
Mouse Liver Processed Synthetic THC Variants Similarly to Natural THC, With One Major Metabolite Dominating ↗
Mice processed synthetic THC variants similarly to natural THC, with the 11-oic acid metabolite dominating at about 95% of total metabolism for one variant.
High-Dose CBD Was Neither Effective Nor Toxic for Huntington's Disease in a Controlled Trial ↗
CBD at approximately 700 mg/day for six weeks showed no significant benefit for Huntington's Disease symptoms in 15 patients, but was well tolerated with no toxicity.
High-Dose Oral CBD Produced Surprisingly Low Blood Levels With a 2-5 Day Elimination Half-Life ↗
Oral CBD at 700 mg/day produced mean plasma levels of only 5.9-11.2 ng/mL with a 2-5 day elimination half-life. No THC was detected, confirming CBD does not convert to THC.
Cannabis Extract Changed How Rat Livers Processed Other Drugs and Chemicals ↗
Chronic cannabis extract boosted specific liver enzymes in rats, including a 3-fold increase in carcinogen-activating AHH. Most effects reversed within a week of stopping.
Chronic THC Altered Rat Hippocampus Structure, but Three Months of Exposure Was Needed ↗
Animal studies showed chronic THC altered the hippocampus in rats, but required at least 3 months of exposure in young animals. Monkey studies did not consistently replicate these findings.
Despite Widespread Use, Scientists Found Little Evidence That Cannabis Activated Brain Reward Pathways ↗
A 1992 review found that despite widespread human use, animals would not self-administer THC and evidence of brain reward pathway stimulation was minimal. The newly discovered cannabinoid receptor was opening new research directions.
The Discovery of Anandamide — Your Brain's Own Cannabis Molecule ↗
The 1992 discovery of anandamide — the brain's own cannabis-like molecule — proving the endocannabinoid system exists and launching an entirely new field of neuroscience.
Molecular Modeling Revealed a "No-Go Zone" on the Cannabinoid Receptor That Blocks Inactive Compounds ↗
Computational modeling identified a "receptor essential volume" near the cannabinoid receptor that explains why some cannabinoid compounds bind effectively while others cannot.
Modifying One Position on THC Created Compounds That Preferentially Targeted the CB2 Immune Receptor ↗
Modifications at the C-1 position of THC-like compounds produced modest selectivity for the CB2 immune receptor over the CB1 psychoactive receptor, with one compound achieving a 4.5-fold preference.
THC Suppressed Multiple Immune Cell Types in Labs and Animals, but Direct Evidence in Humans Was Missing ↗
THC suppressed macrophages, T cells, and NK cells and reduced infection resistance in labs and animals, but direct evidence of increased infections in human marijuana users was unavailable.
Twenty-Five Years of Research Showed Cannabis Modulated Immunity Across Multiple Cell Types and Infections ↗
A 25-year research review found cannabinoids modulated all major immune cell types and altered resistance to multiple infections, while noting the endocannabinoid system's role in immune regulation needed further study.
The Discovery of the Body's Own Cannabis-Like Molecules: Anandamide and 2-AG ↗
A landmark review described the body's own cannabis-like molecules (anandamide and 2-AG), their biochemistry, and introduced the "entourage effect" concept.
CB1 Receptors Were Concentrated in the Part of the Eye That Controls Fluid Pressure ↗
CB1 receptors were concentrated in the rat ciliary body, the eye structure controlling fluid pressure, providing a molecular basis for cannabinoid-based glaucoma treatment.
A Major Review Found THC Caused Cell Death in the Hippocampus and Shared Reward Pathways With Other Drugs of Abuse ↗
A major review found THC caused cell death in the hippocampus, produced persistent cognitive deficits, and activated the same dopamine reward pathways as morphine, alcohol, and nicotine.
Two Weeks of THC Made Rats More Sensitive to Amphetamine, Supporting Cannabis-Psychosis Link ↗
Two weeks of daily THC made rats hypersensitive to amphetamine's psychosis-like effects after withdrawal, supporting a biological mechanism for cannabis-associated psychosis risk.
Mechoulam Reviewed 35 Years of Cannabinoid Research From THC Isolation to Endocannabinoid Discovery ↗
Mechoulam reviewed 35 years from isolating THC to discovering endocannabinoids, noting a synthetic cannabinoid in clinical trials for brain injury while most medical use remained illegal.
Cannabinoid Receptors in Movement Control Centers Suggested Therapeutic Potential for Tics, Dyskinesia, and Tremor ↗
Cannabinoid receptors are concentrated in brain movement centers. Limited clinical evidence suggested cannabis may help Tourette tics, Parkinson's dyskinesia, and some forms of tremor and dystonia.
A Pharmacologist Mapped Out the Full Therapeutic Landscape for Cannabinoid Drugs ↗
A pharmacological roadmap identified clinical potential for CB1 agonists (spasticity, pain), CB1 antagonists (appetite, cognition), CB2 ligands, and endocannabinoid-boosting drugs.
Cannabis Compounds Reduced Spasticity and Tremor in an MS Mouse Model, Published in Nature ↗
Published in Nature, this landmark study showed cannabinoids reduced spasticity and tremor in MS mice, while blocking cannabinoid receptors worsened symptoms, revealing an active endocannabinoid control system.
Ecstasy Users Showed Cognitive Decline While Cannabis-Only Users Did Not Differ From Non-Users ↗
Ecstasy users showed cognitive impairment on attention, memory, and intelligence measures, while cannabis-only users performed identically to drug-free controls.
The Endocannabinoid System May Be Involved in Huntington's, Parkinson's, Schizophrenia, and Tremor ↗
The endocannabinoid system is disrupted in Huntington's, Parkinson's, schizophrenia, and tremor, offering both pathological insights and therapeutic targets including agonists, antagonists, and endocannabinoid modulators.
A Pioneer's Overview of Cannabinoids: From Ancient Use to Modern Medicine ↗
A review by THC discoverer Raphael Mechoulam tracing cannabinoids from ancient use to modern clinical applications in nausea, appetite, multiple sclerosis, arthritis, and neuroprotection.
Does the Brain Build Tolerance to THC's Memory-Disrupting Effects? ↗
Chronic THC treatment in rats did not produce tolerance to memory impairment or hippocampal acetylcholine reduction, with both effects mediated by CB1 receptors but operating on different timescales.
A Synthetic Cannabinoid Eye Drop Lowered Eye Pressure in Treatment-Resistant Glaucoma ↗
A synthetic cannabinoid eye drop reduced eye pressure by up to 31% in 8 glaucoma patients who had not responded to conventional treatments, working through CB1 receptors in the eye.
How Cannabinoids Affect the Brain: Receptors, Memory, Movement, and Appetite ↗
Comprehensive review mapping how cannabinoids affect different brain regions: memory in the hippocampus, movement and reward in the basal ganglia, appetite in the hypothalamus, with neuroprotective properties.
The Brain's Own Cannabis System: Its Role in Memory and Drug Dependence ↗
Review finding that blocking or removing CB1 receptors enhanced memory performance, suggesting the endocannabinoid system normally constrains memory formation, while also modulating opioid dependence.
What Was Known About Cannabis for MS Spasticity and Pain in 2002 ↗
Review of 9 clinical trials and animal research finding cannabinoids reduced spasticity, pain, tremor, and bladder symptoms in MS, with elevated endocannabinoid levels in spastic conditions.
How Cannabinoids Affect the Brain's Reward Center ↗
Electrophysiology study showing cannabinoids strongly inhibited excitatory inputs to the brain's reward center through CB1 receptors, independent of dopamine and opioid systems.
The Body's Own Cannabis System May Help Regulate Fertility ↗
Study discovering endocannabinoids in human reproductive fluids and cannabinoid receptors on sperm, finding that cannabinoid compounds and THC impaired sperm capacitation and fertilizing potential.
Cannabis Compounds May Have Untapped Medical Potential Beyond What Patients Already Report ↗
Lancet Neurology review arguing that cannabinoid therapeutic potential extends beyond MS symptoms to neuroprotection, and that the field was only beginning to appreciate the possibilities.
A Comprehensive Map of What Cannabinoids Could Treat in the Brain ↗
Comprehensive review cataloging cannabinoid therapeutic potential across MS, Parkinson's, neuroprotection, pain, and appetite, highlighting non-psychoactive cannabinoids as potentially offering benefits without psychoactivity.
The Complete Guide to How Cannabis Moves Through Your Body ↗
Comprehensive pharmacokinetics review: inhaled THC peaks in minutes and lasts 2-3 hours; oral THC takes 30-90 minutes and lasts 4-12 hours, with therapeutic applications across pain, nausea, and neuroprotection.
Could Cannabinoids Fight Cancer? What Lab Studies Were Showing ↗
Nature Reviews Cancer paper documenting that cannabinoids inhibited tumor growth in lab and animal studies while being well tolerated, raising the question of anticancer therapeutic potential.
Cannabis and the Brain: A Comprehensive Review Published in Brain ↗
Major Brain journal review finding cannabis cognitive impairments appear reversible with little evidence of brain pathology, and limited evidence for causal psychiatric illness links.
Cannabis Users Process Attention Differently: Brain Wave Evidence ↗
Brain wave study showing chronic cannabis users processed auditory attention differently, with reduced P3 responses to targets and greater effects in early-onset users, undetected by standard tests.
Cannabinoids Protected Against Brain Damage in an MS Animal Model ↗
Animal study showing CB1 receptor knockout mice suffered worse neurodegeneration in MS model, while CB1 activation provided neuroprotection, suggesting cannabis could slow MS disease progression.
How THC Creates Reward and Dependence in the Brain ↗
Comprehensive review documenting reliable THC self-administration in monkeys and major cannabinoid-opioid-dopamine interactions underlying reward and dependence.
Medical Marijuana for Brain Disorders: A Rehabilitation Medicine Perspective ↗
Review from rehabilitation medicine documenting seven therapeutic properties of cannabinoids applicable to neurological disorders: antioxidation, neuroprotection, analgesia, anti-inflammation, immunomodulation, glial modulation, and tumor regulation.
The Case For and Against Cannabis Treatment in MS: Where Did the Evidence Stand in 2004? ↗
Review noting strong animal and patient-report evidence for cannabinoids in MS but acknowledging that objective clinical evidence remained lacking across 10 published reports with 78 patients.
Designing Drugs to Target the Brain's Endocannabinoid Breakdown Enzymes ↗
Pharmacological study identifying compounds that inhibit endocannabinoid breakdown enzymes without activating CB1 receptors, enabling potential non-psychoactive cannabinoid-based therapies.
A Complete Guide to How Cannabinoids Work as Medicine ↗
Pharmacology review mapping CB1 and CB2 receptor distribution and cataloging 13 therapeutic properties of cannabinoids including analgesia, neuroprotection, and antitumor effects.
Could the Body's Cannabis System Protect the Heart? ↗
Comprehensive review finding endocannabinoids play protective roles during cardiovascular emergencies like shock and heart attack, acting through CB1, vanilloid, and possibly novel receptors.
Brain Scans Show Cannabis Users Work Harder to Remember: An fMRI Study ↗
fMRI study showing heavy cannabis users activated more brain regions and recruited additional areas not normally used for spatial memory, suggesting neural compensation for subtle deficits.
What Happens to Cannabis Receptors in the Brain During Withdrawal ↗
Mouse study showing cannabinoid withdrawal produced region-specific CB1 receptor changes: upregulation in motor and emotional areas but downregulation in hippocampus, with behavioral symptoms peaking day 1 and resolving by day 3.
Teen Cannabis Exposure Changed How the Brain's Reward System Responded to Other Drugs ↗
Adolescent but not adult cannabinoid exposure in rats produced lasting cross-tolerance to morphine, cocaine, and amphetamine in dopamine reward neurons, suggesting unique adolescent brain vulnerability.
Very Heavy Cannabis Users Still Showed Decision-Making Deficits and Brain Changes After 25 Days Abstinent ↗
PET imaging study found heavy marijuana users (53-84 joints/week) still had brain activity changes and decision-making deficits after 25 days abstinent, while moderate users performed like non-users.
Review of How Cannabinoids Interact With the Immune System and Their Potential for Treating Inflammation ↗
Review of how cannabinoids interact with immune cells, showing they can modulate cytokine secretion and immune function with potential applications for inflammatory disease treatment.
Comprehensive Review of Cannabis Tolerance and Dependence in Laboratory Animals ↗
Review of animal studies found cannabinoid tolerance develops through receptor down-regulation, withdrawal symptoms are generally milder than with other drugs, and tolerant animals showed no increased vulnerability to morphine.
Review of How the Endocannabinoid System Works and Its Potential for New Treatments ↗
Review of the endocannabinoid signaling system describes how it maintains physiological balance and identifies therapeutic potential for pain, epilepsy, spasticity, eating disorders, and inflammation.
Comprehensive Review of Cannabinoid Pharmacology, Receptor Systems, and Therapeutic Applications ↗
Comprehensive review of 15 years of cannabinoid research catalogs receptor distribution across the body and identifies therapeutic potential for pain, neurological disorders, obesity, and addiction.
Brain Scans Show Chronic Cannabis Smokers Use Different Brain Pathways During Impulse Control Tasks ↗
fMRI pilot study found chronic cannabis smokers used different, more diffuse brain activation patterns during an impulse control task, despite performing within normal limits.
THC Was the Primary Active Ingredient in Marijuana While CBC and CBD Concentrations Made No Difference ↗
Controlled study of 23 marijuana users found varying CBC and CBD concentrations did not change the effects of smoked marijuana, confirming THC as the primary active ingredient.
How the Body's Endocannabinoid System Drives Appetite, Food Motivation, and Weight Regulation ↗
Review shows endocannabinoids stimulate appetite by making food more attractive and more pleasurable, acting through CB1 receptors in the nucleus accumbens and hypothalamus.
Cocaine-Dependent People Who Also Used Cannabis Showed Reduced Brain Stress Responses ↗
fMRI study found cocaine-dependent individuals who also used cannabis showed decreased frontal cortex activation during emotional stress, even after 15+ days of abstinence.
How Cannabinoids and Endocannabinoids May Help Treat Multiple Sclerosis Through Immune Modulation ↗
Review shows cannabinoids may benefit MS by shifting immune responses from harmful Th1 to protective Th2 patterns and providing neuroprotection, with animal model support for endocannabinoid-based therapies.
How the Endocannabinoid System Drives Obesity Through Both Brain Appetite Circuits and Fat Cell Activity ↗
Review shows endocannabinoids promote obesity through dual mechanisms: stimulating brain appetite circuits and directly promoting fat storage in adipose tissue, with CB1 blockers showing promise for both.
CB1 Receptor Blockers Show Promise for Obesity: Early Trial Results Show Weight Loss and Metabolic Improvement ↗
Review confirmed CB1 receptors drive appetite and fat storage. The CB1 blocker rimonabant showed significant weight loss and metabolic improvement in early Phase III obesity trials.
Brief Review of Cannabinoid Therapeutic Potential for Neurological Diseases Including MS, Pain, and Glaucoma ↗
Brief review outlines therapeutic potential of cannabinoid agonists for spasticity, pain, and inflammation, and CB1 antagonists for Parkinson's disease.
Blocking Endocannabinoid Breakdown Could Treat Anxiety, Cancer, and Neurodegenerative Diseases ↗
Review identifies FAAH and MAGL enzymes as key therapeutic targets. Blocking endocannabinoid breakdown could treat anxiety, cancer, and neurodegeneration by boosting the body's own cannabinoid system.
Scientists Developed the First Drugs That Specifically Block Endocannabinoid Production ↗
Researchers developed the first potent and selective inhibitors of DAGL-alpha, the enzyme that produces the endocannabinoid 2-AG, creating essential tools for studying the endocannabinoid system.
Anabolic Steroid Nandrolone Altered Cannabis Reward and Withdrawal Responses in Mice ↗
Mouse study found the anabolic steroid nandrolone blocked THC reward and increased withdrawal severity without changing CB1 receptor binding, suggesting downstream signaling interactions.
CBD Blocked Brain Inflammation Pathways Triggered by Alzheimer's-Related Protein in Cell Study ↗
Cell study found CBD blocked inflammation pathways (p38 MAP kinase, NF-kappaB) triggered by Alzheimer's-associated beta-amyloid protein, adding to evidence of CBD's neuroprotective properties.
CBD-Rich Cannabis Extract Could Not Reverse Memory Deficits Caused by Non-Cannabinoid Drugs in Rats ↗
CBD-rich cannabis extract reversed THC-induced memory deficits but failed to reverse memory impairments caused by anticholinergic or antiglutamatergic drugs, suggesting CBD's effects are cannabinoid-system specific.
Frequent Cannabis Users Showed Normal Working Memory and Attention After One Week of Abstinence ↗
fMRI study of 10 moderate cannabis users after 1 week abstinent found normal working memory and attention performance, with only subtle brain activity changes in one parietal region.
How Cannabinoids Suppress Immune Responses Through Antigen-Presenting Cells ↗
Review shows cannabinoids suppress immune function by affecting antigen-presenting cells and cytokine production, suggesting therapeutic potential for chronic inflammatory diseases.
Endocannabinoid System Modulation Shows Promise for MS, Arthritis, IBD, Asthma, and Autoimmune Diabetes ↗
Review of endocannabinoid system modulation identifies therapeutic potential for MS, rheumatoid arthritis, IBD, atherosclerosis, allergic asthma, and autoimmune diabetes based on cell and animal studies.
CB2 Receptor on Immune Cells Offers Path to Anti-Inflammatory Treatments Without Cannabis-Like High ↗
Review highlights CB2 receptor on immune cells as a target for anti-inflammatory treatments without psychoactive effects, with evidence in autoimmune disease and bone metabolism models.
Study Validates That Brain Scanning Comparisons Between Drug Users and Non-Users Are Reliable ↗
fMRI validation study confirmed cocaine, nicotine, and cannabis users show identical hemodynamic brain responses to controls during finger-tapping, validating drug-user neuroimaging comparisons.
Comprehensive Review: Endocannabinoid System Controls Hormones, Stress Response, Reproduction, and Metabolism ↗
Major endocrinology review describes the endocannabinoid system as a regulator of hormonal axes, stress response, reproduction, and energy balance through both brain and peripheral tissue mechanisms.
Brain Imaging Review: Cannabis Does Not Damage Brain Structure But Changes How It Functions ↗
Systematic review found no consistent structural brain damage from chronic cannabis use, but functional changes including altered cerebellar/frontal activity and compensatory activation during cognitive tasks.
Comprehensive Review: THC Impairs Memory by Disrupting Encoding, Consolidation, and Retrieval ↗
Review found THC transiently impairs memory for new information (not existing memories) in a dose-dependent manner, by disrupting encoding, consolidation, and retrieval through multiple neurotransmitter systems.
Young Adults Exposed to Cannabis Before Birth Showed Altered Brain Activity During Memory Tasks ↗
fMRI study of 18-22 year olds from a 20-year longitudinal study found altered brain activation during memory tasks in those prenatally exposed to marijuana, despite normal task performance.
What Early-Life Cannabis Exposure May Mean for the Developing Brain ↗
Early-life cannabis exposure was linked to subtle cognitive and psychiatric outcomes, with animal studies offering mechanistic clues but not human behavior.
Cannabinoids May Slow MS Progression Through Both Immune and Neuroprotective Mechanisms, But Dose Limits Apply ↗
Review finds cannabinoids could modify MS through immune and neuroprotective mechanisms, but dose constraints prevent achieving immunosuppressive benefits clinically. Neuroprotection may be more achievable.
Overview of the Enzymes That Build and Break Down the Body's Natural Cannabinoids ↗
Review of endocannabinoid metabolism identified multiple enzymes for synthesis and degradation of anandamide and 2-AG, positioning these enzymes as drug targets for addiction and other conditions.
Endocannabinoids Can Block Tumor Blood Supply and Spread in Multiple Cancer Types ↗
Review shows endocannabinoids can inhibit tumor blood vessel formation, cancer cell migration, and metastasis across multiple cancer types, with a favorable safety profile compared to standard chemotherapy.
Scientists Mapped the Enzymes That Break Down a Key Brain Cannabinoid in Mice ↗
Researchers mapped the enzymes that break down the brain cannabinoid 2-AG in mice, finding MAGL handles 85% while two other enzymes manage the rest in different cellular locations.
Prenatal Cannabinoid Exposure Permanently Altered the Endocannabinoid System in Adult Rat Brains ↗
Rats exposed to a synthetic cannabinoid in the womb showed permanent, region-specific changes in their brain's endocannabinoid system as adults.
Brain Imaging Studies Show Altered Neural Activity in Regular Cannabis Users ↗
Review of brain imaging studies found that chronic cannabis users show consistently altered brain function during cognitive tasks, even without clear structural damage.
Researchers Reviewed Evidence That Cannabinoids Could Help Fight Brain Tumors ↗
Review of preclinical evidence found that cannabinoids showed anti-tumor properties against brain cancers in lab and animal studies, including slowing growth and triggering cancer cell death.
Frequent Cannabis Users Showed Less Brain Activity During Memory Tasks Despite Normal Performance ↗
Regular cannabis users showed lower hippocampal brain activity during memory tasks than non-users but performed just as well, with no structural brain differences detected.
How Targeting the Endocannabinoid System Could Lead to New Treatments for Addiction and Obesity ↗
Review described how the endocannabinoid system drives reward-seeking in both addiction and obesity, making targeted CB1 modulators promising but challenging drug candidates.
Scientists Identified a Key Amino Acid in the CB1 Receptor That Determines Which Cannabinoids Can Bind ↗
Mutating a single amino acid in the CB1 receptor eliminated binding for some cannabinoids while leaving others unaffected, revealing multiple binding sites on the receptor.
GASP1 Sends Activated CB1 Receptors to Degradation. A Possible Piece of the Tolerance Puzzle. ↗
Activated CB1 receptors were routed to degradation via GASP1 in cells and neurons, offering a mechanistic link to receptor down-regulation.
Spasticity Relief From Cannabinoids Works Through CB1 Receptors, Not CB2, in MS Mouse Models ↗
Gene-knockout mouse study proved cannabinoids control MS-like spasticity through CB1 receptors, not CB2, meaning therapeutic and psychoactive effects are inherently linked.
Low-Dose THC Changed How Mice Responded to MDMA Rewards in Both Directions ↗
Mouse study found THC enhanced MDMA reward at low doses but reduced it at high doses, with both drugs converging on dopamine signaling in the brain's reward center.
Endocannabinoid-Making Enzymes and CB1 Receptors Are Expressed Together in Mouse Brains ↗
Mouse study found CB1 receptor expression correlated with endocannabinoid enzyme expression, suggesting coordinated regulation, while dietary arachidonic acid had no effect on any of these genes.
Scientists Mapped How the Uterus Controls Endocannabinoid Levels for Successful Embryo Implantation ↗
Mouse study mapped how the uterus creates precise endocannabinoid gradients essential for embryo implantation, with disruption leading to compromised pregnancy outcomes.
Brain Imaging Found Structural Damage in the Corpus Callosum of Heavy Marijuana Users Who Started Young ↗
Brain imaging of 11 heavy marijuana users who started in adolescence found structural white matter damage in the corpus callosum connecting the prefrontal cortices.
How the Endocannabinoid System Could Both Treat MS Symptoms and Slow Disease Progression ↗
Review proposed that the endocannabinoid system could both relieve MS symptoms and slow disease progression, with local endocannabinoid enhancement as a strategy to minimize psychoactive side effects.
THC and CBD Affected Different Brain Regions During a Self-Control Task ↗
fMRI study found THC weakened brain activation in impulse control regions (right frontal, anterior cingulate) while CBD affected entirely different areas, independent of intoxication.
A Drug That Blocks 2-AG Breakdown Revealed Hidden Cannabinoid Effects in Mice ↗
Blocking 2-AG breakdown with a MAGL inhibitor revealed hidden cannabinoid effects in mice, including evidence for cannabinoid receptors beyond the known CB1 and CB2.
Plant Cannabinoids Activate Pain-Sensing Ion Channels Beyond the Known CB1 and CB2 Receptors ↗
Six plant cannabinoids activated the pain-sensing TRPA1 channel (CBC most potent at 60 nM) and blocked the cold-sensing TRPM8 channel, revealing non-CB1/CB2 mechanisms for pain relief.
CB2 Receptors on Immune Cells Can Directly Suppress the Autoimmune Attack in MS ↗
Review showed that the CB2 cannabinoid receptor on immune cells can directly suppress the autoreactive T cells that cause MS nerve damage, offering a potential non-psychoactive therapeutic target.
Olanzapine Reversed THC-Induced Memory Impairment in Rats, but Haloperidol Did Not ↗
Olanzapine reversed THC-induced spatial memory impairment in rats by restoring hippocampal acetylcholine levels, while haloperidol had no effect at any dose tested.
High-Dose CBD Amplified THC's Effects in Mice by Increasing CB1 Receptor Levels ↗
In mice, high-dose CBD unexpectedly amplified low-dose THC's behavioral effects by increasing CB1 receptor expression, challenging the assumption that CBD always counteracts THC.
A Review of the Brain Science Behind Cannabis Addiction ↗
Review of brain science behind cannabis addiction found that cannabinoid receptor systems undergo specific neuroadaptive changes with chronic use, overturning the notion that cannabis is non-addictive.
Two Adjacent Amino Acids in the CB1 Receptor Work Together to Control How Cannabinoids Activate the Receptor ↗
Mutating two adjacent CB1 receptor amino acids individually caused modest effects, but combining them caused a synergistic 50-fold loss in activation, revealing a critical signal transduction switch.
How the Endocannabinoid System Drives Both Food Craving and Fat Storage ↗
Brief review explained how the endocannabinoid system drives both food craving and fat storage, making CB1 receptor blockers potential anti-obesity drugs.
Scientists Found the Endocannabinoid System in Connective Tissue Cells, With Implications for Pain and Bodywork ↗
Database analysis found fibroblasts and connective tissue cells express a full endocannabinoid system that may help regulate pain, inflammation, and tissue remodeling in muscles and fascia.
Cannabis Users Showed Opposite Brain Activity Patterns During Memory: Too Much in One Region, Too Little in Others ↗
fMRI study found cannabis users showed opposite brain patterns during memory: reduced frontal activation alongside increased parahippocampal activity, suggesting compensation for functional deficits.
Nerve Agents Accidentally Revealed What Happens When Both Endocannabinoid Enzymes Are Blocked at Once ↗
Nerve agents that blocked both endocannabinoid enzymes simultaneously caused 10-fold brain cannabinoid increases and THC-like effects, revealing that dual blockade is fundamentally different from single enzyme inhibition.
Chemists Created Powerful New Tools to Control 2-AG Production and Breakdown ↗
Chemists created compounds that inhibit 2-AG production at nanomolar concentrations with high selectivity, providing precision tools for endocannabinoid research.
Why Cannabis Is an "Atypical" Drug of Abuse: Unusual Patterns in Animal Addiction Models ↗
Comprehensive review found cannabinoids only produce reward in animals under narrow conditions, unlike other drugs of abuse, explaining their classification as "atypical" addictive substances.
The Theory That Some Conditions Are Caused by an Endocannabinoid Deficiency ↗
Proposed that migraine, fibromyalgia, and IBS may share a common cause: clinical endocannabinoid deficiency, providing a rationale for cannabinoid-based treatments.
Why Puberty Is a Particularly Risky Time for Cannabis Exposure ↗
Review assembled evidence that the endocannabinoid system's major changes during puberty make adolescent brains especially vulnerable to lasting harm from cannabis exposure.
Pubertal Rats Showed Worse and More Lasting Effects From Cannabinoids Than Adult Rats ↗
Pubertal rats given cannabinoids for 25 days showed persistent memory and social deficits lasting at least 15 days after stopping, while adult rats showed milder, more reversible effects.
High-Fat Diet Changed How the Endocannabinoid System Works in the Pancreas and Fat Tissue ↗
Mice on high-fat diet showed tissue-specific endocannabinoid changes: increased levels in the pancreas (enzyme redistribution) and decreased levels in subcutaneous fat.
A Catalog of All Known FAAH and MAGL Inhibitors and Their Chemical Characteristics ↗
Comprehensive catalog found extensive FAAH inhibitor families but few selective MAGL inhibitors, highlighting a critical gap in the endocannabinoid research toolkit.
The Promise and Problems of CB1 Blockers for Obesity and Metabolic Disease ↗
Review found CB1 receptor antagonists show metabolic benefits for obesity but psychiatric side effects limit use, proposing "neutral antagonists" as a safer next-generation approach.
CBD Directly Activated Glycine Receptors Involved in Pain Processing ↗
CBD enhanced glycine receptor function at low micromolar concentrations and directly activated them at higher concentrations, providing a non-cannabinoid mechanism for pain relief.
Critical Assessment Found CB1 Blockers Were No Better Than Existing Weight Loss Drugs ↗
Critical review found CB1 antagonists for obesity achieved weight loss no better than existing drugs while carrying serious psychiatric side effects, questioning the approach's clinical value.
How THC and CBD Affect Brain Activity During Learning ↗
THC disrupted brain activation in the parahippocampal gyrus and ventrostriatum during verbal learning, with ventrostriatal changes correlating with psychotic symptoms. CBD had no such effects.
Cannabis both calms and panics — the biphasic dose-response explains why the same drug produces opposite anxiety effects ↗
Frequent use and anxiety often appear together, but this 2009 review could not pin down cause and effect.
THC Increased Anxiety and Brain Fear Responses While CBD Reduced Them ↗
In 15 men, THC increased anxiety and skin conductance responses to fearful faces, while CBD reduced amygdala activation and autonomic arousal, demonstrating opposite emotional processing effects.
Natural and Synthetic Cannabinoids: What They Are and How They Might Be Used as Medicine ↗
A review of 2003-2007 patents documented growing interest in cannabinoid isolation, synthesis, and therapeutic applications beyond existing FDA-approved uses of synthetic THC.
In Mice, One Brain Dose of a CB1 Agonist Led to Weeks-Long Tolerance Tied to Gz Proteins ↗
In mice, a single brain dose of a CB1 agonist produced more than two weeks of tolerance and reduced morphine analgesia. Gz proteins were required.
How Platelets Break Down the Endocannabinoid 2-AG ↗
Researchers characterized MAGL in platelets for the first time and found that both MAGL and FAAH contribute to 2-AG breakdown, with human and rabbit platelets showing different hydrolysis rates.
Chronic Cannabis Users Had Reduced Ability to Notice Their Own Errors ↗
Chronic cannabis users showed normal inhibitory control but significantly reduced awareness of their own errors, linked to reduced activation in the anterior cingulate cortex and right insula.
Mice Showed Hyperactivity and Paw Tremors During THC Withdrawal ↗
Mice chronically treated with THC showed hyperlocomotion (4.1x normal) and paw tremors (111 vs 1.1) during precipitated withdrawal, establishing quantifiable measures for studying cannabis dependence.
CBD Shows Promise for Neurodegenerative Diseases: A Review of the Evidence ↗
A review found that CBD demonstrates neuroprotective and anti-inflammatory properties in preclinical studies, making it a promising candidate for neurodegenerative disorders with few existing treatments.
What Heavy Teen Marijuana Use Was Linked To: Slower Thinking, Subtle Brain Differences, and Poorer Sleep ↗
Heavy teen marijuana use was linked to modest cognitive disadvantages, subtle brain differences, and poorer sleep. Some changes persisted past a month and sometimes resolved by three months of abstinence.
Blocking Endocannabinoid-Degrading Enzymes Reduced Neuropathic Pain in Mice ↗
Inhibiting FAAH and MAGL enzymes reduced neuropathic pain in mice through different cannabinoid receptor mechanisms, without the behavioral side effects of direct cannabinoid agonists.
People Could Identify When They Received THC, but No Other Drug Felt the Same ↗
In a drug discrimination study, 8 participants reliably identified THC, but opioid, sedative, and stimulant drugs could not substitute for the THC experience.
Blocking Both Endocannabinoid Enzymes Together Produced THC-Like Effects That Neither Alone Could ↗
A dual FAAH/MAGL inhibitor produced THC-like effects including drug discrimination responses that neither single-enzyme inhibitor could achieve, revealing cooperative endocannabinoid signaling.
Blocking 2-AG Breakdown Raised Brain Levels 8-Fold and Produced Cannabinoid Effects in Mice ↗
The first selective MAGL inhibitor (JZL184) raised mouse brain 2-AG eightfold and produced CB1-dependent analgesia, hypothermia, and reduced movement, establishing 2-AG as a key endocannabinoid modulator.
CBD Reversed THC-Induced Social Withdrawal in Rats at Low Doses ↗
CBD (20 mg/kg) reversed THC-induced social withdrawal in rats at low doses, but the combination of high doses of both compounds impaired social interaction, possibly through sedation.
The Endocannabinoid Signal Linked to Wanting Alcohol Was Suppressed in Abstinent Alcoholics ↗
Alcohol cue imagery increased anandamide levels and correlated with craving in 11 social drinkers, but this endocannabinoid response was absent in 12 abstinent alcoholics with markedly reduced baseline levels.
Chronic Cannabinoid Treatment Produced Antidepressant Effects in Male and Female Rats ↗
Ten days of cannabinoid receptor activation produced antidepressant-like effects in male and female rats through the noradrenergic system, but the effect was eliminated by precipitated withdrawal.
The Endocannabinoid System: A Comprehensive Overview of Its Role Across the Body ↗
A comprehensive review described the endocannabinoid system's role across nearly every organ system, from brain signaling and metabolism to immunity and reproduction.
A Paralyzed MS Patient Experienced Daily Out-of-Body Experiences Triggered by Cannabis ↗
A tetraplegic MS patient experienced daily out-of-body experiences triggered by cannabis treatment for spasticity, with measurable changes in mental body imagery after consumption.
Five Strategies to Make Cannabinoid Medicines Work Without the High ↗
Published three months after rimonabant's withdrawal, this review by Roger Pertwee proposed five strategies for developing cannabinoid medicines without psychoactive side effects — from peripheral restriction to cannabinoid-opioid synergy.
THC Impairs Long-Term Memory by Hijacking a Protein Synthesis Pathway in the Hippocampus ↗
THC impaired long-term memory in mice by activating the mTOR/p70S6K protein synthesis pathway in the hippocampus through CB1 receptors on inhibitory neurons, an effect blocked by rapamycin.
THC Withdrawal Activated the Same Stress Gene in the Brain as Nicotine and Opiate Withdrawal ↗
THC withdrawal induced the Narp gene in the amygdala, the same response seen with opiate and nicotine withdrawal, suggesting a shared molecular mechanism across drug withdrawal.
Ecstasy Users Had Worse Memory Than Controls or Cannabis Users, With Distinct Brain Changes ↗
Ecstasy users showed worse memory performance and distinct brain activation changes compared to both controls and cannabis users, though some neural effects overlapped between ecstasy and cannabis groups.
Boosting the Body's Own Cannabinoids Reduced THC Withdrawal Symptoms in Mice ↗
Both FAAH and MAGL inhibitors reduced THC withdrawal signs in dependent mice without causing dependence or motor impairment, though FAAH knockout mice showed normal withdrawal.
Endocannabinoids Elevated Mood State in Mice but Chronic Nicotine Changed This Response ↗
Endocannabinoid blockade reduced positive and increased negative emotional responses in mice, effects that were altered by chronic nicotine exposure, suggesting interactions between the two systems in mood regulation.
Adolescent Cannabis Users Needed More Brain Effort to Handle Conflicting Information ↗
Young adults with adolescent cannabis use showed worse executive attention performance and stronger right prefrontal brain activation, suggesting less efficient attentional processing.
Long-Term Cannabis Users Showed Altered Brain Patterns During Memory Tasks ↗
Chronic cannabis users (17 years average) showed altered brain electrical patterns during memory encoding, with greater changes linked to longer use and earlier onset.
Long-Term Cannabis Users Had More Errors and Altered Brain Responses When Processing Conflicting Information ↗
Chronic cannabis users showed more Stroop conflict errors and altered brain electrical patterns during conflict resolution, with earlier use onset predicting worse performance.
How Often You Use Cannabis Matters More for Memory-Related Brain Function Than How Long You Have Used ↗
Among 42 cannabis users, higher use frequency was specifically linked to increased parahippocampal brain activation during memory encoding, while duration and age of onset showed no effect on this region.
Starting Cannabis Before Age 16 Was Linked to Less Efficient Brain Function During Working Memory ↗
Cannabis users who started before age 16 showed increased brain activation during working memory tasks compared to later-onset users, independent of total use, suggesting less efficient cortical processing.
THC and CBD Had Opposite Effects on Brain Function Across Multiple Tasks, and CBD Blocked THC Psychosis ↗
THC and CBD had opposite effects on brain activation in the striatum, hippocampus, amygdala, and cortex across four cognitive tasks, and CBD pretreatment blocked THC-induced psychosis in 6 volunteers.
Methamphetamine Exposure Changed How the Brain Responds to Cannabinoids ↗
Methamphetamine neurotoxicity increased CB1 receptor expression across multiple brain regions in rats and reversed the anxiety effects of cannabinoid drugs from anxiogenic to anxiolytic.
In Mice Engineered to Keep Anandamide Around, THC Drove More Tolerance and Withdrawal ↗
In FAAH knockout mice, repeated THC caused stronger tolerance, more CB1 receptor dampening, and bigger withdrawal than repeated anandamide at equally effective doses.
Genetic Variations in the Cannabinoid System Affected How the Brain Responds to Marijuana Cues ↗
In 37 abstinent cannabis users, genetic variants in CNR1 and FAAH genes were associated with greater brain reward-area activation when viewing marijuana cues, with an additive effect of risk alleles.
A Single Amino Acid Change Eliminated Cannabinoid Effects on Pain-Related Glycine Receptors ↗
A single amino acid mutation in the glycine receptor completely abolished the ability of CBD, ajulemic acid, and HU210 to modulate this pain-related receptor, identifying a critical molecular interaction site.
CBD Disrupted the Brain Fear Circuit Connection That Normally Amplifies Anxiety ↗
CBD disrupted the forward neural connection between the amygdala and anterior cingulate during fear processing, the first demonstration that CBD affects brain network dynamics, not just regional activation.
Cannabis Medicines: Balancing Therapeutic Benefits Against Side Effects and Abuse Potential ↗
A review noted that THC-based medicines have established therapeutic uses but significant side effects and abuse potential, driving interest in endocannabinoid system modulators as safer alternatives.
Methamphetamine Brain Damage Increased Endocannabinoid Levels and Alcohol Drinking in Mice ↗
Meth neurotoxicity increased 2-AG endocannabinoid levels and alcohol consumption in mice, effects that were blocked by a CB1 receptor antagonist and mimicked by a MAGL inhibitor.
THC Withdrawal Caused Anxiety-Like Behavior in Mice for the First Time ↗
For the first time, THC withdrawal was shown to produce anxiety-like behavior in mice on the elevated plus-maze, without affecting motor activity, establishing an animal model for cannabis withdrawal anxiety.
Heavy drinking teens had worse memory, but not if they also used marijuana ↗
Among 130 teens, heavy drinking predicted worse verbal memory, but only in those who did not also use marijuana.
How the body's cannabinoid and opioid systems contribute to nicotine addiction ↗
Review of how endocannabinoid and opioid systems modulate nicotine addiction, suggesting new treatment targets.
Brain imaging studies show cannabis affects brain function more than brain structure ↗
Systematic review of 41 brain imaging studies found cannabis affected brain function, especially prefrontal blood flow, but caused minimal structural changes.
Boosting endocannabinoids with URB597 did not prevent morphine craving relapse in rats ↗
The FAAH inhibitor URB597 helped rats forget morphine associations during extinction but did not prevent relapse when exposed to morphine again.
Blocking cannabinoid receptors reversed memory problems caused by ecstasy withdrawal in mice ↗
Blocking CB1 cannabinoid receptors reversed memory impairment during ecstasy withdrawal in mice, linked to hippocampal CB1 receptor upregulation.
Cannabis users showed heightened brain reward response to money but reduced sensitivity to losses ↗
fMRI study found chronic cannabis users had heightened brain reward responses to money and reduced sensitivity to losses compared to non-users.
How cannabinoid and opioid systems interact at the cellular level ↗
Review identified three cellular mechanisms of cannabinoid-opioid interaction: peptide cross-release, receptor-receptor interaction, and converging signaling pathways.
Brain white matter differences appear early in schizophrenia, and adolescent cannabis use may play a role ↗
Review of brain imaging studies found white matter abnormalities in early schizophrenia, with adolescent cannabis use having specific effects on these measures.
Chronic cannabinoid treatment impaired male rat sexual function, but forced withdrawal reversed it ↗
Chronic cannabinoid treatment impaired male rat sexual behavior; forced CB1 receptor blockade restored function while spontaneous withdrawal did not.
How cannabinoids suppress the immune system by triggering immune cell death ↗
Review identified four mechanisms of cannabinoid immunosuppression through CB2 receptors: cell death, proliferation block, cytokine suppression, and regulatory T cell induction.
Recreational drug users (mainly ecstasy and cannabis) needed more brain effort for impulse control ↗
fMRI showed recreational drug users (ecstasy/cannabis) needed more brain activation for impulse control despite normal task performance.
Social isolation in rats changed endocannabinoid gene expression in patterns resembling schizophrenia ↗
Socially isolated rats showed increased endocannabinoid system gene expression in brain regions relevant to schizophrenia, including higher CB1 and lower FAAH in prefrontal areas.
The body breaks down the endocannabinoid anandamide through multiple enzyme pathways with distinct products ↗
Review revealed that P450 enzymes metabolize anandamide into diverse bioactive lipids including CB2 receptor agonists, complicating endocannabinoid drug development.
Cannabis withdrawal physically shrank dopamine neurons and reduced spine density in the brain's reward center ↗
Cannabinoid withdrawal physically shrank VTA dopamine neurons and reduced dendritic spines in the nucleus accumbens shell, supporting a "hypodopaminergic" addicted brain model.
Heavy cannabis-using adolescents had smaller hippocampi even after nearly 7 months of abstinence ↗
Heavy cannabis-using adolescents had smaller hippocampi than controls even after 6.7 months of abstinence, with volume correlated to amount of prior use.
Chronic cannabis extract reduced sperm count, testosterone, and fertility markers in male mice ↗
Chronic cannabis extract reduced sperm count, motility, and testosterone in male mice, with direct effects on testicular cannabinoid receptors.
How the endocannabinoid system regulates fertility in both women and men across species ↗
Review of endocannabinoid roles in reproduction: THC disrupted menstrual cycles and egg development in females, sperm production and motility in males.
Boosting endocannabinoids reduced anxiety during nicotine withdrawal in rats but did not prevent physical symptoms ↗
Boosting endocannabinoids with URB597 reduced anxiety but not physical symptoms during nicotine withdrawal in rats, with anandamide fluctuating across multiple brain regions.
Prenatal cannabis exposure reduced dopamine D2 receptors in offspring brains through lasting genetic changes ↗
Prenatal cannabis decreased D2 receptor expression in human fetal brain reward center; in rats, THC during pregnancy caused lasting epigenetic changes increasing offspring addiction vulnerability.
How cannabinoids reduce brain inflammation by interacting with the Toll-like receptor immune system ↗
Review described how cannabinoids reduce brain inflammation by interacting with Toll-like receptor signaling, part of the innate immune system implicated in neurodegenerative diseases.
CBD reduced Alzheimer's-related brain inflammation and promoted new brain cell growth through the PPARgamma pathway ↗
CBD reduced Alzheimer's-related brain inflammation and stimulated new neuron growth in rats, both through the PPARgamma receptor pathway.
The cannabinoid receptor blocker rimonabant unexpectedly reduced anxiety and hostility in schizophrenia patients ↗
In a small terminated trial, the CB1 antagonist rimonabant reduced anxiety and hostility in schizophrenia patients but did not produce weight loss.
Male cannabis users had slower motor skills and shifted brain activation patterns, linked to higher cortisol levels ↗
Male cannabis users had slower motor skills and shifted brain activation from visual to executive regions, with elevated cortisol levels potentially mediating these effects.
Boosting endocannabinoid 2-AG protected against stomach bleeding caused by common painkillers in mice ↗
Boosting endocannabinoid 2-AG with a MAGL inhibitor prevented NSAID-induced stomach bleeding in mice through CB1 receptors, without tolerance development.
Both endocannabinoid-boosting drugs reduced anxiety-like behavior in mice without the sedation caused by THC ↗
Endocannabinoid-boosting drugs (FAAH and MAGL inhibitors) reduced anxiety-like behavior in mice without sedation, while THC only worked at sedating doses.
Endocannabinoid and serotonin systems interact during nicotine withdrawal to produce depression-like symptoms in mice ↗
Endocannabinoid enhancement reduced depression-like behavior during nicotine withdrawal in mice through serotonin 5-HT1A receptor interaction, suggesting combined targeting for smoking cessation.
Review of how prenatal cannabis and cigarette exposure cause lasting molecular changes in the developing brain ↗
Review of how prenatal cannabis and cigarettes cause lasting brain changes: cannabis altered dopamine D2 receptors through epigenetic mechanisms, potentially programming lifelong addiction vulnerability.
How cannabinoids control nausea and vomiting in the body ↗
Review of how cannabinoids regulate nausea and vomiting, finding both THC and CBD effective through different brain mechanisms.
Blocking endocannabinoid breakdown reduced opioid withdrawal symptoms in mice ↗
Mouse study found that boosting natural endocannabinoids reduced opioid withdrawal symptoms, with the 2-AG pathway more effective than anandamide.
Cannabinoid activation protected brain cells during alcohol withdrawal in lab experiments ↗
Lab study found cannabinoid activation protected brain cells during alcohol withdrawal, while blocking the cannabinoid system worsened damage.
The Paper That Gave Cannabis Its Most Powerful Idea — and Its Most Abused One ↗
The most cited paper in cannabis science: Russo's comprehensive review mapping potential terpene-cannabinoid synergies. Coined the framework for the 'entourage effect' as applied to plant medicine. THC-CBD synergy is confirmed; terpene interactions remain debated.
THC and CBD combination protected brain cells in a Huntington's disease rat model ↗
Rat study showed 1:1 THC:CBD combination protected brain cells from Huntington's disease-like damage through antioxidant mechanisms.
Cocaine withdrawal altered cannabinoid receptors and synaptic plasticity in the amygdala ↗
Rat study found cocaine withdrawal increased cannabinoid receptors and disrupted synaptic plasticity in the amygdala, potentially driving cue-triggered relapse.
What happens when people use both MDMA and cannabis together ↗
Review of 23 studies found MDMA and cannabis co-use produced additive memory deficits, involving CB1-serotonin-dopamine interactions.
Boosting anandamide levels reduced morphine withdrawal symptoms in rats ↗
Rat study found FAAH inhibitor URB597 reduced most morphine withdrawal symptoms across a broad dose range.
THC reduced the brain's error-detection signal in healthy volunteers ↗
THC significantly reduced the brain's error-detection signal (ERN) in 10 healthy volunteers without affecting simple task performance.
A gene variant in the cannabinoid receptor influenced how THC affected brain attention signals ↗
A cannabinoid receptor gene variant influenced how THC affected attention-related brain waves, with CBD in cannabis extract appearing to buffer the effect.
CBD reversed amphetamine-induced brain damage in a rat model of mania ↗
CBD reversed amphetamine-induced oxidative brain damage and increased BDNF in rats, suggesting potential neuroprotective properties relevant to bipolar disorder.
Brain imaging revealed the insula plays a key role in the THC "high" ↗
Brain imaging showed THC increased blood flow and activity in the insula, linking this body-awareness region to the subjective experience of being "high."
THC and CBD had opposite effects on brain areas that process sound and vision ↗
Brain imaging showed THC and CBD had opposite effects on auditory processing regions, with THC's disruption correlating with psychotic symptoms.
THC-dependent mice showed memory problems during withdrawal, some lasting months ↗
Chronic cannabinoid exposure during rat adolescence caused temporary general cognitive impairment but spatial memory deficits lasting at least 75 days.
Comprehensive review of cannabinoids for MS symptoms and disease progression ↗
Review supporting cannabinoid benefits for MS spasticity, pain, and sleep, with emerging preclinical evidence for disease-modifying neuroprotection.
Late-adolescent rats given chronic cannabinoids showed lasting spatial memory problems ↗
Late-adolescent cannabinoid exposure in rats produced recoverable general cognitive deficits but persistent spatial memory impairment lasting at least 75 days.
CB1 blocker failed to reverse nicotine-induced anxiety and may have worsened it in novelty-seeking rats ↗
CB1 antagonist reversed nicotine locomotor sensitization in novelty-seeking rats but failed to reduce and actually worsened nicotine-induced anxiety.
The biology behind why cannabis-based medicines work for MS spasticity ↗
Review explaining the biological rationale for why cannabis-based medicines work for MS spasticity, based on the endocannabinoid system's role in neurotransmission.
New class of MAGL inhibitors with improved selectivity for endocannabinoid research ↗
New HFIP carbamate compounds inhibited the endocannabinoid enzyme MAGL with excellent selectivity, avoiding cross-reactivity with FAAH.
A natural plant compound reduced pain by boosting endocannabinoids without binding to cannabinoid receptors ↗
Beta-amyrin did not bind cannabinoid receptors (correcting prior claims) but potently inhibited 2-AG breakdown, suggesting indirect cannabinoid-based pain relief.
Adolescents using methamphetamine and cannabis showed enlarged brain reward regions and higher novelty seeking ↗
Brain imaging found adolescent methamphetamine and cannabis users had enlarged striatal regions and higher novelty-seeking, with meth exposure correlating to both.
Brain scans predicted which heavy cannabis users would develop worse problems six months later ↗
Brain activity in cognitive control regions predicted which heavy cannabis users would develop worse problems over 6 months, beyond what craving alone predicted.
How four lesser-known cannabinoids move through the body and brain in rats and mice ↗
Pharmacokinetic study showing four lesser-known cannabinoids (CBD, CBDV, THCV, CBG) all cross the blood-brain barrier, with CBD reducing OCD-like behavior in mice.
Brain activity patterns during psychosis overlap with cannabis effects in key regions ↗
Systematic review found first-episode psychosis and cannabis effects both increased anterior cingulate cortex activity, suggesting shared neural mechanisms.
Heated versus unheated cannabis extracts produced very different drug levels in the body ↗
In 9 volunteers, unheated cannabis extract produced nearly double the CBD blood levels and different metabolic profiles compared to heated extract.
Synthetic cannabinoids JWH-018 and JWH-073 acted like THC in monkeys but wore off faster ↗
Synthetic cannabinoids JWH-018 and JWH-073 produced THC-like effects in monkeys but lasted only 1-2 hours versus THC's 4, potentially increasing addiction risk.
Adolescent cannabinoid exposure in mice caused lasting schizophrenia-like brain and behavior changes ↗
Adolescent but not adult cannabinoid exposure in mice produced lasting schizophrenia-like deficits, linked to reduced hippocampal mGluR5 and altered endocannabinoid metabolism.
CB1 blocker rimonabant raised cortisol levels in cannabis-dependent men, hinting at stress axis involvement ↗
In cannabis-dependent men, rimonabant blood levels correlated with cortisol increases, providing human evidence that CB1 receptors modulate the stress hormone system.
Cannabis impairs working memory through brain support cells, not neurons directly ↗
Landmark Cell paper showing cannabis impairs working memory through CB1 receptors on astrocytes (support cells), not on neurons directly.
Long-term cannabis users showed increased brain connectivity that may compensate for impairment ↗
Long-term cannabis users showed normal cognitive performance but increased brain connectivity between control and attention regions, suggesting neural compensation.
Daily Cannabis Use Was Linked to Fewer CB1 Receptors. A Month Without Brought Them Back. ↗
Chronic daily smokers showed lower cortical CB1 receptor availability that returned to control-like levels after about four weeks without cannabis.
Higher-potency synthetic cannabinoids developed less tolerance than THC in monkeys ↗
Monkeys developed 9.2-fold tolerance to THC but only 3.6-4.3-fold cross-tolerance to higher-efficacy synthetic cannabinoids, consistent with receptor theory.
Teen marijuana users had reduced brain blood flow, but it normalized after 4 weeks of abstinence ↗
Teen marijuana users showed reduced brain blood flow in multiple regions, but all differences disappeared after 4 weeks of confirmed abstinence.
CB1 blocker reversed anxiety from stress hormones and cocaine withdrawal in rats ↗
CB1 antagonist reversed anxiety from stress hormones and cocaine withdrawal in rats through brain mechanisms independent of the hormonal stress axis.
Infertile men had lower endocannabinoid levels and altered cannabinoid system in their sperm ↗
Infertile men's sperm showed reduced endocannabinoid levels and absent TRPV1 receptors, identifying potential biomarkers and treatment targets for male infertility.
Schizophrenia patients who previously used cannabis showed different brain activation patterns during cognitive tasks ↗
Schizophrenia patients with cannabis history showed better task-related brain activation and less default-mode activity at rest than non-using patients.
How cannabinoids disrupt memory formation: they suppress the brain's replay signals ↗
Cannabinoids suppressed hippocampal sharp wave-ripples essential for memory consolidation by selectively inhibiting excitatory glutamate signaling.
CBD protected myelin-producing brain cells from inflammatory damage through ER stress reduction ↗
CBD protected myelin-producing brain cells from inflammatory death by reducing ER stress through a mechanism independent of known cannabinoid receptors.
From Teen Years to 38: Heavy, Long-Term Cannabis Use Tracked With Lower Cognitive Scores ↗
The most famous and debated cannabis study: 1,037 New Zealanders followed from birth showed up to 8 IQ points of decline with persistent adolescent-onset use — but subsequent twin studies and meta-analyses suggest the true effect is smaller and partly confounded.
New Chemical Compounds Can Precisely Target the Brain's Cannabis-Processing Enzymes ↗
A new class of chemical compounds can selectively block endocannabinoid-degrading enzymes in the brain, potentially offering pain and mood benefits without full psychoactive effects.
Cannabis and Dopamine: What Animal Brains Show About Reward, Cues, and Withdrawal ↗
Animal data place cannabis squarely in the dopamine reward circuit: dopamine rises with use and cues, and falls during withdrawal. Blocking endocannabinoid signaling blunts these effects.
Caffeine Made THC's Memory-Impairing Effects Worse, Not Better, in Rats ↗
In rats, caffeine did not offset THC's memory effects but actually worsened them, with a subthreshold THC dose impairing memory when combined with caffeine.
How the Endocannabinoid System Interacts With Alcohol Dependence ↗
Comprehensive review found the brain's endocannabinoid system plays a key role in alcohol's rewarding effects and is altered by chronic drinking.
Five Strategies for Making Cannabinoid Medicines More Effective With Fewer Side Effects ↗
Review identified five strategies for making cannabinoid medicines more effective while reducing psychoactive side effects, covering applications from pain to neurodegeneration.
Cannabis May Both Relieve MS Symptoms and Protect Nerve Cells From Damage ↗
Review found cannabinoids may both relieve MS spasticity symptoms and protect nerve cells from disease-related damage.
The Endocannabinoid System Is Present in Embryos Before Brain Development Begins ↗
The endocannabinoid system is active in embryos before brain development begins, suggesting early pregnancy cannabis exposure could disrupt fundamental developmental processes.
Runner's High Has an Endocannabinoid Signature in Humans. Dogs Show It Too. ↗
High-intensity running raised blood endocannabinoids in humans and dogs, not in ferrets and not during walking.
CBD Reduces Nausea and Vomiting by Activating Serotonin Receptors in the Brain ↗
CBD suppressed vomiting and nausea-like behavior in animals by activating serotonin 5-HT1A receptors in a specific brainstem region.
Chronic Cannabis Users Show Brain Activation Changes in Social Thinking That Resemble Psychosis Risk Patterns ↗
Brain imaging found chronic cannabis users had altered activation in social cognition regions, matching patterns seen in psychosis-risk populations.
Cannabinoids Show Promise for Slowing Huntington's Disease Progression in Lab Studies ↗
Preclinical evidence showed cannabinoids, especially the THC/CBD combination in Sativex, had neuroprotective properties relevant to Huntington's disease.
Injecting Cannabinoids Directly Into Muscles Reduced Pain in Rats ↗
Cannabinoid agonists injected directly into muscles reduced pain in rats, with local administration outperforming systemic in one of two models tested.
Alcohol Withdrawal Disrupts the Endocannabinoid System in the Brain's Fear Center ↗
Alcohol withdrawal reduced endocannabinoid system gene expression in the rat amygdala, with repeated withdrawal cycles causing worse disruption.
The Endocannabinoid System: A Master Regulator of Brain Health and Disease ↗
Overview described the endocannabinoid system as a master regulator involved in neuroprotection, pain, memory, neurogenesis, and immune function.
Former Cannabis Users Recovered Learning Ability but Still Had Timing Problems in a Brain Task ↗
Former cannabis users recovered associative learning ability but still showed impaired response timing, suggesting lasting cerebellar changes after quitting.
Adolescent THC Exposure Changed Gene Regulation in the Brain, Making Rats More Vulnerable to Heroin ↗
Adolescent THC exposure in rats altered gene regulation through epigenetic changes in the reward system, directly increasing vulnerability to heroin self-administration.
A THC/CBD Combination Protected Brain Cells in a Huntington's Disease Model ↗
A THC/CBD combination reduced brain cell death and inflammation in a rat Huntington's disease model, working through both CB1 and CB2 receptors.
Blocking Cannabinoid Receptors Improved Memory Problems During Morphine Withdrawal in Mice ↗
Blocking cannabinoid receptors improved memory deficits during morphine withdrawal in mice, with chronic treatment being more effective than a single dose.
THC Impaired Spatial Memory but Not Object Memory in Adolescent Monkeys ↗
THC selectively impaired spatial but not object working memory in adolescent monkeys, suggesting less mature brain functions are more vulnerable.
Cannabinoid Receptor-Expressing Neurons in the Brain's Reward Center Are Fast-Spiking Cells That Control Output ↗
CB1-expressing neurons in the brain's reward center are fast-spiking interneurons that become hyperexcitable during cocaine withdrawal, potentially suppressing reward circuit output.
Different Drug Tools Selectively Boost Either Anandamide or 2-AG in the Living Brain ↗
Research tools for boosting brain endocannabinoids work differently in rats versus mice, with FAAH and MAGL inhibitors selectively targeting anandamide or 2-AG respectively.
Blocking 2-AG Breakdown in the Spinal Cord Powerfully Reduced Pain Signaling in Rats ↗
Spinal administration of an enzyme inhibitor powerfully reduced pain signaling and blocked inflammation-induced sensitization in rats via endocannabinoid mechanisms.
Heavy Cannabis Users' Brains Lit Up in the Habit Region When Shown Positive Cannabis Associations ↗
Brain imaging showed heavy cannabis users activated habit-related brain regions for positive cannabis associations while non-users activated deliberate control regions.
Pregabalin and Topiramate Reduced Anxiety and Motor Symptoms During Cannabis Withdrawal in Mice ↗
Pregabalin and topiramate both reduced anxiety and motor symptoms during cannabinoid withdrawal in mice while reversing brain gene expression changes.
Only Half of Healthy Volunteers Experienced Psychotic Symptoms From THC, and Their Brains Responded Differently ↗
About half of healthy men experienced psychotic symptoms from THC while half did not, with distinctly different brain activation patterns between groups.
Cannabis Impaired Driving-Related Brain Networks Even at Low THC Blood Levels ↗
Brain imaging showed cannabis disrupted attention and executive control networks while increasing self-focused brain activity, even at low blood THC levels.
How Endocannabinoid Enzyme Inhibitors Are Revealing the Different Roles of Anandamide and 2-AG ↗
Review detailed how enzyme-specific inhibitors revealed different roles for anandamide and 2-AG in pain, anxiety, and addiction, guiding therapeutic development.
Schizophrenia Patients Who Used Cannabis Had Better Emotional Memory and More Normal Brain Activity ↗
Schizophrenia patients with cannabis abuse showed better emotional memory and more preserved prefrontal brain activity than non-using patients.
A Common Pesticide Raised Endocannabinoid Levels in Developing Rat Brains ↗
The pesticide chlorpyrifos persistently elevated brain endocannabinoid levels in developing rats, even at the lowest dose tested, through enzyme inhibition.
Cannabis Cues Triggered Craving and Activated Memory and Emotion Brain Regions ↗
Cannabis cues increased craving and activated memory and emotion brain regions, but the brain-craving relationship habituated after the first exposure.
THC's Memory-Damaging Effects Work Through COX-2, and Blocking COX-2 Preserves THC's Medical Benefits ↗
THC impaired memory through COX-2 enzyme induction, and blocking COX-2 eliminated cognitive side effects while preserving THC's Alzheimer's benefits in mice.
How the Cannabinoid System Controls Pain: From THC to Natural Brain Mechanisms ↗
Review described multiple cannabinoid pain-relief mechanisms, including CB2 agonists without psychoactive effects and a novel endocannabinoid circuit in the midbrain.
Could a Natural Fatty Acid (PEA) Help Treat Cannabis Dependence and Withdrawal? ↗
Hypothesis paper proposed PEA, a natural fatty acid with endocannabinoid properties, as a potential treatment for cannabis dependence and withdrawal.
Cannabinoids Show Anti-Cancer Potential in Lab Studies, but Results Remain Contradictory ↗
Review found growing preclinical evidence for cannabinoid anticancer effects across multiple cancer types, but contradictory results and unclear mechanisms limit conclusions.
Adolescent Cannabis Users Showed Abnormal Risk-Taking and Reward Brain Patterns Even After Quitting ↗
Abstinent adolescents with past cannabis use disorder showed abnormal brain patterns during risk-taking and reward processing that persisted after treatment.
Chronic Cannabinoid Treatment Caused Massive Tolerance and Cross-Tolerance With Dopamine Drugs ↗
Chronic cannabinoid treatment in monkeys caused up to 250-fold tolerance and cross-tolerance with methamphetamine and dopamine D2 drugs.
Children of Substance-Using Parents Showed Reduced Error-Processing Brain Activity Before Developing Addiction ↗
Children of substance-using parents showed reduced error-processing brain activity even before any cannabis use, suggesting an inherited vulnerability marker.
Motivational Interviewing Changed Brain Activation in Teen Cannabis Users and Predicted Better Outcomes ↗
Adolescent cannabis users showed increased self-reflection brain activity when hearing their own motivational statements, and this predicted less use one month later.
The CB2 Cannabinoid Receptor Was Required for Nicotine's Rewarding Effects but Not Withdrawal ↗
CB2 cannabinoid receptors were required for nicotine reward but not withdrawal in mice, with an opposite role for cocaine reward, revealing substance-specific effects.
Low-Dose MAGL Inhibitor Maintained Pain Relief and Stomach Protection Without Causing Tolerance ↗
Low-dose MAGL inhibitor maintained pain relief and stomach protection without causing CB1 tolerance or dependence, unlike high doses which caused both.
BDNF-Deficient Male Mice Became Hypersensitive to Cannabinoid Effects on Sensory Gating After Chronic Exposure ↗
Male mice with BDNF deficiency became hypersensitive to cannabinoid effects on sensory gating after chronic young-adult cannabinoid exposure, with increased CB1 receptors in nucleus accumbens.
THC and CBD Suppressed a Key Inflammatory Immune Response Linked to Autoimmune Diseases ↗
THC and CBD suppressed the autoimmune Th17 response (IL-17, IL-6) while CBD boosted anti-inflammatory IL-10, through a novel receptor-independent mechanism.
THC Reduced Pain Unpleasantness Without Reducing Pain Intensity, Working Through the Amygdala ↗
THC reduced pain unpleasantness without changing pain intensity, working through the amygdala by disconnecting emotional from sensory pain processing in the brain.
Cannabis Effects on Brain Structure in Schizophrenia Remain Unclear Despite Extensive Imaging Research ↗
Systematic review found inconclusive evidence for cannabis effects on brain structure in schizophrenia, with no convincing pre-onset structural changes.
Joint Mobilization Relieved Post-Surgical Pain Through Cannabinoid Receptors, Enhanced by FAAH and MAGL Inhibitors ↗
Joint mobilization reduced post-surgical pain through CB1 and CB2 receptors, and FAAH/MAGL inhibitors significantly extended the pain-relieving effect in mice.
Blocking the Enzyme That Breaks Down Anandamide Had Opposite Effects on Nicotine Reward in Mice Versus Rats ↗
FAAH inhibition enhanced nicotine reward in mice but blocked it in rats, with species differences possibly due to non-cannabinoid substrates like OEA and PEA.
CB2 Receptors Were Involved in Nicotine Reward, Reinforcement, and Withdrawal in Mice ↗
CB2 knockout mice showed no nicotine reward, reduced self-administration, and no withdrawal, with CB2 receptors colocalizing with nicotinic receptors in reward circuits.
FAAH Inhibitors Reduced MS-Like Spasticity in Mice Without Cannabis-Like Side Effects ↗
Three FAAH inhibitors reduced MS-model spasticity in mice without psychoactive side effects, definitively confirmed using genetic knockout mice.
Cannabis Use Was Linked to Reduced Cingulate Brain Volume in Both Early Psychosis and At-Risk Patients ↗
Cannabis use was linked to reduced cingulate cortex volume in both at-risk and first-episode psychosis patients, in a brain region rich in cannabinoid receptors.
The Cannabinoid and Opioid Systems Interact Closely, Suggesting Cannabis Could Help Manage Opiate Withdrawal ↗
Review found extensive cannabinoid-opioid interactions in the brain's stress circuits, suggesting endocannabinoid targeting could help manage opiate dependence and withdrawal.
Cannabinoid Treatment Reversed MDMA-Induced Memory Deficits but Not Decision-Making Impairment in Rats ↗
Chronic cannabinoid treatment reversed MDMA-induced memory deficits in rats but did not fix impaired effort-based decision making, showing circuit-specific interactions.
Genetic Background Dramatically Changed Whether Cannabinoid Receptor Knockouts Affected MS-Like Disease in Mice ↗
CB2 knockout effects on MS-model disease completely depended on mouse strain: augmented disease in one background, no effect in another, cautioning against over-interpreting animal cannabinoid studies.
Chronic Marijuana Users Showed Reduced Brain Activation During Memory Retrieval in a Virtual Maze ↗
Chronic marijuana users showed impaired spatial memory retrieval and reduced parahippocampal brain activation during a virtual maze task.
Occasional Stimulant Users With High Cannabis Use Showed the Most Brain Inefficiency During Decision-Making ↗
Occasional stimulant users with high cannabis co-use showed the most brain inefficiency during reward-based decision-making, suggesting additive substance effects.
New synthetic cannabinoid compounds designed to study the CB1 receptor ↗
Researchers created novel adamantyl cannabinoid compounds that serve as precise CB1 receptor probes, with in vivo effects matching their binding profiles in rat models.
Could common antibiotics help reduce cannabis dependence? A hypothesis ↗
A researcher hypothesized that beta-lactam antibiotics might reduce cannabis dependence by boosting brain glutamate transporters, based on parallels with opioid pharmacology.
Cannabis use and brain wave changes in people at ultra-high risk for psychosis ↗
Both healthy cannabis users and people at ultra-high risk for psychosis showed reduced P300 brain wave amplitudes, suggesting overlapping effects on information processing.
CB1 receptor levels increased in the brain reward center during morphine withdrawal in rats ↗
Rats showed increased CB1 receptor expression in a brain reward center throughout morphine withdrawal, and blocking these receptors reduced drug-seeking behavior.
Mice lacking the main 2-AG enzyme still had CB1 receptor signaling through backup pathways ↗
Mouse brain tissue maintained CB1 receptor signaling even when primary 2-AG production enzymes were genetically deleted, revealing backup endocannabinoid production pathways.
Adolescent rats were more vulnerable than adults to lasting memory deficits from a cannabinoid ↗
Chronic cannabinoid exposure in adolescent rats caused lasting spatial memory deficits linked to reduced hippocampal neurogenesis, while adult rats were unaffected.
COX-2 creates inflammatory molecules from endocannabinoids, not just destroys them ↗
Review revealed that COX-2 converts endocannabinoids into novel inflammatory mediators rather than simply destroying them, adding complexity to our understanding of inflammation.
Endocannabinoid-related molecules in semen were linked to sperm quality ↗
Men with poor sperm quality had lower seminal levels of endocannabinoid-related molecules, and adding these molecules improved sperm motility in the lab.
The endocannabinoid system plays important roles in liver disease ↗
Review documented the endocannabinoid system's roles in multiple liver diseases and the potential for peripherally targeted therapies after early drug safety setbacks.
Adolescent cannabis users showed abnormal brain connectivity during impulse control ↗
Adolescent cannabis users showed poorer impulse control and abnormal brain connectivity between parietal and cerebellar regions, a pattern that correlated with recent use.
Lower Dopamine Production Tracked With Higher Apathy Scores in Regular Cannabis Users ↗
In 14 regular users, lower dopamine synthesis in associative striatum tracked with higher apathy. No control group, and dose measures did not explain apathy.
Brain imaging shows cannabis users work harder to maintain memory performance ↗
Review of brain imaging studies found cannabis users consistently showed increased brain activity during memory tasks, suggesting greater neural effort needed to maintain performance.
How marijuana affects immune cells in the brain ↗
Review found THC inhibited brain immune cell migration toward infections, while CBD modulated neuroimmunity differently. Early-life exposure may alter adult immune responses.
A common pesticide disrupted endocannabinoid signaling in developing rat brains ↗
Low-dose pesticide exposure increased brain anandamide levels in developing rats at doses below the traditional toxicity threshold, implicating the endocannabinoid system as a sensitive target.
Brain scans could identify heavy cannabis users with 84-88% accuracy based on connectivity patterns ↗
Machine learning analysis of brain scans classified heavy cannabis users from controls with 84-88% accuracy based on connectivity patterns spanning cerebellum to prefrontal cortex.
Blocking an Orexin-1 Receptor Cut Mice's Drive to Take a Synthetic Cannabinoid ↗
In mice, orexin-1 signaling supported cannabinoid reward. Blocking it reduced self-administration and erased THC-evoked accumbens dopamine.
Review of cannabinoid potential for treating neurological diseases ↗
Review found cannabinoids showed potential for multiple neurological diseases, with established uses in MS, nausea, and appetite stimulation, and emerging evidence for neurodegenerative conditions.
A targeted endocannabinoid enzyme blocker reduced pain without producing a cannabis-like high ↗
A selective endocannabinoid enzyme blocker (KML29) reduced inflammatory and nerve pain in mice without cannabis-like side effects like sedation or immobility.
Brain activity before treatment predicted cannabis abstinence during and after therapy ↗
Cannabis-dependent men showed reduced cognitive control brain activity, and those with greater pre-treatment activation in control and reward regions used less cannabis during and after treatment.
Boosting the Body's Own Cannabinoids Reduced Anticipatory Nausea in Rats ↗
A dual enzyme inhibitor that boosts natural endocannabinoids suppressed anticipatory nausea in rats through CB1 receptor activation, with enhanced effects when combined with anandamide.
Clozapine Reduced Cannabis Craving More Than Risperidone in Patients with Schizophrenia ↗
Clozapine reduced cannabis craving and insula brain activity more than risperidone in patients with schizophrenia and cannabis use disorder over 4 weeks of treatment.
Male and Female Rats Showed Similar THC Withdrawal, with One Exception ↗
First study examining THC dependence in both sexes of adult rats found broadly similar withdrawal signs spanning somatic, cognitive, and affective domains, with females showing more retropulsion.
Many Everyday Activities and Medications May Boost the Body's Own Cannabinoid System ↗
Systematic review found that exercise, massage, acupuncture, several medication classes, and lifestyle factors all upregulate the endocannabinoid system, relevant to conditions like migraine and fibromyalgia.
Activating CB1 Receptors Disrupted Memory-Related Brain Signaling by Altering Protein Production ↗
CB1 receptor activation with a synthetic cannabinoid impaired memory-related brain signaling (LTP) by causing abnormal overproduction of proteins and inhibiting acetylcholine release.
Black Pepper Compound Boosted Endocannabinoid Levels and Produced Cannabis-Like Effects in Mice ↗
Black pepper compound guineensine inhibited endocannabinoid uptake at nanomolar concentrations and produced cannabis-like effects in mice that were blocked by a CB1 antagonist.
Cocaine Exposure Altered the Endocannabinoid System in the Cerebellum of Mice ↗
Mouse study found acute and repeated cocaine exposure produced distinct endocannabinoid and glutamate system changes in the cerebellum, implicating it in addiction processes.
MS Patients Who Used Cannabis Showed More Cognitive Impairment and Altered Brain Activity ↗
MS patients who used cannabis showed worse cognitive performance and more diffuse brain activation on fMRI, suggesting cannabis disrupts compensatory brain mechanisms already strained by MS.
Chronic Cannabis Use Altered Brain Networks Involved in Self-Awareness ↗
Heavy cannabis users showed altered connectivity in self-awareness brain networks, linked to less anxiety but worse memory, that partially persisted after one month of abstinence.
2-AG Was the Key Endocannabinoid Regulating Stress Hormone Recovery in Mice ↗
Mouse study identified 2-AG as the primary endocannabinoid regulating stress hormone recovery, with sex differences in timing and compensatory mechanisms when CB1 signaling is absent.
CBD Could Be a New Approach to Treating Schizophrenia Through Non-Dopamine Pathways ↗
Review presents evidence that CBD could serve as an antipsychotic agent through non-dopamine mechanisms, potentially augmenting standard medications and addressing metabolic and inflammatory components of schizophrenia.
Overview of Cannabinoid Medicine: From MS Spasticity to Epilepsy to Addiction Treatment ↗
Broad review of cannabinoid medicine covered therapeutic potential in MS spasticity, pain, nausea, epilepsy, psychosis, and addiction, contrasting THC and CBD pharmacology.
Neuroinflammation May Connect the Endocannabinoid System to Drug Addiction ↗
Review of 165 studies found drug addiction involves both disrupted endocannabinoid signaling and neuroinflammation, suggesting cannabinoids could address addiction through anti-inflammatory mechanisms.
A Dual Enzyme Inhibitor Boosted Both Endocannabinoids and Had Stronger Behavioral Effects in Rats ↗
Comparison of endocannabinoid enzyme inhibitors in rats found the dual FAAH/MAGL inhibitor JZL195 had enhanced effects over the MAGL-only inhibitor JZL184, with notable species differences from mice.
Revisiting the Theory That Some Chronic Conditions Stem from Endocannabinoid Deficiency ↗
Ten-year review of the clinical endocannabinoid deficiency hypothesis argues growing evidence supports low endocannabinoid tone as a factor in migraine, fibromyalgia, and IBS.
THC Disrupted Learning-Related Brain Changes in Adolescent Rats Only When They Were Actively Training ↗
THC disrupted learning-related hippocampal plasticity and neurogenesis markers in adolescent rats, but only during active training, with no effects in untrained animals.
Cannabis May Increase Psychosis Risk Through Immune System Disruption ↗
Systematic review of 122 studies found exogenous cannabinoids suppress immune function and shift Th1/Th2 balance, potentially creating latent vulnerability to psychosis, especially during adolescence.
From Cannabis Receptors to Clinical Response: The State of CBD for Epilepsy ↗
Review of CBD for epilepsy found strong preclinical support for endocannabinoid system involvement in seizure control and growing anecdotal evidence for CBD, but called for rigorous clinical trials.
Adolescent THC Exposure in Rats Led to Compulsive Heroin Seeking in Their Unexposed Offspring ↗
Unexposed offspring of THC-exposed rats showed compulsive heroin-seeking behavior and altered striatal brain circuitry, suggesting transgenerational epigenetic effects of parental cannabis exposure.
Synthetic Cannabinoids Are Stronger Than THC at Brain Receptors and May Be More Dangerous ↗
Review found synthetic cannabinoids are full CB1 agonists with higher potency than THC (a partial agonist), explaining their increased potential for adverse reactions and toxicity.
Genetic Vulnerability Plus Juvenile Cannabis Exposure Caused Lasting Cognitive Damage in Mice ↗
Mice with a genetic variant in neural cell adhesion showed delayed but lasting cognitive damage from juvenile THC exposure, while normal mice did not, supporting a gene-environment interaction.
THCV Increased Brain Responses to Both Rewarding and Unpleasant Food Stimuli ↗
First human study of THCV found it increased brain responses to both food reward and aversion, suggesting potential for obesity treatment without the depressive effects of rimonabant.
The Endocannabinoid System as a Target for New Pain Medications ↗
Review of endocannabinoid-based pain therapy highlights FAAH and MAGL inhibitors as promising approaches that boost natural pain-modulating molecules locally, potentially avoiding psychoactive effects.
Adolescent Monkeys Given THC for 6 Months Showed Lasting Spatial Memory Impairment ↗
Adolescent monkeys given THC for 6 months showed persistent impairment in spatial working memory (still maturing) but not object working memory (already mature).
The Brain Detected Cannabis Cues Even When They Were Shown Too Quickly to Consciously See ↗
Cannabis cues flashed for 33ms (below conscious awareness) activated reward brain circuits in dependent users, with activation correlating with craving and years of use.
Boosting Both Endocannabinoids Together Was Needed to Mimic THC's Subjective Effects in Rats ↗
Drug discrimination study found that mimicking THC's subjective effects in rats required simultaneously boosting both anandamide and 2-AG through dual enzyme inhibition.
Blocking CB1 Receptors Reduced the Unpleasant Effects of Morphine Withdrawal in Rats ↗
CB1 neutral antagonists reduced the aversive emotional effects of morphine withdrawal in rats, but FAAH inhibitors (which boost anandamide) did not.
A CB2 Receptor Drug Reduced Pancreatic Pain and Protected Tissue in Rats ↗
CB2 receptor agonist reduced pain behaviors and protected pancreatic tissue from damage in a rat model of chronic pancreatitis without affecting brain function.
An Endocannabinoid-Related Compound Blocked Fat Cell Formation Through CB1 Receptors ↗
NADA (an endocannabinoid) inhibited fat cell formation in human stem cells via CB1 receptors, while anandamide promoted it via PPARg, revealing opposing metabolic roles.
Can cannabinoids help with tremor from Parkinson's, MS, and other movement disorders? ↗
Review of cannabinoid potential for tremor in Parkinson's, MS, and other motor disorders found high receptor density in motor brain regions but inconclusive clinical evidence.
Adolescent THC exposure combined with a schizophrenia-linked gene mutation worsened emotional memory in adult mice ↗
Mice with a schizophrenia-linked gene mutation showed worsened emotional memory and reduced brain activity when exposed to THC during adolescence, demonstrating gene-environment interaction.
A comprehensive history and science review of medical cannabis, with a focus on headache and migraine ↗
Comprehensive review of cannabis in medicine found deep historical roots in headache treatment and relevant pharmacology, but almost no controlled clinical trial evidence for migraine.
Brain scans predicted with 100% accuracy when daily cannabis smokers chose to buy cannabis ↗
Brain scans of 17 daily cannabis smokers identified a neural signature that distinguished decisions to purchase cannabis from decisions to decline with 100% accuracy.
How the endocannabinoid system is involved in Alzheimer's disease and could be a treatment target ↗
Review of endocannabinoid system involvement in Alzheimer's disease found it modulates multiple pathological pathways, suggesting potential as a multi-target therapeutic approach.
CB1 receptors on brain cells versus star-shaped support cells control endocannabinoid 2-AG in opposite directions ↗
Mouse study revealed CB1 receptors on glutamate neurons and astrocytes control endocannabinoid 2-AG turnover in opposite directions in the frontal cortex.
Blocking an endocannabinoid-degrading enzyme protected myelin and reduced nerve damage in mice with MS-like disease ↗
Blocking 2-AG breakdown protected myelin-producing cells and reduced demyelination in two mouse models of MS, through CB1 receptor activation and reduced inflammation.
THC impaired the brain's ability to stop unwanted responses, and the impairment correlated with psychotic symptoms ↗
In 36 healthy men, THC impaired response inhibition and reduced left inferior frontal brain activation, with both effects correlating with transient psychotic symptoms.
THC and CBD had opposite effects on brain connectivity in regions involved in attention and salience processing ↗
Brain imaging showed THC and CBD had opposite effects on connectivity between prefrontal, striatal, and hippocampal regions involved in salience processing and attention.
Where CB1 receptors are located in the brain determines how cannabinoids affect memory and appetite ↗
Review showed CB1 receptors produce different effects depending on whether they are on glutamate neurons, GABA neurons, astrocytes, or mitochondria, with implications for targeted therapy.
How cannabinoids regulate immune function in the brain and could treat neuroinflammatory diseases ↗
Review of cannabinoid effects on brain immunity found anti-inflammatory properties relevant to MS, Alzheimer's, and ALS, with CB2 receptors as promising non-psychoactive targets.
Adolescent THC exposure affected heroin reward differently in two rat strains, suggesting genetics shape gateway effects ↗
Adolescent THC exposure affected heroin reward differently in addiction-prone vs. resilient rat strains, suggesting genetics determine whether cannabis acts as a gateway.
CBD increased survival and protected brain function in mice with cerebral malaria ↗
CBD treatment increased survival, prevented memory deficits, and reduced brain inflammation in mice with cerebral malaria by lowering cytokines and increasing BDNF.
Chronic cannabis users had reduced brain activity when learning from mistakes and corrected fewer errors ↗
Brain scans of 15 chronic cannabis users showed reduced activation in error-monitoring and memory regions during a learning task, with lower error-correction rates than controls.
Brain scans showed chronic cannabis users had about 12% fewer CB1 receptors in key brain regions ↗
PET brain imaging showed chronic cannabis users had 11.7% fewer available CB1 receptors globally, with reductions of 11-14% in temporal, cingulate, and reward regions.
Boosting the body's own cannabinoids reduced tic-like behaviors in mice across four genetic strains ↗
The endocannabinoid-boosting drug URB597 reduced tic-like behaviors in all four mouse strains tested, suggesting a potential treatment approach for tic disorders with fewer side effects than THC.
How cannabinoid signaling regulates brain immune responses in neuroinflammatory diseases ↗
Review of cannabinoid regulation of brain immunity found potential therapeutic applications for MS, Alzheimer's, and ALS through modulation of microglial activation and neuroinflammation.
Chronic THC prevented weight gain and changed gut bacteria in obese mice but not lean mice ↗
Chronic THC prevented weight gain and fat accumulation in obese mice and reversed obesity-related gut microbiota changes, without affecting lean mice or causing sedation.
Combined marijuana and nicotine use showed an unusual pattern: smaller hippocampus linked to better memory ↗
Marijuana users had smaller hippocampal volumes, and combined marijuana-nicotine users showed an unusual inverted pattern where smaller hippocampus correlated with better memory.
Intravenous THC caused paranoia in vulnerable individuals by increasing negative emotions and unusual experiences ↗
In 121 paranoia-prone individuals, intravenous THC increased paranoid thoughts through heightened negative emotions and anomalous experiences, not through cognitive impairment.
Cannabinoid compounds reduced physical morphine withdrawal signs in mice but not the emotional aversion to withdrawal ↗
THC and endocannabinoid-boosting drugs reduced physical morphine withdrawal jumping in mice but did not block the emotional aversion, suggesting they address only part of the withdrawal experience.
The endocannabinoid system plays a key role in nicotine addiction and could be targeted for smoking cessation ↗
Review of endocannabinoid system role in nicotine addiction found rimonabant helped smokers quit but had psychiatric risks, prompting research into safer alternative cannabinoid targets.
CBD reduced brain inflammation and reversed schizophrenia-like behaviors in mice, matching the effects of clozapine ↗
CBD reversed social withdrawal, cognitive deficits, and brain inflammation (astrocyte and microglial activation) in a schizophrenia mouse model, matching clozapine's effectiveness.
Acute cannabinoid use impairs habit memory, but chronic use may strengthen it, potentially fueling addiction ↗
Review found acute cannabinoid use impairs habit-based learning while chronic use enhances it, suggesting a novel habit-memory mechanism for cannabis addiction.
CBD triggered the production of immune-suppressive cells in mice through mast cells and a fat-sensing receptor ↗
CBD triggered immune-suppressive cell mobilization in mice through mast cells and PPAR-gamma receptor activation, revealing a specific molecular pathway for CBD's immune effects.
Heavy marijuana use during adolescence predicted worse emotional functioning in the early 20s, with brain changes mediating the link ↗
Heavy adolescent marijuana users showed disrupted emotional development (no improvement in negative emotionality or resilience), with brain activation differences mediating the outcomes.
Estrogen and a CB2 receptor blocker worked synergistically to boost bone cell growth ↗
Combining a CB2 receptor blocker with moderate estrogen produced the same bone cell growth as 10x higher estrogen alone, revealing a synergistic interaction in human osteoblasts.
What the Science Says About Cannabinoids for Movement Disorders ↗
Review of cannabinoid research for movement disorders found possible benefit for tics, potential neuroprotection in animal models, but no clear benefit for Parkinson's symptoms, tremor, or dyskinesias.
High-Dose Cannabis Disrupts the Brain's Error Detection System ↗
EEG study found high-dose THC disrupted automatic error detection in frequent cannabis users, while even low doses impaired conscious error recognition.
How the Brain's Endocannabinoid System Fine-Tunes Inhibitory Signaling ↗
Mouse study discovered multiple interacting mechanisms controlling GABA release in the hippocampus, including constitutively active CB1 receptors and opposing endocannabinoid pathways.
Blocking CB1 Receptors Makes Pesticide Poisoning Worse in Rats ↗
Rat study found blocking CB1 receptors worsened pesticide poisoning, suggesting the endocannabinoid system naturally protects against organophosphorus toxicity.
50 Years After THC: How the Endocannabinoid System Works Throughout the Body ↗
Landmark review by endocannabinoid research pioneers mapped the system's roles across reproduction, bone, skin, immunity, and gut function, establishing it as one of the body's most widespread signaling networks.
How Cannabinoids Regulate Nausea, Vomiting, and Gut Pain ↗
Review found cannabinoid receptors throughout the GI tract regulate nausea and vomiting, but clinical evidence for visceral pain relief in conditions like IBS was lacking.
Vaporized THC Helped Rats Overcome Aversive Memories from Opiate Withdrawal ↗
Vaporized THC at higher doses helped rats extinguish opiate withdrawal memories, while injected THC at a moderate dose prolonged them fourfold, highlighting route-dependent effects.
Young Adult Cannabis Users Show Thinner Cortex and Smaller Thalamus ↗
MRI study found young adult cannabis users had thinner cortex in the fusiform gyrus and smaller thalamic volumes linked to greater impulsivity compared to matched non-users.
New CB1 Receptor Blocker Reduced Food Intake Without Rimonabant's Side Effects ↗
New CB1 receptor blocker ENP11 reduced food intake and blocked endocannabinoid-driven overeating in rats without affecting pain or motor function.
What Research Shows About Marijuana Use During Pregnancy and Breastfeeding ↗
Review found marijuana crosses the placenta and appears in breast milk, with evidence linking prenatal exposure to growth restriction and neurological development effects, though data quality is limited.
Alcohol and Cannabis Have Opposite Effects on the Immune System ↗
Review found alcohol promotes inflammation while cannabinoids suppress it, suggesting cannabinoid-based therapies could potentially counteract alcohol-induced immune damage.
Endocannabinoid Enzymes Play Different Roles in Body Temperature Regulation ↗
Mouse study found MAGL inhibition (raising 2-AG) worsened hypothermia from cold and infection via CB1 receptors, while FAAH inhibition (raising anandamide) had no temperature effect.
Blocking Anandamide Breakdown Eliminated Migraine-Like Pain in Mice ↗
Mice lacking the FAAH enzyme were completely protected from migraine-like pain, and FAAH-inhibiting drugs reproduced this protection through CB1 receptors.
Synthetic Cannabinoid JWH-018 Impairs Sensory Functions Far More Than THC in Mice ↗
Mouse study found synthetic cannabinoid JWH-018 impaired sensory function at very low doses and caused convulsions at high doses, effects not seen with equivalent THC doses.
Non-Psychoactive Cannabinoid CBG Reduced Bladder Contractions in Mice and Humans ↗
CBG was the most effective non-psychoactive cannabinoid at reducing bladder contractions in mice and human tissue, working through a non-CB1/CB2 mechanism.
Understanding Cannabis Addiction: Mechanisms, Withdrawal, and Treatment Targets ↗
Review found no approved cannabis addiction medications but identified promising targets including FAAH inhibitors and allosteric CB1 modulators in animal models of reward, withdrawal, and relapse.
Endocannabinoid Levels Are Elevated in Chronic Hepatitis C and May Worsen Liver Fibrosis ↗
Hepatitis C patients had elevated endocannabinoids that suppressed antiviral immunity and promoted liver scarring, potentially explaining why cannabis worsens liver disease progression.
A Comprehensive Map of 13 Endocannabinoids and Their Actions ↗
Pharmacological review identified 13 probable endocannabinoids in mammalian tissue, including agonists, antagonists, and allosteric modulators, revealing the system's built-in regulatory complexity.
From Lab to Clinic: Therapeutic Opportunities in Cannabinoid Receptor Research ↗
Review highlighted CB1's potential in brain protection and addiction, CB2's potential in ALS, HIV neuroinflammation, and osteoporosis, emphasizing the need for receptor-selective cannabinoid drugs.
New CB2-Selective Compounds Block Inflammation Without Activating Brain Receptors ↗
Researchers designed CB2-selective inverse agonist compounds with no CB1 activity, including novel noncompetitive antagonists, expanding the toolkit for non-psychoactive cannabinoid therapeutics.
Endocannabinoids in Multiple Sclerosis and ALS: From Symptom Relief to Neuroprotection ↗
Review found cannabinoids relieve MS spasticity and showed neuroprotective potential in animal models of both MS and ALS, suggesting possible disease-modifying effects.
Cannabis-Based Cannabinoids Showed Neuroprotective Effects in MS Animal Models ↗
Synthetic CBD slowed MS-related disability in mice possibly via sodium channels, while THC slowed progression without suppressing relapses. A clinical trial subgroup also showed THC benefit.
Why Tobacco and Cannabis Use So Often Go Together ↗
Review found tobacco and cannabis each promote dependence on the other through shared brain chemistry, common smoking route, and bidirectional gateway effects.
Seven New Cannabinoids Discovered in High-Potency Cannabis ↗
Scientists discovered seven new cannabinoids in high-potency cannabis, with one showing higher CB1 binding and more potent THC-like effects than delta-8-THC.
New Pyrrole-Based Compounds Selectively Target CB2 Receptors ↗
Researchers designed pyrrole-based compounds with high CB2 selectivity and antagonist/inverse agonist activity, advancing the development of non-psychoactive anti-inflammatory cannabinoid drugs.
Targeting Pain Nerves Outside the Brain Could Make Cannabinoid Pain Drugs Practical ↗
Review found targeting cannabinoid receptors on peripheral nerves could provide pain relief without psychoactive effects, with promise for diabetic and chemotherapy neuropathy.
MS Patients Who Smoke Cannabis Show More Widespread Brain Volume Loss and Cognitive Impairment ↗
MS patients who smoked cannabis had more widespread cognitive deficits linked to brain volume loss in the thalamus, basal ganglia, and prefrontal regions compared to non-using MS patients.
Cannabis Compound THCV Changes Brain Network Connectivity in Ways Relevant to Obesity ↗
THCV, a cannabis-derived CB1 neutral antagonist, altered brain connectivity in ways relevant to obesity without subjective effects, suggesting potential as a safer alternative to rimonabant.
Endocannabinoid System Changes Across the Menstrual Cycle May Affect Implantation ↗
Study of 49 women found endocannabinoid enzymes in the uterine lining change across the menstrual cycle, with degrading enzymes peaking during the implantation window.
Cannabinoids Disrupt Brain Cell Energy Production at the Mitochondrial Level ↗
All tested cannabinoids, including THC, CBD, and endocannabinoids, inhibited brain mitochondrial energy production through a mechanism independent of cannabinoid receptors.
Past Cannabis Use Linked to Different Hippocampal Shape Changes in Healthy People vs. Schizophrenia ↗
MRI study found past cannabis use was linked to distinct hippocampal shape changes in healthy people (correlated with memory problems) vs. schizophrenia patients (correlated with use duration).
Teen Cannabis Users Show Heightened Amygdala Response to Angry Faces ↗
fMRI study found 14-year-old cannabis users had exaggerated amygdala reactivity to angry faces and impaired cortical threat regulation compared to matched non-users.
Inflammation Suppresses an Endocannabinoid-Degrading Enzyme, Possibly to Self-Limit ↗
Mouse study found inflammation suppresses an endocannabinoid-degrading enzyme in the spleen, potentially boosting anti-inflammatory endocannabinoid signaling as a natural feedback mechanism.
Cannabinoid Withdrawal Is Caused by Receptor Competition, Not Inverse Agonism ↗
Both inverse agonist and neutral antagonist precipitated withdrawal in cannabis-dependent mice, showing withdrawal results from receptor competition, not inverse agonism, and is centrally mediated.
Alcohol and the Endocannabinoid System Work Against Each Other in a Key Brain Region ↗
Alcohol and cannabinoid signaling showed opposing effects at inhibitory synapses in the rat amygdala, with each system blocking the other's actions.
Cannabis Users Show Disrupted Dopamine Receptor Balance in Key Brain Reward Areas ↗
Brain imaging revealed that heavy cannabis users lacked the balanced dopamine receptor signaling between striatal regions that healthy controls displayed during a reaction-time task.
Boosting a Natural Brain Cannabinoid Delayed Seizure Development in Mice ↗
Blocking the enzyme that breaks down the endocannabinoid 2-AG delayed seizure development in a mouse epilepsy model, but had minimal effect once seizures were established.
Mice Without the Anandamide Breakdown Enzyme Were More Sensitive to THC-Like Effects of Other Cannabinoids ↗
Mice lacking the anandamide breakdown enzyme responded normally to THC but showed enhanced sensitivity to the THC-like effects of anandamide and 2-AG boosting drugs.
Adolescent THC Exposure in Rats Changed DNA Markers in Their Offspring's Brain Reward Center ↗
Adolescent THC exposure in rats produced over 1,000 regions of altered DNA methylation in their unexposed offspring's brain reward center, affecting glutamatergic signaling genes.
THC and Endocannabinoid-Boosting Drugs Reduced Brain Reward Signaling in Mice ↗
THC and a 2-AG boosting drug reduced brain reward self-stimulation in mice, while boosting anandamide alone had little effect, all mediated through CB1 receptors.
Prenatal Cannabis Exposure May Alter Offspring Immunity Through Epigenetic Changes ↗
A review of animal research found that prenatal cannabinoid exposure can produce lasting immune dysfunction in offspring through epigenetic mechanisms like altered DNA methylation and microRNA.
Blocking the CB1 Cannabinoid Receptor Reduced Adolescent Binge Drinking in Mice Without Affecting Adults ↗
Blocking CB1 receptors reduced binge alcohol and sucrose consumption in adolescent mice to adult levels, suggesting the endocannabinoid system drives age-related differences in binge drinking.
A GPR55 Receptor Agonist Reduced Morphine Reward and Physical Dependence in Mice ↗
The atypical cannabinoid O-1602, a GPR55 receptor agonist, reduced morphine reward and physical dependence symptoms in mice, suggesting a potential new target for opioid dependence.
Cannabinoid Treatment During Late Adolescence Reversed the Cognitive Damage From Early Life Stress in Rats ↗
Cannabinoid treatment during late adolescence reversed cognitive deficits and reduced anxiety caused by early life stress in rats, with sex-specific differences in brain receptor changes.
Estrogen Suppresses Reproductive Brain Cells Through the Endocannabinoid System ↗
Estradiol suppressed reproductive hormone neurons through a pathway requiring both estrogen receptor beta and endocannabinoid 2-AG/CB1 signaling in mouse brain slices.
Synthetic Cannabinoid JWH-018 and Its Variants Impaired Memory More Potently Than THC in Mice ↗
Synthetic cannabinoid JWH-018 and two halogenated variants impaired memory in mice more potently than THC, disrupting hippocampal synaptic transmission through CB1 receptors.
How the Body Makes and Breaks Down Its Own Cannabinoids ↗
A comprehensive review detailed how anandamide and 2-AG are synthesized from membrane phospholipids and degraded by FAAH, MAGL, and oxidative enzymes.
A FAAH Inhibitor Disrupted Liver Endocannabinoid Balance and Increased Oxidative Stress in Hypertensive Rats ↗
Chronic FAAH inhibition in hypertensive rats further elevated liver endocannabinoid levels but worsened oxidative stress, despite reducing inflammation.
How THC and CBD Work Differently in the Brain and Why It Matters ↗
A pharmacology review explained how CBD can reduce some of THC's psychoactive effects, a relationship that led to the development of the THC/CBD drug Nabiximols.
Rats Exposed to Cannabis Smoke Developed Dependence and Showed a Two-Phase Effect on Activity ↗
Rats exposed to cannabis smoke at human-relevant THC levels showed biphasic activity changes, reduced anxiety, and developed physical dependence confirmed by precipitated withdrawal signs.
What Brain Imaging Reveals About Marijuana's Effects on the Developing Brain ↗
A neuroimaging review found marijuana use is associated with brain structure and function changes, with adolescent-onset use showing the most concerning patterns of alteration.
Two Novel Synthetic Cannabinoids Caused Seizures, Aggression, and Dopamine Release in Mice ↗
Novel synthetic cannabinoids AKB48 and 5F-AKB48 caused seizures, aggression, sensory impairment, and dopamine release in mice, with the fluorinated version being more potent.
Beyond THC: New Drug Strategies That Boost the Brain's Own Cannabinoids ↗
A review examined alternatives to direct cannabinoid receptor activation, including FAAH, MAGL, and COX-2 inhibitors that boost the brain's own cannabinoids for potentially better therapeutic profiles.
The Endocannabinoid System Plays a Key Role in Placenta Development, Which Cannabis May Disrupt ↗
The endocannabinoid system regulates normal placenta development; THC can disrupt trophoblast proliferation, death, and function, providing a mechanism for cannabis-related fetal growth restriction.
Brain Cannabinoid Receptors Drop With Heavy Use, Then Rebound Within Days of Stopping ↗
Heavy users showed lower brain CB1 receptor availability at baseline, but the difference from controls disappeared after two days without cannabis.
Cannabis Users' Brain Cannabinoid Receptors Recovered to Normal Levels in Just 2 Days of Abstinence ↗
PET imaging showed cannabis-dependent males had 15% fewer CB1 receptors than controls, but receptors normalized to control levels after just 2 days of abstinence.
Third-Generation Synthetic Cannabinoids Were Up to 30 Times More Potent Than Earlier Versions ↗
Four third-generation Spice/K2 compounds showed CB1 binding up to 30x higher than JWH-018, with potent dopamine release in the brain's reward center.
Natural Variation in Brain Endocannabinoid Levels Was Linked to Resting Heart Rate in Rats ↗
Natural variation in anandamide levels and FAAH activity in a specific brainstem region correlated with resting heart rate in rats, with anandamide injection increasing heart rate.
CB2 Receptor Drugs Behave Very Differently Depending on Which Cellular Pathway Is Measured ↗
CB2 receptor ligands showed extreme functional selectivity, with drugs behaving as agonists, antagonists, or having no effect depending on which cellular pathway was measured.
The CB2 Cannabinoid Receptor Helps Regulate Sperm Development, and Disrupting It Alters the Timeline ↗
CB2 receptor activation mimicked retinoic acid in stimulating meiotic gene expression in sperm precursors, and both over- and under-activation disrupted the spermatogenic timeline in mice.
A Cannabinoid Receptor Gene Variant Influenced How Much Nicotine Withdrawal Disrupted Brain Function ↗
A CNR1 gene variant moderated how much nicotine withdrawal disrupted brain function, with some genetic profiles showing greater cognitive disruption during deprivation.
Breast Cancer Drug Tamoxifen Binds to Cannabinoid Receptors, Opening Door for New Drug Development ↗
Researchers found that tamoxifen (a breast cancer drug) and its metabolites bind to cannabinoid receptors with varying selectivity, acting as inverse agonists and suggesting a new chemical scaffold for cannabinoid drug development.
Multiple Breast Cancer Drug Classes Show Activity at Cannabinoid Receptors with Improved Properties ↗
Screening 14 breast cancer drugs at cannabinoid receptors identified four with improved binding properties compared to tamoxifen, including compounds with selective CB1 or CB2 receptor activity.
First Study Shows CB1 Receptor Modulator Org27569 Reduces Baseline Signaling Through a Specific Pathway ↗
Researchers demonstrated for the first time that the CB1 receptor allosteric modulator Org27569 acts as an inverse agonist of ERK signaling, reducing baseline receptor activity and blocking cannabinoid-induced receptor internalization.
Combining a Cannabinoid with MDMA Reverses Memory Impairment in Rats Through a Specific Brain Mechanism ↗
Rat study found that MDMA reversed memory impairment caused by a synthetic cannabinoid in the hippocampus through an NMDA receptor-dependent mechanism, potentially explaining why some people combine these substances.
Young Cannabis Users Show Different Brain Activation Patterns When Making Decisions Under Social Pressure ↗
Brain scans revealed that young cannabis users showed unique reward-region activation when following social pressure to conform, with the strength of this activation correlating with how much cannabis they used.
Cannabis Users Show Greater Brain Response to Peer Information and More Effort When Disagreeing with Peers ↗
Cannabis-using young adults showed greater brain activation in the caudate when receiving peer information and took longer to make decisions opposing the group, suggesting heightened neural sensitivity to social influence.
Very Low Doses of a CB1 Blocker Correct Key Features of Fragile X Syndrome in Mice ↗
A CB1 receptor blocker at doses 30-300 times lower than those causing side effects in humans normalized memory and brain signaling in a Fragile X syndrome mouse model, suggesting a potential therapeutic approach.
How the Endocannabinoid System Drives Alcohol-Seeking Behavior and Why Blocking CB1 Receptors Reduces Drinking ↗
Review of animal and human evidence shows chronic alcohol disrupts the endocannabinoid system, and CB1 receptor blockade reduces alcohol consumption and relapse, though psychiatric side effects remain a barrier to clinical use.
PET Imaging Reveals CB1 Receptor Drugs Need Only 20-30% Brain Occupancy for Anti-Obesity Effects ↗
PET brain imaging in primates revealed that CB1 receptor antagonists need only 20-30% receptor occupancy for anti-obesity effects, much lower than expected, suggesting lower doses might avoid psychiatric side effects.
Computer Modeling of the CB2 Receptor Reveals How Its Active and Inactive States Differ and Identifies New Drug Candidates ↗
Computer modeling of the CB2 cannabinoid receptor in active and inactive states identified key structural differences and led to the discovery of two novel compounds, advancing rational drug design for CB2-targeted therapies.
The CB1 Blocker Rimonabant Impairs Smell Through a Separate Receptor in the Olfactory Bulb ↗
Mouse study reveals that the CB1 blocker rimonabant impairs olfactory discrimination through TRPV1 receptors in the olfactory bulb, not through CB1 blockade, suggesting an unexpected mechanism for this drug.
High-Potency Synthetic Cannabinoid AM4054 and Analogs All Produce THC-Like Effects in Rats ↗
Rat drug discrimination study showed high-potency synthetic cannabinoid AM4054 and three analogs all produce THC-like effects through CB1 receptors, with potency varying based on specific structural features.
The Spice Compound AM2201 Is 14 Times More Potent Than THC in Producing THC-Like Effects in Rats ↗
The Spice compound AM2201 was found to be 14 times more potent than THC with a rapid onset and short 60-minute half-life, helping explain the severe adverse effects seen with synthetic cannabinoid products.
Genetic Stress Vulnerability Changes How Repeated Stress Affects Pain and the Endocannabinoid System ↗
Stress-normal and stress-vulnerable rat strains showed opposite pain responses after repeated stress, with matching differences in endocannabinoid system changes in the spinal cord and amygdala.
How the Endocannabinoid System Controls Insulin-Producing Cells and What This Means for Diabetes ↗
Review shows the endocannabinoid system controls insulin-producing beta-cell function through local mechanisms, and peripheral CB1 receptor blockade improves glycemic control in diabetes models.
The Body's Own Cannabis-Like Chemical Causes Fewer Cognitive Problems Than THC in Monkeys ↗
Primate study showed THC impaired multiple cognitive functions while the body's own cannabinoid anandamide and drugs that boost it had minimal cognitive effects, suggesting a path to safer cannabinoid medicines.
The Endocannabinoid System as a Drug Target: A Comprehensive Review of Therapeutic Potential and Setbacks ↗
Comprehensive review of the endocannabinoid system's therapeutic potential across dozens of conditions, addressing both approved drugs and major setbacks in cannabinoid drug development.
Cannabinoids May Protect Retinal Neurons in Glaucoma and Diabetic Eye Disease Beyond Just Lowering Eye Pressure ↗
Review presents evidence that cannabinoids may protect retinal neurons in glaucoma and diabetic eye disease through neuroprotection mechanisms beyond the known effect of lowering eye pressure.
Researchers Create First Chemical Tools to Map the CB1 Receptor's Allosteric Binding Site ↗
Scientists created the first chemical probes to permanently bind and map the CB1 receptor's allosteric site, with lead compound GAT100 showing exceptional potency and improved pharmacological properties.
How Cannabis and Other Drugs Hijack the Brain's Learning and Memory System to Drive Addiction ↗
Review reveals cannabis may enhance hippocampal learning during use (strengthening drug-context memories) while impairing it during withdrawal (driving relapse), creating a cycle that maintains addiction.
Comprehensive Profiling of GAT100 Confirms It as a Superior CB1 Allosteric Modulator for Drug Development ↗
Comprehensive profiling of the CB1 allosteric probe GAT100 across multiple signaling pathways confirmed it as superior to existing modulators, with identification of a critical binding residue for drug design.
Deleting Endocannabinoid Enzymes Reshapes Lipid Signaling Across Eight Brain Regions ↗
Lipidomics study of mice missing key endocannabinoid enzymes revealed sweeping effects on lipid signaling across eight brain regions, extending far beyond endocannabinoids to prostaglandins and dozens of related lipids.
Natural Brain Peptides Slow Gut Movement Through CB1 Receptors, Potentially Enabling Pain Relief Without GI Side Effects ↗
Endogenous cannabinoid peptides slowed gut movement through CB1 receptors in mice, but with lower potency than classical cannabinoids, suggesting potential for pain relief with fewer GI side effects.
Blocking CB1 Receptors Reverses Age-Related Insulin Resistance in Mice ↗
Two weeks of CB1 receptor blockade reversed age-related insulin resistance in aged mice but had no metabolic effect in young mice, suggesting the endocannabinoid system becomes pathologically overactive with aging.
Cannabis Use Thins the Brain's Frontal Cortex in Young Adults, With Distinct Effects in Those With ADHD ↗
MRI study found cannabis use was associated with thinner frontal cortex in young adults, with distinct brain structure patterns emerging in cannabis users who also had persistent ADHD.
Systematic Review Finds Altered Brain Function in Adolescent Cannabis Users Despite Normal Task Performance ↗
Systematic review of 13 brain imaging studies found adolescent cannabis users showed altered frontal-parietal brain function during cognitive tasks while maintaining normal performance, suggesting compensatory mechanisms.
Peripherally Restricted and Neutral CB1 Blockers May Safely Treat Obesity and Diabetes Without Psychiatric Side Effects ↗
Review argues that peripherally restricted and neutral CB1 receptor blockers can provide rimonabant's metabolic benefits for obesity and diabetes without the psychiatric side effects that ended its clinical use.
Your Brain Already Makes Its Own Cannabinoids. Here's How the System Works. ↗
Comprehensive review of the endocannabinoid system — the brain's built-in cannabinoid network that THC hijacks when you use cannabis.
Hemopressin Peptides: A New Class of Endogenous Cannabinoid Modulators With Therapeutic Potential ↗
Review examines hemopressin peptides, naturally occurring molecules that modulate cannabinoid receptors, highlighting their potential for pain relief, appetite control, and blood pressure regulation.
Cannabis Dramatically Reduced Seizures in a Treatment-Resistant Epilepsy Patient, Possibly Through the Rare Cannabinoid CBDV ↗
A treatment-resistant epilepsy patient experienced dramatic seizure reduction with cannabis, and lab experiments suggest the rare cannabinoid CBDV may contribute through effects on the brain's inhibitory GABA system.
CB2 Receptors Can Disrupt Protein Complexes Without Being Activated ↗
CB2 cannabinoid receptors can break apart cellular protein complexes simply by being present, without needing to be activated by any cannabinoid.
Cannabis Use and ADHD Both Linked to Thinner Brain Cortex, But Through Different Mechanisms ↗
Persistent ADHD and frequent cannabis use each independently associated with thinner cortex in a key impulse control brain region in young adults.
Two Synthetic Cannabinoids Are More Dangerous Together Than Either One Alone ↗
Animal study shows two synthetic cannabinoids found in "spice" products produce dangerous effects even at individually sub-threshold doses when combined, suggesting synergistic toxicity.
Blocking CB1 Receptors Produced Antidepressant Effects Through the Opioid System ↗
Mouse study shows a CB1 receptor blocker produced antidepressant effects that were mediated through the opioid system, revealing a mechanistic link between cannabinoid and opioid pathways in depression.
The Endocannabinoid System Keeps Sleep Stable But Does Not Drive the Need to Sleep ↗
Animal research shows the endocannabinoid system stabilizes NREM sleep bouts but does not drive the homeostatic need to sleep, helping explain cannabis's complex effects on sleep.
Cannabis and Cocaine Reduced Impulse Control and Brain Connectivity, But Only in People With Certain Genetics ↗
Controlled trial shows cannabis and cocaine increase impulsivity and reduce brain connectivity, but only in people with a genetic variant predisposing to higher dopamine levels.
ADHD Reduced Brain Activity for Impulse Control Regardless of Cannabis Use ↗
fMRI study finds ADHD reduced impulse control brain activation regardless of cannabis use, while cannabis-using controls recruited compensatory brain regions that ADHD participants could not.
Long-Term Cannabis Use Affected Attention Differently in People With and Without Schizophrenia ↗
Chronic cannabis use reduced attention-related brainwave responses in healthy people but not in those with schizophrenia, suggesting pre-existing endocannabinoid differences in schizophrenia.
Activating CB2 Receptors Reduced Nausea and Vomiting Without Psychoactive Effects ↗
First demonstration that a selective CB2 receptor agonist reduces both vomiting and nausea in animal models, offering a non-psychoactive alternative to THC-based anti-nausea treatments.
Key Differences Between Baboon and Human Cannabinoid Systems Could Affect Drug Testing Results ↗
Comparative genomics reveals important differences between baboon and human endocannabinoid system genes, particularly in CB2 receptors and metabolic enzymes, with implications for translating primate drug studies to humans.
Twelve Years of Evidence: Clinical Endocannabinoid Deficiency Gains Objective Support ↗
The 2016 evidence update that moved CECD from speculation to supported hypothesis: CSF anandamide reduced in migraineurs (p < 0.0001), PET imaging shows CB1 changes in PTSD, platelet studies confirm altered endocannabinoid levels, genetic associations identified.
Adolescent THC Exposure Made Adult Rats Seek More Cannabinoids by Changing Their Reward System ↗
Adolescent THC exposure in rats enhanced adult cannabinoid self-administration and blunted dopamine reward signaling, providing a biological mechanism for increased addiction vulnerability after early cannabis use.
A New Type of CB1 Blocker Reduced Both Nicotine and Cannabis Seeking in Monkeys ↗
A CB1 neutral antagonist reduced both nicotine and cannabis seeking in monkeys without affecting food motivation, offering a potentially safer alternative to the withdrawn drug rimonabant.
A Drug Designed to Boost Natural Endocannabinoids Was Itself Addictive in Monkeys ↗
An endocannabinoid-boosting compound being studied as a potential anti-smoking treatment was itself self-administered by monkeys, raising concerns about abuse potential of this drug class.
Social Rejection in Adolescent Rats Changed Pain Sensitivity Through the Endocannabinoid System ↗
Adolescent rats experiencing social rejection from unresponsive partners developed altered pain sensitivity through endocannabinoid CB1 signaling, linking social and physical pain processing.
THC Suppressed Immune Inflammation by Reprogramming Immune Cells Through MicroRNA ↗
THC suppressed immune inflammation in mice by correcting dysregulated microRNA molecules that control inflammatory T cell development, revealing a precise molecular mechanism.
Prenatal Marijuana Exposure Was Linked to Altered Brain Activity in Young Adults 18-22 Years Later ↗
Young adults prenatally exposed to marijuana showed altered brain activation (increased left posterior activity) during executive function tasks despite normal performance, suggesting neural compensation 18-22 years after exposure.
Cannabis and Cocaine Had Opposite Acute Effects on Impulse Control and Brain Activity ↗
Controlled crossover study finds cocaine enhanced and cannabis impaired impulse control with mirror-image effects on brain electrical activity, both acting on evaluative rather than detection stages of inhibition.
Cannabinoids Impaired Learning But Actually Helped Memory Consolidation in the Cerebellum ↗
Cannabinoids in the cerebellum impaired new learning but enhanced memory consolidation in a specific 1-3 hour window after training, revealing a dual role in memory processing.
The Brain's Anti-Nausea System Works Through a Specific Endocannabinoid in a Specific Brain Region ↗
Nausea selectively increased the endocannabinoid 2-AG in the brain's visceral insular cortex, and boosting 2-AG there reduced nausea by dampening neural activity through CB1 receptors.
Cannabis May Change How Genes Are Expressed, and These Changes Could Pass to the Next Generation ↗
Review finds cannabis can alter epigenetic marks controlling gene expression in brain and body, with emerging evidence suggesting some changes may pass to offspring.
Boosting the Endocannabinoid 2-AG Enhanced Cue-Triggered Nicotine Seeking in Mice ↗
Boosting the endocannabinoid 2-AG did not affect nicotine self-administration but significantly enhanced cue-triggered nicotine seeking in mice, implicating 2-AG in tobacco relapse.
Chronic Cannabinoid Receptor Activation in Human Pancreatic Islets Did Not Impair Function ↗
Human pancreatic islets exposed to cannabinoid receptor agonists for up to 5 days showed gene expression changes but no impairment of insulin secretion or cell survival.
Brain Response to Cannabis Cues Predicted Who Would Have Cannabis Problems 3 Years Later ↗
Brain response to cannabis cues in the left striatum predicted cannabis problem severity 3 years later, independent of how much cannabis was used, suggesting a neural biomarker for addiction risk.
Boosting the Endocannabinoid Anandamide Completely Reversed Social Impairment in Two Autism Mouse Models ↗
Boosting anandamide levels completely reversed social impairment in two autism mouse models (BTBR and Fragile X) through CB1 receptors, identifying FAAH as a novel therapeutic target for ASD.
Comprehensive Brain Imaging Review: How Cannabis Changes Brain Structure and Function ↗
Review of 103 brain imaging studies shows regular cannabis use alters brain structure (hippocampus, amygdala), cognitive function (with compensatory recruitment), dopamine systems, and CB1 receptors.
Heavy Cannabis Users Showed Reduced Brain Activity When Evaluating Emotional Content ↗
fMRI study finds heavy cannabis users show reduced medial prefrontal cortex activity during conscious emotional evaluation of both positive and negative content.
The Appetite-Reducing Effect of Combining Leptin With a CB1 Blocker Required Serotonin Receptors ↗
Serotonin 5-HT1B and 5-HT2C receptors are required for the appetite-suppressing effect of combining leptin with a CB1 blocker, revealing a three-way neuroendocrine interaction in feeding behavior.
An Endocannabinoid-Boosting Drug Enhanced Morphine's Pain Relief Without the Side Effects ↗
MAGL inhibitor MJN110 synergized with morphine for neuropathic pain relief without constipation, cannabis-like effects, or tolerance development after 6 days of dosing.
The Endocannabinoid System Modulates Opiate Withdrawal Through Different Brain Circuits ↗
Review of animal studies shows the endocannabinoid system modulates both physical and emotional opiate withdrawal through distinct brain regions, with CB1 effects varying by location.
Adolescent THC exposure causes lasting brain changes in male rats, but different from females ↗
Adolescent THC exposure produced lasting memory deficits and psychotic-like behaviors in male rats, driven by glutamate signaling disruption and neuroinflammation specifically in the hippocampus.
Natural brain peptides that act on cannabinoid receptors can both help and hurt memory in mice ↗
Natural brain peptides targeting the CB1 cannabinoid receptor had opposite effects on memory depending on brain health: blocking CB1 helped healthy mice, while activating it restored memory in an Alzheimer's model.
Scientists designed cannabinoid-based obesity drugs that work in the body without entering the brain ↗
Researchers designed CB1 receptor blockers that cannot enter the brain, aiming to treat obesity through the cannabinoid system without causing psychiatric side effects.
The body's own cannabinoid system helps regulate immune tolerance in the gut and pancreas ↗
The endocannabinoid anandamide promotes immune tolerance in the gut via CB2 receptors, and capsaicin triggers the same pathway, protecting mice from type 1 diabetes.
Teenage cannabinoid exposure changed how adult mice responded to cocaine withdrawal ↗
Adolescent cannabinoid exposure in mice altered cocaine withdrawal in adulthood, preventing anxiety but worsening depressive symptoms during cocaine cessation.
A mother's high-fat diet during pregnancy altered the endocannabinoid system in offspring fat tissue differently in males and females ↗
Rat pups born to mothers on high-fat diets developed early obesity with sex-specific alterations in cannabinoid receptor expression across different fat tissue types.
Scientists found a cannabinoid-inspired drug that controls muscle spasticity without causing sedation ↗
A cannabinoid-inspired compound (VSN16R) controlled spasticity in MS mice by opening neuronal potassium channels rather than through cannabinoid receptors, achieving a 1,000-fold therapeutic window without sedation.
Protracted withdrawal from THC, opiates, nicotine, and alcohol looked similar in mice, but cocaine withdrawal was strikingly different ↗
Protracted withdrawal from THC, morphine, nicotine, and alcohol produced similar behavioral and molecular patterns in mice, while cocaine withdrawal was strikingly opposite.
CB1 receptors in the brain's reward center are needed to learn that relief feels good ↗
CB1 receptors in the nucleus accumbens were essential for learning relief associations in rats but not for recalling them, revealing a role for cannabinoid signaling in emotional memory formation.
THC-induced anxiety in humans is linked to CB1 receptor density in the amygdala ↗
THC-induced anxiety in healthy men was directly correlated with CB1 receptor density in the amygdala, providing the first human evidence linking individual brain chemistry to vulnerability to cannabis anxiety.
Chronic cannabis users showed weakened brain connections between motivation centers, but they normalized after a month of abstinence ↗
Chronic cannabis users showed weakened brain connections between motivation centers and both frontal and visual processing areas, but these changes began normalizing after one month of abstinence.
A common pesticide disrupted the endocannabinoid system in developing rats' immune and metabolic organs ↗
Low-level pesticide exposure during development inhibited endocannabinoid enzymes in the liver, spleen, and brain of rat pups at doses below traditional neurotoxicity thresholds.
Three new synthetic cannabinoids caused seizures, aggression, and severe toxicity in mice at doses far lower than THC ↗
Three new synthetic cannabinoids showed nanomolar potency and caused seizures, aggression, and neurotoxicity in mice, confirming their much greater danger compared to natural cannabis.
A pesticide that disrupts the endocannabinoid system made developing rat pups less anxious ↗
Low-dose pesticide exposure during rat development elevated endocannabinoid levels and decreased anxiety-like behavior, even at doses below traditional neurotoxicity thresholds.
Hempseed extract improved memory and reduced brain aging markers in rats with accelerated aging ↗
Hemp seed extract improved memory and reduced brain aging markers in rats by boosting antioxidants, reducing inflammation, and decreasing Alzheimer's-related protein changes.
A new peripheral-only CB1 blocker reduced weight and improved insulin resistance in obese mice without affecting appetite ↗
Novel peripherally restricted CB1 blocker TXX-522 produced weight loss and improved insulin sensitivity in obese mice without affecting food intake or entering the brain.
Blocking CB1 receptors in the liver raised blood sugar by activating sympathetic nerves, a warning for obesity drug developers ↗
A potent CB1 blocker raised liver glucose production through sympathetic nerve activation, warning that strong CB1 inverse agonism in weight-loss drugs could worsen blood sugar control.
Comprehensive update on cannabis epidemiology, brain effects, and mental health risks ↗
Comprehensive review finding a disconnect between cannabis's "soft drug" reputation and growing evidence of cognitive impairment, psychosis risk, and gateway effects, particularly in youth.
Both CB1 blockade and CB2 activation reduced cocaine's rewarding and stimulant effects in rats ↗
Both CB1 blockade and CB2 activation independently reduced cocaine reward and motor stimulation in rats, revealing complementary cannabinoid-based strategies for addressing cocaine addiction.
Scientists created ultra-potent inhibitors of the enzyme that makes the brain's main endocannabinoid, affecting feeding behavior ↗
Ultra-potent DAGL inhibitors that block endocannabinoid production reduced feeding in fasting mice, but off-target effects of the chemical scaffold complicate interpretation.
Two drugs thought to only activate CB2 receptors were discovered to also block CB1, complicating past research ↗
Two widely used "selective CB2 agonists" were found to also block CB1 receptors, potentially invalidating conclusions from studies that assumed receptor selectivity.
Temporarily blocking CB2 receptors during vaccination boosted immune responses in both young and old mice ↗
Temporarily blocking CB2 cannabinoid receptors during vaccination boosted antibody responses in both young and aged mice, revealing the endocannabinoid system as a natural vaccine response suppressor.
A brain-derived peptide that modulates cannabinoid receptors reduced food intake in rats without causing weight loss ↗
A natural brain peptide that modulates CB1 cannabinoid receptors reduced food intake in rats but did not produce weight loss, possibly due to compensatory reduction in energy expenditure.
Computer modeling identified a natural compound as a potential drug for treating cannabis withdrawal ↗
Computational drug design identified stemphol as a potential CB1 receptor ligand for treating cannabis withdrawal, though no experimental validation has been performed.
The cannabinoid system interacts with toll-like receptor signaling in multiple sclerosis, revealing how Sativex might work ↗
Review revealing novel interplay between toll-like receptor immune signaling and the cannabinoid system in MS, potentially explaining how Sativex reduces inflammation and symptoms.
Blocking CB1 receptors in the stomach triggers release of a satiety hormone through a specific cellular pathway ↗
CB1 blockade in the stomach triggered release of the satiety hormone nesfatin-1 through the mTOR pathway, revealing a peripheral mechanism for cannabinoid-regulated appetite.
Synthetic cannabinoids produce their main effects through CB1 receptors, just like THC, according to quantitative pharmacological analysis ↗
Quantitative pharmacological analysis confirmed that five synthetic cannabinoids produce their core effects through CB1 receptors, just like THC, rather than through non-CB1 targets.
Boosting the Brain's Own Cannabis-Like Chemical Anandamide Reduced Panic-Like Behavior in Mice ↗
Mouse study showing that boosting anandamide (via FAAH inhibition) reduced panic-like flight responses while boosting 2-AG (via MAGL inhibition) increased them, revealing distinct roles for the two endocannabinoids.
How Sex Hormones Shape the Endocannabinoid System's Response to Alcohol Withdrawal ↗
Animal study revealing sex-specific endocannabinoid system responses to alcohol withdrawal, with males showing anxiety and neurochemical disruption while females were protected by ovarian hormones.
Synthetic "Spice" Cannabinoids Disrupted Brain Communication More Potently Than THC ↗
Brain slice study showing JWH-018 was 47 times more potent than THC at disrupting hippocampal synaptic transmission, with all synthetic cannabinoids tested impairing memory-related brain plasticity.
Oral Cannabis Impaired Memory and Damaged Brain Structures in Rats ↗
Rat study showing 7 days of oral cannabis impaired spatial memory, increased anxiety-like behavior, and caused visible neuronal damage in the cortex and hippocampus.
Scientists Designed a New Drug That Blocks CB1 Receptors Without Entering the Brain to Treat Liver Fibrosis ↗
Medicinal chemistry study creating novel brain-excluded compounds that block CB1 receptors and inhibit iNOS, showing antifibrotic effects in animal models of liver disease.
What We Know About the Behavioral Effects and Risks of Synthetic Cannabinoids ("Spice") ↗
Review consolidating behavioral research on synthetic cannabinoids, finding evidence for abuse potential, tolerance, dependence, and toxicity that often exceeds THC, with significant knowledge gaps remaining.
ADHD and Cannabis Have Separate Effects on Brain Connectivity in Young Adults ↗
Brain imaging study of 75 young adults finding that childhood ADHD and current cannabis use affect separate brain networks, with no evidence that cannabis worsens ADHD-related connectivity changes.
A Drug That Boosts Anandamide and Blocks TRPV1 Showed Antidepressant Effects in Rats ↗
Rat study showing a dual FAAH inhibitor/TRPV1 blocker produced antidepressant effects at a specific dose by enhancing anandamide signaling through CB1 receptors while blocking the opposing TRPV1 pathway.
Heavy Cannabis Use Did Not Shrink the Hippocampus in Young Adults Over 3 Years ↗
Longitudinal study following 20 heavy cannabis users and 23 controls for 39 months, finding no hippocampal volume differences or divergent growth trajectories, regardless of dose or age of onset.
CBD Acts on Two Newly Discovered Brain Receptors Linked to Alzheimer's and Parkinson's ↗
First study identifying GPR3 and GPR6 as novel molecular targets for CBD, with potential implications for Alzheimer's and Parkinson's disease treatment through mechanisms distinct from classical cannabinoid receptors.
Blocking CB1 Receptors Reversed Antipsychotic-Induced Weight Gain Without Reducing Drug Efficacy ↗
Rat study showing CB1 receptor antagonists reversed olanzapine-induced weight gain, metabolic disruption, and liver changes without reducing the antipsychotic's behavioral effectiveness.
How Synthetic Cannabinoids Differ From Natural Cannabis: Stronger Effects, Greater Risks ↗
Review explaining that synthetic cannabinoids are full agonists with higher binding affinity than THC (a partial agonist), producing more intense effects and more severe neurological and cardiovascular complications.
The Most Common Blood Protein May Control How Cannabinoid Drugs Work in Your Body ↗
Computational study showing human serum albumin binds multiple cannabinoid drugs with strong affinity, suggesting this abundant blood protein is a key factor in cannabinoid pharmacokinetics and dosing.
Two Peptides From the Endocannabinoid System Had Opposite Effects on Anxiety and Depression in Rats ↗
Rat study showing two hemoglobin-derived peptides had opposite effects on the endocannabinoid system: hemopressin caused anxiety and depression-like behavior while RVD-hemopressin produced anti-anxiety and antidepressant effects.
The Brain's Cannabis System Changes Differently During Morphine Addiction Versus Relapse ↗
Mouse study showing the endocannabinoid system in the hippocampus undergoes opposite changes during morphine reward (increased endocannabinoid breakdown) versus relapse (increased CB1 receptor expression).
Escalating Teen Cannabis Use Was Linked to Altered Brain Reward Circuits and Worse Outcomes at 22 ↗
Longitudinal study of 158 young men finding escalating adolescent cannabis use disrupted reward-prefrontal brain connectivity, predicting more depression, anhedonia, and lower education at age 22.
How the Brain's Endocannabinoid System Controls Anxiety: A Comprehensive Guide ↗
Comprehensive review of how endocannabinoids modulate anxiety through multiple brain regions, receptors, and mechanisms, explaining why cannabis can both reduce and increase anxiety depending on context.
How Cannabinoid Signaling Works Throughout the Body: An Overview ↗
Overview of the endocannabinoid system's roles across physiological processes including emerging cardioprotective potential, noting that psychoactive side effects and incomplete mechanistic understanding limit therapeutic development.
Where Cannabinoid Medicine Stands After Five Years of THC/CBD Spray Use ↗
Expert review confirming THC/CBD spray efficacy for MS spasticity after five years of clinical use and cataloging expanding research into cannabinoids for pain, Alzheimer's, Parkinson's, Huntington's, and epilepsy.
Brain Mapping Shows How THC Activates Specific Neural Systems in Awake Rats ↗
First fMRI study of THC effects in awake rats showing low-dose THC produced distinct activation patterns in cannabinoid-rich regions, pain circuits, and hippocampal networks.
Functional Selectivity: How Different Cannabinoid Drugs Can Activate Different Pathways Through the Same Receptor ↗
Review explaining how different cannabinoid drugs activate different signaling pathways through the same receptor (functional selectivity), offering a path to safer cannabinoid medicines with fewer side effects.
Evidence That Cannabis Damages the Brain, Especially White Matter ↗
Critical review plus fatal case report finding strong evidence that chronic cannabis use damages brain white matter and impairs cognition, with few objective data supporting cannabis over conventional therapies for neurological conditions.
Why Some People May Be Vulnerable to Suicidal Effects of CB1 Blockers ↗
Rat study showing CB1 inverse agonists produce impulsivity only when serotonin is disrupted, explaining why rimonabant caused suicidal behavior in a vulnerable subpopulation and suggesting neutral antagonists are safer.
How Cannabis and Alcohol Affect the Developing Adolescent Brain ↗
Review of neuroimaging evidence showing cannabis and alcohol alter adolescent brain development, with most cognitive effects resolving after abstinence but attentional deficits persisting.
CBD Reduced Brain Damage and Promoted Recovery After Stroke in Mice ↗
Mouse study showing CBD prevented cognitive and emotional deficits after brain ischemia by reducing inflammation, preventing neuron death, increasing BDNF, and stimulating new brain cell growth.
Could the Endocannabinoid System Influence Your Dreams? ↗
Review proposing that the endocannabinoid system influences dream activity, supported by its known roles in consciousness, emotion, and sleep, and by preliminary evidence of cannabinoid-related nightmare reduction in PTSD.
A Compound That Boosts Anandamide and Blocks TRPV1 Promoted Sleep in Rats ↗
Rat study showing AA-5-HT (dual FAAH/TRPV1 blocker) promoted sleep during active periods, restored sleep after deprivation, and blocked the wake-promoting effects of CBD and modafinil.
Blocking the Enzyme That Breaks Down 2-AG Produces Cannabis-Like Subjective Effects in Mice ↗
Mouse study showing MAGL inhibition (boosting 2-AG) produces cannabis-like subjective effects through CB1 receptors, while FAAH inhibition (boosting anandamide) does not, revealing MAGL as a "brake" preventing endocannabinoid intoxication.
Caffeine and Cannabis Both Alter Brain Chemistry in Young Rats, but in Different Ways ↗
Animal study found that both caffeine and cannabis altered neurotransmitter and enzyme levels in juvenile rat brains, with their combination producing amplified metabolic effects.
The Endocannabinoid System Helps Regulate Uterine Contractions, and Its Activity Shifts Across the Menstrual Cycle ↗
Mouse study found that endocannabinoid levels in the uterus fluctuate across the reproductive cycle, and cannabinoid receptor activation selectively reduces spontaneous uterine contractions.
Boosting 2-AG (but Not Anandamide) Protected Dopamine Neurons in a Mouse Model of Parkinson's Disease ↗
Mouse study found that boosting the endocannabinoid 2-AG through MAGL inhibition protected dopamine neurons in a Parkinson's model, while boosting anandamide through FAAH inhibition did not.
The CB1 Blocker Rimonabant Slowed Colon Cancer Growth by Disrupting a Key Cancer-Promoting Pathway ↗
Lab and animal study found that the CB1 receptor blocker rimonabant inhibited a major cancer-promoting pathway and reduced colon cancer tumor growth in mice.
Cannabis Has Opposite Effects on Brain Signal Processing in Schizophrenia Patients Versus Healthy People ↗
Study found cannabis had opposite effects on brain signal filtering in schizophrenia (improved) versus healthy people (impaired), suggesting fundamental endocannabinoid system differences.
A Compound from Black Pepper Reduces Inflammation and Pain by Boosting the Body's Own Cannabinoids ↗
Mouse study found that guineensine from black pepper produced potent anti-inflammatory and pain-relieving effects by blocking endocannabinoid reuptake, with effects partially mediated through CB1 receptors.
Cannabinoids in Animal Models of Epilepsy: CBD and CBDV Show Consistent Benefits, but THC's Effects Are Complex ↗
Comprehensive review finding that CBD and CBDV consistently reduce seizures in animal models, while THC-like CB1 agonists show complex, context-dependent effects that can be either anti- or pro-seizure.
CBD Disrupted Fear Memory Consolidation in Rats, but Only When Given at a Specific Time Window After Learning ↗
Rat study found CBD disrupted fear memory consolidation when injected into the prefrontal cortex 5 hours (but not immediately) after fear learning, reducing dopamine activity and memory gene expression.
Cannabis Pharmacology Beyond THC and CBD: How Terpenes and Lesser-Known Compounds Contribute to the Plant's Effects ↗
Major pharmacology review arguing that cannabis's therapeutic potential involves far more than THC and CBD, with terpenes and lesser-known compounds providing meaningful synergistic pharmacological activity.
CB1 Cannabinoid Receptors Drive the Memory Problems That Occur During Nicotine Withdrawal ↗
Mouse study found that memory problems during nicotine withdrawal are driven by increased endocannabinoid (2-AG) signaling through CB1 receptors on inhibitory neurons, with associated loss of dendritic spines.
Cannabis Withdrawal Is Real, Driven by CB1 Receptor Changes, and May Be Worse for Women ↗
Review of cannabis withdrawal neurobiology finding CB1 receptor downregulation drives withdrawal symptoms, recovery occurs with abstinence, and women may experience faster and more severe symptoms.
The Endocannabinoid System Controls Metabolism Throughout the Body, Not Just Appetite in the Brain ↗
Review revealing that the endocannabinoid system regulates metabolism throughout the body via peripheral CB1 receptors, opening new treatment avenues after rimonabant's psychiatric side effects ended its use.
THC at High Concentrations Disrupted Developing Human Neurons in the Lab, While Low Doses Had Minimal Effects ↗
Lab study using human-derived neurons found high-dose THC (10 micromolar) disrupted neuronal function during dopaminergic development, while low doses had minimal effects.
CBD Disrupted Both Specific and Generalized Fear Memories Through Cannabinoid Receptors in the Hippocampus ↗
Rat study showing CBD disrupted both specific and generalized fear memory consolidation through anandamide-mediated CB1 and CB2 receptor activation in the dorsal hippocampus.
The Endocannabinoid System Both Suppresses Reproductive Hormones During Infection and Helps Control the Resulting Inflammation ↗
Rat study revealing that endocannabinoids mediate the suppression of reproductive hormones during immune activation through hypothalamic CB1 receptors, while also helping control inflammation.
Medical Cannabis for Brain Disorders: Benefits for Some Conditions, Clear Risks for Schizophrenia and Bipolar Disorder ↗
Review finding cannabis showed benefits for MS, Parkinson's, ALS, and late-stage Alzheimer's, but increased positive symptoms in schizophrenia and worsened bipolar disorder.
CBD Modestly Reduced Some of THC's Behavioral Effects but Produced Unexpected Epigenetic Brain Changes When Given Together Long-Term ↗
Mouse study found CBD modestly reduced some THC behavioral effects but their combination produced unexpected epigenetic changes in the brain's reward pathway not seen with either compound alone.
A Sativex-Like THC+CBD Combination Partially Protected Against Brain Deterioration in a Mouse Model of Huntington's Disease ↗
Mouse study of Huntington's disease found a Sativex-like THC+CBD combination reduced dystonia and partially reversed metabolic brain changes, though motor coordination did not improve.
All Traditional CB1 Receptor Blockers Caused Anxiety-Like Side Effects in Rats, and "Next-Gen" Alternatives Performed Poorly ↗
Head-to-head comparison found all classical CB1 blockers reduced weight but caused anxiety, while next-generation alternatives either caused convulsions or had no activity.
A Drug That Boosts Both Endocannabinoids Enhanced Morphine's Pain Relief and Reduced Heroin-Seeking Behavior in Mice ↗
Mouse study found a dual endocannabinoid-boosting compound reduced pain, enhanced morphine's effects at low doses, and decreased heroin-seeking behavior.
Blocking CB1 Receptors in a Specific Brain Stress Region Prevented the Misery of Opioid Withdrawal in Rats ↗
Rat study found that blocking CB1 receptors in the BNST (a brain stress region) prevented the aversive experience of opioid withdrawal, while boosting 2-AG in the same region did not.
Regular cannabis users showed impaired ability to regulate negative emotions in brain scans ↗
Brain imaging showed regular cannabis users had impaired ability to downregulate negative emotions, with disrupted amygdala-prefrontal cortex communication during regulation tasks.
Psychotic patients who used cannabis as teens had less brain damage than those who did not ↗
Psychotic patients with adolescent cannabis use showed less gray matter loss than those without, suggesting cannabis-associated psychosis may be a distinct subtype with less underlying brain pathology.
Zebrafish larvae absorbed THC and CBD differently and showed distinct behavioral responses to each ↗
Zebrafish larvae metabolized THC and CBD similarly to mammals, with each producing distinct behavioral patterns and their combination altering both absorption and behavior.
Omega-3 fatty acids produce endocannabinoid-like compounds that preferentially activate anti-inflammatory CB2 receptors ↗
Omega-3 derived endocannabinoid-like molecules selectively activated anti-inflammatory CB2 receptors without activating psychoactive CB1, connecting dietary fats to endocannabinoid signaling.
A CB1 receptor blocker that avoided psychiatric side effects reduced binge drinking in mice ↗
A novel CB1 neutral antagonist reduced binge alcohol drinking and dopamine reward signaling in mice without the psychiatric side effects of previous CB1 blockers.
Genetic variations in dopamine genes interacted with early cannabis use to alter hippocampal brain structure ↗
Brain imaging of 59 young men found early cannabis use altered hippocampal subregion volumes, with effects modified by the DAT1 dopamine transporter gene variant.
People who get psychotic symptoms from THC already have different hippocampal brain activity at baseline ↗
People who got psychotic symptoms from THC already had higher hippocampal brain activity during learning under placebo, suggesting a pre-existing neural marker of vulnerability.
The endocannabinoid system shows promise for bladder pain but faces challenges in clinical translation ↗
Review finds strong preclinical evidence for endocannabinoid-based bladder pain treatment but identifies pharmacological challenges including TRPV1 activation and complex enzyme interactions.
Brain scans reveal different patterns of altered function in adult versus adolescent cannabis users ↗
Meta-analysis of 20 fMRI studies found cannabis users show altered brain activation patterns, with different changes in adults (temporal/frontal regions) versus adolescents (parietal/putamen).
The CB1 cannabinoid receptor plays a role in how the tongue detects dietary fat ↗
Mice lacking CB1 cannabinoid receptors showed reduced fat taste preference, with impaired calcium signaling in taste bud cells and lower GLP-1 hormone levels.
THC impairs short-term memory through a specific protein signaling pathway in the hippocampus ↗
THC impairs short-term memory through hippocampal PKC signaling and long-term memory through a separate mTOR pathway, with PKC blockers fully preventing the short-term memory deficit.
A schizophrenia risk gene did not alter the developmental trajectory of the brain's endocannabinoid system in mice ↗
Mice with a schizophrenia risk gene showed normal endocannabinoid system development across 8 time points, suggesting their heightened cannabis sensitivity operates through other mechanisms.
The endocannabinoid system in MS could address both symptoms and disease progression ↗
Comprehensive review finds clinical evidence for cannabinoids managing MS symptoms (spasticity, pain) and preclinical evidence for neuroprotective effects that could slow disease progression.
People who had used cannabis before were less affected by THC than those who had never tried it ↗
THC challenge study found never-users experienced more psychotic symptoms and brain disruption than modest prior users, suggesting even limited cannabis exposure creates tolerance-like neuroadaptation.
Even modest previous cannabis use blunted THC's effects on psychosis symptoms and brain function ↗
THC challenge study found modest prior cannabis users had worse baseline cognition but were protected from THC's psychotic effects, showing tolerance from even limited exposure.
Brain damage from adolescent THC exposure in female rats was reversed by boosting the body's own endocannabinoids ↗
Boosting endocannabinoid levels with a FAAH inhibitor reversed depressive behavior, restored synaptic plasticity, and rescued neurogenesis damaged by adolescent THC in female rats.
CBD reversed mitochondrial damage from iron accumulation in a model of neurodegeneration ↗
CBD rescued mitochondrial damage from iron accumulation in rat brains, restoring ferritin levels, epigenetic regulation, and enzyme activity, supporting its neuroprotective potential.
Cannabinoids affect the brain's glial cells in ways that may be relevant to schizophrenia ↗
Review links cannabinoid receptor activity in glial cells to schizophrenia pathology, suggesting these brain support cells could be a new therapeutic target via the endocannabinoid system.
Comprehensive review of endocannabinoid system targets for treating inflammatory and neuropathic pain ↗
Major review found endocannabinoid system targets produce reliable pain relief in preclinical models with opioid-sparing potential, though clinical translation for enzyme inhibitors lags behind.
Comprehensive review of approved and emerging medical uses of cannabinoids across multiple conditions ↗
Comprehensive review cataloged six approved cannabinoid medications and evidence across pain, epilepsy, cancer, neurodegeneration, PTSD, anxiety, and addiction, spanning the full endocannabinoid system.
Cannabis dampened the brain's reward response to music, but CBD offset this effect ↗
Crossover fMRI study found cannabis dampened the brain's reward response to music in the ventral striatum and other regions, but CBD restored normal connectivity and responses.
Cannabis users had specific gene variants and altered DNA methylation patterns compared to non-users ↗
Case-control study found a CB1 receptor gene variant associated with cannabis use and higher DNA methylation at dopamine receptor genes in users, plus protective effects of education and female sex.
A single dose of CBD increased connectivity between frontal cortex and striatum in healthy volunteers ↗
Crossover fMRI study found 600mg CBD enhanced fronto-striatal brain connectivity in 16 healthy males, offering a potential neural mechanism for its antipsychotic properties.
THC exposure dampened human neuron gene activity in ways resembling patterns seen in schizophrenia ↗
THC exposure dampened human neuron gene responses to stimulation, with changes in synaptic and glutamate pathways overlapping schizophrenia, autism, and intellectual disability gene patterns.
Cannabis use showed limited brain structural changes in schizophrenia and bipolar patients, except for those who started before illness onset ↗
MRI study of 314 schizophrenia/bipolar patients found cannabis use associated with limited brain structural changes, except for cortical thinning in frontal regions among those who started using before illness onset.
Chronic THC exposure in adolescent mice triggered pro-psychotic changes in serotonin receptor signaling ↗
Mouse study found chronic THC rewired serotonin receptors toward a pro-psychotic signaling pattern via the Akt/mTOR pathway. Rapamycin blocked the effect.
Adolescent brain surface area changes after starting alcohol and cannabis differed from alcohol-only users ↗
Longitudinal study of 69 youth found alcohol-only users showed greater brain surface area decreases in the orbitofrontal cortex than those who used both alcohol and cannabis.
Chronic THC impaired working memory in monkeys but did not change dopamine D2/D3 receptor levels ↗
Rhesus monkeys given daily THC for 12 weeks showed persistent working memory deficits (but not other cognitive domains) that recovered within 2 weeks of stopping. Dopamine D2/D3 receptors were unaffected.
Brain volume loss in polysubstance users was linked to total number of substances, not cannabis specifically ↗
Study of 169 men found brain volume loss in the prefrontal cortex was linked to total number of substances used, not any single drug. Cannabis showed no independent effect after controlling for polysubstance use.
Researchers selectively bred mice for THC sensitivity, finding the trait was heritable and linked to anxiety ↗
Selective breeding study found adolescent THC sensitivity in mice was heritable and genetically linked to anxiety-like behavior, pointing to shared genetic factors between cannabis response and anxiety.
Chronic synthetic cannabinoid users showed reduced brain volume and impaired working memory neural activity ↗
First neuroimaging study of synthetic cannabinoid users found reduced gray matter volume across multiple brain regions and impaired neural activity during working memory tasks.
Chronic THC in male mice did not harm sperm function, fertility, or embryo development, contradicting prior assumptions ↗
Mouse study found 30 days of daily THC did not affect sperm function, testicular structure, IVF outcomes, or DNA methylation, contradicting prior assumptions about THC harming male fertility.
Cannabis use disorder altered brain connectivity between prefrontal cortex and striatum during working memory tasks ↗
fMRI study found cannabis use disorder participants showed altered prefrontal-striatal brain connectivity during working memory, with compensatory increases in some pathways offsetting decreases in others.
Cannabis users with high distress intolerance showed enhanced rather than impaired brain conflict-monitoring under stress ↗
EEG study found cannabis users with high distress intolerance showed enhanced brain conflict-monitoring under stress, which was linked to fewer cannabis problems, challenging the stress-impairment model of addiction.
Clozapine reduced cannabis craving and brain cue reactivity more than risperidone in patients with schizophrenia ↗
Randomized study found clozapine reduced cannabis craving and amygdala cue reactivity significantly more than risperidone in schizophrenia patients with cannabis use disorder.
Cannabis-dependent individuals showed hyperconnectivity in dopamine-related brain regions, especially those who started youngest ↗
Human Connectome Project analysis found cannabis-dependent individuals had hyperconnectivity in dopamine-related brain regions (striatum, midbrain), most pronounced in those who started youngest and reported high negative emotionality.
THC lowered eye pressure by 28% in male mice, but CBD counteracted this effect and showed sex-dependent differences ↗
THC lowered mouse eye pressure by 28% via CB1 and GPR18 receptors, with stronger effects in males. CBD had opposing effects on eye pressure and blocked THC's beneficial IOP reduction.
Cannabis use altered DNA methylation in human and rat sperm, with changes in cancer and developmental pathways ↗
Cannabis use altered DNA methylation at nearly 4,000 sites in human sperm, affecting Hippo Signaling and cancer pathways. Same pathways were affected in THC-exposed rat sperm, and changes overlapped with offspring brain methylation.
Adolescent THC Exposure Changed Gene Activity in Rat Brains Through Epigenetic Modifications ↗
THC during adolescence caused epigenetic changes in rat brains that altered gene activity and led to cognitive deficits - effects not seen with adult exposure. Blocking the changes prevented cognitive harm.
Cannabis and Alcohol History Did Not Make Brain Shrinkage Worse in Schizophrenia Patients ↗
Brain imaging found that schizophrenia-related gray matter reductions were the same whether patients had a history of cannabis/alcohol use or not.
Boosting a Natural Brain Cannabinoid Enhanced Fear Memory Through CB2 Receptors in Rats ↗
Boosting the brain's natural cannabinoid 2-AG enhanced fear memory in rats through CB2 receptors and mTOR suppression in the hippocampus - a previously unrecognized pathway.
How Adolescent THC Exposure May Disrupt the Brain's Inhibitory System and Increase Psychosis Risk ↗
Review of preclinical evidence explains how adolescent THC exposure may disrupt the brain's inhibitory GABA system in the prefrontal cortex, potentially triggering schizophrenia-like dopamine dysregulation.
Why Hot Showers and Capsaicin Cream Relieve Cannabinoid Hyperemesis Symptoms ↗
Review of 137 studies explains that hot showers and capsaicin likely relieve CHS symptoms by activating TRPV1 receptors, which share extensive cross-talk with the endocannabinoid system.
Cannabis Compounds Show Promise Against Five Currently Untreatable Brain Diseases ↗
Review argues cannabis compounds (THC, CBD, THCA, CBDA, terpenes) show promise for five currently hard-to-treat neurological conditions including Parkinson, Alzheimer, and brain tumors.
Cannabinoids Significantly Reduced Dystonia in Seven Huntington's Disease Patients ↗
Seven early-onset Huntington's disease patients showed significant improvement in motor symptoms after cannabinoid treatment, with dystonia scores dropping by 35% and additional benefits in gait, behavior, and weight.
Comprehensive Review Finds Cannabis-Using Psychosis Patients May Be Neurobiologically Different ↗
Systematic review of 70 studies (3,000+ patients) found evidence that cannabis-using psychosis patients may have distinct neurobiological profiles from non-using patients, supporting the need for tailored treatments.
Alcohol Dependence Disrupted the Brain's Natural Cannabinoid System in the Amygdala ↗
Alcohol-dependent animals had depleted endocannabinoid (2-AG) levels in the amygdala, linked to anxiety and excessive drinking. Drugs that boosted 2-AG reversed both effects.
Cannabinoid and Glutamate Systems May Jointly Disrupt Brain Oscillations in Psychosis ↗
Review argues that cannabinoid and glutamate systems converge on disrupted GABA interneuron function, unifying two major models of schizophrenia through their shared effects on theta and gamma brain oscillations.
THC Disrupted the Brain's Ability to Filter Sensory Information in Both Humans and Rats ↗
Translational study in humans and rats showed THC disrupts sensory gating through CB1 receptors by altering theta-band brain oscillations, with CBD failing to prevent these effects.
Cannabis Leaves an Epigenetic "Molecular Memory" That Can Persist Across Generations ↗
Review reveals that cannabis exposure during development can create lasting epigenetic changes - modifications to gene expression that persist across the lifespan and have been observed transmitting to the next generation.
Earlier Cannabis Use Was Linked to Slower Reaction Times in Adulthood Through Brain Encoding Changes ↗
Adults who started cannabis earlier had slower reaction times at 28 due to reduced brain encoding activation, but the same pattern appeared after single use, suggesting pre-existing differences rather than drug-caused damage.
Brain Differences Linked to Cannabis Use Actually Existed Before Teens Ever Tried Cannabis ↗
Prospective brain imaging found that neurocognitive differences attributed to early cannabis use actually existed at age 12, before any cannabis use began, supporting a pre-existing risk model.
New Tests Revealed THC Withdrawal in Mice Goes Beyond Physical Symptoms ↗
New mouse behavioral tests showed THC withdrawal includes mood and stress-related symptoms beyond physical signs, with boosting endocannabinoid levels partially reversing withdrawal effects.
Cannabis Actually Normalized Brain Network Connectivity in Schizophrenia Patients ↗
Pilot fMRI found schizophrenia patients had abnormal brain network connectivity that actually normalized after cannabinoid administration, correlating with improved working memory performance.
Brain Imaging Meta-Analysis Found Cannabis Users Have Reduced Cognitive Control and Increased Reward Activity ↗
Neuroimaging meta-analysis found cannabis users consistently show decreased activation in cognitive control regions (ACC, DLPFC) and increased activation in reward regions (striatum).
Brain Changes in Marijuana Users Persisted After 28 Days Without Using ↗
Brain imaging found altered emotional processing circuits in marijuana users that persisted after 28+ days of abstinence, specifically during negative emotions, potentially explaining vulnerability to relapse.
Adolescent THC Exposure Delayed Learning Ability in Adult Rats, but Effects Faded Over Time ↗
Rats given escalating THC during adolescence showed learning delays and sensorimotor gating impairments as adults, but both deficits appeared to diminish over time, suggesting partial neural recovery.
Cannabis smoke triggers many of the same harmful changes in airway cells as tobacco smoke ↗
Lab study found cannabis smoke triggered DNA damage, impaired immune defenses, and caused inflammatory responses in human airway cells strikingly similar to tobacco smoke.
THC plus CBD together reduced MS-like brain inflammation in mice through changes in immune cell gene activity ↗
In a mouse MS model, THC plus CBD together (but not alone) reduced paralysis and brain inflammation by suppressing inflammatory immune cells and altering microRNA gene regulation.
THC plus CBD reduced MS-like symptoms in mice by reshaping gut bacteria ↗
THC+CBD reduced MS-like symptoms in mice partly by reshaping gut bacteria, as confirmed by fecal transplant experiments showing the microbiome changes were causally involved in the therapeutic effect.
CBD helped songbirds recover their learned songs faster after brain injury ↗
CBD helped zebra finches recover their learned songs faster after targeted brain lesions, with higher doses reducing both the severity and duration of vocal impairment.
Teens on synthetic cannabinoids were far more likely to have coma and seizures than those using regular cannabis ↗
Adolescents in the ED after synthetic cannabinoid use had 3.4x higher odds of coma and 3.9x higher odds of seizures than those using traditional cannabis, showing a distinct and more dangerous toxicity profile.
Could the endocannabinoid system hold clues for treating bipolar disorder? ↗
A review found the endocannabinoid system may contribute to bipolar disorder pathophysiology, with CB2 receptor activation emerging as a potential mood-stabilizing target, though evidence remains limited.
Cannabinoids show promise for Tourette syndrome but rigorous evidence is nearly nonexistent ↗
A systematic review found strong biological rationale and patient reports supporting cannabinoids for Tourette syndrome, but only two small trials exist, leaving efficacy and safety largely undetermined.
A comprehensive profile of THC: from ancient medicine to modern controversy ↗
A comprehensive review of THC covers its pharmacology as a CB1 partial agonist, approved uses for pain and nausea, and ongoing debates about psychosis risk, cognitive effects, and addiction potential in 192 million users worldwide.
How the endocannabinoid system influences alcohol addiction and fetal alcohol disorders ↗
A comprehensive review details how alcohol alters the endocannabinoid system to drive addiction, how CB1 receptors contribute to alcohol reward, and how ECS disruption contributes to fetal alcohol spectrum disorders.
Distinct endocannabinoid system functions in alcohol addiction and fetal alcohol effects ↗
A review distinguishes the endocannabinoid system's role in alcohol addiction (CB1 in reward circuits) from its role in fetal alcohol disorders (developmental ECS disruption), suggesting different therapeutic targets.
The synthetic cannabinoid AKB48 stimulated reward pathways at low doses and caused dangerous effects at high doses in rats ↗
AKB48 stimulated dopamine reward pathways at low doses but caused hypothermia, catalepsy, and cardiac depression at higher doses, with all effects mediated through CB1 receptors.
Teen cannabis use disorder was linked to dulled brain responses to threatening situations ↗
An fMRI study found adolescent cannabis use disorder was linked to reduced brain activation in threat-processing regions including the amygdala, an effect not seen with alcohol use disorder.
Brain function changes from cannabis use persisted in teens even after a month of abstinence ↗
A meta-analysis found altered brain network function in teen cannabis users even after 25+ days of abstinence, when cognitive test performance had already recovered.
Chronic cannabis use consistently alters cerebellum structure and function, affecting memory and decision-making ↗
A review of 40 studies found chronic cannabis use consistently increases cerebellar gray matter volume, alters resting brain activity, and impairs memory and decision-making.
A comprehensive review of human brain imaging reveals how cannabis affects executive function, emotion, memory, and reward ↗
A comprehensive neuroimaging review found cannabis affects executive, emotional, reward, and memory brain systems through direct and indirect pathways, with adolescent use carrying particular risk for lasting changes.
THC boosted brain activity in attention networks, and a common gene variant influenced the effect ↗
THC increased brain activity in attention and salience networks, with the COMT gene variant determining how executive networks responded, linking dopamine genetics to cannabis susceptibility.
Adolescent cannabis or THC exposure in rats did not produce lasting anxiety, depression, or cognitive effects in adulthood ↗
Adolescent cannabis smoke and THC exposure in rats produced no lasting anxiety, depression, or cognitive effects in adulthood, suggesting human associations may involve non-cannabinoid factors.
Decades of research show cannabis affects brain structure and cognition, raising questions for medical use ↗
A review found substantial evidence that cannabis affects brain structure and cognition, particularly during adolescence, while paradoxically some cannabinoid compounds are approved for medical use in children.
Only cannabis-dependent users, not regular users, showed smaller hippocampi in a large multi-site study ↗
A large multi-site study found only cannabis-dependent users, not regular non-dependent users, showed smaller hippocampi, regardless of dose, suggesting dependence involves unique brain changes.
Cannabis modulates six major brain neurotransmitter systems, with profound implications for mental health ↗
A review found cannabinoid receptors modulate dopamine, serotonin, noradrenaline, GABA, glutamate, and opioid systems, explaining the broad spectrum of cannabis effects on mental health.
Adolescent synthetic cannabinoid users showed thinner brain cortex, especially those with ADHD ↗
Adolescent synthetic cannabinoid users had thinner frontal cortex than controls, with ADHD comorbidity producing additional brain changes, suggesting interactive effects on the developing brain.
Combining a cannabinoid with a serotonin drug synergistically prevented seizures in rats ↗
A cannabinoid and serotonin drug synergistically prevented seizures in rats when combined, though neither worked alone, revealing a novel CB1/5-HT2B anti-seizure interaction.
A single low dose of IV THC caused symptoms in 94% of healthy volunteers, with women experiencing more negative effects ↗
A controlled study found a single low IV dose of THC caused symptoms in 94% of healthy volunteers, with women experiencing significantly more negative effects and all physical reactions.
Cannabis-using youth showed weaker brain circuit activation when trying to resolve mental conflicts ↗
Cannabis-using youth showed weaker frontostriatal brain circuit activation during cognitive conflict tasks, suggesting self-regulation circuit changes appear early in the course of cannabis use.
THC blocks nausea signals by activating CB1 receptors in the brain ↗
Animal study showing THC and synthetic cannabinoids suppress substance P-induced vomiting through CB1 receptor activation, helping explain why cannabinoids work against nausea resistant to standard treatments.
Can CBD work as a new kind of antipsychotic? ↗
Review of evidence suggesting CBD has antipsychotic properties through a unique non-dopamine mechanism, potentially offering a new treatment class for psychotic disorders with fewer side effects.
How alcohol and cannabis together change gene activity at different life stages ↗
Review exploring how combined alcohol and cannabis exposure alters gene activity through epigenetic mechanisms across different life stages, with potential for lasting and even intergenerational effects.
Cannabinoid exposure during pregnancy may weaken the developing immune system through epigenetic changes ↗
Review showing cannabinoids cross the placenta and may impair fetal immune development through cytokine disruption, lymphoid cell death, and epigenetic changes with potentially lifelong consequences.
Boosting endocannabinoids in tissue reduced heightened pain in a depression mouse model ↗
Mouse study shows depression-induced pain amplification involves changes in brain endocannabinoid levels, and locally boosting endocannabinoids reduced the heightened pain response only in depressed animals.
Lancet review finds strong evidence for CBD in severe epilepsy but not for other neurological disorders ↗
Lancet Neurology review finds strong RCT evidence for CBD in severe childhood epilepsies and some cannabis treatments for MS, but no demonstrated benefit for Huntington's, ADHD, or dementia.
Cannabinoid-based medications show promise for treating addiction to other substances ↗
Review of cannabinoid-based addiction treatments finds promising newer strategies including neutral CB1 antagonists, CB2 agonists, and CBD after the rimonabant setback, with some entering clinical trials.
Blocking CB1 receptors in the gut reduces alcohol drinking through a ghrelin-hunger hormone pathway ↗
Mouse study reveals a peripheral CB1 blocker reduces alcohol drinking by suppressing active ghrelin production in the stomach, working through gut-to-brain vagal nerve signaling without entering the brain.
Adolescent cannabis users may have more cognitive problems than adult users, but the picture is complex ↗
Systematic review comparing adolescent and adult cannabis users suggests teens may be more vulnerable to executive function deficits, especially heavy users, but these effects may reverse with sustained abstinence.
Cannabinoid anticonvulsant effects partly work through ATP-sensitive potassium channels ↗
Mouse study reveals cannabinoid receptor activation raises seizure thresholds partly by reducing hippocampal ATP and opening ATP-sensitive potassium channels, adding a new mechanism to cannabinoid anticonvulsant effects.
Boosting endocannabinoids in the hippocampus prevented both cardiovascular and anxiety responses to stress in rats ↗
Rat study shows boosting endocannabinoids in the hippocampus prevented both the immediate cardiovascular stress response and delayed anxiety 24 hours later, both through CB1 receptor signaling.
A neutral CB1 blocker reduced heroin use in rats without causing depression-like side effects ↗
Rat study shows the neutral CB1 antagonist AM4113 reduces heroin self-administration without the depression-like side effects that derailed rimonabant, pointing toward a safer cannabinoid-based opioid addiction treatment.
Cannabis from ancient medicine to modern concern: the developing brain is most at risk ↗
Review for fetal/neonatal specialists covers how the endocannabinoid system guides brain development and why exogenous cannabinoids during pregnancy, infancy, or adolescence can disrupt normal neural development.
CBD blocks THC's psychosis-like effects in the brain by reversing a specific molecular signaling pathway ↗
Rat study identifies ERK1-2 phosphorylation in the hippocampus as the molecular mechanism by which THC causes psychosis-like dopamine dysregulation and CBD reverses it.
Paternal cannabinoid exposure altered sperm epigenetics and impaired offspring growth in mice ↗
Mouse study shows paternal cannabinoid (CB2) exposure alters sperm DNA methylation and reduces offspring growth through epigenetic changes transmitted in sperm to the placenta.
Adolescent cannabinoid exposure left lasting marks on reward processing in the adult prefrontal cortex of rats ↗
Rat study shows adolescent cannabinoid exposure produces lasting reductions in prefrontal cortex activity during reward processing in adulthood, suggesting disrupted brain maturation.
Chronic cannabis use downregulates CB1 receptors, which may mirror changes seen in psychosis ↗
First systematic review of cannabis effects on the endocannabinoid system finds chronic use downregulates CB1 receptors in a pattern that may overlap with changes observed in psychosis.
Recency and frequency of teen cannabis use matter most for brain health, but preexisting differences also play a role ↗
Prospective neuroimaging studies find recency, frequency, and age of onset of teen cannabis use predict brain health outcomes, with preexisting brain differences also contributing to vulnerability.
CBD reduced diabetic nerve pain in rats through serotonin receptors, not cannabinoid receptors ↗
Rat study shows CBD reduces diabetic nerve pain through spinal cord serotonin 5-HT1A receptors rather than cannabinoid receptors, with chronic treatment restoring depleted serotonin levels.
Why only some teens develop cognitive problems from cannabis: a genetic vulnerability in brain support cells ↗
Mouse study shows adolescent THC only caused lasting memory impairment when combined with genetic vulnerability in astrocytes (support cells), operating through an inflammatory pathway blockable by a COX-2 inhibitor.
Cannabis-using teens showed heightened brain activity to cannabis images in reward and attention regions ↗
First US adolescent fMRI cannabis cue study shows 41 cannabis-using youth had heightened brain activation to cannabis images in reward and attention regions.
Computer training that reduced cannabis approach bias didn't change brain cue responses in teens ↗
Substudy of 37 cannabis-using youth found approach avoidance training that reduced cannabis use in a larger trial did not significantly change brain cue reactivity on fMRI, with only trend-level effects.
Cannabinoids reduced a brain appetite signal in sleep-deprived mice, with insulin resistance linked to CB2 receptors ↗
Mouse study finds cannabinoids reduce a brain appetite signal (nesfatin-1) through both CB1 and CB2 receptors, with CB2 activation separately linked to increased insulin resistance.
Synthetic cannabinoid CUMYL-4CN-BINACA causes seizures at extremely low doses in mice ↗
CUMYL-4CN-BINACA caused seizures in mice at the lowest dose reported for any synthetic cannabinoid, acting through CB1 receptors.
Depression-prone rats show reduced endocannabinoid signaling, with differences between brain hemispheres ↗
Depression-model rats showed reduced endocannabinoid signaling with notable hemisphere-specific differences in prefrontal cortex and hippocampus.
Cannabinoid exposure can cause lasting cognitive and psychiatric problems, especially in adolescents ↗
Review of multiple evidence types consistently links cannabinoid exposure to persistent cognitive deficits and psychosis risk, with adolescence as a critical vulnerability window.
Endocannabinoid enzyme inhibitors had mixed effects on schizophrenia-like symptoms in mice ↗
Low-dose FAAH inhibition improved memory in a mouse schizophrenia model, but higher doses of both FAAH and MAGL inhibitors worsened cognitive and behavioral symptoms.
THC reduced gut inflammation and prevented lymph node scarring in SIV-infected monkeys ↗
THC suppressed gut inflammation, preserved intestinal barrier integrity, and prevented lymph node fibrosis in all treated SIV-infected macaques.
Adolescent THC unexpectedly improved dopamine function in rats with prenatal immune disruption ↗
Adolescent THC unexpectedly attenuated dopamine dysfunction caused by prenatal immune activation in rats, challenging the simple two-hit model of schizophrenia.
Theoretical pathway maps how pesticide-contaminated cannabis could harm fetal brain development ↗
Theoretical adverse outcome pathway proposes that cannabis contaminated with organophosphate pesticides may compound developmental neurotoxicity through overlapping molecular targets.
CB2 receptor drug AM1710 relieved chemo-induced pain and delayed morphine tolerance in mice ↗
CB2 agonist AM1710 reliably reduced chemo-induced nerve pain and delayed morphine tolerance in mice, but was ineffective for inflammatory or surgical pain.
CB1 and CB2 receptors had opposite effects on clozapine heart damage in mice ↗
Mouse study shows CB1 antagonists and CB2 agonists protect against clozapine-induced heart damage, with opposite cannabinoid receptor roles in cardiotoxicity.
Synthetic cannabinoid JWH-018 impairs memory by raising brain endocannabinoid levels and lowering BDNF ↗
JWH-018 impaired memory by elevating brain endocannabinoids (suppressing FAAH and MAGL) and reducing BDNF, with all effects reversible by CB1 receptor blockade.
Cannabinoids consistently facilitate extinction of traumatic memories in animal and human studies ↗
Review of animal and human studies finds cannabinoid-facilitated extinction of traumatic memories with large effect sizes, acting through prefrontal cortex, amygdala, and hippocampus.
Meta-analysis confirms regular cannabis users have smaller hippocampus and orbitofrontal cortex ↗
Meta-analysis of 30 neuroimaging studies found regular cannabis users have significantly smaller hippocampus and orbitofrontal cortex volumes.
CB2 receptor manipulation reduced alcohol reward in mice while endocannabinoid levels dropped in brain reward regions ↗
Alcohol conditioning decreased endocannabinoid levels in mouse brain reward regions, and CB2 receptor blockade reduced alcohol's rewarding effects.
THC disrupted brain connectivity by boosting striatal glutamate and dopamine in occasional users ↗
Human neuroimaging study shows THC increases striatal glutamate and disrupts brain connectivity, with these changes predicting subjective high and attention deficits.
HIV and regular marijuana use together produced greater brain activation changes than either alone ↗
fMRI study found combined HIV and regular marijuana use produced synergistic brain activation changes in the fronto-insular cortex during cognitive tasks.
Prospective study finds no link between adolescent cannabis use and adult brain structure ↗
Prospective study following boys from age 13 to their 30s found no association between adolescent cannabis use patterns and adult brain structure in 14 regions.
Peripherally restricted CB1 blocker caused far less anxiety than rimonabant in mice ↗
Novel peripherally restricted CB1 antagonist TM38837 was 10x less fear-promoting than rimonabant in mice while maintaining anti-obesity efficacy in previous studies.
Marijuana use in adolescents altered BDNF levels, with onset age influencing the magnitude of change ↗
Longitudinal study of 500 adolescents found marijuana use caused BDNF alterations (not vice versa), with age of onset influencing the pattern of neurotrophin changes.
Adolescent THC rewired prefrontal cortex neurons in rats, with gene changes overlapping schizophrenia ↗
Adolescent THC caused premature dendritic pruning and altered gene networks in rat PFC neurons, with dysregulated networks overlapping schizophrenia-associated pathways.
Meta-analysis finds elevated endocannabinoid levels in the brains and blood of people with psychosis ↗
JAMA Psychiatry meta-analysis of 18 studies finds elevated anandamide in CSF and blood of schizophrenia patients, highest early in illness and inversely related to symptom severity.
Vaporized THC and sleep in rats: only a 1-hour NREM bump at top dose ↗
Rats showed more NREM sleep only for 1 hour after the highest vaporized THC dose, only in the light phase.
Adenosine A2A receptor blockers reversed chronic cannabinoid-induced memory deficits in rats ↗
Chronic A2A receptor antagonism (istradefylline) reversed cannabinoid-induced memory deficits and partially rescued hippocampal synaptic plasticity in rats.
Review details how CB1 receptors drive insulin resistance and obesity, and the promise and pitfalls of blocking them ↗
Review maps how CB1 receptor activation drives hepatic insulin resistance and obesity, highlighting peripheral-only CB1 blockade as a promising therapeutic approach.
A single hit of vaporized THC suppressed brain gamma waves in rats for at least a week ↗
A single session of vaporized THC suppressed gamma-frequency brain activity in multiple rat brain regions, and most effects were still present a week later.
CBD improved memory and social behavior in a female rat model of schizophrenia ↗
CBD reversed memory and social deficits in female rats from a schizophrenia model, but reduced social behavior in healthy rats.
THC in urine linked to worse working memory and altered brain activity in a large study ↗
In over 1,000 people, testing positive for THC was linked to worse working memory and altered brain activity, but past cannabis use history was not.
Overexpressing a cannabinoid receptor protein in rat brains produced schizophrenia-like symptoms ↗
Overexpressing a cannabinoid receptor regulatory protein (CNRIP1) in rat brains produced schizophrenia-like behavioral and dopamine system changes.
How prenatal cannabis exposure alters brain chemistry in offspring ↗
Prenatal cannabis exposure alters dopamine, serotonin, GABA, and other neurotransmitter systems in offspring, with effects that vary by brain region and sex.
CBD altered brain activity in people with autism but not in controls ↗
A single dose of CBD altered brain activity in regions implicated in autism (cerebellum, fusiform gyrus) in men with ASD but not in neurotypical controls.
CBD shifted glutamate and GABA levels in the brain, but differently in people with autism ↗
CBD modulated brain glutamate and GABA levels, but in opposite directions for people with autism versus neurotypical controls.
Marijuana and depression together have additive negative effects on verbal memory and brain structure ↗
Young adults with both marijuana use and depression had worse verbal memory and thinner cortex than those with either condition alone, suggesting additive harm.
The endocannabinoid system controls fear and pain differently depending on which part of the prefrontal cortex is involved ↗
Endocannabinoid signaling in different prefrontal cortex subregions had opposing effects on pain suppression and fear behavior in rats.
Schizophrenia patients who used cannabis showed better brain processing than those who did not ↗
Schizophrenia patients who used cannabis showed better auditory processing (MMN) than non-using patients, possibly reflecting a less impaired subgroup.
People with cannabis use disorder have an automatic attentional pull toward cannabis-related images ↗
Cannabis users showed involuntary attentional capture by cannabis cues within 125-200 ms, along with more errors and poorer selective attention.
CBD reduced brain inflammation and improved memory in diabetic rats with impaired brain blood flow ↗
CBD improved memory and reduced brain inflammation in diabetic middle-aged rats with impaired cerebral blood flow, through anti-inflammatory rather than neuroplasticity mechanisms.
THC plus stress during adolescence impaired fear extinction in adult mice ↗
Neither THC nor stress alone caused lasting anxiety-like brain changes, but the combination during adolescence impaired fear extinction in adult mice.
Ultra-Low THC Doses Protected Mouse Brains From Injury. Regular Doses Did the Opposite. ↗
Mouse studies showed THC at doses thousands of times below the psychoactive threshold protected against brain injury and cognitive decline, while standard doses impaired cognition.
Non-psychoactive cannabinoids protected neurons in an Alzheimer's drug screening model ↗
Nine of 11 cannabinoids protected neurons in an Alzheimer's drug screening model, removed amyloid, and worked through both receptor-dependent and independent mechanisms.
Brain imaging studies show altered cannabinoid signaling across multiple psychiatric disorders ↗
PET brain imaging found altered CB1 receptor binding across cannabis use disorder, alcohol use disorder, schizophrenia, PTSD, and eating disorders.
In Rats, Low-Dose THC Felt Rewarding Through CB1 Receptors. Higher Doses Felt Aversive Through CB2. ↗
Rat study found THC enhances brain reward at low doses (CB1) but suppresses it at high doses (CB2) — a biological explanation for why more weed doesn't mean more fun.
Early CBD treatment prevented schizophrenia-like symptoms from developing in a rat model ↗
CBD given during adolescence prevented schizophrenia-like symptoms and normalized cannabinoid receptor changes in a rat model, while haloperidol did not.
CBD restores brain network disruption caused by THC ↗
Brain imaging study found THC disrupted key brain networks, with feeling "stoned" linked to disruption of the posterior cingulate cortex, while CBD restored salience network changes.
A cannabis compound showed strong anti-nicotine effects in rodent addiction models ↗
Cannabis-related compound delta-8-THCV reduced nicotine addiction across all seven rodent models tested, including self-administration, relapse, and withdrawal.
Brain network patterns may predict who will respond to CBD for epilepsy ↗
EEG brain network analysis distinguished CBD responders from non-responders in refractory epilepsy, with key differences in the beta frequency band.
How CBD changes brain activity: a systematic review of neuroimaging studies ↗
Systematic review of 17 neuroimaging studies found CBD consistently modulated brain activity in regions relevant to psychosis and anxiety, often opposite to THC effects.
THC given after concussions helped some symptoms in adolescent rats ↗
Adolescent rat study found THC given after concussions reduced anxiety, depression, and memory deficits, but THC before injury had no effect.
Cannabinoid receptor activation impairs fear extinction in adolescent rats but improves it in adults ↗
A cannabinoid agonist that improved fear extinction in adult rats impaired it in adolescent and juvenile rats, with younger animals showing higher CB1 receptor levels in brain regions tied to fear processing.
Narrative review explores whether the adolescent brain is more vulnerable to cannabis effects ↗
A narrative review found consistent evidence linking adolescent cannabis use to alterations in brain structure, function, and connectivity, with some changes appearing to persist into adulthood.
Systematic review finds cannabis users show altered brain activation during memory tasks ↗
A systematic review of 12 neuroimaging studies found cannabis users show altered brain activation during memory tasks, with verbal memory particularly affected and some evidence suggesting a causal role for cannabis.
Single dose of CBD increased blood flow to the hippocampus in healthy adults ↗
A small crossover trial found that 600mg of CBD increased blood flow to the hippocampus by an average of 15 mL/100g/min, with increased orbitofrontal blood flow correlating with faster working memory reaction times.
A genetic variant in the P2RX7 gene may increase risk of psychotic experiences among cannabis users ↗
A genome-wide study found a P2RX7 gene variant associated with psychotic experiences in cannabis users, replicated in a second cohort. THC and CBD affected the P2X7 receptor differently depending on genotype.
Prenatal THC exposure in rats led to impaired emotional memory and increased alcohol-seeking in adolescent offspring ↗
Adolescent rat offspring exposed to THC during fetal development showed impaired emotional memory, reduced neuropeptide Y neurons, and increased alcohol-seeking behavior, suggesting prenatal THC may create lasting vulnerability.
Synthetic cannabinoids produced significantly more seizures than THC in mice ↗
Synthetic cannabinoids JWH-073 and AM-2201 caused significantly more seizures in mice than THC, while endogenous cannabinoid analogs caused none, with effects mediated through CB1 receptors.
EEG brain patterns during simulated driving correlated with cannabis-impaired lane-keeping ↗
A small crossover trial found cannabis-intoxicated drivers showed decreased theta brain waves that correlated with worse lane-keeping in a simulator, suggesting EEG patterns could help identify cannabis impairment.
Review finds endocannabinoid system modulation shows promise for treating tobacco addiction ↗
A review found CB1 neutral antagonists and FAAH inhibitors show the most promise among endocannabinoid-based approaches for tobacco addiction, after the CB1 inverse agonist rimonabant was withdrawn due to psychiatric side effects.
Large study found slower startle responses predicted psychosis conversion, with cannabis altering sensory gating differently in at-risk individuals ↗
In a large NAPLS study of 543 individuals at clinical high risk for psychosis, slower startle responses predicted psychotic conversion (especially in females), and cannabis use showed opposite effects on sensory gating compared to healthy controls.
Synthetic cannabinoid URB447 reduced brain injury and white matter damage in newborn rats after oxygen deprivation ↗
A synthetic cannabinoid that blocks CB1 and activates CB2 receptors reduced brain injury and white matter damage in newborn rats even when given 3 hours after oxygen deprivation.
Prenatal cannabinoid exposure reduced ovarian egg reserve in adult rat offspring ↗
Female rat offspring exposed to a cannabinoid agonist prenatally had reduced ovarian reserve in adulthood, an effect mediated by CB1 receptors. The delay between exposure and impact suggests a programmed developmental effect.
Review of 63 neuroimaging studies finds adolescent cannabis users show brain changes, but causation remains unclear ↗
A review of 63 neuroimaging studies found adolescent cannabis users show altered frontoparietal brain structure and function, but adult studies examining onset age gave mixed results, leaving the question of adolescent-specific vulnerability unresolved.
Endocannabinoid 2-AG in the brain's pain-processing region modulated fear-driven pain suppression via CB2 receptors ↗
In rats, increasing the endocannabinoid 2-AG in the anterior cingulate cortex reduced fear-driven pain suppression via CB2 (not CB1) receptors, revealing an unexpected role for brain CB2 receptors in pain modulation.
Both activating and blocking cannabinoid receptors during early adolescence reduced sociability in rats ↗
Both activating and blocking cannabinoid receptors during early adolescence impaired sociability in rats, suggesting the endocannabinoid system must be precisely balanced for normal social development. Effects were transient.
Major review maps the expanded endocannabinoid system and its therapeutic potential across neurological diseases ↗
A Nature Reviews Neurology article describes the expanded "endocannabinoidome" beyond CB1/CB2 and reviews its involvement in neurological diseases, noting approved therapies for MS and epilepsy and potential applications across neurodegeneration.
CBD reduced pain sensitivity in a mouse model of Parkinson's disease ↗
CBD reversed the increased pain sensitivity in a mouse model of Parkinson's disease, with effects mediated through CB1 receptors and potentially by increasing endogenous anandamide levels.
Cannabinoid agonist HU-210 reduced sucrose consumption in rats through CB1 receptor-mediated motor impairment ↗
The cannabinoid agonist HU-210 paradoxically reduced sucrose intake in rats by impairing licking motor mechanics via CB1 receptors, while rimonabant reduced intake through what may be reward devaluation.
Review examines whether cannabis effects on hippocampus and dopamine pathways explain psychosis risk ↗
A review found clear evidence that cannabis affects hippocampal function but weaker evidence for increased striatal dopamine, suggesting the cannabis-psychosis pathway may be more about hippocampal dysfunction than direct dopamine effects.
CB1 receptor positive allosteric modulator unexpectedly antagonized opioid pain relief in morphine-withdrawn rats ↗
A CB1 receptor positive allosteric modulator unexpectedly antagonized opioid pain relief in the PAG of morphine-withdrawn rats, challenging assumptions about cannabinoid-opioid synergy.
Review maps CBD's diverse molecular targets including serotonin, TRPV1, and cannabinoid receptors ↗
A review found CBD acts on diverse molecular targets including serotonin 5-HT1A receptors, TRPV1 channels, and cannabinoid receptors, explaining its broad therapeutic profile across anxiety, pain, and epilepsy.
Prenatal THC selectively damaged hippocampal interneurons in male offspring, explaining sex-specific memory deficits ↗
Prenatal THC exposure selectively destroyed CCK-containing hippocampal interneurons in male but not female mice, causing lasting memory deficits and disrupted brain oscillations through a CB1 receptor-dependent mechanism.
Cannabis users who developed psychosis showed widespread grey matter loss compared to cannabis users without psychosis ↗
A pilot MRI study found cannabis users who developed psychosis had widespread grey matter loss in frontal, temporal, and insular regions compared to non-psychotic cannabis users, suggesting psychosis involves brain changes beyond what cannabis use alone produces.
Synthetic cannabinoid JWH-018 produced nausea-like behavior in rats via CB1 receptors with stress hormone activation ↗
The synthetic cannabinoid JWH-018 produced nausea-like behavior in rats through CB1 receptors, with elevated stress hormones, supporting the theory that cannabinoid hyperemesis syndrome involves stress response dysregulation.
THC-induced nausea involves stress response dysregulation and is not blocked by standard anti-nausea drugs ↗
THC-induced nausea in rats was blocked by six different stress-response inhibitors and a benzodiazepine, but not by the standard anti-emetic ondansetron, supporting the hypothesis that CHS is a stress-mediated condition.
Review finds cannabis affects the adolescent brain differently than adult brain through disrupted neuronal growth ↗
A review found THC disrupts neuronal growth factor production through CB1 receptors, with adolescent brains showing different structural and behavioral effects than adult brains, compounded by decades of increasing THC potency.
Leading researcher describes the expanded endocannabinoidome as a platform for non-psychoactive cannabinoid therapies and gut-brain connections ↗
A leading endocannabinoid researcher describes the expanded endocannabinoidome as a platform for non-psychoactive cannabinoid therapies and highlights its connection to the gut-brain axis in neuropsychiatric disorders.
Nicotinic acetylcholine receptors play a role in THC dependence, with human genetic confirmation ↗
Specific nicotinic receptor subtypes (alpha3beta4, alpha6beta4) modulated THC withdrawal in mice, with human genetic variants in the same genes associated with cannabis disorder, identifying new medication targets.
Animal model review finds adolescent cannabis exposure interacts with early-life stress to increase schizophrenia-like outcomes ↗
A review of animal models found adolescent cannabis exposure interacted synergistically with early-life maternal deprivation and immune activation to produce schizophrenia-like outcomes, with important sex differences.
THC withdrawal reduced motivation for sucrose in mice, modeling the anhedonia of cannabis cessation ↗
Rimonabant-precipitated THC withdrawal in mice significantly reduced motivation for sucrose rewards, modeling the anhedonia of human cannabis withdrawal. A CB1 positive allosteric modulator did not prevent this effect.
Cannabis combined with anabolic steroid nandrolone produced greater neurotoxicity than either drug alone in adolescent rats ↗
Combining cannabis and the anabolic steroid nandrolone in adolescent rats produced synergistic neurotoxicity: worse cognition, more anxiety and aggression, and greater brain damage through oxidative stress and apoptosis.
Cannabinoid compounds protected brain cells from damage caused by high glucose and Alzheimer's-linked proteins ↗
Cell study found five cannabinoid agents protected rat brain cells from combined high glucose and amyloid beta damage, with the FAAH inhibitor URB597 showing the strongest neuroprotection.
Inhaled cannabis vapor lowered heart rate and blood pressure but increased anxiety-like behavior in mice ↗
Mouse inhalation study found vaporized cannabis (10.3% THC) decreased heart rate and blood pressure while promoting anxiety-like behavior and altering brain activation patterns.
Study found no evidence that cannabis terpenes interact with cannabinoid receptors ↗
Lab study found five common cannabis terpenes had no detectable activity at CB1 or CB2 receptors and did not modify THC, CBD, or endocannabinoid binding or function.
Synthetic cannabinoids worsened alcohol-related motor impairment in mice by reducing brain glutamate ↗
Mouse study found synthetic cannabinoids combined with alcohol caused worse motor impairment than either alone, mediated by reduced glutamate signaling in the cerebellum via CB1 receptors.
CBD reduced the rewarding effects of cocaine in rats through CB2, serotonin, and TRPV1 receptors ↗
Rat study found CBD reduced cocaine self-administration and reward by attenuating dopamine release in the nucleus accumbens, working through CB2, serotonin 5-HT1A, and TRPV1 receptors.
Synthetic cannabinoid EG-018 showed unusual properties as a weak partial agonist at cannabinoid receptors ↗
Lab and animal testing found the synthetic cannabinoid EG-018 has high cannabinoid receptor affinity but behaves as a weak partial agonist, producing limited effects only via intravenous administration.
Mega-analysis of 400 THC infusions confirms THC induces psychosis-like symptoms in nearly half of healthy volunteers ↗
Mega-analysis of 400 IV THC infusions found psychosis-like symptoms in 45% of healthy volunteers, with effects increasing with dose and decreasing with regular cannabis use history.
Activating CB1 receptors raised seizure threshold in mice with brain-infecting parasites ↗
Mouse study found CB1 receptor activation and endocannabinoid boosting raised seizure thresholds in Toxoplasma-infected mice, while CB1 blockade worsened seizure vulnerability.
CBD's anti-seizure effects in mice depend on the TRPV1 receptor ↗
Mouse study found CBD's anti-seizure effects were abolished in mice lacking the TRPV1 receptor, strongly implicating this receptor in CBD's mechanism of action against seizures.
Higher-grade brain tumors expressed more cannabinoid receptors, especially CB2 in blood vessels ↗
Study of 45 brain tumor patients found cannabinoid receptor expression increased with tumor grade, with CB2 particularly elevated in blood vessels of high-grade astrocytomas.
Meta-analysis confirms a single dose of THC induces psychotic, negative, and other psychiatric symptoms with large effect sizes ↗
Meta-analysis of 15 controlled studies confirms THC induces psychotic, negative, and general psychiatric symptoms with large effect sizes in healthy people, while CBD shows no consistent protective effect.
Cannabinoids were more potent in older mice, and low doses had opposite effects in young versus old animals ↗
Mouse study found cannabinoids were more potent in aged mice than young adults, with stronger pain relief and movement suppression, suggesting elderly users may need lower doses.
Long-term THC shifted brain reward circuit control from rational to emotional regions in rats ↗
Rat study found long-term THC weakened prefrontal cortex control of the brain's reward center while strengthening emotional region (amygdala/hippocampus) input, potentially explaining cannabis-related cognitive and psychiatric effects.
Boosting endocannabinoids reduced fear in traumatized rats through CB2 receptors, not CB1 ↗
Rat study found endocannabinoid-boosting drugs reduced persistent fear after predator stress through CB2 (not CB1) receptors, with CB2 gene expression upregulated in the prefrontal cortex by stress.
CB2 receptor drug enhanced morphine pain relief while reducing morphine reward and physical dependence in mice ↗
Mouse study found the CB2 agonist LY2828360 synergized with morphine for neuropathic pain relief while blocking morphine reward and partially reducing physical dependence.
A CB2 receptor drug reduced cocaine-seeking behavior in rodents ↗
CB2 inverse agonist Xie2-64 reduced cocaine self-administration and relapse-like behavior in rats without affecting food motivation, suggesting a new approach to cocaine addiction treatment.
Primates can learn to distinguish between cannabinoid receptor activation and blockade ↗
Squirrel monkeys learned to discriminate the CB1 antagonist rimonabant from placebo, and THC blocked this discrimination, confirming CB1-mediated subjective effects of cannabinoid blockade.
Brain imaging shows how cannabis odor cues activate reward regions in at-risk young adults ↗
fMRI study of 54 young adults found that those at higher risk for cannabis use disorder showed stronger brain activation in reward regions when exposed to cannabis odor cues.
How alcohol hijacks the endocannabinoid system in the brain and liver ↗
Review of 20 years of research found that alcohol produces its addictive brain effects and liver damage largely through the endocannabinoid system, particularly CB1 receptors.
CB1 receptors help the brain choose between navigation strategies ↗
Blocking CB1 receptors in mice impaired spatial learning and shifted navigation strategies, with altered brain activity in the hippocampus, striatum, and amygdala.
Single CBD dose did not change reward-related brain activity in healthy volunteers ↗
Double-blind fMRI study found a single 600mg CBD dose did not alter reward-related brain activity or motivation in 23 healthy volunteers.
How cannabis compounds disrupt timing ability by desynchronizing brain regions ↗
CB1 activation in rats disrupted synchronization between hippocampus and entorhinal cortex, causing time overestimation on a precise timing task.
Activating CB2 receptors reduced bladder inflammation in mice ↗
CB2 agonist JWH-133 reduced bladder pain, inflammation, and urinary frequency in mice with cystitis through an autophagy-dependent mechanism.
Both CB1 blocking and CB2 activation reduced cocaine reward in mice ↗
Both CB1 blockade and CB2 activation independently reduced cocaine reward and sensitization in mice, both preventing hippocampal neuronal activation.
Cannabis use disorder alters how the brain connects stress responses to emotional processing ↗
fMRI study found cannabis use disorder altered brain connectivity between emotion and stress circuits, with stronger amygdala-hypothalamus signaling correlated to perceived stress.
Adolescent cannabinoid exposure caused lasting sleep changes into adulthood in rats ↗
Rats exposed to cannabinoid agonist during adolescence showed persistent sleep disruption in adulthood, with decreased wakefulness and increased REM sleep.
Cannabis dependence blurs the brain boundary between thinking and feeling ↗
Study of 1,206 young adults found that cannabis dependence, but not recreational use, was associated with a breakdown in normal brain separation between cognitive and emotional processing.
Combining serotonin and cannabinoid drugs improved a schizophrenia-related brain function in mice ↗
Combining a serotonin 5-HT2A blocker with CB1 blocker improved prepulse inhibition in a schizophrenia mouse model, while neither cannabinoid drug worked alone.
Prior nicotine exposure changed how THC affects the brain differently by age and sex ↗
In 112 rats, prior nicotine exposure altered THC brain effects depending on age and sex: adult males showed reduced THC response while adolescent females showed potentiated effects.
Treadmill exercise improved memory through the endocannabinoid system in rats with brain inflammation ↗
Treadmill exercise reversed memory deficits from brain inflammation in rats by modulating CB1/CB2 receptors and inflammatory enzymes in the hippocampus.
First study finds elevated endocannabinoid levels in the spinal fluid of Tourette syndrome patients ↗
First CSF study found significantly elevated endocannabinoids (AEA, 2-AG) in Tourette syndrome patients, with 2-AG correlating to ADHD severity.
Cannabis hyperemesis syndrome is a growing gut-brain disorder with limited treatment options ↗
Review describes cannabis hyperemesis syndrome as a gut-brain disorder caused by CB1 receptor changes in chronic users, with hot bathing, capsaicin, and haloperidol as management options.
CBD may control seizures by regulating methionine through a previously unknown metabolic pathway ↗
Researchers discovered CBD inhibits methionine synthesis through one-carbon metabolism, a new mechanism validated in Dravet syndrome mouse and rat seizure models.
Cannabinoid receptor compounds enhanced the antidepressant effects of atypical medications in mice ↗
Mouse study found cannabinoid receptor compounds enhanced antidepressant effects of tianeptine and agomelatine without changing brain drug levels, suggesting true synergy.
CB2 cannabinoid receptor compounds boosted the effectiveness of common antidepressants in mice ↗
Mouse study found both CB2 agonist and inverse agonist enhanced three classes of conventional antidepressants without changing brain drug levels.
CBD dramatically normalized the brain waves of a 9-year-old with Lennox-Gastaut syndrome ↗
A 9-year-old with Lennox-Gastaut syndrome achieved complete seizure control and dramatic EEG normalization on CBD, an improvement not previously described.
CB1 worsens and CB2 protects the heart during ischemia, but cannabis also raises cardiovascular risk factors ↗
Review found CB1 worsens and CB2 protects heart inflammation during ischemia, while cannabis use may trigger arrhythmias and metabolic dysfunction.
CBD disrupted fear memory formation through different brain receptors depending on timing after the event ↗
Rat study found CBD disrupted fear memory consolidation within a 1-hour window, using CB1/CB2 receptors immediately but PPARγ receptors at the 1-hour mark.
CB2 receptors on immune cells could be a drug target for HIV-related brain inflammation ↗
Review proposes CB2 receptors as drug targets for HIV brain inflammation, noting cannabis-using HIV patients have lower inflammatory monocyte levels.
CBD produced antidepressant-like effects in mice by regulating DNA methylation in brain regions linked to depression ↗
Mouse study found CBD produced antidepressant effects by normalizing stress-induced DNA methylation changes in prefrontal cortex and hippocampus.
CB1 receptors were 20% elevated in the prefrontal cortex of people who died with major depression ↗
Postmortem study found CB1 receptors 20% elevated in prefrontal cortex of people with major depression, with unchanged CB2 and increased mTOR activity.
Adolescent cannabinoid exposure reprogrammed how the rat brain responds to cocaine at molecular and epigenetic levels ↗
PNAS study found adolescent cannabinoid exposure reprogrammed the rat brain response to cocaine at epigenomic, transcriptomic, and proteomic levels, specifically during adolescence.
THC and nicotine both altered DNA methylation at neurodevelopmental genes in rat sperm, including autism candidates ↗
THC altered DNA methylation at 7 neurodevelopmental genes in rat sperm, overlapping with nicotine effects and enriched for autism candidate genes.
Cannabis use linked to widespread methylation changes in autism gene DLGAP2 in human sperm ↗
Cannabis use linked to widespread methylation changes in autism gene DLGAP2 in human sperm, with similar changes found in rat offspring brains after paternal THC exposure.
Only the lowest THC dose helped schizophrenia-like symptoms in rats, while higher doses made them worse ↗
In a rat schizophrenia model, only the lowest THC dose (0.1 mg/kg) reversed social withdrawal, while higher doses worsened symptoms in healthy rats.
Paternal THC exposure before conception caused lasting cholinergic brain deficits in rat offspring through middle age ↗
Paternal THC exposure in rats caused dose-dependent, lifelong cholinergic brain deficits in offspring from adolescence through middle age.
Amygdala hyper-reactivity at age 14 predicted cannabis use 5 years later in a dose-response fashion ↗
IMAGEN study found right amygdala hyper-reactivity at age 14 predicted cannabis use at 19 in a dose-response pattern, with cannabis exposure altering normal amygdala development.
Cannabis use was linked to elevated inflammatory marker sgp130 in schizophrenia but not bipolar disorder ↗
Cannabis use elevated the anti-inflammatory marker sgp130 in 401 schizophrenia patients but not 242 bipolar patients, suggesting diagnosis-specific immune modulation.
CB1 receptor gene expression changes across brain development and is altered in schizophrenia, with COMT genotype modifying the trajectory ↗
Postmortem brain study found CB1 receptor expression is highest fetally, drops after birth, is decreased in schizophrenia, and follows a COMT-genotype-dependent trajectory.
Allosteric CB1 ligands reduced eye pain and inflammation in a mouse corneal injury model ↗
Novel allosteric CB1 receptor ligands reduced corneal pain and inflammation in mice, especially when combined with low-dose THC, suggesting a new approach for eye pain treatment.
Chemotherapy-treated mice had lower endocannabinoid levels in their paws, and restoring them relieved pain ↗
Mice with chemotherapy-induced nerve pain had depleted endocannabinoid levels in their paw tissue. Restoring 2-AG locally reversed pain sensitivity through both CB1 and CB2 receptors.
Heavy cannabis use was linked to lower BDNF levels in first-episode psychosis patients but not in healthy volunteers ↗
Heavy cannabis use was linked to lower BDNF levels in first-episode psychosis patients who had never taken antipsychotics, but not in healthy volunteers, suggesting vulnerability-specific effects.
The synthetic cannabinoid AB-FUBINACA caused physical dependence in mice despite its short duration of action ↗
AB-FUBINACA produced classic cannabinoid effects that cleared rapidly from the brain but still induced physical dependence after just 5 days of twice-daily dosing in mice.
The terpene terpineol showed antidepressant effects in mice through cannabinoid and dopamine receptors ↗
Terpineol reduced depressive-like behavior in an inflammatory mouse model, with effects mediated through CB1, CB2 cannabinoid receptors and D2 dopamine receptors.
Endocannabinoid drugs reduced anxiety but did not erase fear memories in a rat PTSD model ↗
A CB1 agonist reduced anxiety but not conditioned fear in rats modeling PTSD, suggesting endocannabinoid drugs may help with PTSD-related anxiety without erasing fear memories.
Plant-derived and synthetic cannabinoids worked through different receptor combinations in mice ↗
THC required both CB1 and CB2 receptors for pain relief and catalepsy, while synthetic cannabinoid XLR11 needed only CB1. GPR55 deletion enhanced cannabinoid responses, suggesting it normally opposes them.
Two weeks of CBD changed DNA methylation patterns in mouse brain tissue ↗
Two weeks of daily CBD altered DNA methylation at 3,323 sites in mouse hippocampus, affecting genes linked to neural development and psychiatric conditions.
GPR55 knockout mice had worse glucose tolerance, and the receptor partly mediated weight effects of rimonabant and THCV ↗
GPR55 knockout mice had impaired glucose tolerance on any diet, and the weight-reducing effects of rimonabant and THCV were partly dependent on this receptor.
Chronic CBD treatment did not improve behavioral symptoms in a tau-based Alzheimer's mouse model ↗
Chronic CBD at 50 mg/kg did not improve motor, anxiety, or cognitive measures in 4-month-old TAU58/2 transgenic male mice, despite previous success in amyloid-based AD models.
Lower brain FAAH levels were linked to more severe psychotic symptoms in untreated patients ↗
The first PET study of brain FAAH in psychosis found lower enzyme levels predicted more severe positive psychotic symptoms (large effect size), suggesting FAAH as a potential biomarker and treatment target.
A CB2 agonist relieved nerve pain in mice even without CB1 receptors, working through anti-inflammatory pathways ↗
The CB2 agonist AM1710 reversed neuropathic pain in mice with or without CB1 receptors by boosting anti-inflammatory IL-10 and suppressing pro-inflammatory cytokines in the spinal cord.
Cannabis-related psychotic-like experiences in teens were partly explained by changes in a specific brain region ↗
A longitudinal brain imaging study of 706 teens found that cannabis-related psychotic-like experiences were partially mediated by reduced growth of the uncus in the parahippocampal gyrus between ages 14 and 19.
A CB2 inverse agonist reduced brain inflammation and neuronal death after prolonged seizures in mice ↗
A CB2 inverse agonist given after prolonged seizures were stopped prevented brain inflammation, reduced neuronal death, and improved behavior in mice, suggesting a potential post-seizure neuroprotective therapy.
Eight minor cannabinoids showed activity at CB1 and CB2 receptors in cells and produced cannabinoid-like effects in mice ↗
A comprehensive study of 8 phytocannabinoids found partial agonist activity at CB1 and/or CB2 receptors for multiple minor compounds, with several producing cannabinoid-like behavioral effects in mice.
Two months of daily THC caused retinal damage in mice through inflammation and oxidative stress ↗
Two months of daily THC injections caused retinal damage in mice, with increased photoreceptor death driven by inflammation and oxidative stress.
Cannabis-dependent men performed worse on cognitive tasks under stress, linked to reduced precuneus brain activity ↗
Cannabis-dependent men showed worse cognitive performance under stress with reduced precuneus brain activity, despite experiencing similar levels of subjective stress as controls.
Cannabinoids stopped cocaine-induced seizures by restoring glycine receptor function, not through CB1/CB2 ↗
Cannabinoids stopped cocaine-induced seizures in mice by restoring glycine receptor function, working independently of CB1 and CB2 receptors through a novel molecular mechanism.
Seven days of CBD at high doses produced antidepressant effects in mice by increasing serotonin and noradrenaline ↗
Seven days of high-dose CBD produced antidepressant-like effects in mice by increasing hippocampal serotonin and noradrenaline, the same neurotransmitters targeted by conventional antidepressants.
Teenage Cannabis Use Accelerates Brain Cortex Thinning in the Regions That Matter Most ↗
Longitudinal MRI study of 799 European teenagers found dose-dependent prefrontal cortical thinning associated with cannabis use from age 14 to 19, concentrated in CB1 receptor-rich brain regions.
A meta-analysis found no major brain volume differences in cannabis-using teens, but age and sex modulated subtle effects ↗
A meta-analysis of brain imaging studies found no significant gray matter volume differences between cannabis-using and non-using teens, but age and sex influenced subtle, region-specific patterns.
Both Tobacco and Cannabis Smoking Activated the Same Inflammatory Immune Pathway in Young Adults ↗
Both cannabis and tobacco smoking activated the same inflammatory immune pathway (GPR15 on helper T cells), accounting for half of smoking's pro-inflammatory effect.
Cannabigerolic acid showed anticonvulsant effects in Dravet syndrome mice but had proconvulsant effects at high doses in another seizure model ↗
CBGA showed anticonvulsant effects in Dravet syndrome mice and potentiated clobazam, but was proconvulsant in another seizure model and at high doses, revealing a complex therapeutic profile.
Endocannabinoid system enzymes MAGL and FAAH show promise as targets for treating Alzheimer's-related cognitive decline ↗
Preclinical research suggests that blocking endocannabinoid-degrading enzymes (MAGL and FAAH) could protect brain cells from Alzheimer's-related damage, reduce inflammation, and potentially improve cognitive function.
Cannabis exposure during pregnancy and adolescence can reprogram developing brain circuits through epigenetic changes ↗
A Nature Reviews Neuroscience paper found cannabis exposure during pregnancy and adolescence impairs brain development through epigenetic changes that persist into adulthood and can be passed to future generations.
Cannabinoids reshape the immune system partly by changing which microRNAs cells produce ↗
Cannabinoids alter immune function by changing which microRNAs immune cells produce. These tiny RNA molecules regulate gene expression, providing a molecular mechanism for the anti-inflammatory effects observed with cannabinoid use.
A gene variant and its epigenetic state both influence how THC affects fear processing in the brain ↗
In a controlled THC study of 36 men, both a genetic variant (AKT1 rs1130233) and DNA methylation independently influenced how THC affected fear-related brain activity, with the epigenetic state partially mediating the genetic effect.
Regular cannabis use starting in adolescence disrupts brain regions responsible for learning new information ↗
An fMRI study found adolescent-onset cannabis users learned new words significantly slower than non-users. Brain imaging revealed disrupted activation in the parahippocampal gyrus, midbrain, and thalamus during learning.
A THC-based combination treatment reduced tic severity by over 20% in adults with Tourette's syndrome ↗
A pilot trial of 16 adults with treatment-resistant Tourette's found a THC/PEA combination reduced tics by over 20% within one week. Twelve of 16 participants chose to continue treatment in the extension phase.
Limited evidence does not clearly show cannabis worsens brain outcomes in youth with ADHD ↗
A systematic review of 11 studies found no clear evidence that cannabis compounds cognitive deficits in youth with ADHD, though neuroimaging showed brain differences. The evidence is limited and potentially underpowered.
Blocking a key enzyme in Alzheimer's patients' immune cells shifted them from inflammatory to protective ↗
Blocking the enzyme FAAH in immune cells from Alzheimer's patients reduced inflammation and shifted cells toward a protective state, suggesting endocannabinoid system modulation could offer a new therapeutic approach.
THC causes repetitive swimming in zebrafish that mirrors psychosis-like behavior ↗
THC caused dose-dependent repetitive behavior in zebrafish that was reduced by an antipsychotic and a CB2 receptor blocker but not a CB1 blocker, offering a new model for studying cannabis-psychosis links.
CBD may help clear toxic protein buildup in neurodegenerative diseases ↗
Review of preclinical evidence suggests CBD may help clear toxic protein aggregates in neurodegenerative diseases by modulating the proteostasis network, though human data remains limited.
L-theanine prevented long-term brain and behavior changes from adolescent THC exposure in rats ↗
L-theanine pretreatment in adolescent rats prevented the long-term dopamine dysregulation, molecular changes, and behavioral abnormalities caused by THC exposure.
Brain scans show similar abnormalities in schizophrenia patients whether or not they used cannabis ↗
Meta-analysis of 10 MRI studies found schizophrenia patients with and without cannabis use showed overlapping brain volume reductions, with no significant differences between groups.
Brain development differences both predict and result from adolescent substance use ↗
Systematic review of 38 longitudinal studies found that brain development delays, especially in executive functioning, both precede and result from adolescent substance use, with harm tied to frequency and recovery tied to duration.
Perinatal THC exposure altered dopamine and cannabinoid gene regulation in rats, and CBD reversed the damage ↗
Rats exposed to THC around birth showed lasting epigenetic changes in dopamine receptor genes and schizophrenia-like behaviors, but adolescent CBD treatment reversed the damage. Similar epigenetic changes were found in human schizophrenia patients.
Boosting endocannabinoids reduced anxiety and depression from meth withdrawal in mice ↗
URB597, which boosts natural endocannabinoids, prevented anxiety and depression in mice during methamphetamine withdrawal through CB1, CB2, and TRPV1 receptor pathways.
Blocking CB2 receptors during adolescence impaired one type of reward learning but not another in adult rats ↗
Blocking CB2 receptors during adolescence in rats impaired Pavlovian reward learning in adulthood but left instrumental conditioning intact, revealing a selective role for CB2 in reward system development.
How Endocannabinoids Shape Dopamine Signals for Reward, Timing, and Avoiding Danger ↗
Review showing 2-AG endocannabinoids gate dopamine value signals across reward, timing, and threat avoidance — explaining why cannabis broadly affects motivation.
CBD reduced cocaine withdrawal symptoms and normalized brain gene changes in mice ↗
CBD reversed behavioral symptoms and molecular brain changes during spontaneous cocaine withdrawal in mice, normalizing dopamine and cannabinoid receptor gene expression.
Omega-3 fatty acid derivative DHEA reduced seizures in mice by activating CB1 receptors ↗
Mouse study found the omega-3 endocannabinoid DHEA was more potent than DHA in raising seizure thresholds, acting through CB1 receptors, while the EPA-derived EPEA had no effect.
Early cannabis use linked to drug-induced psychosis while later use linked to schizophrenia in homeless adults ↗
Study of 437 homeless adults found cannabis use before age 15 was linked to substance-induced psychosis while use after 15 was linked to schizophrenia, with corresponding brain differences.
Adolescent cannabinoid exposure reduced cocaine reward in adult mice and changed epigenetic markers ↗
Adolescent cannabinoid exposure in mice reduced cocaine reward in adulthood and increased a DNA methylation enzyme in the prefrontal cortex, without affecting anxiety or depression.
CB1 and CB2 receptors in a brain anxiety region had opposite effects on anxiety in rats ↗
Rat study found CB1 and CB2 receptors in a key anxiety brain region (BNST) have opposite effects: blocking CB1 reduced anxiety while blocking CB2 increased it.
THC and CBD had age-dependent effects on tic-like behaviors in mice, with CBD potentially worsening tics in juveniles ↗
Mouse model of Tourette syndrome found THC reduced some tic-like behaviors but caused catalepsy, while CBD had no benefit in juveniles and increased head twitching in both age groups.
Boosting both endocannabinoids simultaneously reduced migraine-like pain in rats ↗
Dual endocannabinoid enzyme inhibition reduced migraine-like pain and CGRP levels in rats through CB1 receptors, affecting both central and peripheral inflammatory markers.
Chronic morphine increased CB2 receptors on spinal neurons in rats ↗
Rat study found chronic morphine significantly increased CB2 cannabinoid receptor expression on spinal neurons, more than nerve injury alone, suggesting a mechanism for opioid-cannabinoid treatment synergy.
Brain imaging shows THC and CBD have opposite effects in key brain regions linked to psychosis ↗
Systematic review found THC and CBD have opposite brain effects, with THC increasing and CBD decreasing activation, particularly in regions linked to psychosis.
Alcohol, but not cannabis, was linked to thinner brain cortex in young adults ↗
Twin study of 436 young adults found alcohol misuse was associated with thinner cortex in cognitive control brain regions, reflecting both genetic predisposition and direct exposure. Cannabis showed no such effects.
Female mice developed tolerance to THC pain relief faster than males in chronic pain model ↗
Mouse study found females developed tolerance to THC pain relief faster than males in a chemotherapy-induced neuropathic pain model, with effects mediated primarily through CB1 receptors.
Nicotine may mask cognitive deficits from cannabis use in young people ↗
Systematic review of 12 studies found that nicotine co-use may mask cannabis-related cognitive deficits in young people, while neuroimaging research on co-use effects remains extremely limited.
THC did not increase running motivation in mice despite popular beliefs about cannabis and exercise ↗
Mouse study found that acute THC did not affect running preference, performance, or motivation, even though CB1 receptors were necessary for running drive, contradicting popular beliefs about cannabis enhancing exercise.
Mice with reduced Reelin protein showed worse behavioral outcomes after adolescent THC exposure ↗
Mice with reduced Reelin protein showed worse social, behavioral, and stress outcomes after adolescent THC exposure than normal mice, suggesting genetic factors influence cannabis vulnerability.
A brain-sparing CB1 blocker improved metabolic syndrome in obese mice ↗
Mouse study found a brain-sparing CB1 receptor blocker reduced weight gain, improved glucose metabolism, and reversed fatty liver without the psychiatric risks that ended rimonabant.
The Endocannabinoid-Dopamine Partnership: From Basic Survival Drives to Achievement and Addiction ↗
Review of how endocannabinoids and dopamine work as partners across Maslow's hierarchy — from survival drives to achievement — and how cannabis disrupts that partnership.
CBD protected brain tissue from stroke-like damage while THC made it worse ↗
Lab study found CBD protected rat brain tissue from simulated stroke damage while THC worsened it, with different receptor mechanisms mediating each effect.
Cannabis terpenes activated cannabinoid receptors and enhanced cannabinoid effects in mice ↗
Study found four cannabis terpenes activated CB1 receptors and produced cannabinoid-like effects in mice, with selective enhancement of cannabinoid activity providing first strong evidence for the entourage effect.
Heavy alcohol and cannabis use during adolescence linked to brain changes and cognitive effects ↗
A systematic review of 43 longitudinal studies found heavy adolescent alcohol use was associated with widespread brain structure changes, while heavy cannabis use showed more localized effects. Co-use studies generally found alcohol effects were more pronounced.
Alcohol addiction linked to blunted brain alpha waves, independent of cannabis use ↗
A MEG study of 45 adults who used both alcohol and cannabis found that alcohol use disorder was associated with blunted occipital alpha brain wave responses, with no independent effect from cannabis use disorder.
Anandamide-like compound protected against Alzheimer's symptoms in mice via cannabinoid receptors ↗
An anandamide analog improved memory and reduced amyloid-beta in Alzheimer's model mice by activating CB2 cannabinoid receptors and promoting autophagy, a cellular cleanup process.
Cannabinoid receptor GPR18 activation relieved bladder pain and overactivity in rats ↗
In a rat model of interstitial cystitis, activating the cannabinoid receptor GPR18 reduced pain and improved bladder function by inhibiting TRPV1 pain receptors in nerve tissue.
Cannabis smoking linked to oral bacteria that caused brain changes in mice ↗
A study found chronic cannabis smokers had elevated oral Actinomyces meyeri bacteria. When this bacterium was fed to mice for six months, it decreased activity and increased amyloid-beta production in their brains.
CB1 receptor modulator showed antipsychotic potential without THC-like side effects in rats ↗
A CB1 receptor positive allosteric modulator called GAT211 showed antipsychotic-like effects in rats by reducing dopamine-related hyperactivity, unlike THC which did not block the same signaling pathway.
CBD protected rat brains from ischemia damage by preserving hippocampal synaptic connections ↗
CBD treatment in rats protected hippocampal neurons from ischemia damage, preserved dendritic spines and BDNF levels, and prevented ischemia-induced memory deficits.
CBD's brain protection after ischemia involved multiple receptor types in mice ↗
CBD prevented anxiety, memory loss, and depressive behavior after brain ischemia in mice, working through four different receptor systems including CB1, CB2, serotonin, and PPAR-gamma.
Cannabis use and depression affected different brain regions during emotion regulation ↗
An fMRI study of 74 young adults found that depression and cannabis use each independently altered brain activation during emotion regulation, but in different temporal lobe regions.
Does the enzyme that breaks down anandamide play a role in alcohol use disorder? ↗
Systematic review finds FAAH plays a role in alcohol use disorder biology, with inhibition reducing withdrawal symptoms but potentially increasing alcohol preference.
Does CBD affect glutamate levels in the brains of people with early psychosis? ↗
Small crossover trial finds CBD increases hippocampal glutamate in psychosis patients, correlating with reduced symptom severity.
Does CBD normalize brain activity patterns altered by psychosis? ↗
fMRI study finds single CBD dose partially normalizes altered brain activation in psychosis patients toward patterns seen in healthy controls.
Do males and females respond differently to the synthetic cannabinoid MMB-Fubinaca? ↗
Animal study finds the synthetic cannabinoid MMB-Fubinaca produces stronger effects in males than females, all through CB1 receptors.
Do cannabis users show neurological differences regardless of whether they have psychosis? ↗
Study finds cannabis users show elevated neurological soft signs regardless of psychosis status, suggesting cannabinoids affect brain circuits involved in motor and sensory processing.
Does cannabis use affect working memory through changes in hippocampal size? ↗
Brain scan study of 408 individuals finds cannabis use frequency linked to smaller hippocampal volume, which mediated the relationship with working memory impairment.
Does CBD prevent psychosis-like behavior in mice through epigenetic changes? ↗
Mouse study finds CBD prevents psychosis-like behavior with effects lasting 24 hours, involving DNA methylation changes in brain regions implicated in schizophrenia.
Does earlier cannabis use change brain structure networks in people with first psychosis? ↗
Study of 102 psychosis patients finds earlier cannabis use linked to altered cerebellar brain network structure previously implicated in schizophrenia.
Can CBD protect newborn nerve cells after injury? ↗
Rat study finds CBD enhances motor neuron survival by 54% after neonatal nerve injury, with sustained benefits at 8 weeks through CB1 receptor-dependent mechanisms.
Cannabis, Dopamine, and Addiction: How the Endocannabinoid System Modulates the Brain's Reward Circuit ↗
Cannabis activates the same dopamine reward pathway as all drugs of abuse. The endocannabinoid system's role in modulating these signals may offer new targets for treating addiction broadly.
How does prenatal cannabinoid exposure affect the cerebellum of offspring? ↗
Rat study finds prenatal cannabinoid exposure paradoxically enhances mitochondrial function and promotes neuronal survival in offspring cerebellum, unlike harmful effects seen in other brain regions.
Can medical cannabis reduce autism-like behaviors in a genetic mouse model? ↗
Mouse autism model shows medical cannabis reduces repetitive behavior by 70% and anxiety, with THC appearing more important than CBD for core symptom improvement.
Do prenatal alcohol and cannabis have opposing effects on brain cells? ↗
Rat study finds prenatal alcohol and THC have opposing effects on hippocampal inhibitory neurons, with sex-specific effects and complex interactions when both are present.
Can EEG brain waves detect cannabis intoxication? ↗
Small crossover study finds specific EEG changes during cannabis intoxication, including decreased theta power and altered brain connectivity, suggesting potential for objective intoxication detection.
Does maternal cannabis use affect the placenta and child anxiety? ↗
PNAS study links maternal cannabis use to suppressed placental immune genes, elevated cortisol, and increased anxiety and hyperactivity in children aged 3-6.
How does vaped THC affect adolescent male and female rats differently? ↗
Animal study finds adolescent female rats metabolize vaped THC differently than males, with higher active metabolite levels and greater behavioral sensitivity at lower doses.
Does prenatal THC exposure create a dopamine system primed for psychosis? ↗
Rat study finds prenatal THC creates a latent dopamine dysfunction in offspring that emerges as psychotic-like behavior only when triggered by stress or drug challenge.
Psychosis Without Cannabis History Shows Worse Eye Movement Control ↗
Study of 91 participants found that psychosis patients without cannabis history had worse smooth pursuit eye movements than those with cannabis history, suggesting less severe neurobiological impairment in cannabis-associated psychosis.
How Cannabis Cues Light Up the Brain in Regular Users ↗
Systematic review of 18 fMRI studies found regular cannabis users show consistently heightened brain activity in reward, executive control, and memory regions when exposed to cannabis cues, with preliminary links to craving.
Brain Scans Show Cannabis Downregulates Receptors in Women, Just Like in Men ↗
PET imaging found women with cannabis use disorder had lower CB1 receptor levels in key brain regions than non-users, while healthy women naturally had higher CB1 levels than healthy men.
Cannabis Affects Brain Volume Differently in Males and Females, and Fitness May Help ↗
Study of 74 young people found cannabis affected brain volume differently by sex (females had more, males had less), while higher aerobic fitness was linked to greater brain volume overall.
Cannabinoid Receptor Changes in HIV-Positive Brains May Explain Cognitive Problems ↗
Brain tissue analysis found altered cannabinoid receptor expression and distribution in HIV-associated cognitive disorders, with CB1 levels correlating with memory and processing speed deficits.
Cannabis Use During Pregnancy Altered Fetal Brain Connectivity Patterns ↗
Fetal brain imaging found prenatal cannabis exposure altered hippocampal connectivity to multiple brain regions, with patterns linked to less favorable outcomes at age 5.
Blocking the CB1 receptor reduced cholesterol problems and artery disease in mice, even without obesity ↗
CB1 receptor blockade with rimonabant reduced atherosclerotic lesions by 64% and improved lipid profiles in lean mice, showing cardiovascular benefits independent of weight loss.
Heavy cannabis users showed accelerated cerebellar thickening over 3 years compared to non-users ↗
Three-year MRI study found heavy cannabis users showed accelerated cerebellar thickening in regions linked to cognition and motor control, with changes tied to earlier onset of cannabis use.
THC metabolite 11-OH-THC was up to 31 times more potent than THC in mice, with sex differences in rats ↗
Animal study found THC's primary metabolite (11-OH-THC) was 7-31 times more potent than THC in mice, with female rats significantly more sensitive to THC than males.
CB2 receptor activation reduced fentanyl-induced respiratory depression in mice ↗
Mouse study found a CB2 cannabinoid receptor agonist protected against fentanyl-induced respiratory depression without affecting breathing on its own, confirmed through knockout mice.
A CB1 neutral antagonist blocked fentanyl effects in rats without the side effects of rimonabant ↗
CB1 neutral antagonist AM4113 blocked fentanyl discrimination in rats at lower doses and without the side effects of rimonabant, showing promise as a novel approach to opioid use disorder.
Synthetic cannabinoid XLR-11 caused significant liver damage in mice after just 5 days ↗
Five days of synthetic cannabinoid XLR-11 caused pronounced liver necrosis in mice, driven by oxidative stress, inflammation, and cell death pathways.
Nano-coated CBD reduced Alzheimer-like brain plaques and improved memory in rats ↗
Nano-chitosan-coated CBD reduced amyloid plaques, increased brain cannabinoid receptors, and improved memory performance in an Alzheimer rat model.
Scientists identified the mechanism behind cannabis-induced dry mouth: CB1 receptors on salivary gland nerves ↗
Researchers identified that THC causes dry mouth by activating CB1 receptors on nerve fibers in salivary glands, and CBD dose-dependently reverses this effect.
Few sex differences found in acute cannabis effects at moderate vaporized doses ↗
Combined RCT data from 40 participants found minimal sex differences in acute vaporized cannabis effects, with males showing only slightly better divided attention and higher metabolite levels.
Review explores medical cannabis and CBD potential for Malawi, including possible neuroprotective role in malaria ↗
A review of CBD science following Malawi's cannabis legalization highlights epilepsy treatment, neuroprotective potential, and a novel proposal for malaria-related brain injury.
Rat study finds high-THC cannabis smoke impairs working memory but not attention, while high-CBD smoke does not ↗
A rat study found high-THC cannabis smoke impaired working memory but not attention, while high-CBD smoke caused no cognitive deficits.
Review maps how epigenetic changes regulate cannabinoid receptors in health and disease ↗
A review details how DNA methylation, histone changes, and RNA networks regulate cannabinoid receptor expression in health and disease.
Boosting anandamide in adolescent rats reversed schizophrenia-like cognitive and social deficits through CB1 and CB2 receptors ↗
Boosting anandamide in adolescent rats reversed schizophrenia-like cognitive and social deficits through distinct CB1 and CB2 receptor pathways.
CBD disrupts fear memory reconsolidation through CB1 receptors in specific prefrontal cortex regions in rats ↗
CBD disrupted fear memory reconsolidation in rats through CB1 receptors in the anterior cingulate and prelimbic cortex, not the infralimbic cortex.
Cannabis extract outperformed pure CBD at reducing brain immune cell inflammation through multiple molecular pathways ↗
A CBD-and-terpene-enriched cannabis extract reduced brain immune cell inflammation more effectively than pure CBD alone, through multiple molecular pathways.
Review warns cannabis exposure in autistic individuals may increase psychosis risk through epigenetic mechanisms ↗
A review warns that cannabis exposure in autistic individuals may increase psychosis risk through epigenetic effects on shared genetic pathways, with potential intergenerational consequences.
The mirror-image form of CBD is 10 times more potent at blocking CB1 receptor signaling and activates sphingosine receptors ↗
The synthetic mirror image of CBD, (+)-CBD, was 10 times more potent at blocking CB1 signaling than natural (-)-CBD and activated an entirely different receptor system.
Endocannabinoid 2-AG reduces fear and anxiety in rats through CB1 and CB2 receptors in a key brain defense region ↗
Boosting the endocannabinoid 2-AG in a brain defense region reduced fear and anxiety in rats through both CB1 and CB2 receptors.
Metabolites of the deadly synthetic cannabinoid 5F-MDMB-PINACA retain potency and show unusual CB1 receptor behavior ↗
The deadly synthetic cannabinoid 5F-MDMB-PINACA produces metabolites that remain active at CB1 receptors with atypical pharmacology, potentially explaining its severe toxicity.
Marijuana improved spatial learning in both young and old female rats, but combined with estrogen had negative effects in older rats ↗
Marijuana improved spatial learning in female rats, but combining it with estrogen in older rats produced negative cognitive effects through the GPR30 receptor.
Adolescent cannabis vapor exposure produced opposite brain changes in male and female mice on MRI ↗
Adolescent cannabis vapor exposure produced opposite brain changes in male and female mice: structural changes in females and functional connectivity disruption with cognitive deficits in males.
Review argues multi-cannabinoid combinations may treat Alzheimer's more effectively than CBD or THC alone ↗
A review argues that combining CBD and THC may treat Alzheimer's more effectively than either alone, based on preclinical evidence of complementary neuroprotective mechanisms.
Cannabinoids for Parkinson's and Dementia in Older Adults: Promising Biology, Almost No Clinical Proof ↗
Preclinical evidence for cannabinoids in Parkinson's and Alzheimer's is promising, but older adults are using them off-label despite almost no clinical trial data.
Medical cannabis patients showed improved brain white matter structure after 3-6 months of treatment, with CBD exposure linked to improvements ↗
Medical cannabis patients showed improved brain white matter coherence on MRI over 6 months, contrasting with impairments in recreational users, with CBD exposure linked to improvements.
Cannabis users show higher schizotypy traits and aberrant salience but normal salience processing on lab tasks ↗
Cannabis users reported more schizotypy traits and subjective aberrant salience experiences, but showed normal salience processing on an objective lab task.
Could boosting natural endocannabinoids help treat migraine pain? ↗
Blocking the enzymes that break down natural endocannabinoids could offer a new approach to migraine pain without cannabis-related psychoactive effects.
CBD reduced viral activity markers released from HIV-infected immune cells ↗
Lab study showed CBD reduced inflammatory vesicles released from HIV-infected immune cells, potentially by lowering viral activity.
Exercise consistently raises endocannabinoid levels in the body ↗
Meta-analysis confirmed that acute exercise consistently increases endocannabinoid levels, potentially explaining mood and pain benefits of physical activity.
CBD blocked THC-induced nausea in rats through serotonin receptors ↗
CBD blocked THC-induced nausea in rats through 5-HT1A serotonin receptors and also reversed THC-induced stress hormone elevation.
Rare cannabinoids altered the endocannabinoid system in skin cells ↗
Four rare cannabinoids (CBG, CBC, THCV, CBGA) each uniquely modulated the endocannabinoid system in human skin cells but shared common effects on receptor binding.
Parrots lost their CB2 cannabinoid receptor gene and are more vulnerable to brain inflammation ↗
Parrots naturally lack the CB2 cannabinoid receptor gene, making their brains more vulnerable to inflammation and demonstrating CB2's protective role.
A CB1 receptor enhancer reduced opioid withdrawal symptoms in mice without cannabis-like side effects ↗
A CB1 receptor enhancer fully blocked withdrawal-induced diarrhea and weight loss in opioid-dependent mice without cannabis-like side effects.
CBD may affect psychiatric disorders by changing how genes are turned on and off ↗
Research suggests CBD may work partly by changing DNA methylation patterns, offering a new explanation for its broad effects on anxiety, depression, and psychosis.
Chronic cannabis use may impair the brain's error-correction system through the cerebellum ↗
Review and computational model suggest chronic cannabis use impairs the cerebellum's ability to process sensory errors, explaining observed motor learning deficits.
Acidic cannabinoids, especially CBGA, blocked a key inflammatory pathway in immune cells ↗
Minor acidic cannabinoids, especially CBGA, potently blocked a key calcium-driven inflammatory pathway in immune cells, while CBD and THC did not.
A cannabinoid receptor agonist broadly suppressed inflammatory gene activity in human brain cells ↗
A synthetic cannabinoid broadly suppressed inflammatory gene expression in human astrocytes through CB1-independent mechanisms involving neuroprotective transcription factors.
How cannabis and cannabinoids affect reproductive hormones and fertility ↗
Review found THC disrupts reproductive hormones, egg development, and sperm function through the hypothalamic-pituitary-gonadal axis, though mostly from preclinical evidence.
CBD disrupted fear memory reconsolidation in female rats through hippocampal CB1 receptors ↗
CBD disrupted fear memory reconsolidation in female rats through hippocampal CB1 receptors, reducing fear behavior for over a week without reinstatement.
Regular cannabis users showed better facial emotion recognition, including those with schizophrenia ↗
Large study of 6,229 people found lifetime cannabis use was linked to better facial emotion recognition across schizophrenia patients, siblings, and healthy controls.
A neutral CB1 blocker reduced cocaine-seeking behavior in animals without the side effects of rimonabant ↗
A neutral CB1 antagonist reduced cocaine-seeking behavior and relapse in rodents through dopamine pathways without the side effects seen with rimonabant.
CB2 receptors may play a key role in alcohol addiction ↗
Converging evidence from animal models and human studies suggests CB2 cannabinoid receptors play an important role in alcohol addiction biology.
Blocking endocannabinoid signaling combined with stress hormones made fear memories stronger and more generalized ↗
Combining stress hormones with a CB1 blocker turned normal fear memories into intense, generalized ones resembling traumatic memories in rats.
Schizophrenia with heavy cannabis use showed different brain structure than cannabis-induced psychosis ↗
Brain imaging showed schizophrenia patients with cannabis use had thinner cortex than cannabis-induced psychosis patients, supporting distinct pathophysiology.
Boosting endocannabinoid levels disrupted habit formation in mice ↗
Boosting either major endocannabinoid (anandamide or 2-AG) disrupted habitual behavior formation in mice, suggesting potential for preventing compulsive drug seeking.
A portable brain scanner detected THC impairment more accurately than field sobriety tests ↗
Portable brain imaging with machine learning detected THC impairment with 76% accuracy and only 10% false positives, outperforming field sobriety tests.
CB2 receptors play a complex, age- and sex-dependent role in motor tics ↗
CB2 receptors suppress motor tics in adult mice but may generate them in juveniles, with sex differences potentially relevant to Tourette syndrome prevalence.
THC and CBD each affected brain responses to unexpected sounds differently based on cannabis use history ↗
Controlled trial showed THC and CBD each altered brain responses to unexpected sounds, with CBD modifying THC's effects differently in frequent vs less-frequent users.
How THC and CBD affect the brain's reward system, and what that means for psychosis ↗
THC modulates reward-related brain regions in ways that correlate with psychotic symptoms. CBD appears to act in the opposite direction on the same regions.
Where THC acts in the brain depends on dose and how many cannabinoid receptors are present ↗
Meta-analysis of 372 participants found THC's brain effects are dose-dependent and track with CB1 receptor density across regions.
Large meta-analysis maps how youth cannabis use changes brain activation patterns ↗
Meta-analysis of 45 fMRI studies (2,702 youth) found cannabis users showed altered activation in prefrontal and cingulate regions, varying by sex, severity, and psychiatric comorbidity.
The arthritis drug celecoxib did not ease cannabis withdrawal and actually increased craving ↗
In 15 daily cannabis smokers, the COX-2 inhibitor celecoxib did not reduce withdrawal symptoms or change endocannabinoid levels, and it increased cannabis craving.
Chronic THC caused significant testicular shrinkage and hormone changes in monkeys ↗
Six rhesus macaques given daily THC edibles experienced 58% testicular volume loss and hormone shifts consistent with testicular failure, in a dose-dependent pattern.
Male and female mice develop tolerance to THC through different molecular mechanisms ↗
Blocking CB1 receptor desensitization delayed THC tolerance in male mice but not females, revealing sex-specific mechanisms. Females were also less sensitive to cannabinoid pain relief.
Brain imaging reveals distinct structural, functional, and neurochemical signatures of heavy cannabis use ↗
Multimodal brain imaging of 24 heavy cannabis users found distinct structural and functional changes linked to serotonin, dopamine, and opioid receptor systems.
Cannabis with equal THC and CBD causes less anxiety than THC alone, especially in calm users ↗
Cannabis with equal THC and CBD caused less anxiety than THC alone. CBD fully blocked THC anxiety in calm users but not in those with high baseline anxiety.
Cannabis use changes blood biomarker patterns in people with schizophrenia ↗
Schizophrenia patients with cannabis use disorder showed different blood biomarker patterns than those with schizophrenia alone, with elevated serotonin receptors and inflammation markers absent in dual-diagnosis patients.
Prenatal CBD exposure disrupted early development in mouse pups differently by sex ↗
Mouse pups exposed to CBD prenatally showed sex-specific disruptions: males gained extra weight and changed vocalizations, while females had impaired motor and discrimination abilities.
Animal evidence supports classifying cannabis smoke and THC as developmental toxicants ↗
Animal studies consistently show prenatal cannabis/THC exposure causes cognitive, emotional, and drug sensitivity changes in offspring, supporting their classification as developmental toxicants.
THC-only cannabis vapor worsened brain activity disruptions in a schizophrenia model, but balanced THC/CBD did not ↗
In a schizophrenia rat model, THC-only cannabis vapor worsened brain oscillation deficits while balanced THC/CBD vapor preserved or enhanced brain activity.
THC withdrawal in mice disrupts dopamine, sleep, and behavior, especially in males ↗
THC withdrawal in mice disrupted dopamine release, sleep patterns, and behavior in ways that mirror human withdrawal, with more pronounced effects in males.
How the endocannabinoid system could be a therapeutic target for multiple sclerosis ↗
Beyond relieving MS symptoms, cannabinoids and ECS modulators may promote oligodendrocyte survival and myelination, suggesting potential disease-modifying effects.
In young adults with bipolar disorder, a brain response to stress was linked to less cannabis use and better mood outcomes ↗
Young adults with bipolar disorder showed a unique brain response to stress that correlated with less cannabis use and better depression outcomes over one year.
First meta-analysis finds altered endocannabinoid levels in fibromyalgia patients ↗
First meta-analysis finds fibromyalgia patients have altered levels of endocannabinoid-like molecules, supporting endocannabinoid system involvement in chronic widespread pain.
Cannabis users had worse verbal memory but adolescents were not more vulnerable than adults ↗
Cannabis users showed worse verbal memory than controls, but adolescent users (16-17) were not more impaired than adult users (26-29), challenging the adolescent vulnerability hypothesis.
Adolescent THC caused lasting memory deficits in female rodents by disrupting synaptic plasticity and estrogen signaling ↗
Adolescent THC exposure caused lasting, sex-specific hippocampal damage in rodents, with females more severely affected through disrupted estrogen-endocannabinoid signaling.
Daily THC in Adolescent Mice Disrupted Immune Cells in the Brain Until Young Adulthood ↗
Daily THC during adolescence disrupted brain immune cell (microglia) function in mice through young adulthood, impairing responses to infection and stress. Effects were adolescent-specific and eventually resolved.
Cannabis Use Linked to Weaker Brain Connectivity in Adults with Childhood ADHD ↗
Brain imaging found adults with childhood ADHD who used cannabis had weaker thalamus-parietal connections than non-users, while non-users had stronger-than-typical connectivity in these regions.
Massive Review: How Cannabis Affects the Developing Adolescent Brain ↗
The largest neuroimaging review of adolescent cannabis use (90 studies, 9,441 participants) found evidence of altered brain structure and function in frontoparietal, frontolimbic, frontostriatal, and cerebellar regions.
CB2 Receptors in Skin Cells Suppressed Chemo-Induced Nerve Pain in Mice ↗
Mouse study identified CB2 cannabinoid receptors in skin immune cells as the mechanism for suppressing chemotherapy-induced nerve pain, working through a peripheral pathway that avoids psychoactive effects.
A Cannabinoid Hypothesis of Schizophrenia: How Cannabis May Trigger Psychosis ↗
Researchers proposed a "cannabinoid hypothesis" of schizophrenia describing multiple biological pathways through which THC may trigger psychosis, paralleling established dopamine and serotonin hypotheses.
How TRPV1 Channels Explain Both Cannabis Pain Relief and Hyperemesis Syndrome ↗
Review identified the TRPV1 ion channel as the common mechanism behind both cannabis pain relief and cannabinoid hyperemesis syndrome, explaining why capsaicin and hot showers treat CHS.
Alcohol and Cannabis Together Shrank Brain Gray Matter Faster Than Either Alone ↗
Longitudinal brain imaging of 724 adolescents found combined alcohol and cannabis use accelerated gray matter decline in five brain regions, with neither substance alone producing the same effect.
Non-Right-Handedness in Schizophrenia Linked to Cannabis Use Disorder ↗
Study of 667 schizophrenia patients found very high non-right-handedness (42.4%), which was associated with cannabis use disorder and learning disabilities, suggesting shared neurodevelopmental origins.
Adolescent Mice That Self-Administered Synthetic Cannabinoid Developed Lasting Brain Changes ↗
First study showing adolescent mice voluntarily self-administered synthetic cannabinoid JWH-018, leading to lasting compulsive behaviors and brain neuroinflammation in adulthood.
Long-Term Cannabis Users Lost 5.5 IQ Points and Had Smaller Hippocampi by Midlife ↗
A 45-year cohort study found long-term cannabis users lost 5.5 IQ points from childhood, had poorer learning and processing speed, and smaller hippocampi by midlife, specific to cannabis over other substances.
Cannabis May Affect Depression Risk Through Epigenetic Changes to Depression Genes ↗
Cross-referencing cannabis methylation studies with depression genetics found multiple depression-associated genes are epigenetically regulated by cannabis, suggesting a molecular mechanism for the cannabis-depression link.
An Endocannabinoid-Boosting Drug Reduced Tics in Tourette Syndrome ↗
Phase 1 crossover trial found a single dose of an endocannabinoid-boosting drug (MAGL inhibitor) significantly reduced tics and premonitory urges in 20 adults with Tourette syndrome.
Adolescents Were More Cognitively Impaired by THC Than Adults at the Same Doses ↗
RCT found adolescents (18-20) showed cognitive impairments and brain wave changes from THC that adults (30-40) did not, despite both groups feeling equally intoxicated.
CBD Reduced Heroin Withdrawal Symptoms and Normalized Brain Chemistry in Mice ↗
CBD reduced anxiety, agitation, and physical withdrawal symptoms in heroin-dependent mice while normalizing gene expression changes in brain reward regions.
RCTs on Cannabinoids for Movement Disorders Show Mixed Results Across Conditions ↗
Systematic review of RCTs found cannabinoids improved Tourette tics and some Parkinson's symptoms but showed no benefit for dystonia. Evidence is limited by small, heterogeneous trials.
Bayesian Modeling Suggests Adolescent Cannabis Use Causes Faster Brain Cortex Thinning ↗
Causal modeling of 637 IMAGEN study adolescents found a directional relationship from cannabis use to accelerated prefrontal cortical thinning, consistent with cannabis affecting brain development.
CBD for Autism: Promising Preclinical and Early Clinical Signals, but Evidence Is Still Thin ↗
Review found CBD shows biological plausibility and early promise for ASD symptoms through the endocannabinoid system, but clinical evidence is limited and the authors caution against premature use.
Cannabis Hyperemesis Syndrome: How the Same System That Prevents Nausea Can Also Cause It ↗
Review explained how chronic cannabis use flips the endocannabinoid system from antiemetic to proemetic, causing CHS, and provided key differences from cyclic vomiting syndrome.
Why Adolescent Brains Are Uniquely Vulnerable to Cannabis: The Endocannabinoid-Dopamine Connection ↗
Review explained how the developing endocannabinoid system makes adolescent brains uniquely sensitive to THC, particularly through disruption of still-maturing dopamine circuits linked to psychosis and addiction.
Genetic Variants for Substance Use and Brain Structure Share Common Pathways ↗
Genetics study found shared genetic links between brain cortical structure and substance use behaviors, with cannabis use genetics correlating with insula surface area differences.
Daily THC Edibles During Pregnancy Impaired Placental Function in Rhesus Monkeys ↗
Rhesus monkeys given daily THC edibles during pregnancy showed reduced placental blood flow, lower fetal oxygen, decreased amniotic fluid, and placental tissue damage with microinfarctions.
Prenatal THC exposure caused sex-specific brain and behavior changes in rat offspring ↗
Rat study found prenatal THC caused sex-specific brain lipid disruptions and neuropsychiatric-like behaviors in offspring, with males more persistently affected.
Cannabis exposure altered DNA methylation at autism-linked genes in lab-grown sperm cells ↗
Lab model of human sperm development showed cannabis exposure altered DNA methylation at autism-linked and imprinted genes.
Brain imaging showed less damage in cannabis-induced psychosis compared to schizophrenia with cannabis use ↗
Brain imaging study of 60 participants found cannabis-induced psychosis had fewer white matter abnormalities and more gray matter than schizophrenia with cannabis use.
Largest fMRI study found no reward processing differences between cannabis users and non-users ↗
Largest fMRI study of cannabis and reward processing (125 participants) found no differences between users and non-users in reward anticipation, with adolescents showing no extra vulnerability.
Smoking high-THC cannabis changed DNA methylation enzyme levels in blood cells within hours ↗
Study of 24 cannabis users found smoking high-THC cannabis changed DNA methylation enzyme levels in blood cells within hours, a potential link to psychosis risk.
THC improved memory and movement recovery after traumatic brain injury in mice ↗
Mice given THC for 3 days after brain injury recovered working memory and motor function, with increased brain repair factors BDNF, GDNF, and G-CSF.
Large genetic study identified shared DNA between smoking, cannabis use, and schizophrenia ↗
Genome-wide study of 780,000+ people found shared genetic factor explaining 8.6% of schizophrenia risk, highlighting NCAM1 as a key gene linking smoking, cannabis, and psychosis.
American Heart Association statement warned marijuana may adversely affect brain health ↗
American Heart Association scientific statement concluded marijuana may adversely affect brain health through cognitive impairment and increased stroke risk, especially during neurodevelopment.
Synthetic Cannabinoid Convulsions Are Not True Seizures, Mouse Study Suggests ↗
Mouse study found four synthetic cannabinoids caused convulsions that were not true brain seizures on EEG, suggesting standard anti-seizure drugs like diazepam may be ineffective.
Targeting Brain Immune Cells With Cannabinoids Reduced Inflammation and Protected Neurons in Lab Study ↗
Lab study found synthetic cannabinoids targeting either CB1 or CB2 receptors reduced brain immune cell inflammation and protected neurons from secondary damage via MAPK suppression.
Synthetic Cannabinoid Prevented Medium-Severity Convulsions in Both Male and Female Rats ↗
In adolescent rats, synthetic cannabinoid WIN 55,212-2 prevented medium-severity convulsions in both sexes and increased hippocampal CaMKII signaling.
Brain Glutamate Levels Were Lower in Cannabis Users and Linked to Craving During Abstinence ↗
Study of 20 cannabis users found brain glutamate levels were lower than controls during 21 days of abstinence, with declining glutamate strongly correlated with increasing craving.
Adolescent THC Exposure Changed Gene Networks in Mouse Brains Differently by Sex ↗
Mouse study found adolescent THC exposure changed brain gene networks differently by sex, with four key driver genes also linked to human cannabis use disorder vulnerability.
CBD-Enriched Cannabis Extract Changed Hippocampal Proteins in Adolescent Rats Without Affecting Behavior ↗
Adolescent rats given CBD-enriched cannabis extract showed no behavioral changes but had significant hippocampal synaptic protein alterations, suggesting hidden molecular effects during brain development.
Traumatic Brain Injury Disrupts the Brain's Endocannabinoid System, Worsening Damage ↗
Mouse study found traumatic brain injury depleted endocannabinoids by increasing their metabolizing enzymes, contributing to brain barrier damage, reduced blood flow, and anxiety.
10-Year Study Shows Adolescent Cannabis Use Linked to Different Brain Changes Than Young Adult Use ↗
10-year study of 704 people found adolescent cannabis initiation caused prefrontal cortex thinning linked to later drug use, while young adult initiation affected temporal areas linked to psychotic symptoms.
Mice Showed Sleep Disruption After Stopping Cannabinoid Treatment ↗
Mouse study found cannabinoid cessation reduced sleep during normal sleep periods, providing an animal model for human cannabis withdrawal sleep disturbance.
Cannabis use linked to lower levels of a psychosis-associated brain enzyme ↗
Translational study found psychosis patients with prior cannabis use had lower CDK5 (a psychosis-linked enzyme) and fewer social deficits than those without cannabis history.
Cannabis extracts produced different pain relief than pure THC-CBD blends at the same ratio ↗
Animal study found a whole cannabis extract and a pure 1:1 THC:CBD mix produced different pain-relief patterns and engaged different brain receptors, despite matching THC:CBD ratios.
Male and female rat brains develop endocannabinoid signaling on different timelines ↗
Animal study found the endocannabinoid system in the prefrontal cortex develops on different timelines in male and female rats, with females maturing earlier.
Repeated exposure to a synthetic cannabinoid caused lasting cognitive and brain changes in mice ↗
Mouse study found 7 days of synthetic cannabinoid JWH-018 produced psychotic-like symptoms and lasting brain changes in memory, social behavior, and neuroplasticity persisting 15+ days after stopping.
Injected vs. smoked cannabis had different effects on inflammation in pregnant rats ↗
Pregnant rat study found injected THC/CBD increased fetal inflammation while smoked cannabis reduced it, showing route of administration fundamentally changes outcomes.
Synthetic cannabinoid caused lasting brain metabolism changes and memory deficits in adult mice ↗
Mouse study found synthetic cannabinoid WIN 55,212-2 caused lasting brain metabolism reductions and memory deficits that persisted after prolonged abstinence, especially when exposure occurred in early adulthood.
CBD reversed social behavior and brain changes caused by adolescent binge drinking in rats ↗
CBD reversed social behavior deficits, abnormal stress responses, and brain plasticity changes caused by adolescent binge drinking and social stress in a rat model.
Cannabis products labeled indica and sativa had different effects on cognitive effort in rats ↗
Rats given oral cannabis oil labeled indica were less willing to exert cognitive effort for rewards compared to sativa-labeled oil with identical THC/CBD content, suggesting other compounds matter.
CBD improved memory in adolescent rats that were exposed to THC before birth ↗
CBD given during adolescence rescued memory deficits and restored brain plasticity markers in rats prenatally exposed to THC, suggesting a potential therapeutic window.
CBD reduced Alzheimer's-related brain damage and improved cognition in mice ↗
Mouse study found CBD protected against Alzheimer's-related cognitive deficits by modulating microglial activity and inflammatory gene expression.
Cannabis and childhood trauma interacted to lower the age when psychosis first appeared ↗
Multi-site study of 1,185 people found cannabis and childhood trauma interacted to predict earlier psychosis onset, with hippocampal volume as a biological mediator.
Synthetic Cannabinoid WIN55,212-2 Caused Anxiety and Reduced Activity in Mice, With Female Mice Less Affected ↗
Synthetic cannabinoid WIN55,212-2 caused anxiety and reduced activity in mice dose-dependently, with female mice less affected.
Blocking an Endocannabinoid-Degrading Enzyme Protected Rat Brain Cells From Toxic Damage ↗
Blocking the enzyme that degrades the brain's main endocannabinoid protected rat brain tissue through multiple receptor pathways.
CB1 Cannabinoid Receptors Are Concentrated in Pain-Processing Spinal Cord Regions in Both Rats and Humans ↗
CB1 cannabinoid receptors are concentrated in spinal cord pain-processing regions in both rats and humans, consistent across sex.
Prenatal THC Exposure Altered Hippocampal Development in Mice Through a Specific Gene Pathway ↗
Prenatal THC altered mouse hippocampal development through the CB1 receptor and MEF2C pathway, with effects rescued by a CB1 blocker.
Blocking the Brain's Endocannabinoid System Triggered a Full Stress Response in Rats, Even Without Any Stressor ↗
Multiple methods of blocking endocannabinoid signaling in rats all triggered full stress responses, proving this system actively suppresses stress at rest.
Prenatal Cannabinoid Exposure Caused Memory Deficits in Adolescent Rats by Disrupting a Key Neural Adhesion Molecule ↗
Prenatal cannabinoid exposure caused adolescent rat memory deficits through reduced PSA-NCAM and imbalanced glutamate signaling, with PSA administration rescuing the impairment.
How Cannabis Tolerance Builds: What Happens to Your Brain's CB1 Receptors ↗
Chronic cannabis use reduces CB1 receptor number and responsiveness throughout the brain — with significant sex differences — explaining why the same dose stops working over time.
CBD Inhibited a Brain Enzyme Linked to Neurodegeneration at Nanomolar Concentrations in Lab Tests ↗
Computational screening and lab testing found CBD selectively inhibits brain enzyme PDE9 at nanomolar concentrations, suggesting a potential neuroprotective mechanism.
CBD Injected Into the Amygdala Reversed Empathy-Related Pain Sensitivity in Mice Through Serotonin Receptors ↗
CBD injected into the amygdala reversed pain sensitivity caused by living with a partner in chronic pain, working through serotonin 5-HT3 receptors.
A Systematic Review Found CB2 Cannabinoid Receptors Play a Key Role in Regulating Food Intake ↗
Systematic review of 13 animal studies found CB2 cannabinoid receptors in brain reward areas are necessary for modulating food intake and energy balance.
Cross-Species Comparison Found Surprisingly Little Overlap in Endocannabinoid Receptor Distribution Between Mice, Rats, and Monkeys ↗
Cross-species analysis found only 5 of 14 endocannabinoid receptors had matching expression across mice, rats, and monkeys, revealing a translational research challenge.
Researchers Identified How CBD Prevents Seizures: By Blocking a Lipid That Tips the Brain Toward Overexcitation ↗
Study revealed CBD prevents seizures by blocking a lipid (LPI) that simultaneously boosts excitatory and weakens inhibitory signaling in the hippocampus through GPR55 receptors.
A Clinical Review of FAAH, the Enzyme That Breaks Down Endocannabinoids, Found Broad Therapeutic Potential But Disappointing Drug Trials ↗
Clinical review found FAAH enzyme modulates mood, pain, reward, and appetite, but drug trials targeting it have underperformed relative to animal model predictions.
Prenatal THC Caused Long-Term Cognitive Problems in Rat Offspring Through Sex-Specific Mechanisms in the Prefrontal Cortex and Hippocampus ↗
Prenatal THC caused lasting cognitive deficits in both male and female rats through radically different sex-specific mechanisms involving neural activity, proteins, and fatty acid depletion.
A Review Found Adolescent Cannabis Use Causes Lasting Cognitive Changes Through Epigenetic and Synaptic Mechanisms ↗
Review found adolescent cannabis use causes lasting cognitive changes through epigenetic modifications and synaptic disruptions, worsened by high-potency products and early initiation.
A Comprehensive Review of CBD's Effects on Brain Function Found Promise for Multiple Conditions but Called for Better Regulation ↗
Comprehensive review found CBD has documented benefits for epilepsy, anxiety, and pain, with emerging evidence for cognition and sleep, but called for better product regulation.
A Systematic Review Found Cannabinoids Can Cause Brain Damage Leading to Psychiatric, Cognitive, and Neurological Disorders ↗
Systematic review of 30 human studies found cannabinoids can cause psychiatric, cognitive, and neurological brain damage, with synthetic cannabinoids posing the greatest risk.
A Review Found Converging Evidence That Adolescent Cannabis Use Reduces Cognition, But Debate Continues Over Reversibility ↗
Review found converging evidence that frequent adolescent cannabis use reduces cognition, but debate continues about whether effects persist after quitting and whether brain imaging findings replicate.
Adolescents and adults showed different brain reward responses to cannabis in a controlled fMRI experiment ↗
Controlled fMRI study found THC blunted reward-related brain activity in adults but not adolescents. Adding CBD partially offset the effect in adults.
CBD reduced the negative emotional effects of opioid withdrawal in rats through serotonin receptors ↗
Rat study found CBD prevented the negative emotional conditioning associated with opioid withdrawal through 5-HT1A serotonin receptor activation.
CBD and terpene blends improved social behavior in an autism mouse model ↗
CBD and cannabis-inspired terpene blends both improved social behavior in an autism mouse model within 30 minutes of administration.
CB1 receptor expression changed in brain immune cells of an Alzheimer's mouse model ↗
Electron microscopy study found CB1 receptor expression increases in reactive microglia but stays proportionally constant in astrocytes in an Alzheimer's mouse model.
Blocking a fatty acid transport protein reduced anxiety in rats through CB2 receptors in the prefrontal cortex ↗
Rat study reveals a novel FABP5-CB2 cannabinoid receptor pathway in the prefrontal cortex that regulates anxiety behavior.
THC and CBD had different effects on brain growth factor in the adolescent hippocampus ↗
Animal study found THC and CBD had distinct effects on BDNF and TrkB expression in the adolescent hippocampus, suggesting different impacts on brain development.
A hemoglobin-derived peptide promoted deep sleep through the CB1 cannabinoid receptor in mice ↗
Mouse study found a hemoglobin-derived peptide promoted deep sleep through CB1 cannabinoid receptors, revealing new endocannabinoid sleep regulation pathways.
Review covers how plant and body-made cannabinoids affect brain diseases ↗
Review examines how plant and endogenous cannabinoids affect CNS diseases, finding diverse pharmacological activities with varying levels of clinical evidence.
Synthetic cannabinoid AB-FUBINACA damaged memory and hippocampal cells in mice ↗
Mouse study showed the synthetic cannabinoid AB-FUBINACA damaged hippocampal cells and impaired memory through oxidative stress, inflammation, and reduced BDNF and NMDA receptor expression.
Brain reward circuit shows reduced dopamine activity during THC withdrawal in rats ↗
Rat study found THC withdrawal reduced dopamine neuron firing in the brain's reward center, with functional changes in the habenula-RMTg circuit that may drive negative withdrawal states.
How cannabinoids affect long-term memory formation through synaptic plasticity ↗
Review found cannabinoid effects on memory and synaptic plasticity are contradictory, depending on dose, timing, brain region, and receptor interactions, highlighting biological complexity.
Computational analysis maps how phytocannabinoids may treat neurodegenerative diseases ↗
Computational analysis mapped how 8 phytocannabinoids interact with neurodegenerative disease targets through ErbB and PI3K-Akt pathways, with effects varying by sex, age, and disease.
Prenatal cannabis exposure linked to brain structure differences and ADHD in adolescents ↗
ABCD Study of 9,000+ adolescents linked prenatal cannabis exposure to frontal/parietal brain differences, with some changes partially explaining the pathway to ADHD.
Frequent cannabis users reported impaired sensory filtering and altered body awareness ↗
Frequent cannabis users reported difficulty filtering sensory stimuli and heightened emotional body awareness compared to non-users, with effects increasing with more use days.
CBD and THC relieve pain through different receptor systems in worm models ↗
In C. elegans worm models, CBD and THC both reduced pain responses but through entirely different receptor systems, with CBD effects wearing off within 6 hours while THC effects persisted.
Endocannabinoids travel in tiny cell-derived particles during COVID-19 and increase with disease severity ↗
COVID-19 patients showed significantly higher endocannabinoid concentrations in extracellular vesicles than in plasma, with levels increasing alongside disease severity, suggesting EVs serve as an endocannabinoid delivery system during infection.
A theory explaining why psychosis-linked drugs can also relieve psychiatric symptoms ↗
New theoretical framework explains how cannabis and other psychotomimetic drugs can both relieve psychiatric symptoms (compensation) and increase psychosis risk (sensitization) through the same neurotransmitter systems.
THC blocked immune cell development by eliminating oxidative stress through a novel mechanism ↗
THC prevented bone marrow cells from becoming macrophages by eliminating reactive oxygen species through two mechanisms, both independent of known cannabinoid receptors, revealing a novel pathway for cannabis-related immune effects.
THC raised endocannabinoid levels in healthy volunteers, but adding CBD made no difference ↗
Crossover RCT of 46 healthy volunteers found THC inhalation acutely raised anandamide and related lipids, but co-administered CBD at 10-30 mg did not influence these endocannabinoid changes.
The endocannabinoid and stress hormone systems interact in complex ways to influence psychosis risk ↗
Systematic review of 41 studies reveals the endocannabinoid and stress hormone (HPA) systems interact bidirectionally in psychosis: THC affects stress hormones while childhood trauma alters endocannabinoid signaling.
High-dose oral CBD raised anandamide levels 1.6-fold, and adding THC boosted the effect to 2.1-fold ↗
Clinical trials in 75 volunteers found 800 mg oral CBD raised anandamide 1.6-fold, while combining CBD with THC boosted it to 2.1-fold, revealing a dose threshold and synergistic effect relevant to psychiatric treatment.
How Chronic Pain Rewires the Brain's Reward System — And Why That Makes Cannabis and Opioid Misuse More Likely ↗
Chronic pain and addiction share a common neurobiological root — reduced dopamine signaling — explaining why pain patients who self-medicate with opioids or cannabis are vulnerable to escalating into misuse.
Antioxidant NAC prevented anxiety and depression caused by adolescent THC exposure in rats ↗
In adolescent rats, THC exposure caused lasting anxiety and depression-like behaviors linked to brain changes in the nucleus accumbens. The antioxidant NAC prevented all of these effects.
Prenatal THC and CBD exposure caused different brain and behavior changes in male vs female rat offspring ↗
Prenatal THC, CBD, and THC+CBD exposure all caused low birth weight and sex-specific brain and behavioral changes in adolescent rats, with disrupted endocannabinoid signaling in the prefrontal cortex and hippocampus.
Blocking the CB2 cannabinoid receptor triggered a strong anti-tumor immune response against brain cancer in mice ↗
Blocking the CB2 cannabinoid receptor in mice with glioblastoma improved survival from 28 to 40+ days by reducing immunosuppressive macrophages and boosting cancer-killing T cells in the tumor.
Cannabis disrupted brain network connectivity equally in teens and adults, and adding CBD did not make it safer ↗
Controlled fMRI study found vaporized cannabis disrupted five major brain networks equally in teens and adults, and CBD co-administration did not reduce THC effects, challenging assumptions about CBD safety.
Children exposed to cannabis before birth showed subtle changes in brain white matter tracts involved in emotion and memory ↗
In 11,530 children from the ABCD Study, prenatal cannabis exposure was linked to subtle but reliable reductions in white matter integrity of the fornix, a brain pathway important for emotion and memory.
People at risk for cannabis use disorder showed more fluid and unstable brain connectivity patterns on fMRI ↗
Brain imaging study found people at risk for cannabis use disorder had more fluid and unstable dynamic brain connectivity patterns across multiple networks compared to controls.
Cannabis and nicotine had opposite effects on brain cortex thickness in teens and young adults ↗
MRI study of 223 teens and young adults found cannabis and nicotine each thinned the frontal cortex, but using both together partially offset the nicotine-related thinning effect.
Schizophrenia patients with cannabis history showed better cognitive performance and more brain activity than non-users ↗
An fMRI study found first-episode schizophrenia patients with cannabis history had better cognitive control and higher prefrontal brain activity than non-cannabis-using patients.
Rats exposed to THC in the womb showed stronger reward-seeking behavior and higher relapse vulnerability, especially males ↗
Prenatal THC exposure in rats amplified dopamine reward responses and opioid-seeking behavior, with male offspring showing greater vulnerability to relapse.
An 8-Year Study Tracked Whether Light Cannabis Use Changes the Adolescent Brain ↗
An 8-year study found that light cannabis use in late adolescence was associated with conduct problems but not with cognitive decline or changes in reward-related brain activity.
How Cannabis Changes Gene Expression Through Epigenetics ↗
A scoping review found that cannabis exposure alters DNA methylation at genes tied to dopamine signaling, neurodevelopment, and cell survival, with links to psychiatric symptoms.
Brain Wiring Differences in People With Cannabis Use Disorder ↗
An MRI study found that people with cannabis use disorder had increased structural brain connectivity in some regions and decreased white matter density in others.
CBD Improved Memory in a Rat Model of Fragile X Syndrome Through a Specific Brain Receptor ↗
CBD rescued memory deficits in Fragile X model rats through hippocampal GPR55 receptors, pointing to a specific mechanism for cognitive benefits in neurodevelopmental disorders.
How Cannabis Affects Eye Movements Relevant to Driving ↗
A systematic review found THC acutely impairs eye movement control and chronic cannabis users show lasting visual scanning deficits, with potential for roadside impairment testing.
Medical Cannabis Extracts Protected Brain Cells From Alzheimer's-Related Damage in Lab Tests ↗
Lab tests showed THC/THCA-dominant cannabis extracts protected brain cells from Alzheimer's-related amyloid-beta toxicity, but not by preventing plaque formation.
Boosting a Natural Brain Cannabinoid Blocked Opioid Reward Without Reducing Pain Relief ↗
Boosting the endocannabinoid 2-AG in mice blocked opioid reward without reducing pain relief, suggesting a potential strategy to make opioid treatment less addictive.
Activating CB1 Receptors Protected Against Brain Damage From Excitotoxicity in Mice ↗
A mouse study showed CB1 receptor activation protected against glutamate-induced brain damage by reducing oxidative stress through the NOX-2 pathway.
The Endocannabinoid System in the Cervix Changes During Pregnancy and May Contribute to Preterm Birth ↗
A mouse study found endocannabinoid levels rise in the cervix during pregnancy, and inflammation-induced disruption promotes premature cervical remodeling.
Natural and Synthetic Cannabinoids Protected Brain Mitochondria From Toxic Damage ↗
Cannabinoids protected brain mitochondria from toxic damage by activating mitochondrial CB1 receptors.
Cannabinoid receptor complexes are elevated in the brains of people with multiple sclerosis ↗
First identification of cannabinoid receptor complexes (CB1-GPR55 and CB2-GPR55) in human brain tissue, with significant upregulation in multiple sclerosis patients.
Four weeks without cannabis reversed brain network changes and improved cognition in people with MS ↗
Four weeks of cannabis abstinence restored default mode network activity and improved cognition across multiple domains in people with MS who were frequent users.
Brain differences in children predicted who would start using substances before age 15 ↗
In nearly 10,000 children, brain structural differences including thinner prefrontal cortex and larger overall brain volume preceded and predicted substance use initiation before age 15.
Cannabis Users' Self-Assessed 'Readiness to Drive' Predicted Actual Driving Impairment — But Not Perfectly ↗
After controlled THC dosing, cannabis users who felt unsafe to drive showed more impairment — but some who felt safe were still impaired, especially experienced users.
Blocking CB2 receptors on brain immune cells reduced neuroinflammation from graft-versus-host disease in mice ↗
CB2 receptors on brain microglia drove neuroinflammation in graft-versus-host disease, and a brain-penetrant CB2 blocker selectively reduced it without worsening the systemic immune response.
Prenatal THC exposure showed narrow effects on fetal muscle but triggered inflammation-related gene changes in primates ↗
Primate pilot study found prenatal THC exposure had narrow effects on fetal muscle development overall, but activated inflammation and cytokine pathways suggesting potential for longer-term tissue damage.
Adolescent THC did not worsen schizophrenia-like symptoms in rats with prenatal immune activation ↗
In a rat schizophrenia vulnerability model, adolescent THC impaired social behavior but did not worsen or interact with prenatal immune activation-induced cognitive deficits.
People with HIV had altered endocannabinoid levels, but cannabis use frequency did not change immune markers ↗
People with HIV showed higher inflammation and lower endocannabinoid levels, but cannabis use frequency did not alter these immune measures.
How Cannabis May Change the Adolescent Brain at the Cellular Level ↗
A translational study connecting mouse neuroscience with human brain imaging identified specific genes and cell types that may explain cannabis-related cortical thinning in adolescents.
Mouse Model of Prenatal THC Exposure Shows Anxiety, Depression, and Increased Alcohol Preference in Offspring ↗
A mouse model of high-dose prenatal THC exposure found offspring developed anxiety, depression, cognitive problems, and increased alcohol preference, with sex-dependent effects.
Comprehensive Review of CBD's Potential for Brain Disorders ↗
Review of 170 articles maps CBD's neuroprotective mechanisms across brain disorders.
Prenatal Cannabinoid Exposure Caused Sex-Specific Changes in Breathing, Heart Function, and Anxiety in Adult Rats ↗
Adult rats exposed to a synthetic cannabinoid before birth showed sex-specific changes in breathing control, cardiovascular function, and anxiety behavior.
Prenatal Cannabis Exposure Altered Dopamine Brain Circuits in Mouse Offspring But Did Not Increase Cocaine-Seeking ↗
Prenatal cannabis oil exposure altered VTA dopamine neurons in male mice (disinhibited firing) but did not increase cocaine-seeking in either sex.
Three Synthetic Cannabinoids Caused Lasting Anxiety, Motor Problems, and Memory Impairment in Mice ↗
Three synthetic cannabinoids caused prolonged anxiety, motor disruption, and endocannabinoid system dysregulation in mice, with one also impairing memory.
THC Activates Brain Support Cells (Astrocytes) Differently Depending on Age and Sex ↗
Systematic review found THC increases key astrocyte (brain support cell) markers, with effects varying by developmental stage and sex across 12 studies.
Periodontitis Combined With Stress Disrupts the Brain Endocannabinoid System in Rats ↗
In rats with both gum disease and chronic stress, the brain endocannabinoid system was disrupted with reduced CB1 receptors and metabolic enzymes, alongside increased neuroinflammation.
Endocannabinoid Receptors Show Strikingly Different Patterns Across Mice, Rats, and Primates ↗
Comparison of 14 endocannabinoid receptors across mice, rats, and macaques found zero receptors with matching expression patterns.
Prenatal Alcohol and Cannabinoid Co-Exposure Reduced Fetal Brain Blood Flow More Than Either Drug Alone in Mice ↗
In pregnant mice, combined alcohol and cannabinoid exposure reduced fetal brain blood flow more than either drug alone, and reduced cerebroplacental ratios predicted perinatal death with 81% sensitivity.
Prenatal THC Exposure Altered Fetal Brain Development in Rhesus Monkeys ↗
Daily THC edible exposure throughout pregnancy in rhesus macaques altered fetal brain growth, histology, and molecular pathways involved in axonal guidance.
CBD Reduced Gut Symptoms of Opioid Withdrawal in Mice ↗
Mouse study found CBD dose-dependently reduced gastrointestinal symptoms of opioid withdrawal, with consistent effects across both sexes during precipitated withdrawal.
Cannabis Leaf Extract Showed Anti-Inflammatory and Antidepressant Effects in Mice ↗
Cannabis leaf extract reduced depression-like behavior and brain inflammation in mice, with effects attributed to the combined action of THCA and the terpene B-caryophyllene.
CBD Improved Social Behavior and Reduced Repetitive Actions in Autism Mouse Model ↗
CBD improved social deficits (at 20 mg/kg) and reduced repetitive behaviors and hyperactivity (at 50 mg/kg) in a mouse model of autism, suggesting dose-dependent targeting of different symptoms.
Cannabinoid Receptor-Activating Compounds Killed Brain Cancer Cells in the Lab ↗
Lab study found two cannabinoid receptor-activating compounds killed glioma cancer cells while sparing normal brain cells, working through the PI3K/Akt pathway.
The Terpene D-Limonene Reduced THC-Induced Anxiety in Humans ↗
Double-blind trial found the terpene d-limonene selectively reduced THC-induced anxiety and paranoia without affecting other THC effects, providing first rigorous human evidence for a cannabis entourage effect.
Cannabinoid Treatment Reduced Alzheimer's Plaques and Improved Memory in Mice ↗
Ninety-day cannabinoid treatment in Alzheimer's model mice reduced amyloid plaque deposits, improved memory, and decreased brain inflammation markers.
CBGA Was the Most Potent Cannabinoid at Blocking a Channel Linked to Cancer and Kidney Disease ↗
CBGA was the most potent cannabinoid at blocking TRPM7 ion channels, which are involved in cancer, stroke, and kidney disease, working through the channel's kinase domain.
How Cannabis Triggers Psychosis Through the Brain's Endocannabinoid System ↗
Review of the past decade of research explains how cannabis triggers psychosis by disrupting the endocannabinoid system during adolescent brain development, affecting synaptic pruning and neurotransmitter signaling.
NIDA Leaders Highlight Major Gaps in Cannabis Research Despite Decades of Study ↗
NIDA leaders identify critical research gaps: effects of high-THC cannabis during brain development, therapeutic endocannabinoid system manipulation, and CUD treatment strategies.
Prenatal THC Created Sex-Specific Stress Vulnerability Through Dopamine Changes in Rats ↗
Rat study found prenatal THC disrupted stress hormone receptors and dopamine signaling specifically in male offspring, causing stress vulnerability that was correctable with a developmental intervention.
10 'Minor' Cannabinoids Tested for Pain Relief: THCP and CBC Were the Most Potent ↗
Systematic testing of 10 minor cannabinoids on pain neurons found THCP and CBC most potent at reducing pain signaling — expanding the analgesic toolkit beyond THC and CBD.
CBD Outperformed a Common Antipsychotic in Treating Autism-Like Behaviors in Zebrafish ↗
In a zebrafish autism model, CBD reversed hyperactivity and aggression more effectively than risperidone and normalized underlying neurobiological markers.
Stress Hormone Activates the Endocannabinoid System to Suppress Pain Signals in the Brain ↗
Rodent brain study reveals stress hormone corticosterone triggers endocannabinoid (2-AG) production in a pain-control region, reducing inhibitory GABA signaling through CB1 receptors.
Babies Exposed to Cannabis in the Womb Had Smaller Brain Volume in Their First Month of Life ↗
Neonatal MRI found lower total brain volume in infants exposed to cannabis in utero — in a carefully controlled study excluding alcohol, tobacco, and other drug exposure.
CB1 Receptors in the Brain's Reward Circuit Link Anxiety to How Animals Learn From Rewards ↗
Mouse study finds CB1 receptors on dopamine neurons in the VTA-to-NAc circuit link trait anxiety to enhanced reward learning.
Weight Loss Drug Danuglipron May Bind to Cannabinoid Receptors Better Than THC ↗
Computational study: oral weight loss drug danuglipron showed higher binding affinity for cannabinoid receptors CB1 and CB2 than THC or endocannabinoids.
Could the Endocannabinoid System Help Treat Malignant Hyperthermia? ↗
Review proposes endocannabinoid system modulation as potential adjunctive therapy for malignant hyperthermia, based on CB1-mediated calcium regulation in muscle.
CBD Helps Rats Forget Meth-Associated Memories Through Dopamine Receptors in the Hippocampus ↗
Rat study: CBD accelerated extinction of meth-seeking behavior and prevented relapse. Both effects required D1 dopamine receptors in the hippocampal dentate gyrus.
Mouse study suggests endocannabinoid receptors help mediate anti-inflammatory effects in colitis ↗
A mouse study found that CB1 and CB2 cannabinoid receptors are involved in the anti-inflammatory action of a muscarinic receptor drug in colitis, revealing crosstalk between the cholinergic and endocannabinoid systems in gut inflammation.
CBD relieves nerve pain in mice partly through the opioid system ↗
CBD reduced nerve pain in mice through a mechanism involving peripheral mu and delta opioid receptors, suggesting it may engage the body's own pain-relief pathways without being an opioid itself.
CBD and THC nanoemulsions showed anticonvulsant and antioxidant effects in mice ↗
Nanoemulsion-delivered CBD, THC, and their combinations reduced seizures and brain oxidative stress in mice, with low-dose combinations matching the anticonvulsant drug valproic acid in delaying seizure progression.
Dual-action drugs targeting cannabinoid and PPAR receptors reduced binge eating in rats ↗
Two drugs that simultaneously target cannabinoid CB1 and PPAR receptors reduced binge eating in rats and corrected disrupted appetite-regulating brain pathways, offering a potentially safer dual-target approach than CB1 blockers alone.
Nanoencapsulated CBD reduced panic-like behaviors in mice at very low doses ↗
Nanoencapsulated CBD reduced panic-like responses in mice confronted by a venomous snake at much lower doses than standard CBD, with confirmed delivery to fear-processing brain regions via both injection and nasal routes.
CBD/THC extract reduced inflammation and improved movement after spinal cord injury in rats ↗
A cannabis extract with equal parts CBD and THC reduced neuroinflammation, prevented tissue damage expansion, and improved movement recovery in rats after spinal cord injury, working across both acute and chronic phases.
Cannabinoids shaped brain activity and new neuron growth in zebrafish ↗
In zebrafish, CB1 cannabinoid receptors maintained excitatory brain activity in cognitive regions, while cannabinoid exposure reduced neural stem cell proliferation but increased the survival and integration of newly born neurons.
CB2 cannabinoid receptor effects on the blood-brain barrier in HIV depended on receptor levels ↗
In HIV blood-brain barrier models, CB2 cannabinoid receptor activation improved barrier integrity in cells with high receptor expression but worsened damage in cells with low expression, suggesting individual variation may determine whether cannabis helps or harms.
Review explores how the endocannabinoid system connects stress, nausea, vomiting, and cannabis hyperemesis ↗
A review examines the endocannabinoid system's role in regulating nausea, vomiting, and stress, explaining how chronic cannabis use may dysregulate these processes and contribute to the paradoxical vomiting seen in CHS and CVS.
Prenatal THC exposure altered dopamine receptor genes and brain cell excitability in adolescent male rats ↗
Prenatal THC exposure reprogrammed dopamine receptor expression in the prefrontal cortex of adolescent rats through epigenetic changes, with male offspring showing the strongest effects on D2 receptors, neuron excitability, and neural guidance systems.
Cannabinol (CBN) showed anti-inflammatory effects in skin cells through a TRPV1 receptor mechanism ↗
CBN reduced pro-inflammatory cytokines and increased anti-inflammatory markers in human skin cells, with the key finding that its reduction of itch-associated IL-31 was mediated specifically through TRPV1 receptors.
CBD altered brain copper distribution in healthy mice but not in Alzheimer's model mice ↗
Chronic CBD treatment increased brain copper in healthy female mice but not in Alzheimer's model mice, disrupting the coordinated regulation of metals across brain regions in the disease model, suggesting CBD's brain effects differ between healthy and diseased states.
CBD triggered autophagy and cell death in amyloid-expressing cells while showing side effects in healthy cells ↗
CBD selectively induced beneficial cell death in amyloid-beta-expressing cells while causing side effects in healthy cells, with FAAH involvement helping to rescue dysfunction in amyloid-expressing worm models, revealing context-dependent effects.
High-fat/high-sugar diet impaired memory through overactivation of the brain's endocannabinoid system ↗
A high-fat/high-sugar diet impaired mouse memory by overactivating the hippocampal endocannabinoid system and mTOR pathway, with CB1 receptor blockade or mTOR inhibition rescuing the memory deficits.
Scientists discovered a new form of brain signaling where cannabinoid and acetylcholine systems work together ↗
Scientists discovered muscarinic cannabinoid suppression of excitation (MCSE), a new form of brain signaling where simultaneous muscarinic and cannabinoid receptor activation produces a precise ~10-minute inhibition of excitatory transmission.
THC changes how fat cells handle fatty acids, potentially affecting liver fat accumulation ↗
Cell studies showed THC enhanced fat cell development and changed how fat cells handled fatty acids over time, which influenced how much fat accumulated in liver cells.
How chronic substance use changes the body's own cannabis-like chemicals ↗
A review of 15 studies found chronic substance use generally increases anandamide levels in the blood, suggesting the body's endocannabinoid system is disrupted across multiple types of addiction.
Inhaled CBD reduced two key neuroinflammation pathways in Alzheimer's disease mice ↗
In Alzheimer's mice, inhaled CBD reduced two key neuroinflammation pathways (IDO and cGAS) and lowered proinflammatory cytokines, suggesting a multi-target anti-inflammatory mechanism.
Cannabinoid receptors on stress-related brain cells shape how mice respond to threats ↗
Mice lacking cannabinoid CB1 receptors on stress-related norepinephrine neurons showed altered responses to various stressors, but the direction of change depended on the specific stress context.
THC impairs movement by shifting the brain's excitation-inhibition balance in the prefrontal cortex ↗
Mouse study found THC impairs movement by increasing inhibitory neuron activity in the prefrontal cortex and paradoxically triggering the brain's own endocannabinoid release during movement.
A common synthetic cannabinoid caused oxidative damage and cell death in rat brain and testes ↗
A rat study found the synthetic cannabinoid CUMYL-4CN-BINACA caused dose-dependent oxidative damage, inflammation, and cell death in both brain and testicular tissue after just 14 days.
CBD triggered cellular cleanup that reduced a Parkinson's-linked protein through CB1 receptors ↗
CBD activated cellular autophagy and reduced alpha-synuclein levels in neuroblastoma cells through CB1 receptor signaling, suggesting a mechanism relevant to Parkinson's disease.
CBD protected nerve cells from a Parkinson's toxin by activating antioxidant defenses ↗
CBD protected nerve cells from a Parkinson's-relevant toxin by activating the Nrf2 antioxidant pathway, reducing oxidative stress, and preventing cell death in culture.
Blocking an endocannabinoid-degrading enzyme protected worm dopamine neurons from Parkinson's-like damage ↗
In worms, blocking the enzyme that breaks down endocannabinoids protected dopamine neurons from Parkinson's-like damage through antioxidant mechanisms, with effects confirmed in a genetic knockout strain.
Trauma reminders increased cannabis craving by activating reward circuits in the brain ↗
Brain scans of 27 cannabis users with trauma histories showed that trauma reminders increased cannabis craving and activated reward circuits, revealing a potential neural pathway from trauma to problematic cannabis use.
Blocking CB1 receptors alongside activating NOP receptors worsened colitis in mice ↗
Combining a CB1 blocker with a NOP receptor activator worsened colitis in mice, revealing a cautionary interaction between the endocannabinoid and nociceptin systems.
Removing CB1 receptors from the hypothalamus reduced joint damage during aging in mice ↗
Mice lacking CB1 receptors in the hypothalamus had less joint damage and lower stress hormones with aging, suggesting the brain's cannabinoid system influences peripheral joint health.
Blood levels of the body's own cannabinoids showed limited connection to pain sensitivity in healthy adults ↗
In 91 healthy adults, blood endocannabinoid levels showed no broad association with pain sensitivity, though anandamide was linked to pressure pain thresholds.
Nano-Formulated CBD Rapidly Suppressed Neuropathic Pain in Mice Without Side Effects ↗
A nano-formulated CBD preparation fully suppressed neuropathic pain in mice with a single dose by selectively quieting overactive pain circuits.
Combining Anti-Inflammatory Lipids with Cannabinoids Enhanced Pain Relief in Diabetic Rats ↗
Combining an anti-inflammatory lipid mediator with cannabinoid receptor agonists produced enhanced pain relief in diabetic rats beyond either treatment alone.
How Cannabinoid Compounds Reshape Energy Metabolism in Brain Support Cells ↗
Cannabinoid receptor ligands reshaped energy metabolism in brain astrocytes, triggering calcium signaling, glycogen depletion, and increased metabolic output primarily through CB1 pathways.
Blood Markers of the Endocannabinoid System Differed in Substance Use Disorder With and Without ADHD ↗
Blood levels of endocannabinoid-related molecules differed in substance use disorder patients, with distinct patterns when ADHD was also present.
Lifelong Diet Composition Shaped How Adolescent THC Exposure Affected Adult Rat Behavior ↗
Lifelong dietary fatty acid composition influenced adult rat behavior and modified adolescent THC effects on anxiety and impulsivity.
Cannabis Users Showed Brain Network Patterns Associated With Younger Brains in UK Biobank Study ↗
UK Biobank analysis of 25,000+ people found cannabis users had brain network patterns resembling younger brains and better cognitive performance.
Postmortem brain study reveals altered endocannabinoid gene expression in people with alcohol use disorder ↗
Postmortem brain analysis found CB1 receptor gene expression elevated up to 125% and CB2 expression halved in people with long-term alcohol use disorder.
Cannabidiolic acid outperformed riluzole as a neuroprotective treatment in an ALS mouse model ↗
CBDA was the most effective of five cannabinoids tested in ALS mice, outperforming standard medication riluzole in preserving motor neurons and shifting brain immune cells toward an anti-inflammatory state.
Stress increases cocaine use in both sexes, but the cannabinoid system plays different roles in males versus females ↗
Stress increased cocaine use equally in male and female rats, but cannabinoid CB1 receptor blockade reduced intake through different patterns in each sex.
Stress disrupts brain reward circuit plasticity in male rats but not females, and the endocannabinoid system is responsible ↗
Stress eliminated a form of synaptic plasticity in the brain's insular-to-reward pathway in male rats only, dependent on the endocannabinoid system.
Women with fibromyalgia have elevated endocannabinoid levels linked to pain and poor fitness ↗
Women with fibromyalgia had elevated plasma anandamide that correlated with higher pain and lower fitness, while PAG-thalamus brain connectivity was linked to physical activity.
Oral CBD slowed disease progression and improved cognitive deficits in ALS mice differently by sex ↗
Oral CBD delayed disease progression (by weight) and improved specific cognitive and social deficits in ALS mice in a sex-dependent manner, but did not rescue motor function.
Anorexia nervosa involves coordinated shutdown of the endocannabinoid system through dual epigenetic changes ↗
Anorexia nervosa involves coordinated epigenetic suppression of the endocannabinoid system: reduced cannabinoid receptors and increased endocannabinoid degradation simultaneously impair appetite signaling.
Endocannabinoids and brain peptides interact in complex ways relevant to depression and anxiety treatment ↗
Review maps bidirectional interactions between endocannabinoids and nine neuropeptide systems in the brain, revealing complex regulatory networks relevant to depression and anxiety treatment.
Adolescent THC exposure caused lasting brain connectivity and social behavior changes in mice ↗
Mice given THC during adolescence showed lasting social deficits, sensorimotor gating problems, and disrupted cortico-striatal brain connectivity with altered dopamine receptor balance persisting into adulthood.
CBD Improved Memory and Reduced Anxiety in an Alzheimer's Mouse Model ↗
Alzheimer's model mice given daily CBD for two months showed improved memory, less anxiety, and reduced brain oxidative stress.
Endocannabinoid Levels Track with Pancreatitis Stage and Pain ↗
Case-control study of 231 people found anandamide levels rose with pancreatitis severity while 2-AG dropped with pain intensity.
Blocking Cannabinoid Receptors in Newborn Mice Produced ADHD and Tourette-Like Behaviors ↗
Disrupting cannabinoid receptors in newborn mice produced a combined ADHD/Tourette-like phenotype with vocal tics, hyperactivity, and learning deficits, especially in males.
Heavy Lifetime Cannabis Use Linked to Lower Brain Activity During Memory Tasks ↗
Brain imaging of 1,003 young adults found heavy lifetime cannabis users had significantly lower brain activation during working memory tasks.
The Endocannabinoid System Drives Immune Cell Infiltration in Eosinophilic Esophagitis ↗
Study found the endocannabinoid system drives eosinophil infiltration in eosinophilic esophagitis, with CB2 receptor blocking reducing inflammation in mice.
Lifetime Cannabis Use Linked to Larger Brain Volumes and Better Cognition in Middle-Aged and Older Adults ↗
UK Biobank data from adults aged 40-70 found lifetime cannabis use associated with larger brain volumes in key regions and better cognitive performance.
Cannabis Use Lowered a Key Endocannabinoid in People with Schizophrenia ↗
Study of 93 people found lifetime cannabis use lowered the endocannabinoid 2-AG in schizophrenia patients, while non-clozapine antipsychotics altered CB2 receptors.
Cannabis Use During Pregnancy Disrupted Blood Vessel Function in the Placenta ↗
Placental tissue study found cannabis use completely eliminated endocannabinoid-mediated blood vessel relaxation and greatly reduced nitric oxide signaling.
Chronic Cannabis Users Had Shorter Telomeres, Suggesting Accelerated Biological Aging ↗
Case-control study of 60 people found chronic cannabis users had significantly shorter telomeres than age-matched controls, suggesting accelerated biological aging.
Depression and Cannabis Use May Share Brain Reward Processing Deficits, But Evidence Is Inconsistent ↗
Systematic review found depression and cannabis use share brain reward processing regions but no consistent biomarkers, with cannabis amotivation vastly understudied (only 2 studies).
How Cannabis Use May Generalize Stress Responses Through Brain Changes in Rats ↗
Rat study found THC+CBD use caused stress responses to generalize to neutral stimuli via astrocyte changes in the nucleus accumbens, but only in males.
How Cannabis Causes "the Munchies": It Boosts Motivation to Eat, Not Just Appetite ↗
PNAS study found cannabis vapor increased food intake in humans and rats by boosting eating motivation and overriding food reward signals, without altering hunger hormones.
CBD Reduces Brain Activation in a Reward Region During Alcohol Cue Exposure ↗
Crossover fMRI trial found 800 mg CBD reduced precuneus activation during alcohol cue exposure in AUD participants, though craving and mood were unaffected.
Cannabichromene Killed Pancreatic Cancer Cells Through Multiple Cell Death Pathways ↗
Preclinical study found cannabichromene killed pancreatic cancer cells through multiple death pathways (apoptosis and ferroptosis) via TRPV1 and CB2 receptors, with tumor inhibition confirmed in mice.
CBD-Rich Cannabis Extract Outperformed Pure CBD Against Brain Inflammation in Mice ↗
Mouse study found CBD-rich cannabis extract was more effective than pure synthetic CBD against brain inflammation, reducing anxiety, cognitive deficits, and oxidative stress.
People with Autism Have Lower Levels of a Key Endocannabinoid ↗
Meta-analysis found people with autism had significantly lower blood anandamide levels, and animal models showed reduced brain endocannabinoids, with symptom improvement when levels were raised.
Women Cannabis Users Show Different Brain Responses to Cannabis Cues Than Men ↗
fMRI study found women cannabis users had blunted brain responses to cannabis cues compared to men, with unique brain-craving links found only in women.
Adolescent THC Exposure Caused Lasting Brain and Motivation Problems in Monkeys ↗
Six months of daily THC during adolescence in monkeys produced persistent brain connectivity changes in reward regions and lasting motivational deficits into adulthood.
THCV Can Either Mimic or Block THC Effects in Rats Depending on Dose ↗
In rats trained to recognize THC, THCV partially mimicked THC at moderate doses (54.6% substitution) but blocked THC effects at higher doses, with an inverted U-shaped response pattern.
Brain Stimulation Study Shows Cannabis Users Have Heightened Cortical Excitability ↗
TMS measurements showed cannabis users had increased cortical excitability, reduced intracortical inhibition, and delayed motor inhibition compared to controls, with changes correlating to addiction severity.
Meta-Analysis Finds Cannabis Users Have Lower Levels of Key Brain Chemicals ↗
First meta-analysis of brain spectroscopy studies found cannabis users had lower GABA and neural health markers in the anterior cingulate cortex, and lower glutamate in the basal ganglia.
IV THC Causes Pupil Constriction and Dampened Light Reflexes, Not Dilation ↗
A placebo-controlled trial found THC caused pupil constriction (not dilation) and dampened the pupillary light reflex for at least 5 hours in cannabis-naive volunteers.
Brain Imaging Finds CB1 Receptor Levels Linked to Emotional Numbing in PTSD, Not Overall Diagnosis ↗
PET imaging of 62 participants found CB1 receptor availability was not different in PTSD overall but was significantly linked to emotional numbing symptoms, suggesting a specific endocannabinoid role.
Prenatal Cannabis Exposure Linked to Risks Across Multiple Organ Systems in Offspring ↗
A review finds prenatal cannabis exposure affects multiple organ systems beyond neurodevelopment, including cardiovascular, metabolic, and growth outcomes.
Anandamide Shows Stronger Pain-Blocking Effects Than 2-AG on Migraine-Related Nerve Fibers in Mice ↗
In mouse meningeal preparations, anandamide showed stronger suppression of pain-related firing than 2-AG, pointing to FAAH inhibition as a migraine target.
Mouse Study Maps How Direct vs. Indirect Endocannabinoid Manipulation Affects Anxiety ↗
In mice, FAAH inhibition reduced anxiety while CB1 blockade and CB2 manipulation increased it.
Synthetic Cannabinoid 4F-MDMB-BUTICA Causes Developmental Toxicity and Gene Changes in Zebrafish ↗
4F-MDMB-BUTICA caused mortality, deformities, behavioral changes, and gene expression alterations in zebrafish embryos.
Study Quantifies Exactly How Much THC Reaches the Fetal Brain During Pregnancy ↗
Fetal brain THC reaches 35-50% of maternal blood. A model predicts 3.7 nM THC from 10mg inhaled.
CBD Nanoparticles Restore Gut-Brain-Bone Axis in Stressed Rats, Matching or Exceeding Standard Antidepressants ↗
CBD nanoparticles restored gut barrier function, reduced inflammation, and normalized metabolites in stressed rats, performing comparably to standard antidepressants.
CBD and Its Metabolites Reduce Human Neural Stem Cell Viability at Clinically Relevant Concentrations ↗
CBD and its metabolites reduced human neural stem cell viability at clinically relevant concentrations and altered differentiation markers, raising prenatal safety concerns.
Interspecies Differences in Cannabinoid Receptor Distribution May Explain Why Animal Pain Studies Do Not Translate to Humans ↗
A review finds significant species differences in cannabinoid receptor distribution that may explain why animal cannabinoid pain studies fail to translate to human clinical trials.
Daily Cannabis Users Show Normal Brain Value Signals for Cannabis But Disrupted Signals for Non-Drug Rewards ↗
An fMRI study found daily cannabis users had normal brain value signals for cannabis but disrupted signals for food rewards, supporting reward-narrowing theories of addiction.
How Cannabis Reshapes Brain Communication—and Why Chronic Users Are Different ↗
Cannabis disrupted brain connectivity patterns in all users, but chronic users showed persistent network changes even when sober—suggesting lasting brain adaptation.
Recreational Drug Users Had More Difficulty Recalling Personal Memories ↗
A lab study found recreational drug users, including cannabis users, recalled fewer specific personal memories than non-users, even after accounting for sleep, health, and alcohol.
Heavy Cannabis Use Was Linked to Thinning of a Brain Region Involved in Decision-Making Over Three Years ↗
A three-year brain imaging study found heavy cannabis users developed significant thinning in a brain region crucial for decision-making, with greater thinning linked to more severe use patterns.
Cannabinoids Showed Significant Neuroprotective Effects in Animal Models of Stroke ↗
A meta-analysis of 26 animal studies found cannabinoids significantly reduced brain damage after stroke, with CBD showing the most consistent benefits across multiple protective pathways.
Adolescent Cannabinoid Exposure Produced Schizophrenia-Like Behavior Across 359 Animal Experiments ↗
A massive meta-analysis of 359 animal experiments confirmed that adolescent cannabinoid exposure consistently produces schizophrenia-like behavioral changes including memory impairment, social deficits, and disrupted sensory gating.
Brain Imaging Identified a Neural Network That Predicts Problem Cannabis Use Across Three Independent Samples ↗
Machine learning identified a brain connectivity pattern that predicted problem cannabis use across three independent samples, including college students, European teens, and treatment-seeking adults.
THC Exposure During Adolescence Damaged Testicular Function in Mice More Than Adult Exposure ↗
Mice given THC during adolescence had reduced sperm counts and testicular damage as young adults, while the same exposure in adulthood caused milder reproductive effects.
CBD Showed Protective Effects Against Parkinson-Like Symptoms in Mice, Especially as Preventive Treatment ↗
CBD protected dopamine neurons and delayed motor symptoms in a progressive Parkinson mouse model, with preventive treatment working better than treatment started after symptom onset.
THC and CBD Produce Largely Non-Overlapping Molecular Effects Across Species and Tissues ↗
Analysis of 105 datasets found THC and CBD have largely different molecular effects: CBD consistently suppressed inflammation while THC primarily affected neuronal signaling.
The Brain's Endocannabinoid System Acts as a Built-In Stress Buffer Through Specific Neural Circuits ↗
A Nature Reviews Neuroscience review mapped how the brain's endocannabinoid system regulates anxiety and stress through specific neural circuits, suggesting endocannabinoid-boosting drugs as future treatments.
Cannabis-Induced Munchies Work Through the Brain's Orexin System by Triggering More Frequent Meals ↗
Rat study found cannabis-induced overeating works by triggering more frequent meals through the brain's orexin system, and blocking this pathway eliminated the munchies effect.
CBD Reduced Depression-Like Behavior and Protected Memory in Socially Isolated Mice ↗
CBD reduced depression-like symptoms and protected memory in socially isolated mice, but unexpectedly increased anxiety in non-stressed mice, highlighting CBD's context-dependent effects.
The Endocannabinoid System May Hold the Key to Better PTSD Treatments ↗
A review found the endocannabinoid system regulates fear and extinction learning in PTSD, with preliminary evidence that cannabinoid-based treatments like nabilone can help, though self-medication carries risks.
CBD Reduced Seizures and Brain Damage in a Rat Model of Post-Traumatic Epilepsy ↗
CBD reduced seizures and brain damage in rats with post-traumatic epilepsy by targeting the TRPV1 channel, suggesting a potential preventive treatment for epilepsy after brain injury.
THC and CBD Had Opposite Effects on Brain Connectivity and Blood Flow in Rats ↗
Brain imaging in rats showed THC increased connectivity and blood flow while CBD decreased connectivity, and combining them produced moderate effects, providing biological evidence for how CBD moderates THC.
Blood Metabolites Could Distinguish Cannabis Intoxication From Mere Use With 80% Accuracy ↗
A metabolomics study identified blood markers that distinguished cannabis intoxication from mere use with 80% accuracy, potentially solving the problem of detecting actual impairment rather than just consumption.
Two Synthetic Cannabinoids Boosted Nerve Cell Growth but Damaged Mitochondria in Lab Cells ↗
Lab study found two common synthetic cannabinoids promoted nerve cell growth through CB1 receptors while simultaneously damaging mitochondria, raising concerns about neurodevelopmental effects.
New Tools Are Revealing How the Endocannabinoid System Works in Real Time in Living Brains ↗
A review describes how new biosensor and imaging technologies are enabling researchers to track endocannabinoid signaling at individual synapses in living brains for the first time.
Ketamine Does Not Mimic or Block the Subjective Effects of THC or Morphine in Rats ↗
Rat study found ketamine does not mimic THC or morphine effects but combining ketamine with THC produced notable sedation, relevant for clinical and recreational polydrug use.
What Happens When Children Accidentally Consume Cannabis Products ↗
Review explains why children are more vulnerable to cannabis intoxication than adults, with immature metabolism and unique brain receptor patterns amplifying THC effects.
CB1 Receptors Help Maintain the Blood-Testis Barrier During Sperm Production ↗
Mouse study shows CB1 cannabinoid receptors are essential for maintaining the blood-testis barrier during sperm production, with deletion causing barrier leakage and slower spermatogenesis.
Blocking an Endocannabinoid-Degrading Enzyme Relieved Migraine Pain in Mice Without Tolerance ↗
A drug that boosts natural endocannabinoids by blocking their degradation enzyme relieved both acute and chronic migraine pain in mice without losing effectiveness over repeated dosing.
Prenatal THC Exposure Affected Mouse Offspring Differently Based on Their Inborn Temperament ↗
Prenatal THC increased anxiety in dominant mice offspring but decreased it in submissive ones, revealing that inborn temperament determines how prenatal cannabis exposure affects behavior.
Brain Cell CB1 Receptors on Star-Shaped Cells Explain Why Amphetamine Affects Males and Females Differently ↗
Mouse study found amphetamine disrupted endocannabinoid-dependent brain plasticity through astrocyte CB1 receptors in males only, revealing a sex-specific mechanism in the reward system.
Endocannabinoids and Kisspeptin Both Slow New Brain Cell Growth Through a Shared Pathway ↗
Rat study found endocannabinoids and kisspeptin both inhibit hippocampal neurogenesis through TRPV1 receptors, revealing a new regulatory partnership for adult brain cell production.
Cannabinoids May Communicate Between Brain Cells Via Tiny Vesicles, Opening New Treatment Possibilities ↗
Review proposes that cannabinoids interact with extracellular vesicles to create a signaling network relevant to neuropsychiatric disorders, with potential for biomarker-guided personalized treatment.
Scientists Found the Specific Brain Cells Behind THC's Cognitive Impairment and a Way to Prevent It ↗
Researchers identified a specific group of astrocytes that drive THC-induced cognitive impairment and showed that dampening their overactivity prevents spatial learning deficits in mice.
Activating Cannabinoid Receptors Reduced Brain Damage After Bleeding Strokes in Mice ↗
Mouse study shows cannabinoid receptor activation reduces brain damage after intracerebral hemorrhage by suppressing NOX-2 and the NLRP3 inflammasome.
Blood Endocannabinoid Levels Tracked With Anxiety Severity and Treatment Response in Youth ↗
Study of 199 youth found blood endocannabinoid levels tracked with anxiety severity, and 2-AG increases during SSRI treatment predicted better response in adolescents with GAD.
Stress Did Not Release Stored THC Into the Bloodstream of Regular Cannabis Users ↗
Cold water immersion stress test did not release stored THC into the blood or cause intoxication in 15 regular cannabis users, despite triggering measurable stress and fat breakdown.
Long-Term Cannabis Use Leaves Marks on DNA, Dunedin Study Finds ↗
The Dunedin Study found long-term cannabis users have distinct DNA methylation patterns, suggesting lasting epigenetic effects from decades of use.
CBD Shows Promise Against Alzheimer's in Lab and Computer Studies ↗
Review finds CBD targets multiple Alzheimer's pathways in preclinical studies, with computer modeling revealing potential gene targets for future research.
28 Synthetic Cannabinoids Tested Show Full Agonism and Unpredictable Activity ↗
Lab testing of 28 synthetic cannabinoids finds most are potent full agonists unlike THC, with unpredictable pharmacological behavior that defies simple structure-activity predictions.
Activating Cannabis Receptors Causes Abnormal Brain Insulation in Developing Zebrafish ↗
Activating CB1 receptors in developing zebrafish causes myelin to wrap around cell bodies instead of nerve fibers, revealing a new way cannabinoids could disrupt brain development.
Seven Months of CBD Improved Memory and Reduced Brain Inflammation in Aging Mice ↗
Aging mice given oral CBD for 7 months showed reduced brain inflammation and improved cognitive function across multiple brain region-specific tasks.
Cannabinoid Receptors Play Significant Role in Ovarian Function in Mice ↗
Mouse study finds cannabinoid receptors significantly regulate ovarian follicle development, estrogen production, and blood vessel formation, with CB2 receptors playing a key role.
Low-Dose CBD Was Safe for Parkinson's Patients but Showed Limited Cognitive Benefit ↗
Parkinson's RCT finds 26 mg/day CBD was safe but showed limited cognitive benefit beyond naming scores, with the low dose potentially below the therapeutic threshold.
THC Destabilizes Brain Cell Scaffolding, Offering a Mechanism for Memory Effects ↗
Lab study reveals THC directly destabilizes microtubules by altering tubulin protein structure, proposing a new molecular mechanism for cannabis-related memory impairment.
Recent Cannabis Use Doesn't Worsen Brain Wave Abnormalities in Psychosis ↗
EEG study of 93 psychosis patients finds brain activity abnormalities are equally present regardless of recent cannabis use, suggesting they are core features of psychosis, not cannabis effects.
Synthetic Cannabinoid Improved Memory and Reduced Alzheimer's Plaques in Mice ↗
Alzheimer's mice treated with a synthetic cannabinoid for 42 days showed improved memory and motor function plus reduced brain plaques and inflammation.
CBD and the Endocannabinoid System Offer Multiple Paths to Treating Childhood Epilepsy ↗
Review maps endocannabinoid system dysregulation in childhood epilepsy and outlines emerging treatment strategies beyond CBD, including allosteric modulators and enzyme inhibitors.
Prenatal Infection Plus Adolescent THC Leaves Hidden Brain Changes in Rats ↗
Two-hit rat study finds prenatal immune activation plus adolescent THC causes hidden brain changes visible on imaging and gene expression, even before behavioral symptoms appear.
Cannabinoid Drug Prevented Memory Loss in a Rat Dementia Model ↗
Low-dose cannabinoid treatment prevented spatial memory loss in rats by indirectly boosting the cholinergic system through cannabinoid receptor activation in cortical regions.
Endocannabinoid System Critical for Migrating Brain Cells, Disruption Causes Catastrophic Damage ↗
Mouse embryo study discovers that both too much and too little endocannabinoid signaling causes catastrophic membrane ruptures in 40% of migrating brain cells during development.
CBD Protected Rat Brains From Liver Disease-Induced Damage ↗
CBD reduced brain inflammation, oxidative stress, and cognitive impairment in rats with liver disease-induced brain dysfunction through multiple anti-inflammatory pathways.
Cannabis Affects the Brain Differently Depending on Your Age ↗
A narrative review of cannabis effects across the lifespan found that prenatal and adolescent exposure carries the highest neurological risk, while cannabis use among older adults is rising fastest with the least risk awareness.
CBD Reduced Involuntary Movements from Parkinson's Medication in Rats Without Reducing Its Benefits ↗
CBD reduced involuntary movements caused by Parkinson's medication in rats without diminishing the drug's motor benefits, working through CB1, PPARy receptors, and endocannabinoid pathways.
CBD Reversed Brain and Gut Damage From Fetal Alcohol Exposure in Mice ↗
Chronic CBD from weaning reversed anxiety, brain molecular changes, gut microbiota dysbiosis, and increased alcohol motivation in mice with fetal alcohol exposure, with effects varying by sex.
THC Changed How the Hippocampus Communicates in Female Rats, Depending on Estrogen ↗
THC altered hippocampal neurotransmission in female rats, but the direction of effects depended on whether estrogen was present, revealing a complex hormone-cannabinoid interaction in the brain.
What We Know (and Don't Know) About the Endocannabinoid System and PTSD Treatment ↗
A review found consistent preclinical evidence that endocannabinoid modulation can improve PTSD-related behaviors, but human research remains mixed and insufficient to support clinical cannabinoid therapy for PTSD.
Men With Opioid Use Disorder Had 15% Lower Brain Cannabis Receptor Levels ↗
A brain imaging study found men with opioid use disorder had 15% lower cannabinoid CB1 receptor availability than healthy controls, particularly in emotion-processing regions.
A CBD-CBC Combination Best Reversed Sleep Deprivation Damage in Mice ↗
Among multiple cannabinoid treatments tested in sleep-deprived mice, a CBD+CBC combination was the most effective at reversing memory impairment, depression, and brain inflammation.
Cannabis Use Amplified a Brain Marker of Psychosis Risk in Early-Stage Patients ↗
A PET imaging study found cannabis use was linked to significantly lower brain MAO-B (an astrocyte marker) in early psychosis and high-risk individuals, particularly in striatal regions associated with dopamine.
Could Cannabis Trigger Psychosis by Disrupting Glutamate Brain Pathways? ↗
A review proposes that cannabis may trigger psychosis in genetically vulnerable individuals by disrupting glutamate signaling in the brain's default mode network, and outlines how to test this hypothesis.
Prenatal Cannabis Exposure Left Lasting Marks on Children's DNA Through at Least Age 27 ↗
Two longitudinal studies found prenatal cannabis exposure was linked to DNA methylation changes in neurodevelopment genes, persisting from birth through age 27 across two countries.
84 of 99 Brain Imaging Studies Found Cannabis Changes Young Brains ↗
A scoping review of 99 neuroimaging studies found that 85% detected differences in brain structure, function, or chemistry in cannabis users aged 14-25, though research quality was generally low.
Cannabis Impairs Attention While Nicotine Enhances It, But Both Harm Developing Brains ↗
A review found cannabis impairs attention while nicotine enhances it in adults, but both substances harm attention development when exposure occurs prenatally.
Prenatal THC Combined With Stress Caused Worse Behavioral and Brain Problems in Mouse Offspring ↗
A mouse study found prenatal THC combined with maternal stress caused additive harm to maternal behavior and offspring brain development, with sex-specific effects on anxiety, motivation, and gene expression.
CBD's Anti-Addiction Effects on Methamphetamine Work Through Hippocampal Dopamine Receptors ↗
CBD sped up extinction and prevented reinstatement of methamphetamine-seeking in rats, effects that were partially blocked by inhibiting D2 dopamine receptors in the hippocampus.
A Synthetic Cannabinoid Rescued Memory Deficits in Alzheimer's Mice ↗
A synthetic cannabinoid rescued memory deficits, reduced brain inflammation, and restored glucose metabolism in Alzheimer's mice without increasing anxiety.
The Body's Own Cannabis System May Play a Role in ADHD ↗
A review of 13 studies found emerging evidence that the endocannabinoid system may contribute to ADHD, with preclinical links between altered cannabinoid signaling and hyperactivity.
THC Slowed Thinking More in Lighter Cannabis Users Than Heavier Ones ↗
Placebo-controlled experiment found THC impaired cognitive efficiency more in lighter users than heavier ones, supporting the role of tolerance in moderating acute effects.
Endocannabinoid Levels May Be Disrupted Early in Multiple Sclerosis ↗
Small study found a trend toward lower anandamide levels in newly diagnosed MS patients, with teriflunomide treatment linked to stronger endocannabinoid coordination.
Prenatal Cannabinoid Exposure Impaired Breathing and Heart Reflexes in Young Rats ↗
Animal study found prenatal cannabinoid exposure impaired breathing reflexes and cardiovascular responses in juvenile rats, with sex-specific effects.
CBD Reversed Autism-Related Behavioral Problems in a Mouse Model ↗
Single-dose CBD reversed social deficits, repetitive behaviors, and cognitive problems in a mouse autism model, though it did not affect stereotyped movements.
PET Imaging Shows the Brain's Cannabinoid System Changes Early in Alzheimer's, Differently in Males and Females ↗
PET imaging in Alzheimer's mice showed the brain's cannabinoid system changes early in disease, with sex-dependent patterns that could guide treatment approaches.
Activating Cannabinoid Receptors Worsened ADHD-Like Behaviors in Adolescent Rats, Especially Females ↗
Rat study found activating cannabinoid receptors during adolescence worsened ADHD-like hyperactivity and risk-taking, with stronger effects in females.
Cannabinoid Receptor Activation Reduced Impulsivity in Highly Impulsive Rats, With Lasting Effects ↗
Cannabinoid receptor activation reduced impulsive decision-making specifically in highly impulsive rats, with effects lasting at least two weeks after the last dose.
How CBD Fights Seizures Through the Brain's Inflammation System ↗
CBD fights seizures through multiple mechanisms including neuroinflammation reduction, modulation of several receptor systems, and oxidative stress reduction.
When During Pregnancy THC Exposure Happens May Determine the Brain Effects ↗
Rat study found THC exposure at different pregnancy timepoints produced different effects on brain immune cells and social behavior—timing matters, not just exposure.
Prenatal THC Exposure Affected Brain Development and Social Behavior Differently Depending on Timing ↗
Rat study found prenatal THC exposure during early vs late pregnancy produced opposite effects on brain immune cell activity and social behavior.
Prenatal Cannabis Exposure Disrupts Brain Chemical Systems in Animal and Limited Human Studies ↗
Systematic review found strong animal evidence that prenatal cannabinoid exposure disrupts brain neurotransmitter systems, but identified a critical lack of human studies on this topic.
CBD Combined With Nitroprusside Prevented Schizophrenia-Like Symptoms in Rats, With Sex Differences ↗
Combined CBD and sodium nitroprusside during early brain development prevented schizophrenia-like symptoms in rats, with stronger effects in females than males.
College Students With Stronger Stress Responses Used Cannabis More Frequently ↗
College students with stronger parasympathetic nervous system responses to stress used cannabis more frequently, suggesting physiological stress sensitivity may drive substance use.
CBD Improved Memory and Reduced Alzheimer's Markers in Mouse Model ↗
CBD improved spatial memory and simultaneously reduced amyloid plaques, tau tangles, neuroinflammation, and oxidative stress in an Alzheimer's mouse model.
Cannabis and Exercise May Have Overlapping Effects on Brain Health Through Shared Pathways ↗
Review found cannabis and exercise share overlapping effects on brain health through inflammation, blood flow, and neuroplasticity pathways, with potential for both beneficial and harmful interactions.
PTSD Shows Different Biological Signatures in Men and Women: Endocannabinoid vs Inflammatory ↗
Men with PTSD showed depleted endocannabinoid levels while women showed elevated inflammatory markers, suggesting PTSD operates through different biological mechanisms by sex.
Activating Cannabis Receptors During Adolescence Permanently Alters Brain Rhythms ↗
Rats exposed to cannabinoid receptor activation during adolescence showed lasting disruptions in hippocampal brain rhythms critical for memory—even in adulthood.
Adolescent Cannabis Receptor Activation Disrupts Adult Brain Rhythms (Preprint) ↗
Preprint companion to RTHC-00197 with additional detail: sex-balanced cohorts and extended testing confirm lasting hippocampal theta disruptions from adolescent cannabinoid exposure.
Prenatal Cannabis Exposure Linked to Self-Regulation Problems That Emerge as Children Grow ↗
Systematic review of 33 studies found prenatal cannabis exposure linked to emerging self-regulation problems in young children, becoming more apparent after age 2 through multiple neurobiological pathways.
Adding Antioxidants to CBD Boosted Its Anti-Aggression and Antidepressant Effects in Stressed Mice ↗
Combining low-dose CBD with resveratrol or alpha-lipoic acid matched high-dose CBD for reducing aggression and depression in PTSD-model mice, though anxiety was unaffected.
Inhaled Cannabis for Diabetic Nerve Pain: A 5-Year Follow-Up Study ↗
Five-year observational study of 52 patients found inhaled cannabis associated with dramatic pain reduction (9.0 to 2.0) in treatment-resistant diabetic neuropathy, plus opioid-sparing effects.
CBD Reversed Memory Problems and Brain Cell Damage in a Mouse Model of Schizophrenia ↗
CBD reversed memory deficits, restored protective brain cells, and reduced neuroinflammation in a mouse model of schizophrenia, working through serotonin and cannabinoid receptor pathways.
Activating CB2 Receptors While Blocking Dopamine D4 Reduced Binge Eating More Than Either Alone in Mice ↗
Mouse study found that combining a CB2 cannabinoid receptor activator with a dopamine D4 blocker reduced binge eating more effectively than the dopamine blocker alone.
Combining Endocannabinoid Boosters With Anti-Inflammatory Drugs Reduced Post-Surgical Pain in Mice ↗
Mouse study found that boosting endocannabinoids via MAGL inhibition reduced post-surgical pain through CB2 receptors, with additive benefit when combined with an NSAID at sub-threshold doses.
How Cannabis Affects Men and Women Differently: A Scoping Review ↗
Scoping review highlights growing evidence that cannabis affects males and females differently, with sex-based variations in sensitivity, tolerance, withdrawal, and behavioral outcomes.
FAAH Gene Expression Altered in Chronic Migraine Patients, Linked to Psychiatric Symptoms ↗
Small study found FAAH, the enzyme that breaks down endocannabinoids, is specifically altered in chronic migraine patients, with changes correlating to headache severity and psychiatric symptoms.
Could the Endocannabinoid System Explain Why Different Depression Treatments All Work? ↗
Narrative review proposes the endocannabinoid system as a unifying mechanism behind diverse treatments for treatment-resistant depression, from brain stimulation to psychedelics.
CBD Nanoemulsion Reduced Both Anxiety and Panic Responses in Rats at Lower Doses ↗
CBD delivered via lipid nanoemulsion reduced anxiety and panic responses in rats at a low chronic dose (2.5 mg/kg), working through serotonin neurons in the brainstem.
Fitter Adults With Depression Have Lower Endocannabinoid Levels in Their Blood ↗
Study of 80 adults with depression found higher physical fitness associated with lower resting plasma endocannabinoid levels, suggesting a more regulated system.
Cannabis Increases Spontaneous Mind-Wandering and Impairs the Ability to Control It ↗
Controlled study found cannabis significantly increases spontaneous mind-wandering and impairs the ability to regulate attention in regular users.
How the Brains of People Seeking Cannabis Use Disorder Treatment Respond to Cannabis Cues ↗
fMRI study of 65 treatment-seeking CUD patients found increased brain activation to cannabis cues in executive and reward regions, with an unexpected inverse relationship between craving and reward area activation.
The Spinal Endocannabinoid System Can Both Relieve and Worsen Nerve Pain, Depending on Conditions ↗
Review reveals the spinal endocannabinoid system has dual effects on neuropathic pain: typically relieving it, but paradoxically promoting pain under certain pathological conditions.
Prenatal Cannabis Exposure Had Opposite Metabolic Effects in Male and Female Mouse Offspring ↗
Mouse study found prenatal cannabis exposure impaired metabolic control in female but not male offspring, with paradoxically different effects depending on diet.
Cannabis-Linked Oral Bacteria Can Reach the Brain and Cause Anxiety in Mice ↗
Mouse study found oral bacteria enriched in cannabis smokers can cause anxiety through metabolites that impair mitochondrial function and GABA signaling in the brain, without bacteria reaching the brain.
How the Endocannabinoid System Influences Cancer: A Mini-Review ↗
Mini-review summarizes preclinical evidence that cannabinoids can inhibit tumor growth, trigger cancer cell death, and suppress blood vessel formation, though clinical translation faces major challenges.
How Prenatal Infections May Interact With Cannabis to Affect Schizophrenia Risk ↗
A review of the two-hit hypothesis of schizophrenia found that animal studies do not consistently show adolescent cannabis worsening outcomes after prenatal immune activation, complicating the expected risk narrative.
CBD Nanoemulsion Protected Against Parkinson's-Like Brain Damage in Rats ↗
A CBD nanoemulsion protected against Parkinson's-like damage in both the brain and gut of rats, normalizing oxidative stress markers, reducing abnormal protein aggregation, and improving behavior.
Commercial CBD Products Caused Neurotoxicity Linked to Heavy Metal Contamination ↗
Two commercial CBD powders containing heavy metals (lead, chromium, zinc) caused oxidative stress, antioxidant enzyme inhibition, and mitochondrial damage in human neuronal cells at concentrations of 10-50 micrograms/mL.
Omega-3 Supplements Reversed Prenatal THC Brain Effects in Male Rats Only ↗
Omega-3 supplementation reversed cognitive and emotional deficits from prenatal THC exposure in male rat offspring but not females, while brain lipid metabolism disruptions persisted in both sexes.
CBD Increased Cell Damage Under Stress by Blocking a Key Potassium Channel ↗
Lab study found CBD blocks Kv2.1 potassium channels in a dose-dependent manner, increasing cell vulnerability to stress-induced damage, a finding with implications for both safety and potential anti-cancer applications.
Prenatal Cannabis Modified the Effects of Insecticide Exposure on Child Behavior ↗
Study of 197 mother-child pairs found prenatal insecticide exposure (not cannabis itself) was the primary predictor of altered child behavior, but cannabis exposure modified the insecticide-tobacco mixture effects in sex-specific ways.
Boosting Endocannabinoid Levels Restored Motor Learning in Huntington's Disease Mice ↗
Three weeks of a drug that boosts brain endocannabinoid levels restored motor learning and synaptic plasticity in Huntington's disease mice, suggesting the endocannabinoid system as a therapeutic target for early HD symptoms.
CBD Protected Against Meth-Induced Brain Damage by Blocking a Pain-Sensing Channel ↗
CBD protected against methamphetamine-induced brain damage in cells and mice by directly binding to and blocking TRPV1 channels, preventing the calcium overload, oxidative stress, and cell death that drive meth-related neurological harm.
Cannabis Use Disorder Linked to Changes in Dopamine Gene Methylation and Personality Traits ↗
Study of 490 males found cannabis use disorder associated with altered DAT1 dopamine gene methylation, which correlated with higher neuroticism and anxiety, suggesting epigenetic pathways for cannabis's psychological effects.
Daily THC Causes Inflammation in Adolescent Brain Amygdala — CBD Prevents It ↗
Multi-species study found daily THC causes inflammatory gliosis specifically in the adolescent amygdala through astrocyte CB1 receptors. CBD co-treatment prevented the inflammation but not all neural changes.
Blocking CB2 Receptors Improves Sleep but Activating Them Improves Memory in Parkinson's Model ↗
Rat Parkinson's study found blocking CB2 receptors improved sleep while activating them improved memory, revealing paradoxical endocannabinoid roles in non-motor symptoms.
Alcohol Dilates Fetal Brain Arteries Through CB1 Receptors, Differently in Males and Females ↗
Baboon study found alcohol dilates fetal brain arteries through CB1 cannabinoid receptors, with effects differing between male and female fetuses and across brain regions.
What Happens to Babies Exposed to Cannabis Before Birth ↗
Evidence links prenatal cannabis to low birth weight, preterm birth, and lasting brain changes in children—with THC potency having risen from 5% to 30%.
Endocannabinoid System Changes in the Retina May Predict Alzheimer's Disease Before Brain Plaques Form ↗
Alzheimer's mouse study found endocannabinoid system disruption and immune activation in the retina before brain plaques formed, suggesting the eye as an early diagnostic window.
How THC Disrupts Spatial Memory by Silencing GABA Neurons in the Prefrontal Cortex ↗
CB1 activation in the prefrontal cortex impaired spatial memory formation in mice by reducing GABA release—a specific mechanism explaining THC's memory effects.
CBD Prevents Alzheimer's-Like Cognitive Decline in Rats Through CB1 Receptor Activation and Inflammation Reduction ↗
Rat study found chronic CBD prevented Alzheimer's-like cognitive decline by activating CB1 receptors and reducing brain inflammation, amyloid-beta, and tau pathology.
Review: Cannabinoids Show Anti-Inflammatory Potential Across Alzheimer's, Parkinson's, ALS, and MS ↗
Review found cannabinoids show anti-inflammatory therapeutic potential across six neurodegenerative and neuroinflammatory conditions by simultaneously targeting neural and immune pathways.
Cannabis During Pregnancy May Delay a Critical Switch in How Baby Brains Wire Themselves ↗
Prenatal cannabis exposure may delay GABA's developmental switch from excitatory to inhibitory—disrupting the precise timing that guides how the fetal brain wires itself.
Prenatal THC Changed the Chemical Composition of Offspring's Brain Tissue ↗
Advanced imaging revealed prenatal THC reduced copper in offspring brain tissue and altered neurochemistry in emotion-processing circuits—molecular fingerprints of exposure.
What Do Clinical Trials Actually Show About Cannabis for Mental Health? ↗
Scoping review of RCTs found thin and mixed evidence for cannabis treating mental health conditions — CBD shows some anxiety promise but most psychiatric evidence remains inconclusive.
Prenatal THC Slowed Brain Growth in Mice From Fetus to Adulthood ↗
Longitudinal mouse MRI study found prenatal THC caused enlarged ventricles in embryos followed by sustained brain growth deceleration into adulthood, with females more affected.
What Animal Studies Show About Cannabis and Tobacco During Pregnancy ↗
Review of animal studies shows prenatal THC and nicotine each disrupt development through epigenetic changes, with sex-specific effects persisting into adulthood.
HHC Gummy Sold as THC: A Dissociative ER Case With Serum Proof ↗
One ED case: a “THC” gummy was analytically confirmed as HHC, with dissociative-like symptoms.
Prenatal THC Activated Schizophrenia-Linked Genes in Rat Placentas ↗
Prenatal THC in rats altered placental expression of genes previously linked to schizophrenia in human studies, with sex-specific effects and fetal growth restriction.
Endocannabinoid-metabolizing enzymes in tumors helped colon cancer evade the immune system in mice ↗
Mouse study reveals endocannabinoid-metabolizing enzymes help colon tumors evade the immune system; blocking the pathway improved immunotherapy.
Older adults had lower baseline endocannabinoid levels but showed larger increases after cannabis use than younger adults ↗
Older adults had lower baseline endocannabinoid levels but showed larger increases after cannabis use than younger adults.
Ultra-low-dose THC given before Alzheimer symptoms appeared reduced brain inflammation in mice, with different brain regions affected by sex ↗
Monthly ultra-low-dose THC prevented cognitive decline in Alzheimer mice, with sex-specific anti-inflammatory patterns.
Daily CBD did not rescue behavior or brain volume in an aggressive Alzheimer mouse model, but did reduce microglial reactivity ↗
Daily CBD in Alzheimer mice reduced brain immune cell reactivity but did not improve cognition, behavior, or brain volume.
The Two Endocannabinoids Talk to Different Brain Cells ↗
Nature Neuroscience study reveals 2-AG and anandamide have completely separate cellular targets in the hippocampus, with 2-AG signaling to neurons and anandamide signaling to astrocytes.
How CBD Interacts With the Brain: Mapping Its Many Receptor Targets for Parkinson's ↗
Review maps CBD's extensive receptor interactions beyond the endocannabinoid system, highlighting both therapeutic potential and complexity for Parkinson's disease.
Endocannabinoid System Found to Play a Role in Chemotherapy-Caused Hearing Loss ↗
Study reveals cisplatin chemotherapy disrupts the endocannabinoid system in hearing cells, and blocking CB2 receptors may protect against the damage.
Endocannabinoid System Genes Are Disrupted in Inflamed Bowel Disease Tissue ↗
Study of IBD patient biopsies found 6 of 10 endocannabinoid system genes dysregulated in inflamed tissue, with CB2 and GPR55 receptors upregulated.
How Alcohol Changes Your Endocannabinoid Levels and What That Means for How Drunk You Feel ↗
First study showing alcohol decreases 2-AG endocannabinoid levels, with the drop linked to less drug liking, suggesting the endocannabinoid system mediates alcohol reward.
Brain Regions That Shrink Most in Parkinson's Psychosis Are Rich in CB1 Cannabinoid Receptors ↗
Study links gray matter loss in Parkinson's psychosis to CB1 cannabinoid receptor brain distribution, suggesting the endocannabinoid system may play a role in these symptoms.
Smoking Synthetic Cannabinoids Creates Unknown Toxic Chemicals That Damage the Brain ↗
Systematic review reveals smoking synthetic cannabinoids creates unknown toxic chemicals with brain-damaging potential, with only 9 studies ever investigating these breakdown products.
Long-Term Cannabis Use Linked to Impaired Automatic Movement Learning ↗
Study found longer cannabis use history linked to weaker automatic movement learning and elevated resting brain activity, suggesting altered baseline neural dynamics.
Hemp's Potential for Brain Diseases: A Review of Seeds, Leaves, and Flowers ↗
Review found hemp-derived compounds from seeds, leaves, and flowers show neuroprotective potential across epilepsy, Alzheimer's, Parkinson's, and MS — mostly in preclinical studies.
Two Lesser-Known Cannabinoids Reduced Pain Through Multiple Receptor Pathways ↗
Study finds lesser-known cannabinoids CBV and THCV reduce pain through both vanilloid and cannabinoid receptor pathways in a genetic model organism.
Female Mice Developed Greater THC Tolerance Than Males, Especially With HIV ↗
Mouse study shows females develop greater THC tolerance than males after 90 days, with chronic THC increasing anxiety in females and HIV status adding neuroinflammatory complexity.
Cannabis Terpenes Directly Activate Cannabinoid Receptors, Supporting the Entourage Effect ↗
Study shows 16 cannabis terpenes selectively activate CB1 and CB2 receptors at THC-comparable potency, providing molecular evidence for the entourage effect.
CB1 Activation Reduced Fear Memories in Stressed Female Rats But May Hinder Extinction ↗
Study in female rats finds CB1 activation reduces acute fear but may impair fear extinction, with important implications for cannabis use in PTSD treatment.
How Cannabinoids May Fight the Deadliest Brain Cancer Through Autophagy ↗
Review details how cannabinoids activate autophagy-mediated cell death in glioblastoma, with promising preclinical evidence and early clinical safety data.
Endocannabinoids Are Stored in Adrenal Stress Hormone Packages and Influence Hormone Production ↗
Study reveals endocannabinoids are stored alongside stress hormones in adrenal glands and directly modulate hormone production, connecting the ECS to the peripheral stress response.
Cannabis and Linden Tree Extracts Together Showed Powerful Neuroprotective Synergy ↗
Study finds cannabis and linden tree extracts together produce synergistic neuroprotection, fully restoring cell viability and shifting brain immune cells to anti-inflammatory states.
Cannabigerol showed inconsistent anti-inflammatory effects and was genotoxic at higher doses in brain immune cells ↗
A cell study found CBG was genotoxic at moderate concentrations, highly toxic at high concentrations, and failed to reduce neuroinflammation in microglial cells, challenging claims of CBG as a safe anti-inflammatory cannabinoid.
THC at concentrations found in drivers' blood caused neurotoxicity through oxidative stress in lab cells ↗
THC at concentrations found in the blood of traffic accident drivers caused dose-dependent neurotoxicity in human neuronal cells, including oxidative stress, mitochondrial damage, and early cell death signals.
Opioid users showed blunted endocannabinoid stress response compared to healthy controls ↗
Healthy controls increased 2-AG endocannabinoid levels after social stress while chronic opioid users showed a blunted response, suggesting a dysfunctional stress buffer that may contribute to opioid vulnerability and relapse.
Testing 11 New Synthetic Cannabinoids: Most Were More Potent Than THC ↗
Rodent testing of 11 DEA-flagged synthetic cannabinoids found most significantly more potent than THC, with indazole and indole classes showing the highest potency.
Low-dose THC boosted dopamine and GABA in the brain's reward center, while high doses decreased dopamine in mice ↗
Mouse study found low-dose THC increased dopamine and GABA in the brain's reward center while high doses decreased dopamine, and a partial CB1 agonist produced no reward-related effects.
Higher endocannabinoid levels appeared to buffer the link between childhood trauma and inflammation in people with borderline personality disorder ↗
Study of women with BPD found that higher endocannabinoid levels appeared to buffer the link between childhood trauma and inflammation (IL-6), suggesting endocannabinoids may modulate trauma-immune interactions.
Cannabis-based medicines show the strongest evidence for Tourette syndrome among movement and neurodegenerative disorders ↗
Review finds strongest evidence for cannabis-based medicines in Tourette syndrome (tic and comorbidity improvement), with limited but promising evidence for Parkinson's and Huntington's disease.
The body's own cannabinoids killed glioblastoma cells by disrupting their mitochondria, through a receptor pathway beyond the usual cannabinoid targets ↗
Lab study found the body's own cannabinoids (anandamide and oleamide) selectively killed glioblastoma cells by disrupting mitochondrial function through PPAR-gamma receptors, while sparing normal brain cells.
Synthetic Cannabinoid Increased a Key Brain Growth Protein in Adolescent Rats ↗
Synthetic cannabinoid increased BDNF expression in adolescent rat prefrontal cortex, hippocampus, and cerebellum — potentially disrupting precisely timed brain development.
THC-induced anxiety in mice involves crosstalk between cannabinoid and adenosine receptor systems in the brain ↗
Mouse study found THC-induced anxiety involves crosstalk between cannabinoid CB1 and adenosine A2A receptors in the hippocampus, suggesting adenosine system modulation could influence cannabis anxiety effects.
Prenatal cannabis exposure may affect offspring mental health by altering the immune system, but the research is still early ↗
Review found prenatal cannabis exposure reduces placental inflammation markers, which was linked to behavioral issues in offspring, though research is still early.
THC produced the same physiological effects in HIV-model rats and healthy controls without worsening HIV-related motivation deficits ↗
THC produced consistent physiological effects in HIV-model rats without worsening motivation deficits, and chronic use showed tolerance to acute motivational impacts.
A Single THC Dose in Newborn Rats Caused Memory Problems in Females But Not Males ↗
Single neonatal THC dose caused lasting spatial memory deficits in female rats but not males, with altered dendritic structure in both sexes — revealing stark sex-specific vulnerability.
Inhaled CBD before brain tumor implantation significantly reduced glioblastoma growth in mice ↗
First preclinical evidence that 14 days of inhaled CBD pretreatment significantly reduced glioblastoma tumor growth in mice by modulating immune checkpoint markers.
CBD reduced a "don't eat me" signal on leukemia cells and triggered cell death through a specific mitochondrial pathway ↗
CBD reduced CD47 (an immune evasion signal) on leukemia cells and triggered apoptosis through VDAC-1 oligomerization, a specific mitochondrial mechanism.
Adolescent cannabis use was linked to cortical thinning, especially in males, and some brain differences existed before use began ↗
Longitudinal brain imaging of 136 teens found cannabis use linked to cortical thinning (especially in males), while pre-existing brain differences also predicted who would use cannabis.
The endocannabinoid system plays a central role in headache disorders, and targeting it could offer new treatments ↗
Review found the endocannabinoid system regulates key headache mechanisms including pain signaling, inflammation, and cortical excitability, with sex differences shaping treatment responses.
Cannflavin B, a non-psychoactive cannabis compound, improved social behavior and brain function in an autism rat model ↗
Cannflavin B, a non-psychoactive cannabis flavonoid, normalized social behavior, reduced anxiety in females, and corrected brain wave abnormalities in an adolescent rat model of autism.
People who use both cannabis and tobacco together may actually perform better cognitively than those who use either substance alone ↗
Systematic review of 39 studies found cannabis and tobacco co-users showed similar cognitive and brain function to non-users, suggesting the substances may offset each other's impairments.
CBD Reduced Depression-Like Behavior in Mice by Repairing Cellular Power Plants ↗
CBD reversed depression-like behavior in mice by restoring mitochondrial function, reducing oxidative stress, and decreasing neuroinflammation in the hippocampus.
THC and CBD both reduced testosterone production in lab-grown adrenal cells, contradicting findings from human cannabis users ↗
Both THC and CBD reduced testosterone production in adrenal cells in vitro, contradicting the finding that cannabis users have higher testosterone, suggesting indirect mechanisms in the body.
The Cloning of CB1 — The Brain's Most Abundant Receptor and the Reason Cannabis Works ↗
The 1990 cloning of the CB1 cannabinoid receptor gene — revealing the most abundant GPCR in the mammalian brain and the molecular target through which cannabis works.
The Discovery of CB2 — The Immune System's Cannabinoid Receptor ↗
The 1993 cloning of CB2 — the immune system's cannabinoid receptor — explaining why cannabis modulates inflammation and opening a therapeutic target for pain without psychoactivity.
The Discovery of 2-AG — The Brain's Primary Endocannabinoid and the Molecule That Actually Runs the System ↗
The discovery of 2-AG — the endocannabinoid 170× more abundant than anandamide — establishing it as the brain's primary retrograde signaling molecule and the true workhorse of the endocannabinoid system.
The Four Rules of Endocannabinoid Signaling — Why This System Doesn't Work Like Anything Else in the Brain ↗
The landmark review that explained why endocannabinoid signaling is fundamentally different from every other neurotransmitter system — four rules that define how the brain's cannabis system works.
The First Photograph of CB1 — Seeing the Brain's Cannabinoid Receptor at Atomic Resolution ↗
The first crystal structure of the human CB1 receptor — 26 years after the gene was cloned, scientists could finally see what the most abundant receptor in the brain actually looks like.
GPR55: The Orphan Receptor That Might Be the Third Cannabinoid Receptor — Or Might Not ↗
The 2007 paper proposing GPR55 as a third cannabinoid receptor — activated by THC and endocannabinoids but with fundamentally different pharmacology from CB1 and CB2.
The Endocannabinoid System as Neural Shield — What Happens to the Brain When It Fails ↗
A 2018 review mapping the endocannabinoid system's neuroprotective role across Huntington's, Alzheimer's, Parkinson's, epilepsy, and cancer — revealing the ECS as a neural shield whose failure precedes disease.
The Study That Showed THC Can Kill Brain Cancer Cells — And Why You Can't Smoke Your Way There ↗
Landmark Nature Medicine study showing THC caused brain tumor regression in rats through a ceramide-mediated cell death pathway that selectively killed cancer cells while sparing normal tissue — opening the field of cannabinoid anticancer research.
The Endocannabinoid System Is Over 500 Million Years Old ↗
Endocannabinoid system genes traced back 500+ million years across the animal kingdom — proving the ECS is among the most ancient and essential signaling systems in biology.
The Endocannabinoid System and the Brain: Mechoulam's Masterwork Review ↗
Mechoulam's definitive review of how the brain's own cannabis system regulates anxiety, mood, memory, and reward — and why dose determines whether the effect is therapeutic or harmful.