Cannabis Neuroscience Research

Distinct endocannabinoids specifically signal to astrocytes or neurons in the adult mouse hippocampus.

Noriega-Prieto, Jose Antonio · 2026

In the hippocampus, 2-AG activates CB1 receptors on neurons to depress synaptic transmission, while anandamide activates CB1 receptors on astrocytes to potentiate adjacent synapses.

Independent brain cortical signatures of risk for adolescent cannabis use and consequences of such use are moderated by sex.

Watts, Jeremy J · 2026

In years when adolescents used more cannabis than their personal average, cortical thickness was lower (p = 0.047).

Brain Function Outcomes of Recent and Lifetime Cannabis Use.

Gowin, Joshua L · 2025

Using Human Connectome Project data, heavy lifetime cannabis users (>1,000 uses, n=88) showed significantly lower brain activation during a working memory task compared to nonusers, with a moderate effect size (Cohen d = -0.28).

Lifetime Cannabis Use Is Associated with Brain Volume and Cognitive Function in Middle-Aged and Older Adults.

Guha, Anika · 2025

Using UK Biobank data from participants aged 40-70 (mean age 54.5), lifetime cannabis use was positively associated with regional brain volume in CB1-rich areas including the caudate, putamen, hippocampus, and amygdala.

Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity.

Kumar, Aditya R · 2025

Fetal brain/maternal plasma THC ratios: 0.50 (T1), 0.45 (T2), 0.35 (T3 umbilical).

Systematic review and meta-analysis on the effects of chronic peri-adolescent cannabinoid exposure on schizophrenia-like behaviour in rodents.

Li, Zhikun · 2025

Across 359 experiments from 108 articles, CB1 receptor agonists (both natural and synthetic cannabinoids) during adolescence impaired working memory (g=-0.56), novel object recognition (g=-0.66), novel object location recognition (g=-0.70), social novelty preference (g=-0.52), social motivation (g=-0.21), pre-pulse inhibition (g=-0.43), and sucrose preference (g=-0.87).

Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.

Loomba, Niharika · 2025

Endocannabinoid signaling modulates innate avoidance, conditioned fear, and stress responsivity through specific cortical-cortical and cortical-subcortical circuits.

DNA methylation profiles of long-term cannabis users in midlife: a comprehensive evaluation of published cannabis-associated methylation markers in a representative cohort.

Meier, Madeline H · 2025

Analysis of the Dunedin Multidisciplinary Health and Development Study revealed that decades of cannabis use was associated with specific DNA methylation changes, a type of epigenetic modification that can alter gene expression without changing the DNA sequence itself..

Dysregulation of the Cannabinoid System in Childhood Epilepsy: From Mechanisms to Therapy.

Montebello, Gloria · 2025

The endocannabinoid system regulates neuronal excitability from early life through aging.

Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course.

Noble, Alexandra J · 2025

Prenatal cannabis exposure was associated with genome-wide significant DNA methylation differences at birth, 7 years, 15-17 years, and 27 years.

Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks.

Ertl, Natalie · 2024

Cannabis caused significant reductions in within-network connectivity in the default mode, executive control, salience, hippocampal, and limbic striatal networks compared to placebo.

The First "Hit" to the Endocannabinoid System? Associations Between Prenatal Cannabis Exposure and Frontolimbic White Matter Pathways in Children.

Evanski, Julia M · 2024

Prenatal cannabis exposure was associated with lower fractional anisotropy (a measure of white matter integrity) in the right and left fornix.

Neuroanatomical Variability and Substance Use Initiation in Late Childhood and Early Adolescence.

Miller, Alex P · 2024

Among 9,804 children, 35.3% initiated substance use before age 15.

Vaporized D-limonene selectively mitigates the acute anxiogenic effects of Δ9-tetrahydrocannabinol in healthy adults who intermittently use cannabis.

Spindle, Tory R · 2024

Co-administration of 30mg THC with 15mg d-limonene significantly reduced ratings of "anxious/nervous" and "paranoid" compared to 30mg THC alone.

Cannabis and Cannabinoid Signaling: Research Gaps and Opportunities.

Valentino, Rita J · 2024

Despite decades of cannabis pharmacology research, major knowledge gaps remain in: (1) enduring consequences of cannabis exposure during critical brain development windows, (2) effects of large daily doses of high-THC cannabis, (3) therapeutic opportunities from endocannabinoid system manipulation, and (4) strategies to treat cannabis use disorder and cannabis toxicity..

Differential associations of adolescent versus young adult cannabis initiation with longitudinal brain change and behavior.

Albaugh, Matthew D · 2023

Adolescent cannabis initiation (14-19) was associated with cortical thinning in dorsolateral and ventrolateral prefrontal cortex that persisted into young adulthood and partially mediated associations with later cocaine, ecstasy, and cannabis use at age 22.

Characterization of childhood trauma, hippocampal mediation and Cannabis use in a large dataset of psychosis and non-psychosis individuals.

Del Re, Elisabetta C · 2023

Among 1,185 participants (397 controls, 209 bipolar-I, 279 schizoaffective, 300 schizophrenia), cannabis use and childhood trauma interacted in survival analysis to predict earlier psychosis onset.

Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.

Rosenberg, Evan C · 2023

LPI increased excitatory presynaptic release probability and evoked synaptic strength in hippocampal CA3-CA1 connections while simultaneously weakening inhibitory signaling by decreasing GABA receptor (GABAARgamma2) and gephyrin puncta.

Cannabis in Adolescence: Lasting Cognitive Alterations and Underlying Mechanisms.

Scheyer, Andrew F · 2023

Cannabis use during adolescence causes lasting aberrations in synaptic development, often secondary to epigenetic changes.

Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis.

Gunasekera, Brandon · 2022

THC had neuromodulatory effects across a core network of brain regions central to many cognitive tasks and processes.

A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth.

Hammond, Christopher J · 2022

Cannabis-using youth showed greater activation in the rostral medial prefrontal cortex during executive control tasks and decreased activation in the dorsal medial prefrontal cortex and dorsal anterior cingulate during social cognition and emotion processing, compared to non-using peers..

Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis.

Hutten, Nadia R P W · 2022

Both THC and THC/CBD increased state anxiety compared to placebo, but anxiety after THC/CBD was significantly lower than after THC alone.

Animal evidence considered in determination of cannabis smoke and Δ9 -tetrahydrocannabinol (Δ9 -THC) as causing reproductive toxicity (developmental endpoint); Part II. Neurodevelopmental effects.

Iyer, Poorni · 2022

Prenatal cannabis smoke or THC exposure in animals produced: impaired locomotor and exploratory behavior (rats), memory and learning deficits, attention deficits, increased separation-induced vocalizations, reduced social interaction, increased anxiety, and enhanced sensitivity to morphine and heroin rewarding effects in adulthood.

The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age-matched controls.

Lawn, W · 2022

Cannabis users had significantly worse verbal episodic memory than controls (p=0.007).

Systematic review of structural and functional neuroimaging studies of cannabis use in adolescence and emerging adulthood: evidence from 90 studies and 9441 participants.

Lichenstein, Sarah D · 2022

Across 90 studies including 9,441 participants (3,924 cannabis users, 5,517 non-users), preliminary evidence pointed to alterations in frontoparietal, frontolimbic, frontostriatal, and cerebellar regions among adolescent and emerging adult cannabis users..

Alcohol and cannabis co-use and longitudinal gray matter volumetric changes in early and late adolescence.

Luo, Xi · 2022

Co-use of alcohol and cannabis predicted faster gray matter volume decline (-0.046 to -0.138 cm3/year) in the caudal middle frontal cortex, fusiform, inferior frontal, superior temporal, and supramarginal gyri.

Long-Term Cannabis Use and Cognitive Reserves and Hippocampal Volume in Midlife.

Meier, Madeline H · 2022

Long-term cannabis users showed a mean 5.5-point IQ decline from childhood to age 45, poorer learning and processing speed relative to childhood IQ, and informant-reported memory and attention problems.

Genome-wide identification of the shared genetic basis of cannabis and cigarette smoking and schizophrenia implicates NCAM1 and neuronal abnormality.

Song, Weichen · 2022

A common genetic factor of cannabis and cigarette smoking explained 8.6% of schizophrenia heritability.

Use of Marijuana: Effect on Brain Health: A Scientific Statement From the American Heart Association.

Testai, Fernando D · 2022

Cannabinoid receptors are concentrated in brain areas critical for cognition and behavior, especially during neurodevelopment.

Association of Cannabis Use During Adolescence With Neurodevelopment.

Albaugh, Matthew D · 2021

Cannabis use between ages 14 and 19 was associated with accelerated, dose-dependent cortical thinning in bilateral prefrontal cortex, spatially correlated with CB1 cannabinoid receptor density.

Neuropsychological and neurophysiological predictors and consequences of cannabis and illicit substance use during neurodevelopment: a systematic review of longitudinal studies.

Debenham, Jennifer · 2021

High-quality evidence showed that delayed or irregular neurodevelopment in executive functioning, particularly emotional perception, may predispose young people to higher frequency substance use.

The Effects of Alcohol and Cannabis Use on the Cortical Thickness of Cognitive Control and Salience Brain Networks in Emerging Adulthood: A Co-twin Control Study.

Harper, Jeremy · 2021

Greater alcohol misuse was linked to thinner cortex in prefrontal, temporal, insula, and parietal regions, predominantly right-lateralized.

Alcohol and Cannabis Use and the Developing Brain.

Lees, Briana · 2021

Heavy alcohol use was associated with widespread decreases in gray matter volume and slowed white matter growth, while heavy cannabis use was linked to decreased subcortical volume and increased cortical thickness.

Cannabinoids and the expanded endocannabinoid system in neurological disorders.

Cristino, Luigia · 2020

Beyond the classical CB1/CB2 system, an expanded "endocannabinoidome" includes biochemically related mediators with their own receptors and enzymes.

Psychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies.

Ganesh, Suhas · 2020

44.75% of THC infusions produced clinically meaningful positive psychosis symptoms.

Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis.

Hindley, Guy · 2020

THC produced large effect sizes for total symptoms (SMC 1.10), positive/psychotic symptoms (SMC 0.91), and negative symptoms (SMC 0.78) compared to placebo.

Reduced Segregation Between Cognitive and Emotional Processes in Cannabis Dependence.

Manza, Peter · 2020

Using Human Connectome Project data from 89 cannabis-dependent individuals, 87 recreational users, and matched controls, researchers found that cognitive and emotional measures were significantly correlated in the cannabis-dependent group only.

Longitudinal associations between amygdala reactivity and cannabis use in a large sample of adolescents.

Spechler, Philip A · 2020

Right amygdala reactivity to angry faces at age 14 (before cannabis use) significantly predicted cannabis use at age 19 in a dose-response fashion.

Cannabinoid receptor CNR1 expression and DNA methylation in human prefrontal cortex, hippocampus and caudate in brain development and schizophrenia.

Tao, Ran · 2020

CNR1 expression is high in fetal prefrontal cortex and hippocampus, then drops dramatically after birth.

Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.

Banister, Samuel D · 2019

THC primarily acts as a partial agonist at CB1 receptors, producing its distinctive intoxication.

The neuropsychopharmacology of cannabis: A review of human imaging studies.

Bloomfield, Michael A P · 2019

Cannabis and THC acutely affect executive, emotional, reward, and memory processing through direct CB1 effects and indirect effects on glutamate, GABA, and dopamine systems.

Alteration to hippocampal volume and shape confined to cannabis dependence: a multi-site study.

Chye, Yann · 2019

Cannabis users as a whole (n=140) did not differ from controls (n=121) in hippocampal volume or shape.

Safety, efficacy, and mechanisms of action of cannabinoids in neurological disorders.

Friedman, Daniel · 2019

Randomized controlled trials provide evidence of CBD's anti-seizure effects for Lennox-Gastaut and Dravet syndromes.

Exposure to cannabinoids can lead to persistent cognitive and psychiatric disorders.

Krebs, Marie-Odile · 2019

Cannabis use is associated with dose-dependent cognitive deficits and a 2-fold or greater increase in psychosis risk.

Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.

Lisboa, Sabrina F · 2019

Direct or indirect CB1 receptor activation consistently facilitated extinction of aversive/traumatic memories across animal and human studies.

Does regular cannabis use affect neuroanatomy? An updated systematic review and meta-analysis of structural neuroimaging studies.

Lorenzetti, Valentina · 2019

Regular cannabis users had significantly smaller volumes of the hippocampus (SMD=0.14) and both medial (SMD=0.30) and lateral (SMD=0.19) orbitofrontal cortex compared to controls.

Associations between adolescent cannabis use frequency and adult brain structure: A prospective study of boys followed to adulthood.

Meier, Madeline H · 2019

Four adolescent cannabis use trajectories were identified: non-users/infrequent, desisters, escalators, and chronic-frequent users.

Measuring Disturbance of the Endocannabinoid System in Psychosis: A Systematic Review and Meta-analysis.

Minichino, Amedeo · 2019

CSF anandamide was significantly elevated in schizophrenia (SMD 0.97, p<.001).

Residual effects of cannabis use in adolescent and adult brains - A meta-analysis of fMRI studies.

Blest-Hopley, Grace · 2018

Researchers conducted separate meta-analyses of fMRI studies comparing brain function in adult and adolescent cannabis users to non-users during various cognitive tasks. In adult cannabis users (530 users vs 580 controls across 13 studies), brain activation was increased in the superior and posterior temporal regions and inferior frontal gyrus, while decreased in the visual cortex, insula, and middle temporal gyrus.

The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain.

Donvito, Giulia · 2018

This comprehensive review examined the entire endocannabinoid system as a source of pain treatment targets, covering CB1 and CB2 receptors plus the enzymes that make and break down endocannabinoids (FAAH and MAGL). In preclinical models, cannabinoid receptor agonists and inhibitors of endocannabinoid-regulating enzymes (FAAH and MAGL) produced reliable antinociceptive (pain-reducing) effects across multiple inflammatory and neuropathic pain models. A particularly notable finding: these compounds offered opioid-sparing effects, meaning they could reduce the amount of opioid medication needed for pain control. Clinical studies showed that medicinal cannabis or cannabinoid-based medications relieve pain in cancer, multiple sclerosis, and fibromyalgia.

Medical Use of Cannabinoids.

Fraguas-Sánchez, Ana Isabel · 2018

This extensive review covered the therapeutic landscape of cannabinoids across dozens of medical conditions. Six cannabinoid medications had already received regulatory approval: nabilone and dronabinol capsules for chemotherapy nausea and vomiting, dronabinol capsules and oral solution for anorexia, THC:CBD oromucosal spray (Sativex) for MS-related spasticity and cancer pain, and CBD oral solution (Epidiolex) for Dravet and Lennox-Gastaut epilepsy syndromes. Beyond approved uses, the review found evidence supporting potential applications in inflammatory and neuropathic pain, various cancer types (brain, breast, prostate), neurodegenerative diseases (Parkinson's, Huntington's, Alzheimer's), PTSD and anxiety disorders, irritable bowel syndrome, eye diseases, and substance abuse disorders (particularly alcohol and opioid). The endocannabinoid system's involvement in energy balance, appetite, blood pressure, pain modulation, nausea, memory, learning, and immune response explains the breadth of potential therapeutic applications..

Are cannabis-using and non-using patients different groups? Towards understanding the neurobiology of cannabis use in psychotic disorders.

Sami, Musa Basseer · 2018

Cannabis use is associated with increased risk of developing psychotic disorders, increased hospitalization, longer hospital stays, and treatment failure.

Early Cannabis Use and Neurocognitive Risk: A Prospective Functional Neuroimaging Study.

Tervo-Clemmens, Brenden · 2018

At age 12, before any cannabis use, teens who would initiate cannabis by 15 already showed activation differences in frontoparietal (increased) and visual association (decreased) regions, and poorer executive planning scores.

Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

Yanes, Julio A · 2018

Cannabis users showed decreased activation in the anterior cingulate cortex (linked to cognitive control) and dorsolateral prefrontal cortex (linked to attention).

Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System

Zou, S · 2018

The review documented ECS involvement across five major neurological conditions: (1) Huntington's disease: progressive loss of CB1 receptors occurs as an early marker BEFORE actual neurodegeneration begins; CB1 knockout worsens motor performance and striatal atrophy.

The Endocannabinoid System and Anxiety.

Lisboa, S F · 2017

This comprehensive chapter reviewed how the endocannabinoid system influences anxiety across both human anxiety disorders and animal models. The system's effects on anxiety are remarkably complex.

Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.

Rosenberg, Evan C · 2017

The review surveyed decades of preclinical research on plant cannabinoids in models of seizures, epilepsy, epileptogenesis (the development of epilepsy), and seizure-related neuroprotection. In simple acute seizure models, activating CB1 receptors typically reduced seizures, and blocking them worsened seizures.

Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.

Russo, Ethan B · 2017

This major review, authored by leading cannabis researchers, argued that the pharmacology of cannabis cannot be reduced to THC and CBD alone.

MECHANISMS IN ENDOCRINOLOGY: Endocannabinoids and metabolism: past, present and future.

Simon, Vincent · 2017

This review charted the evolution of understanding about the endocannabinoid system (ECS) and metabolism.

Rapid Changes in CB1 Receptor Availability in Cannabis Dependent Males after Abstinence from Cannabis.

D'Souza, Deepak Cyril · 2016

Using high-resolution PET imaging, researchers measured CB1 receptor availability in 11 cannabis-dependent males and 19 matched healthy controls. At baseline (while using cannabis), dependent subjects showed 15% lower CB1 receptor availability across nearly all brain regions compared to controls, a large effect (Cohen's d = -1.11).

Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation.

Spronk, Desirée B · 2016

In a double-blind, placebo-controlled crossover study, 38 healthy drug-using volunteers received cocaine, cannabis, and placebo in separate sessions and performed a Go/NoGo impulse control task. Cocaine improved performance: faster reaction times, better accuracy, and increased prefrontal NoGo-P3 brain activity (reflecting enhanced evaluative processing).

Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users.

Weinstein, Aviv · 2016

This comprehensive review synthesized 103 structural and functional brain imaging studies of cannabis users published between 2000 and 2016, providing the most complete picture to date of how cannabis affects the human brain. Structural findings: Regular cannabis use was associated with volumetric and tissue changes, particularly in the hippocampus (memory) and amygdala (emotion).

Crystal Structure of the Human Cannabinoid Receptor CB1

Hua, T · 2016

The 2.8 angstrom crystal structure of human CB1 was solved in complex with AM6538, a stabilizing antagonist specifically designed for this purpose.

How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

Freeman, Daniel · 2015

This was the largest study of intravenous THC, randomizing 121 individuals with existing paranoid ideation to receive THC, placebo, or THC with prior cognitive awareness training.

Endocannabinoid signaling at the periphery: 50 years after THC.

Maccarrone, Mauro · 2015

Written by many of the scientists who discovered key components of the endocannabinoid system, this comprehensive review examined how endocannabinoids function throughout the body beyond the brain. The endocannabinoid system was found to control fundamental biological processes including cell survival, death, and differentiation across nearly every organ system.

Endocannabinoids and Their Pharmacological Actions.

Pertwee, Roger G · 2015

This comprehensive review catalogued 13 endogenous compounds that likely function as endocannabinoids based on being detected in mammalian tissue and binding to cannabinoid receptors. Beyond the well-known anandamide and 2-AG, the review identified 11 additional endocannabinoids including noladin ether, virodhamine, oleamide, and docosahexaenoylethanolamide.

Chemical probes of endocannabinoid metabolism.

Blankman, Jacqueline L · 2013

The review described the development and application of chemical tools that selectively block the enzymes degrading each major endocannabinoid.

The endocannabinoid system and the brain.

Mechoulam, Raphael · 2013

Mechoulam and Parker systematically reviewed how the endocannabinoid system regulates brain function across seven major domains: anxiety, depression, neurogenesis, reward, cognition, learning, and memory.

The acute effects of cannabinoids on memory in humans: a review.

Ranganathan, Mohini · 2006

This comprehensive review of human studies found that acute THC administration impairs immediate and delayed free recall of information presented after drug administration but does not affect recall of information learned before THC was given. The effects are dose-dependent and delay-dependent, with greater impairment at higher doses and longer delays.

Pharmacokinetics and pharmacodynamics of cannabinoids.

Grotenhermen, Franjo · 2003

The review provided a detailed account of how THC and other cannabinoids are absorbed, distributed, metabolized, and eliminated.

Cannabis and the brain.

Iversen, Leslie · 2003

All known central effects of THC were mediated through CB1 receptors, with particularly high expression on GABAergic interneurons in the hippocampus, amygdala, and cerebral cortex.

Cannabinoids: reward, dependence, and underlying neurochemical mechanisms--a review of recent preclinical data.

Tanda, Gianluigi · 2003

Strong and persistent THC self-administration was demonstrated in squirrel monkeys at doses matching those humans self-administer when smoking marijuana, providing the first reliable direct measure of THC's reinforcing effects.

The molecular logic of endocannabinoid signalling

Piomelli, D · 2003

The review articulated the defining molecular logic of endocannabinoid signaling through four unique properties: (1) On-demand synthesis — endocannabinoids are produced from membrane phospholipid precursors in response to calcium influx, not stored in vesicles like classical neurotransmitters; (2) Lipid nature — as lipids derived from arachidonic acid, they cannot be stored in aqueous vesicles and cross cell membranes freely; (3) Retrograde direction — they travel from postsynaptic to presynaptic neurons, the reverse of classical neurotransmission; (4) Short-range local action — they are rapidly degraded by local enzymes (FAAH for anandamide, MAGL for 2-AG) and do not circulate systemically.

Cannabinoids control spasticity and tremor in a multiple sclerosis model.

Baker, D · 2000

Using a mouse model of MS (chronic relapsing experimental allergic encephalomyelitis) that produces spasticity and tremor similar to human MS, researchers tested multiple cannabinoid compounds. Four different cannabinoid receptor agonists, including THC, all quantitatively reduced both tremor and spasticity in the diseased mice.

Recent advantages in cannabinoid research.

Mechoulam, R · 1999

Writing 35 years after his group first isolated THC, Mechoulam described the trajectory from an isolated plant molecule to a complete biological system. The path was: THC isolation, receptor discovery (CB1 and CB2), and identification of endogenous ligands (anandamide and 2-AG).

Endocannabinoids.

Mechoulam, R · 1998

This review, authored by Raphael Mechoulam and colleagues who played central roles in discovering the endocannabinoid system, described two molecules the body produces naturally that activate the same receptors as THC. Anandamide and 2-arachidonoyl glycerol (2-AG) were identified as the principal endocannabinoids.

A second endogenous cannabinoid that modulates long-term potentiation

Stella, N · 1997

sn-2 arachidonylglycerol (2-AG) was identified in brain tissue at concentrations 170 times greater than anandamide.

Molecular characterization of a peripheral receptor for cannabinoids

Munro, S · 1993

A gene encoding a novel G-protein-coupled receptor was cloned from the human promyelocytic leukemia cell line HL-60.

Isolation and structure of a brain constituent that binds to the cannabinoid receptor

Devane, William A. · 1992

Arachidonylethanolamide (anandamide), an arachidonic acid derivative, was isolated from porcine brain tissue by screening lipid extracts for compounds that bind the cannabinoid receptor.

Structure of a cannabinoid receptor and functional expression of the cloned cDNA

Matsuda, L A · 1990

A complementary DNA (cDNA) encoding a G protein-coupled receptor (GPCR) was cloned from a rat brain library.

Age differences in endocannabinoid tone are ameliorated after recent cannabis use.

Morris, Alan W J · 2026

Older adults (55-71) had lower baseline AEA and DEA vs.

Cannabidiol and Parkinson's disease: Investigating receptor interactions and their therapeutic implications.

Okrah, Eric A · 2026

CBD exerts effects through the endocannabinoid system and numerous non-cannabinoid receptors, neurotransmitters, and enzymes.

Altered endocannabinoid system gene expression in inflammatory bowel disease mucosa: New perspectives in inflammatory bowel disease management.

Pelisenco, Iulia Andreea · 2026

In IBD patients, FAAH, PPARG, and TRPV1 were significantly downregulated in inflamed mucosa compared to non-inflamed tissue and controls.

Effects of acute alcohol administration on endocannabinoids and relation to subjective effects.

Petrie, Gavin N · 2026

Acute alcohol consumption decreased 2-AG concentrations compared to placebo.

Gray Matter Volume Loss in Parkinson's Disease Psychosis and Cannabinoid Receptor Gene Expression in the Brain.

Pisani, Sara · 2026

There was a significant association between gray matter volume loss in Parkinson's disease psychosis and CB1 receptor gene expression across brain regions (r = 0.337, p < 0.001).

Neurotoxic potential of synthetic cannabinoids' pyrolysis products.

Pita, Filipa · 2026

Synthetic cannabinoids undergo structural changes when heated during smoking, generating novel, frequently unidentified toxicants.

Unveiling Neurological Benefits: A Review of Hemp Leaf, Flower, Seed Oil Extract, and Their Phytochemical Properties in Neurological Disorders.

Purushothaman, Atchuthan · 2026

This review synthesized evidence on how different parts of the hemp plant — seeds, leaves, and flowers — contain distinct bioactive compound profiles with relevance to neurological disorders. Flowers are richest in cannabinoids (particularly CBD) and terpenes, which interact with the endocannabinoid system, neurotransmitter receptors, and inflammatory pathways.

Effects of acute THC challenge on behavior and neuroinflammation in HIV-1 Tg26 mice vary based on HIV status, chronic THC history, and sex.

Ravula, Havilah P · 2026

Chronic THC history (90 days) led to tolerance across behavioral measures, reducing THC-induced hypothermia, pain relief, and sedation, especially in females.

Selective activation of cannabinoid receptors by cannabis terpenes.

Raz, Noa · 2026

Multiple cannabis terpenes produced dose-dependent activation of both CB1 and CB2 receptors, reaching 10-60% of THC's maximal activation.

Cannabinoids and the autophagy-related signaling in brain Tumors: From mechanistic insights to therapeutic Frontiers in glioblastoma.

Rejili, Mokhtar · 2026

Glioblastoma harbors alterations in the endocannabinoid system including changes in CB1 and CB2 receptor expression.

Dopamine, γ-aminobutyric acid, and glutamate balance in the nucleus accumbens shell: Differential effects of cannabinoid 1 receptor agonists Δ9-Tetrahydrocannabinol, AM11101, and AM8936.

Smith, Evan C · 2026

Low-dose THC increased dopamine and GABA in the nucleus accumbens shell, while high-dose THC decreased dopamine.

The Use of Cannabis-Based Medicine in Selected Neurological Disorders.

Szejko, Natalia · 2026

The best evidence for cannabis-based medicine efficacy in movement/neurodegenerative disorders is for Tourette syndrome, where THC-containing preparations improved tics and psychiatric comorbidities.

Endocannabinoid Modulation in Headache: Mechanisms, Models, and Translational Therapies.

Wen, Jie · 2026

The endocannabinoid system modulates trigeminovascular firing, CGRP release, neurogenic inflammation, cortical spreading depression, and glial activation after brain injury.

Cannabis and nicotine/tobacco co-use and its association with cognitive and neural outcomes: A systematic review.

Yeap, Zac J S · 2026

People who co-used cannabis and nicotine/tobacco showed similar working memory performance, resting-state brain connectivity, and task-based brain activation compared to people without substance use.

Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray.

Coutens, Basile · 2025

In the ventrolateral periaqueductal gray (vlPAG), corticosterone activates putative membrane-bound glucocorticoid receptors, which stimulate 2-AG synthesis.

In utero chronic cannabis exposure is associated with lower total brain volume in the first month of postnatal life.

Crume, Tessa L · 2025

Studying prenatal cannabis exposure is extremely difficult because most pregnant cannabis users also use tobacco, alcohol, or other substances, making it nearly impossible to isolate cannabis's independent effects.

Cannabinoid CB1 receptor in dopaminergic circuit from ventral tegmental area to nucleus accumbens links trait anxiety with reward learning.

Cui, Chi · 2025

High trait anxiety mice exhibited increased reward learning.

D1-like dopamine receptors in the dentate gyrus mediate cannabidiol's facilitation of extinction and prevention of reinstatement in methamphetamine-induced conditioned place preference.

Danesh, Elaheh · 2025

CBD enhanced extinction of meth-conditioned place preference and prevented reinstatement.

Endocannabinoid signaling in stress, nausea, and vomiting.

DeVuono, Marieka V · 2025

The endocannabinoid system normally regulates nausea, vomiting, and anxiety.

Changes in peripheral endocannabinoid levels in substance use disorders: a review of clinical evidence.

Elliott, Georgia O · 2025

Across substance use disorders, anandamide (AEA) concentrations were usually elevated, while 2-AG was measured less often and showed mixed results.

The contribution of baseline circulating endocannabinoids to individual differences in human pain sensitivity: a quantitative sensory testing study.

Fatemi, S A · 2025

Serum eCB/NAE concentrations were not affected by sex, FAAH genotype, or cannabis use.

Neural Signatures of Cannabis Use: Reversing Cognitive Aging via Whole-Brain Functional Network Connectivity.

Fu, Zening · 2025

Cannabis use and healthy aging were associated with overlapping brain network configurations, particularly between subcortical-sensorimotor and subcortical-cerebellar regions, but with significantly reversed effects.

Preclinical evaluation of cannabidiolic acid as a neuroprotective agent in TDP-43 transgenic mice, an experimental model of amyotrophic lateral sclerosis.

García-Toscano, Laura · 2025

Among five phytocannabinoids tested, CBDA at 10 mg/kg was the most effective, improving motor coordination, reducing neuronal cell death and neuroinflammation, and shifting microglia from pro-inflammatory to anti-inflammatory.

Repeated footshock stress enhances cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1.

Gaulden, Andrew D · 2025

Footshock stress increased cocaine self-administration in both sexes.

Sex-dependent effects of stress on aIC-NAc circuit neuroplasticity: Role of the endocannabinoid system.

Gauthier, Manon · 2025

Under basal conditions, males showed equal proportions of LTP and LTD in the insular cortex-to-NAc pathway, while females predominantly showed LTP.

Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1G93 A) mouse model of amyotrophic lateral sclerosis.

Ghimire, Sandip · 2025

CBD (36 mg/kg/day oral) ameliorated weight loss in female SOD1G93A mice, tended to restore sociability in males, strengthened social recognition memory in females, and improved prepulse inhibition in younger females.

Coordinated epigenetic dysregulation of CNR1 and FAAH genes drives endocannabinoid system dysfunction in anorexia nervosa.

Gilardini, Federica · 2025

A novel bidirectional epigenetic dysregulation was discovered: CNR1 (cannabinoid receptor 1) promoter hypermethylation coupled with FAAH (endocannabinoid-degrading enzyme) promoter hypomethylation.

Role of interplay between endocannabinoids and neuropeptides in pathogenesis and therapy of depressive and anxiety disorders.

Gołyszny, Miłosz · 2025

The hypothalamus is the primary site of proven bidirectional endocannabinoid-neuropeptide interactions.

Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice.

Gómez-Acero, Laura · 2025

Adolescent THC exposure impaired social interaction and increased vulnerability to sensorimotor gating deficiencies (similar to those in heavy cannabis users).

Placental Endocannabinoid System: Focus on Preeclampsia and Cannabis Use.

Harhangi, Madhavi S · 2025

The study found three distinct patterns: (1) In healthy pregnancies, anandamide relaxed placental arteries via CB1 and CB2 receptors.

A Systematic Review: Investigating Biomarkers of Anhedonia and Amotivation in Depression and Cannabis Use.

Hinckley, Jesse D · 2025

Across 46 articles, brain regions most frequently associated with anhedonia across neuroimaging studies were the anterior cingulate cortex, nucleus accumbens, and medial prefrontal cortex, which are the same regions implicated in cannabis-related reward processing deficits.

Cannabis produces acute hyperphagia in humans and rodents via increased reward valuation for, and motivation to, acquire food.

Hume, Catherine · 2025

Vaporized cannabis acutely and robustly increased energy intake in humans (within 30 minutes, regardless of dose or gender) and rats (within 60 minutes, regardless of macronutrient content, satiation, or sex).

Cannabidiol attenuates precuneus activation during appetitive cue exposure in individuals with alcohol use disorder.

Hurzeler, Tristan · 2025

In 22 non-treatment-seeking AUD participants, 800 mg CBD did not affect alcohol cue-elicited brain activation in pre-specified regions of interest.

Alterations of the endocannabinoid system in autism spectrum disorder: a systematic review and meta-analysis.

Jia, Xinlei · 2025

Blood anandamide (AEA) levels were significantly lower in individuals with ASD (SMD=-0.79, p=0.002) compared to controls.

Unravelling gender differences in cannabis cue-reactivity in individuals who use cannabis.

Kaag, A M · 2025

Women cannabis users showed blunted neural cue-reactivity in the right insula and putamen compared to male users, a pattern opposite to controls.

Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity.

Kangas, Brian D · 2025

Adolescent monkeys treated daily with THC for 6 months showed persistent alterations in medial orbitofrontal cortex, caudate, and ventral striatum functional connectivity that lasted after discontinuation.

The changing landscape of cannabis use: impact on maternal health and neonatal outcomes.

Krishnan, Parvathy · 2025

Beyond the well-documented cognitive and neurodevelopmental effects, prenatal cannabis exposure is associated with fetal growth restriction, altered cardiovascular development, hematologic changes, gastrointestinal effects, and increased long-term risk for obesity, diabetes, and cardiovascular disease.

Interspecies differences in the expression of cannabinoid receptors at the tissue and cellular levels.

Lawley, Sydney · 2025

CB1 and CB2 receptor expression differs substantially between species in terms of tissue distribution, cellular localization, and co-expressed markers.

Cannabis Perturbs Dynamic Brain States.

Lege, Katharina S · 2025

This neuroimaging trial used a sophisticated approach—dynamic functional connectivity analysis—to examine how vaporized cannabis affects brain network organization in real time.

Abnormal Cortical Thickness Development in Young Adults With Heavy Cannabis Use: A Longitudinal Study.

Li, Wei · 2025

At three-year follow-up, heavy cannabis users showed significant cortical thinning in the left lateral orbitofrontal cortex compared to both their own baseline and control subjects.

Exploring the neuroprotective effects and underlying mechanisms of medical cannabinoids in ischemic stroke: a systematic meta-analysis with bibliometric mapping of cerebral ischemia research.

Li, Xiaoqun · 2025

Across 26 studies, cannabinoids significantly reduced cerebral infarct volume, improved neurological function, increased cerebral blood flow, and decreased blood-brain barrier permeability, brain water content, cell death, oxidative stress markers, and inflammatory markers (TNF-alpha, IL-1beta).

Identification and External Validation of a Problem Cannabis Risk Network.

Lichenstein, Sarah D · 2025

A whole-brain machine learning approach identified a "problem cannabis risk network" from reward task brain connectivity data in college students.

Comparative analysis of 105 datasets across species and tissues reveals differential transcriptomic responses to cannabinoids THC and CBD.

Liu, Ruoshui · 2025

CBD datasets showed more differentially expressed genes and enriched pathways across species.

The Endocannabinoid System in PTSD: Molecular Targets for Modulating Fear and Anxiety.

Lyndon, Stanley · 2025

The endocannabinoid system plays a pivotal role in regulating fear learning and extinction.

Metabolomic profiling of cannabis use and cannabis intoxication in humans.

Madrid-Gambin, Francisco · 2025

Occasional and chronic cannabis users had distinctly different metabolic fingerprints at baseline (not intoxicated).

Integrating endocannabinoid signaling, CCK interneurons, and hippocampal circuit dynamics in behaving animals.

Malhotra, Shreya · 2025

New biosensors and imaging tools can now track endocannabinoid signaling at individual synapses in behaving animals.

Acute cannabis intoxication among the paediatric population.

Malta, Ginevra · 2025

THC effects in children typically emerge within 2 hours of ingestion, with severe symptoms developing by 4 hours.

Circulating endocannabinoids in children and adolescents: associations with anxiety and the impact of selective serotonin reuptake inhibitors.

Marusak, Hilary A · 2025

After adjusting for BMI, age, sex, and time of day, higher AEA and lower 2-AG were associated with more severe anxiety symptoms.

Cannabidiol and Alzheimer Disease: A Comprehensive Review and In Silico Insights Into Molecular Interactions.

Mello-Hortega, João V · 2025

CBD has demonstrated effects on amyloid plaques, tau protein, neuroinflammation, oxidative stress, and cholinergic pathways in preclinical Alzheimer's models.

In vitro pharmacological activity of twenty-eight synthetic cannabinoid receptor agonists at the type 1 and 2 cannabinoid receptors.

Mercier, Gabrielle · 2025

Twenty-eight synthetic cannabinoid receptor agonists were evaluated for receptor binding and signaling.

Cannabidiol and cognitive functions/inflammatory markers in Parkinson's disease: A double-blind randomized controlled trial at Buriram Hospital (CBD-PD-BRH trial).

Mitarnun, Witoon · 2025

Among 51 Parkinson's patients completing the trial, low-dose CBD (26 mg/day) was safe with no serious side effects.

Influence of recent cannabis use on altered spectral entropy modulation and connectivity strength in patients with psychosis.

Molina, Vicente · 2025

Both cannabis-using and non-using psychosis patients showed impaired spectral entropy modulation and elevated connectivity strength compared to 86 healthy controls.

Age-Related Effects of Cannabis and Cannabinoids on Brain and Behavior.

Murray, Conor H · 2025

Recent epidemiological data suggest a potential reversal in escalating cannabis use rates among pregnant women and adolescents, but use among older adults continues to climb with low risk perception.

Understanding the Role of Endocannabinoids in Posttraumatic Stress Disorder.

Ney, Luke · 2025

Preclinical literature is reasonably consistent in showing that endocannabinoid system modulation can affect fear memory processes relevant to PTSD.

Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state.

Nisha Aji, Kankana · 2025

Cannabis use had a significant effect on MAO-B availability (F=12.57, p=0.001, Cohen's f=0.57), with a significant group-by-cannabis interaction (p=0.03) showing lower MAO-B in cannabis-using clinical groups.

The Relationship of glutamate signaling to cannabis use and schizophrenia.

Niznikiewicz, Margaret · 2025

The review synthesizes three lines of evidence: cannabis is associated with psychosis in a subset of users, glutamate dysregulation is a feature of schizophrenia, and cannabis affects the glutamate system.

Cannabis use in adolescence and young adulthood and its effects on brain structure and function: a scoping review.

Nosko, Lilith · 2025

Of 99 studies meeting inclusion criteria (from 3,901 initially screened), 84 (85%) found differences in brain structure, function, and/or metabolite concentrations in cannabis users aged 14-25 compared to non-using controls.

The Effects of THC and Nicotine on Attention: A Narrative Review.

Oleszak, Kennedy · 2025

Cannabis impairs selective attention and creates attentional bias toward cannabis cues.

Effects of prenatal cannabinoid use on the monoamine system in the fetoplacental unit: A systematic review of animal and human studies.

Portillo, Ramon · 2025

After screening 18,252 papers, only 16 animal and 4 human studies met criteria.

Sex differences in endocannabinoid and inflammatory markers associated with posttraumatic stress disorder.

Rajasekera, Therese A · 2025

Among 88 PTSD patients and 85 matched controls, male PTSD patients had significantly decreased levels of AEA, arachidonic acid, and OEA compared to male controls and female subgroups.

Systematic review: the impact of maternal pre-and postnatal cannabis use on the behavioral and emotional regulation in early childhood.

Reyentanz, Emely · 2025

From 1,061 screened articles, 33 were included.

Sex-specific responses to cannabis exposure: Implications for behavior and beyond.

Rogers, Sophia · 2025

This scoping review synthesized evidence on sex-specific behavioral responses to cannabis.

Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions.

Rosa, Ilenia · 2025

This review synthesizes evidence that diverse non-monoaminergic treatments for treatment-resistant depression all influence the endocannabinoid system.

The effects of cannabis on mind-wandering.

Safati, Adrian Berk · 2025

In a three-session ABA design (abstinent-cannabis-abstinent), cannabis use was associated with a large increase in spontaneous mind-wandering during a metronome timing task.

Exploring the Utility of a Functional Magnetic Resonance Imaging Cannabis Cue-Reactivity Paradigm in Treatment-Seeking Adults With Cannabis Use Disorder.

Sahlem, Gregory L · 2025

In 65 treatment-seeking participants with moderate or severe CUD, viewing cannabis images (vs neutral) activated bilateral prefrontal cortex, anterior cingulate, visual cortex, and striatum.

Dual Role of the Spinal Endocannabinoid System in Response to Noxious Stimuli: Antinociceptive Pathways and Neuropathic Pain Mechanisms.

Saldaña, Raquel · 2025

This review reveals that the spinal endocannabinoid system's role in pain is context-dependent.

The endocannabinoid system in cancer biology: a mini-review of mechanisms and therapeutic potential.

Salum, Kaio Cezar Rodrigues · 2025

This review summarizes how the endocannabinoid system influences cancer through CB1 and CB2 receptor activation.

Methylation Status of the DAT1 Dopamine Transporter Gene in Individuals With Cannabis Use Disorder: Associations With Personality Traits.

Suchanecka, Aleksandra · 2025

Individuals with CUD showed altered DAT1 methylation levels compared to controls.

Astrogliosis Occurs Selectively in Amygdala of Adolescent Primate and Rodent Following Daily Δ9-Tetrahydrocannabinol, Prevented by Cannabidiol Co-Treatment.

Sun, Yalin · 2025

THC induced GFAP and complement factor-B upregulation (proinflammatory gliosis) exclusively in the adolescent amygdala, not in other brain regions or adults.

Cannabidiol prevents cognitive and social deficits in a male rat model of Alzheimer's disease through CB1 activation and inflammation modulation.

Toledano, Roni Shira · 2025

STZ-induced Alzheimer's rats showed impaired object recognition, location memory, and social behavior, along with elevated amyloid-beta, tau phosphorylation, TREM2, APOEε4, TNFα, NF-κB1, and IL-1β in the hippocampus.

The interaction between cannabinoids and long-term synaptic plasticity: A survey on memory formation and underlying mechanisms.

Azarfarin, Maryam · 2024

Evidence on cannabinoid effects on LTP and memory is contradictory.

Alterations in self-reported sensory gating and interoception in individuals frequently using cannabis.

Bloomer, Bess F · 2024

Cannabis users reported impaired sensory gating across subscales (d=0.37-0.44, all p<0.05) and heightened affect-related interoceptive awareness (d=0.21-0.61, all p<0.05) compared to non-users.

Biobehavioral Interactions between Endocannabinoid and Hypothalamicpituitary- adrenal Systems in Psychosis: A Systematic Review.

Colizzi, Marco · 2024

Both systems show independent contributions to psychosis risk, but they also interact bidirectionally: cannabis use affects endocannabinoid tone, stress exposure alters the HPA axis, and crucially, THC also affects the HPA axis while childhood trauma affects endocannabinoid signaling, revealing cross-system perturbation..

The risk of cannabis use disorder is mediated by altered brain connectivity: A chronnectome study.

Fazio, Giovanni · 2024

At-risk individuals (n=39) spent more time in a brain state with higher within-network and reduced between-network connectivity across subcortical, sensory-motor, visual, cognitive-control, and default-mode networks compared to controls (n=55).

The Combined Effects of Nicotine and Cannabis on Cortical Thickness Estimates in Adolescents and Emerging Adults.

Hernandez Mejia, Margie · 2024

Both cannabis and nicotine users had thinner frontal cortices bilaterally compared to non-users.

Using Task-fMRI to Explore the Relationship Between Lifetime Cannabis Use and Cognitive Control in Individuals With First-Episode Schizophrenia.

Lesh, Tyler A · 2024

First-episode schizophrenia patients with cannabis history (FES+CAN, n=48) showed higher cognitive control performance and higher dorsolateral prefrontal cortex (DLPFC) activation during task-based fMRI compared to patients without cannabis history (FES-CAN, n=28).

Light Cannabis Use and the Adolescent Brain: An 8-years Longitudinal Assessment of Mental Health, Cognition, and Reward Processing.

Macedo, Inês · 2024

Teens who used cannabis weekly or monthly between ages 19 and 22 showed more conduct problems than non-users, but no differences in cognitive performance or reward-related brain activity.

White matter alterations associated with chronic cannabis use disorder: a structural network and fixel-based analysis.

Maleki, Suzan · 2024

Compared to 38 healthy controls, 56 individuals with CUD had significantly increased structural connectivity across 9 brain connections involving the right parietal cortex and regions including left orbitofrontal cortex, temporal pole, hippocampus, and putamen.

A systematic review of oculomotor deficits associated with acute and chronic cannabis use.

Manning, Brooke · 2024

Across 20 studies, acute THC consumption increased saccadic latency, reduced accuracy, and impaired inhibitory control.

The effects of cannabis abstinence on cognition and resting state network activity in people with multiple sclerosis: A preliminary study.

Meza, Cecilia · 2024

The cannabis withdrawal group showed increased activation at day 28 in the left posterior cingulate, right angular gyrus, left hippocampus, and right medial prefrontal cortex compared to baseline.

Type 2 cannabinoid receptor expression on microglial cells regulates neuroinflammation during graft-versus-host disease.

Moe, Alison · 2024

CB2 receptor expression on microglia induced an activated inflammatory phenotype that promoted accumulation of donor-derived proinflammatory T cells, regulated chemokine gene networks, and caused neuronal cell death in GVHD.

Changes in Immune-Related Biomarkers and Endocannabinoids as a Function of Frequency of Cannabis Use in People Living With and Without HIV.

Murray, Conor H · 2024

PLWH had higher TNFR2 (p=0.013) and CD27 (p=0.004) and lower anandamide (p=0.027) and OEA (p=0.007) versus HIV-negative men.

Cells and Molecules Underpinning Cannabis-Related Variations in Cortical Thickness during Adolescence.

Navarri, Xavier · 2024

In mice, THC exposure caused spine loss and reduced dendritic complexity in frontal cortex pyramidal cells.

A Systematic Review of Delta-9-Tetrahydrocannabinol (∆9-THC) in Astrocytic Markers.

Ramos-Jiménez, Christian · 2024

Both GFAP and nestin expression increased in adulthood following adolescent and adult THC exposure.

The Role of Cannabis in the Development of Psychosis.

Türkoğlu, Özge · 2024

Earlier age of cannabis use onset, genetic predisposition, and heavy/high-potency use all independently increase psychosis risk.

Disruption of tonic endocannabinoid signalling triggers cellular, behavioural and neuroendocrine responses consistent with a stress response.

Petrie, Gavin N · 2023

CB1 receptor antagonist/inverse agonist AM251, neutral antagonist NESS243, and NAPE-PLD inhibitor LEI401 all uniformly increased PVN Fos expression, unmasked stress-linked behaviors (grooming), and increased circulating corticosterone, mimicking the effects of actual stress.

Role of the CB2 Cannabinoid Receptor in the Regulation of Food Intake: A Systematic Review.

Rodríguez-Serrano, Luis Miguel · 2023

CB2 receptors in brain reward areas modulate food intake.

Roadmap For The Expression Of Canonical and Extended Endocannabinoid System Receptors and Proteins in Peripheral Organs of Preclinical Animal Models.

Rosado-Franco, J J · 2023

Of 14 canonical and extended endocannabinoid receptors examined across 7 peripheral organs, only CB2, GPR18, GPR55, TRPV2, and FAAH had identical expression patterns in mice, rats, and rhesus macaques.

Fatty Acid Amide Hydrolase: An Integrative Clinical Perspective.

Santoso, Anugrah D · 2023

FAAH is highly expressed in both the central nervous system and peripheral tissues.

Prenatal THC exposure induces long-term, sex-dependent cognitive dysfunction associated with lipidomic and neuronal pathology in the prefrontal cortex-hippocampal network.

Sarikahya, Mohammed H · 2023

Both sexes showed long-term cognitive deficits and hyperactive prefrontal pyramidal neurons.

Cannabidiol and brain function: current knowledge and future perspectives.

Schouten, Moniek · 2023

CBD has documented therapeutic effects for epileptic seizures, psychosis, anxiety, neuropathic pain, and inflammation.

Cannabinoids and Brain Damage: A Systematic Review on a Frequently Overlooked Issue.

Scopetti, Matteo · 2023

Cannabinoid consumption is associated with psychiatric disorders, neurocognitive impairment, neurological disorders, and in some cases of acute consumption of synthetic cannabinoids, death.

Impact of Adolescent Cannabis Use on Neurocognitive and Brain Development.

Scott, J Cobb · 2023

Converging evidence shows that ongoing, frequent cannabis use in adolescence is associated with small reductions in cognitive functioning.

The Effects of Acute Cannabis With and Without Cannabidiol on Neural Reward Anticipation in Adults and Adolescents.

Skumlien, Martine · 2023

Adults showed reduced ventral striatum activation during reward anticipation after THC, while adolescents did not.

Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials.

Arkell, Thomas R · 2022

After controlling for BMI and plasma THC, relatively few sex differences emerged.

The effects of acute Cannabis smoke or Δ9-THC injections on the trial-unique, nonmatching-to-location and five-choice serial reaction time tasks in male Long-Evans rats.

Barnard, Ilne L · 2022

High-THC cannabis smoke and THC injections impaired working memory on the TUNL task but had no effect on attention, impulsivity, or perseveration on the 5-CSRTT.

Molecular Insights into Epigenetics and Cannabinoid Receptors.

Basavarajappa, Balapal S · 2022

Epigenetic mechanisms including DNA methylation, histone protein modifications, and RNA regulatory networks significantly influence cannabinoid receptor (CB1 and CB2) gene expression, contributing to both normal function and disease states..

Anandamide Hydrolysis Inhibition Reverses the Long-Term Behavioral and Gene Expression Alterations Induced by MK-801 in Male Rats: Differential CB1 and CB2 Receptor-Mediated Effects.

Bauminger, Hagar · 2022

The anandamide hydrolysis inhibitor URB597, given in late adolescence, reversed both novel object recognition deficits (via CB2 receptors) and social interaction abnormalities (via CB1 receptors) induced by early-adolescence MK-801 administration, while also normalizing glutamate and GABA marker expression in the prefrontal cortex..

Medial prefrontal cortex mechanisms of cannabidiol-induced aversive memory reconsolidation impairments.

Bayer, Hugo · 2022

Systemic CBD reduced Zif268/Egr1 protein (a synaptic plasticity marker for reconsolidation) in the anterior cingulate and prelimbic cortex but not the infralimbic cortex.

Metabolites of Synthetic Cannabinoid 5F-MDMB-PINACA Retain Affinity, Act as High Efficacy Agonists and Exhibit Atypical Pharmacodynamic Properties at CB1 Receptors.

Cabanlong, Christian V · 2022

5F-MDMB-PINACA and its metabolite M2 showed nanomolar affinity and high efficacy at CB1 receptors.

Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study.

Coleman, James R · 2022

Female mice showed altered fractional anisotropy and apparent diffusion coefficient (measures of brain microstructure) in forebrain and hindbrain.

Increased White Matter Coherence Following Three and Six Months of Medical Cannabis Treatment.

Dahlgren, Mary Kathryn · 2022

FA values (indicating white matter integrity) significantly increased in corpus callosum regions after 3 and 6 months of MC treatment.

Latent inhibition, aberrant salience, and schizotypy traits in cannabis users.

Dawes, Christopher · 2022

Current cannabis use was associated with higher "disorganized" and "cognitive-perceptual" schizotypy scores and higher aberrant salience inventory scores.

A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System.

Desai, Shreya · 2022

The meta-analysis of 10 studies showed consistent increases in both anandamide (AEA) and 2-AG following acute exercise across different exercise types (running, cycling), species (humans, mice), and health conditions.

Cannabinoid receptor 2 evolutionary gene loss makes parrots more susceptible to neuroinflammation.

Divín, Daniel · 2022

All parrots (Psittaciformes) have a nonfunctional CB2 gene due to chromosomal rearrangements.

Cannabis and Cannabinoids in Reproduction and Fertility: Where We Stand.

Fonseca, Bruno M · 2022

THC indirectly decreases GnRH secretion from the hypothalamus, leading to disruptions in multiple reproductive hormones.

The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Fusar-Poli, Laura · 2022

Better facial emotion recognition was associated with lifetime regular cannabis use across all three groups: schizophrenia patients (B=1.36), siblings (B=2.17), and healthy controls (B=3.10).

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies.

García-Gutiérrez, María Salud · 2022

CB2 receptor activation or blockade modulated alcohol-related behaviors in rodents.

Surface-based brain morphometry in schizophrenia vs. cannabis-induced psychosis: A controlled comparison.

Ghosh, Abhishek · 2022

Schizophrenia with heavy cannabis use (SZC) showed the lowest cortical thickness, depth, and gyrification, followed by cannabis-induced psychosis (CIP), then healthy controls.

Identification of ∆9-tetrahydrocannabinol (THC) impairment using functional brain imaging.

Gilman, Jodi M · 2022

In 169 cannabis users given oral THC or placebo in a crossover design, prefrontal cortex oxygenated hemoglobin increased after THC only in participants classified as impaired.

Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity.

Greenwood, Lisa-Marie · 2022

THC and CBD both increased duration and intensity MMN amplitude in less-frequent users.

Cannabinoids, reward processing, and psychosis.

Gunasekera, Brandon · 2022

THC modulated activity in the striatum, midbrain, insula, and anterior cingulate during reward processing, with some effects correlating with the severity of THC-induced psychotic symptoms.

Impact of cyclooxygenase-2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers.

Haney, Margaret · 2022

Compared to placebo, celecoxib improved some subjective sleep measures but did not affect mood, cannabis self-administration, or circulating endocannabinoid levels.

Chronic exposure to delta-9-tetrahydrocannabinol impacts testicular volume and male reproductive health in rhesus macaques.

Hedges, Jason C · 2022

For each 1 mg/7 kg/day increase in THC dose, bilateral testicular volume decreased by 11.8 cm3.

Sex-specific mechanisms of tolerance for the cannabinoid agonists CP55,940 and delta-9-tetrahydrocannabinol (Δ9-THC).

Henderson-Redmond, Angela N · 2022

The S426A/S430A mutation, which blocks CB1 receptor desensitization via the GRK/beta-arrestin2 pathway, conferred partial resistance to THC tolerance in male mice but did not alter tolerance in female mice.

Multimodal MRI data fusion reveals distinct structural, functional and neurochemical correlates of heavy cannabis use.

Hirjak, Dusan · 2022

Two transmodal components significantly differed between heavy cannabis users and controls.

Cannabis use selectively modulates circulating biomarkers in the blood of schizophrenia patients.

Ibarra-Lecue, Inés · 2022

Platelet serotonin 2A receptors, active Akt protein, anandamide, other lipid mediators, and pro-inflammatory IL-6 were all significantly increased in schizophrenia patients.

In utero exposure to cannabidiol disrupts select early-life behaviors in a sex-specific manner.

Iezzi, Daniela · 2022

Male pups from CBD-treated dams gained more weight than controls.

Cannabis Vapor Exposure Alters Neural Circuit Oscillatory Activity in a Neurodevelopmental Model of Schizophrenia: Exploring the Differential Impact of Cannabis Constituents.

Jenkins, Bryan W · 2022

NVHL rats (schizophrenia model) had reduced baseline gamma power in multiple brain regions.

Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice.

Kesner, Andrew J · 2022

THC withdrawal produced altered striatal dopamine release, sleep disturbances that mimic clinical observations (disrupted sleep architecture), and affect-related behavioral changes.

Cannabinoid and endocannabinoid system: a promising therapeutic intervention for multiple sclerosis.

Khan, Hina · 2022

Clinical studies confirm cannabinoids relieve MS pain, tremors, and spasticity.

Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis.

Kurlyandchik, Inna · 2022

Plasma levels of oleoylethanolamide and stearoylethanolamide were significantly increased in fibromyalgia patients compared to controls.

Persistent sexually dimorphic effects of adolescent THC exposure on hippocampal synaptic plasticity and episodic memory in rodents.

Le, Aliza A · 2022

Adolescent THC exposure produced selective, lasting deficits in synaptic plasticity in two hippocampal pathways, primarily in females.

Frequent Low-Dose Δ9-Tetrahydrocannabinol in Adolescence Disrupts Microglia Homeostasis and Disables Responses to Microbial Infection and Social Stress in Young Adulthood.

Lee, Hye-Lim · 2022

Daily THC from postnatal day 30 to 44 produced microglia dysfunction in both male and female mice that persisted to young adulthood (PND70) but receded by PND120.

A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse.

Lin, Xiaoyan · 2022

CB2 agonists (AM1710 and LY2828360) suppressed paclitaxel-induced mechanical and cold allodynia in mice.

A Cannabinoid Hypothesis of Schizophrenia: Pathways to Psychosis.

Little, Rachel · 2022

The review describes several putative pathways from cannabis to psychosis, integrating evidence about the endocannabinoid system, THC's effects on dopamine and glutamate signaling, and the connection between cannabis use and first-episode psychosis..

TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids.

Louis-Gray, Kathleen · 2022

TRPV1 activation in the central descending pain pathway (RVM and PAG) mediates antinociception, while peripheral TRPV1 activation mediates nociception.

Handedness as a neurodevelopmental marker in schizophrenia: Results from the FACE-SZ cohort.

Mallet, Jasmina · 2022

Among 667 schizophrenia patients, 42.4% were non-right-handed and 34.1% mixed-handed.

Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice.

Margiani, Giulia · 2022

Adolescent mice acquired JWH-018 self-administration behavior that was specifically reward-driven and blocked by a CB1 antagonist.

Endocannabinoid Modulation Using Monoacylglycerol Lipase Inhibition in Tourette Syndrome: A Phase 1 Randomized, Placebo-Controlled Study.

Müller-Vahl, Kirsten R · 2022

A single 40 mg dose of Lu AG06466 (a MAGL inhibitor that raises 2-AG endocannabinoid levels) showed an overall trend of tic reduction across all scales, with 2 of 3 tic scales (including the Yale Global Tic Severity Score) showing significant improvement versus placebo at various timepoints.

Adolescents are more sensitive than adults to acute behavioral and cognitive effects of THC.

Murray, Conor H · 2022

Adolescents (18-20) showed dose-dependent impairments in reaction time, response accuracy, and time perception with THC (7.5 and 15 mg) that adults (30-40) did not exhibit.

Randomized controlled trials on the use of cannabis-based medicines in movement disorders: a systematic review.

Oikonomou, P · 2022

In Parkinson's disease, no RCT showed motor symptom improvement, though nabilone improved quality of life and reduced dyskinesia in one trial.

Bayesian causal network modeling suggests adolescent cannabis use accelerates prefrontal cortical thinning.

Owens, Max M · 2022

All Bayesian causal network algorithms strongly suggested a directional relationship from adolescent cannabis use to accelerated cortical thinning in the prefrontal cortex, even after accounting for demographics, psychopathology, childhood adversity, and other substance use..

Cannabidiol for the treatment of autism spectrum disorder: hope or hype?

Pedrazzi, João F C · 2022

Preclinical data show CBD modulates the endocannabinoid system, which appears altered in ASD patients.

Endocannabinoid system and cannabis hyperemesis syndrome: a narrative update.

Perisetti, Abhilash · 2022

The endocannabinoid system produces biphasic effects: acute cannabis use is antiemetic, but chronic heavy use can trigger a proemetic response leading to CHS.

Cannabis exposure during adolescence: A uniquely sensitive period for neurobiological effects.

Peters, K Z · 2022

The endocannabinoid system changes during adolescence affect how it modulates developing dopamine circuits.

Shared Genetic Etiology between Cortical Brain Morphology and Tobacco, Alcohol, and Cannabis Use.

Rabinowitz, Jill A · 2022

Eight significant negative genetic correlations were found between brain measures and substance use, including between alcohol consumption and cortical thickness.

Chronic prenatal delta-9-tetrahydrocannabinol exposure adversely impacts placental function and development in a rhesus macaque model.

Roberts, Victoria H J · 2022

THC-exposed pregnancies showed significantly decreased amniotic fluid volume (p<0.001), reduced placental perfusion (p<0.05), and lower fetal oxygen availability (p<0.05).

Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls.

Skumlien, Martine · 2022

Cannabis users and controls had similar neural responses during reward anticipation and in reward-related brain regions during feedback.

Age- and Sex-Related Cortical Gray Matter Volume Differences in Adolescent Cannabis Users: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

Allick, Aliyah · 2021

No regions showed significant gray matter volume differences between 357 cannabis-using and 404 typically developing youth.

Cannabis and synaptic reprogramming of the developing brain.

Bara, Anissa · 2021

Cannabis exposure during prenatal/perinatal and adolescent periods disrupts the endocannabinoid system's role in neurodevelopment, impairing synaptic plasticity.

Are Schizophrenic disorders with or without early cannabis use neurobiologically distinct disease entities? A meta-analysis of magnetic resonance imaging studies.

De Peri, Luca · 2021

Both schizophrenia patients with cannabis use (n=227) and without (n=238) showed reduced whole brain, total grey matter, and hippocampal volumes compared to healthy controls (n=366).

Differential effects of cannabis exposure during early versus later adolescence on the expression of psychosis in homeless and precariously housed adults.

Gicas, Kristina M · 2021

Early cannabis exposure (by age 15) was associated with increased risk of substance-induced psychosis (OR=1.09, p<0.05).

The Yin and Yang of Cannabis: A Systematic Review of Human Neuroimaging Evidence of the Differential Effects of Δ9-Tetrahydrocannabinol and Cannabidiol.

Gunasekera, Brandon · 2021

Despite heterogeneous methods, an overall pattern of opposite THC and CBD effects was evident, primarily from head-to-head challenge studies.

The Influence of Cannabis and Nicotine Co-use on Neuromaturation: A Systematic Review of Adolescent and Young Adult Studies.

Hernandez Mejia, Margie · 2021

Cannabis and nicotine showed independent negative cognitive effects, but when used together, nicotine appeared to mask some cannabis-related cognitive deficits.

Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity.

LaVigne, Justin E · 2021

All four terpenes activated CB1 receptors in vitro and produced cannabinoid tetrad behaviors in mice (pain relief, immobility, hypothermia, reduced movement).

Contribution of Fatty Acid Amide Hydrolase to Alcohol Use Disorder: A Systematic Review.

Niemela, Greta · 2021

FAAH inhibition showed promise for reducing alcohol withdrawal symptoms, including anxiety and reinstatement of alcohol intake.

Cannabis use-related working memory deficit mediated by lower left hippocampal volume.

Paul, Subhadip · 2021

Higher frequency of cannabis use was associated with lower working memory scores and smaller bilateral hippocampal volumes.

Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis.

Penzel, Nora · 2021

Earlier cannabis initiation was linked to greater cerebellar gray matter volume in a network previously identified as altered in schizophrenia, independent of confounders.

Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring.

Rompala, Gregory · 2021

Children exposed to maternal cannabis had increased hair cortisol levels, greater anxiety, aggression, and hyperactivity on BASC-2 assessments, and reduced vagal tone (high-frequency HRV) at baseline.

Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users: a systematic review of fMRI studies.

Sehl, Hannah · 2021

Across 18 studies involving 918 participants, cannabis users showed greater brain activation to cannabis cues versus neutral stimuli in the striatum, prefrontal cortex (anterior cingulate, middle frontal), and parietal cortex (posterior cingulate/precuneus), with preliminary links between craving and activity in the amygdala, striatum, and orbitofrontal cortex..

Cerebellar thickness changes associated with heavy cannabis use: A 3-year longitudinal study.

Wang, Yanpei · 2021

Both lobule VI and Crus I had higher rates of thickness increase in cannabis users than controls.

The Impact of Cannabidiol on Human Brain Function: A Systematic Review.

Batalla, Albert · 2020

In healthy volunteers, CBD enhanced fronto-striatal resting state connectivity and had opposite effects to THC during emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital).

Is the Adolescent Brain at Greater Vulnerability to the Effects of Cannabis? A Narrative Review of the Evidence.

Blest-Hopley, Grace · 2020

Adolescent cannabis users show altered functional connectivity within established brain circuits, with largely increased functional activation compared to controls.

A Systematic Review of Human Neuroimaging Evidence of Memory-Related Functional Alterations Associated with Cannabis Use Complemented with Preclinical and Human Evidence of Memory Performance Alterations.

Blest-Hopley, Grace · 2020

Twelve fMRI studies showed cannabis users had altered brain activation during memory tasks compared to non-users.

Cannabinoids and psychotic symptoms: A potential role for a genetic variant in the P2X purinoceptor 7 (P2RX7) gene.

Boks, Marco P · 2020

A SNP in the P2RX7 gene (rs7958311) was associated with increased psychotic-like experiences in regular cannabis users (p = 1.10 x 10^-7) and was replicated in the IMAGEN cohort (p = 0.020).

Novel therapeutic and drug development strategies for tobacco use disorder: endocannabinoid modulation.

Butler, Kevin · 2020

CB1 receptor neutral antagonists and fatty acid amide hydrolase (FAAH) inhibitors demonstrated positive effects across multiple addiction-related factors including nicotine reinforcement, cue-induced reinstatement, and withdrawal.

Evidence of Slow Neural Processing, Developmental Differences and Sensitivity to Cannabis Effects in a Sample at Clinical High Risk for Psychosis From the NAPLS Consortium Assessed With the Human Startle Paradigm.

Cadenhead, Kristin S · 2020

CHR participants who converted to psychosis had significantly slower startle latency than non-converters, driven by female participants.

Cannabis Use in Adolescence: A Review of Neuroimaging Findings.

Chye, Yann · 2020

Adolescent cannabis users showed alterations mainly in frontal and parietal regions and associated brain activation related to inhibitory control, reward, and memory.

Do the effects of cannabis on the hippocampus and striatum increase risk for psychosis?

Daniju, Y · 2020

Using the MAM rodent model as a framework, the review found clear evidence that cannabis/cannabinoids affect hippocampal and medial temporal lobe function and structure.

Diversity of molecular targets and signaling pathways for CBD.

de Almeida, Douglas L · 2020

CBD's effects are mediated through multiple molecular mechanisms rather than a single target.

Different Effects of Cannabis Abuse on Adolescent and Adult Brain.

Dhein, Stefan · 2020

THC activation of CB1 receptors diminishes neuronal growth factor production and affects signaling cascades involved in synapse formation.

The endocannabinoidome as a substrate for noneuphoric phytocannabinoid action and gut microbiome dysfunction in neuropsychiatric disorders
.

Di Marzo, Vincenzo · 2020

The endocannabinoidome extends beyond classical CB1/CB2 to include numerous lipid mediators, receptors, and enzymes involved in neuropsychiatric disorders.

Neuronal nicotinic acetylcholine receptors mediate ∆9 -THC dependence: Mouse and human studies.

Donvito, Giulia · 2020

Alpha3beta4 nAChR antagonist/partial agonist reduced THC withdrawal signs.

Adolescent cannabinoid exposure interacts with other risk factors in schizophrenia: A review of the evidence from animal models.

Dunn, Ariel L · 2020

When adolescent cannabinoid exposure was combined with early-life adversity in animal models, patterns of synergistic and protective effects emerged.

Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors.

Finlay, David B · 2020

None of the five terpenes tested (myrcene, alpha-pinene, beta-pinene, beta-caryophyllene, and limonene) showed direct interactions with CB1 or CB2 receptors, either alone or in mixtures.

Anticonvulsive Properties of Cannabidiol in a Model of Generalized Seizure Are Transient Receptor Potential Vanilloid 1 Dependent.

Gray, Royston A · 2020

CBD at 50 and 100 mg/kg significantly raised seizure thresholds in wildtype mice but not in TRPV1 knockout mice.

The expression level of cannabinoid receptors type 1 and 2 in the different types of astrocytomas.

Hashemi, Mansoureh · 2020

CB1 receptor expression was increased in tumor tissue across grades.

Altered Corticolimbic Control of the Nucleus Accumbens by Long-term Δ9-Tetrahydrocannabinol Exposure.

Hwang, Eun-Kyung · 2020

Long-term THC weakened prefrontal cortex glutamate input to the nucleus accumbens shell and strengthened input from the basolateral amygdala and ventral hippocampus.

Cannabinoid CB2 receptors mediate the anxiolytic-like effects of monoacylglycerol lipase inhibition in a rat model of predator-induced fear.

Ivy, Devon · 2020

JZL184 (MGL inhibitor) dose-dependently suppressed predator-induced fear (ED50 = 4 mg/kg).

The cannabinoid CB2 receptor agonist LY2828360 synergizes with morphine to suppress neuropathic nociception and attenuates morphine reward and physical dependence.

Iyer, Vishakh · 2020

LY2828360 and morphine produced synergistic pain relief for chemotherapy-induced neuropathy.

Interactions Between Alcohol and the Endocannabinoid System.

Kunos, George · 2020

The review consolidates 20 years of evidence showing that alcohol increases endocannabinoid signaling, which mediates both its rewarding/addictive neural effects and its toxic effects in the liver (fatty liver disease).

Altered Effective Connectivity of Central Autonomic Network in Response to Negative Facial Expression in Adults With Cannabis Use Disorder.

Ma, Liangsuo · 2020

Compared to 23 controls, 23 people with cannabis use disorder showed stronger amygdala-to-hypothalamus connectivity and amygdala-to-fusiform gyri connectivity when viewing fearful/angry faces.

Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome.

Müller-Vahl, Kirsten R · 2020

In the first study measuring CSF endocannabinoids in Tourette syndrome, both AEA (anandamide, p=0.0018) and 2-AG (p=0.0003) were significantly elevated in 20 TS patients compared to 19 controls.

Cannabis hyperemesis syndrome: an update on the pathophysiology and management.

Perisetti, Abhilash · 2020

CHS is characterized by cyclic nausea and vomiting worsened by cannabis, with compulsive hot bathing/showers for relief.

A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models.

Perry, Christopher J · 2020

Using the model organism Dictyostelium, researchers identified that CBD activity depends partly on the glycine cleavage system, linked to folate one-carbon metabolism (FOCM).

Cannabinoid-sensitive receptors in cardiac physiology and ischaemia.

Puhl, Sarah-Lena · 2020

Both CB1 and CB2 receptors and their endogenous ligands (anandamide and 2-AG) are upregulated in the ischemic heart.

A time-dependent contribution of hippocampal CB1 , CB2 and PPARγ receptors to cannabidiol-induced disruption of fear memory consolidation.

Raymundi, Ana Maria · 2020

CBD (10-30 pmol) injected into the dorsal hippocampus impaired fear memory consolidation when given immediately or 1 hour after conditioning, but not at 3 hours.

Targeting Cannabinoid Receptor 2 on Peripheral Leukocytes to Attenuate Inflammatory Mechanisms Implicated in HIV-Associated Neurocognitive Disorder.

Rizzo, Michael D · 2020

HIV patients using medical marijuana had lower levels of circulating CD16+ (activated) monocytes compared to non-cannabis users.

Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder.

Salort, Glòria · 2020

In postmortem prefrontal cortex (BA9) of 23 MDD subjects versus 19 controls, CB1 receptor density was increased by 20% (p=0.02).

Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

Scherma, Maria · 2020

Adolescent rats pre-exposed to the synthetic cannabinoid WIN showed cross-sensitization to cocaine, correlating with histone hyperacetylation and decreased HDAC6 in the prefrontal cortex.

Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin.

Schrott, Rose · 2020

THC exposure via oral gavage altered DNA methylation at seven neurodevelopmentally active genes in rat sperm.

Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.

Schrott, Rose · 2020

Using RRBS, cannabis use was associated with significant hypomethylation of the autism-linked gene DLGAP2 in human sperm.

Paternal Δ9-Tetrahydrocannabinol Exposure Prior to Mating Elicits Deficits in Cholinergic Synaptic Function in the Offspring.

Slotkin, Theodore A · 2020

After 28 days of THC exposure (0, 2, or 4 mg/kg/day) in male rats, followed by mating with drug-naive females, offspring showed dose-dependent decreases in hemicholinium-3 binding (presynaptic acetylcholine activity) with regionally selective increases in choline acetyltransferase.

Cannabis Use Is Associated With Increased Levels of Soluble gp130 in Schizophrenia but Not in Bipolar Disorder.

Szabo, Attila · 2020

Screening 13 plasma inflammatory markers, cannabis users in the schizophrenia group had significantly elevated soluble gp130 (sgp130) compared to non-users (p=0.002, surviving multiple testing correction).

Cannabis use influence on peripheral brain-derived neurotrophic factor levels in antipsychotic-naïve first-episode psychosis.

Toll, A · 2020

Among 70 drug-naive first-episode psychosis patients and 57 healthy volunteers, cannabis use was associated with reduced BDNF levels only in the psychosis group.

Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis.

Watts, Jeremy J · 2020

FAAH did not differ significantly between 27 patients with psychotic disorders and 36 healthy controls.

Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus.

Yu, Tao · 2020

Psychotic-like experiences were associated with reduced expansion of the right uncus between ages 14 and 19 (p=0.002).

Impaired cognitive performance under psychosocial stress in cannabis-dependent men is associated with attenuated precuneus activity.

Zhao, Weihua · 2020

During stress but not during a no-stress condition, cannabis users showed impaired performance on mental arithmetic compared to controls.

Adolescent exposure to Δ9-tetrahydrocannabinol delays acquisition of paired-associates learning in adulthood.

Abela, Andrew R · 2019

THC-exposed rats took longer to learn a paired-associates learning task in adulthood, particularly with visually identical stimuli.

Neuropsychiatric Sequelae in Adolescents With Acute Synthetic Cannabinoid Toxicity.

Anderson, Sarah Ann R · 2019

Synthetic cannabinoid-only exposure (n=107) was associated with 3.4x higher odds of coma/CNS depression (OR 3.42, 95% CI 1.51-7.75) and 3.9x higher odds of seizures (OR 3.89, 95% CI 1.39-10.94) compared to cannabis-only exposure (n=86).

Endocannabinoid System and Alcohol Abuse Disorders.

Basavarajappa, Balapal S · 2019

Alcohol alters endocannabinoid levels and CB1 receptor expression in brain addiction circuits.

Distinct functions of endogenous cannabinoid system in alcohol abuse disorders.

Basavarajappa, Balapal S · 2019

The ECS plays a major role in the motivation to abuse alcohol, with chronic alcohol consumption modulating endocannabinoids and CB1 receptor expression in brain addiction circuits.

Threat Responsiveness as a Function of Cannabis and Alcohol Use Disorder Severity.

Blair, Robert James R · 2019

Increasing CUD symptomatology was associated with decreased responding to looming threat stimuli in regions including rostral frontal cortex, fusiform gyrus, and amygdala.

Regular cannabis use is associated with altered activation of central executive and default mode networks even after prolonged abstinence in adolescent users: Results from a complementary meta-analysis.

Blest-Hopley, Grace · 2019

Adolescent cannabis users abstinent for over 25 days showed significantly greater activation in central executive and default mode network components compared to non-using controls.

Cerebellar alterations in cannabis users: A systematic review.

Blithikioti, Chrysanthi · 2019

The three most consistent findings across 40 studies were: (1) increased cerebellar gray matter volume after chronic use, (2) altered cerebellar resting state activity after acute or chronic use, and (3) deficits in memory, decision-making, and associative learning (cerebellar-dependent tasks).

Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype.

Bossong, Matthijs G · 2019

THC increased perfusion in bilateral insula, medial superior frontal cortex, and left orbital frontal gyrus.

Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives.

Burggren, Alison C · 2019

Decades of research link recreational cannabis use to cognitive impairment across multiple domains, structural and functional brain differences associated with early and heavy use, and heightened risks during adolescence when brain development is ongoing.

Modulatory effects of cannabinoids on brain neurotransmission.

Cohen, Koby · 2019

CB1 and CB2 receptors interact with six major neurotransmitter systems: dopamine, serotonin, noradrenaline, GABA, glutamate, and opioids.

Descriptive Psychopathology of the Acute Effects of Intravenous Delta-9-Tetrahydrocannabinol Administration in Humans.

Colizzi, Marco · 2019

In the 20 minutes after THC, 94% experienced at least mild symptoms (19% moderate-severe).

Deficient Functioning of Frontostriatal Circuits During the Resolution of Cognitive Conflict in Cannabis-Using Youth.

Cyr, Marilyn · 2019

Cannabis-using youth (n=28) showed decreased conflict-related activation in ventromedial prefrontal cortex, striatum, pallidum, and thalamus compared to healthy controls (n=32) during a Simon task.

Cannabidiol as a potential treatment for psychosis.

Davies, Cathy · 2019

CBD shows potential as a novel antipsychotic with a unique non-dopamine-D2 mechanism of action.

Cannabinoid exposure during pregnancy and its impact on immune function.

Dong, Catherine · 2019

Cannabinoids mediate robust immunomodulation by altering cytokine levels, causing apoptosis of lymphoid cells, and inducing suppressor cells.

Potential of Cannabinoid Receptor Ligands as Treatment for Substance Use Disorders.

Galaj, Ewa · 2019

Neutral CB1R antagonists (AM4113), CB2R agonists (JWH133, Xie2-64), and phytocannabinoids (CBD, beta-caryophyllene, THCV) show therapeutic potential for SUDs in animals.

Age-related differences in the impact of cannabis use on the brain and cognition: a systematic review.

Gorey, Claire · 2019

General executive functioning appears more impaired in adolescent frequent cannabis users compared to adult users.

Cannabis: An ancient friend or foe? What works and doesn't work.

Henschke, Philip · 2019

The endocannabinoid system is critical for brain development across fetal, infant, and adolescent stages.

A systematic review of phytocannabinoid exposure on the endocannabinoid system: Implications for psychosis.

Jacobson, Maya R · 2019

The most established finding is CB1 receptor downregulation after chronic and recent cannabis exposure.

Cannabis and the developing brain: What does the evidence say?

Jacobus, Joanna · 2019

Across two prospective studies (3 and 6 years), recency, frequency, and age of onset of cannabis use were the key variables predicting poorer neural health outcomes.

Cannabinoid Attenuation of Intestinal Inflammation in Chronic SIV-Infected Rhesus Macaques Involves T Cell Modulation and Differential Expression of Micro-RNAs and Pro-inflammatory Genes.

Kumar, Vinay · 2019

THC-treated SIV-infected macaques showed downregulated pro-inflammatory microRNAs and genes, higher expression of tight junction proteins (occludin, claudin-3), reduced T cell activation, increased anti-inflammatory macrophages, and complete prevention of lymph node fibrosis seen in all vehicle-treated animals..

Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity.

Mason, Natasha L · 2019

THC increased striatal glutamate concentrations and reduced functional connectivity (FC) between the nucleus accumbens and cortical areas, indicating increased dopamine activity.

Synergistic effects of marijuana abuse and HIV infection on neural activation during a cognitive interference task.

Meade, Christina S · 2019

The MJ+/HIV+ group showed the greatest activation increase in the left fronto-insular cortex during cognitive interference, beyond what either marijuana or HIV produced alone.

Marijuana use among adolescents is associated with deleterious alterations in mature BDNF.

Miguez, Maria Jose · 2019

Pre-existing BDNF levels did not differ between groups, but marijuana use predicted subsequent BDNF alterations (p=0.001).

Adolescent exposure to Δ9-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons.

Miller, Michael L · 2019

THC exposure disrupted normal PFC development by inducing premature spine pruning and dendritic atrophy.

Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications.

Nagappan, Arulkumar · 2019

CB1 receptor activation in the liver promotes insulin resistance via increased energy intake/storage, impaired glucose and lipid metabolism, enhanced oxidative stress, and inflammatory responses.

Urinary tetrahydrocannabinol is associated with poorer working memory performance and alterations in associated brain activity.

Owens, Max M · 2019

A positive urine THC screen was associated with worse working memory and differential brain response during an N-back task.

Prenatal cannabinoid exposure and altered neurotransmission.

Pinky, Priyanka D · 2019

Prenatal cannabinoid exposure alters multiple neurotransmitter systems including dopamine, serotonin, GABA, glutamate, and opioid systems.

The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD).

Pretzsch, Charlotte M · 2019

CBD significantly increased fractional amplitude of low-frequency fluctuations (fALFF) in the cerebellar vermis and right fusiform gyrus across all participants, but post-hoc analysis showed this was driven by the ASD group with no significant change in controls.

Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder.

Pretzsch, Charlotte Marie · 2019

Across groups, CBD increased subcortical glutamate (Glx) but decreased cortical Glx.

Marijuana use and major depressive disorder are additively associated with reduced verbal learning and altered cortical thickness.

Radoman, Milena · 2019

MDD and marijuana use had additive effects on memory recall and cortical thickness in the middle temporal gyrus.

Endocannabinoid signaling in psychiatric disorders: a review of positron emission tomography studies.

Sloan, Matthew E · 2019

Cannabis users consistently had decreased CB1 receptor binding compared to controls, normalizing after short abstinence periods.

Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity.

Wall, Matthew B · 2019

Both cannabis strains reduced functional connectivity in the default mode network (DMN) and salience network compared to placebo.

Associations between adolescent cannabis use and brain structure in psychosis.

Abush, Hila · 2018

Researchers examined brain structure in 109 people with psychotic disorders, comparing those with and without a history of adolescent cannabis use.

Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC.

Bhattacharyya, Sagnik · 2018

Researchers gave 36 healthy men either 10 mg oral THC or placebo in a randomized crossover design and measured both psychotic symptoms and brain activity during a verbal learning task using fMRI.

Potential of Endocannabinoids to Control Bladder Pain.

Bjorling, Dale E · 2018

Bladder-related pain is one of the most common forms of visceral pain, and opioids remain a primary treatment despite their well-known side effects.

Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment Induced by Delta9-Tetrahydrocannabinol.

Busquets-Garcia, Arnau · 2018

Using a novel object recognition test in mice, researchers dissected the molecular mechanisms behind THC's effects on memory and made a key discovery: short-term and long-term memory impairment from THC operate through entirely different molecular pathways. THC impaired short-term memory specifically through activation of protein kinase C (PKC) in the hippocampus.

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases.

Chiurchiù, Valerio · 2018

This extensive review examined both clinical and preclinical evidence for cannabinoid-based interventions in MS.

Previous cannabis exposure modulates the acute effects of delta-9-tetrahydrocannabinol on attentional salience and fear processing.

Colizzi, Marco · 2018

Twenty-four healthy men participated in a double-blind THC challenge study, divided into 12 never-users (fewer than 5 lifetime joints) and 12 abstinent modest users (about 25 lifetime joints).

Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects, cognition and brain function by previous cannabis exposure.

Colizzi, Marco · 2018

Using the same 24-participant THC challenge design, this companion study focused on cognitive processing and psychotomimetic effects.

Adult Cellular Neuroadaptations Induced by Adolescent THC Exposure in Female Rats Are Rescued by Enhancing Anandamide Signaling.

Cuccurazzu, Bruna · 2018

Female rats exposed to THC during adolescence developed depressive-like behaviors and measurable brain changes in adulthood.

Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and Emotion.

Freeman, Tom P · 2018

Researchers gave 16 cannabis users three different treatments across separate sessions: cannabis with CBD, cannabis without CBD, and placebo, then measured brain responses to music using fMRI. Cannabis without CBD dampened the brain's response to music in several key regions: bilateral auditory cortex, right hippocampus, right amygdala, and right ventral striatum (a core reward region).

Cortical thickness, cortical surface area and subcortical volumes in schizophrenia and bipolar disorder patients with cannabis use.

Hartberg, Cecilie Bhandari · 2018

Researchers compared brain scans of patients with schizophrenia or bipolar disorder who had used cannabis (132 patients) against those who had not (182 patients) and 277 healthy controls. After controlling for confounders including tobacco and alcohol use, cannabis-using patients showed reduced cortical thickness in the caudal middle frontal gyrus compared to non-user patients and healthy controls. However, when patients with co-occurring alcohol and other illicit drug use were excluded, these findings were no longer significant.

Adolescent Brain Surface Area Pre- and Post-Cannabis and Alcohol Initiation.

Infante, M Alejandra · 2018

Researchers obtained brain scans from 69 adolescents at baseline (ages 12-14, before any substance use) and again at follow-up (ages 17-21). Participants were split into three groups: alcohol-only initiators, alcohol-plus-cannabis initiators, and minimal-use controls. All groups showed surface area decreases over time (consistent with normal brain maturation), but the pattern differed by substance use. A significant group-by-time interaction appeared in three regions: bilateral medial orbitofrontal cortices and right insula.

Chronic Δ9-THC in Rhesus Monkeys: Effects on Cognitive Performance and Dopamine D2/D3 Receptor Availability.

John, William S · 2018

Six adult male rhesus monkeys were tested on cognitive tasks using touchscreen tests (CANTAB) before and during 12 weeks of daily THC (1.0-2.0 mg/kg). Acute THC impaired cognitive performance in a task-specific manner and reduced food-motivated responding and body temperature. During chronic treatment, THC produced persistent residual impairment only to working memory, measured 22 hours after each dose.

The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.

Kaag, A M · 2018

Researchers measured gray matter volume in 169 men across six groups ranging from non-users to heavy polysubstance users (alcohol, tobacco, cocaine, and cannabis). The number of substances used was negatively associated with volume in the dorsal and ventral medial prefrontal cortex (mPFC).

Fronto-striatal effective connectivity of working memory in adults with cannabis use disorder.

Ma, Liangsuo · 2018

Researchers compared brain connectivity between 23 adults with cannabis use disorder and 23 demographically matched controls during a working memory (N-back) task. Compared to controls, CUD participants showed reduced modulatory connectivity from the right dorsolateral prefrontal cortex (R-DLPFC) to the left caudate during working memory. However, CUD participants showed increased connectivity in three other prefrontal-striatal pathways: left DLPFC to left caudate, right DLPFC to right caudate, and right ventrolateral PFC to left caudate. The authors interpreted this as a compensatory pattern: the CUD brain may recruit additional prefrontal-striatal connections to maintain working memory performance when the primary pathway is impaired..

Comparing the effect of clozapine and risperidone on cue reactivity in male patients with schizophrenia and a cannabis use disorder: A randomized fMRI study.

Machielsen, Marise W J · 2018

Thirty-eight patients with schizophrenia (30 with cannabis use disorder, 8 without) and 20 healthy controls were included.

Subcortical Local Functional Hyperconnectivity in Cannabis Dependence.

Manza, Peter · 2018

Researchers examined resting-state brain connectivity in subcortical regions using data from 441 young adults in the Human Connectome Project. Thirty cannabis-dependent subjects were compared to 30 controls matched on age, sex, education, BMI, anxiety, depression, and alcohol/tobacco use. Cannabis-dependent individuals showed markedly increased local functional connectivity in several subcortical regions: ventral striatum (where the nucleus accumbens is located), midbrain (where dopamine-producing neurons reside), brainstem, and lateral thalamus. These hyperconnectivity effects occurred without significant differences in subcortical brain volumes. The effects were most pronounced in individuals who began cannabis use earliest in life and who reported high levels of negative emotionality. The researchers interpreted these findings as reflecting changes in dopaminergic circuits implicated in both psychosis and habit formation/reward processing..

Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.

Miller, Sally · 2018

Researchers tested topical THC and CBD on intraocular pressure (IOP) in mice. A single topical application of THC lowered IOP by approximately 28% for 8 hours in male mice.

Cannabinoid exposure and altered DNA methylation in rat and human sperm.

Murphy, Susan K · 2018

Researchers compared DNA methylation in sperm from human cannabis users versus non-users, and from THC-exposed versus unexposed rats. In human sperm, cannabis users differed from non-users by at least 10% methylation at 3,979 CpG sites. Pathway analysis identified Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02).

Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex.

Prini, Pamela · 2018

Adolescent THC exposure increased levels of the histone modification H3K9me3 and the enzyme Suv39H1 in the prefrontal cortex, altering expression of genes tied to synaptic plasticity.

Impact of substance use disorder on gray matter volume in schizophrenia.

Quinn, Margaret · 2018

Using voxel-based morphometry, researchers found that schizophrenia patients had reduced gray matter in several brain regions regardless of substance use history.

Effects of Adolescent THC Exposure on the Prefrontal GABAergic System: Implications for Schizophrenia-Related Psychopathology.

Renard, Justine · 2018

The review synthesizes evidence that adolescent THC exposure targets schizophrenia-related molecular pathways in the prefrontal cortex and mesolimbic dopamine system.

Cannabis Therapeutics and the Future of Neurology.

Russo, Ethan B · 2018

The review presents evidence supporting cannabis-based interventions for intractable epilepsy, brain tumors, Parkinson disease, Alzheimer disease, and traumatic brain injury/CTE.

Deficient endocannabinoid signaling in the central amygdala contributes to alcohol dependence-related anxiety-like behavior and excessive alcohol intake.

Serrano, Antonia · 2018

Alcohol dependence decreased baseline 2-AG levels and increased glutamate and GABA in the central amygdala.

Cannabinoid-glutamate interactions and neural oscillations: implications for psychosis.

Sherif, Mohamed A · 2018

CB1Rs and NMDARs have direct and indirect interactions in brain regions implicated in schizophrenia (hippocampus, frontal cortex, cerebellum).

Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans.

Skosnik, Patrick D · 2018

Both THC and THC+CBD disrupted P50 sensory gating in humans and reduced evoked theta and gamma oscillations.

High times for cannabis: Epigenetic imprint and its legacy on brain and behavior.

Szutorisz, Henrietta · 2018

Cannabinoid exposure during critical developmental periods creates epigenetic changes (modifications to how genes are read) that persist long after exposure ends.

Adolescent cannabis use and brain systems supporting adult working memory encoding, maintenance, and retrieval.

Tervo-Clemmens, Brenden · 2018

Earlier cannabis age of onset was associated with longer reaction times and reduced posterior parietal cortex activation during encoding, which mediated the age-of-onset effect.

Altered orbitofrontal activity and dorsal striatal connectivity during emotion processing in dependent marijuana users after 28 days of abstinence.

Zimmermann, Kaeli · 2018

After 28+ days of abstinence, dependent marijuana users showed increased medial orbitofrontal cortex (mOFC) activity during negative emotional stimuli, stronger mOFC-dorsal striatal and mOFC-amygdala coupling, and increased mOFC-dorsal striatal resting connectivity compared to controls.

Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.

Bhattacharyya, Sagnik · 2017

In 14 healthy males studied with both fMRI and PET imaging, a 10mg oral dose of THC induced anxiety and changed how the right amygdala responded while processing fearful faces.

Attenuated frontal and sensory inputs to the basal ganglia in cannabis users.

Blanco-Hinojo, Laura · 2017

Resting-state brain imaging in 28 chronic cannabis users and 29 controls revealed two key connectivity changes.

Cannabis; Epidemiological, Neurobiological and Psychopathological Issues: An Update.

De Luca, Maria Antonietta · 2017

The review synthesized evidence across three domains.

Toll-like receptor signalling as a cannabinoid target in Multiple Sclerosis.

Fitzpatrick, John-Mark K · 2017

Toll-like receptors (TLRs) are immune sensors that trigger inflammatory responses and play a pivotal role in the development of MS (as shown in animal models).

Apparent CB1 Receptor Rimonabant Affinity Estimates: Combination with THC and Synthetic Cannabinoids in the Mouse In Vivo Triad Model.

Grim, T W · 2017

Using pA2 and pKB analyses (quantitative pharmacological methods), researchers determined that the CB1 receptor antagonist rimonabant produced consistent rightward shifts in the dose-response curves of five synthetic cannabinoids (A-834,735D, WIN55,212-2, CP55,950, JWH-073, CP47,497) and THC. The similarity of the rimonabant affinity estimates across all compounds indicates that CB1 receptors, and not other pharmacological targets, largely mediate the central effects of these synthetic cannabinoids (catalepsy, pain relief, and temperature reduction). This is important because some researchers have speculated that the increased dangers of synthetic cannabinoids might be due to non-CB1 targets, but this quantitative analysis suggests their core pharmacological effects operate through the same receptor as THC..

Tripping with Synthetic Cannabinoids ("Spice"): Anecdotal and Experimental Observations in Animals and Man.

Järbe, Torbjörn U C · 2017

This review consolidated the scientific literature on "Spice" compounds, synthetic cannabinoids originally designed as research tools that became widely abused recreational drugs. In behavioral assays comparing synthetic cannabinoids to THC, the synthetic compounds generally produced similar effects but often at greater potency or with additional toxicity.

Longitudinal study of hippocampal volumes in heavy cannabis users.

Koenders, L · 2017

This longitudinal study tracked hippocampal volumes in 20 heavy cannabis users and 23 matched controls over approximately 39 months using manual brain tracing, considered the gold standard for hippocampal measurement. At baseline, there were no differences in hippocampal volume between heavy users and non-users.

Focus on cannabinoids and synthetic cannabinoids.

Le Boisselier, R · 2017

This review provided a state-of-the-art overview of both natural and synthetic cannabinoids, explaining why synthetic versions produce more extreme effects. The key pharmacological difference: THC is a partial agonist at CB1 receptors (it activates them partially), while most synthetic cannabinoids are full agonists (they activate receptors to their maximum).

Nucleus accumbens functional connectivity at age 20 is associated with trajectory of adolescent cannabis use and predicts psychosocial functioning in young adulthood.

Lichenstein, Sarah D · 2017

Following 158 young men from a longitudinal study that began in infancy, researchers identified three distinct trajectories of cannabis use from ages 14 to 19: stable high use, escalating use, and stable low use. The trajectory of cannabis use significantly affected functional connectivity between the nucleus accumbens (the brain's reward center) and the medial prefrontal cortex.

Cannabinoid signaling in health and disease.

Lu, Yan · 2017

This review provided a broad overview of the endocannabinoid system and its therapeutic potential, with particular attention to an emerging area: cardioprotection. The endocannabinoid system is involved in a wide range of physiological processes, and several cannabinoids can be prescribed in Canada for conditions including nausea and pain.

Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others?

Maccarrone, Mauro · 2017

This expert review assessed the state of cannabinoid therapeutics roughly five years after THC/CBD oromucosal spray (Sativex) entered clinical practice for multiple sclerosis spasticity. For MS spasticity, clinical trials confirmed the spray's efficacy and tolerability, establishing it as the most widely used prescription cannabinoid medicine internationally.

Functional selectivity at G-protein coupled receptors: Advancing cannabinoid receptors as drug targets.

Mallipeddi, Srikrishnan · 2017

This review examined the concept of functional selectivity (biased agonism) at cannabinoid receptors, a phenomenon where different drugs binding to the same receptor can trigger different cellular responses. Traditionally, receptors were viewed as simple on/off switches.

Adverse Structural and Functional Effects of Marijuana on the Brain: Evidence Reviewed.

Mandelbaum, David E · 2017

This critical review focused specifically on evidence for structural and functional brain damage from cannabis, combined with neuropathological findings from a fatal case of cannabis-induced psychosis. The literature review found strong evidence that chronic cannabis abuse causes cognitive impairment and brain damage, particularly to white matter (the brain's communication cables), where CB1 cannabinoid receptors are abundant. The fatal case provided direct neuropathological evidence of white matter damage in a person who died from cannabis-induced psychosis, complementing the imaging-based evidence from living subjects. Regarding therapeutic claims, the review concluded that contrary to popular perception, there are few objective data supporting preferential use of cannabis over conventional therapy for neurological conditions such as multiple sclerosis, epilepsy, or schizophrenia.

Cannabis and alcohol use, and the developing brain.

Meruelo, A D · 2017

This review examined how cannabis and alcohol affect the adolescent brain during a period when white and grey matter are still maturing and sex hormones are driving structural changes. Neuroimaging studies revealed differences in brain development between substance-using and non-using adolescents, including altered white matter myelination and grey matter volumes.

Opposing Effects of Cannabis Use on Late Auditory Repetition Suppression in Schizophrenia Patients and Healthy Control Subjects.

Rentzsch, Johannes · 2017

Researchers measured how the brain filters repeated auditory signals in four groups: schizophrenia patients with and without cannabis use, and healthy controls with and without cannabis use.

Cannabis Withdrawal: A Review of Neurobiological Mechanisms and Sex Differences.

Schlienz, Nicolas J · 2017

The review synthesized preclinical and clinical research on cannabis withdrawal, identifying several key findings. Long-term cannabis use downregulates CB1 receptors throughout the brain.

Pros and Cons of Medical Cannabis use by People with Chronic Brain Disorders.

Suryadevara, Uma · 2017

The review examined evidence on cannabis use across six brain disorders, finding a mixed picture that varied dramatically by condition. Neurological disorders with some benefit: Cannabis reduced pain and spasticity in multiple sclerosis, decreased tremor, rigidity, and pain in Parkinson's disease, and improved quality of life in ALS by helping appetite, pain, and spasticity.

Metabolism of endocannabinoids.

Biernacki, Michał · 2016

This review provided a detailed account of how the body produces and breaks down its two main endocannabinoids: anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Both are synthesized from phospholipids in cell membranes.

Delta-9-tetrahydrocannabinol and cannabidiol: Separating the chemicals from the "weed," a pharmacodynamic discussion.

Boggs, Douglas Lee · 2016

This review examined the pharmacodynamic interplay between THC and CBD, the two most studied of the 70+ phytocannabinoids in cannabis. THC directly activates CB1 and CB2 cannabinoid receptors, producing its well-known psychoactive effects.

Effects of Marijuana Use on Brain Structure and Function: Neuroimaging Findings from a Neurodevelopmental Perspective.

Brumback, T · 2016

This review examined neuroimaging evidence on how marijuana affects brain structure and function, with a focus on developmental timing. A wide range of research has documented neurocognitive deficits associated with marijuana use, particularly when use begins during childhood or adolescence.

Beyond the Direct Activation of Cannabinoid Receptors: New Strategies to Modulate the Endocannabinoid System in CNS-Related Diseases.

Chicca, Andrea · 2016

This review examined strategies for modulating the endocannabinoid system that go beyond directly activating CB1 and CB2 receptors, which has produced limited therapeutic success due to CB1-mediated side effects. Alternative approaches include inhibitors of the enzymes that break down endocannabinoids (FAAH for anandamide, MAGL for 2-AG, ABHD6, and ABHD12), as well as COX-2 inhibitors, diacylglycerol lipase inhibitors, and blockers of the endocannabinoid membrane transporter. The review also discussed polypharmacological approaches that combine mild inhibition of multiple targets simultaneously.

The endocannabinoid system: A novel player in human placentation.

Costa, M A · 2016

This review examined how the endocannabinoid system participates in normal human placenta development and how cannabis use may disrupt this process. The endocannabinoid system is expressed in human placentas and plays roles in trophoblast cell proliferation, apoptosis (programmed cell death), differentiation, and function.

Roles for the endocannabinoid system in ethanol-motivated behavior.

Henderson-Redmond, Angela N · 2016

This review synthesized evidence showing that the endocannabinoid system plays a central role in alcohol-motivated behavior.

Endocannabinoid regulation of β-cell functions: implications for glycaemic control and diabetes.

Jourdan, T · 2016

Pancreatic beta-cells, which produce insulin, contain all components of the endocannabinoid system.

Endocannabinoid System: A Multi-Facet Therapeutic Target.

Kaur, Rimplejeet · 2016

This review provides a panoramic view of the endocannabinoid system as a therapeutic target, covering its role across a remarkable range of conditions: nausea, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disease, cancer, obesity, metabolic syndrome, Parkinson's, Huntington's, Alzheimer's, and Tourette's syndrome. Approved drugs at the time included nabilone and dronabinol (for chemotherapy-induced nausea) and Sativex (for MS spasticity).

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction.

Kutlu, Munir Gunes · 2016

This review examined how drugs of abuse, including cannabis, interact with the hippocampus, a brain region critical for learning and memory, to contribute to addiction. The relationship between cannabis and hippocampal function follows a two-phase pattern.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

Lisdahl, Krista M · 2016

Researchers compared brain structure in young adults with and without childhood ADHD who did or did not use cannabis regularly.

Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

Lorenzetti, Valentina · 2016

Adolescence is a critical period for brain development, particularly in regions with high cannabinoid receptor density.

Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes.

Lu, Dai · 2016

The endocannabinoid system's overactivation in visceral obesity drives metabolic dysfunction through CB1 receptors.

Go/No Go task performance predicts cortical thickness in the caudal inferior frontal gyrus in young adults with and without ADHD.

Newman, Erik · 2016

Researchers examined the inferior frontal gyrus, a brain region central to stopping yourself from acting impulsively.

Endocannabinoid Signaling Regulates Sleep Stability.

Pava, Matthew J · 2016

Using multiple pharmacological tools, researchers mapped how the endocannabinoid system regulates sleep in mice.

Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes.

Ramaekers, J G · 2016

Researchers gave 122 regular drug users acute doses of cannabis, cocaine, and placebo and measured cognitive impulsivity and brain connectivity.

ADHD and cannabis use in young adults examined using fMRI of a Go/NoGo task.

Rasmussen, Jerod · 2016

Researchers compared brain function during an impulse control task (Go/NoGo) across four groups: ADHD with and without cannabis use, and controls with and without cannabis use. Participants with ADHD made significantly more errors on the task and showed less activation in frontal and parietal brain regions and frontal-striatal circuits, regardless of whether they used cannabis.

Attentional dysfunction in abstinent long-term cannabis users with and without schizophrenia.

Rentzsch, Johannes · 2016

Researchers measured attention-related brainwave responses (P300) in four groups: schizophrenia patients with and without chronic cannabis use, and healthy controls with and without chronic cannabis use.

Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.

Russo, Ethan B · 2016

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Adolescent Δ(9)-Tetrahydrocannabinol Exposure Alters WIN55,212-2 Self-Administration in Adult Rats.

Scherma, Maria · 2016

Adolescent rats received increasing doses of THC for 11 consecutive days during the equivalent of human adolescence.

Blockade of Nicotine and Cannabinoid Reinforcement and Relapse by a Cannabinoid CB1-Receptor Neutral Antagonist AM4113 and Inverse Agonist Rimonabant in Squirrel Monkeys.

Schindler, Charles W · 2016

Researchers compared two types of CB1 receptor blockers in squirrel monkeys: rimonabant (an inverse agonist that was withdrawn from the market due to psychiatric side effects) and AM4113 (a newer neutral antagonist). Both compounds reduced nicotine and THC self-administration and prevented relapse triggered by drug cues or priming doses.

Prenatal marijuana exposure impacts executive functioning into young adulthood: An fMRI study.

Smith, Andra M · 2016

Thirty-one young adults (ages 18-22) from the Ottawa Prenatal Prospective Study, a long-running longitudinal study, underwent fMRI during four executive function tasks: visuospatial working memory, response inhibition, verbal working memory, and interference control. Sixteen had been prenatally exposed to marijuana while 15 had not.

Cannabinoid modulation of memory consolidation within the cerebellum.

Steinmetz, Adam B · 2016

Researchers injected cannabinoid compounds directly into the cerebellar cortex of rats at different time points relative to eyeblink conditioning, a form of motor learning that depends on the cerebellum. When given before training sessions, the cannabinoid agonist WIN55,212-2 and drugs that increase or decrease endocannabinoid levels all impaired learning.

Endocannabinoid regulation of nausea is mediated by 2-arachidonoylglycerol (2-AG) in the rat visceral insular cortex.

Sticht, Martin A · 2016

Researchers identified the precise brain mechanism by which the endocannabinoid system suppresses nausea.

Epigenetic Effects of Cannabis Exposure.

Szutorisz, Henrietta · 2016

This review examined the emerging field of cannabis epigenetics, where researchers study how cannabis exposure changes gene expression without altering the DNA sequence itself. Accumulating evidence from both human and animal studies showed that cannabinoids can modify epigenetic marks, including DNA methylation and histone modifications, in brain tissue and peripheral cells.

Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later.

Vingerhoets, W A M · 2016

Researchers scanned the brains of 31 treatment-naive frequent cannabis users while they viewed cannabis-related images and neutral images.

Enhancement of Anandamide-Mediated Endocannabinoid Signaling Corrects Autism-Related Social Impairment.

Wei, Don · 2016

Researchers tested whether enhancing the endocannabinoid system could correct the core social impairment seen in autism spectrum disorder (ASD).

Abnormal medial prefrontal cortex activity in heavy cannabis users during conscious emotional evaluation.

Wesley, Michael J · 2016

Researchers used fMRI to compare brain activity between 16 heavy cannabis users and 17 non-using controls as they evaluated emotional images from a standardized set (IAPS). Both groups identified the same images as emotional and showed similar activation in visual, midbrain, and middle cingulate regions.

The Selective Monoacylglycerol Lipase Inhibitor MJN110 Produces Opioid-Sparing Effects in a Mouse Neuropathic Pain Model.

Wilkerson, Jenny L · 2016

Researchers combined morphine with MJN110, a selective MAGL inhibitor that boosts 2-AG levels, in a mouse model of neuropathic pain (chronic constriction injury). When used alone, both drugs reduced pain in a dose-dependent manner.

Effect of Pharmacological Modulation of the Endocannabinoid System on Opiate Withdrawal: A Review of the Preclinical Animal Literature.

Wills, Kiri L · 2016

This review synthesized animal research on how manipulating the endocannabinoid system affects opiate withdrawal.

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

Arjmand, Shokouh · 2015

This review examined the potential of cannabinoid-based compounds to treat tremor associated with Parkinson's disease, multiple sclerosis, Huntington's disease, and forms of ataxia.

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been ….

Baron, Eric P · 2015

This extensive review traced the history of medicinal cannabis from ancient use through its prominence in 19th-century medicine, when it was widely prescribed for headache, to its prohibition driven by political rather than scientific factors.

The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer's disease.

Bedse, Gaurav · 2015

This review examined the role of endocannabinoid signaling in Alzheimer's disease (AD) pathology.

Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis.

Bhattacharyya, Sagnik · 2015

Researchers gave 36 healthy men with minimal cannabis exposure either 10mg of oral THC or placebo in a double-blind crossover design, then scanned their brains during a task requiring them to withhold automatic responses (Go/No-Go task). THC increased inhibition errors and reduced inhibition efficiency compared to placebo.

Cannabinoid modulation of functional connectivity within regions processing attentional salience.

Bhattacharyya, Sagnik · 2015

Researchers administered THC, CBD, or placebo to healthy occasional cannabis users and scanned their brains during a task involving processing novel and salient stimuli.

Dissecting the cannabinergic control of behavior: The where matters.

Busquets-Garcia, Arnau · 2015

This review examined how the location of CB1 receptors across different brain cell types and subcellular compartments determines the specific behavioral effects of cannabinoids.

Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function.

Cabral, Guy A · 2015

This review examined how cannabinoid signaling interacts with the brain's immune system.

[18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users.

Ceccarini, Jenny · 2015

Researchers used a specialized PET imaging technique with the radioligand [18F]MK-9470 to measure CB1 receptor availability in 10 chronic cannabis users within the first week after their last use.

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses.

Chiurchiù, Valerio · 2015

This review examined how cannabinoid signaling regulates the brain's immune responses, challenging the outdated view that the brain is immunologically isolated.

Role of the endogenous cannabinoid system in nicotine addiction: novel insights.

Gamaleddin, Islam Hany · 2015

This review compiled evidence for the endocannabinoid system's involvement in nicotine addiction.

The influence of cannabinoids on learning and memory processes of the dorsal striatum.

Goodman, Jarid · 2015

This review examined how cannabinoids affect the dorsal striatum, a brain region that controls habit formation and stimulus-response (S-R) learning.

Brain activation to negative stimuli mediates a relationship between adolescent marijuana use and later emotional functioning.

Heitzeg, Mary M · 2015

Researchers tracked 40 participants from the Michigan Longitudinal Study, comparing 20 heavy marijuana users with 20 minimal-use controls.

The therapeutic potential of cannabinoids for movement disorders.

Kluger, Benzi · 2015

This comprehensive review examined basic science, animal, and clinical evidence for cannabinoids across multiple movement disorders.

The role of cannabinoids in regulation of nausea and vomiting, and visceral pain.

Malik, Zubair · 2015

This review mapped cannabinoid receptors (CB1, CB2, and potentially GPR55) throughout the gastrointestinal tract and examined their roles in food intake, nausea, gastric secretion, motility, visceral sensation, inflammation, and cell proliferation. The strongest evidence supported cannabinoid involvement in regulating nausea and vomiting, where the endocannabinoid system has provided new mechanistic insights.

Marijuana use in pregnancy and lactation: a review of the evidence.

Metz, Torri D · 2015

This review examined the evidence on marijuana use during pregnancy and lactation, noting that 3-30% of pregnant women use marijuana depending on the population studied. THC freely crosses the placenta and is found in breast milk.

Alcohol Versus Cannabinoids: A Review of Their Opposite Neuro-Immunomodulatory Effects and Future Therapeutic Potentials.

Nair, Madhavan P · 2015

This review compared the immunomodulatory effects of alcohol and cannabinoids, finding that they produce largely opposite effects on the immune system. Alcohol promotes inflammation by increasing pro-inflammatory cytokines and disrupting immune cell function, contributing to organ damage in chronic drinkers.

Cannabinoid abuse and addiction: Clinical and preclinical findings.

Panlilio, L V · 2015

This review synthesized research on the mechanisms of cannabinoid abuse, withdrawal, and relapse from both human and animal studies. The review described how cannabinoids produce rewarding effects through CB1 receptor activation in the brain's reward circuitry, how tolerance develops through receptor downregulation, and how withdrawal symptoms emerge when chronic stimulation stops.

Minireview: From the bench, toward the clinic: therapeutic opportunities for cannabinoid receptor modulation.

Picone, Robert P · 2015

This minireview examined therapeutic opportunities from modulating CB1 and CB2 receptors across several disease areas. For CB1: the receptor protects against excitotoxic brain damage, and CB1 modulation could limit addiction liability.

Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

Pryce, Gareth · 2015

This review examined the role of the endocannabinoid system in multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), two neurodegenerative conditions sharing the symptom of spasticity. Anecdotal reports of cannabis relieving MS symptoms were confirmed by animal models and clinical trials, leading to the approval of medicinal cannabis (nabiximols) for MS spasticity.

A review of co-morbid tobacco and cannabis use disorders: possible mechanisms to explain high rates of co-use.

Rabin, Rachel Allison · 2015

This review examined why tobacco and cannabis are so frequently used together and why co-use complicates treatment of both substances. The evidence showed bidirectional effects: tobacco use increases the likelihood of becoming cannabis dependent, and cannabis use promotes transition to heavier tobacco use.

Peripherally Restricted Cannabinoids for the Treatment of Pain.

Romero-Sandoval, E Alfonso · 2015

This review examined strategies to use cannabinoids for pain treatment while avoiding central nervous system effects.

Multiple sclerosis, cannabis, and cognition: A structural MRI study.

Romero, Kristoffer · 2015

Researchers compared 20 MS patients who smoked cannabis for symptom relief with 19 matched MS patients who did not.

Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat.

Spechler, Philip A · 2015

Researchers used fMRI to compare 70 fourteen-year-olds with cannabis use history to 70 carefully matched never-using controls while they watched short videos of angry and neutral faces. Cannabis users showed significantly greater bilateral amygdala reactivity to angry faces compared to neutral faces.

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

Basu, P P · 2014

This review documented the endocannabinoid system's extensive involvement in liver disease.

Response inhibition and elevated parietal-cerebellar correlations in chronic adolescent cannabis users.

Behan, B · 2014

Adolescent heavy cannabis users and matched non-using controls completed a Go/No-Go task (requiring them to inhibit a habitual response) during brain imaging.

Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies.

Bossong, Matthijs G · 2014

This review synthesized neuroimaging studies examining both acute THC effects and long-term effects of cannabis use on learning and memory in adults and adolescents.

Resting state functional magnetic resonance imaging reveals distinct brain activity in heavy cannabis users - a multi-voxel pattern analysis.

Cheng, H · 2014

Researchers used an advanced multi-voxel pattern analysis technique to identify brain differences in heavy male cannabis users compared to controls during resting-state fMRI (no task being performed).

Cannabinoids: new promising agents in the treatment of neurological diseases.

Giacoppo, Sabrina · 2014

This review evaluated the state of cannabinoid research for neurological diseases.

Cannabis abstinence during treatment and one-year follow-up: relationship to neural activity in men.

Kober, Hedy · 2014

Twenty cannabis-dependent men completed an fMRI cognitive control task before starting a 12-week treatment trial.

The effect of clozapine and risperidone on attentional bias in patients with schizophrenia and a cannabis use disorder: An fMRI study.

Machielsen, Marise Wj · 2014

In a randomized trial of 36 patients with schizophrenia and cannabis use disorder, those treated with clozapine showed larger reductions in subjective craving and decreased activation of the insula during a cannabis-word Stroop task compared to those on risperidone.

Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

McPartland, John M · 2014

The review identified multiple categories of clinical interventions that enhance the endocannabinoid system.

Effects of cannabis on cognition in patients with MS: a psychometric and MRI study.

Pavisian, Bennis · 2014

Compared to matched MS patients who did not use cannabis, cannabis-using MS patients performed significantly worse on two cognitive measures: the more demanding version of the Paced Auditory Serial Addition Test (processing speed) and the 10/36 Spatial Recall Test (visual memory). On fMRI during a working memory task, cannabis users showed more diffuse cerebral activation across all difficulty levels and made more errors on the most demanding task.

Functional connectivity alterations in brain networks relevant to self-awareness in chronic cannabis users.

Pujol, Jesus · 2014

Compared to 29 controls, 28 heavy cannabis users showed increased functional connectivity within the core of the Default Mode Network and Insula Network, and enhanced anticorrelation between these two networks.

Cannabinoids and schizophrenia: therapeutic prospects.

Robson, P J · 2014

Standard antipsychotic drugs fail to adequately control symptoms in approximately one-third of schizophrenia patients.

Therapeutic potential of cannabinoid medicines.

Robson, P J · 2014

The review covers the endocannabinoid system's role in immune response, appetite, cognition, emotion, perception, motor coordination, body temperature, sleep, and bone metabolism.

Immune system: a possible nexus between cannabinoids and psychosis.

Suárez-Pinilla, Paula · 2014

The review identified a clear dichotomy: endocannabinoids (produced naturally in the body) generally enhanced immune responses, while exogenous cannabinoids (from cannabis) had immunosuppressant effects.

Cannabis, cannabidiol, and epilepsy--from receptors to clinical response.

Szaflarski, Jerzy P · 2014

The review covers three key areas.

Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential.

Tai, Sherrica · 2014

The review highlights a critical pharmacological difference between natural THC and synthetic cannabinoids: THC is a relatively weak partial agonist at CB1 receptors, while the majority of synthetic cannabinoids are full agonists with higher binding affinity.

Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin on food reward and aversion in healthy volunteers.

Tudge, Luke · 2014

Twenty healthy volunteers received either 10mg THCV or placebo in a double-blind crossover design.

The endocannabinoid system as a potential therapeutic target for pain modulation.

Ulugöl, Ahmet · 2014

The review outlines the shift in cannabinoid pain research from directly activating cannabinoid receptors to enhancing the body's own endocannabinoid system.

Repeated Δ9-tetrahydrocannabinol exposure in adolescent monkeys: persistent effects selective for spatial working memory.

Verrico, Christopher D · 2014

Seven pairs of adolescent male rhesus monkeys, matched for baseline cognitive ability, received either THC or vehicle intravenously 5 days/week for 6 months.

Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals.

Wetherill, Reagan R · 2014

Twenty treatment-seeking cannabis-dependent individuals were shown cannabis, sexual, and aversive images for only 33 milliseconds (too fast for conscious perception) using a backward-masking technique during fMRI.

Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers.

Atakan, Z · 2013

In a double-blind, placebo-controlled study, 21 healthy men with minimal cannabis experience received 10 mg oral THC or placebo.

Weed or wheel! FMRI, behavioural, and toxicological investigations of how cannabis smoking affects skills necessary for driving.

Battistella, Giovanni · 2013

Thirty-one male occasional cannabis smokers underwent fMRI while performing a visuo-motor tracking task after smoking cannabis or placebo.

Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

Chen, Rongqing · 2013

Published in the journal Cell, this study identified COX-2 (cyclooxygenase-2) as the key mediator of THC's memory-impairing effects.

Targeting the cannabinoid system for pain relief?

Chiou, Lih-Chu · 2013

The review covered multiple cannabinoid pain-relief strategies: exogenous cannabinoids (THC acting mainly through CB1), CB2-selective agonists (which avoid psychoactive effects), and endocannabinoid enzyme inhibitors (FAAH and MAGL inhibitors).

Analysis of tolerance and behavioral/physical dependence during chronic CB1 agonist treatment: effects of CB1 agonists, antagonists, and noncannabinoid drugs.

Desai, Rajeev I · 2013

Squirrel monkeys chronically treated with the potent CB1 agonist AM411 developed enormous tolerance to cannabinoid agonists, with up to 250-fold rightward shifts in potency.

Repeated low-dose administration of the monoacylglycerol lipase inhibitor JZL184 retains cannabinoid receptor type 1-mediated antinociceptive and gastroprotective effects.

Kinsey, Steven G · 2013

The MAGL inhibitor JZL184 blocks the enzyme that breaks down the endocannabinoid 2-AG, boosting natural cannabinoid signaling.

Cannabinoids decrease the th17 inflammatory autoimmune phenotype.

Kozela, Ewa · 2013

Researchers studied immune cells that cause experimental autoimmune encephalitis (a model of multiple sclerosis) in mice.

Amygdala activity contributes to the dissociative effect of cannabis on pain perception.

Lee, Michael C · 2013

Healthy volunteers received either THC or placebo before a capsaicin-induced pain and hyperalgesia model with fMRI brain imaging.

Cannabis abuse and brain morphology in schizophrenia: a review of the available evidence.

Malchow, Berend · 2013

The review examined MRI studies comparing schizophrenia patients with and without cannabis abuse, as well as high-risk individuals.

Peripheral and spinal activation of cannabinoid receptors by joint mobilization alleviates postoperative pain in mice.

Martins, D F · 2013

Mice underwent plantar incision surgery and received ankle joint mobilization 24 hours later.

Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine.

Navarrete, Francisco · 2013

CB2 knockout mice showed three key deficits in nicotine responses: they did not develop conditioned place preference (reward), they self-administered significantly less nicotine (reinforcement), and they showed no somatic withdrawal signs after chronic nicotine exposure.

Control of experimental spasticity by targeting the degradation of endocannabinoids using selective fatty acid amide hydrolase inhibitors.

Pryce, G · 2013

Mice with experimental autoimmune encephalomyelitis (EAE, a model of MS) developed spasticity that was treated with three different FAAH inhibitors (CAY100400, CAY100402, URB597).

Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal.

Scavone, J L · 2013

The review detailed how cannabinoid and opioid receptors interact at the molecular level, particularly in the locus coeruleus-norepinephrine (LC-NE) system, a key circuit in the negative effects of opiate addiction.

Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of multiple sclerosis.

Sisay, Sofia · 2013

CB2 receptor knockout mice on a C57BL/6 background developed more severe EAE (MS model), consistent with prior reports.

Young adults at risk for stimulant dependence show reward dysfunction during reinforcement-based decision making.

Stewart, Jennifer L · 2013

One hundred sixty-one occasional stimulant users and 48 controls performed a decision-making task during fMRI.

Effects of cannabis use on event related potentials in subjects at ultra high risk for psychosis and healthy controls.

van Tricht, Mirjam J · 2013

Researchers measured brain wave responses (event-related potentials, or ERPs) in 48 ultra-high-risk (UHR) subjects and 50 healthy controls, split into cannabis users and non-users within each group.

The biology that underpins the therapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis.

Baker, David · 2012

This review connected the biology of MS to the biology of the endocannabinoid system, explaining why cannabis-based medicines work for spasticity at a fundamental level.

Approach-bias predicts development of cannabis problem severity in heavy cannabis users: results from a prospective FMRI study.

Cousijn, Janna · 2012

Thirty-three heavy cannabis users and 36 controls completed an fMRI task measuring automatic approach and avoidance tendencies toward cannabis-related images.

Resting state abnormalities in psychosis compared to acute cannabinoids and opioids challenges: a systematic review of functional imaging studies.

Denier, Niklaus · 2012

This systematic review compared resting-state brain activity in three conditions: first-episode psychosis (FEP), acute cannabinoid effects, and acute opioid effects, using data from 22 neuroimaging studies. Results within each condition group were highly conflicting, with different studies showing different patterns.

Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

Han, Jing · 2012

This study overturned a fundamental assumption about how cannabis impairs memory.

Functional connectivity in brain networks underlying cognitive control in chronic cannabis users.

Harding, Ian H · 2012

Twenty-one current cannabis users with over 10 years of near-daily use were compared to 21 matched controls during a cognitive control task (Multi-Source Interference Task).

Altered cerebral blood flow and neurocognitive correlates in adolescent cannabis users.

Jacobus, Joanna · 2012

Twenty-three heavy adolescent marijuana users (200+ lifetime use days) and 23 matched controls underwent brain perfusion scans at baseline and after 4 weeks of monitored abstinence (confirmed by urine testing).

Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate release.

Maier, Nikolaus · 2012

Using both in vivo and in vitro recordings in mice, researchers demonstrated that activating CB1 receptors suppressed sharp wave-ripples (SWRs) in the hippocampus.

Persistent cannabis users show neuropsychological decline from childhood to midlife

Meier, Madeline H. · 2012

People who used cannabis persistently across early adulthood showed declines across multiple neuropsychological domains by age 38 compared to their own pre-use performance at age 13.

A review of the interactions between alcohol and the endocannabinoid system: implications for alcohol dependence and future directions for research.

Pava, Matthew J · 2012

The review compiled 50 years of research on the relationship between the endocannabinoid system and alcohol.

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

Pertwee, Roger G · 2012

Three cannabinoid medicines were already in clinical use at the time: Cesamet (nabilone), Marinol (dronabinol), and Sativex (THC with CBD).

Potential control of multiple sclerosis by cannabis and the endocannabinoid system.

Pryce, Gareth · 2012

The review examined two distinct roles for cannabinoids in MS.

Endocannabinoids in nervous system health and disease: the big picture in a nutshell.

Skaper, Stephen D · 2012

The review provided a broad overview of the endocannabinoid system (ECS), describing how its two main signaling molecules, anandamide and 2-AG, regulate brain function through cannabinoid receptors.

The manifold actions of endocannabinoids on female and male reproductive events.

Bari, Monica · 2011

The review traced the role of endocannabinoids in reproductive biology across the evolutionary spectrum from invertebrates to mammals. In females, chronic THC exposure was found to disrupt the menstrual cycle, suppress egg development (oogenesis), and impair embryo implantation and development.

Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring.

DiNieri, Jennifer A · 2011

This study combined human fetal tissue analysis with a rat model to investigate how prenatal cannabis exposure affects the developing brain's reward system. In human fetal subjects, prenatal cannabis exposure specifically decreased dopamine D2 receptor (DRD2) gene expression in the nucleus accumbens, the brain's key reward region.

Cannabinoids and innate immunity: taking a toll on neuroinflammation.

Downer, Eric J · 2011

The review connected two important biological systems: the cannabinoid system and the Toll-like receptor (TLR) system, which mediates innate immunity in the brain. TLRs are pattern recognition receptors that detect threats and trigger inflammatory responses.

Molecular mechanisms of maternal cannabis and cigarette use on human neurodevelopment.

Morris, Claudia V · 2011

The review examined molecular mechanisms through which prenatal cannabis and cigarette exposure disrupted brain development. Prenatal cannabis exposure specifically altered dopamine D2 receptor gene expression in the fetal brain's reward center (nucleus accumbens), potentially through epigenetic mechanisms including DNA methylation and histone modification.

Regulation of nausea and vomiting by cannabinoids.

Parker, Linda A · 2011

This review pulled together decades of research on how the endocannabinoid system regulates nausea and vomiting.

Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

Russo, Ethan B · 2011

This review, which became one of the most cited papers in cannabis science, examined how non-cannabinoid plant compounds, particularly terpenes, might contribute to the therapeutic effects of whole-plant cannabis beyond what THC or CBD alone can do. Russo cataloged eight major cannabis terpenes (limonene, myrcene, pinene, linalool, beta-caryophyllene, caryophyllene oxide, nerolidol, and phytol) and their documented pharmacological effects.

Evidence for involvement of the insula in the psychotropic effects of THC in humans: a double-blind, randomized pharmacological MRI study.

van Hell, Hendrika H · 2011

Twenty-three subjects underwent pharmacological MRI after receiving THC or placebo.

Modulation of auditory and visual processing by delta-9-tetrahydrocannabinol and cannabidiol: an FMRI study.

Winton-Brown, Toby T · 2011

Fourteen healthy volunteers were scanned with fMRI on three occasions after receiving THC (10 mg), CBD (600 mg), or placebo.

Role of cannabinoids in multiple sclerosis.

Zajicek, John P · 2011

This review covered both the endocannabinoid system biology and clinical evidence for cannabinoids in MS.

Chronic use of cannabis and poor neural efficiency in verbal memory ability.

Battisti, Robert A · 2010

Twenty-four chronic cannabis users (mean 17 years of near-daily use) and 24 non-using controls were tested on a verbal memory task while brain electrical activity (ERPs) was recorded. Cannabis users showed poorer recall.

Chronic cannabis users show altered neurophysiological functioning on Stroop task conflict resolution.

Battisti, Robert A · 2010

Twenty-one chronic cannabis users (mean 16.4 years near-daily use, unintoxicated) and 19 controls completed a Stroop color-naming task while ERPs were recorded. Cannabis users made significantly more errors specifically on incongruent trials (where the word meaning conflicts with the ink color, like "RED" written in blue).

Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology.

Bhattacharyya, Sagnik · 2010

In a two-part study, 15 healthy men completed four tasks during fMRI after receiving THC (10 mg), CBD (600 mg), or placebo. THC and CBD had opposite effects on brain activation across all four tasks: - In the striatum during verbal recall - In the hippocampus during response inhibition - In the amygdala while viewing fearful faces - In the superior temporal cortex during speech processing - In the occipital cortex during visual processing In a second experiment with 6 volunteers, CBD pretreatment prevented the acute psychotic symptoms normally induced by intravenous THC. This demonstrated that the two main cannabis compounds have fundamentally opposing brain effects, and that CBD can actively block THC-induced psychosis..

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

Gerra, Gilberto · 2010

This review covered the pharmacology, therapeutic uses, and toxicology of cannabis-derived medications. Existing clinical applications included Sativex (THC/CBD extract) for MS symptoms, nabilone and dronabinol for chemotherapy-induced nausea, and dronabinol for appetite stimulation.

Endogenous cannabinoid and opioid systems and their role in nicotine addiction.

Maldonado, Rafael · 2010

The review detailed how the endogenous cannabinoid and opioid systems interact with dopamine-driven reward pathways that underlie nicotine addiction.

Neuroimaging in cannabis use: a systematic review of the literature.

Martín-Santos, R · 2010

Researchers systematically reviewed 66 brain imaging studies, of which 41 met inclusion criteria.

Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

Parolaro, D · 2010

The review synthesized evidence for three main mechanisms through which the cannabinoid and opioid systems interact: 1.

Diffusion tensor imaging in the early phase of schizophrenia: what have we learned?

Peters, Bart D · 2010

The review examined diffusion tensor imaging (DTI) studies in first-episode schizophrenia patients and people at high risk for psychosis.

Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.

Rieder, Sadiye Amcaoglu · 2010

The review catalogued how cannabinoids mediate immunosuppression through four broad mechanisms: 1.

Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases: physiological and pharmacological implications.

Snider, Natasha T · 2010

The review focused on an underappreciated aspect of endocannabinoid biology: the oxidation of anandamide by cytochrome P450 enzymes. While FAAH is the primary enzyme that breaks down anandamide, several P450 enzymes (CYP3A4, CYP4F2, CYP4X1, and the highly variable CYP2D6) also metabolize anandamide into structurally diverse lipid products. Critically, one P450-derived epoxide of anandamide was found to be a potent agonist at CB2 receptors.

A critical review of the cannabinoid receptor as a drug target for obesity management.

Akbas, F · 2009

This critical review assessed how close CB1 cannabinoid receptor antagonists were to being ideal anti-obesity drugs. The mechanisms were sound: CB1 antagonists reduced food intake centrally (brain) and may increase energy expenditure peripherally (thermogenesis in animal studies). However, the clinical reality was disappointing.

Cannabis and anxiety: a critical review of the evidence

Crippa, Jose Alexandre S. · 2009

Acute anxiety reactions and panic attacks were commonly reported during cannabis intoxication.

Naturally occurring and related synthetic cannabinoids and their potential therapeutic applications.

Galal, Ahmed M · 2009

This review covered the landscape of naturally occurring cannabinoids (phytocannabinoids) and their synthetic analogs, focusing on patents filed between 2003 and 2007. The review noted that while psychotropic effects of cannabis are mainly attributed to THC, cannabinoids also affect the cardiovascular, immune, and endocrine systems through interactions with CB1 and CB2 receptors. The FDA had approved synthetic THC (dronabinol/Marinol) in 1985 for chemotherapy-related nausea and in 1992 as an appetite stimulant for AIDS patients.

Cannabidiol: a promising drug for neurodegenerative disorders?

Iuvone, Teresa · 2009

This review examined the evidence for CBD as a treatment for neurodegenerative diseases, which involve progressive neuron loss and are among the leading causes of death in industrialized countries. Inflammation was identified as a common factor across diverse neurodegenerative conditions, contributing to the progressive nature of neurodegeneration. Preclinical evidence showed CBD has both neuroprotective and anti-inflammatory properties.

Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain.

Kinsey, S G · 2009

Researchers tested whether blocking the enzymes that degrade endocannabinoids could reduce neuropathic pain in mice with sciatic nerve injury. FAAH inhibitors (URB597 and OL-135), which increase anandamide levels, reduced both mechanical and cold allodynia.

Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo.

Long, Jonathan Z · 2009

Researchers developed JZL195, a drug that simultaneously blocks both FAAH and MAGL, the enzymes that break down the endocannabinoids anandamide and 2-AG. JZL195 produced analgesia, reduced movement, and catalepsy, covering a broader range of cannabinoid-like effects than blocking either enzyme alone. Critically, in drug discrimination tests (where animals indicate whether a drug feels like THC), dual FAAH/MAGL blockade produced THC-like responses, but inhibiting either enzyme alone did not. This revealed that anandamide and 2-AG pathways have both unique and overlapping functions.

Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects.

Long, Jonathan Z · 2009

Researchers developed JZL184, the first potent and selective inhibitor of MAGL, the enzyme that breaks down the endocannabinoid 2-AG. When administered to mice, JZL184 raised brain 2-AG levels eightfold without altering anandamide levels, confirming that MAGL is the primary enzyme responsible for 2-AG degradation in the brain. Mice treated with JZL184 exhibited analgesia, hypothermia, and reduced movement, all classic cannabinoid effects that were blocked by a CB1 receptor antagonist, confirming they were mediated through the cannabinoid system. These findings established that 2-AG endogenously modulates several behavioral processes traditionally associated with cannabis pharmacology..

Endocannabinoid system: An overview of its potential in current medical practice.

Mouslech, Zadalla · 2009

This extensive review covered the endocannabinoid system (ECS) across multiple body systems. In the brain, CB1 receptors are concentrated in areas controlling motor function, emotional responses, motivated behavior, and energy balance.

Emerging strategies for exploiting cannabinoid receptor agonists as medicines.

Pertwee, Roger G · 2009

Five strategies for improving cannabinoid therapeutics while reducing psychoactive side effects: (1) peripheral restriction — drugs that cannot cross the blood-brain barrier; (2) tissue-specific delivery — intrathecal, transdermal, topical routes; (3) receptor upregulation — exploiting disease-induced increases in receptor density; (4) CB2 selectivity — targeting immune receptors that don't cause intoxication; (5) multi-targeting — synergistic combinations, especially cannabinoid-opioid at sub-effective doses..

Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.

Puighermanal, Emma · 2009

Researchers discovered that THC activates the mTOR/p70S6K pathway in the mouse hippocampus, a signaling cascade that controls new protein synthesis. This activation correlated with THC-induced memory impairment.

Inhibitors of endocannabinoid-metabolizing enzymes reduce precipitated withdrawal responses in THC-dependent mice.

Schlosburg, Joel E · 2009

Researchers tested whether increasing endocannabinoid levels could ease THC withdrawal in dependent mice. Both the FAAH inhibitor URB597 (which raises anandamide) and the MAGL inhibitor JZL184 (which raises 2-AG) significantly attenuated withdrawal signs precipitated by the CB1 antagonist rimonabant in THC-dependent mice. Importantly, subchronic URB597 administration did not itself produce cannabinoid dependence, and neither inhibitor impaired motor coordination on the rotarod test. Interestingly, FAAH knockout mice (born without the enzyme) showed identical withdrawal responses as normal mice, suggesting that constitutive absence of FAAH throughout the development of dependence does not affect withdrawal, while acute FAAH inhibition during withdrawal does..

The endocannabinoid system and multiple sclerosis.

Baker, David · 2008

This review examined the dual potential of the endocannabinoid system in MS: symptom management and disease modification. For symptom relief, the evidence showed that spasticity is tonically (continuously) regulated by the endocannabinoid system, and clinical trials suggested cannabis can relieve pain, spasms, and spasticity.

Neural basis of Delta-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition.

Borgwardt, Stefan J · 2008

Fifteen healthy volunteers performed a Go/No-Go task (requiring them to withhold a response on certain trials) under three conditions: THC, CBD, or placebo, in a double-blind crossover design with fMRI. THC attenuated activation in the right inferior frontal gyrus and anterior cingulate cortex, two brain regions well established as critical for response inhibition (the ability to stop an action once initiated). CBD produced a different pattern entirely: it deactivated the left temporal cortex and insula, regions not typically associated with response inhibition. Importantly, these brain changes were not explained by differences in anxiety, intoxication, sedation, or psychotic-like symptoms between conditions, suggesting direct pharmacological effects on brain function rather than secondary consequences of feeling impaired..

Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

De Petrocellis, Luciano · 2008

Researchers tested six plant cannabinoids (CBD, THC, CBD acid, THC acid, cannabichromene/CBC, and cannabigerol/CBG) on two ion channels involved in pain sensing: TRPA1 and TRPM8. All six cannabinoids activated TRPA1 channels (which detect chemical irritants and contribute to inflammatory pain).

Direct suppression of autoreactive lymphocytes in the central nervous system via the CB2 receptor.

Dittel, B N · 2008

This review focused on the CB2 cannabinoid receptor's role in controlling autoimmune inflammation in the central nervous system. While THC activates both CB1 (mainly brain) and CB2 (mainly immune system) receptors, the generation of mice lacking specific cannabinoid receptors has allowed researchers to separate these functions.

Neurobiology of cannabis addiction.

Jain, Raka · 2008

This review summarized the neurobiological basis of cannabis addiction, covering several key themes. The discovery of cannabinoid receptors (CB1 and CB2) and their endogenous ligands (anandamide and 2-AG) provided a molecular framework for understanding how cannabis produces dependence.

Endocannabinoids and the neurochemistry of gluttony.

Kirkham, Tim · 2008

This brief review outlined how the endocannabinoid system drives overeating through two complementary mechanisms. First, endocannabinoids acting at CB1 receptors in the brain increase appetite by enhancing both food craving (wanting) and food enjoyment (liking).

Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users.

Nestor, Liam · 2008

Two experiments examined learning and memory in cannabis users.

Activation of the endocannabinoid system by organophosphorus nerve agents.

Nomura, Daniel K · 2008

Researchers discovered that certain organophosphorus compounds (normally studied as nerve agents) simultaneously inhibit both MAGL and FAAH, the two main enzymes that break down endocannabinoids in the brain. This dual blockade produced greater than 10-fold increases in brain levels of both 2-AG and anandamide and caused robust CB1-dependent behavioral effects (reduced movement, catalepsy, hypothermia, pain insensitivity) that mirrored those of directly administering THC. This was strikingly different from blocking FAAH alone, which produces only analgesic and anxiolytic effects without cognitive impairment or cannabinoid-like intoxication. An unexpected finding: brain arachidonic acid levels decreased by amounts equivalent to the 2-AG increases, revealing that endocannabinoid and eicosanoid (inflammatory lipid) signaling pathways are coordinately regulated in the brain..

Behavioral pharmacology of cannabinoids with a focus on preclinical models for studying reinforcing and dependence-producing properties.

Panagis, George · 2008

This comprehensive review examined preclinical (animal) evidence for the reinforcing and dependence-producing properties of cannabinoids. The central finding was that cannabinoids behave differently from other drugs of abuse in standard laboratory paradigms.

Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure.

Schneider, Miriam · 2008

This review assembled evidence from human and animal studies showing puberty is a uniquely vulnerable period for cannabis exposure. The endocannabinoid system undergoes significant maturation during puberty, with changes in CB1 receptor density, endocannabinoid levels, and enzyme expression across brain regions.

Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats.

Schneider, Miriam · 2008

Researchers gave pubertal rats (postnatal day 40-65) and adult rats (postnatal day 80+) daily injections of the synthetic cannabinoid WIN 55,212-2 for 25 days and tested behavior at three time points: immediately after the first dose, 24 hours after stopping, and 15 days after stopping. Pubertal-treated rats showed persistent deficits in both object and social recognition memory, indicating impaired short-term information processing.

Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet.

Starowicz, Katarzyna M · 2008

Researchers fed mice standard or high-fat diets for up to 14 weeks and mapped the endocannabinoid system in their pancreatic and fat tissues. In the pancreas, they found that CB1 receptors and endocannabinoid-producing enzymes were primarily located in alpha cells (which make glucagon), while degrading enzymes were in beta cells (which make insulin).

Overview of the chemical families of fatty acid amide hydrolase and monoacylglycerol lipase inhibitors.

Vandevoorde, Séverine · 2008

This review cataloged and compared all known synthetic inhibitors of FAAH and MAGL, the two primary enzymes that break down the endocannabinoids anandamide and 2-AG. FAAH inhibitors fell into two groups: substrate-inspired compounds (mimicking the fatty acid chains of anandamide, oleamide, or PEA) and structurally novel compounds (carbamates, oxazolopyridines, imidazolidines, and even some NSAIDs).

Pharmacotherapeutic targeting of the endocannabinoid signaling system: drugs for obesity and the metabolic syndrome.

Vemuri, V Kiran · 2008

This review detailed the pharmacological rationale for targeting the endocannabinoid system in obesity and metabolic syndrome. The endocannabinoid system promotes food intake (through brain CB1 receptors) and energy storage as fat (through peripheral CB1 receptors).

Cannabinoid control of neuroinflammation related to multiple sclerosis.

Baker, D · 2007

This review from the British Journal of Pharmacology examined whether cannabinoids can modify the neuroinflammatory process driving MS, beyond just controlling symptoms. Experimental studies revealed two mechanisms: synthetic cannabinoids can indirectly suppress the immune response through CB1 receptor signaling in nerve centers that control systemic immunosuppression, and can directly inhibit lymphocyte and macrophage/microglial function through CB2 receptors. However, the review concluded that these immunosuppressive effects, which could reduce relapsing attack frequency, would probably not be achieved clinically through medical cannabis use due to dose constraints: the doses needed for immunosuppression would likely cause unacceptable psychoactive effects. A more promising avenue was cannabinoid modulation of the glial response within damaged CNS tissue, which could slow the progressive neurodegeneration accounting for disability accumulation in MS..

Critical enzymes involved in endocannabinoid metabolism.

Basavarajappa, Balapal S · 2007

This review provided an integrative overview of the enzymes controlling endocannabinoid levels.

A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol.

Blankman, Jacqueline L · 2007

Using proteomic techniques on mouse brain tissue, researchers identified three enzymes primarily responsible for breaking down 2-arachidonoylglycerol (2-AG), one of the brain's main endocannabinoids. Monoacylglycerol lipase (MAGL) accounted for approximately 85% of total 2-AG hydrolysis in the brain.

Functional imaging studies in cannabis users.

Chang, Linda · 2007

This review examined the existing neuroimaging literature on cannabis users, covering both acute THC administration studies and chronic use studies. Acute THC studies (mostly using PET) consistently found that THC increases brain activation in frontal, paralimbic, and cerebellar regions, matching the drug's known behavioral effects. For chronic users, the picture was different.

Effects of frequent cannabis use on hippocampal activity during an associative memory task.

Jager, Gerry · 2007

Twenty frequent cannabis users and 20 matched non-users underwent functional MRI while performing an associative memory task (learning to link pairs of items together). Cannabis users showed significantly lower activation in the parahippocampal regions and right dorsolateral prefrontal cortex compared to non-users.

Targeted modulators of the endogenous cannabinoid system: future medications to treat addiction disorders and obesity.

Janero, David R · 2007

This review outlined how the endocannabinoid system regulates reward-driven behaviors that underlie both addiction and obesity.

Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors.

Pryce, G · 2007

Researchers tested cannabinoid effects on spasticity in both normal mice and mice genetically lacking CB1 receptors, all with experimental autoimmune encephalomyelitis (a model of MS). Some CB2-selective agonists (like RWJ400065) appeared to reduce spasticity.

Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation.

Wang, Haibin · 2007

Researchers mapped the endocannabinoid system in the mouse uterus during embryo implantation, focusing on both anandamide and 2-AG. 2-AG was present at levels one order of magnitude (roughly 10x) higher than anandamide in the uterus, but both showed the same spatial pattern: lower levels at implantation sites and higher levels at interimplantation sites. These gradients were created by region- and stage-specific expression of four key enzymes: NAPE-PLD and FAAH (for anandamide synthesis and breakdown) and DAGLalpha and MAGL (for 2-AG synthesis and breakdown).

The orphan receptor GPR55 is a novel cannabinoid receptor

Ryberg, E · 2007

GPR55 binds to and is activated by the cannabinoid ligand CP55940 and by THC (EC50 = 8 nM, remarkably potent).

Cannabinoid-induced immune suppression and modulation of antigen-presenting cells.

Klein, Thomas W · 2006

This review examined how the endocannabinoid system, originally discovered through neuroscience research, also regulates immune function.

The cannabinergic system as a target for anti-inflammatory therapies.

Lu, Dai · 2006

This review examined how modulating the endocannabinoid system affects immune function.

A validation of event-related FMRI comparisons between users of cocaine, nicotine, or cannabis and control subjects.

Murphy, Kevin · 2006

A critical concern in brain imaging research on drug users is whether drugs' effects on blood vessels could alter the fMRI signal, making comparisons with non-users unreliable.

The emerging role of the endocannabinoid system in endocrine regulation and energy balance.

Pagotto, Uberto · 2006

This comprehensive review published in Endocrine Reviews detailed the endocannabinoid system's emerging role in regulating hormonal function.

Brain neuroimaging in cannabis use: a review.

Quickfall, Jeremy · 2006

This systematic review examined both structural and functional neuroimaging studies of cannabis use.

Effects of prenatal marijuana on visuospatial working memory: an fMRI study in young adults.

Smith, Andra M · 2006

Researchers scanned 31 participants from the Ottawa Prenatal Prospective Study (16 prenatally exposed to cannabis, 15 non-exposed) at age 18-22 using fMRI during a visuospatial working memory task.

Evolutionary origins of the endocannabinoid system.

McPartland, John M · 2006

By searching for endocannabinoid system genes across twelve species spanning the tree of life, McPartland and colleagues traced the evolutionary origins of every major ECS component.

Cannabinoid tolerance and dependence: a review of studies in laboratory animals.

González, Sara · 2005

This extensive review compiled evidence from laboratory animal studies on cannabinoid tolerance and dependence.

Cannabinoids.

Grotenhermen, Franjo · 2005

This comprehensive review covered 15 years of research since the discovery of the endocannabinoid system.

Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids.

Ilan, A B · 2005

Twenty-three healthy marijuana users (12 men, 11 women) participated in four sessions where they smoked marijuana cigarettes under blinded conditions.

Endocannabinoids in the regulation of appetite and body weight.

Kirkham, T C · 2005

This review compiled evidence on the endocannabinoid system's role in appetite and body weight regulation.

The endocannabinoid system and the treatment of obesity.

Pagotto, Uberto · 2005

This review detailed how the endocannabinoid system contributes to obesity through two parallel mechanisms.

Cannabinoids and the regulation of ingestive behaviour.

Vickers, S P · 2005

This review compiled evidence on how cannabinoids regulate eating behavior, covering both exogenous (plant-derived) and endogenous cannabinoids.

Medical marijuana: emerging applications for the management of neurologic disorders.

Carter, Gregory T · 2004

Cannabis contains over 60 different cannabinoids with capacity for neuromodulation through direct, receptor-based mechanisms at many levels within the nervous system.

Towards cannabis and cannabinoid treatment of multiple sclerosis.

Croxford, J Ludovic · 2004

The review identified a gap between promising preclinical evidence and disappointing clinical results.

Pharmacology of cannabinoids.

Grotenhermen, Franjo · 2004

THC acts as an agonist at both CB1 and CB2 receptors distributed across the central nervous system and peripheral tissues including spleen, leukocytes, reproductive and urinary tracts, endocrine glands, arteries, and heart.

Cannabinoid pharmacology in the cardiovascular system: potential protective mechanisms through lipid signalling.

Hiley, C Robin · 2004

The review documented multiple mechanisms by which cannabinoids affect the cardiovascular system.

Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study.

Kanayama, Gen · 2004

Using functional MRI, 12 heavy cannabis users (6-36 hours after last use) showed increased activation in brain regions typically used for spatial working memory (prefrontal cortex, anterior cingulate) compared to 10 controls.

Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons.

Pistis, Marco · 2004

After just 3 days of cannabinoid treatment followed by a 2-week washout, adolescent-treated rats showed long-lasting changes in how their dopamine neurons responded to other drugs.

The therapeutic potential of cannabis.

Baker, David · 2003

The review drew parallels between the cannabinoid and opioid research fields, noting that in both cases, study of drug-producing plants led to discovery of endogenous control systems with central roles in neurobiology.

Therapeutic potential of cannabinoids in CNS disease.

Croxford, J Ludovic · 2003

The review mapped cannabinoid therapeutic potential across multiple CNS conditions.

Cannabinoids: potential anticancer agents.

Guzmán, Manuel · 2003

Beyond their established palliative effects in cancer patients (preventing nausea, vomiting, pain, and stimulating appetite), cannabinoids had been shown to inhibit tumor cell growth in cell cultures and animal models.

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

Pryce, Gareth · 2003

Using experimental allergic encephalomyelitis (EAE), an animal model of MS, researchers demonstrated that the cannabinoid system was neuroprotective.

Cannabinoids on the brain.

Irving, Andrew J · 2002

The review synthesized research on how cannabinoids interact with the brain across multiple systems.

Endocannabinoids in cognition and dependence.

Lichtman, A H · 2002

The review synthesized evidence from two approaches: pharmacological blockade of CB1 receptors using SR141716A, and genetic knockout mice lacking the CB1 receptor.

Cannabinoids and multiple sclerosis.

Pertwee, Roger G · 2002

Clinical evidence from 8 trials in MS patients and 1 in spinal cord injury showed that cannabis, THC, and nabilone produced objective or subjective relief from spasticity, pain, tremor, and nocturia.

The role of cannabinoids in neurodegenerative diseases.

Glass, M · 2001

This review synthesized the rapidly growing understanding of the endocannabinoid system's role in neurological disease. The endocannabinoid system, consisting of two receptors (CB1, CB2) and two endogenous ligands (anandamide, 2-AG), is involved in normal movement control, memory formation, and appetite regulation.

The cannabinoids: an overview. Therapeutic implications in vomiting and nausea after cancer chemotherapy, in appetite promotion, in multiple sclerosis and in neuroprotection.

Mechoulam, R · 2001

The review traced cannabinoid science from historical use in Assyria and China through to the identification of CB1 and CB2 receptors and the discovery of endogenous cannabinoids.

Impaired cognitive performance in drug free users of recreational ecstasy (MDMA).

Gouzoulis-Mayfrank, E · 2000

Researchers compared cognitive performance across three carefully matched groups of 28 participants each: ecstasy users (who also used cannabis), cannabis-only users, and non-users.

Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation

Galve-Roperh, I · 2000

Intratumoral administration of THC and the synthetic cannabinoid WIN-55,212-2 caused considerable regression of malignant gliomas in rat and mouse models.

The effects of cannabinoids on the brain.

Ameri, A · 1999

This extensive review covered the full spectrum of cannabis effects on the brain, from molecular mechanisms to behavioral consequences. A striking finding was that recent research had revealed THC-induced cell death in the hippocampus, with neuron shrinkage and DNA fragmentation, effects the review stated had been "underestimated for a long time." Cognitive deficits, particularly in concentration and memory, appeared to persist after withdrawal. At the receptor level, the review detailed how CB1 receptors mediate THC's effects through G proteins, inhibiting calcium channels and stimulating potassium channels.

Cannabis in movement disorders.

Müller-Vahl, K R · 1999

Cannabinoid CB1 receptors are densely concentrated in the basal ganglia output nuclei (globus pallidus and substantia nigra), the brain circuits that control voluntary movement.

Cannabis and cannabinoids: pharmacology and rationale for clinical use.

Pertwee, R G · 1999

This review provided a comprehensive pharmacological roadmap for cannabinoid therapeutics.

Drugs and immunity: cannabinoids and their role in decreased resistance to infectious disease.

Cabral, G A · 1998

This review synthesized the evidence on THC and immune function, finding consistent immunosuppressive effects across multiple experimental models. THC decreased host resistance to bacterial, protozoan, and viral infections in lab and animal studies.

Marijuana, immunity and infection.

Klein, T W · 1998

This review synthesized 25 years of research across three major areas of cannabinoid immunology. First, cannabinoids affected the function of all major immune cell types: T and B lymphocytes, natural killer cells, and macrophages.

Neurobiology of marijuana abuse.

Abood, M E · 1992

This review highlighted a puzzling disconnect in cannabis research.

Controlled clinical trial of cannabidiol in Huntington's disease.

Consroe, P · 1991

Based on encouraging preliminary findings, researchers conducted a rigorous controlled trial of CBD in 15 Huntington's Disease patients who were not taking neuroleptic medications. Patients received either oral CBD (10 mg/kg/day, averaging about 700 mg/day) or placebo (sesame oil) for six weeks each in a double-blind, randomized crossover design.

Neurotoxicology of cannabis and THC: a review of chronic exposure studies in animals.

Scallet, A C · 1991

Multiple laboratories had reported that chronic exposure to THC or marijuana extracts produced persistent changes in the rat hippocampus, a brain region critical for learning and memory. The review identified two critical factors determining whether neurotoxic effects appeared: age during exposure and duration of exposure.

Review of cannabinoids and their antiemetic effectiveness.

Vincent, B J · 1983

This review synthesized the growing body of evidence on cannabinoid antiemetics.

Adult Rat Offspring Exposed to THC during Gestation Exhibit Distinct Biomolecular Changes Identified by X-ray Fluorescence Imaging and Fourier Transform Infrared Spectroscopy in Cortico-Limbic Circuits.

Black, Tallan · 2026

Most prenatal cannabis studies measure outcomes at the behavioral or anatomical level.

Randomised Controlled Trial Evidence on Medicinal Cannabis for Treatment of Mental Health and Substance Use Disorders: A Scoping Review.

Cooling, Sophie · 2026

This scoping review mapped all available randomized controlled trial evidence on medicinal cannabis for mental health conditions classified by the DSM-5.

Impact of prenatal delta-9-tetrahydrocannabinol exposure on mouse brain development: a fetal-to-adulthood magnetic resonance imaging study.

Cupo, Lani · 2026

Using MRI brain scans at nine timepoints from gestation through adulthood, researchers tracked what happened to mouse brains after prenatal THC exposure.

Prenatal Cannabis and Tobacco: Studies in Animal Models.

Edenfield, R Clayton · 2026

This comprehensive review synthesized animal model research on prenatal exposure to both cannabis (primarily THC) and tobacco (primarily nicotine).

Dissociative-like Neurotoxicity Following Analytically Confirmed Exposure To Hexahydrocannabinol (HHC).

Greene, Shaun L · 2026

In this individual case, a 32-year-old man developed a dissociative-like neurologic syndrome plus gastrointestinal symptoms after ingesting a single gummy sold as a THC product.

Identifying established human placental markers of schizophrenia in rodents after gestational ∆9-tetrahydrocannabinol exposure†.

Kocsis, Andrea M · 2026

This study tested whether prenatal THC exposure in rats would alter the same placental genes that human genomic studies have linked to schizophrenia risk.

CYP4X1/sEH-Dependent Endocannabinoid Metabolism Drives Fibroblast-Mediated Immunosuppression to Limit Immunotherapy in Colon Cancer.

Mo, Min · 2026

CYP4X1 and sEH enzymes metabolize endocannabinoids to produce 14,15-EET-EA, which acts on GPR119 receptors in cancer-associated fibroblasts.

Sex-dependent effects of ultra-low-dose-THC preventive treatment on neuroinflammation and cognitive decline in 5xFAD mice.

Nitzan, Keren · 2026

ULD-THC attenuated AD-related cognitive decline in both sexes.

The effects of chronic cannabidiol administration on brain pathology and behavioral deficits found in the tau P301s-line PS19 mouse model of Alzheimer's disease.

Nixon, Abigail G · 2026

CBD did not improve cognitive or motor behavior and did not restore hippocampal volume.

Unraveling Endocannabinoid Signaling Pathways in Cisplatin-Induced Ototoxicity.

Palaniappan, Sakthimala · 2026

Cisplatin treatment downregulated CB2 receptors and disrupted the 2-AG metabolic pathway in auditory hair cells.

Longer chronic cannabis use in humans is associated with impaired implicit motor learning and supranormal resting state cortical activity.

Prashad, Shikha · 2026

Comparing 30 regular cannabis users to 32 non-users, researchers found that longer duration of cannabis use was associated with a smaller implicit motor learning index — meaning these individuals were less able to unconsciously learn movement sequences. Implicit motor learning was measured using the serial reaction time task, where participants respond to visual cues that follow a hidden repeating pattern.

Cannabivarin and tetrahydrocannabivarin modulate nociception via vanilloid channels and cannabinoid-like receptors in Caenorhabditis elegans.

Rahmani, Nasim · 2026

Both CBV and THCV produced dose-dependent antinociceptive effects in C.

Effects of chronic mild stress and CB1 receptor activation on hippocampal-dependent fear conditioning in female adolescent rats.

Reich, Christian G · 2026

Chronic mild stress enhanced trace fear conditioning (episodic fear memories) in adolescent female rats.

Illuminating chromaffin granules: compartmentalization of endocannabinoids in bovine adrenal glands supports role in hormone modulation.

Roukens, Jaap-Jan · 2026

N-acylethanolamines including anandamide predominated in the adrenal cortex while 2-AG was concentrated in the medulla.

Could cannabigerol protect against neuroinflammation? Insights from an in vitro microglial study.

Santos, Júlia Maiara Dos · 2026

CBG at 100 microM reduced cell viability by ~80%, increased nitric oxide ~400% and reactive oxygen species ~900%.

Evaluation of THC-induced neurotoxicity via oxidative stress in undifferentiated SH-SY5Y cells.

Sanz-Pérez, A · 2026

THC at 73.75 and 150 ng/mL significantly reduced cell viability (to 76.5% and 64.6% at 48 hours) and caused morphological changes.

Endocannabinoid response to social stress in chronic non-medical prescription opioid users.

Schmid, Vinzenz K · 2026

A significant GROUP x TIME interaction was found for 2-AG.

Behavioral pharmacology of novel synthetic indazole, indole, and benzimidazole cannabinoids in rodents.

Shetty, Ritu A · 2026

The DEA identified 11 synthetic cannabinoids of concern, and researchers tested each one in rodent models for two key properties: how strongly they suppressed movement (locomotor depression) and whether rats trained to recognize THC also recognized these compounds (drug discrimination). In locomotor tests, most of the 11 compounds were more potent than THC (which had an ED50 of 3.3 mg/kg).

The role of the endocannabinoid system in the interplay of adverse childhood experiences and interleukin 6 in individuals with borderline personality disorder.

Spohrs, Jennifer · 2026

People with BPD had higher IL-6 levels than healthy controls.

The Anti-proliferative Effects of Anandamide and Oleamide in Glioblastoma Cell Lines Recruit Mitochondrial and PPAR-γ Receptor Modulation.

Torres-Román, Ana Laura · 2026

Anandamide (AEA) and oleamide (ODA) reduced glioblastoma cell viability and increased lipid peroxidation compared to normal astrocytes.

Administration of the Synthetic Cannabinoid WIN55,212-2 Increases BDNF Expression Levels in the Adolescent Rat Brain.

Torres, Alejandro Guadalupe · 2026

Adolescent male rats received the synthetic cannabinoid WIN55,212-2 (a dual CB1/CB2 receptor agonist) via injection every 48 hours from postnatal day 30 to 44 — corresponding to human adolescence.

Involvement of Adenosine A2A Receptors in Anxiety-Like Behaviors in Tetrahydrocannabinol-Treated Mice.

Ün, Burçin · 2026

THC induced anxiety-like behavior in mice.

Effects of prenatal cannabis exposure on offspring mental health: A focus on the role of the immune system.

Vecchiarelli, Haley A · 2026

In both human and rodent studies using vaporized exposure, cannabis use during pregnancy was associated with reduced pro-inflammatory cytokine levels in the placenta.

THC induced similar physiological effects on HIV transgenic rats and their controls without affecting HIV-induced deficits in effortful motivation.

Vemuri, Sunitha · 2026

THC at 3 mg/kg reduced pain sensitivity, body temperature, and locomotor activity across all genotypes, with some sex-dependent effects.

Sexually Dimorphic Effects of a Single Neonatal Δ9-tetrahydrocannabinol Exposure on Neuronal Dendritic Morphology and Cognitive Functions in Rats.

Wadhwa, Meetu · 2026

Rat pups received a single injection of THC (5 mg/kg) or vehicle at postnatal day 3 — a period corresponding to late pregnancy/early postnatal brain development in humans.

Cannabidiol as a Prophylactic Agent Against Glioblastoma Growth: A Preclinical Investigation.

Wang, Lei P · 2026

Fourteen days of inhaled CBD pretreatment before tumor implantation significantly reduced glioblastoma burden compared to both placebo and 3-day CBD groups.

Cannabidiol Regulates CD47 Expression and Apoptosis in Jurkat Leukemic Cells Dependent upon VDAC-1 Oligomerization.

Wang, Lixing · 2026

CBD reduced CD47 surface expression and triggered apoptosis in Jurkat leukemic cells.

Cannflavin B ameliorates behavioural and neuronal systems alterations in adolescent rats exposed to prenatal valproic acid.

Williams, Olivia O F · 2026

Cannflavin B (0.2 mg/kg) was well tolerated and ameliorated most VPA-induced changes.

Cannabidiol Alleviates LPS-Induced Depressive-Like Behaviors Via Improving Mitochondria Function.

Zhao, Junning · 2026

Researchers induced depression-like behaviors in mice using lipopolysaccharide (LPS), a bacterial toxin that triggers neuroinflammation.

Tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit androgen biosynthesis in H295R cells.

Zufferey, Fanny · 2026

THC and CBD both reduced DHEA, androstenedione, and testosterone production in H295R cells dose-dependently.

Modulatory Effects of "Minor" Cannabinoids in an in vitro Model of Neuronal Hypersensitivity.

Anand, Uma · 2025

Cannabis produces over 100 cannabinoids, but research has focused almost exclusively on THC and CBD.

Comparative Analysis of Cannabidiol and Risperidone on Behavioral and Neurochemical Outcomes, and Neurodevelopment Markers in a Zebrafish Model of Embryonic Exposure to Sodium Valproate.

Costa, Karla C M · 2025

CBD treatment reversed VPA-induced hyperlocomotion and aggression in zebrafish, reduced lipid peroxidation, restored anandamide levels, and normalized markers of glial function.

Molecular docking of danuglipron uncovers potential crossovers between GLP-1R and the endocannabinoid system.

Dailey, Kiersten A · 2025

Danuglipron showed higher binding affinity for both CB1 and CB2 receptors than THC, anandamide, or 2-AG in computational docking experiments, suggesting potential cross-reactivity between GLP-1 receptor agonists and the endocannabinoid system..

The endocannabinoid system & malignant hyperthermia: From molecular signaling towards clinical implications.

Dalle, Simon · 2025

CB1 receptor activation inhibits PKA-mediated phosphorylation of RYR1 and L-type calcium channels, potentially reducing the excessive calcium release that causes malignant hyperthermia.

Crosstalk between M1 muscarinic acetylcholine receptor and endocannabinoid system promotes attenuation of inflammation in ulcerative colitis.

de Aguiar Magalhães, Diva · 2025

When researchers administered CB1 or CB2 receptor antagonists before treating colitis-induced mice with McN-A-343 (a muscarinic receptor agonist), the drug's anti-inflammatory benefits were significantly reversed, with increased intestinal damage, pro-inflammatory cytokines, oxidative stress, and NF-kB expression..

Cannabidiol engages the peripheral endogenous opioid system to produce analgesia in neuropathic mice.

de Almeida, Douglas Lamounier · 2025

CBD at 20 mg/kg produced significant antinociception in mice with sciatic nerve injury.

Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole.

de Aquino, Pedro Everson Alexandre · 2025

In acute seizure tests, CBD and THC at 3-10 mg/kg and their 1:1 combinations increased latency to generalized seizures and improved survival.

Targeting the endocannabinoid/paracannabinoid systems in binge eating behavior: Efficacy of dual ligands in a preclinical model.

de Ceglia, Marialuisa · 2025

OLHHA (CB1 antagonist/PPAR-alpha agonist) at 0.3 mg/kg and OLS (PPAR-alpha/TRPV1 agonist) at 6 mg/kg reduced aberrant palatable food consumption during binge eating tests.

Unravelling a potential therapeutic effect of polymeric lipid-core nanoencapsulated cannabidiol on anxiety- and panic-like behaviours elicited by Bothrops jararaca lancehead pit vipers.

de Paula Rodrigues, Bruno Mangili · 2025

Polymeric lipid-core nanoencapsulated CBD at low doses significantly reduced defensive attention, flat-back approach, and escape behaviors in mice facing a pit viper.

Cannabidiol/tetrahydrocannabinol-enrich extract decreases neuroinflammation and improves locomotor outcome following spinal cord injury.

Del Core, Julián · 2025

After acute spinal cord injury, the cannabis extract increased anti-inflammatory (arginase-1 positive) microglial cells at the injury site, decreased pro-inflammatory microglia and reactive astrocytes, downregulated inflammatory genes (IL-1beta, TNF-alpha, IL-6, C3), and upregulated anti-inflammatory markers (ARG-1, MRC).

Cannabinoids Shape Synaptic Activity and Adult Neurogenesis in the Zebrafish Pallium.

Deleglise, Emilia Beatriz · 2025

CB1 receptors were found in glutamatergic neurons of the zebrafish pallium.

Contrasting cannabinoid receptor 2 (CB2R)-mediated responses in two different models of Blood Brain Barrier in the context of HIV.

Delorme-Walker, Violaine · 2025

Both endothelial cell lines responded similarly to HIV-conditioned media (increased permeability, decreased tight junction proteins).

Prenatal Delta-9-Tetrahydrocannabinol Exposure Induces Transcriptional Alterations in Dopaminergic System with Associated Electrophysiological Dysregulation in the Prefrontal Cortex of Adolescent Rats.

Di Bartolomeo, Martina · 2025

Prenatal cannabis exposure increased mRNA levels of dopamine D1 and D2 receptors in the prefrontal cortex, with a particularly strong effect on D2 in males.

Cannabinol modulates the endocannabinoid system and shows TRPV1-mediated anti-inflammatory properties in human keratinocytes.

Di Meo, Camilla · 2025

CBN increased CB1 gene expression and TRPV1 protein expression and function in keratinocytes.

Cannabidiol Modulates Brain Copper Homeostasis in Wild-Type-Like But Not Alzheimer's Disease Transgenic Female Mice: Implications for Neuroprotective Therapy.

Dosseto, Anthony · 2025

CBD elevated whole-brain copper in wild-type mice but not APP/PS1 transgenic mice.

In vivo and In vitro Crosstalk Among CBD, Aβ, and endocannabinoid system enzymes and receptors.

Duan, Fangyuan · 2025

CBD induced autophagy and apoptosis specifically in amyloid-beta-expressing cells via LC3B and Caspase-3 pathways, while producing side effects in non-pathological cells.

Obesogenic diet impairs memory consolidation via the hippocampal endocannabinoid system.

Ducourneau, Eva-Gunnel · 2025

Obesogenic diet consumption impaired long-term object recognition memory, and this was prevented by post-training CB1 receptor blockade, which also normalized hippocampal overactivation.

Muscarinic cannabinoid suppression of excitation, a novel form of coincidence detection.

Dvorakova, Michaela · 2025

Coincident activation of muscarinic acetylcholine receptors and endocannabinoid-mediated depolarization-induced suppression of excitation produced a ~40% inhibition of excitatory transmission lasting ~10 minutes.

Distinct Adipocyte Responses to Δ9-Tetrahydrocannabinol (THC) Exposure Govern Hepatic Lipid Accumulation in an Obesogenic Setting.

Eitan, Adi · 2025

THC produced a biphasic response in mature fat cells: initially increasing free fatty acid release, then improving fat storage by day 18 with smaller lipid droplets and enhanced lipid handling.

Rethinking Alzheimer's: Harnessing Cannabidiol to Modulate IDO and cGAS Pathways for Neuroinflammation Control.

Emami Naeini, Sahar · 2025

CBD treatment reduced both IDO and cGAS expression in the brains of 5XFAD Alzheimer's mice, with corresponding decreases in TNF-alpha, IL-1beta, and IFN-gamma.

Stress reactivity is modulated by cannabinoid type-1 receptors in norepinephrine and epinephrine neurons in a context-dependent manner.

Engborg, Christopher B · 2025

Mice lacking CB1 receptors in NE/E neurons showed reduced avoidance after restraint stress, increased escape behavior to visual threats, and reduced immobility in forced swim, but normal baseline anxiety and unchanged heart rate responses to foot shock..

Behavioral Decoding Reveals Cortical Endocannabinoid Potentiation during Δ9-THC Impairment.

English, Anthony · 2025

THC increased GABAergic (inhibitory) neuron activity in the medial prefrontal cortex before movement initiation, shifting the excitatory/inhibitory balance.

Synthetic cannabinoid CUMYL-4CN-BINACA induces oxidative stress, ER stress, and apoptosis in brain and testicular tissues of male albino rats.

Eren Demir, Erdem · 2025

Subacute exposure produced dose-dependent increases in oxidative damage markers and decreases in antioxidant defenses across both organs.

Cannabidiol induces autophagy via CB1 receptor and reduces α-synuclein cytosolic levels.

Erustes, Adolfo G · 2025

CBD enhanced autophagic flux (increased LC3-II accumulation and GFP-LC3-positive vesicles) and reduced cytosolic alpha-synuclein in neuroblastoma cells.

Cannabidiol Extracted from Cannabis sativa L. Plant Shows Neuroprotective Impacts Against 6-HODA-Induced Neurotoxicity via Nrf2 Signal Transduction Pathway.

Esfandi, Afsaneh · 2025

CBD increased cell survival, decreased apoptosis, reduced reactive oxygen species and lipid peroxidation, and improved antioxidant capacity in 6-OHDA-exposed cells.

The Inhibition of Fatty Acid Amide Hydrolase-4 Affords Neuroprotection in a Toxic Model Induced by 6-Hydroxydopamine in Caenorhabditis elegans Nematodes.

Estrada-Valencia, Rubén · 2025

The FAAH-4 inhibitor JZL184 protected dopaminergic neurons from 6-OHDA damage, increased worm survival, and improved food-seeking behavior.

Trauma and cannabis cue-induced reward circuit functional connectivity in cannabis users with trauma histories.

Ethier-Gagnon, Mikaela A · 2025

Trauma cues increased cannabis craving and negative affect while decreasing positive affect.

Combined CB1 antagonist AM6545 and NOP agonist SCH221510 worsen DSS-induced colitis in mice.

Fabisiak, Adam · 2025

Mice with DSS-induced colitis treated with both AM6545 and SCH221510 showed significantly worse macroscopic disease scores and altered signaling compared to SCH221510 alone..

Ablation of hypothalamic Cnr1 leads to reduced meniscal mineral volume and articular cartilage damage in aging male mice.

Farhat, Eli · 2025

Hypothalamus-specific CB1 knockout mice showed reduced frailty at 17 months, less meniscal mineral volume loss, fewer blood vessels in the meniscus, and less cartilage damage.

Rapid suppression of neuropathic pain and somatosensory hyperactivity by nano-formulated cannabidiol.

Feng, Jingyu · 2025

An inclusion-complex-enhanced nano-micelle formulation (CBD-IN) significantly improved CBD delivery to the brain and fully suppressed both allodynia and hyperalgesia in a neuropathic pain mouse model with a single dose, while leaving normal sensorimotor and cognitive functions intact..

Aspirin-triggered lipoxin A4 reduces neuropathic pain and anxiety-like behaviours in male diabetic rats: antinociceptive enhancement by cannabinoid receptor agonists.

Ferreira, Matheus Vinícius · 2025

Aspirin-triggered lipoxin A4 (ATL) reduced mechanical hyperalgesia in diabetic rats both acutely and cumulatively.

Cannabinoid Ligand-Mediated Glycogen Depletion in Astrocytes Is Associated With Increased Intracellular Calcium, Energy Metabolism, and Membrane Dynamics.

Fink, Katja · 2025

CB1-selective agonist ACEA triggered rapid, transient calcium elevations in rat astrocytes, while CB2-biased ligands AM1241 and Gp1a produced sustained metabolic effects including prolonged increases in intracellular glucose and lactate.

Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis.

Flores-López, María · 2025

SUD patients had lower plasma 2-AG and 2-LG and elevated acylethanolamides vs controls.

Lifelong dietary Omega-3, -6, and -9 ratios shape adult behavior and response to adolescent THC exposure in rats.

Frajerman, Ariel · 2025

In 164 rats fed omega-3, -6, or -9 enriched diets from conception, diet significantly affected social behavior, anxiety, cognitive flexibility, and impulse control.

Endocannabinoid system gene expression in mesocorticolimbic brain regions of individuals with alcohol use disorder: A descriptive study.

García-Gutiérrez, María Salud · 2025

Individuals with AUD showed higher CNR1 expression in the prefrontal cortex (+125%) and nucleus accumbens (+78%), lower CNR2 expression in both regions (-50% and -49%), and region-specific differences in GPR55, FAAH, and MGLL expression..

Investigation of endocannabinoids in plasma and their correlation with physical fitness and resting state functional connectivity of the periaqueductal grey in women with fibromyalgia: An exploratory secondary study.

Ghafouri, Bijar · 2025

Significantly higher anandamide (AEA) concentrations were found in fibromyalgia patients compared to controls.

Cannabidiol improves learning and memory deficits and alleviates anxiety in 12-month-old SAMP8 mice.

Goodland, Monica N · 2025

In SAMP8 mice (a model for Alzheimer's disease), high-dose CBD (30 mg/kg daily for two months) significantly improved learning and memory in T-maze and novel object recognition tests.

Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.

Goodman, Marc T · 2025

In a case-control study of 231 participants, circulating anandamide (AEA) levels were significantly higher in pancreatitis patients compared to controls, with the highest levels in acute pancreatitis.

A Tourette Syndrome/ADHD-like Phenotype Results from Postnatal Disruption of CB1 and CB2 Receptor Signalling.

Gorberg, Victoria · 2025

Postnatal exposure to the CB1 blocker rimonabant in wild-type, CB1 knockout, and CB2 knockout mice produced distinct behavioral outcomes.

The Endocannabinoid System Drives Eosinophil Infiltration During Eosinophilic Esophagitis.

Gruden, Eva · 2025

In esophageal biopsies from patients with active eosinophilic esophagitis (EoE), the enzyme that breaks down the endocannabinoid 2-AG (monoacylglycerol lipase, MGL) was decreased, leading to elevated 2-AG levels.

Endocannabinoid system alterations in schizophrenia: association with cannabis use and antipsychotic medication.

Haddad, Natalia Mansur · 2025

In a study of 93 individuals (29 treatment-resistant schizophrenia on clozapine, 31 on other antipsychotics, 33 controls), those reporting lifetime cannabis use had significantly lower plasma 2-AG levels (p=0.011), and this remained the only significant factor in models controlling for confounders.

Assessment of leukocyte telomere length as a cellular aging marker through a quantitative PCR-based technique in individuals with a chronic addiction to the psychoactive drug delta-9-tetrahydrocannabinol. (Case control study).

Hassan, S · 2025

Among 30 chronic THC users and 30 age-matched controls (ages 30-65), cannabis users had significantly shorter leukocyte telomere length (LTL) (t(58)=-4.25, p<0.001).

Differential inhibitory effects of endocannabinoids on neuronal firing of mouse meningeal afferents.

Krivoshein, Georgii · 2025

AEA reduced meningeal nerve firing more profoundly and for longer than 2-AG.

The Effects of Indirect and Direct Modulation of Endocannabinoid System Function on Anxiety-Related Behavior in Mice Assessed in the Elevated Plus Maze Test.

Kruk-Slomka, Marta · 2025

CB1 antagonist AM 251 was anxiogenic.

Embryotoxicity Evaluation of Novel Synthetic Cannabinoid 4F-MDMB-BUTICA Using Zebrafish Embryos.

Kullebi, Berşan · 2025

LC50: 1.932 mg/L; EC50: 0.960 mg/L at 120 hours.

Cannabidiol Lipid Nanoparticles Stabilize Gut-Brain-Bone Axis Integrity and Enhance Neuroplasticity in Stressed Rats: A Comparison with Atomoxetine and Escitalopram.

Lapmanee, Sarawut · 2025

Stressed rats showed 2.03-fold increase in IL-6, 1.89-fold TNF-alpha, decreased BDNF and osteocalcin, and disrupted gut metabolites (SCFAs dropped from 155.3 to 94.83 umol/L).

The effects of cannabidiol and its main metabolites on human neural stem cells.

Latham, Leah E · 2025

CBD, 7-OH-CBD, and 7-COOH-CBD all dose-dependently reduced NSC viability.

Value signals guiding choices for cannabis versus non-drug rewards in people who use cannabis near-daily.

Lawn, Will · 2025

Subjective value signals for cannabis appeared in vmPFC, ventral striatum, and dorsal PCC as expected.

Recreational substance use is linked with difficulty in recalling personal experiences.

Levent, Adnan · 2025

Participants who reported recreational substance use recalled significantly fewer specific autobiographical memories than non-users and were more likely to omit responses entirely.

Adolescent exposure to Δ9-tetrahydrocannabinol impairs testicular function in young adult male mice.

Lim, Jinhwan · 2025

Adolescent THC exposure (postnatal days 30-43) decreased sperm numbers, increased seminiferous tubule degeneration, and impaired steroidogenesis with dysregulated expression of key enzymes (StAR protein and CYP17A1).

Preventive beneficial effects of cannabidiol in a reserpine-induced progressive model of parkinsonism.

Lima, Alvaro C · 2025

In mice given low-dose reserpine to progressively develop Parkinson-like symptoms, CBD (0.5 mg/kg) delayed the appearance of catalepsy and abnormal mouth movements.

Cannabinoid-Induced Hyperphagia is Mediated by Increased Meal Frequency and the Orexin-1 Receptor in Male Rats.

Lord, Magen N · 2025

Orally consumed cannabinoid edibles caused overeating by increasing meal frequency, not meal size.

Chronic cannabidiol administration modulates depressive and cognitive alterations induced by social isolation in male mice.

Lucindo, Marcel S S · 2025

CBD mitigated anhedonia (loss of pleasure) and reduced immobility in the tail suspension test in socially isolated mice.

Cannabidiol ameliorates seizures and neuronal damage in ferric chloride-induced posttraumatic epilepsy by targeting TRPV1 channel.

Ma, Lin · 2025

CBD reduced seizure severity, decreased EEG amplitude and total power, and lowered spike wave discharges in a ferric chloride-induced post-traumatic epilepsy model.

Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study.

MacNicol, Eilidh · 2025

THC increased whole-brain functional connectivity and clustering coefficient, with elevated blood flow in cortical and subcortical regions.

The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA enhance in vitro neurodifferentiation of NG108-15 cells, along with PGC-1α dysregulation and mitochondrial dysfunction.

Malheiro, Rui Filipe · 2025

Both synthetic cannabinoids enhanced neurite outgrowth at biologically relevant concentrations below 1 micromolar.

Effects of ketamine enantiomers on morphine and THC subjective effects in rats.

Malikowska-Racia, Natalia · 2025

In drug discrimination tests, no form of ketamine (R-, S-, or racemic) substituted for the subjective effects of either morphine or THC.

Cannabinoid Receptors Modulate Physiological Remodelling of the Blood-Testis Barrier.

Manfrevola, Francesco · 2025

CB1 knockout mice showed disrupted expression of blood-testis barrier components and infiltration of blood cells into seminiferous tubules, specifically at the Stage VIII-IX transition of the sperm production cycle.

Enhancement of the endocannabinoid system through monoacylglycerol lipase inhibition relieves migraine-associated pain in mice.

Mangutov, Elizaveta · 2025

The MAGL inhibitor ABD-1970 blocked cephalic allodynia in both acute and chronic nitroglycerin-induced migraine models.

Personality-based intergenerational effects of prenatal THC exposure in an inherited mouse model of social dominance and submissiveness.

Mari, Mohamed · 2025

In selectively bred dominant mice, prenatal THC exposure reduced body weight and increased anxiety-like behaviors.

Astroglial CB1 Reveal Sex-Specific Synaptic Effects of Amphetamine.

Mariani, Yamuna · 2025

Amphetamine impaired astroglial CB1 receptor-dependent synaptic plasticity in the nucleus accumbens of male mice but not females.

Adult Neurogenesis Is Regulated by the Endocannabinoid and Kisspeptin Systems.

Marino, Marianna · 2025

Both anandamide and kisspeptin-10 reduced hippocampal neurogenesis by dampening ERK signaling.

Cannabinoids and Extracellular Vesicles as Potential Biomarkers and Therapeutic Targets in Neuropsychiatric Disorders: A Hypothesis-Driven Review.

Marques, Bruno L · 2025

Emerging evidence indicates a bidirectional relationship: endocannabinoids can be loaded into extracellular vesicles for intercellular signaling, while THC and CBD alter EV release and cargo composition.

An astrocytic ensemble at vHip-NAc synapses modulates cognitive impairments induced by chronic tetrahydrocannabinol exposure.

Martín-Monteagudo, Cristina · 2025

THC increased astrocytic calcium activity and glutamate release in the nucleus accumbens via the ventral hippocampus circuit.

Cannabinoid Receptors Reduced Early Brain Damage by Regulating NOX-2 and the NLRP3 Inflammasome in an Animal Model of Intracerebral Hemorrhage.

Martínez-Torres, Ari Misael · 2025

WIN55,212-2 treatment after intracerebral hemorrhage significantly reduced hematoma formation, brain edema, blood-brain barrier disruption, and motor impairments.

Does acute stress induced via cold water immersion increase blood THC concentrations in regular cannabis users?

McCartney, Danielle · 2025

Cold water immersion (10 minutes at 10 degrees C) produced a small but significant stress response (increased heart rate, blood pressure, decreased calmness) and increased plasma free fatty acids and glycerol.

Activation of cannabinoid receptor CB1 leads to aberrant myelination in development.

Miramontes, Tania G · 2025

A cannabinoid agonist (WIN 55,212-2) caused oligodendrocytes to wrap myelin around neuronal cell bodies instead of only axons in developing zebrafish spinal cords.

Effects of cannabidiol (CBD) treatment on age-related cognitive decline in C57 mice.

Mirza Agha, Behroo · 2025

Fourteen-month-old mice given oral CBD for 7 months showed reduced inflammatory response in the brain and improvements in age-related cognitive decline when tested between 19-21 months of age across tasks measuring perirhinal cortex, hippocampal, amygdala, and motor function..

The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary.

Mirzaie, Vida · 2025

CB2 receptor blocking increased primary, preantral, and antral follicles along with ovarian volume, weight, and estrogen levels.

Structural changes of tubulin by interacting with Δ9-tetrahydrocannabinol: in-vitro and theoretical studies.

Mohammadkhani, Mina · 2025

THC reduced microtubule polymerization in a concentration-dependent manner and caused significant changes in tubulin secondary structure as measured by circular dichroism spectroscopy.

The synthetic cannabinoid WIN 55,212-2 attenuates cognitive and motor deficits and reduces amyloid load in 5XFAD Alzheimer mice.

Möller, Johanna E L · 2025

Aged 5XFAD Alzheimer's mice treated with WIN 55,212-2 for 42 days showed improved rotarod motor performance, rescued water maze memory deficits, and reduced amyloid plaque burden and astrogliosis in the cortex and hippocampus compared to vehicle-treated controls..

A Hidden Mark of a Troubled Past: Neuroimaging and Transcriptomic Analyses Reveal Interactive Effects of Maternal Immune Activation and Adolescent THC Exposure Suggestive of Increased Neuropsychiatric Risk.

Moreno-Fernández, Mario · 2025

While adolescent THC did not trigger visible behavioral disruptions, PET brain scans revealed alterations dependent on the combination of prenatal immune activation and THC.

Cannabinoid agonist WIN55,212-2 prevents scopolamine-induced impairment of spatial memory in rats.

Moreno-Rodríguez, Marta · 2025

Subchronic low-dose WIN55,212-2 (0.5 mg/kg) prevented scopolamine-induced spatial memory impairment in Barnes maze testing.

The role of endocannabinoid signaling in the cytoskeleton functionality in migrating neurons.

Morozov, Yury M · 2025

About 40% of migrating neurons in both CB1 receptor knockout mice and wild-type mice exposed to cannabinoid agonists showed nuclear envelope ruptures or "piercing nuclear hernias" (PNH), a novel form of cell pathology.

Cannabidiol and low-dose γ-radiation regulate alterations consequences of hepatic-encephalopathy induced by thioacetamide: neuroprotective and anti-inflammatory role.

Mostafa, Dalia M · 2025

CBD (20 mg/kg for 7 days) significantly reduced oxidative stress and inflammation in rats with liver damage-induced brain dysfunction.

Cannabidiol improves L-DOPA-induced dyskinesia and modulates neuroinflammation and the endocannabinoid, endovanilloid and nitrergic systems.

Nascimento, Glauce Crivelaro · 2025

CBD (30 mg/kg) and its fluorinated derivative PECS-101 (3 and 30 mg/kg) significantly reduced abnormal involuntary movements in L-DOPA-treated rats without reducing L-DOPA's motor benefits.

Cannabidiol modulates brain molecular alterations, gut microbiota dysbiosis and alcohol self-administration in a mouse model of fetal alcohol spectrum disorder.

Navarrete, F · 2025

Mice with prenatal alcohol exposure showed increased anxiety and depression-like behavior, sex-dependent changes in brain receptors and neurotransmitters, and gut microbiota dysbiosis.

Exogenous Administration of Delta-9-Tetrahydrocannabinol Affects Adult Hippocampal Neurotransmission in Female Wistar Rats.

Neves, Ana M · 2025

In the hippocampus of ovariectomized female rats, THC increased cholinergic receptor (CHRNA7), glutamate transporter (VGLUT), and GABA receptor expression when estrogen was absent, but decreased these same markers when estrogen was present.

A Preliminary Investigation of Brain Cannabinoid Receptor Type 1 (CB1R) Availability in Men with Opioid Use Disorder.

Nia, Anahita Bassir · 2025

Average CB1R availability (measured by volume of distribution) was 15% lower across 13 brain regions in men with OUD compared to healthy controls (p=0.04).

Long-term cannabinoid therapy can ameliorate chronic sleep deprivation-induced behavioral and neuroinflammatory changes in mice.

Niazi, Nasar Ullah Khan · 2025

Chronic sleep deprivation caused memory impairment, depression-like behavior, microglial activation, and elevated pro-inflammatory cytokines in mice.

Concurrent maternal stress and THC exposure during pregnancy alters adolescent behavioral outcomes and corticolimbic molecular programs.

Olusakin, Jimmy · 2025

All exposure groups (THC alone, stress alone, combined) showed impaired maternal behavior, with additive effects in the combined group.

Cannabidiol mechanism of action on modulating extinction and reinstatement of methamphetamine-seeking behavior: Targeting D2-like dopamine receptors in the hippocampus.

Omidiani, Seyed Erfan · 2025

A D2-like receptor antagonist (Sulpiride) at 1 and 4 micrograms significantly attenuated CBD's acceleration of methamphetamine conditioned place preference extinction (p<0.01, p<0.05).

Chronic exposure to a synthetic cannabinoid improves cognition and increases locomotor activity in Tg4-42 Alzheimer's disease mice.

Ott, Frederik W · 2025

Therapeutic WIN 55,212-2 treatment rescued recognition memory and spatial reference deficits.

Biochemical Role of the Endocannabinoid System in the Pathophysiology of Attention Deficit Hyperactivity Disorder: A Narrative Review and Future Directions.

Özmeral Erarkadaş, Kübra · 2025

Eleven preclinical and 2 clinical studies showed alterations in endocannabinoid system components linked to ADHD-related behaviors.

Acute effects of Δ9-tetrahydrocannabinol on computational measures of neurocognitive processes are related to recent cannabis use among adolescents and young adults.

Paige, K J · 2025

Overall, 7.5mg oral THC did not significantly alter cognitive performance compared to placebo.

Dysregulation of the endocannabinoid system - a key factor in the progression of multiple sclerosis?

Paraschiv, Andreea-Cristina · 2025

Newly diagnosed MS patients in acute relapse showed a non-significant trend toward lower plasma anandamide (AEA) compared to healthy controls (mean difference -5.95 ng/ml, p=0.098).

Prenatal cannabinoid exposure affects central cardiorespiratory control in young male and female rats.

Patrone, Luis Gustavo A · 2025

Prenatal cannabinoid exposure (WIN 55,212-2) caused lasting impairments in cardiorespiratory control in juvenile rats.

Acute cannabidiol treatment reverses behavioral impairments induced by embryonic valproic acid exposure in male mice.

Pedrazzi, J F C · 2025

In mice prenatally exposed to valproic acid (a model of autism), acute CBD at 30-60 mg/kg reversed pre-pulse inhibition deficits, decreased repetitive marble-burying, improved social interaction time, and restored object recognition memory.

Sex- and age-specific sensitivities of the endocannabinoid system in Alzheimer's disease revealed by PET imaging with [18F]FMPEP-d 2 and [18F]MAGL-2102.

Pees, Anna · 2025

PET imaging revealed dynamic changes in cannabinoid receptor 1 (CB1) and MAGL enzyme availability across Alzheimer's disease progression.

Age- and sex-dependent participation of the endocannabinoid system in locomotion and risk assessment of an ADHD rat model.

Penna, Daniel Bussinger de Souza · 2025

During adolescence, cannabinoid receptor activation aggravated hyperactivity and risky behaviors in ADHD model rats, with more pronounced effects in females.

"Modulatory role of baseline impulsivity on the acute and persistent effects of CB1 agonism on impulsive choice".

Pérez-Valenzuela, Enzo · 2025

The CB1/2 receptor agonist WIN 55,212-2 reduced impulsive choice in rats classified as highly impulsive but had no effect in low-impulsivity rats.

Epilepsy, neuroinflammation and cannabidiol What do we know thus far?

Pesántez Ríos, Gabriela · 2025

One of the challenges in understanding CBD's anti-seizure action is that it doesn't work through a single, clean mechanism the way most drugs do.

Timing matters: modeling the effects of gestational cannabis exposure on social behavior and microglia in the developing amygdala.

Pham, Aidan L · 2025

Cannabis is the most commonly used illicit drug during pregnancy, with rates rising as legalization expands.

Timing matters: modeling the effects of gestational cannabis exposure on social behavior and microglia in the developing amygdala.

Pham, Aidan L · 2025

Postnatal THC exposure (modeling late pregnancy) produced sex-specific changes in microglial phagocytosis during brain development and altered social behavior during the juvenile period.

Prophylactic efficacy of cannabidiol and sodium nitroprusside in a ketamine-model of schizophrenia: sex-dependent effects on positive-like and cognitive impairments.

Prado, Daniel B A · 2025

Rats pretreated with CBD and sodium nitroprusside (SNP) during brain development (postnatal days 12-32) and later challenged with ketamine showed sex-dependent responses.

Substance Use is Associated With College Students' Acute Parasympathetic Nervous System Responses to Challenge.

Rahal, Danny · 2025

Among 152 college students, those with larger declines in parasympathetic activity (vagal withdrawal) during a stress challenge task used cannabis more frequently.

Cannabidiol as a multifaceted therapeutic agent: mitigating Alzheimer's disease pathology and enhancing cognitive function.

Raïch, Iu · 2025

In the 5xFAD Alzheimer's mouse model, CBD decreased pTau and amyloid-beta aggregation, reduced their transport between brain regions, shifted microglia toward a neuroprotective M2 phenotype, reduced inflammatory cytokine release, and partially reversed neurite formation loss.

Considering the Effects of Cannabinoids and Exercise on the Brain: A Narrative Review.

Rajaei, Amir Yahya · 2025

The review identified mechanistic overlaps between cannabinoid and exercise effects on brain function through three key pathways: inflammation (both can be anti-inflammatory), vascular function (both affect cerebral blood flow), and neuroplasticity (both modulate brain-derived neurotrophic factor and synaptic plasticity).

Altered Network Function in Hippocampus After Sub-Chronic Activation of Cannabinoid Receptors in Early Adolescence.

Rehn, Johanna · 2025

The hippocampus—the brain's memory center—has an unusually high density of CB1 cannabinoid receptors.

Altered network function in hippocampus after sub-chronic activation of Cannabis receptors in peri-adolescence.

Rehn, Johanna · 2025

This is the preprint (bioRxiv) version of the study published as RTHC-00197.

The neuroprotective effect of cannabidiol is enhanced by resveratrol and alpha-lipoic acid in social isolation.

Ricciardi, Federica · 2025

Low-dose CBD (2.5 mg/kg) was ineffective alone, but when combined with resveratrol (20 mg/kg) or alpha-lipoic acid (10 mg/kg), it restored attack latency, reduced aggression, and decreased immobility in the tail suspension test to levels comparable to high-dose CBD (10 mg/kg).

Long-Term Efficacy and Safety of Inhaled Cannabis Therapy for Painful Diabetic Neuropathy: A 5-Year Longitudinal Observational Study.

Robinson, Dror · 2025

52 patients with painful diabetic neuropathy who had failed at least three prior pain medications used inhaled medical cannabis (20% THC) as add-on therapy for five years.

Cannabidiol reverses microglia activation and deficits of parvalbumin interneurons and their perineuronal nets in a MK-801-induced mouse model of schizophrenia.

Rodrigues da Silva, Naielly · 2025

Chronic MK-801 treatment (an NMDA receptor blocker) caused memory deficits and reduced gamma brain wave power in mice.

Coadministration antagonist dopamine receptor D4 with CB2 receptor agonist decreases binge-like intake of palatable food in mice.

Rodríguez-Serrano, Luis Miguel · 2025

In mice given 1-hour access to palatable food, a dopamine D4 receptor antagonist (L-745870) reduced binge-like intake.

Combined Endocannabinoid and Cyclooxygenase Inhibition Additively Attenuates Post-Surgical Pain.

Rodriguez, Carl E B · 2025

MAGL inhibitors (JZL184 and MJN110) reduced mechanical pain sensitivity after hindpaw surgery in mice.

Genetic characterization of the endocannabinoid system and psychiatric features in patients with migraine and medication overuse headache.

Romozzi, Marina · 2025

FAAH (fatty acid amide hydrolase), the enzyme that breaks down the endocannabinoid anandamide, showed significantly lower gene expression in medication overuse headache (MOH) patients compared to episodic migraine (EM) patients.

A cannabidiol (CBD) lipid-based nanoemulsion induces anxiolytic- and panicolytic-like effects and increases FosB/deltaFosB immunoreactivity in serotonergic cells of the dorsal raphe.

Rosário, Bárbara A · 2025

Chronic oral CBD nanoemulsion (2.5 mg/kg for 21 days) produced anxiolytic and panicolytic effects in rats tested on the elevated T-maze.

Associations of cardiorespiratory fitness and muscular fitness with plasma levels of endocannabinoids and their analogues in adults with diagnosed depression: SONRIE study.

Ruiz-Muñoz, Manuel · 2025

Among 80 adults with mild-to-moderate depression, better cardiorespiratory fitness and jump performance were inversely associated with plasma levels of both main endocannabinoids: anandamide and 2-AG.

Sex differences in the effects of maternal voluntary oral Cannabis consumption on the metabolic outcomes of high-fat diet in adult offspring.

Sallam, Nada A · 2025

Pregnant mice consumed cannabis extract (5 mg/kg THC daily) from early gestation through postnatal day 10.

Cannabis-enriched oral Actinomyces induces anxiety-like behavior via impairing mitochondria and GABA signaling.

Salman, Tabinda · 2025

Actinomyces species, previously found to be enriched in chronic cannabis smokers' oral microbiome, induced anxiety-like behaviors in mice when inoculated orally.

Maternal Immune Activation and the Endocannabinoid System: Focus on Two-Hit Models of Schizophrenia.

Santoni, Michele · 2025

Despite theoretical expectations, several preclinical studies failed to show that adolescent cannabinoid exposure worsened behavioral or neurological outcomes in animals exposed to maternal immune activation, challenging the straightforward two-hit model..

Neuroprotective effects of a cannabidiol nanoemulsion in a rotenone-induced rat model of Parkinson's disease: Insights into the gut-brain axis.

Santos, Júlio César Claudino Dos · 2025

CBD nanoemulsion treatment restored glutathione levels (which had dropped 38-47% from rotenone treatment), reduced alpha-synuclein accumulation in both the striatum and duodenum, and normalized glial activation markers GFAP and IBA1 to control levels..

Oxidative stress and mitochondrial dysfunction in neuronal cells induced by commercial CBD products.

Sanz-Pérez, A · 2025

Treatment with commercial CBD samples at 50 micrograms/mL significantly increased reactive oxygen species, reduced the GSH/GSSG ratio (indicating oxidative stress), elevated lipid peroxidation, inhibited key antioxidant enzymes (CAT, SOD, GPx, GR), and decreased mitochondrial content in neuroblastoma cells..

Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.

Sarikahya, Mohammed H · 2025

Omega-3 supplementation normalized many neuronal and neurochemical abnormalities in male offspring's prefrontal cortex, nucleus accumbens, and ventral hippocampus.

Cannabidiol Enhances Stress-Induced Cellular Damage: Potential Contribution of Kv2.1 Inhibition.

Sayehmiri, Fatemeh · 2025

CBD enhanced Kv2.1 channel inactivation in a dose-dependent manner (3-3000 nM), and cells expressing Kv2.1 that were treated with CBD showed marked morphological deterioration and decreased viability under nutrient deprivation, despite Kv2.1 normally being protective in stressed cells..

Associations of prenatal tobacco and insecticide co-exposures with neurobehavioral responses among children born to pregnant women exposed to cannabis.

Sehgal, Neha · 2025

Prenatal insecticides (pyrethroids and organophosphates) were the primary exposures associated with child neurobehavior.

Upregulation of endocannabinoid signaling in vivo restores striatal synaptic plasticity and motor performance in Huntington's disease mice.

Sepers, Marja D · 2025

Three weeks of oral JZL184 (a 2-AG degradation inhibitor) significantly increased 2-AG levels in striatal tissue.

Cannabidiol attenuates methamphetamine-induced oxidative neurotoxicity via regulating transient receptor potential vanilloid type 1.

Shen, Baoyu · 2025

In METH users' brain tissue, TRPV1 overactivation, calcium overload, oxidative stress, and apoptosis were observed.

Evidence on the effect of in-utero cannabis exposure in neonates.

Thayyil, Basel · 2025

This review synthesizes the accumulating evidence on what happens when a developing fetus is exposed to cannabis—a question of increasing urgency as both cannabis use during pregnancy and THC potency rise simultaneously. The pharmacological reality is concerning.

Cannabinoid type 1 receptors in the mice prefrontal cortex regulate object location memory acquisition via GABAergic neurons.

Tokutake, Tomohiro · 2025

This study zeroed in on a specific question: which phase of memory does THC-like activation in the prefrontal cortex disrupt, and through what mechanism? The researchers injected a CB1 receptor agonist (ACPA) directly into the prefrontal cortex of mice before different stages of two memory tests.

Neurodevelopmental effects of exogenous cannabinoids on endocannabinoid and GABAergic neurotransmission.

Wiley, Miles T · 2025

This review presents a fascinating and underappreciated mechanism by which prenatal cannabis could affect brain development: the GABA switch. Here's the background: during early brain development, GABA—which becomes the brain's primary inhibitory neurotransmitter in adults—actually functions as an excitatory signal.

Cannabidiol and Tetrahydrocannabinol Antinociceptive Activity is Mediated by Distinct Receptors in Caenorhabditis elegans.

Boujenoui, Fatma · 2024

CBD and THC both reduced the nocifensive response to noxious heat in C.

Extracellular Vesicles and Endocannabinoid Signaling in Patients with COVID-19.

Brandes, Florian · 2024

Except for anandamide, endocannabinoid concentrations (2-AG, SEA, PEA, OEA) were significantly higher in extracellular vesicles than in plasma, and these EV-endocannabinoid levels increased with COVID-19 severity.

Delta-9-Tetrahydrocannabinol Blocks Bone Marrow-Derived Macrophage Differentiation through Elimination of Reactive Oxygen Species.

Carter, Taylor H · 2024

THC blocked M-CSF-induced macrophage differentiation from bone marrow cells through a receptor-independent mechanism.

Unveiling the link between chronic pain and misuse of opioids and cannabis.

Dagher, Merel · 2024

Over 50 million Americans live with chronic pain, and many don't receive adequate treatment.

The Impacts of Adolescent Cannabinoid Exposure on Striatal Anxiety- and Depressive-Like Pathophysiology Are Prevented by the Antioxidant N-Acetylcysteine.

De Felice, Marta · 2024

Adolescent THC exposure caused lasting anxiety- and depressive-like behaviors in rats, along with molecular and neuronal abnormalities in the nucleus accumbens.

Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus.

DeVuono, Marieka V · 2024

Prenatal THC and CBD exposure (alone and combined) caused low birth weight and sex-specific changes in adolescent rats: altered anxiety, temporal order memory, social cognition, and sensorimotor gating.

Endocannabinoid Receptor 2 Function is Associated with Tumor-Associated Macrophage Accumulation and Increases in T Cell Number to Initiate a Potent Antitumor Response in a Syngeneic Murine Model of Glioblastoma.

Duan, Jin · 2024

CB2 receptor antagonist AM630 induced a potent antitumor response in glioblastoma-bearing mice, with 50% survival at day 40 when all control mice (median survival 28 days) and CB2 agonist-treated mice (median survival 21 days) had died.

Epigenetic effects of cannabis: A systematic scoping review of behavioral and emotional symptoms associated with cannabis use and exocannabinoid exposure.

Machado, Ana Sofia · 2024

Across 37 included studies, cannabis exposure was most consistently associated with global hypomethylation and changes at specific genes related to dopamine signaling (DRD2, COMT), cellular function (AKT1, STAT3), and neural development (NCAM1, DLGAP2).

Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors.

Manduca, Antonia · 2024

CBD corrected short-term recognition memory deficits in Fmr1 knockout rats.

Medicinal cannabis extracts are neuroprotective against Aβ1-42-mediated toxicity in vitro.

Marsh, Dylan T · 2024

Five proprietary cannabis extracts were tested against amyloid-beta toxicity in PC12 cells.

Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia.

Martínez-Rivera, Arlene · 2024

Pharmacologically boosting 2-AG levels via MAGL inhibition attenuated opioid reward in both conditioned place preference and self-administration paradigms without affecting opioid analgesia.

CB1 Receptor Activation Provides Neuroprotection in an Animal Model of Glutamate-Induced Excitotoxicity Through a Reduction of NOX-2 Activity and Oxidative Stress.

Martínez-Torres, Ari Misael · 2024

WIN55,212-2 reduced brain injury, improved motor activity, decreased ROS production, lowered neuroinflammation markers (TNF-alpha, NF-kB, Iba-1), and reduced edema in a glutamate excitotoxicity model.

Endocannabinoid regulation in the cervix during pregnancy: insights into molecular mechanisms of premature labor.

Marvaldi, Carolina · 2024

Anandamide and 2-AG increased in the cervix of pregnant mice.

Anandamide and WIN 55212-2 Afford Protection in Rat Brain Mitochondria in a Toxic Model Induced by 3-Nitropropionic Acid: an In Vitro Study.

Maya-López, Marisol · 2024

Both anandamide and WIN 55212-2 ameliorated 3-NP toxic effects on brain mitochondria.

Heteromers Formed by GPR55 and Either Cannabinoid CB1 or CB2 Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients.

Menéndez-Pérez, Carlota · 2024

Using proximity ligation assays and immunohistochemistry on postmortem brain samples, researchers identified CB1R-GPR55 and CB2R-GPR55 heteromers in the human prefrontal cortex for the first time.

Predicting changes in driving performance in individuals who use cannabis following acute use based on self-reported readiness to drive.

Miller, Ryan · 2024

Can cannabis users tell when they shouldn't drive? This study takes a more granular approach than the French study (RTHC-00093) by examining not just whether self-assessment correlates with impairment, but what factors make self-assessment more or less accurate. Regular cannabis users (at least monthly) were dosed with cannabis containing approximately 6.18% THC, then drove on a simulator at 30, 90, and 180 minutes post-dose.

Effects of in utero delta-9-tetrahydrocannabinol (THC) exposure on fetal and infant musculoskeletal development in a preclinical nonhuman primate model.

Moellmer, Samantha A · 2024

RNA analysis of fetal and infant skeletal muscle using a 770-gene neuroinflammatory panel revealed that prenatal THC exposure had narrow overall effects on muscle development.

Lack of interactions between prenatal immune activation and Δ9-tetrahydrocannabinol exposure during adolescence in behaviours relevant to symptom dimensions of schizophrenia in rats.

Moreno-Fernández, Mario · 2024

MIA impaired working memory and sensorimotor gating but surprisingly increased sociability.

Fetal Cannabinoid Syndrome: Behavioral and Brain Alterations of the Offspring Exposed to Dronabinol during Gestation and Lactation.

Navarro, Daniela · 2024

Offspring exposed to dronabinol (10 mg/kg twice daily) from gestational day 5 through postnatal day 21 displayed increased anxiogenic and depressive-like behaviors, cognitive impairment, disrupted reward system function, and increased alcohol consumption motivation at postnatal day 60.

A narrative review of the therapeutic and remedial prospects of cannabidiol with emphasis on neurological and neuropsychiatric disorders.

Omotayo, Oluwadara Pelumi · 2024

CBD antagonizes pro-inflammatory cytokines, regulates oxidative stress, downregulates TNF-alpha, restores BDNF and serotonin across neurological disorders..

Long-term effects on cardiorespiratory and behavioral responses in male and female rats prenatally exposed to cannabinoid.

Patrone, Luis Gustavo A · 2024

Males showed increased chemosensitivity to CO2 and O2, while females exhibited decreased sensitivity.

Oral pre- and early postnatal cannabis exposure disinhibits ventral tegmental area dopamine neuron activity but does not influence cocaine preference in offspring in mice.

Peterson, Colleen S · 2024

Male offspring had decreased GABAergic input, depolarized resting membrane potential, and increased spontaneous firing of VTA dopamine neurons.

Timeframe Analysis of Novel Synthetic Cannabinoids Effects: A Study on Behavioral Response and Endogenous Cannabinoids Disruption.

Pineda Garcia, Jorge Carlos · 2024

All three synthetic cannabinoids (MDMB-CHMINACA, 5F-ADB-PINACA, APICA) caused locomotor disruption and sustained anxiety at all time points (1, 3, 5 hours).

Cannabidiol Reduced the Severity of Gastrointestinal Symptoms of Opioid Withdrawal in Male and Female Mice.

Scicluna, Rhianne L · 2024

CBD at 10, 30, and 100 mg/kg dose-dependently reduced gastrointestinal symptoms (diarrhea, fecal output, weight loss) during both precipitated and spontaneous oxycodone withdrawal in male mice and during precipitated withdrawal in female mice.

In Vitro and In Vivo Anti-Inflammatory and Antidepressant-like Effects of Cannabis sativa L. Extracts.

Shin, Joonyoung · 2024

Cannabis leaf extract (30 mg/kg) reduced immobility in the forced swimming test and increased sucrose preference in LPS-challenged mice, suggesting antidepressant effects.

Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism.

Shrader, Sarah H · 2024

High-dose CBD (50 mg/kg) reduced repetitive self-grooming and hyperlocomotion in BTBR mice.

Fatty Acid Amides Suppress Proliferation via Cannabinoid Receptors and Promote the Apoptosis of C6 Glioma Cells in Association with Akt Signaling Pathway Inhibition.

Silva, Nágila Monteiro da · 2024

Two fatty ethanolamides (FAA1 and FAA2) reduced C6 glioma cell viability, proliferation, and migratory potential in a dose-dependent manner.

Exploring Cannabinoids with Enhanced Binding Affinity for Targeting the Expanded Endocannabinoid System: A Promising Therapeutic Strategy for Alzheimer's Disease Treatment.

Stanciu, Gabriela Dumitrita · 2024

Chronic treatment with JWH-133 (a selective CB2 agonist) and Cannabis sativa extract reduced anxiety-like behavior and partially reversed recognition memory deficits in APP/PS1 mice.

Cannabigerolic Acid (CBGA) Inhibits the TRPM7 Ion Channel Through its Kinase Domain.

Suzuki, Sayuri · 2024

CBGA had the strongest inhibitory effect on TRPM7 channels among all major and minor cannabinoids tested.

Sex-specific maladaptive responses to acute stress upon in utero THC exposure are mediated by dopamine.

Valeria, Serra · 2024

Only male offspring prenatally exposed to THC showed a compromised balance of stress hormone receptors (mineralocorticoid and glucocorticoid) in the ventral tegmental area, alongside stress-induced disruption of sensorimotor gating (PPI).

Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus.

Aguiar, Andrey F L · 2023

CBD-enriched extract (3 mg/kg/day CBD for 15 days) did not affect food intake, locomotion, or cognitive performance in adolescent rats.

Altered endocannabinoid metabolism compromises the brain-CSF barrier and exacerbates chronic deficits after traumatic brain injury in mice.

Ahluwalia, Meenakshi · 2023

TBI increased expression of enzymes that break down endocannabinoids (MAGL, FAAH, Cox-2), leading to reduced 2-AG and AEA levels in plasma.

Sleep disturbance after cessation of cannabis administration in mice.

Asano, Takashi · 2023

During cannabinoid administration, there was no difference in sleep/wake patterns between treated and control mice.

Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids.

Barrera-Conde, Marta · 2023

First-episode psychosis patients with prior cannabis use (FEP/c) had lower CDK5 and higher PSD95 levels compared to those without cannabis use (FEP/nc), and showed fewer social functioning deficits.

A type II cannabis extract and a 1:1 blend of Δ(9)-tetrahydrocannabinol and cannabidiol display distinct antinociceptive profiles and engage different endocannabinoid targets when administered into the subarachnoid space.

Benredjem, Besma · 2023

When injected into the spinal fluid of rats with diabetic neuropathy, a type II cannabis extract and a 1:1 THC:CBD mix produced different antinociceptive responses despite equivalent THC content.

Sexually Dimorphic Adolescent Trajectories of Prefrontal Endocannabinoid Synaptic Plasticity Equalize in Adulthood, Reflected by Endocannabinoid System Gene Expression.

Bernabeu, Axel · 2023

Endocannabinoid-mediated long-term depression (eCB-LTD) was present in juvenile female rats but only appeared at puberty in males.

Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.

Bilel, Sabrine · 2023

Repeated JWH-018 treatment (6 mg/kg daily for 7 days) induced psychomotor agitation, reduced social dominance and recognition memory, impaired prepulse inhibition, disrupted hippocampal long-term potentiation, decreased BDNF expression, and altered endocannabinoid system components in the striatum and hippocampus, all persisting 15+ days after last exposure..

Characterization of cannabinoid plasma concentration, maternal health, and cytokine levels in a rat model of prenatal Cannabis smoke exposure.

Black, Tallan · 2023

Pregnant rats exposed to high-THC or high-CBD cannabis smoke from gestational day 6-20 showed different inflammatory profiles than those receiving injected THC or CBD.

Chronic exposure to a synthetic cannabinoid alters cerebral brain metabolism and causes long-lasting behavioral deficits in adult mice.

Bouter, Caroline · 2023

Treatment with WIN 55,212-2 (3 mg/kg) led to hypometabolism in the hippocampus, cerebellum, amygdala, and midbrain, persisting even after prolonged abstinence.

Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats.

Brancato, Anna · 2023

Rats exposed to binge-like alcohol during adolescence showed compromised defensive social behavior, blunted stress responses, and abnormal dopamine/glutamate plasticity in the nucleus accumbens.

Divergent effects of oral cannabis oil extracts marketed as C. indica or C. sativa on exertion of cognitive effort in rats.

Brodie, Hannah G · 2023

Both cannabis products (matched for THC and CBD content) slowed response times at higher doses, but only the indica-labeled oil at 10 mg/kg THC reduced the proportion of trials where rats chose high-effort/high-reward options.

CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity.

Castelli, Valentina · 2023

Prenatal THC exposure (2 mg/kg, gestational days 5-20) impaired spatial and configural memory and disrupted hippocampal plasticity markers in adolescent rats.

Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration.

Chen, Long · 2023

CBD demonstrated protective effects against amyloid-beta toxicity both in cell cultures and in mice, ameliorating cognitive impairment.

Behavioral, biochemical and histopathological toxic profiles induced by sub-chronic cannabimimetic WIN55, 212-2 administration in mice.

Omran, Ghada A · 2023

WIN55,212-2 produced dose-dependent anxiogenic effects and reduced locomotor activity, with female mice less compromised than males.

Monoacylglycerol Lipase Inhibition Prevents Short-Term Mitochondrial Dysfunction and Oxidative Damage in Rat Brain Synaptosomal/Mitochondrial Fractions and Cortical Slices: Role of Cannabinoid Receptors.

Paredes-Ruiz, Karen Jaqueline · 2023

JZL184 attenuated 3-NP-induced mitochondrial dysfunction and lipid peroxidation.

Cannabinoid CB1 Receptor Expression and Localization in the Dorsal Horn of Male and Female Rat and Human Spinal Cord.

Parnell, Jessica · 2023

CB1 immunoreactivity was significantly higher in the superficial vs deep dorsal horn in both species, conserved across sex.

Effects of prenatal exposure to THC on hippocampal neural development in offspring.

Peng, Hao · 2023

THC administration during gestational days 5.5-12.5 altered neuronal cell composition in offspring hippocampus at PND21.

Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity.

Pinky, Priyanka D · 2023

Prenatal WIN55,212-2 caused hippocampal-dependent memory deficits in adolescent offspring associated with decreased long-term potentiation, enhanced long-term depression, and imbalanced GluN2A/GluN2B signaling.

Mechanisms of cannabinoid tolerance.

Piscura, Mary K · 2023

Anyone who uses cannabis regularly knows tolerance is real: the same dose produces weaker effects over time.

Virtual screening and in vitro experiments highlight cannabidiol as a drug-like phosphodiesterase 9 inhibitor.

Ribaudo, Giovanni · 2023

Computational screening of 7 phytocannabinoids and 4 terpenes identified CBD as a potential PDE9 ligand with a calculated binding energy of -9.1 kcal/mol and stable molecular dynamics interaction.

The Reversal of Empathy-Induced Hypernociception in Male Mice by Intra-Amygdala Administration of Midazolam and Cannabidiol Depends on 5-HT3 Receptors.

Rodrigues Tavares, Lígia Renata · 2023

Mice housed with chronic pain partners showed hypernociception and increased 5-HT3 receptor and GAD67 expression in the amygdala.

Effects of the cannabinoid CB1-receptor neutral antagonist AM4113 and antagonist/inverse agonist rimonabant on fentanyl discrimination in male rats.

AlKhelb, Dalal · 2022

AM4113 (0.32-1.0 mg/kg) effectively blocked fentanyl discrimination at doses that did not reduce food-maintained responding.

Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model.

Alzu'bi, Ayman · 2022

XLR-11 treatment caused upregulation of oxidative stress genes (NOX2, NOX4, iNOS), inflammatory markers (TNF-alpha, IL-1beta, IL-6), and pro-apoptotic gene Bax.

The Effect of Cannabidiol Coated by Nano-Chitosan on Learning and Memory, Hippocampal CB1 and CB2 Levels, and Amyloid Plaques in an Alzheimer's Disease Rat Model.

Amini, Mohammadali · 2022

Nano-chitosan-coated CBD significantly reduced escape latency and travel distance in memory tests while increasing time in the target zone.

Cannabinoid CB1 receptors regulate salivation.

Andreis, Kelsey · 2022

CB1 receptors are expressed on cholinergic nerve axons innervating the submandibular gland but not on gland cells.

Medical cannabis and cannabidiol: A new harvest for Malawi.

Bandawe, Gama · 2022

CBD has an established role in treating epilepsy (FDA-approved Epidiolex) and emerging evidence for antipsychotic and neuroprotective properties, with the authors proposing potential adjunctive use for neuropsychological complications of malaria..

Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling.

Borgonetti, Vittoria · 2022

The cannabis extract significantly reduced pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in activated microglia, while pure CBD only partially reduced them and beta-caryophyllene was ineffective.

Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis.

Bortoletto, Riccardo · 2022

Cannabis exposure in autistic individuals may exert disruptive epigenetic effects on brain regions critical to schizophrenia pathophysiology.

Differential Enantiomer-Specific Signaling of Cannabidiol at CB1 Receptors.

Bosquez-Berger, Taryn · 2022

(+)-CBD had a 5-fold lower inhibition constant for displacing a CB1 agonist and was approximately 10 times more potent at inhibiting depolarization-induced suppression of excitation (DSE), a form of endocannabinoid-mediated synaptic plasticity.

Anti-aversive effect of 2-arachidonoylglycerol in the dorsolateral periaqueductal gray of male rats in contextual fear conditioning and Vogel tests.

Brianis, Rayssa C · 2022

2-AG injected into the dorsolateral PAG reduced contextual fear expression and produced anxiolytic effects in the Vogel conflict test, both dependent on CB1 and CB2 receptor activation.

The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages.

Chahkandi, Mohadeseh · 2022

Marijuana alone improved spatial learning in both young and old female rats.

Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer's disease.

Coles, Madilyn · 2022

CBD reversed and prevented cognitive deficits in AD rodent models through anti-inflammatory, antioxidant, and neuroprotective mechanisms.

Cannabinoids in Late Life Parkinson's Disease and Dementia: Biological Pathways and Clinical Challenges.

Costa, Alana C · 2022

This review confronted a growing clinical reality: older adults with Parkinson's disease and dementia are increasingly using cannabinoids, but the evidence supporting this use is almost entirely preclinical.

Inhibiting Endocannabinoid Hydrolysis as Emerging Analgesic Strategy Targeting a Spectrum of Ion Channels Implicated in Migraine Pain.

Della Pietra, Adriana · 2022

MAGL and FAAH, the enzymes that degrade endocannabinoids, are distributed differently across brain regions involved in migraine pain.

Cannabinoids Reduce Extracellular Vesicle Release from HIV-1 Infected Myeloid Cells and Inhibit Viral Transcription.

DeMarino, Catherine · 2022

CBD significantly reduced the concentration of extracellular vesicles (EVs) released from HIV-1 infected U1 monocytes and primary macrophages.

Cannabidiol Interferes with Establishment of Δ9-Tetrahydrocannabinol-Induced Nausea Through a 5-HT1A Mechanism.

DeVuono, Marieka V · 2022

CBD (5 mg/kg) blocked the establishment of THC-induced conditioned gaping (a measure of nausea) in rats, and this effect was reversed by a 5-HT1A receptor antagonist (WAY-100635).

Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes.

Di Meo, Camilla · 2022

CBG, CBC, THCV, and CBGA each produced distinct patterns of gene and protein expression changes in ECS components of human keratinocytes.

The Cannabinoid Receptor Type 1 Positive Allosteric Modulator ZCZ011 Attenuates Naloxone-Precipitated Diarrhea and Weight Loss in Oxycodone-Dependent Mice.

Dodu, Julien C · 2022

ZCZ011 completely eliminated naloxone-precipitated diarrhea and weight loss in oxycodone-dependent mice and reduced paw flutters by about half.

Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry: New Insights from In Vivo and In Silico Models.

Domingos, Luana B · 2022

CBD appears to regulate DNA methylation both directly, by binding to methylation enzymes (DNMTs), and indirectly, through neurotransmitter-mediated signaling pathways.

Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation.

F Amil, Adrián · 2022

Chronic cannabis use causes CB1 receptor downregulation in the cerebellum, which the researchers propose leads to a generalized underestimation of sensory errors.

Acidic Cannabinoids Suppress Proinflammatory Cytokine Release by Blocking Store-operated Calcium Entry.

Faouzi, Malika · 2022

Several minor cannabinoids, mainly the carboxylic acid derivatives and especially CBGA, demonstrated high potency in blocking store-operated calcium entry (SOCE) in immune cell lines.

The Cannabinoid Receptor Agonist, WIN-55212-2, Suppresses the Activation of Proinflammatory Genes Induced by Interleukin 1 Beta in Human Astrocytes.

Fields, Jerel Adam · 2022

Transcriptomic analysis showed WIN treatment robustly inhibited the inflammatory response triggered by IL1-beta in human astrocytes.

Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction.

Franzen, Jaqueline M · 2022

Systemic CBD reduced freezing behavior for over a week in female rats when given during the reconsolidation window (within 6 hours of memory reactivation).

Therapeutic potential of PIMSR, a novel CB1 receptor neutral antagonist, for cocaine use disorder: evidence from preclinical research.

Galaj, Ewa · 2022

PIMSR dose-dependently inhibited cocaine self-administration, shifted the dose-response curve downward, decreased motivation to seek cocaine, and reduced cue-induced reinstatement.

Interactions of Noradrenergic, Glucocorticoid and Endocannabinoid Systems Intensify and Generalize Fear Memory Traces.

Gazarini, Lucas · 2022

Low doses of adrenaline, corticosterone, or the CB1 antagonist AM251 had no individual effects on fear memory.

The effects of fatty acid amide hydrolase inhibition and monoacylglycerol lipase inhibition on habit formation in mice.

Gianessi, Carol A · 2022

Both FAAH inhibition (increasing anandamide) and MAGL inhibition (increasing 2-AG) disrupted habit formation during operant training in mice.

Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex.

Gorberg, Victoria · 2022

CB2 knockout mice showed higher frequencies of repetitive behaviors.

Neural functional connectivity changes to psychosocial stress in young adults with bipolar disorder and preliminary associations with clinical trajectories.

Kirsch, Dylan E · 2022

People with bipolar disorder showed increased right amygdala-rostral prefrontal cortex connectivity during stress compared to controls.

Thalamocortical functional connectivity and cannabis use in men with childhood attention-deficit/hyperactivity disorder.

Lee, Sanghyun · 2022

Cannabis-using adults with childhood ADHD (n=18) had significantly decreased thalamic-parietal functional connectivity compared to non-users (n=15).

The Cannabis-Induced Epigenetic Regulation of Genes Associated with Major Depressive Disorder.

Mohammad, Guldar Sayed · 2022

Cross-referencing cannabis methylation studies with the largest depression GWAS revealed that multiple depression-associated genes are epigenetically regulated by cannabis exposure.

CBD-mediated regulation of heroin withdrawal-induced behavioural and molecular changes in mice.

Navarrete, Francisco · 2022

Mice given CBD (10 and 20 mg/kg) during spontaneous heroin withdrawal showed significantly reduced anxiety-like behavior, motor hyperactivity, and somatic withdrawal signs compared to untreated heroin-dependent mice..

Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry.

Sarikahya, Mohammed H · 2022

Prenatal THC exposure induced lasting behavioral and neuronal changes in male and female rat offspring resembling neuropsychiatric conditions, with profound disruption of fatty acid pathways in the developing brain..

Cannabis alters DNA methylation at maternally imprinted and autism candidate genes in spermatogenic cells.

Schrott, Rose · 2022

In an in vitro human spermatogenesis model, cannabis exposure significantly altered DNA methylation at maternally imprinted genes (SGCE, GRB10, PEG3) and autism candidate genes (HCN1, NR4A2) in spermatogonial stem cell-like and spermatid-like cells..

White Matter Microstructure and Gray Matter Volume in Cannabis-Induced Psychosis and Schizophrenia With Cannabis Use.

Shah, Raghav · 2022

Participants with schizophrenia and cannabis use (SZC) had widespread white matter microstructural abnormalities, while those with cannabis-induced psychosis (CIP) had fewer WM disruptions and greater gray matter volumes in the cerebellum and frontal regions..

Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.

Smith, Robert C · 2022

The 13.4% THC group showed significantly increased CB2 and DNMT3A mRNA levels at 4 hours post-smoking compared to placebo.

Administration of Δ9-Tetrahydrocannabinol Following Controlled Cortical Impact Restores Hippocampal-Dependent Working Memory and Locomotor Function.

Song, Shijie · 2022

THC-treated mice exhibited marked improvement in Y-maze working memory performance and recovered to normal rotarod performance by 2 weeks after brain injury.

Convulsant doses of abused synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA and JWH-018 do not elicit electroencephalographic (EEG) seizures in male mice.

Wilson, Catheryn D · 2022

Convulsant doses of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 did not produce seizure patterns on EEG despite causing visible convulsions.

Synthetic cannabinoids reduce the inflammatory activity of microglia and subsequently improve neuronal survival in vitro.

Young, Alexander P · 2022

Pro-inflammatory microglia released cytotoxic factors that killed cultured neurons.

Behavioral and Molecular Responses to Exogenous Cannabinoids During Pentylenetetrazol-Induced Convulsions in Male and Female Rats.

Zirotti Rosenberg, Antonella · 2022

WIN prevented convulsions of medium severity in both female and male rats.

Lower dACC glutamate in cannabis users during early phase abstinence.

Zuo, Chun S · 2022

dACC glutamate was significantly lower in cannabis users compared to controls from baseline through day 21 of abstinence (F=5.90, p=0.022).

Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions.

Zuo, Yanning · 2022

THC-treated mice showed memory and social behavior changes in late adolescence.

Chronic administration of synthetic cannabidiol induces antidepressant effects involving modulation of serotonin and noradrenaline levels in the hippocampus.

Abame, Melkamu Alemu · 2021

Only the high dose (100 mg/kg) produced antidepressant effects in the forced swim test after 7 days of administration.

Inflammatory biomarker relationships with helper T cell GPR15 expression and cannabis and tobacco smoking.

Andersen, Allan M · 2021

In a cohort of 62 primarily African American young adults, researchers measured a specific immune marker: GPR15 expression on helper T cells.

Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy.

Anderson, Lyndsey L · 2021

Screening identified CBGA, CBDVA, and CBGVA as novel anticonvulsants.

The role of endocannabinoid pathway in the neuropathology of Alzheimer's disease: Can the inhibitors of MAGL and FAAH prove to be potential therapeutic targets against the cognitive impairment associated with Alzheimer's disease?

Bajaj, Shivanshu · 2021

MAGL and FAAH inhibitors have shown potential to protect neurons from amyloid-beta toxicity, reduce tau phosphorylation, combat oxidative stress, and stimulate neurotrophins that support brain repair.

Cannabinoid-induced changes in the immune system: The role of microRNAs.

Bhatt, Hirva K · 2021

Cannabinoid exposure changes the expression of specific microRNAs in various immune cell types, and these miRNA changes appear to drive many of the observed anti-inflammatory and immunomodulatory effects of cannabinoids acting through CB1 and CB2 receptors..

Epigenetic Mediation of AKT1 rs1130233's Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing.

Blest-Hopley, Grace · 2021

The number of A alleles at AKT1 rs1130233 and methylation percentage at the CpG11-12 site independently predicted greater THC effects on parahippocampal/amygdala activation during fear processing.

Disrupted parahippocampal and midbrain function underlie slower verbal learning in adolescent-onset regular cannabis use.

Blest-Hopley, Grace · 2021

Cannabis users showed significantly slower learning across repeated trials (p = 0.032).

A Phase-2 Pilot Study of a Therapeutic Combination of Δ9-Tetrahydracannabinol and Palmitoylethanolamide for Adults With Tourette's Syndrome.

Bloch, Michael H · 2021

THX-110 (combination of THC max 10 mg/day and PEA 800 mg/day) produced statistically significant tic improvement within one week.

Neurodevelopmental Effects of Cannabis Use in Adolescents and Emerging Adults with ADHD: A Systematic Review.

Cawkwell, Philip B · 2021

No study found an additive or interaction effect between ADHD and cannabis use on neuropsychological tasks of executive function.

Anti-Inflammatory Effects of Fatty Acid Amide Hydrolase Inhibition in Monocytes/Macrophages from Alzheimer's Disease Patients.

Chiurchiù, Valerio · 2021

AD patients had lower CB1 and CB2 expression on B-lymphocytes and monocytes, with higher FAAH levels in monocytes.

THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior.

Dahlén, Amelia · 2021

THC caused dose-dependent behavioral stereotypy (repetitive circular swimming) in adult zebrafish.

Emerging potential of cannabidiol in reversing proteinopathies.

Dash, Raju · 2021

CBD has been shown in preclinical models to reduce oxidative stress, neuroinflammation, and protein misfolding across multiple neurodegenerative disease models.

l-Theanine Prevents Long-Term Affective and Cognitive Side Effects of Adolescent Δ-9-Tetrahydrocannabinol Exposure and Blocks Associated Molecular and Neuronal Abnormalities in the Mesocorticolimbic Circuitry.

De Felice, Marta · 2021

L-theanine pretreatment before adolescent THC exposure prevented long-term dysregulation of dopamine activity in both the prefrontal cortex and ventral tegmental area, blocked downregulation of GSK-3 and Akt signaling (biomarkers linked to psychiatric risk), and prevented the development of affective and cognitive abnormalities in adulthood..

Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal Δ9-tetrahydrocannabinol-exposed rats.

Di Bartolomeo, Martina · 2021

Perinatal THC exposure increased both Cnr1 (CB1) and Drd2 (D2 receptor) mRNA levels in the adult rat prefrontal cortex, with reduced DNA methylation at the Drd2 regulatory region.

URB597 abrogates anxiogenic and depressive behaviors in the methamphetamine-withdrawal mice: Role of the cannabinoid receptor type 1, cannabinoid receptor type 2, and transient receptor potential vanilloid 1 channels.

Ebrahimi-Ghiri, Mohaddeseh · 2021

Methamphetamine (30 mg/kg) caused anxiety and depression behaviors 3 days after withdrawal.

Discordant Effects of Cannabinoid 2 Receptor Antagonism/Inverse Agonism During Adolescence on Pavlovian and Instrumental Reward Learning in Adult Male Rats.

Ellner, Danna · 2021

Rats treated with the CB2 receptor antagonist/inverse agonist SR144528 during adolescence (postnatal days 28-41) showed significantly slower acquisition of the Pavlovian autoshaping task in adulthood (F(2,19)=5.964, p=0.010).

Endocannabinoid modulation of dopamine release during reward seeking, interval timing, and avoidance.

Everett, Thomas J · 2021

This review detailed how the endocannabinoid 2-AG acts as a gatekeeper for dopamine signaling across three distinct behaviors.

Cannabidiol Modulates Behavioural and Gene Expression Alterations Induced by Spontaneous Cocaine Withdrawal.

Gasparyan, Ani · 2021

Mice undergoing spontaneous cocaine withdrawal showed increased motor activity, somatic signs, and anxiety.

The ω-3 endocannabinoid docosahexaenoyl ethanolamide reduces seizure susceptibility in mice by activating cannabinoid type 1 receptors.

Ghanbari, Mohammad-Mahdi · 2021

DHEA (100-300 uM) significantly increased seizure threshold within 10 minutes, more potently than its parent molecule DHA (which required 300 uM and 15 minutes).

Adolescent cannabinoid exposure modulates the vulnerability to cocaine-induced conditioned place preference and DNMT3a expression in the prefrontal cortex in Swiss mice.

Gobira, P H · 2021

Adolescent WIN55,212-2 exposure did not alter anxiety or depression in adulthood.

CB1 and CB2 receptors in the bed nucleus of the stria terminalis differently modulate anxiety-like behaviors in rats.

Gomes-de-Souza, Lucas · 2021

Both CB1 and CB2 receptor gene expression were confirmed in the anterior and posterior BNST.

Different responses of repetitive behaviours in juvenile and young adult mice to Δ9 -tetrahydrocannabinol and cannabidiol may affect decision making for Tourette syndrome.

Gorberg, Victoria · 2021

THC dose-dependently reduced some DOI-induced repetitive behaviors (ear scratch > grooming > head twitch) differently in juvenile versus young adult mice.

Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine.

Greco, Rosaria · 2021

The dual FAAH/MAGL inhibitor JZL195 significantly reduced nitroglycerin-induced trigeminal hyperalgesia and pain-associated behavior, likely via CB1 receptors.

Morphine Induces Upregulation of Neuronally Expressed CB2 Receptors in the Spinal Dorsal Horn of Rats.

Grenier, Patrick · 2021

CB2 receptors were predominantly expressed on neurons (NeuN-labeled cells) rather than microglia in the spinal dorsal horn.

Sex Differences in Tolerance to Delta-9-Tetrahydrocannabinol in Mice With Cisplatin-Evoked Chronic Neuropathic Pain.

Henderson-Redmond, Angela N · 2021

Female mice developed tolerance to the anti-allodynic (pain-relieving) effects of both 6 mg/kg and 10 mg/kg THC faster than males.

Cannabis and exercise: Effects of Δ9-tetrahydrocannabinol on preference and motivation for wheel-running in mice.

Hurel, Imane · 2021

While blocking or deleting CB1 receptors decreased running preference and performance, adding THC (which activates CB1 receptors) did not increase either.

Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice.

Iemolo, Attilio · 2021

Heterozygous Reeler mice (reduced Reelin) treated with THC during adolescence showed impaired social behaviors, elevated disinhibitory phenotypes, and increased stress reactivity compared to wild-type mice given the same THC treatment.

Peripherally Selective CB1 Receptor Antagonist Improves Symptoms of Metabolic Syndrome in Mice.

Khan, Nayaab · 2021

The peripheral CB1 antagonist RTI1092769 inhibited weight gain, improved glucose utilization, and significantly reduced liver triglycerides and steatosis in mice on a high-fat diet.

Endocannabinoid and dopaminergic system: the pas de deux underlying human motivation and behaviors.

Laksmidewi, A A A Putri · 2021

This review framed the endocannabinoid-dopamine interaction through Maslow's hierarchy of needs — an unusual but clarifying lens.

Neuroprotective Effects of Cannabidiol but Not Δ9-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with Cannabis Extracts and Selected Cannabinoids.

Landucci, Elisa · 2021

CBD and the CBD-rich FM2 extract protected against ischemic brain damage in hippocampal slices.

Occipital neural dynamics in cannabis and alcohol use: independent effects of addiction.

Lew, Brandon J · 2021

Participants meeting criteria for alcohol use disorder displayed significantly blunted occipital alpha (8-16 Hz) responses during visual-spatial processing, and this effect scaled with AUD symptom severity.

N-linoleyltyrosine exerts neuroprotective effects in APP/PS1 transgenic mice via cannabinoid receptor-mediated autophagy.

Long, Chun-Mei · 2021

N-linoleyltyrosine (NITyr) improved motor coordination and spatial memory in APP/PS1 mice, reduced amyloid-beta levels in the hippocampus, and upregulated autophagy markers.

Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1.

Lu, Qudong · 2021

Intrathecal injection of Resolvin D2 (a GPR18 agonist) increased paw withdrawal threshold and micturition interval in rats with cyclophosphamide-induced cystitis.

Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain.

Luo, Zhenwu · 2021

Cannabis smokers showed oral microbial dysbiosis with increased Streptococcus and Actinomyces and decreased Neisseria.

Antipsychotic potential of the type 1 cannabinoid receptor positive allosteric modulator GAT211: preclinical in vitro and in vivo studies.

McElroy, Dan L · 2021

GAT211 dose-dependently reduced locomotor activity, prevented MK-801-induced hyperlocomotion (a model of psychosis), and limited dopamine D2 receptor-mediated ERK phosphorylation in neuronal cells.

Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity.

Meyer, Erika · 2021

CBD (10 mg/kg) attenuated ischemia-induced memory deficits in both radial maze and object location tasks.

Differential contribution of CB1, CB2, 5-HT1A, and PPAR-γ receptors to cannabidiol effects on ischemia-induced emotional and cognitive impairments.

Mori, Marco Aurélio · 2021

CBD prevented anxiety-like behavior, memory impairments, and despair-like behaviors after cerebral ischemia.

Emotion regulation in emerging adults with major depressive disorder and frequent cannabis use.

Nichols, Emily S · 2021

MDD showed an interaction with emotion regulation in the middle temporal gyrus, while cannabis use showed an interaction in the superior temporal gyrus.

Cannabidiol modulation of hippocampal glutamate in early psychosis.

O'Neill, Aisling · 2021

Compared to placebo, CBD produced a significant increase in hippocampal glutamate (p=0.035) and a significantly greater decrease in symptom severity on the PANSS scale (p=0.032).

Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis.

O'Neill, Aisling · 2021

Psychosis patients on placebo showed altered prefrontal activation during verbal encoding and altered mediotemporal and prefrontal activation during recall, along with greater hippocampal-striatal connectivity.

Sex-dependent pharmacological profiles of the synthetic cannabinoid MMB-Fubinaca.

Oliveira da Cruz, José F · 2021

MMB-Fubinaca activated CB1 receptors with much greater potency than the standard cannabinoid agonist WIN55,512-2 in both mouse and human brain tissue.

Neurological Soft Signs in Cannabis Use Disorder with or without Psychosis: A Comparative Study from India.

Parmar, Arpit · 2021

Total NES scores were significantly higher in CUD with psychosis (20.53) and CUD without psychosis (15.93) compared to healthy controls (6.20, p<0.001).

Cannabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatum.

Pedrazzi, João F C · 2021

CBD (30 and 60 mg/kg) attenuated amphetamine- and MK-801-induced disruption of prepulse inhibition, similar to clozapine.

Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy.

Perez, Matheus · 2021

CBD increased spinal motor neuron survival by approximately 54% at both 5 days and 8 weeks post-injury.

A Brain on Cannabinoids: The Role of Dopamine Release in Reward Seeking and Addiction.

Peters, Kate Z · 2021

This Cold Spring Harbor review laid out the definitive case for how cannabis engages the brain's addiction circuitry.

Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring.

Pinky, Priyanka D · 2021

Prenatal WIN55,212-2 exposure reduced oxidative stress and nitrite content in offspring cerebellum, enhanced mitochondrial Complex I and IV activities, increased pro-survival signaling (pP38), and decreased pro-apoptotic factors (caspase-3, pERK, pJNK).

Behavioral aspects and neurobiological properties underlying medical cannabis treatment in Shank3 mouse model of autism spectrum disorder.

Poleg, Shani · 2021

CBD-enriched medical cannabis oil reduced repetitive grooming by over 70% and alleviated anxiety in Shank3 mutant mice.

Prenatal alcohol and cannabis exposure can have opposing and region-specific effects on parvalbumin interneuron numbers in the hippocampus.

Reid, Hannah M O · 2021

In the dorsal CA1, ethanol and ethanol+THC groups showed increased parvalbumin interneuron numbers, while THC alone decreased them.

Alterations in Electroencephalography Theta as Candidate Biomarkers of Acute Cannabis Intoxication.

Richard, Christian D · 2021

Cannabis intoxication was associated with decreased theta band power (3-5 Hz) during resting state, reduced P400 and late positive potential amplitudes during attention and memory tasks, elevated frontal coherence, and diminished anterior-posterior coherence in the theta band.

Pharmacokinetic and pharmacodynamic properties of aerosolized ("vaped") THC in adolescent male and female rats.

Ruiz, C M · 2021

Female adolescent rats had higher 11-OH-THC levels than males in blood and brain after vaped THC exposure.

Mesolimbic dopamine dysregulation as a signature of information processing deficits imposed by prenatal THC exposure.

Sagheddu, Claudia · 2021

Pre-pubertal male rats exposed prenatally to THC showed reduced population activity of VTA dopamine neurons but more tonically active neurons, enhanced sensitivity to D2 receptor activation by apomorphine, and stress-induced disruption of sensorimotor gating (PPI).

Eye movements in patients in early psychosis with and without a history of cannabis use.

Sami, Musa Basseer · 2021

Among 91 participants across four groups, early psychosis patients without cannabis history had significantly worse smooth pursuit velocity gain compared to those with cannabis history (effect size g=0.76-0.86), suggesting less severe neurobiological alterations in cannabis-associated psychosis..

Brain imaging of cannabinoid type I (CB1 ) receptors in women with cannabis use disorder and male and female healthy controls.

Spindle, Tory R · 2021

Females with CUD (n=10) showed significantly lower CB1 receptor availability than female healthy controls (n=10) in the hippocampus, amygdala, cingulate, and insula.

Cannabis Use and Brain Volume in Adolescent and Young Adult Cannabis Users: Effects Moderated by Sex and Aerobic Fitness.

Sullivan, Ryan M · 2021

No overall brain volume differences were found between cannabis users and controls, but sex-by-cannabis interactions revealed that female users had greater frontal and temporal volumes while male users had less volume compared to same-sex controls.

Alterations in Brain Cannabinoid Receptor Levels Are Associated with HIV-Associated Neurocognitive Disorders in the ART Era: Implications for Therapeutic Strategies Targeting the Endocannabinoid System.

Swinton, Mary K · 2021

Immunoblot analysis showed CB1 and CB2 receptors were differentially expressed in frontal cortices of HAND versus neurocognitively unimpaired HIV-positive brains.

Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity.

Thomason, Moriah E · 2021

Fetuses exposed to cannabis prenatally showed altered hippocampal connectivity to dorsolateral, medial, and superior frontal cortex, insula, anterior temporal, and posterior cingulate regions.

Cannabinoid type 1 receptor inverse agonism attenuates dyslipidemia and atherosclerosis in APOE∗3-Leiden.CETP mice.

van Eenige, Robin · 2021

In lean mice with dyslipidemia, 20 weeks of rimonabant treatment reduced VLDL-TG production by 52%, lowered non-HDL-C by 19%, raised HDL-C by 57%, and decreased atherosclerotic lesion size by 64% with reduced severity (28% vs.

Sex, species and age: Effects of rodent demographics on the pharmacology of ∆9-tetrahydrocanabinol.

Wiley, Jenny L · 2021

11-OH-THC showed 7- to 31-fold greater potency than THC for catalepsy and hypothermia in mice and 7- to 9-fold greater potency in drug discrimination.

Cannabinoid CB2 Receptor Activation Attenuates Fentanyl-Induced Respiratory Depression.

Zavala, Carmen A · 2021

Co-administration of LY2828360 (3 mg/kg) with fentanyl (0.2 mg/kg) attenuated respiratory depression in wild-type mice but not CB2 knockout mice, confirming the effect was CB2-mediated.

Global brain network dynamics predict therapeutic responsiveness to cannabidiol treatment for refractory epilepsy.

Anderson, David E · 2020

Patients who achieved >70% seizure reduction (responders) showed increased network integration (higher global efficiency, lower degree) and increased segregation (higher modularity) in the beta frequency band compared to non-responders.

Investigating the cumulative effects of Δ9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats.

Bhatt, Dhyey · 2020

THC after repeated mild TBI was beneficial for 3 of 6 behavioral outcomes: reducing anxiety, reducing depressive-like behaviors, and improving short-term working memory deficits.

Developmental differences in the effects of CB1/2R agonist WIN55212-2 on extinction of learned fear.

Bisby, Madelyne A · 2020

WIN55212-2, a CB1/CB2 receptor agonist, improved fear extinction in adult rats but impaired extinction acquisition in both adolescent and juvenile rats.

The effects of acute cannabidiol on cerebral blood flow and its relationship to memory: An arterial spin labelling magnetic resonance imaging study.

Bloomfield, Michael A P · 2020

CBD increased cerebral blood flow in the hippocampus by an average of 15 mL/100g/min compared to placebo (Cohen's d = 0.75, p = 0.004).

In utero Δ9-tetrahydrocannabinol exposure confers vulnerability towards cognitive impairments and alcohol drinking in the adolescent offspring: Is there a role for neuropeptide Y?

Brancato, Anna · 2020

In utero THC-exposed adolescent rats showed impaired aversive limbic memory (but intact neutral memory), decreased NPY-positive neurons in limbic regions, altered Homer protein expression, and increased alcohol consumption, relapse, and compulsive-like drinking behavior in operant chambers..

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.

Breivogel, Chris S · 2020

JWH-073 and AM-2201 produced significantly more convulsions than THC, HU-210, methanandamide, or CBD.

EEG biomarkers acquired during a short, straight-line simulated drive to predict impairment from cannabis intoxication.

Brown, Timothy L · 2020

Standard deviation of lane position (SDLP) was significantly worse and heart rate elevated during THC sessions compared to placebo.

The Synthetic Cannabinoid URB447 Reduces Brain Injury and the Associated White Matter Demyelination after Hypoxia-Ischemia in Neonatal Rats.

Carloni, Silvia · 2020

URB447 strongly reduced brain injury when given before hypoxia-ischemia.

Prenatal cannabinoid exposure alters the ovarian reserve in adult offspring of rats.

Castel, Pierre · 2020

Young adult rats (PND90) exposed prenatally to the CB1/CB2 agonist WIN55212 had decreased ovarian reserve, an effect reversed by prenatal CB1 receptor blockade with SR141716.

Attenuation of fear-conditioned analgesia in rats by monoacylglycerol lipase inhibition in the anterior cingulate cortex: Potential role for CB2 receptors.

Corcoran, Louise · 2020

MGL inhibition (increasing 2-AG) in the ACC attenuated fear-conditioned analgesia.

Disrupting the endocannabinoid system in early adolescence negatively impacts sociability.

Cossio, Daniela · 2020

Both the CB1/CB2 agonist CP55,940 and the CB1 antagonist AM251, given daily from PND 25-39, reduced sociability in adolescent rats without affecting anxiety.

Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson's disease.

Crivelaro do Nascimento, Glauce · 2020

The Parkinson's model (6-OHDA) decreased thermal and mechanical pain thresholds.

Microstructure analysis of the effects of the cannabinoid agents HU-210 and rimonabant in rats licking for sucrose.

D'Aquila, Paolo S · 2020

HU-210 reduced licking by decreasing burst number and intra-burst lick rate (a motor competence index).

Positive allosteric modulation of the cannabinoid type-1 receptor (CB1R) in periaqueductal gray (PAG) antagonizes anti-nociceptive and cellular effects of a mu-opioid receptor agonist in morphine-withdrawn rats.

Datta, Udita · 2020

Intra-PAG DAMGO (opioid agonist) dose-dependently reversed morphine-induced hyperalgesia.

Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure.

de Salas-Quiroga, Adán · 2020

Adult male mice exposed to THC prenatally showed altered hippocampal oscillations, brain hyperexcitability, and spatial memory impairment.

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study.

Delvecchio, Giuseppe · 2020

CIP patients showed extensive grey matter decreases in right superior frontal gyrus, precentral, superior temporal gyrus, bilateral insula, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus compared to non-psychotic chronic cannabis users.

Nausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018.

DeVuono, Marieka V · 2020

JWH-018 at 1 and 3 mg/kg produced conditioned gaping (nausea).

Role of the stress response and the endocannabinoid system in Δ9-tetrahydrocannabinol (THC)-induced nausea.

DeVuono, Marieka V · 2020

Antalarmin (CRH antagonist), MJN110 (2-AG elevator), URB597 (AEA elevator), propranolol, WAY-100635, and chlordiazepoxide all blocked THC-induced conditioned gaping.

Precipitated Δ9-THC withdrawal reduces motivation for sucrose reinforcement in mice.

Eckard, M L · 2020

Precipitated THC withdrawal (via rimonabant) caused large decreases in break point, overall response rate, and run rate on a progressive-ratio schedule in THC-treated but not vehicle-treated mice.

Combined neurotoxic effects of cannabis and nandrolone decanoate in adolescent male rats.

El-Shamarka, Marwa El-Sayed · 2020

Combined cannabis + nandrolone caused learning/spatial memory deficits, hypo-locomotion, anxiety, and aggression.

Cannabinoid-profiled agents improve cell survival via reduction of oxidative stress and inflammation, and Nrf2 activation in a toxic model combining hyperglycemia+Aβ1-42 peptide in rat hippocampal neurons.

Elmazoglu, Zubeyir · 2020

All five cannabinoid agents preserved cell viability, stimulated mitochondrial membrane potential, and reduced oxidative damage and inflammation.

Acute neuroradiological, behavioral, and physiological effects of nose-only exposure to vaporized cannabis in C57BL/6 mice.

Farra, Yasmeen M · 2020

Cannabis inhalation decreased heart rate and blood pressure but promoted anxiety-like behavior in the open field test.

Synthetic cannabinoids enhanced ethanol-induced motor impairments through reduction of central glutamate neurotransmission.

Funada, Masahiko · 2020

Synthetic cannabinoids enhanced ethanol-induced motor impairment on a rotarod test.

Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-HT1A and TRPV1 receptor mechanisms.

Galaj, Ewa · 2020

CBD (10-40 mg/kg) reduced cocaine self-administration, shifted the cocaine dose-response curve downward, and lowered break-points for cocaine seeking.

In vitro and in vivo pharmacological evaluation of the synthetic cannabinoid receptor agonist EG-018.

Gamage, Thomas F · 2020

EG-018 had high affinity for CB1 (21 nM) and CB2 (7 nM) but behaved as a weak partial agonist, unlike typical synthetic cannabinoids.

Cannabinoid receptors and the proconvulsant effect of toxoplasmosis in mice.

Ghanbari, Mohammad-Mahdi · 2020

The CB1 agonist ACEA, the endocannabinoid-boosting agent JZL184, and the CB2 antagonist AM630 all raised seizure thresholds in both healthy and Toxoplasma-infected mice.

Age-dependent hormesis-like effects of the synthetic cannabinoid CP55940 in C57BL/6 mice.

Hodges, Erik L · 2020

CP55940 produced greater antinociception (pain relief) and locomotor inhibition in aged (21-24 month) compared to young-adult (4 month) mice.

Xie2-64, a novel CB2 receptor inverse agonist, reduces cocaine abuse-related behaviors in rodents.

Jordan, Chloe J · 2020

Xie2-64, a CB2 receptor inverse agonist, dose-dependently reduced cocaine self-administration and blocked cocaine-primed reinstatement (relapse) in rats.

Cannabinoid Antagonist Drug Discrimination in Nonhuman Primates.

Kangas, Brian D · 2020

Squirrel monkeys were trained to discriminate rimonabant (a CB1 antagonist/inverse agonist) from vehicle in a drug discrimination paradigm.

FMRI activation to cannabis odor cues is altered in individuals at risk for a cannabis use disorder.

Kleinhans, Natalia M · 2020

Using fMRI, researchers found that young adults with higher cannabis use disorder risk showed greater activation in the ventral striatum and orbitofrontal cortex when exposed to cannabis odor cues compared to neutral odors.

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study.

Laricchiuta, Daniela · 2020

Mice treated with CB1 antagonist AM251 showed impaired spatial learning on a Circular Hole Board task and shifted their navigation strategy patterns.

The acute effects of cannabidiol on the neural correlates of reward anticipation and feedback in healthy volunteers.

Lawn, Will · 2020

In a double-blind, placebo-controlled crossover study, 23 healthy participants showed no differences in reward-related brain activity (measured by fMRI during a monetary incentive delay task) after 600mg CBD compared to placebo.

Activation of cannabinoid type 1 receptors decreases the synchronization of local field potential oscillations in the hippocampus and entorhinal cortex and prolongs the interresponse time during a differential-reinforcement-of-low-rate task.

Liao, Wan-Ting · 2020

CB1 receptor activation in the medial entorhinal cortex reduced gamma amplitude synchronization and theta-gamma coupling between the hippocampal CA1 region and MEC.

Cannabinoid receptor 2 activation decreases severity of cyclophosphamide-induced cystitis via regulating autophagy.

Liu, Qinggang · 2020

In mice with cyclophosphamide-induced cystitis, CB2 agonist JWH-133 significantly reduced pain sensitivity, decreased urinary frequency, and alleviated bladder inflammation and oxidative stress.

The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice.

Lopes, Jadna B · 2020

CB1 antagonist AM251 inhibited acquisition and expression of cocaine sensitization and conditioned place preference (CPP).

Exposure to the cannabinoid agonist WIN 55, 212-2 in adolescent rats causes sleep alterations that persist until adulthood.

Macías-Triana, Lorena · 2020

Adolescent rats exposed to WIN 55,212-2 (a cannabinoid agonist) for 14 days during adolescence (postnatal days 30-44) showed significant sleep disturbances when tested as adults (postnatal day 80): decreased wakefulness and enhanced REM sleep.

Effects of combined 5-HT2A and cannabinoid receptor modulation on a schizophrenia-related prepulse inhibition deficit in mice.

Marques, Adriana M · 2020

Neither the CB1 agonist WIN 55,212-2 nor the CB1 inverse agonist rimonabant alone affected prepulse inhibition (PPI) or blocked MK-801-induced PPI deficits.

Effects of chronic nicotine exposure on Δ9-tetrahydrocannabinol-induced locomotor activity and neural activation in male and female adolescent and adult rats.

Miladinovic, T · 2020

In 112 rats, chronic nicotine followed by a washout period altered responses to THC challenge.

Treadmill exercise improves LPS-induced memory impairments via endocannabinoid receptors and cyclooxygenase enzymes.

Moosavi Sohroforouzani, Azam · 2020

Rats with LPS-induced neuroinflammation showed cognitive impairment in the water maze.

Influence of the CB1 and CB2 cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice.

Poleszak, Ewa · 2020

In mouse forced swim and tail suspension tests, sub-effective doses of CB receptor ligands enhanced antidepressant activity: oleamide (CB1 agonist) potentiated tianeptine; AM251 (CB1 antagonist) enhanced both tianeptine and agomelatine; AM630 (CB2 inverse agonist) augmented both drugs in the forced swim test only.

Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice.

Poleszak, Ewa · 2020

Sub-effective doses of JWH133 (CB2 agonist, 0.25 mg/kg) and AM630 (CB2 inverse agonist, 0.25 mg/kg) each significantly enhanced the antidepressant effects of imipramine (15 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg) in both forced swim and tail suspension tests.

Effect of Cannabinoids on Electroencephalography of a Child with Lennox-Gastaut Syndrome.

Prakash, Vikram · 2020

A 9-year-old boy with Lennox-Gastaut syndrome of unknown etiology treated with highly purified CBD (Epidiolex) achieved complete seizure control and near-normalization of EEG background activity.

CBD modulates DNA methylation in the prefrontal cortex and hippocampus of mice exposed to forced swim.

Sales, Amanda J · 2020

CBD (10 mg/kg) produced antidepressant-like behavior in the forced swim test.

Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model.

Seillier, Alexandre · 2020

In PCP-treated rats (schizophrenia model), only the lowest THC dose (0.1 mg/kg) reversed social interaction deficits and normalized elevated anandamide in the nucleus accumbens.

Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation.

Thapa, Dinesh · 2020

The CB1 allosteric ligand GAT228 reduced pain on its own, while GAT229 and GAT211 reduced pain when combined with a low dose of THC.

Peripheral deficiency and antiallodynic effects of 2-arachidonoyl glycerol in a mouse model of paclitaxel-induced neuropathic pain.

Thomas, Amal · 2020

2-AG levels were significantly reduced in the paw skin but not in the brain or spinal cord of paclitaxel-treated mice.

The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice.

Trexler, Kristen R · 2020

AB-FUBINACA at 2+ mg/kg produced catalepsy, antinociception, hypothermia, and reduced locomotion, all blocked by CB1 antagonist rimonabant.

Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor.

Vieira, Graziela · 2020

Terpineol at 100-200 mg/kg reduced immobility time in the tail suspension test.

Endocannabinoid modulating drugs improve anxiety but not the expression of conditioned fear in a rodent model of post-traumatic stress disorder.

Vimalanathan, Akshayan · 2020

Acute WIN55,212-2 (CB1 agonist) reduced anxiety in "weak extinction" rats but did not affect fear recall.

Different receptor mechanisms underlying phytocannabinoid- versus synthetic cannabinoid-induced tetrad effects: Opposite roles of CB1 /CB2 versus GPR55 receptors.

Wang, Xiao-Fei · 2020

CB1 deletion abolished tetrad effects for all three cannabinoids.

Subacute cannabidiol alters genome-wide DNA methylation in adult mouse hippocampus.

Wanner, Nicole M · 2020

CBD-treated mice had 3,323 differentially methylated loci with a slight skew toward global hypomethylation.

High fat-fed GPR55 null mice display impaired glucose tolerance without concomitant changes in energy balance or insulin sensitivity but are less responsive to the effects of the cannabinoids rimonabant or Δ(9)-tetrahydrocannabivarin on weight gain.

Wargent, Edward T · 2020

GPR55 knockout mice had worse glucose tolerance than wildtype mice on both standard and high-fat diets, despite no differences in body weight, composition, food intake, or energy expenditure.

Chronic cannabidiol (CBD) treatment did not exhibit beneficial effects in 4-month-old male TAU58/2 transgenic mice.

Watt, Georgia · 2020

TAU58/2 transgenic mice showed reduced body weight, reduced anxiety, impaired motor function, and increased freezing in fear conditioning compared to wildtype.

Peripheral versus central mechanisms of the cannabinoid type 2 receptor agonist AM1710 in a mouse model of neuropathic pain.

Wilkerson, Jenny L · 2020

AM1710 reversed mechanical allodynia to sham levels in CB1 knockout, heterozygous, and wildtype mice via both peripheral (i.p.) and spinal (i.t.) routes.

Inverse Agonism of Cannabinoid Receptor Type 2 Confers Anti-inflammatory and Neuroprotective Effects Following Status Epileptics.

Yu, Ying · 2020

Status epilepticus downregulated CB1 but slightly upregulated CB2 in the hippocampus.

In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa.

Zagzoog, Ayat · 2020

THC, THCA, THCV, CBD, CBDA, CBDV, CBG, and CBC were tested for receptor binding, cAMP inhibition, beta-arrestin2 recruitment, and in vivo effects.

Systemic administration with tetrahydrocannabinol causes retinal damage in BALB/c mice.

Zhang, Z · 2020

THC at 1-2 mg/kg daily for 2 months caused functional loss on electroretinography, increased photoreceptor cell apoptosis, elevated inflammatory markers (TNF-alpha, IL-1beta, IL-6), and increased oxidative stress markers in retinal tissue.

Cannabinoids Rescue Cocaine-Induced Seizures by Restoring Brain Glycine Receptor Dysfunction.

Zou, Guichang · 2020

Systemic cannabinoid administration alleviated cocaine-induced seizures independently of CB1 and CB2 receptors.

Transcriptomic and barrier responses of human airway epithelial cells exposed to cannabis smoke.

Aguiar, Jennifer A · 2019

Cannabis smoke induced gene expression profiles that overlapped significantly with tobacco smoke, including DNA replication stress, oxidative stress responses, impaired epithelial barrier function, suppressed antiviral pathways, and increased inflammatory mediator production..

Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways.

Al-Ghezi, Zinah Zamil · 2019

THC+CBD combination (10 mg/kg each) attenuated experimental autoimmune encephalomyelitis in mice by reducing brain-infiltrating inflammatory T cells and pro-inflammatory molecules while increasing anti-inflammatory markers.

Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome.

Al-Ghezi, Zinah Zamil · 2019

THC+CBD treatment reduced a mucin-degrading gut bacterium (Akkermansia muciniphila) that was elevated in EAE mice, lowered brain LPS levels, and increased beneficial short-chain fatty acids.

Cannabidiol improves vocal learning-dependent recovery from, and reduces magnitude of deficits following, damage to a cortical-like brain region in a songbird pre-clinical animal model.

Alalawi, Ali · 2019

CBD at 10 and 100 mg/kg effectively reduced the time required to recover vocal phonology and syntax after brain microlesions in zebra finches.

Bipolar disorder and the endocannabinoid system.

Arjmand, Shokouh · 2019

The endocannabinoid system exerts neuromodulatory effects on neurotransmitter systems critical for emotion regulation.

The Potential of Cannabinoid-Based Treatments in Tourette Syndrome.

Artukoglu, Bekir B · 2019

There is a strong biological rationale for cannabinoid effects on tics, and many patients report improvement with cannabis.

Pharmacological and Behavioral Effects of the Synthetic Cannabinoid AKB48 in Rats.

Bilel, Sabrine · 2019

AKB48 at low doses (0.25 mg/kg) preferentially stimulated dopamine release in the nucleus accumbens shell (reward center) and impaired visual reflexes at 0.3 mg/kg.

Effects in rats of adolescent exposure to cannabis smoke or THC on emotional behavior and cognitive function in adulthood.

Bruijnzeel, Adriaan W · 2019

Despite testing both cannabis smoke and THC at multiple doses during the adolescent period (P29-49 or P35-45), adult rats showed no significant effects on anxiety (open field, elevated plus maze), depression (sucrose preference, forced swim), or cognition (novel object recognition) after abstinence until P70.

Cortical Thickness and Subcortical Volumes in Adolescent Synthetic Cannabinoid Users with or Without ADHD: a Preliminary Study.

Çolak, Çiğdem · 2019

SC users with and without ADHD had reduced cortical thickness in left caudal middle frontal and left superior frontal areas compared to controls.

Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats.

Colangeli, Roberto · 2019

WIN55,212-2 (CB1 agonist at 2 mg/kg) and RO60-0175 (5-HT2B/2C agonist at 3 mg/kg) were ineffective alone against EEG seizures but combined they reduced seizure incidence, severity, and increased latency to seizure onset.

Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor.

Darmani, Nissar A · 2019

Delta-9-THC, WIN55,212-2, and CP55,940 all dose-dependently suppressed vomiting triggered by substance P and the selective NK1 receptor agonist GR73632 in least shrews.

The epigenetic modulation of alcohol/ethanol and cannabis exposure/co-exposure during different stages.

Dobs, Yasminah Elsaadany · 2019

Both alcohol and cannabis independently modulate the epigenome through chromatin modification and remodeling, affecting gene activation and silencing.

Endocannabinoid modulation of inflammatory hyperalgesia in the IFN-α mouse model of depression.

Fitzgibbon, Marie · 2019

Repeated IFN-alpha treatment increased formalin-evoked pain behavior in mice.

Targeting Peripheral CB1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis.

Godlewski, Grzegorz · 2019

The peripheral CB1R inverse agonist JD5037 reduced ethanol drinking in wild-type mice but not in mice lacking CB1R, ghrelin, or the ghrelin receptor.

Activation of ATP-sensitive K-channel promotes the anticonvulsant properties of cannabinoid receptor agonist through mitochondrial ATP level reduction.

Haj-Mirzaian, Arvin · 2019

WIN 55,212-2 at 10 mg/kg significantly increased clonic seizure threshold via CB1 (blocked by AM-251) but not CB2 (AM-630 had no effect).

Role of the endocannabinoid system in the dorsal hippocampus in the cardiovascular changes and delayed anxiety-like effect induced by acute restraint stress in rats.

Hartmann, Alice · 2019

The FAAH inhibitor URB597 injected into the dorsal hippocampus prevented stress-induced cardiovascular responses (heart rate increase, blood pressure rise, temperature drop) and delayed anxiety.

Cannabinoid CB1 receptor neutral antagonist AM4113 inhibits heroin self-administration without depressive side effects in rats.

He, Xiang-Hu · 2019

AM4113 dose-dependently inhibited heroin self-administration but not cocaine or methamphetamine self-administration.

Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus through Bidirectional Control of ERK1-2 Phosphorylation.

Hudson, Roger · 2019

Intra-hippocampal THC increased VTA dopamine neuron firing and bursting, decreased GABA frequency, and amplified oscillatory activity via ERK1-2 phosphorylation.

Paternal activation of CB2 cannabinoid receptor impairs placental and embryonic growth via an epigenetic mechanism.

Innocenzi, Elisa · 2019

JWH-133 (CB2 agonist) exposure in male mice decreased sperm count, impaired placental development, and reduced offspring growth.

Effects of chronic cannabinoid exposure during adolescence on reward preference and mPFC activation in adulthood.

Jacobs-Brichford, Eliza · 2019

Adult rats that received WIN 55,212-2 during adolescence (postnatal days 30-60) showed subtle changes in choice behavior and significantly reduced mPFC neural activity during lever presses and reward delivery in a probabilistic reward task, suggesting impaired excitatory-inhibitory balance from adolescent exposure..

Cannabidiol attenuates mechanical allodynia in streptozotocin-induced diabetic rats via serotonergic system activation through 5-HT1A receptors.

Jesus, Carlos Henrique Alves · 2019

Acute CBD (0.3 and 3 mg/kg) reduced mechanical allodynia in diabetic rats.

Adolescent Δ9-Tetrahydrocannabinol Exposure and Astrocyte-Specific Genetic Vulnerability Converge on Nuclear Factor-κB-Cyclooxygenase-2 Signaling to Impair Memory in Adulthood.

Jouroukhin, Yan · 2019

Astrocyte-specific expression of DN-DISC1 combined with adolescent THC synergistically impaired recognition memory in adult mice.

Investigating a novel fMRI cannabis cue reactivity task in youth.

Karoly, Hollis C · 2019

Cannabis-using youth showed greater whole-brain activation to cannabis cues compared to non-cannabis cues in brain regions underlying incentive salience, reward, and visual attention.

Preliminary evidence that computerized approach avoidance training is not associated with changes in fMRI cannabis cue reactivity in non-treatment-seeking adolescent cannabis users.

Karoly, Hollis C · 2019

CAAT training shifted approach bias toward avoidance while sham training increased approach bias (trend p=0.055).

Effects of cannabinoid modulation on hypothalamic nesfatin-1 and insulin resistance.

Kaya, Oktay · 2019

WIN 55,212-2 reduced brain nesfatin-1 immunoreactivity in sleep-deprived mice, an effect prevented by either CB1 or CB2 antagonists.

CUMYL-4CN-BINACA Is an Efficacious and Potent Pro-Convulsant Synthetic Cannabinoid Receptor Agonist.

Kevin, Richard C · 2019

CUMYL-4CN-BINACA acted as a potent CB1 receptor agonist and produced seizures at a lower dose than any previously tested synthetic cannabinoid.

Hemisphere-dependent endocannabinoid system activity in prefrontal cortex and hippocampus of the Flinders Sensitive Line rodent model of depression.

Kirkedal, C · 2019

2-AG was lower in the left hippocampus and left prefrontal cortex of depression-prone FSL rats compared to controls.

Effects of Fatty Acid Amide Hydrolase Inhibitors Acute Administration on the Positive and Cognitive Symptoms of Schizophrenia in Mice.

Kruk-Slomka, Marta · 2019

URB 597 (FAAH inhibitor) at 0.3 mg/kg attenuated MK-801-induced memory impairment, but at 1 mg/kg it worsened it.

Δ9-Tetrahydrocannabinol During Adolescence Attenuates Disruption of Dopamine Function Induced in Rats by Maternal Immune Activation.

Lecca, Salvatore · 2019

Rats exposed to maternal immune activation (MIA) had fewer active dopamine neurons, lower firing rates, and altered activity patterns.

Adverse outcome pathway of developmental neurotoxicity resulting from prenatal exposures to cannabis contaminated with organophosphate pesticide residues.

Leung, Maxwell C K · 2019

The proposed adverse outcome pathway shows that cannabinoids and chlorpyrifos share molecular targets affecting neurodevelopment.

Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal.

Li, Ai-Ling · 2019

AM1710 produced sustained relief from paclitaxel-induced nerve pain without tolerance.

Opposite effects of cannabinoid CB1 and CB2 receptors on antipsychotic clozapine-induced cardiotoxicity.

Li, Liliang · 2019

Clozapine decreased endocannabinoid levels and caused myocardial inflammation and fibrosis in mice.

Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory.

Li, Ren-Shi · 2019

JWH-018 elevated anandamide and 2-AG levels in the hippocampus by suppressing the enzymes that break them down (FAAH and MAGL).

Alcohol-induced conditioned place preference is modulated by CB2 cannabinoid receptors and modifies levels of endocannabinoids in the mesocorticolimbic system.

Martín-Sánchez, Ana · 2019

Alcohol-conditioned place preference was associated with decreased anandamide and other N-acylethanolamines in the medial prefrontal cortex and ventral midbrain.

The Cannabinoid CB1 Antagonist TM38837 With Limited Penetrance to the Brain Shows Reduced Fear-Promoting Effects in Mice.

Micale, Vincenzo · 2019

Oral TM38837 required 10x higher doses than rimonabant to produce comparable fear-promoting effects (100 mg/kg vs 10 mg/kg).

Acute effect of vaporized Cannabis on sleep and electrocortical activity.

Mondino, Alejandra · 2019

A single vaporized dose of Cannabis with THC 11.5% (and negligible other cannabinoids) was linked to a short-lived increase in NREM sleep (non-REM sleep, a deeper non-dream sleep stage), but only at the 200 mg dose and only during the first hour of the light phase.

Memory deficits induced by chronic cannabinoid exposure are prevented by adenosine A2AR receptor antagonism.

Mouro, Francisco M · 2019

Chronic istradefylline (3 mg/kg/28 days) reversed memory deficits (Novel Object Recognition Test) caused by chronic WIN 55,212-2 (1 mg/kg/28 days).

EXTENDED ATTENUATION OF CORTICOSTRIATAL POWER AND COHERENCE AFTER ACUTE EXPOSURE TO VAPOURIZED Δ9 TETRAHYDROCANNABINOL IN RATS.

Nelong, Tapia Foute · 2019

Vaporized THC suppressed gamma power (>32-100 Hz) in the dorsal striatum, orbitofrontal cortex, and prefrontal cortex of rats, with most changes still present a week after a single exposure..

Cannabidiol improves behavioural and neurochemical deficits in adult female offspring of the maternal immune activation (poly I:C) model of neurodevelopmental disorders.

Osborne, Ashleigh L · 2019

Three weeks of CBD treatment (10 mg/kg) restored recognition memory and social interaction in female poly I:C offspring.

Ventral hippocampal overexpression of Cannabinoid Receptor Interacting Protein 1 (CNRIP1) produces a schizophrenia-like phenotype in the rat.

Perez, Stephanie M · 2019

Viral-mediated overexpression of CNRIP1 in the ventral hippocampus caused impairments in latent inhibition and social interaction (behavioral correlates of schizophrenia) and increased dopamine neuron population activity in the ventral tegmental area, a putative marker of psychosis..

The prefrontal cortical endocannabinoid system modulates fear-pain interactions in a subregion-specific manner.

Rea, Kieran · 2019

The CB1 receptor antagonist AM251 attenuated fear-conditioned analgesia (FCA) when injected into the infralimbic or prelimbic cortex, but reduced freezing only in the infralimbic region.

Impact of Chronic Cannabis Use on Auditory Mismatch Negativity Generation in Schizophrenia Patients.

Roser, Patrik · 2019

Schizophrenia patients without cannabis use showed reduced frontocentral MMN to duration deviants compared to healthy controls, as expected.

Neural and behavioral correlates of attentional bias to cannabis cues among adults with cannabis use disorders.

Ruglass, Lesia M · 2019

Cannabis users had more difficulty ignoring cannabis distractors (selective attention failure), committed more errors when cannabis cues were present, and showed an augmented and earlier N1 ERP component (125-200 ms post-stimulus) to cannabis cues, indicating an involuntary early perceptual bias toward cannabis-related stimuli..

Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats.

Santiago, Amanda Nunes · 2019

Diabetes worsened cognitive deficits from chronic cerebral hypoperfusion in middle-aged rats.

Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood.

Saravia, Rocio · 2019

Adolescent mice given both THC and stress showed impaired cued fear extinction in adulthood, with decreased neuronal activity in the basolateral amygdala and infralimbic prefrontal cortex.

Beneficial and deleterious effects of cannabinoids in the brain: the case of ultra-low dose THC.

Sarne, Yosef · 2019

This review examined what happens when you give mice THC at doses so low they produce no detectable behavioral effects — 3 to 4 orders of magnitude below what it takes to get a mouse "high." The results were striking: these ultra-low doses protected against various types of brain injury, including carbon monoxide toxicity, MDMA-induced damage, and age-related cognitive decline. The proposed mechanism was preconditioning.

Efficacy of Cannabinoids in a Pre-Clinical Drug-Screening Platform for Alzheimer's Disease.

Schubert, David · 2019

Nine of 11 cannabinoids protected cells in four distinct neurodegeneration assays (proteotoxicity, trophic loss, oxidative stress, energy loss).

Cannabinoid CB1 and CB2 receptor mechanisms underlie cannabis reward and aversion in rats.

Spiller, Krista J · 2019

Using electrical brain stimulation in rats, researchers mapped out how THC affects the brain's reward system at different doses.

Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia.

Stark, Tibor · 2019

Peripubertal CBD treatment (30 mg/kg/day from PND 19-39) reversed social interaction deficits and cognitive impairment in MAM rats.

Δ8 -Tetrahydrocannabivarin has potent anti-nicotine effects in several rodent models of nicotine dependence.

Xi, Zheng-Xiong · 2019

Delta-8-THCV (which acts as a CB1 antagonist and CB2 agonist) significantly reduced nicotine self-administration in rats, blocked both cue-induced and nicotine-induced relapse to nicotine-seeking, attenuated nicotine-induced conditioned place preference, and reduced nicotine withdrawal symptoms including anxiety, somatic signs, and pain hypersensitivity in mice..

Analysis of the Uptake, Metabolism, and Behavioral Effects of Cannabinoids on Zebrafish Larvae.

Achenbach, John C · 2018

Researchers used zebrafish larvae as a high-throughput model to study how cannabinoids are absorbed, metabolized, and affect behavior.

n-3 polyunsaturated N-acylethanolamines are CB2 cannabinoid receptor-preferring endocannabinoids.

Alharthi, Nahed · 2018

The endocannabinoid system produces a family of signaling molecules called N-acylethanolamines (NAEs), of which anandamide is the most famous.

Cannabinoid-1 receptor neutral antagonist reduces binge-like alcohol consumption and alcohol-induced accumbal dopaminergic signaling.

Balla, Andrea · 2018

Previous CB1 receptor blockers like rimonabant were effective against obesity and nicotine addiction but were withdrawn because they caused depression and suicidal ideation.

The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users.

Batalla, Albert · 2018

Researchers examined hippocampal brain structure in 59 young men aged 18-30, including 30 chronic cannabis users who started regular use before age 16 and 29 controls.

Orosensory Detection of Dietary Fatty Acids Is Altered in CB₁R-/- Mice.

Brissard, Léa · 2018

Researchers discovered that the CB1 cannabinoid receptor, the same receptor activated by THC, plays a previously unknown role in the tongue's ability to detect and prefer dietary fats. Mice genetically engineered to lack CB1 receptors showed significantly lower preference for solutions containing rapeseed oil or the fatty acid linoleic acid compared to normal mice.

The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice.

Chesworth, Rose · 2018

Researchers tracked the development of the endocannabinoid system across eight time points from birth to adulthood in mice carrying a mutation in neuregulin 1 (Nrg1), a known schizophrenia risk gene.

Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: Reversal by cannabidiol.

da Silva, Vanessa Kappel · 2018

Iron accumulation in the brain is recognized as a contributing factor in neurodegenerative diseases.

Cannabinoids and glial cells: possible mechanism to understand schizophrenia.

de Almeida, Valéria · 2018

This review examined the intersection of two lines of research: glial cell dysfunction in schizophrenia and the endocannabinoid system's effects on glial cells. Glial cells, which include oligodendrocytes, microglia, and astrocytes, perform essential functions in the brain including myelination, metabolic support, and immune response.

Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.

Gerra, Maria Carla · 2018

Researchers compared genetic variants and DNA methylation patterns between 40 cannabis users and 96 control subjects. A variant in the CNR1 gene (which codes for the CB1 cannabinoid receptor) was significantly associated with cannabis use (p=0.01).

Probing the endocannabinoid system in healthy volunteers: Cannabidiol alters fronto-striatal resting-state connectivity.

Grimm, Oliver · 2018

Researchers conducted a crossover pharmacological fMRI study giving 16 healthy male volunteers placebo, 10mg oral THC, and 600mg oral CBD in separate sessions, then measuring resting-state brain connectivity. CBD significantly increased connectivity between frontal cortex regions and the striatum compared to placebo.

THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders.

Guennewig, Boris · 2018

Researchers exposed neurons derived from human induced pluripotent stem cells (hiPSCs) to THC and analyzed the effects on gene expression. Both acute and chronic THC exposure dampened the neurons' transcriptional response when stimulated with potassium chloride (which mimics neuronal activation).

Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway.

Ibarra-Lecue, Inés · 2018

Researchers exposed mice to chronic THC during an early developmental window and then examined serotonin 2A receptor (5-HT2AR) function in the frontal cortex. Chronic THC shifted the receptor toward coupling with inhibitory G-proteins (Gαi1, Gαi3, Gαo, and Gαz) rather than the standard Gαq/11 pathway.

Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).

Kasten, Chelsea R · 2018

Researchers selectively bred mice for sensitivity or resistance to the locomotor effects of a single THC dose (10 mg/kg) during adolescence. THC-locomotor sensitivity proved to be moderately heritable, with the strongest heritability estimates seen in females from the F2 to S3 generations. An important correlated trait emerged: mice selected for THC-locomotor sensitivity also showed increased anxiety-like activity in the open field test, suggesting shared genetic factors between THC sensitivity and anxiety. This is the first demonstration that adolescent THC-locomotor sensitivity can be influenced through selective breeding, establishing a genetic basis for individual differences in cannabis response..

The effects of synthetic cannabinoids (SCs) on brain structure and function.

Livny, A · 2018

Fifteen chronic synthetic cannabinoid (SC) users and 15 healthy controls underwent MRI scans while performing cognitive tasks. SC users showed reduced total gray matter volume compared to controls, along with reduced volume in specific regions: middle frontal gyrus, frontal orbital gyrus, inferior frontal gyrus, insula, anterior cingulate cortex, and precuneus. On a working memory task (N-back), SC users performed worse behaviorally and showed diminished brain activation in the precuneus, cuneus, lingual gyrus, hippocampus, and cerebellum. On a response inhibition task (Go-No-Go), no group differences were found in either performance or brain activation. This was the first study showing both overall and region-specific gray matter volume reductions in chronic SC users, and the first to demonstrate impaired neural mechanisms for working memory specifically..

Effect of chronic THC administration in the reproductive organs of male mice, spermatozoa and in vitro fertilization.

López-Cardona, A P · 2018

Researchers gave male mice daily THC (10 mg/kg) for 30 days and compared reproductive outcomes to vehicle-treated controls. THC treatment decreased cannabinoid receptor 1 (Cnr1) gene expression in the brain cortex but not in the testes. Testicular and epididymal weight showed no differences between groups.

Distress intolerance moderation of neurophysiological markers of response inhibition after induced stress: Relations with cannabis use disorder.

Macatee, Richard J · 2018

Researchers tested whether high distress intolerance (difficulty tolerating negative emotions) would lead to stress-induced impairment of response inhibition in frequent cannabis users. Cannabis users with high and low distress intolerance completed a Go/No-Go task during EEG recording before and after a laboratory stressor. Contrary to the hypothesis, cannabis users with high distress intolerance showed enhanced conflict-monitoring neural activity (N2 amplitude) after stress rather than impairment.

Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation.

Ratano, Patrizia · 2018

The MAGL inhibitor JZL184, which boosts 2-AG levels, enhanced memory consolidation when given right after training in a fear-based learning task.

Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment.

Richards, John R · 2018

Capsaicin and hot water both activate TRPV1 receptors, which share extensive cross-talk with the endocannabinoid system.

Cannabinoids for Treatment of Dystonia in Huntington's Disease.

Saft, Carsten · 2018

UHDRS motor scores improved from 70.9 to 60.6 (mean change 10.3 points, 95% CI 6.0-14.6, p=0.018).

Novel behavioral assays of spontaneous and precipitated THC withdrawal in mice.

Trexler, Kristen R · 2018

THC withdrawal (both precipitated and spontaneous) caused increased plasma corticosterone, suppressed marble burying (suggesting anxiety/anhedonia), increased struggling in the tail suspension test (despair-like behavior), and classic somatic withdrawal signs.

Understanding marijuana's effects on functional connectivity of the default mode network in patients with schizophrenia and co-occurring cannabis use disorder: A pilot investigation.

Whitfield-Gabrieli, Susan · 2018

At baseline, schizophrenia patients showed DMN hyperconnectivity (correlated with positive symptom severity) and reduced anticorrelation between the DMN and executive control network compared to controls.

Endocannabinoid system acts as a regulator of immune homeostasis in the gut.

Acharya, Nandini · 2017

The endocannabinoid anandamide (AEA) and its receptor CB2 regulate immune tolerance in the gut and pancreas.

Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice.

Aguilar, María A · 2017

Mice pre-treated with the synthetic cannabinoid WIN 55212-2 during adolescence and then given chronic cocaine in adulthood showed a modified withdrawal profile compared to controls. Adolescent cannabinoid exposure prevented the anxiety increase normally seen during cocaine withdrawal.

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.

Almeida, Mariana M · 2017

Maternal high-fat diet during pregnancy and nursing produced early obesity in rat pups, with enlarged white fat cells and increased lipid in brown fat tissue.

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

Baker, David · 2017

VSN16R, designed as an analog of the endocannabinoid anandamide, controlled spasticity in a mouse model of multiple sclerosis (experimental encephalomyelitis) with a therapeutic window over 1,000-fold, meaning effective doses were far below those causing side effects. Surprisingly, VSN16R did not work through the known cannabinoid receptors (CB1, CB2, or GPR55).

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol.

Becker, Jérôme A J · 2017

After extended abstinence, mice that had been chronically treated with morphine, nicotine, THC, or alcohol all showed a common behavioral profile: reduced social recognition, increased motor stereotypies (repetitive behaviors), and increased anxiety.

Intra-accumbal blockade of endocannabinoid CB1 receptors impairs learning but not retention of conditioned relief.

Bergado Acosta, Jorge R · 2017

When the CB1 receptor blocker rimonabant was injected directly into the nucleus accumbens before conditioning, rats failed to learn relief associations.

Inhibition of Endocannabinoid-Metabolizing Enzymes in Peripheral Tissues Following Developmental Chlorpyrifos Exposure in Rats.

Buntyn, Robert W · 2017

Rat pups exposed to chlorpyrifos (CPF) from day 10 to 16 showed inhibition of fatty acid amide hydrolase (FAAH), the enzyme that breaks down anandamide, in the brain, spleen, and liver at all tested doses (0.5, 0.75, 1.0 mg/kg).

Pharmaco-toxicological effects of the novel third-generation fluorinate synthetic cannabinoids, 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice. In vitro and in vivo studies.

Canazza, Isabella · 2017

In vitro testing revealed that all three synthetic cannabinoids (5F-ADBINACA, AB-FUBINACA, STS-135) had nanomolar affinity for both mouse and human CB1 and CB2 receptors, making them far more potent than THC.

Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.

Carr, Russell L · 2017

Rat pups exposed to chlorpyrifos (CPF) daily from postnatal day 10 to 16 at doses of 0.5, 0.75, and 1.0 mg/kg showed inhibition of FAAH (the enzyme that breaks down anandamide) at all doses, leading to elevated anandamide levels.

Extract of Fructus Cannabis Ameliorates Learning and Memory Impairment Induced by D-Galactose in an Aging Rats Model.

Chen, Ning-Yuan · 2017

Rats given D-galactose to induce accelerated aging and memory impairment showed significant improvement when simultaneously treated with hemp seed extract (EFC).

Novel Peripherally Restricted Cannabinoid 1 Receptor Selective Antagonist TXX-522 with Prominent Weight-Loss Efficacy in Diet Induced Obese Mice.

Chen, Wei · 2017

TXX-522, designed based on rimonabant's core structure but engineered for minimal brain penetration, showed potent anti-obesity effects in high-fat diet mice.

Cannabinoid CB1 receptor inverse agonist MJ08 stimulates glucose production via hepatic sympathetic innervation in rats.

Chen, Wei · 2017

MJ08, a CB1 receptor antagonist/inverse agonist more potent than rimonabant, was found to stimulate hepatic glucose production (HGP) in a dose-dependent manner in perfused rat livers.

Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats.

Delis, Foteini · 2017

The CB1 antagonist rimonabant (3 mg/kg) decreased both the learning and expression of cocaine-induced place preference and reduced cocaine's stimulant effects on movement.

Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding.

Deng, Hui · 2017

Through systematic medicinal chemistry, researchers created DH376 (compound 38), an inhibitor of diacylglycerol lipase (DAGL) with picomolar (trillionths of a molar) potency.

Two Janus Cannabinoids That Are Both CB2 Agonists and CB1 Antagonists.

Dhopeshwarkar, Amey · 2017

Two compounds (GW405833 and AM1710) that have been extensively used in research as selective CB2 receptor agonists were discovered to also antagonize CB1 receptor signaling.

Transient Cannabinoid Receptor 2 Blockade during Immunization Heightens Intensity and Breadth of Antigen-specific Antibody Responses in Young and Aged mice.

Dotsey, Emmanuel · 2017

The study first demonstrated that immune cells (macrophages and dendritic cells) produce the endocannabinoid 2-AG when activated by antigens, and that 2-AG levels increase in both blood and lymph nodes during vaccination.

Anorexigenic effects induced by RVD-hemopressin(α) administration.

Ferrante, Claudio · 2017

Daily injections of RVD-hemopressin(alpha) (10 nmol) for 14 days reduced food intake in rats.

Cannabinoid Type 1 Receptor (CB1) Ligands with Therapeutic Potential for Withdrawal Syndrome in Chemical Dependents of Cannabis sativa.

Ferreira, Jaderson V · 2017

Researchers used computational chemistry tools to screen for potential drug candidates to treat cannabis withdrawal syndrome, focusing on compounds that could interact with the CB1 cannabinoid receptor.

Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway.

Folgueira, Cintia · 2017

When rats were treated with the CB1 inverse agonist rimonabant, food intake decreased and gastric secretion of Nucb2/nesfatin-1 (a satiety peptide) increased.

Enhanced anandamide signaling reduces flight behavior elicited by an approaching robo-beetle.

Heinz, Daniel E · 2017

Using a novel behavioral task that confronted mice with an erratically moving robo-beetle, researchers found that the two main endocannabinoids in the brain have opposite effects on fear and panic responses. Blocking the enzyme FAAH (which breaks down anandamide) with the drug URB597 reduced flight behavior and increased tolerance to the approaching beetle.

Sex- and hormone-dependent alterations in alcohol withdrawal-induced anxiety and corticolimbic endocannabinoid signaling.

Henricks, Angela M · 2017

This study revealed striking sex differences in how the endocannabinoid system responds to alcohol withdrawal. Male rats exposed to chronic alcohol vapor showed increased anxiety-like behavior during withdrawal, along with reduced anandamide in the amygdala and reduced 2-AG in the prefrontal cortex.