2009 / Review / Moderate evidenceA review found that cannabinoids show analgesic potential in preclinical and clinical studies, with particular promise as opioid-sparing agents that could reduce opioid dose requirements.
2009 / Case Control / Moderate evidenceIn a study of 636 NPC patients and 615 controls across North Africa, marijuana smoking independently elevated nasopharyngeal cancer risk, separate from cigarette smoking effects.
2009 / Randomized Controlled Trial / Preliminary evidenceIn 15 men, THC increased anxiety and skin conductance responses to fearful faces, while CBD reduced amygdala activation and autonomic arousal, demonstrating opposite emotional processing effects.
2009 / Review / Moderate evidenceA review of 2003-2007 patents documented growing interest in cannabinoid isolation, synthesis, and therapeutic applications beyond existing FDA-approved uses of synthetic THC.
2009 / Animal Study / Preliminary evidenceA cell culture study found that a cannabis extract containing THC increased glucose uptake, reduced fat cell formation, and restored insulin sensitivity in insulin-resistant cells.
2009 / Animal Study / Preliminary evidenceIn mice, a single brain dose of a CB1 agonist produced more than two weeks of tolerance and reduced morphine analgesia. Gz proteins were required.
2009 / Animal Study / Preliminary evidenceResearchers characterized MAGL in platelets for the first time and found that both MAGL and FAAH contribute to 2-AG breakdown, with human and rabbit platelets showing different hydrolysis rates.
2009 / Cross Sectional / Preliminary evidenceChronic cannabis users showed normal inhibitory control but significantly reduced awareness of their own errors, linked to reduced activation in the anterior cingulate cortex and right insula.
2009 / Animal Study / Preliminary evidenceMice chronically treated with THC showed hyperlocomotion (4.1x normal) and paw tremors (111 vs 1.1) during precipitated withdrawal, establishing quantifiable measures for studying cannabis dependence.
2009 / Randomized Controlled Trial / Moderate evidenceIn 24 non-daily users, cognitive and motor impairment increased linearly with THC dose (up to 69 mg), but some individuals showed no motor impairment even at blood THC above 40 ng/mL.
2009 / Animal Study / Preliminary evidenceIn rats, 14 days of CBD reduced T cells, B cells, and white blood cells at 5 mg/kg while sparing natural killer cells. A lower dose actually increased NKT cells.
2009 / Cross Sectional / Moderate evidenceIn 284 population-sampled young adults, moderate cannabis and ecstasy use was associated with dose-related episodic memory decrements and increased attention lapses, though effect sizes were small.
2009 / Review / Moderate evidenceA review found that CBD demonstrates neuroprotective and anti-inflammatory properties in preclinical studies, making it a promising candidate for neurodegenerative disorders with few existing treatments.
2009 / Review / Moderate evidenceA literature review described cannabis addiction as a chronic brain disease involving dopamine and serotonin pathways, with chronic use producing lasting effects on cognitive and reward brain circuits.
2009 / Review / Preliminary evidenceHeavy teen marijuana use was linked to modest cognitive disadvantages, subtle brain differences, and poorer sleep. Some changes persisted past a month and sometimes resolved by three months of abstinence.
2009 / Animal Study / Moderate evidenceInhibiting FAAH and MAGL enzymes reduced neuropathic pain in mice through different cannabinoid receptor mechanisms, without the behavioral side effects of direct cannabinoid agonists.
2009 / Systematic Review / Moderate evidenceA systematic review of six RCTs found combined THC/CBD extracts showed a trend toward reduced MS spasticity, with significant subjective improvement but no significant changes on objective clinical measures.
2009 / Review / Moderate evidenceAfter rimonabant was pulled from the market due to psychiatric side effects, this commentary argued for continuing endocannabinoid research with better safety measures rather than abandoning the therapeutic potential of the system.
2009 / Randomized Controlled Trial / Preliminary evidenceIn a drug discrimination study, 8 participants reliably identified THC, but opioid, sedative, and stimulant drugs could not substitute for the THC experience.
2009 / Animal Study / Moderate evidenceA dual FAAH/MAGL inhibitor produced THC-like effects including drug discrimination responses that neither single-enzyme inhibitor could achieve, revealing cooperative endocannabinoid signaling.
2009 / Animal Study / Moderate evidenceThe first selective MAGL inhibitor (JZL184) raised mouse brain 2-AG eightfold and produced CB1-dependent analgesia, hypothermia, and reduced movement, establishing 2-AG as a key endocannabinoid modulator.
2009 / Animal Study / Preliminary evidenceCBD (20 mg/kg) reversed THC-induced social withdrawal in rats at low doses, but the combination of high doses of both compounds impaired social interaction, possibly through sedation.
2009 / Cross Sectional / Preliminary evidenceAlcohol cue imagery increased anandamide levels and correlated with craving in 11 social drinkers, but this endocannabinoid response was absent in 12 abstinent alcoholics with markedly reduced baseline levels.
2009 / Randomized Controlled Trial / Preliminary evidenceIn a 12-week trial of 50 marijuana-dependent participants, buspirone showed a non-significant trend toward more negative drug tests overall, but a significant effect among those who completed treatment.
2009 / Animal Study / Preliminary evidenceTen days of cannabinoid receptor activation produced antidepressant-like effects in male and female rats through the noradrenergic system, but the effect was eliminated by precipitated withdrawal.
2009 / Review / Moderate evidenceA comprehensive review described the endocannabinoid system's role across nearly every organ system, from brain signaling and metabolism to immunity and reproduction.
2009 / Animal Study / Preliminary evidenceCBD (5 mg/kg daily) reduced bone loss, inflammatory cytokines, and RANKL/RANK expression in rats with experimentally induced periodontal disease over 30 days.
2009 / Case Report / Preliminary evidenceA tetraplegic MS patient experienced daily out-of-body experiences triggered by cannabis treatment for spasticity, with measurable changes in mental body imagery after consumption.
2009 / Review / Moderate evidencePublished three months after rimonabant's withdrawal, this review by Roger Pertwee proposed five strategies for developing cannabinoid medicines without psychoactive side effects — from peripheral restriction to cannabinoid-opioid synergy.
2009 / Review / Moderate evidenceA review found that cannabinoids showed predominantly inhibitory effects on tumor growth, migration, angiogenesis, and metastasis in preclinical studies, though immunosuppressive properties could complicate in vivo effects.
2009 / Longitudinal Cohort / Strong evidenceIn 50,087 Swedish men followed for 33 years, the apparent link between cannabis use and suicide (OR 1.62) was fully explained by pre-existing psychological and behavioral problems (adjusted OR 0.88).
2009 / Animal Study / Moderate evidenceTHC impaired long-term memory in mice by activating the mTOR/p70S6K protein synthesis pathway in the hippocampus through CB1 receptors on inhibitory neurons, an effect blocked by rapamycin.
2009 / Randomized Controlled Trial / Preliminary evidenceOpioid-dependent patients who used cannabis intermittently during naltrexone treatment stayed 133 days vs 35 days for abstainers or consistent users, replicating a previous finding.
2009 / Case Report / Preliminary evidenceA patient experienced suicidal ideation immediately after cannabis use on two separate occasions, independent of depression or life stressors, suggesting an acute pharmacological trigger in a vulnerable individual.
2009 / Randomized Controlled Trial / Moderate evidenceAfter smoking the same THC dose, occasional cannabis users were impaired on 3 of 4 cognitive tasks while heavy users showed impairment only on motor inhibition at high blood levels, demonstrating functional tolerance.
2009 / Cross Sectional / Preliminary evidenceAmong 350 medical cannabis patients, 66% used cannabis as a substitute for prescription drugs, 40% for alcohol, and 26% for illicit drugs, citing fewer side effects and better symptom control.
2009 / Animal Study / Preliminary evidenceTHC withdrawal induced the Narp gene in the amygdala, the same response seen with opiate and nicotine withdrawal, suggesting a shared molecular mechanism across drug withdrawal.
2009 / Cross Sectional / Preliminary evidenceEcstasy users showed worse memory performance and distinct brain activation changes compared to both controls and cannabis users, though some neural effects overlapped between ecstasy and cannabis groups.
2009 / Longitudinal Cohort / Moderate evidenceAmong 464 cannabis users from a twin-family study, those who experienced stronger subjective effects were 3-12 times more likely to become heavy users, even after controlling for genetic risk.
2009 / Cross Sectional / Preliminary evidenceHeroin users showed fearful-avoidant attachment, ecstasy users showed mixed insecure patterns, and cannabis users were mainly dismissing or secure, suggesting different drugs serve different emotional regulation needs.
2009 / Animal Study / Moderate evidenceBoth FAAH and MAGL inhibitors reduced THC withdrawal signs in dependent mice without causing dependence or motor impairment, though FAAH knockout mice showed normal withdrawal.
2009 / Review / Moderate evidenceCannabis impaired automatic driving functions and prompted compensatory behavior, while alcohol impaired complex tasks without compensation. Combining both eliminated compensation and multiplied impairment.
2009 / Review / Moderate evidenceRCTs found no objective Ashworth scale improvement with cannabinoids for MS spasticity, but patients reported significant improvement in spasticity (p=0.01), spasms, sleep, and pain.
2009 / Longitudinal Cohort / Moderate evidenceAmong 3,459 bipolar patients followed for 12 months, cannabis users had less treatment compliance, more mania, more psychosis, and higher overall illness severity with little evidence of confounding.
2009 / Animal Study / Preliminary evidenceEndocannabinoid blockade reduced positive and increased negative emotional responses in mice, effects that were altered by chronic nicotine exposure, suggesting interactions between the two systems in mood regulation.
2009 / Case Report / Preliminary evidenceA 20-year-old developed dependence on Spice Gold over 8 months, with physical withdrawal including elevated blood pressure (180/90), tachycardia (125 bpm), sweating, and tremor resembling cannabis withdrawal.
2010 / Cross Sectional / Preliminary evidenceYoung adults with adolescent cannabis use showed worse executive attention performance and stronger right prefrontal brain activation, suggesting less efficient attentional processing.
2010 / Systematic Review / Moderate evidenceA systematic review found only 7 RCTs on treating cannabis use in psychosis/depression, with preliminary evidence supporting medication treatment of the primary disorder and longer psychological interventions.
2010 / Cross Sectional / Moderate evidenceChronic cannabis users (17 years average) showed altered brain electrical patterns during memory encoding, with greater changes linked to longer use and earlier onset.
2010 / Cross Sectional / Moderate evidenceChronic cannabis users showed more Stroop conflict errors and altered brain electrical patterns during conflict resolution, with earlier use onset predicting worse performance.