2016 / Systematic Review / Strong evidenceA systematic review of 21 studies found that biomarker patterns in urine, blood, oral fluid, and hair can distinguish passive cannabis exposure from active use, though extreme exposure can trigger positive tests.
2016 / Review / Moderate evidenceA review explored novel CVS treatments and challenged the assumption that cannabis straightforwardly causes hyperemesis, suggesting the endocannabinoid system itself may be a treatment target.
2016 / Review / Moderate evidenceA comprehensive review detailed how anandamide and 2-AG are synthesized from membrane phospholipids and degraded by FAAH, MAGL, and oxidative enzymes.
2016 / Animal Study / Preliminary evidenceChronic FAAH inhibition in hypertensive rats further elevated liver endocannabinoid levels but worsened oxidative stress, despite reducing inflammation.
2016 / Review / Moderate evidenceA review found medical marijuana shows promise for cancer symptoms with preclinical anticancer signals, but evidence-based dosing is lacking and legal barriers hinder research.
2016 / Longitudinal Cohort / Strong evidenceA study of 34,000+ US adults found cannabis use predicted a 6.2x higher risk of substance use disorders over three years, but was not associated with mood or anxiety disorders.
2016 / Cross Sectional / Preliminary evidenceA survey of 244 chronic pain patients at a Michigan dispensary found medical cannabis use was associated with 64% less opioid use, fewer medication side effects, and 45% better quality of life.
2016 / Review / Moderate evidenceA pharmacology review explained how CBD can reduce some of THC's psychoactive effects, a relationship that led to the development of the THC/CBD drug Nabiximols.
2016 / Review / Moderate evidenceCannabis impairs driving by increasing lane weaving and following distance, with cognitive deficits lasting weeks after cessation and combined alcohol-cannabis use worsening impairment.
2016 / Case Report / Preliminary evidenceA case of severe cannabis hyperemesis worsened with prescription THC, providing direct evidence that THC drives the condition. Symptoms resolved after 12 months of cannabis abstinence.
2016 / Meta Analysis / Strong evidenceA meta-analysis found cannabis use associated with 2.6x suicide death risk, 1.4x suicidal ideation risk, and 2.2x suicide attempt risk, with heavy use approximately doubling these figures.
2016 / Case Report / Preliminary evidenceA case report described CHS being mistaken for eating disorder purging in a patient with a real history of anorexia nervosa, diagnosed only after collateral history and drug screening.
2016 / Cross Sectional / Moderate evidenceIn a study of 344 Aboriginal women, 20.5% used cannabis during pregnancy, and their babies were 565g lighter with 3.9x higher odds of low birth weight after adjusting for social factors.
2016 / Animal Study / Preliminary evidenceRats exposed to cannabis smoke at human-relevant THC levels showed biphasic activity changes, reduced anxiety, and developed physical dependence confirmed by precipitated withdrawal signs.
2016 / Review / Moderate evidenceA neuroimaging review found marijuana use is associated with brain structure and function changes, with adolescent-onset use showing the most concerning patterns of alteration.
2016 / Case Report / Preliminary evidenceA 16-year-old developed a perforated duodenal ulcer after 3 years of synthetic cannabinoid use, requiring emergency surgery with successful recovery.
2016 / Cross Sectional / Preliminary evidenceAmong 80 rehab patients, those with ADHD started using substances earlier, and earlier cannabis onset in ADHD patients predicted more severe later cannabis and cocaine use.
2016 / Animal Study / Preliminary evidenceNovel synthetic cannabinoids AKB48 and 5F-AKB48 caused seizures, aggression, sensory impairment, and dopamine release in mice, with the fluorinated version being more potent.
2016 / Cross Sectional / Moderate evidenceAnalysis of 430 US poison center calls for edible marijuana found children under 5 were most affected (25%), calls rose yearly, and 91% came from states with decriminalized cannabis.
2016 / Longitudinal Cohort / Moderate evidenceMothers' tobacco and alcohol use predicted earlier alcohol onset in children, while fathers' marijuana combined with alcohol use was also significant, challenging the focus on paternal risk.
2016 / Cross Sectional / Moderate evidenceGenetic risk scores for schizophrenia predicted cannabis and cocaine involvement, while depression genetic risk predicted cannabis use and severe cocaine dependence, in 2,573 participants.
2016 / Longitudinal Cohort / Preliminary evidenceIn 116 veterans attempting cannabis cessation, PTSD symptoms predicted declining friend support over 6 months, but only among those who relapsed in the first month.
2016 / Case Report / Preliminary evidenceExpert clinicians discussed the assessment and management of an adolescent marijuana use disorder, sharing clinical reasoning in a case conference format.
2016 / Review / Moderate evidenceA policy review criticized simplistic youth drug prevention and recommended the IOM three-tiered model with Student Assistance Programs and stable marijuana tax funding.
2016 / Randomized Controlled Trial / Moderate evidenceAn internet-based prevention program improved alcohol and cannabis knowledge in 1,103 Australian students and reduced alcohol use, but had no effect on cannabis use or cannabis intentions.
2016 / Review / Moderate evidenceA review examined alternatives to direct cannabinoid receptor activation, including FAAH, MAGL, and COX-2 inhibitors that boost the brain's own cannabinoids for potentially better therapeutic profiles.
2016 / Review / Strong evidenceRandomized trials provide Class 1-2 evidence for cannabinoids treating MS spasticity and pain, but cognitive side effects are a particular concern in this already-impaired population.
2016 / Cross Sectional / Moderate evidenceAmong nearly 30,000 adults over 50, marijuana-only users had 1.5x higher odds of depression vs. non-users, though they fared better than users of other illicit drugs.
2016 / Case Report / Preliminary evidenceSix CHS cases at one Spanish hospital showed a 6.1-year average diagnostic delay, highlighting persistent clinical unawareness despite the condition being described over a decade earlier.
2016 / Review / Moderate evidenceSynthetic cannabinoid dependence and withdrawal are underrecognized problems with no established treatment, though benzodiazepines and quetiapine may provide some relief.
2016 / Review / Moderate evidenceThe endocannabinoid system regulates normal placenta development; THC can disrupt trophoblast proliferation, death, and function, providing a mechanism for cannabis-related fetal growth restriction.
2016 / Cross Sectional / Preliminary evidenceNew Jersey medical marijuana patients waited nearly 6 months on average to get treatment, with chronic pain and spasticity as the top conditions and half referred by physicians.
2016 / Observational / Preliminary evidenceHeavy users showed lower brain CB1 receptor availability at baseline, but the difference from controls disappeared after two days without cannabis.
2016 / Observational / Strong evidencePET imaging showed cannabis-dependent males had 15% fewer CB1 receptors than controls, but receptors normalized to control levels after just 2 days of abstinence.
2016 / Review / Moderate evidenceCannabinoids modestly reduce cancer pain and are useful backup antiemetics, dronabinol improves taste disturbances, and preclinical data show anticancer potential through multiple mechanisms.
2016 / Animal Study / Preliminary evidenceFour third-generation Spice/K2 compounds showed CB1 binding up to 30x higher than JWH-018, with potent dopamine release in the brain's reward center.
2016 / Animal Study / Preliminary evidenceNatural variation in anandamide levels and FAAH activity in a specific brainstem region correlated with resting heart rate in rats, with anandamide injection increasing heart rate.
2016 / Review / Preliminary evidenceA theoretical review proposed cannabinoids as potential psoriasis treatments based on the endocannabinoid system's intersection with immune and nervous system pathways involved in the disease.
2016 / Pilot Study / Moderate evidenceThe clinical program that turned CBD into the first FDA-approved cannabis-derived drug. Open-label trial: 214 patients, 36.5% seizure reduction. NEJM RCT: 120 Dravet patients, seizures dropped from 12.4 to 5.9/month vs placebo (p=0.01). Epidiolex approved June 2018.
2016 / Animal Study / Preliminary evidenceCB2 receptor ligands showed extreme functional selectivity, with drugs behaving as agonists, antagonists, or having no effect depending on which cellular pathway was measured.
2016 / Animal Study / Preliminary evidenceCB2 receptor activation mimicked retinoic acid in stimulating meiotic gene expression in sperm precursors, and both over- and under-activation disrupted the spermatogenic timeline in mice.
2016 / Retrospective Cohort / Strong evidenceAnalysis of 2,638 driver fatalities found cannabis and amphetamines elevated crash risk, while prescription opioids, benzodiazepines, and antidepressants alone did not significantly increase crash responsibility.
2016 / Observational / Moderate evidenceAnalysis of 38,681 DEA-seized samples showed cannabis THC tripled from ~4% to ~12% between 1995–2014 while CBD nearly disappeared.
2016 / Cross Sectional / Preliminary evidenceAmong 273 pregnant former smokers, 14% had a lifetime cannabis use disorder, with having multiple psychiatric disorders as the overwhelming strongest predictor (36x odds).
2016 / Cross Sectional / Strong evidenceAmong 5,677 young Swiss men, ADHD was independently associated with earlier drug initiation, riskier use patterns, and more substance disorders, even after controlling for antisocial personality.
2016 / Observational / Preliminary evidenceA CNR1 gene variant moderated how much nicotine withdrawal disrupted brain function, with some genetic profiles showing greater cognitive disruption during deprivation.
2016 / Cross Sectional / Moderate evidenceNational survey data from 2002-2014 showed probationers and parolees had substance use disorder rates four to nine times higher than the general population, with marijuana dependence significantly elevated but still less common than alcohol disorders.
2016 / Longitudinal Cohort / Strong evidenceA 3-year prospective study of the US population found cannabis use was not associated with increased risk of developing anxiety disorders, though people with panic disorder were more likely to start using cannabis.
2016 / Observational / Moderate evidenceReal-world registry and observational data from over 1,100 patients across four European countries showed the THC:CBD spray Sativex had strong continuation rates and no evidence of addiction during long-term MS spasticity treatment.
2016 / Longitudinal Cohort / Moderate evidenceA study of nearly 10,000 Australian twins found that while lifetime cannabis use and self-injury share genetic roots, early cannabis use before age 17 appears to carry independent risk for self-harm even after accounting for genetics.