Pharmacology & Therapeutics
October 20, 2018
Michael Bloomfield, Chandni Hindocha, Sebastian F Green et al.
236 citations
Cannabis and its primary psychoactive component, THC, acutely alter executive, emotional, reward, and memory processing by directly interacting with the endocannabinoid system and indirectly affecting glutamatergic, GABAergic, and dopaminergic systems. Cannabidiol, a non-intoxicating cannabinoid, may offset some of these acute effects. Heavy repeated cannabis use, especially during adolescence, is associated with adverse effects that increase the risk of mental illnesses such as addiction and psychosis. This review synthesizes human neuroimaging research on the acute and chronic neuropsychopharmacology of cannabis, covering effects during development, implications for psychosis and cannabis use disorder, and methodological considerations.
Frontiers in Psychiatry
February 9, 2023
Kees Kramers, Arnt Schellekens, Metten Somers et al.
119 citations
A systematic review of psilocybin-assisted therapy for substance use disorders identified four clinical trials (six articles) involving 151 patients, with doses from 6 to 40 mg. Three studies focused on alcohol use disorder and one on tobacco use disorder. In a pilot study (n=10), heavy drinking days decreased significantly. In another single-arm study (n=31), 32% achieved complete alcohol abstinence over an average of 6 years. A double-blind, placebo-controlled RCT (n=95) found significantly fewer heavy drinking days with psilocybin versus placebo. In a pilot study (n=15), smoking abstinence at 26 weeks was 80% and at 52 weeks 67%. All trials indicated beneficial effects, but larger RCTs are needed.
Drug and Alcohol Dependence
August 11, 2023
Teuntje A. D. Pelgrim, Johannes G. Ramaekers, Matthew B. Wall et al.
3 citations
THC, the main psychoactive component of cannabis, reduces functional connectivity in the salience network—a brain system involved in processing awareness and salient information—specifically weakening connections from the right insula to the left insula and anterior cingulate cortex. A trend toward decreased connectivity was also observed in the hippocampus-midbrain-striatum network, which may relate to acute psychotic-like effects. The COMT Val158Met genotype modulated subjective responses: individuals with the Met/Met genotype experienced the strongest dysphoric reactions and showed reduced connectivity in the hippocampus-midbrain-striatum network after THC. These findings suggest that prefrontal dopamine levels influence the acute effects of cannabis.
Psychedelic Medicine
October 8, 2025
Pim B. van der Meer, Nout Schukking, Miranda G. Dik et al.
A systematic review of clinical trials found limited evidence that psychoactive tryptamines other than psilocybin and ibogaine are effective for treating substance use disorders. Four trials involving 176 patients with alcohol use disorder tested dipropyltryptamine and diethyltryptamine. Abstinence rates ranged from 10% to 38% at 26 weeks of follow-up, and severity of alcohol use did not differ between the tryptamine and control groups. Adverse effects were poorly reported. The review concludes that studies are scarce and show limited evidence for effectiveness in treating addictive disorders.
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2021
Brandon Gunasekera, Cathy Davies, Grace Blest‐hopley et al.
preprint
A single dose of delta-9-tetrahydrocannabinol (THC) alters brain activation signals in a widespread network of regions, with some areas showing increased and others decreased activity. The magnitude of these changes is directly related to the local expression of the cannabinoid type-1 (CB1) receptor, but not the type-2 (CB2) receptor. THC increased activation in the anterior cingulate, superior frontal cortices, middle temporal and occipital gyri, striatum, amygdala, thalamus, and cerebellum crus II, while decreasing it in the middle temporal gyrus, superior temporal gyrus, angular gyrus, precuneus, cuneus, inferior parietal lobule, and cerebellum lobule IV/V. A dose-response relationship was observed in certain brain regions.