There is increasing recognition of the roles of the endocannabinoid system in neurobiological
processes and behavioral domains relevant to addiction. The non-psychoactive phytocannabinoid
cannabidiol (CBD) has attracted considerable attention due to its lack of abuse potential, its excellent safety
profile, its unique and complex pharmacology, and evidence that it affects anxiety and stress response in
animal models and humans. There is a growing body of preclinical data demonstrating that CBD produces
marked and persisting decreases in alcohol self-administration and preference for alcohol, and alcohol-,
cue- and stress-induced reinstatement of alcohol-seeking behavior, yet there are few studies of the effects
of CBD in humans with addictive disorders, and none in alcohol dependent patients.
The goal of the proposed project is to begin rigorous study of the clinically relevant effects of CBD in
patients with severe alcohol use disorder (AUD). This double-blind, randomized proof-of-concept study (n =
40) is designed to assess feasibility and contrast effects of extended (8 weeks) treatment with CBD to those
of placebo in AUD patients. Participants with AUD will be randomized to receive either placebo or 600mg
CBD/day (PO) for 4 weeks, immediately followed by 1200mg CBD/day (PO) for an additional 4 weeks (8
total weeks). These doses were chosen to reproduce serum CBD levels reported to reduce alcohol-seeking
behavior in animal studies. Measures will include circulating levels of CBD, safety measures (THC serum
levels, adverse events, cognitive and motoric function), and physiological and psychological domains
relevant to AUD (including self-reported craving, depression, and anxiety, and responses to personalized
scripts designed to elicit stress- and cue-induced craving and anxiety). Assessments will be conducted
following 1 day, 1 week, and 4 weeks of treatment with each dose of CBD vs. placebo, and 1 and 4 weeks
after the cessation of treatment. Drinking outcomes across 8 weeks of treatment and 4 weeks of follow-up
will also be assessed as an exploratory outcome.
The proposed study is innovative and significant from both scientific and clinical perspectives. There
is an urgent need for novel treatments for AUD, particularly strategies that target underlying addiction
pathophysiology. Based on animal data, CBD, with mechanisms of action quite distinct from currently used
medications, may induce persisting disease-modifying changes with relatively brief treatment exposure.
Clinically relevant effects would have significant implications for drug development and for the mechanistic
understanding of AUD and perhaps other addictive disorders.