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.

Public Health Relevance

(Relevance) The naturally-occurring, non-psychoactive phytocannabinoid cannabidiol (CBD) has been shown to benefit several aspects of behavior and cognition relevant to addiction without producing any of the intoxicating or psychotomimetic effects typically associated with tetrahydrocannabinol (THC). However, CBD has not been extensively examined in humans with addictive disorders, and limited data exists on CBD's safety in human alcohol use disorder (AUD) populations. This study investigates the safety and impact of CBD on AUD-related domains in AUD patients to provide information about the therapeutic potential and mechanism of CBD's effects in the treatment of alcoholism.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Exploratory/Developmental Grants (R21)
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National Institute on Alcohol Abuse and Alcoholism Initial Review Group (AA)
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Falk, Daniel Evan
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New York University
Schools of Medicine
New York
United States
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