Development of Tetrahydrocannabivarin as a Treatment for Smokers

University Of California Los Angeles, Los Angeles CA

Investigators

Abstract

ABSTRACT Tobacco use is the leading cause of preventable death and disease in the United States. The majority of smokers report the desire to quit smoking; however only 3-5% of unaided quit attempts are successful; highlighting the need for TUD treatments. Currently, there are only three classes of FDA-approved pharmacotherapies for smoking cessation. While these medications have shown effectiveness in increasing abstinence during randomized clinical trials, the benefit of using such treatments decreases over the course of a year, and long-term quit rates rarely exceed 30%. Thus, innovations in treatment approaches are needed to reach further reductions in tobacco use. Δ9-Tetrahydrocannabivarin (Δ9-THCV) is a phytocannabinoid, which is thought to be a CB1 receptor antagonist and partial CB2 receptor agonist. Δ9-THCV has shown initial promise as a novel therapeutic for nicotine dependence and addictive disorders. Evidence from several animal models indicates that THCV reduces nicotine self-administration, reduces cue- and nicotine-induced relapse-like behavior, and improves nicotine withdrawal symptoms. The proposed study consists of a randomized, double- blind, counter-balanced, crossover human laboratory study of Δ9-Tetrahydrocannabivarin (Δ9-THCV) for daily smokers. A total of 32 daily smokers will complete two outpatient study visits after 5 days underΔ9-THCV and matched placebo, during which they will undergo a Smoking Lapse task to assess: (a) the ability to resist smoking, (b) cigarette smoking self-administration, (c) subjective craving, (d) withdrawal, and (e) subjective effects of nicotine. This study will test the initial efficacy of Δ9-THCV, which is essential for understanding the clinical potential of this naturally occurring cannabinoid as a treatment for smoking cessation. Given the wide prevalence cigarette use and the high acceptability of naturally-occurring products, such as cannabinoids, as therapeutic agents, the proposed study has the potential to be transformative in uncovering the therapeutic benefits of Δ9-THCV.