Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal

Abstract

BACKGROUND AND AIMS: Cannabidiol (CBD), a non-intoxicating cannabinoid, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side-effects and research showing it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette-related stimuli and increased craving and withdrawal; (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette-related stimuli, craving and withdrawal and not produce any side-effects. DESIGN: Randomized, double-blind crossover study with a fixed satiated session followed by two overnight abstinent sessions. SETTING: UK laboratory. PARTICIPANTS: Thirty non-treatment seeking, dependent cigarette smokers recruited from the community. INTERVENTION AND COMPARATOR: 800mg oral CBD or matched placebo (PBO) in a counterbalanced order MEASUREMENTS: AB to pictorial tobacco cues was recorded using a visual probe task and an explicit rating task. Withdrawal, craving, side-effects, heart rate and blood pressure were assessed repeatedly. FINDINGS: When participants received placebo, tobacco abstinence increased AB (p=.001, d =.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (p=.007, d= .704) and no longer differed from satiety (p=.82). Compared with placebo, CBD also reduced explicit pleasantness of cigarette images (p=.011; d=.514). Craving (Bayes Factor: 7.07) and withdrawal (Bayes Factor: 6.48) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence. CONCLUSIONS: A single 800mg oral dose of cannabidiol (CBD) reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. CBD did not influence tobacco craving or withdrawal or any subjectively rated side-effects.