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

Abstract

Background and AimsCannabidiol (CBD), a non‐intoxicating cannabinoid found in cannabis, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side effects and research showing that 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; and (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette‐related stimuli, craving and withdrawal and not produce any side effects.DesignRandomized, double‐blind cross‐over study with a fixed satiated session followed by two overnight abstinent sessions.SettingUK laboratory.ParticipantsThirty non‐treatment‐seeking, dependent cigarette smokers recruited from the community.Intervention and comparator800 mg oral CBD, or matched placebo (PBO) in a counterbalanced orderMeasurementsAB 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.FindingsWhen participants received PBO, tobacco abstinence increased AB (P = 0.001, d = 0.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (P = 0.007, d = 0.704) and no longer differed from satiety (P = 0.82). Compared with PBO, CBD also reduced explicit pleasantness of cigarette images (P = 0.011; d = 0.514). Craving (Bayes factor = 7.08) and withdrawal (Bayes factor = 6.95) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence.ConclusionsA single 800‐mg oral dose of cannabidiol reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. Cannabidiol did not influence tobacco craving or withdrawal or any subjectively rated side effects.

Cigarette smoking quit ratios among adults in the USA with cannabis use and cannabis use disorders, 2002–2016

“…Our results suggest that any reported cannabis use was associated with significantly lower smoking quit ratios, relative to those who did not use cannabis. Cannabidiol has been proposed as a treatment for a number of addictive substances,44 and studies have begun to examine cannabidiol as a method of reducing cigarette smoking 45 46. While these studies, and studies of other cannabinoid agents,47 find promising results for cigarette smoking behaviours, the simple ad hoc use of cannabis in the current sample did not appear to improve cigarette smoking quit ratios.…”

Anti-inflammatory agents for smoking cessation? Focus on cognitive deficits associated with nicotine withdrawal in male mice

“…As a whole, these data indicate that cannabidiol might improve cognitive performance during nicotine withdrawal through the modulation of inflammation and cell proliferation. Interestingly, preliminary findings in humans show that cannabidiol reduces cigarette consumption (Morgan et al, 2013), and pleasantness of cigarette cues after overnight abstinence (Hindocha et al, 2018a) in tobacco smokers. In contrast, a recent study has shown that acute administration of a single dose of cannabidiol did not improve memory performance in tasks previously shown to be impaired during cigarette abstinence (Hindocha et al, 2018b).…”

“…Interestingly, a potential usefulness of cannabidiol in tobacco addiction has been shown in recent clinical studies (Morgan et al, 2013;Hindocha et al, 2018a). Thus, cannabidiol administration reduces cigarette consumption in tobacco smokers (Morgan et al, 2013), and the salience and pleasantness of cigarette cues after overnight abstinence in dependent smokers (Hindocha et al, 2018a).…”

Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme

“…Endocannabinoid signaling is terminated by enzymes such as FAAH. FAAH inhibition is a mechanism that is currently being investigated as a treatment of CUD in humans . The rs324420 single‐nucleotide polymorphism (SNP) of the FAAH enzyme is a C‐to‐A polymorphism, which results in a proline to a threonine substitution at codon 129.…”

“…We focused upon three endophenotypes of CUD, which are distinct but related processes. Firstly, attentional processing is an important transdiagnostic marker for depression, anxiety, and drug dependence . THC‐to‐CBD ratio predicts attentional bias to cannabis cues when intoxicated, with those using more CBD in their cannabis strains showing reduced attentional bias .…”