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.

RationaleDepressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome.ObjectivesThe objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients’ emotional processing biases.MethodsSeventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin.ResultsWe found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010).ConclusionsPsilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.Electronic supplementary materialThe online version of this article (10.1007/s00213-017-4754-y) contains supplementary material, which is available to authorized users.

Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.

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