The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers
C. Hindocha, T. P. Freeman, M. Grabski, H. Crudgington, A. C. Davies, J. B. Stroud,
R. K. Das, W. Lawn, C. J. A. Morgan & H. V. Curran
Scientific Reports, 2018, 8, 7568
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.
Nicotine withdrawal consists of multiple physiological, affective and cognitive symptoms that can peak within hours of stopping smoking (1–3). Grabski, et al. (4) recently conducted a meta-analysis of cognitive tasks sensitive to tobacco abstinence. Abstinent smokers, in comparison to satiated smokers, show greater impulsivity on two specific tasks, delay discounting (defined as the degree to which one prefers smaller, immediate rewards over larger, more delayed rewards (5)) and response inhibition (the ability to stop a pre-potent response e.g. craving for cigarettes; a marker of executive functioning; and theoretically important for successful smoking cessation (6)). Abstinent smokers also showed impaired arithmetic and recognition memory ability, both of which includes a core component of working memory and were therefore interpreted as potential evidence for effects of abstinence on working memory (7,8). Therefore, pharmacotherapies targeting improving cognition during tobacco abstinence may be useful for the treatment of tobacco use disorders.
Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, may have a novel application in nicotine withdrawal9. Thus far, CBD has been shown to reduce craving in both pre-clinical and clinical models of heroin addiction (10,11). Furthermore, it may have a specific utility in cigarette smoking. Morgan, et al. (12) found that a single week of ad-hoc CBD via inhaler, compared to placebo, reduced cigarette smoking by almost 40%, however craving was unaffected. Hindocha et al. (9) found that 800 mg oral CBD, in comparison to placebo, reversed attentional bias away cigarette cues, and reduced explicit liking of cigarette stimuli but this also occured in the absence of changes in withdrawal and craving. CBD may also have pro-cognitive effects and has, in multiple studies, been shown to protect against the detrimental cognitive effects of THC, and particularly in the domains of verbal episodic and recognition memory (13–16). In regards to impulsivity, Bhattacharyya, et al. (17) found opposite effects of THC and CBD in the para-hippocampal gyrus during a response inhibition task. Borgwardt, et al. (18) found CBD deactivated the left temporal cortex and insula but was not associated with increases in regional activity relative to placebo. Finally, no research has investigated the effects of CBD on delayed discounting.
Experimental medicine approaches to study tobacco abstinence are cost-effective and mechanistic evaluations of a medication, and may facilitate drug discovery (19). We hypothesise that after overnight cigarette abstinence in dependent cigarettes smokers, CBD would improve performance in working and verbal episodic memory and on impulsivity tasks, in comparison to placebo.