Nabilone Impairs Spatial and Verbal Working Memory in Healthy Volunteers

Background: Memory impairments and psychosis-like experiences can be adverse effects of cannabis use. However, reports on the cognitive impact of cannabis use are not consistent. There are also limited studies on the psychotomimetic effects of cannabinoid compounds to reveal the association between cannabis and psychosis. Therefore, we investigated the effect of acute cannabinoid intoxication on verbal working memory (VWM) and spatial working memory (SWM) following oral doses of the synthetic cannabinoid agonist, nabilone (1-2 mg, oral). We further investigated the effect of nabilone on psychosis-like experiences (schizotypy scores) and associations of schizotypy with VWM and SWM. Methods: Healthy participants (n=28) completed spatial and digit span tasks across different delay conditions (0, 6, 12, and 18 sec) after receiving nabilone (1-2 mg, PO) or placebo in a randomized, double-blind, counterbalanced, crossover manner. A subset of participants completed a short battery of schizotypy measures (n=25). Results: Nabilone impaired VWM (p=0.03, weak effect size η²=0.02) and SWM (p=0.00016, η²=0.08). Nabilone did not significantly change overall schizotypy scores. Schizotypy scores were negatively correlated with working memory (WM) averaged across all delays and both modalities, under placebo (ρ=-0.41, p=0.04). In addition, there were significant negative correlations between occasions of cannabis use and overall WM averaged scores across drug treatments (ρ=-0.49, p=0.007) and under placebo (ρ=-0.45, p=0.004). The results showed that the drug effect in the less frequent cannabis users was more pronounced on the SWM (p<0.01) and VWM (p<0.01), whereas there appeared to be little drug effect in the frequent cannabis users. Conclusion: Low doses of synthetic cannabinoid impaired SWM and VWM, indicating that exogenous activation of the cannabinoid system influences cognitive performance. Further, the results replicated previous findings that schizotypy is correlated with deficits in WM. Clinical Trial Registry Name: Nabilone and caffeine effects on the perceptions of visually, auditory, tactile and multimodal illusions in healthy volunteers. Clinical Trial Registration Number: CT-2018-CTN-02561 (Therapeutic Goods Administration Clinical Trial Registry) and ACTRN12618001292268 (The Australian New Zealand Clinical Trials Registry).