Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function

Abstract

The main active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC), can acutely induce psychotic symptoms and impair episodic and working memory. Another major constituent, cannabidiol (CBD), may attenuate these effects. This study aimed to determine the effects of THC and CBD, both alone and in combination on psychotic symptoms and memory function. A randomised, double-blind crossover design compared the effects of (i) placebo, (ii) THC 8 mg, (iii) CBD 16 mg and (iv) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser. Using an experimental medicine approach to predict treatment sensitivity, we selected 48 cannabis users from the community on the basis of (1) schizotypal personality questionnaire scores (low, high) and (2) frequency of cannabis use (light, heavy). The Brief Psychiatric Rating Scale (BPRS), Psychotomimetic States Inventory (PSI), immediate and delayed prose recall (episodic memory), 1- and 2-back (working memory) were assessed on each day. Results indicated that THC increased overall scores on the PSI, negative symptoms on BPRS, and robustly impaired episodic and working memory. Co-administration of CBD did not attenuate these effects. CBD alone reduced PSI scores in light users only. At a ratio of 2:1, CBD does not attenuate the acute psychotic and memory impairing effects of vaporised THC. Frequent cannabis users may show a blunted anti- psychotic response to CBD, which is of concern due to the high rates of cannabis use disorders in patients with schizophrenia.

Fig. 1

Effects of THC and CBD alone and in combination, along with placebo, across the whole sample on subscales of psychotomimetic symptoms (PSI). THC and THC + CBD increased perceptual distortions (b) and cognitive disorganisation (c) but not other subscales (a; d; e; f). THC = T (Black shading), THC + CBD = T (grey shading), CBD = C, Placebo = P

Fig. 2

Analysis of effects of THC, CBD, the combination and placebo in low frequency (light) and high frequency (heavy) cannabis users on total psychotomimetic symptom scores

Fig. 3

Effects of THC, CBD, the combination and placebo on positive and negative symptoms on the Brief Psychiatric Rating Scale

Fig. 4

Effects of THC, CBD, the combination and placebo on episodic memory on the prose recall task

Fig. 5

Working memory. Effects of THC, CBD, the combination and placebo on working memory in the N back task, for a d′ an index of discriminability, and b reaction time on the task