Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: a placebo-controlled trial

Abstract

Background: Cannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research.

Method: The individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions.

Results: Cannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of 'stoned' and 'dizzy' induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure.

Conclusions: Relative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences.

Keywords: Cannabis; co-administration; drug-interaction; marijuana; memory; psychosis; tobacco.

Fig. 1.

Drug administration was conducted using ‘joints’, the most common method of administering cannabis (Hindocha et al. 2016). ‘Study drug’ region contained a mixture of 66.67 mg cannabis (active or placebo) and 311 mg tobacco (active or placebo) dependent on condition (see Table 1). The ‘placebo tobacco filler’ region contained 311 mg of placebo tobacco at the bottom of the joint (nearest to the mouth), which was not smoked. This filler was added to improve compliance with the fixed inhalation procedure (see online Supplementary Materials), as puff volume typically decreases towards the end of the joint, probably due to rising heat (Van Der Pol et al. 2014). The stop line is the point at which participants stopped smoking the joint, separating the two regions. It was marked 1 cm after the ‘study drug’ to ensure complete inhalation.

Fig. 2.

(a and b) Immediate recall (a) and delayed recall (b) under each drug condition for both story 1 (where encoding was not intoxicated) and story 2 (where encoding was intoxicated). Under delayed recall, for story 2, we found CAN-TOB in comparison with CAN, improves delayed recall but this was not the case for immediate recall, therefore suggesting effects on retrieval of information that had previously been successfully encoded. Error bars show ±s.e.m.

Fig. 3.

(a–d) Number of correct responses (a & b) and d′ (c & d) for cannabis v. placebo (a & c) and tobacco v. placebo (b & d) for the N-back. Error bars show ±s.e.m.

Fig. 4.

(a–f) carbon monoxide (CO), cardiovascular (heart rate (HR), systolic and diastolic blood pressure (mmHg)) and self-reported effects for stoned and dizzy for all time points before (T1) and after (T2–T5) each drug administration. Error bars show ±s.e.m.