Cannabis and Cognitive Functioning: From Acute to Residual Effects, From Randomized Controlled Trials to Prospective Designs

Abstract

In recent years, several jurisdictions have revised their regulation policy toward both medical and recreational use of cannabis. These changes have elicited concerns regarding how legalization impacts academic achievement and work performance. This review evaluates the acute and long-term (residual) association between cannabis use and cognitive functioning that underlies poor academic and work performance. Relative to other reviews, this article focuses on cross-over randomized controlled trials and prospective designs given that they allow to test the impairing effects of cannabis exposure at the within-subject level. Acute cannabis cognitive effects are discussed separately for known confounding factors such as levels of delta-9-tetrahydrocannabinol (Δ⁹-THC), Δ⁹-THC:cannabidiol ratio, previous cannabis use and, comorbidity with psychosis-spectrum disorders. The cognitive residual effects of cannabis are detailed in relation to duration of abstinence, frequency of use, comorbidity with psychosis-spectrum disorders, types of cognitive domains assessed, and age of cannabis use initiation. Moreover, considering the fact that adequate longitudinal studies can make inferences about causality between cannabis use and impaired cognitive functioning when disentangling between-subject from within-subject variation, proofs for the three main non-mutually exclusive hypotheses about this relationship will be presented: i) the cognitive vulnerability hypothesis as part of the more general common antecedent hypothesis, ii) the concurrent cannabis impairing hypothesis, and iii) the neurotoxic hypothesis of cannabis. Current research provides evidence for mild to moderate acute cannabis effects on episodic and working memory, processing speed, and executive functions. Mild residual impairing effects were also observed in these exact same cognitive domains, suggesting that adverse effects following cannabis intoxication persist at least days or weeks following cannabis abstinence. Relative to adult-onset, adolescent-onset cannabis use seems to explain the dose-response relationship and is associated with longer lasting residual effects even in mild users (<weekly). The association between cannabis and cognition is likely explained by common antecedents, such that genetic and shared environment factors predispose individuals to both cannabis use and cognitive deficits, and to a lesser degree, neurotoxic effects.

Keywords: cannabis; cognition; delta-9-tetrahydrocannabinol; longitudinal design; memory.

Figure 1

Representation of the cognitive vulnerability, concurrent, and neurotoxicity hypotheses relative to the association between cannabis use and cognitive functioning. The cognitive vulnerability hypothesis (represented by the green square) posits that before onset of cannabis use, future cannabis users already exhibit cognitive deficits. The common antecedent hypothesis, which offers a more general framework than the cognitive vulnerability hypothesis, posits that unknown common factors could be responsible for cannabis use onset and mild cognitive deteriorations, without cannabis use being the causal factor of the aforementioned cognitive deficits. Black dotted arrows allow to investigate the neurotoxic hypothesis by testing if previous cannabis use (t−1) predicts subsequent cognitive functioning (t), while controlling for frequency of cannabis use at time t. Lastly, black bidirectional arrows between cognitive abilities and cannabis use at every time-point represent the concurrent hypothesis. Indeed, cognitive performance at time t is associated with cannabis use at time t, without necessarily persisting effects through time.