Data_Sheet_1_Cannabis and Cognitive Functioning: From Acute to Residual Effects, From Randomized Controlled Trials to Prospective Designs.docx

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 (