Moderators of the acute effects of cannabis in humans

The changing landscape of cannabis regulation has rapidly increased the availability of medicinal and recreational cannabis products. Understanding the consequences of cannabis use is a growing public health concern worldwide. More information is needed to inform policy and consumer education to reduce the potential harms associated with the drug. An important research priority is, therefore, to better understand which factors influence the acute effects of cannabis. A systematic review aimed to evaluate whether cannabidiol (CBD) might influence the effects of Δ9-tetrahydrocannabinol (THC). The review included 16 experimental studies reported in 23 academic articles. A broad range of outcomes were investigated, and findings across studies were mixed. Although CBD might reduce some of the negative effects of THC, there are still many unanswered questions about the dose, and the ratio between THC and CBD needed to improve the safety profile of cannabis. A mega-analysis of four experimental studies (n=128) used multilevel linear models and moderation analyses to investigate whether an individual's personality traits and recent cannabis use history predict their acute response to cannabis or THC. Increased frequency of cannabis use was associated with the development of differential tolerance to the subjective intoxication and psychotomimetic effects of THC. More frequent cannabis use was associated with higher levels of psychosis-like effects when not intoxicated. High trait schizotypy did not moderate the effect of THC on psychotomimetic experiences. A critical appraisal focusses on the research process and statistical considerations taken during the development and implementation of the mega-analysis.