THC Titration of High-Potency Cannabis Concentrates: A Randomized Cross-Over Trial

High-potency cannabis use is associated with public health risks, such as cannabis use disorder, psychotic disorders, and impaired cognition. Legal markets in the US and Canada are geared towards the commercialization of high-tetrahydrocannabinol (THC) products, including concentrates as high as 90-95%. The cannabis industry has resisted regulation of higher-potency products claiming that cannabis consumers naturally self-titrate their use, but the limited evidence to date suggests that even though consumers may use less cannabis as potency rises, consuming higher potency products still leads to greater THC consumption. The investigators will use a randomized crossover trial to evaluate the ability of 36 regular cannabis consumers (18 females and 18 males) to self-titrate the THC dose when vaping concentrates to achieve the desired psychoactive effects. The investigators will also characterize and compare the subjective, cognitive, physiological, and pharmacokinetic effects between cannabis concentrates of different potencies (30%, 60%, and 90% THC). Working with US scientists, the setting of this study will be Toronto, Canada, in the context of federal legalization of cannabis, unique access to cannabis products not available in the US for research purposes, and an encouraging regulatory environment. The investigators will test commercial products that are representative of the THC ranges available in the legal market. Aim 1: To evaluate the ability of regular cannabis consumers to self-titrate their THC dose when vaping concentrates of different potencies. The investigators will compare markers of titration (biological: THC blood levels; behavioral: inhalation topography; subjective: self-reported levels of intoxication) over a range of potencies for a comprehensive characterization of titration practice. The investigators hypothesize that participants will be able to partially but not proportionally reduce THC intake with increase in THC potency. In other words, the investigators anticipate that the proportional decrease in blood THC levels will be lower than the proportional increase in THC concentrations. Aim 2: To compare the cognitive impairment, physiological effects, and addiction liability of consuming lower versus higher THC potency concentrates. The investigators hypothesize that cognitive impairment and physiological effects will be less pronounced with lower-THC concentrates in a dose-response fashion. The investigators will also explore differences in addiction liability between potencies as higher THC concentrations may result in greater dysphoric reactions. These acute effects may be related to long term harms such as accidents, CVD events, and CUD. Exploratory Aim: To explore sex differences in titration efficiency, blood THC concentrations, cognitive impairment, physiological effects, and addiction liability. The investigators propose to analyze sex differences in our primary and secondary outcomes (e.g., whether females will be able to titrate more efficiently than males). This experimental evidence will provide data on the potential acute harms related to concentrates and inform policy decisions on the need to decrease access and/or prevent their initiation and implement information and education campaigns to increase awareness on the risks of using them.