High confusion: evaluating effects of popular cannabis isolates on driving performance

Cannabis consumption is associated with increased crash risk. However, methodological and cannabis product heterogeneity across clinical research has complicated interpretation of which specific cannabinoid(s) cause impairment. Cannabis material contains over 100 unique cannabinoids, although most researchers and consumers are only interested in ∆⁹-tetrahydrocannabinol (∆⁹-THC) and cannabidiol (CBD). However, existing studies use full or broad-spectrum products, containing a mix of cannabinoids with the target compounds being the major components. Additionally, cannabis dosing studies have yet to adopt standardized dosing units or data harmonization measures that enable collection of comparable data across studies. Furthermore, cannabis clinical trial participant demographics do not represent those of the current cannabis user population. This hinders translatability and generalizability of results from those works. It is critical to systematically study popular cannabinoids in isolation and through standardized methods to inform risk, maximize benefits, and translate findings across disciplines.

To eliminate potential confounding variables and characterize the pharmacokinetics and pharmacodynamics of ∆⁹-THC we will administer Δ⁹-THC isolates, CBD isolates, and a placebo to participants whose demographics represent that of the current cannabis user population. This work will (1) characterize the pharmacokinetics of ∆⁹-THC and its major metabolites in venous blood, oral fluid, and dried capillary blood spots, following administration of a known amount of ∆⁹-THC isolate in healthy volunteers; and (2) compare effects of acute ∆⁹-THC isolate administration on cognition and driving performance to a CBD isolate and a placebo, in healthy volunteers. This work uses a double-blind, placebo-controlled crossover study with a balanced, demographically representative, and adequately powered participant pool. Results are directly translational through use of standardized dosing units (5mg/unit), assessment protocols from the PhenX Toolkit, and adoption of driving performance definitions and measures from the Society of Automotive Engineers (SAE) Recommended Practice Document J2944.