PROJECT SUMMARY/ABSTRACT As cannabis legalization has expanded, many novel products have emerged. Oral cannabis products (or “edibles”) are among the most popular. Similar to traditional forms of cannabis, edibles that contain delta-9- tentrahydrocannabinol (THC) as the primary constituent have abuse liability and can produce unwanted negative effects (e.g., cognitive/psychomotor impairment, panicked reactions). Cannabis users often report that edibles produce highly unpredictable effects, making these products prone to eliciting adverse events. Edibles are responsible for most emergency room visits related to cannabis over-intoxication. Inconsistency in cannabis edible effects likely stems, in part, from the large variety of formulations within this diverse product category. Preclinical research has shown that THC absorption is markedly increased when ingested in lipid or “nanoemulsion” formulations relative to non-lipid or non-nanoemulsion formulations; nanoemulsion is a process used to make cannabinoids more hydrophilic and purportedly, more bioavailable. Thus, these formulation characteristics may directly impact the magnitude of THC absorption and THC-related acute effects in humans. However, controlled clinical research on cannabis edibles is limited and few studies have evaluated if the formulation of these products influences pharmacokinetic (PK) or pharmacodynamic (PD) outcomes. The proposed, double-blind, placebo-controlled human laboratory study will compare the PK and PD effects of 3 popular types of cannabis edibles: THC-infused chocolates, gummies, and drinks. We hypothesize that THC absorption and resultant PD effects will be significantly greater for the chocolate (high lipid concentration) and drink (nanoemulsion formulation) relative to the gummy (low lipid concentration and no nanoemulsion). Healthy adults will attend 9 outpatient laboratory sessions. For each session, they will consume 1 of 3 cannabis edible formulations (chocolate, gummy, or nanoemulsion drink) at either 0mg THC (placebo), 10mg THC, or 25mg THC (i.e., 2 and 5 Standard THC Units, STUs); sessions will be preceded by 8 hrs of monitored overnight fasting. Sessions will be completed in a randomized order and separated by at least 1 week. PD assessments will include a battery of cognitive/psychomotor performance tasks and a subjective drug effect questionnaire, all shown to be sensitive to cannabis at the proposed STUs. Blood plasma will be collected to quantify concentrations of THC and its primary metabolites (11-OH-THC, THCCOOH). This project will determine whether the formulation of cannabis edibles influences PK/PD effects when THC doses are held constant, which is of growing importance given initiatives to utilize STUs for research and regulatory purposes. Data generated from this project can potentially inform educational efforts to reduce the incidence of adverse events caused by cannabis edibles and provide insight into whether cannabis edible formulation ...