PROJECT SUMMARY There is a growing trend in the use of vaping devices used to administer liquid concentrates containing Δ9- tetrahydrocannabinol (THC). However, there is a gap in our knowledge and understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of THC delivered from this new generation of cannabis products. The literature on nicotine vaping has clearly shown that vaping product characteristics and user behaviors influence the PK/PD of vaped substances. Additionally, most cannabis consumers who vape liquid cannabis concentrates also report concurrent use of nicotine-containing vaping products (e-cigarettes). Building on strategies used to establish the evidence base on the PK/PD of nicotine-containing vaping products, this project will examine the PK/PD profile of THC-containing liquid concentrates delivered through vaping devices WITH and WITHOUT co-use of nicotine through completion of three specific aims: Aim 1 is to examine how vaping product characteristics and user behaviors impact the PK/PD of THC. Aim 1 will characterize the PK/PD variability in real-world settings. This will be achieved by using a mobile laboratory bus to recruit current vapers of THC-containing liquids and examine their PK/PD. Study participants will use their own commercially obtained THC cartridges ad lib through their usual vaping device. In Aim 2, a controlled laboratory paradigm will be used to compare the PK/PD profiles of equivalent standard THC units delivered from vaping liquids vs smoked cannabis. Aim 3 will assess the PK/PD profiles of THC vaping liquids sequentially administered with nicotine using a double-blind, placebo-controlled, randomized within-subjects trial design. This highly innovative approach will offer a significant advantage over the existing literature by combining naturalistic observational methods and controlled laboratory assessments to provide a depiction of the PK/PD of THC delivered through vaping liquids. The findings will be directly relevant for the existing cannabis market and consumers who use these products. This project will improve our understanding of the PK/PD effects of THC by characterizing the PK/PD profiles of THC vaping liquid formulations and devices used by cannabis consumers, establishing differences in the effects of these products relative to smoked cannabis, and providing necessary data on how co-use of vaped nicotine and THC may impact THC PK/PD. Data from this project will be highly relevant for informing future regulatory and consumer safety efforts for THC vaping products.