Wednesday, April 2, 2025
4/2/2025
Effect of Cannabinoids on Tobacco Product Demand and Pharmacodynamics - PROJECT SUMMARY Cannabis and tobacco are two of the most widely used drugs and are frequently used together. People who use both cannabis and tobacco tend to have higher rates of problematic cannabis use and dependence, sustained long-term tobacco use, and poorer outcomes during treatment for tobacco use disorders. With rates of cannabis use on the rise, understanding the mechanisms driving cannabis and tobacco co-use is imperative for developing effective policy and public health efforts aimed at decreasing co-use rates. Although cannabis and tobacco co- use is common, mechanism(s) underlying co-use remain unclear. Preliminary work by our group shows that delta-9-tetrahydrocannabinol (THC) can alter the subjective experience of commonly used tobacco products including combustible cigarettes and e-cigarettes. Preclinical evidence supports this interaction by documenting increases in motivation to use nicotine, including less price sensitive nicotine demand in THC-exposed rodents. Human laboratory data are needed to extend this work by comprehensively determining effects across the range of commercially-relevant THC and nicotine doses and routes of administration. We will concurrently conduct two full-factorial laboratory studies to determine the impact of acute THC administration on the dose-related motivational, subjective, and physiological effects of two widely used tobacco products – combustible cigarettes (Study 1) and electronic cigarettes (Study 2; “e-cigarettes”). Participants in both studies will receive pretreatment with placebo or active THC. Following THC pre-treatment, participants will self-administer a combustible cigarette containing a randomized nicotine dose (Study 1) or an e-cigarette containing a randomized nicotine dose (Study 2) using a standardized puff procedure. We will use NIDA standardized products (SPECTRUM cigarettes and SREC e-cigarettes) to ensure consistency across study years and applicability to other ongoing research. A battery of craving, mood, withdrawal, and subjective drug effect measures will be collected before and after nicotine product administration. Participants will then complete an incentivized demand task previously validated by the study team to evaluate cigarette and e-cigarette use motivation and increase experimental rigor through experienced consequences of task performance. Participants will be randomized to either smoked or vaporized THC administration to evaluate the effect of congruent versus incongruent routes of THC and tobacco administration on study outcomes. We hypothesize that THC will in a dose-orderly manner increase motivations to use tobacco as well as decrease tobacco craving and increase positive affect with tobacco use. Understanding the influence of cannabis on tobacco use across varied routes of administration and a broad nicotine dose range will inform key regulatory policies within the cannabis and tobacco regulatory fields to include cannabis standard unit dosing and nicotine reduction policies.
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