This research will examine the behavioral effects of smoked marijuana and oral cannabinoids in moderate marijuana smokers. A major objective of the research involves the development and testing of new methodologies for studying the effects of marijuana and related drugs in human subjects. One study presents a simple procedure for delivering standardized doses of marijuana smoke to subjects. This procedure should substantially reduce between-subject variability in smoke administration, thus permitting the determination of more accurate dose-effect relationships. Another study examines the effect of depth of inhalation on the absorption of smoke components (carbon monoxide and THC). This study will provide basic information on the usefulness of expired air carbon monoxide level as a quantitative index of marijuana smoke inhalation. Two additional studies are designed to evaluate the use of a cumulative dosing procedure for determining dose-effect functions for the effects of smoked marijuana within a single experimental session. Such a procedure would save valuable time and effort in future studies examining changes in sensitivity to marijuana. The remaining studies are oriented around the properties of cannabinoids that are related to dependence potential (subject effects, reinforcing and discriminative stimulus effects, and behavioral toxicity. Three studies use a discrete-choice self-administration procedure to evaluate the reinforcing properties of smoked marijuana, oral THC and nabilone, respectively. Two studies utilize a drug discrimination paradigm to examine the discriminative stimulus properties or oral THC. The five studies will provide a basic methodology for studying the reinforcing and discriminative stimulus properties (and by inference the dependence potential) of new cannabinoid compounds as they become available for therapeutic use. The final study is designed to evaluate the residual (""""""""hangover"""""""") effects produced by a simulated """"""""weekend binge"""""""" of combined marijuana smoking and alcohol drinking. Such residual effects are potentially of great practical importance, since alcohol and marijuana are frequently used together, and residual behavioral toxicity has been demonstrated to occur with each drug taken by itself.
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