Human Laboratory Evaluation of the Synthetic Cannabinoid Nabilone for Cannabis-Use Disorders

Treatment admission and relapse rates for cannabis-use disorders are comparable to other abused drugs, but no pharmacological treatments exist. The endogenous cannabinoid system is integral in cannabis intoxication and cannabis dependence; however, clinical studies have evaluated only one cannabinoid medication, Ä9- THC. Consistent with key drug dependence medication attributes, Ä9-THC reduces the abuse-related effects of cannabis and alleviates withdrawal symptoms, and increased retention in a clinical trial. However, because Ä9- THC is the active constituent of cannabis, it cannot be differentiated from cannabis in urine toxicology screening, making the objective verification of cannabis abstinence difficult, and thereby limiting its clinical utility. We have begun to evaluate the therapeutic potential of the synthetic cannabinoid nabilone, which is not cross-reactive in urine assays for cannabis use. Those studies demonstrated that nabilone effects overlap with Ä9-THC and that acute dose combinations of nabilone and Ä9-THC are well tolerated in cannabis users. The proposed study will determine whether nabilone maintenance attenuates the reinforcing effects of smoked cannabis. Maintenance dosing will be tested because it more closely resembles clinical treatment. Selfadministration procedures will be used because the reinforcing effects of a drug are central to its abuse and self-administration procedures predict the effectiveness of pharmacotherapies. Cannabis use in the natural environment will also be monitored during nabilone maintenance as an exploratory outcome, as reductions in use would provide a compelling signal of therapeutic effectiveness. Data from this pilot study will be used in an R01 application to expand on positive preliminary findings by testing additional subjects, doses and comparator drugs.