Separate and combined effects of the cannabinoid agonists nabilone and Δ ⁹-THC in humans discriminating Δ ⁹-THC

Background: Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ ⁹-tetrahydrocannabinol (Δ ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment. Methods: Six cannabis users learned to discriminate 30mg oral Δ ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ ⁹-THC (0, 5, 15 and 30mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected. Results: Δ ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ ⁹-THC leftward/upward and enhanced Δ ⁹-THC effects on the other outcome measures. Conclusions: These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.