Substitution Profile of the Cannabinoid Agonist Nabilone in Human Subjects Discriminating [DELTA]9-Tetrahydrocannabinol

Objectives: The central effects of Delta super(9)-tetrahydrocannabinol ( Delta super(9)-THC), the primary active constituent of cannabis, are attributed to cannabinoid CB sub(1) receptor activity, although clinical evidence is limited. Drug discrimination has proven useful for examining the neuropharmacology of drugs, as data are concordant with the actions of a drug at the receptor level. The aim of this study was to determine the profile of behavioral and physiological effects of the cannabinoid agonist nabilone in humans trained to discriminate Delta super(9)-THC. Methods: Six cannabis users learned to identify when they received oral Delta super(9)-THC (25 mg) or placebo and then received a range of doses of the cannabinoid agonists nabilone (1, 2, 3, and 5 mg) and Delta super(9)-THC (5, 10, 15, and 25 mg). The dopamine reuptake inhibitor methylphenidate (5, 10, 20, and 30 mg) was included as a negative control. Subjects completed the Multiple-Choice Procedure, and self-report, task performance, and physiological measures were collected. Results: Nabilone shared discriminative-stimulus effects with the training dose of Delta super(9)-THC, produced subject-rated drug effects that were comparable to those of Delta super(9)-THC, and increased heart rate. Methylphenidate did not engender Delta super(9)-THC-like discriminative-stimulus effects. Conclusions: These data demonstrate that the interoceptive effects of nabilone are similar to Delta super(9)-THC in cannabis users. The overlap in their behavioral effects is likely due to their shared mechanism as CB sub(1) receptor agonists. Given the relative success of agonist replacement therapy to manage opioid, tobacco, and stimulant dependence, these results also support the evaluation of nabilone as a potential medication for cannabis-use disorders.