Evaluation of cannabinoid agonists using punished responding and midazolam discrimination procedures in squirrel monkeys

Rationale  Clinical studies have suggested that marijuana and nabilone have anxiolytic effects in humans, yet studies of anxiolytic-like effects of cannabinoid agonists in mice and rats have yielded mixed results. Objective  The purpose of the present study was to compare the effects of cannabinoid agonists and clinically used anxiolytic drugs in monkeys using punished responding and midazolam discrimination procedures. Methods  Monkeys were trained to discriminate an i.m. injection of 0.3 mg/kg midazolam from saline or, in a separate group, to respond under a multiple schedule of food reinforcement composed of punished and nonpunished components. Effects of the cannabinoid agonists Δ⁹-tetrahydrocannabinol (Δ⁹-THC; 0.01–3 mg/kg), WIN 55,212-2 (0.03–1 mg/kg) and CP 55,940 (0.003–0.03 mg/kg), and the benzodiazepine midazolam (0.01–1 mg/kg) and the barbiturate pentobarbital (1–18 mg/kg) were evaluated. Results  Δ⁹-THC and CP 55,940 did not have antipunishment effects and Δ⁹-THC and WIN 55,212-2 did not produce midazolam-like discriminative stimulus effects up to doses that substantially decreased response rate. In contrast, pentobarbital, like midazolam, increased punished responding at doses comparable to those that substituted for the midazolam discriminative stimulus. Conclusion  Cannabinoid agonists do not have anxiolytic-like effects in behavioral procedures commonly used to characterize benzodiazepines and other drugs in squirrel monkeys.