Interactions between mu opioid receptor agonists and cannabinoid receptor agonists CP55940 and WIN55212–2 in rhesus monkeys: evaluation of treatment‐ and abuse‐related effects

Abstract

Mu opioid receptor agonists and cannabinoid receptor agonists can be combined to possibly enhance therapeutic effectiveness (e.g., pain treatment); however, it is unclear whether combinations of these drugs enhance abuse liability. These studies examined the effects of cannabinoid receptor agonists CP55940 and WIN55212‐2 on the antinociceptive, discriminative stimulus, and positive reinforcing effects of mu opioid receptor agonists in rhesus monkeys. In one group (n=3), CP55940 (0.001–0.056 mg/kg), and WIN55212‐2 (0.1–1.78 mg/kg) shifted morphine dose‐effect curves leftward up to 8 fold. In monkeys discriminating 3.2 mg/kg morphine from saline (n=3), CP55940 and WIN55212‐2 shifted the morphine discriminative stimulus dose‐effect curves rightward up to 7 fold. In monkeys (n=4) self‐administering heroin (0.32–32.0 μg/kg/infusion), CP55940 and WIN55212‐2 shifted the heroin dose‐effect curves rightward (up to 15 fold) and downward. Cannabinoid receptor agonists CP55940 and WIN55212‐2 enhanced the antinociceptive effects but not the discriminative stimulus or positive reinforcing effects of mu opioid receptor agonists. These data support the view that combining mu opioid receptor agonists and cannabinoid receptor agonists might enhance treatment effectiveness without enhancing abuse liability. Supported by USPHS Grants R01DA05018, K05DA017918 (CPF) and T32DA031115 (DRM).