Effects of cannabidiol (CBD), ∆ 9 -tetrahydrocannabinol (THC), and CBD/THC mixtures on fentanyl self-administration in a food drug choice procedure in rhesus monkeys

The use of cannabinoids as adjuvants to opioid therapies to mitigate the problematic side effects of opioids or to decrease the doses of opioids necessary to relieve pain is an area of intense interest. In rhesus monkeys, ∆⁹ -tetrahydrocannabinol (THC) enhances the acute antinociceptive effects of opioids. However, THC does not enhance other effects of opioids including physical dependence, ventilatory depression, reinforcing effects, or discriminative stimulus effects. Evidence from rodent studies suggest other phytocannabinoids like cannabidiol (CBD) might decrease the reinforcing effects of several classes of drugs of abuse, including opioids. The present studies sought to assess the impact of THC, CBD, and THC/CBD mixtures on i.v. fentanyl self-administration in rhesus monkeys (n=4) in a food drug choice procedure. Experimental sessions consisted of 2 forced trials followed by up to 30 choice trials where animals had the opportunity to respond on one lever for a sucrose pellet and another for an i.v. infusion (fentanyl or vehicle). Fentanyl dose was adjusted for each animal to find the largest dose that occasioned <20% drug choice (0.0001 mg/kg/infusion), and the smallest dose that elicited >80% drug choice (0.001 or 0.0032 mg/kg/infusion). CBD (10-17.8 mg/kg), THC (0.032-1 mg/kg), and THC/CBD mixtures (dose ratios of 1:10 and 1:32) were delivered i.v. 15 minutes prior to testing sessions. CBD or THC alone did not affect choice for either dose of fentanyl. THC/CBD mixtures similarly did not produce an increase in choice for the small dose of fentanyl, or a decrease for the large dose of fentanyl. The present studies suggest that phytocannabinoids such as THC or CBD, alone or in combination, do not enhance or diminish the rewarding effects of fentanyl. These results add to the body of evidence that phytocannabinoids might be a safe option to enhance the antinociceptive effects of opioids without enhancing their rewarding properties.