Effects of Opioid/Cannabinoid Mixtures on Impulsivity and Memory in Rhesus Monkeys

Abstract

The current opioid epidemic underscores the need for safe and effective pharmacotherapies for treating pain. Combining opioid receptor agonists with drugs that relieve pain through actions at non‐opioid mechanisms (e.g., cannabinoid receptors) could be a useful strategy for reducing the dose of opioid needed to achieve pain relief in the absence of reinforcing (abuse) or respiratory‐depressant (overdose) effects, thereby reducing the risks associated with the use of opioids alone. Opioid/cannabinoid mixtures might be useful for treating pain; individually, opioids and cannabinoids have modest effects on cognition, and it is important to determine whether those effects occur with mixtures. The present study used delay discounting and delayed matching‐to‐sample tasks to determine the effects of the mu opioid receptor agonist morphine (0.32 – 5.6 mg/kg), the cannabinoid CB1/CB2 receptor agonist CP55940 (0.0032 – 0.1 mg/kg), and morphine/CP55940 mixtures on impulsivity (n=3) and memory (n=4) in rhesus monkeys. In the delay discounting task, monkeys could respond on one lever to receive one pellet delivered immediately or on a second lever to receive three pellets delivered immediately or after a delay (30 – 180 sec). In the delayed matching‐to‐sample task, 20 touches on a colored rectangle (e.g., blue), displayed on a touch‐sensitive screen, presented comparison stimuli, one of which matched the original stimulus (e.g., blue rectangle), either immediately or after a delay (2 – 64 sec). Touching the matching stimulus delivered a pellet with audio and visual feedback; touching the non‐matching stimulus terminated the trial. Data were analyzed using a two‐way ANOVA with dose and delay as factors. Given alone, each drug decreased rate of responding without modifying choice; morphine/CP55940 mixtures reduced choice of one pellet in a delay dependent manner, with monkeys instead choosing delayed delivery of the larger number of pellets. With the exception of one dose in one monkey, performance was not altered by morphine alone or CP55940 alone in the delayed matching‐to‐sample task. Morphine/CP55940 mixtures decreased accuracy in two monkeys, but the doses of each drug in the mixture were equal to or greater than doses that decreased accuracy or response rate with either drug alone. In both tasks, rate‐decreasing effects of morphine/CP55940 mixtures were additive. Overall, these data provide additional evidence supporting the notion that opioid/cannabinoid mixtures that are effective for treating pain do not have greater, and in some cases have less, adverse effects compared with larger doses of each drug alone.Support or Funding InformationSupported by: National Institute on Drug Abuse grants R01DA05018, R01DA029254, T32DA031115, and F32DA043348, and the Welch Foundation Grant AQ‐0039. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.