Research ReportsEffects of opioid/cannabinoid mixtures on impulsivity and memory in rhesus monkeysMinervini, Vanessaa,,b; France, Charles P.a,,b,,c Author Information Departments of aPharmacology bAddiction Research, Treatment, & Training Center of Excellence cPsychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Received 13 February 2019 Accepted as revised 12 January 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.behaviouralpharm.com. Correspondence to Charles P. France, PhD, Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive (Mail Code 7764), San Antonio, TX 78229, USA, E-mail: [email protected] Behavioural Pharmacology: April 2020 - Volume 31 - Issue 2&3 - p 233-248 doi: 10.1097/FBP.0000000000000551 Buy SDC Metrics Abstract The opioid epidemic underscores the need for safer and more effective treatments for pain. Combining opioid receptor agonists with drugs that relieve pain through nonopioid mechanisms could be a useful strategy for reducing the dose of opioid needed to treat pain, thereby reducing risks associated with opioids alone. Opioid/cannabinoid mixtures might be useful in this context; individually, opioids and cannabinoids have modest effects on cognition, and it is important to determine whether those effects occur with mixtures. Delay discounting and delayed matching-to-sample tasks were used to examine 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. Alone, each drug decreased rate of responding without modifying choice in the delay-discounting task, and 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, accuracy in the delayed matching-to-sample task was not altered by either drug alone. Morphine/CP55940 mixtures decreased accuracy in two monkeys, but the doses in the mixture were equal to or greater than doses that decreased accuracy or response rate with either drug alone. Rate-decreasing effects of morphine/CP55940 mixtures were additive. These data support the notion that opioid/cannabinoid mixtures that might be effective for treating pain do not have greater, and might have less, adverse effects compared with larger doses of each drug alone. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.