TY - JOUR
T1 - Effects of opioid/cannabinoid mixtures on impulsivity and memory in rhesus monkeys
AU - Minervini, Vanessa
AU - France, Charles P.
N1 - Funding Information:
This work was supported by the National Institute on Drug Abuse grants R01DA005018, 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.
Funding Information:
We thank Lisa R. Gerak and David R. Maguire for their helpful comments on the data and previous drafts of this manuscript. This work was supported by the National Institute on Drug Abuse grants R01DA005018, 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.
Publisher Copyright:
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved
PY - 2020
Y1 - 2020
N2 - 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 (0.32-5.6mg/kg), the cannabinoid CB1/CB2 receptor agonist CP55940 (0.0032-0.1mg/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.
AB - 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 (0.32-5.6mg/kg), the cannabinoid CB1/CB2 receptor agonist CP55940 (0.0032-0.1mg/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.
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U2 - 10.1097/FBP.0000000000000551
DO - 10.1097/FBP.0000000000000551
M3 - Article
C2 - 32101988
AN - SCOPUS:85082099515
VL - 31
SP - 233
EP - 248
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
SN - 0955-8810
IS - 2
ER -