Effects of the synthetic cannabinoid receptor agonist JWH-018 on abuse-related effects of opioids in rhesus monkeys

Drug Alcohol Depend. 2019 Sep 1;202:33-38. doi: 10.1016/j.drugalcdep.2019.04.024. Epub 2019 Jun 29.


Opioid abuse remains a public health crisis despite a tremendous outpouring of resources to address the problem. One factor that might complicate this issue is polydrug abuse. While cannabis is increasingly available due to legalization by states, phytocannabinoids do not appear to alter the abuse-related effects of opioids. Synthetic cannabinoids, which are not pharmacologically identical to phytocannabinoids, are also increasingly available, and differences among cannabinoids might affect their interactions with opioids. This study assessed the impact of one synthetic cannabinoid, JWH-018, on the effects of two μ opioid receptor agonists using two procedures that address different aspects of abuse. First, four monkeys could choose to self-administer the opioid remifentanil alone (0.32 μg/kg/infusion) or a mixture containing 0.32 μg/kg/infusion remifentanil and JWH-018 (1-10 μg/kg/infusion). On separate occasions, monkeys could choose between remifentanil available alone or combined with 100 μg/kg/infusion cocaine. While monkeys chose the remifentanil/cocaine mixture over remifentanil alone, they responded equally for remifentanil alone and the remifentanil/JWH-018 mixture. The ability of JWH-018 to reinstate extinguished responding previously maintained by heroin was examined in four other monkeys. When presented with drug-associated stimuli, heroin, but not JWH-018, reinstated responding, and when combined, JWH-018 did not increase the potency of heroin. While opioids and synthetic cannabinoids, including JWH-018, are abused, these results indicate that JWH-018 does not modify the behavioral effects of opioids in monkeys in a manner that would predict greater abuse liability of cannabinoid/opioid mixtures, a result that is consistent with a growing literature on mixtures of opioids and phytocannabinoids.

Keywords: Cannabinoid; Heroin; JWH-018; Opioid; Reinstatement; Remifentanil; Rhesus monkey; Self-administration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Cannabinoid Receptor Agonists / pharmacology*
  • Cannabinoids / pharmacology
  • Cocaine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Indoles / pharmacology*
  • Macaca mulatta
  • Male
  • Naphthalenes / pharmacology*
  • Opioid-Related Disorders
  • Remifentanil / pharmacology*
  • Self Administration


  • Analgesics, Opioid
  • Cannabinoid Receptor Agonists
  • Cannabinoids
  • Drug Combinations
  • Indoles
  • Naphthalenes
  • 1-pentyl-3-(1-naphthoyl)indole
  • Cocaine
  • Remifentanil