NDLI: Impact of efficacy at the µ-opioid receptor on antinociceptive effects of combinations of µ-opioid receptor agonists and cannabinoid receptor agonists.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Maguire, David R. France, Charles P.
Description	Author Affiliation: Maguire DR ( Department of Pharmacology (D.R.M., C.P.F.) and Department of Psychiatry (C.P.F.), University of Texas Health Science Center at San Antonio, San Antonio, Texas.); France CP ( Department of Pharmacology (D.R.M., C.P.F.) and Department of Psychiatry (C.P.F.), University of Texas Health Science Center at San Antonio, San Antonio, Texas france@uthscsa.edu.)
Abstract	Cannabinoid receptor agonists, such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC), enhance the antinociceptive effects of µ-opioid receptor agonists, which suggests that combining cannabinoids with opioids would improve pain treatment. Combinations with lower efficacy agonists might be preferred and could avoid adverse effects associated with large doses; however, it is unclear whether interactions between opioids and cannabinoids vary across drugs with different efficacy. The antinociceptive effects of µ-opioid receptor agonists alone and in combination with cannabinoid receptor agonists were studied in rhesus monkeys (n = 4) using a warm water tail withdrawal procedure. Etorphine, fentanyl, morphine, buprenorphine, nalbuphine, Δ(9)-THC, and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol) each increased tail withdrawal latency. Pretreatment with doses of Δ(9)-THC (1.0 mg/kg) or CP 55,940 (0.032 mg/kg) that were ineffective alone shifted the fentanyl dose-effect curve leftward 20.6- and 52.9-fold, respectively, and the etorphine dose-effect curve leftward 12.4- and 19.6-fold, respectively. Δ(9)-THC and CP 55,940 shifted the morphine dose-effect curve leftward only 3.4- and 7.9-fold, respectively, and the buprenorphine curve only 5.4- and 4.1-fold, respectively. Neither Δ(9)-THC nor CP 55,940 significantly altered the effects of nalbuphine. Cannabinoid receptor agonists increase the antinociceptive potency of higher efficacy opioid receptor agonists more than lower efficacy agonists; however, because much smaller doses of each drug can be administered in combinations while achieving adequate pain relief and that other (e.g., abuse-related) effects of opioids do not appear to be enhanced by cannabinoids, these results provide additional support for combining opioids with cannabinoids to treat pain.
File Format	HTM / HTML
ISSN	00223565
e-ISSN	15210103
DOI	10.1124/jpet.114.216648
Journal	Journal of Pharmacology and Experimental Therapeutics
Issue Number	2
Volume Number	351
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2014-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Macaca Mulatta Drug Therapy Receptors, Opioid, Mu Pharmacology Discipline Pharmacology Cannabinoid Receptor Agonists Cannabinoids Pain Animals Analgesics Discipline Therapeutics Agonists Pain Measurement Drug Combinations
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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