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Eur J Pharmacol. 2018 Jan 15;819:217-224. doi: 10.1016/j.ejphar.2017.11.038. Epub 2017 Nov 26.

Antinociceptive effects of mixtures of mu opioid receptor agonists and cannabinoid receptor agonists in rats: Impact of drug and fixed-dose ratio.

Author information

1
Departments of Pharmacology, the University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229, USA; Addiction Research, Treatment & Training Center of Excellence, the University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229, USA.
2
Departments of Pharmacology, the University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229, USA; Departments of Psychiatry, the University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229, USA; Addiction Research, Treatment & Training Center of Excellence, the University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229, USA. Electronic address: france@uthscsa.edu.

Abstract

Pain is a significant clinical problem, and there is a need for effective pharmacotherapies with fewer adverse effects than currently available drugs (e.g., mu opioid receptor agonists). Cannabinoid receptor agonists enhance the antinociceptive effects of mu opioid receptor agonists, but it remains unclear which drugs and in what proportion will yield the most effective and safest treatments. The antinociceptive effects of the mu opioid receptor agonists etorphine and morphine alone and in combination with the cannabinoid receptor agonists Δ9-THC and CP55940 were studied in male Sprague-Dawley rats (n = 16) using a warm water tail withdrawal procedure. The ratio of opioid to cannabinoid (3:1, 1:1, and 1:3) varied for each mixture. Drugs administered alone or as pairwise mixtures of an opioid and a cannabinoid dose-dependently increased tail withdrawal latency. Mixtures with morphine produced supra-additive (CP55940) and additive (Δ9-THC) effects, whereas mixtures with etorphine and either cannabinoid were sub-additive. The interactions were not different among ratios for a particular mixture. The nature of the interaction between opioids and cannabinoids with regard to antinociceptive effects varies with the particular drugs in the mixture, which can have implications for designing combination therapies for pain.

KEYWORDS:

Antinociception; Cannabinoid receptor agonist; Drug-drug interactions; Rats; Thermal nociception; mu opioid receptor agonist

PMID:
29183835
PMCID:
PMC5766417
[Available on 2019-01-15]
DOI:
10.1016/j.ejphar.2017.11.038
[Indexed for MEDLINE]

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