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The Enhancement of Morphine Antinociception in Mice by Î9-Tetrahydrocannabinol

Smith, F·1998·Pharmacology Biochemistry and Behavior

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Abstract

We have previously reported that intracerebroventricular or intrathecal administration of inactive doses of delta9-tetrahydrocannabinol (THC) greatly enhance the antinociceptive potency of morphine in the mouse tail-flick test. Experiments were conducted to test the hypothesis that morphine's potency would be enhanced in mice receiving THC and morphine by conventional per os (p.o.) and subcutaneously (s.c.) routes of administration. Antinociception was measured in the tail-flick test of radiant heat after administration of different combinations of THC and morphine p.o. and s.c. Subcutaneous administration of THC (4 and 25 mg/kg) increased the potency of s.c. morphine 8.5- and 22.3-fold, respectively, while s.c. THC (25 mg/kg) increased the potency of p.o. morphine 3.1-fold. Per os administration of THC (10 and 20 mg/kg) increased the potency of s.c. and p.o. morphine 11.4-fold and 7.6-fold, respectively. Thus, morphine's potency was significantly increased regardless of the enteral and parenteral routes of THC and morphine administration. The synthetic receptor selective cannabinoid CP-55, 940 (0.1 mg/kg, s.c.) also enhanced morphine's potency. Finally, the ability of the CB1 receptor antagonist SR141716A to antagonize the enhancement of morphine by THC indicates that THC was acting through a cannabinoid receptor mechanism.

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Authors: Smith, F.
Affiliations: Virginia Commonwealth University Medical Center (US)
Corresponding author: Smith, F
ORCID: Smith, F
Venue: Pharmacology Biochemistry and Behavior
Publisher: Elsevier BV
Published: 1998-06
Volume: 60
Issue: 2
Pages: 559-566
ISSN: 0091-3057 (ISSN-L)
DOI: 10.1016/s0091-3057(98)00012-4
OpenAlex: W2016026978
Cited by: 146
References: 44
Citations by year: 2026: 1 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 1 · 2015: 6 · 2014: 3 · 2013: 3 · 2012: 6
FWCI: 5.96
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology Biochemistry and Behavior (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (K02-00186)
National Institute on Drug Abuse (DA 05274, DA‐03672)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords: morphine, delta-9-tetrahydrocannabinol, antinociception, cannabinoid receptors, CB1 receptor, CP55,940, SR141716A, route of administration, tail-flick test, analgesia
MeSH terms: Analgesics, Opioid, Animals, Drug Synergism, Hallucinogens, Male, Mice, Inbred ICR, Morphine, Pain Measurement, Reaction Time, Receptors, Drug, Dronabinol, Receptors, Cannabinoid, Mice

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The Enhancement of Morphine Antinociception in Mice by Î9-Tetrahydrocannabinol

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The Enhancement of Morphine Antinociception in Mice by Î9-Tetrahydrocannabinol