Cited by 87Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsNeuropeptides and Animal Physiology

Potentiation of Δ9-tetrahydrocannabinol-induced analgesia by morphine in mice: involvement of μ- and κ-opioid receptors

Reche, Ignacio, Fuentes, José A, Ruiz-Gayo, Mariano·1996·European Journal of Pharmacology

Abstract

The antinociceptive effect of peripheral delta 9-tetrahydrocannabinol was examined in mice previously treated with an inactive dose of morphine. The ED50 of delta 9-tetrahydrocannabinol was significantly reduced by morphine, both in the tail-flick test (0.85 vs. 2.10 mg/kg) and in the hot-plate test (1.51 vs. 4.71 mg/kg and 0.73 vs. 2.47 mg/kg in jumping and paw-lick responses, respectively). The synergistic effect between morphine and delta 9-tetrahydrocannabinol was partially blocked by the cannabinoid receptor antagonist, SR-141,716 A [(N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichorophenyl)-4-methyl-3 -pyrazolecarboxamide, hydrochloride)], at a dose of 2 mg/kg (i.p.) as well as by the opioid receptor antagonist naloxone, at the dose of 1 mg/kg (s.c.). Such an effect was also blocked by i.t. nor-binaltorphimine (a kappa-selective opioid receptor antagonist) given at 20 micrograms/mouse as well as by beta-funaltrexamine (a mu-selective opioid receptor antagonist) at a dose of 2 nmol/mouse (i.c.v., 24 h before the test). Accordingly, the mu-opioid receptor agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin) potentiated the effect of delta 9-tetrahydrocannabinol. These data show that the synergism between morphine and delta 9-tetrahydrocannabinol appears to involve cannabinoid as well as mu-supraspinal and kappa-spinal opioid receptors.

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Crossref · 10.1016/s0014-2999(96)00752-2

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Authors
Reche, I., Fuentes, J. A., & Ruiz-Gayo, M.
Affiliations
Universidad Complutense de Madrid (ES)
Venue
European Journal of Pharmacology
Publisher
Elsevier BV
Published
1996-12
Volume
318
Issue
1
Pages
11-16
ISSN
0014-2999 (ISSN-L)
OpenAlex
W2011204298
Cited by
87
References
25
Citations by year
2026: 1 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 6
FWCI
4.22
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Pfizer
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
delta-9-tetrahydrocannabinol, morphine, analgesia, opioid-cannabinoid interaction, mu-opioid receptor, kappa opioid receptor, synergistic effect, antinociception, SR141716A, naloxone, nor-binaltorphimine, beta-funaltrexamine, DAMGO, cannabinoid receptor antagonists
MeSH terms
Analgesia, Analgesics, Opioid, Animals, Binding Sites, Drug Synergism, Male, Morphine, Naltrexone, Narcotic Antagonists, Pain Measurement, Dronabinol, Receptors, Opioid, mu, Receptors, Opioid, kappa, Mice

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