Potentiation of Δ9-tetrahydrocannabinol-induced analgesia by morphine in mice: involvement of μ- and κ-opioid receptors
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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Morphine pre-administration shifted the dose-response curve for delta-9-THC to the left (a 2.5-fold shift for the tail-flick test and a 3-fold shift for the hot plate test).
“Morphine pre-administration shifted the dose-response curve for delta-9-THC to the left (a 2.5-fold shift for the tail-flick test and a 3-fold shift for the hot plate test).”
From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Reche 1996
A greater than additive effect was observed, with a clear leftward shift of the graph, for the morphine and delta-9-THC combination.
“Greater than additive effect observed, clear leftward shift of graph”
From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Reche 1996
The analgesic effect of delta-9-THC was blocked by SR-141,716 (cannabinoid antagonist) and naloxone.
“Analgesic effect blocked by SR-141,716 (cannabinoid antagonist) and naloxone”
From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Reche 1996
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Neurobiología de la drogadicción. Cannabis
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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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