BACKGROUND AND PURPOSE: Much of the opioid epidemic arose from abuse of prescription opioid drugs. This study sought to determine if the combination of a cannabinoid with an opioid could produce additive or synergistic effects on pain, allowing reduction in the opioid dose needed for maximal analgesia. EXPERIMENTAL APPROACH: Pain was assayed using the formalin test in mice and the carrageenan assay in rats. Morphine and two synthetic cannabinoids were tested: WIN55,212-2 (WIN), which binds to both CB1 and CB2 receptors, and possibly TRPV1 channels; and GP1a, which has activity at CB2 receptors and is reported to inhibit fatty acid amide hydrolase, thus raising levels of endogenous cannabinoids. KEY RESULTS: Morphine in combination with WIN in the formalin test gave synergistic analgesia. Studies with selective antagonists showed that WIN was acting through CB1 receptors. Morphine in combination with GP1a in the formalin test was sub-additive. In the carrageenan test, WIN had no added effect when combined with morphine, but GP1a with morphine showed enhanced analgesia. Both WIN and Gp1a used alone had analgesic activity in the formalin pain test, but not in the carrageenan pain test. CONCLUSIONS AND IMPLICATIONS: The ability of a cannabinoid to produce an additive or synergistic effect on analgesia when combined with morphine varies with the pain assay and may be mediated by CB1 or CB2 receptors. These results hold the promise of using cannabinoids to reduce the dose of opioids for analgesia in certain pain conditions.
BACKGROUND AND PURPOSE: Much of the opioid epidemic arose from abuse of prescription opioid drugs. This study sought to determine if the combination of a cannabinoid with an opioid could produce additive or synergistic effects on pain, allowing reduction in the opioid dose needed for maximal analgesia. EXPERIMENTAL APPROACH: Pain was assayed using the formalin test in mice and the carrageenan assay in rats. Morphine and two synthetic cannabinoids were tested: WIN55,212-2 (WIN), which binds to both CB1 and CB2 receptors, and possibly TRPV1 channels; and GP1a, which has activity at CB2 receptors and is reported to inhibit fatty acid amide hydrolase, thus raising levels of endogenous cannabinoids. KEY RESULTS:Morphine in combination with WIN in the formalin test gave synergistic analgesia. Studies with selective antagonists showed that WIN was acting through CB1 receptors. Morphine in combination with GP1a in the formalin test was sub-additive. In the carrageenan test, WIN had no added effect when combined with morphine, but GP1a with morphine showed enhanced analgesia. Both WIN and Gp1a used alone had analgesic activity in the formalinpain test, but not in the carrageenan pain test. CONCLUSIONS AND IMPLICATIONS: The ability of a cannabinoid to produce an additive or synergistic effect on analgesia when combined with morphine varies with the pain assay and may be mediated by CB1 or CB2 receptors. These results hold the promise of using cannabinoids to reduce the dose of opioids for analgesia in certain pain conditions.
Authors: Stephen Ph Alexander; Arthur Christopoulos; Anthony P Davenport; Eamonn Kelly; Neil V Marrion; John A Peters; Elena Faccenda; Simon D Harding; Adam J Pawson; Joanna L Sharman; Christopher Southan; Jamie A Davies Journal: Br J Pharmacol Date: 2017-12 Impact factor: 8.739
Authors: Suzanne Nielsen; Pamela Sabioni; Jose M Trigo; Mark A Ware; Brigid D Betz-Stablein; Bridin Murnion; Nicholas Lintzeris; Kok Eng Khor; Michael Farrell; Andrew Smith; Bernard Le Foll Journal: Neuropsychopharmacology Date: 2017-03-22 Impact factor: 7.853
Authors: Saadet Inan; Toby K Eisenstein; Mia N Watson; Menahem Doura; Joseph J Meissler; Christopher S Tallarida; Xiaohong Chen; Ellen B Geller; Scott M Rawls; Alan Cowan; Martin W Adler Journal: J Pharmacol Exp Ther Date: 2018-09-24 Impact factor: 4.030
Authors: Xiaohong Chen; Alan Cowan; Saadet Inan; Ellen B Geller; Joseph J Meissler; Scott M Rawls; Ronald J Tallarida; Christopher S Tallarida; Mia N Watson; Martin W Adler; Toby K Eisenstein Journal: Br J Pharmacol Date: 2019-07-24 Impact factor: 8.739
Authors: Michael R Ruff; Saadet Inan; Xiang Qun Shi; Joseph J Meissler; Martin W Adler; Toby K Eisenstein; Ji Zhang Journal: Life Sci Date: 2022-07-09 Impact factor: 6.780
Authors: Yang Yu; Quentin K Tsang; Josue Jaramillo-Polanco; Alan E Lomax; Stephen J Vanner; David E Reed Journal: J Neurosci Date: 2022-07-05 Impact factor: 6.709
Authors: Arianna Giorgetti; Jennifer P Pascali; Paolo Fais; Guido Pelletti; Andrea Gabbin; Giorgia Franchetti; Giovanni Cecchetto; Guido Viel Journal: Life (Basel) Date: 2021-05-14