The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets

Isabelle I. Simoneau, Maged S. Hamza, Heriberto P. Mata, Erin M. Siegel, Todd W Vanderah, Frank Porreca, Alexandros Makriyannis, T. Philip Malan

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Background: Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in Animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. Methods: Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg at the end of the experiments. All drugs were injected subcutaneously. WIN55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was administered 25 min before morphine. Retches and vomits were counted at 5-min intervals for 30 min after morphine injection. Results: Retching and vomiting responses increased with increasing morphine doses up to 1.0 mg/kg, above which the responses decreased. Previous administration of naloxone prevented morphine-induced retching and vomiting. WlN55,212-2 dose-dependently reduced retching and vomiting. The ED50 was 0.05 mg/kg for retches and 0.03 mg/kg for vomits. At 0.13 mg/kg, retching decreased by 76% and vomiting by 92%. AM251, a CB1 receptor-selective antagonist, blocked the antiemetic actions of WIN55,212-2, but AM630, a CB2 receptor-selective antagonist, did not. Conclusions: These results demonstrate that WIN55,212-2 prevents opioid-induced vomiting and suggest that the antiemetic activity of WIN55,212-2 occurs at CB1 receptors. This is consistent with findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated.

Original languageEnglish (US)
Pages (from-to)882-887
Number of pages6
JournalAnesthesiology
Volume94
Issue number5
StatePublished - May 2001

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Cannabinoid Receptor Agonists
Ferrets
Opioid Analgesics
Vomiting
Cannabinoid Receptor CB1
Morphine
Antiemetics
Cannabinoid Receptor CB2
Cannabinoid Receptors
Cannabinoids
Naloxone
Nausea
Radiotherapy
Central Nervous System
Drug Therapy
Injections

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Simoneau, I. I., Hamza, M. S., Mata, H. P., Siegel, E. M., Vanderah, T. W., Porreca, F., ... Malan, T. P. (2001). The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets. Anesthesiology, 94(5), 882-887.

The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets. / Simoneau, Isabelle I.; Hamza, Maged S.; Mata, Heriberto P.; Siegel, Erin M.; Vanderah, Todd W; Porreca, Frank; Makriyannis, Alexandros; Malan, T. Philip.

In: Anesthesiology, Vol. 94, No. 5, 05.2001, p. 882-887.

Research output: Contribution to journalArticle

Simoneau, II, Hamza, MS, Mata, HP, Siegel, EM, Vanderah, TW, Porreca, F, Makriyannis, A & Malan, TP 2001, 'The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets', Anesthesiology, vol. 94, no. 5, pp. 882-887.
Simoneau, Isabelle I. ; Hamza, Maged S. ; Mata, Heriberto P. ; Siegel, Erin M. ; Vanderah, Todd W ; Porreca, Frank ; Makriyannis, Alexandros ; Malan, T. Philip. / The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets. In: Anesthesiology. 2001 ; Vol. 94, No. 5. pp. 882-887.
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abstract = "Background: Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in Animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. Methods: Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg at the end of the experiments. All drugs were injected subcutaneously. WIN55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was administered 25 min before morphine. Retches and vomits were counted at 5-min intervals for 30 min after morphine injection. Results: Retching and vomiting responses increased with increasing morphine doses up to 1.0 mg/kg, above which the responses decreased. Previous administration of naloxone prevented morphine-induced retching and vomiting. WlN55,212-2 dose-dependently reduced retching and vomiting. The ED50 was 0.05 mg/kg for retches and 0.03 mg/kg for vomits. At 0.13 mg/kg, retching decreased by 76{\%} and vomiting by 92{\%}. AM251, a CB1 receptor-selective antagonist, blocked the antiemetic actions of WIN55,212-2, but AM630, a CB2 receptor-selective antagonist, did not. Conclusions: These results demonstrate that WIN55,212-2 prevents opioid-induced vomiting and suggest that the antiemetic activity of WIN55,212-2 occurs at CB1 receptors. This is consistent with findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated.",
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AU - Siegel, Erin M.

AU - Vanderah, Todd W

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AU - Makriyannis, Alexandros

AU - Malan, T. Philip

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N2 - Background: Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in Animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. Methods: Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg at the end of the experiments. All drugs were injected subcutaneously. WIN55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was administered 25 min before morphine. Retches and vomits were counted at 5-min intervals for 30 min after morphine injection. Results: Retching and vomiting responses increased with increasing morphine doses up to 1.0 mg/kg, above which the responses decreased. Previous administration of naloxone prevented morphine-induced retching and vomiting. WlN55,212-2 dose-dependently reduced retching and vomiting. The ED50 was 0.05 mg/kg for retches and 0.03 mg/kg for vomits. At 0.13 mg/kg, retching decreased by 76% and vomiting by 92%. AM251, a CB1 receptor-selective antagonist, blocked the antiemetic actions of WIN55,212-2, but AM630, a CB2 receptor-selective antagonist, did not. Conclusions: These results demonstrate that WIN55,212-2 prevents opioid-induced vomiting and suggest that the antiemetic activity of WIN55,212-2 occurs at CB1 receptors. This is consistent with findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated.

AB - Background: Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in Animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. Methods: Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg at the end of the experiments. All drugs were injected subcutaneously. WIN55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was administered 25 min before morphine. Retches and vomits were counted at 5-min intervals for 30 min after morphine injection. Results: Retching and vomiting responses increased with increasing morphine doses up to 1.0 mg/kg, above which the responses decreased. Previous administration of naloxone prevented morphine-induced retching and vomiting. WlN55,212-2 dose-dependently reduced retching and vomiting. The ED50 was 0.05 mg/kg for retches and 0.03 mg/kg for vomits. At 0.13 mg/kg, retching decreased by 76% and vomiting by 92%. AM251, a CB1 receptor-selective antagonist, blocked the antiemetic actions of WIN55,212-2, but AM630, a CB2 receptor-selective antagonist, did not. Conclusions: These results demonstrate that WIN55,212-2 prevents opioid-induced vomiting and suggest that the antiemetic activity of WIN55,212-2 occurs at CB1 receptors. This is consistent with findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated.

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