Charles W Schindler1, Benjamin R Gramling2, Zuzana Justinova3, Eric B Thorndike3, Michael H Baumann2. 1. Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States; Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States. Electronic address: cschind@helix.nih.gov. 2. Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States. 3. Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States.
Abstract
BACKGROUND: The misuse of synthetic cannabinoids is a persistent public health concern. Because these drugs target the same cannabinoid receptors as the active ingredient of marijuana, Δ9-tetrahydrocannabinol (THC), we compared the effects of synthetic cannabinoids and THC on body temperature and cardiovascular parameters. METHODS: Biotelemetry transmitters for the measurement of body temperature or blood pressure (BP) were surgically implanted into separate groups of male rats. THC and the synthetic cannabinoids CP55,940, JWH-018, AM2201 and XLR-11 were injected s.c., and rats were placed into isolation cubicles for 3h. RESULTS: THC and synthetic cannabinoids produced dose-related decreases in body temperature that were most prominent in the final 2h of the session. The rank order of potency was CP55,940>AM2201=JWH-018>THC=XLR-11. The cannabinoid inverse agonist rimonabant antagonized the hypothermic effect of all compounds. Synthetic cannabinoids elevated BP in comparison to vehicle treatment during the first h of the session, while heart rate was unaffected. The rank order of potency for BP increases was similar to that seen for hypothermia. Hypertensive effects of CP55,940 and JWH-018 were not antagonized by rimonabant or the neutral antagonist AM4113. However, the BP responses to both drugs were antagonized by pretreatment with either the ganglionic blocker hexamethonium or the α1 adrenergic antagonist prazosin. CONCLUSIONS: Our results show that synthetic cannabinoids produce hypothermia in rats by a mechanism involving cannabinoid receptors, while they increase BP by a mechanism independent of these sites. The hypertensive effect appears to involve central sympathetic outflow. Published by Elsevier B.V.
BACKGROUND: The misuse of synthetic cannabinoids is a persistent public health concern. Because these drugs target the same cannabinoid receptors as the active ingredient of marijuana, Δ9-tetrahydrocannabinol (THC), we compared the effects of synthetic cannabinoids and THC on body temperature and cardiovascular parameters. METHODS: Biotelemetry transmitters for the measurement of body temperature or blood pressure (BP) were surgically implanted into separate groups of male rats. THC and the synthetic cannabinoidsCP55,940, JWH-018, AM2201 and XLR-11 were injected s.c., and rats were placed into isolation cubicles for 3h. RESULTS:THC and synthetic cannabinoids produced dose-related decreases in body temperature that were most prominent in the final 2h of the session. The rank order of potency was CP55,940>AM2201=JWH-018>THC=XLR-11. The cannabinoid inverse agonist rimonabant antagonized the hypothermic effect of all compounds. Synthetic cannabinoids elevated BP in comparison to vehicle treatment during the first h of the session, while heart rate was unaffected. The rank order of potency for BP increases was similar to that seen for hypothermia. Hypertensive effects of CP55,940 and JWH-018 were not antagonized by rimonabant or the neutral antagonist AM4113. However, the BP responses to both drugs were antagonized by pretreatment with either the ganglionic blocker hexamethonium or the α1 adrenergic antagonist prazosin. CONCLUSIONS: Our results show that synthetic cannabinoids produce hypothermia in rats by a mechanism involving cannabinoid receptors, while they increase BP by a mechanism independent of these sites. The hypertensive effect appears to involve central sympathetic outflow. Published by Elsevier B.V.
Entities:
Keywords:
Blood pressure; Body temperature; Cannabinoids; Rat; THC
Authors: Hideaki Yano; Pramisha Adhikari; Sett Naing; Alexander F Hoffman; Michael H Baumann; Carl R Lupica; Lei Shi Journal: ACS Chem Neurosci Date: 2020-04-30 Impact factor: 4.418
Authors: Charles W Schindler; Eric B Thorndike; Kenner C Rice; John S Partilla; Michael H Baumann Journal: J Pharmacol Exp Ther Date: 2019-03-21 Impact factor: 4.030
Authors: Jeremy Carlier; Ariane Wohlfarth; Bonita D Salmeron; Karl B Scheidweiler; Marilyn A Huestis; Michael H Baumann Journal: J Pharmacol Exp Ther Date: 2018-09-28 Impact factor: 4.030
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