Schindler Charles W, Gramling Benjamin R, Justinova Zuzana, Thorndike Eric B, Baumann Michael H
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.
Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States.
Drug Alcohol Depend. 2017 Oct 1;179:387-394. doi: 10.1016/j.drugalcdep.2017.07.029. Epub 2017 Aug 18.
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, Δ-tetrahydrocannabinol (THC), we compared the effects of synthetic cannabinoids and THC on body temperature and cardiovascular parameters.
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.
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 α adrenergic antagonist prazosin.
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.
合成大麻素的滥用一直是一个公共卫生问题。由于这些药物与大麻的活性成分Δ-四氢大麻酚（THC）作用于相同的大麻素受体，我们比较了合成大麻素和THC对体温及心血管参数的影响。
将用于测量体温或血压（BP）的生物遥测发射器通过手术植入不同组的雄性大鼠体内。皮下注射THC和合成大麻素CP55,940、JWH-018、AM2201和XLR-11，然后将大鼠放入隔离小室3小时。
THC和合成大麻素可使体温呈剂量依赖性下降，在实验的最后2小时最为明显。效力顺序为CP55,940>AM2201 = JWH-018>THC = XLR-11。大麻素反向激动剂利莫那班可拮抗所有化合物的降温作用。与溶媒处理相比，在实验的第1小时内，合成大麻素可使血压升高，而心率未受影响。血压升高的效力顺序与体温下降相似。利莫那班或中性拮抗剂AM4113未拮抗CP55,940和JWH-018的升压作用。然而，用神经节阻滞剂六甲铵或α肾上腺素能拮抗剂哌唑嗪预处理可拮抗这两种药物的血压反应。
我们的结果表明，合成大麻素通过涉及大麻素受体的机制使大鼠体温降低，而它们通过独立于这些位点的机制升高血压。升压作用似乎涉及中枢交感神经流出。
