Benowitz N L, Jones R T
J Clin Pharmacol. 1981 Aug-Sep;21(S1):214S-223S. doi: 10.1002/j.1552-4604.1981.tb02598.x.
Safe therapeutic use of cannabinoids for prolonged periods of time requires an appreciation of pharmacologic actions with both acute and repetitive administration. Cardiovascular effects of acute delta 9-tetrahydrocannabinol (THC) administration included increased sympathetic and reduced parasympathetic tone, although sympathetic reflex responses were impaired. Thus, supine tachycardia and increased blood pressure with upright hypotension are observed. With repetitive dosing, there is a transition from increased to decreased sympathetic activity and from decreased to increased parasympathetic activity, and blood volume substantially increases. As a result, supine bradycardia and decreased blood pressure with tolerance to orthostatic hypotension are observed. Relevance of these observations to management of patients with THC, including considerations of potential drug interactions, is discussed. In other experiments, THC and cannabidiol were found to inhibit metabolism of other drugs (antipyrine and barbiturates) metabolized by liver mixed-function oxidase enzymes. Potential inhibition of drug metabolism must be considered in evaluating responses to chemotherapeutic agents in cancer patients receiving THC and responses to coadministered anticonvulsants in epileptic patients receiving cannabidiol.
长时间安全治疗性使用大麻素需要了解急性和重复给药时的药理作用。急性给予δ9 - 四氢大麻酚（THC）的心血管效应包括交感神经张力增加和副交感神经张力降低，尽管交感神经反射反应受损。因此，会观察到仰卧位心动过速以及直立性低血压时血压升高。重复给药时，交感神经活动从增加转变为减少，副交感神经活动从减少转变为增加，且血容量大幅增加。结果，会观察到仰卧位心动过缓和血压降低以及对直立性低血压产生耐受性。讨论了这些观察结果与THC患者管理的相关性，包括对潜在药物相互作用的考虑。在其他实验中，发现THC和大麻二酚会抑制由肝脏混合功能氧化酶代谢的其他药物（安替比林和巴比妥类药物）的代谢。在评估接受THC的癌症患者对化疗药物的反应以及接受大麻二酚的癫痫患者对联合使用的抗惊厥药的反应时，必须考虑药物代谢的潜在抑制作用。
