Pre-clinical interaction of ayahuasca, a brew used in spiritual movements, with morphine and propofol

ABSTRACT Ayahuasca is a beverage with psychoactive properties used in religious and ceremonial rituals by some religious groups. The main active components of ayahuasca are dimethyltryptamine and the harmala alkaloids with β-carboline structure acting as monoamine oxidase A inhibitors. This combination produces a pronounced activation of serotonergic pathways and presents potential interaction with other psychotropics. The objective of this study was to investigate the possible interactions between ayahuasca and agents employed in general anesthesia. The pharmacological interactions between ayahuasca and morphine or propofol were evaluated in mice using doses of 12, 120 and 1200 mg/kg (0.1 to 10 times the average dose consumed by humans in religious rituals). Ayahuasca alone showed an antinociceptive effect in the writhing and formalin tests, and intensified the analgesic effect of morphine in the hot plate test. Concerning the pharmacological interactions between ayahuasca and propofol, the results were opposite; ayahuasca intensified the depressant effect of propofol in the rotarod test, but decreased the sleeping time induced by propofol. These set of results showed the occurrence of some interactions between ayahuasca and the drugs morphine and propofol, possibly by both pharmacokinetics and pharmacodynamics mechanisms.

摘要：死藤水（Ayahuasca）是一种具有精神活性的饮品，被部分宗教团体应用于宗教与仪式典礼之中。其主要活性成分为二甲基色胺（dimethyltryptamine）与具有β-咔啉结构（β-carboline structure）的骆驼蓬生物碱（harmala alkaloids），后者可作为单胺氧化酶A抑制剂（monoamine oxidase A inhibitors）。二者联合可显著激活5-羟色胺能通路（serotonergic pathways），且存在与其他精神药物发生相互作用的潜在风险。本研究旨在探究死藤水与全身麻醉（general anesthesia）常用药物之间可能存在的相互作用。
研究以小鼠为实验对象，采用12、120及1200 mg/kg的给药剂量（该剂量范围为宗教仪式中人类平均摄入剂量的0.1至10倍），评估了死藤水与吗啡（morphine）或丙泊酚（propofol）之间的药理学相互作用。
单独使用死藤水时，其在扭体试验（writhing test）与福尔马林试验（formalin test）中可表现出抗伤害感受效应，并在热板试验（hot plate test）中增强了吗啡的镇痛效应。而死藤水与丙泊酚的相互作用结果则相反：在旋转棒试验（rotarod test）中，死藤水可增强丙泊酚的中枢抑制效应，但却缩短了丙泊酚诱导的睡眠时间。
上述一系列结果表明，死藤水与吗啡、丙泊酚之间确实存在一定的相互作用，其机制可能同时涉及药代动力学（pharmacokinetics）与药效动力学（pharmacodynamics）途径。