Mash Deborah C, Kovera Craig A, Buck Billy E, Norenberg Michael D, Shapshak Paul, Hearn W Lee, Sanchez-Ramos Juan
Departments of Neurology, Psychiatry, Orthopedics, and Pathology, University of Miami School of Medicine, Miami, Florida 33136, USA; Department of Neurology, University of South Florida, Tampa 33620, Florida; Metro-Dade County Medical Examiner Department, Miami, Florida 33101, USA.
Ann N Y Acad Sci. 1998 May;844(1):274-292. doi: 10.1111/j.1749-6632.1998.tb08242.x.
The potential for deriving new psychotherapeutic medications from natural sources has led to renewed interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for the treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.
从天然来源研发新型心理治疗药物的潜力，引发了人们对雨林植物重新产生兴趣，将其作为开发抗成瘾药物的先导化合物来源。伊波加因是一种吲哚生物碱，存在于原产于赤道非洲的雨林灌木——伊博格（夹竹桃科）的根部。伊波加因被当地居民低剂量用于对抗疲劳、饥饿，高剂量则用作宗教仪式中的圣礼。美国和欧洲成瘾者自助组织的成员声称，伊波加因能促进长期戒除包括精神兴奋剂和可卡因在内的成瘾物质。轶事报道证明，单剂量的伊波加因可消除戒断症状，并在较长时间内减少对药物的渴望。伊波加因所谓的抗成瘾特性需要在人体中进行严格验证。我们已启动一项单次给药的耐受性递增研究，以评估伊波加因治疗可卡因依赖的安全性。该研究的主要目的是确定安全性、药代动力学和剂量效应，并确定可卡因依赖患者的相关疗效参数。通过分析一期试验中伊波加因及其去甲基代谢物（去甲伊波加因）的浓度-时间数据，并进行体外实验以阐明母体药物和代谢物代谢过程中涉及的具体处置过程，来评估伊波加因在人体中的药代动力学和药效学特征。开展伊波加因在人体中的临床安全性研究将有助于确定未来是否有理由进行疗效试验。
