Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea.

Ibogaine, an indole alkaloid from the rain forest shrub Tabernanthe iboga, has been used by indigenous peoples in equatorial Africa to combat fatigue and hunger and as a religious sacrament. Anecdotal reports from addict self-help groups claim a single dose eliminates withdrawal symptoms and reduces drug cravings for extended periods, but these purported antiaddictive properties require rigorous validation. A rising tolerance study with single administration has been initiated to assess ibogaine's safety for treating cocaine dependency, with primary objectives to determine safety, pharmacokinetics, dose effects, and relevant efficacy parameters. Pharmacokinetic and pharmacodynamic characteristics are assessed via concentration-time data from the Phase I trial and in vitro experiments on metabolism.

Study at a glance

Abstract

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.