The use of the hallucinogen ibogaine as an anti-addiction agent has been described in several case reports, dating back to the eighties. The anti-addiction properties of ibogaine have been confirmed in a large body of animal work. Ibogaine has been shown to be effective in reducing withdrawal severity and substance use for a variety of substances, including cocaine and opiates. Animal studies also show some potentially dangerous adverse reactions, including cerebellar toxicity and potential cardiac effects. While pharmacological treatment options for opiate and cocaine dependence are still limited, ibogaine assisted treatment might be a promising new option. Therefore more systematic studies on its toxicity and efficacy are warranted. In our studies we address these two research questions: is ibogaine treatment for opiate dependence safe and effective for treating opiate withdrawal and relapse prevention? A secondary objective is to explore the pharmacokinetic properties of ibogaine.

Animal work: first we performed a systematic review and meta-analysis of animal studies on ibogaine. Thirty studies were included in the systematic review, of which 27 could be analyzed in meta-analysis. Human studies: fifteen opiate dependent patients will be treated with ibogaine (10 mg/kg), on top of treatment as usual. Ibogaine toxicity will be assessed through close monitoring with electrocardiography, with QTc prolongation as main outcome measure, repeated assessments of ataxia using the (SARA) and observation of psychotic symptoms by using the Delirium Observations Scale (DOS). Ibogaine efficacy will be measured, using repeated evaluations of opiate withdrawal severity (Subjective Opiate Withdrawal Scale: SOWS; Objective Opiate Withdrawal Scale: OOWS), craving intensity (using a Visual Analogue Scale) and substance use, with a six-month follow-up. Clinical observations in ibogaine treated individuals will be compared with a cohort of opiate dependent patients treated with a rapid detoxification procedure. Both acute and long-term effects will be linked with serum ibogaine and noribogaine levels.

Animal work: overall, ibogaine reduced drug self-administration, particularly during the first 24 hours after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 hours after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm as well as on its neuropharmacological working mechanisms are limited. Human studies: human data are still being collected. Treatment of the first patients confirmed strong effects of ibogaine on heart rhythm (QTc prolongation) and ataxia, while the opiate withdrawal symptoms were relatively mild. The first observations on the clinical effect of ibogaine on craving and substance use will also be shared.

Based on our meta-analysis of animal data, there is strong evidence that ibogaine is effective in reducing drug self-administration in animals. This warrants further studies into the clinical efficacy of ibogaine in substance dependent patients in reducing craving and substance use. Our first clinical experiences in a limited number of patients confirm that ibogaine treatment may be effective in reducing opiate withdrawal, but can potentially have transient cardiac and cerebellar toxicity.

The authors have not supplied his declaration of competing interest.