OPEN Foundation

M. Belgers

Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study

Abstract

Background and aims: Ibogaine is an indole alkaloid used in rituals of the African Bwiti tribe. It is also used in non-medical settings to treat addiction. However, ibogaine has been linked to several deaths, mainly due to cardiac events called torsades des pointes preceded by QTc prolongation as well as other safety concerns. This study aimed to evaluate the cardiac, cerebellar and psychomimetic safety of ibogaine in patients with opioid use disorder.

Design: A descriptive open-label observational study.

Setting: Department of psychiatry in a university medical center, the Netherlands.

Participants: Patients with opioid use disorder (n = 14) on opioid maintenance treatment with a lasting wish for abstinence, who failed to reach abstinence with standard care.

Intervention and measurements: After conversion to morphine-sulphate, a single dose of ibogaine-HCl 10 mg/kg was administered and patients were monitored at regular intervals for at least 24 hours assessing QTc, blood pressure and heart rate, scale for the assessment and rating of ataxia (SARA) to assess cerebellar side effects and the delirium observation scale (DOS) to assess psychomimetic effects.

Findings: The maximum QTc (Fridericia) prolongation was on average 95ms (range 29-146ms). Fifty percent of subjects reached a QTc of over 500ms during the observation period. In six out 14 subjects prolongation above 450ms lasted beyond 24 hours after ingestion of ibogaine. No torsades des pointes were observed. Severe transient ataxia with inability to walk without support was seen in all patients. Withdrawal and psychomimetic effects were mostly well-tolerated and manageable (11/14 did not return to morphine within 24 hours, DOS scores remained below threshold).

Conclusions: This open-label observational study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia.

Knuijver, T., Schellekens, A., Belgers, M., Donders, R., van Oosteren, T., Kramers, K., & Verkes, R. (2022). Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study. Addiction (Abingdon, England), 117(1), 118–128. https://doi.org/10.1111/add.15448

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Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

Abstract

Abstract unavailable for this article.
Knuijver, T., Belgers, M., Markus, W., Verkes, R. J., van Oosteren, T., & Schellekens, A. (2018). Hallucinogen persisting perception disorder after ibogaine treatment for opioid dependence. Journal of clinical psychopharmacology38(6), 646-648., 10.1097/JCP.0000000000000966
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Ibogaine and addiction in the animal model, a systematic review and meta-analysis

Abstract

Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h 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. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.

Belgers, M., Leenaars, M., Homberg, J. R., Ritskes-Hoitinga, M., Schellekens, A. F. A., & Hooijmans, C. R. (2016). Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Translational psychiatry, 6(5), e826. http://dx.doi.org/10.1038/tp.2016.71
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Treatment of heroin dependence with ibogaine

Abstract

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 (10mg/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 24hours after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24hours 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.

Schellekens, A., Oosteren, T., Knuijver, T., & Belgers, M. (2016). Treatment of heroin dependence with ibogaine. European Psychiatry, 33, S10-S11. http://dx.doi.org/10.1016%2Fj.eurpsy.2016.01.799
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