Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study

This open-label study (n=14, 8 at follow-up) found that treatment with ibogaine resulted in lower opioid addiction (ASI-Lite) and depression (BDI-II) scores up to 12 months later.

Abstract

“Background: The psychoactive indole alkaloid ibogaine has been associated with encouraging treatment outcomes for opioid dependence. The legal status of ibogaine in New Zealand provides a unique opportunity to evaluate durability of treatment outcomes. 

Objective: To examine longitudinal treatment effects over a 12-month period among individuals receiving legal ibogaine treatment for opioid dependence. 

Method: This observational study measured addiction severity as the primary outcome in 14 participants (50% female) over 12 months post-treatment using the Addiction Severity Index-Lite (ASI-Lite) following a single ibogaine treatment by either of two treatment providers. Secondary effects on depression were assessed via the Beck Depression Inventory-II (BDI-II). The Subjective Opioid Withdrawal Scale (SOWS) was collected before and immediately after treatment to measure opioid withdrawal symptoms. 

Results: Nonparametric comparisons via Friedman Test between baseline and 12-month follow-up for participants completing all interviews (n = 8) showed a significant reduction for the ASI-Lite drug use (p = 0.002) composite score. Reductions in BDI-II scores from baseline to 12-month follow-up were also significant (p < 0.001). Significant reductions in SOWS scores for all participants (n = 14) were also observed acutely after treatment (p = 0.015). Patients with partial data (n = 4) also showed reductions in ASI-Lite drug use scores and family/social status problems. One patient enrolled in the study died during treatment.

Conclusion: A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months. Ibogaine’s legal availability in New Zealand may offer improved outcomes where legislation supports treatment providers to work closely with other health professionals.”

Authors: Geoffrey E. Noller, Chris M. Frampton & Berra Yazar-Klosinski

Summary

The psychoactive indole alkaloid ibogaine has been associated with encouraging treatment outcomes for opioid dependence. A 12-month observational study of 14 participants showed that a single ibogaine treatment reduced opioid withdrawal symptoms and achieved significant reductions in addiction severity.

Introduction

Opioid dependence is a debilitating condition associated with increased morbidity and mortality, limited treatment response, and high relapse rate. It is difficult to achieve remission even with combined medication-assisted therapies due to lack of adherence, underutilization, and limited or ineffective adoption by treatment providers.

Ibogaine, a psychoactive indole alkaloid derived from the root bark of the West African shrub Tabernanthe iboga, has been used in religious rituals among the Gabonese Fang people as a stimulant and appetite suppressant.

Ibogaine’s potential for treating opioid dependence was discovered in 1962 by Howard Lotsof. Typically administered as a single-dose treatment on a few occasions, ibogaine is well tolerated and has no effect on vital signs or adverse effects.

Ibogaine was found to have numerous functional targets with complex pharmacology in studies aiming to elucidate mechanism of action. Noribogaine was found to be the principal active moeity responsible for interrupting psychological and physiological effects of opiate dependence in rats.

This study aimed to evaluate durability of ibogaine treatment outcomes covering 12-month post-treatment in 14 participants seeking ibogaine treatment for opioid dependence. Acute withdrawal symptoms and long-term depression symptoms were also evaluated as potential contributors to treatment response.

Ethical review, treatment providers, and participants

The study was approved by the Health and Disability Multi-region Ethics Committee in February 2012 and was a non-interventional/observational study on the effects of ibogaine prescribed in accordance with regulatory authorization.

Participants who independently sought treatment were recruited through two ibogaine providers offering treatments on a fee-for-service basis. One provider offered treatment in a clinic, the other in a private practice setting, with post-treatment supervision extending beyond the typical three days of treatment.

Participants had to be 18 years or older, able to communicate in English, and committed to regular contact for 12 months post-treatment via phone or Skype.

Drug

All participants received 200 mg capsules of ibogaine HCL, initially from a European manufacturer and later from a Canadian manufacturer.

Participants received 25-55 mg/kg of ibogaine with concomitant benzodiazepine and sleep aids, administered over 24 – 96 hours. Initial dosage was selected based on patient characteristics and provider experience, and dosage was adjusted based on patient response and provider assessment.

Data collection and outcome measures

The investigator collected data in person at treatment sites, at baseline and immediately post-treatment. She attempted to contact participants’ affiliates to independently verify responses, and conducted brief conversations with participants at interviews 4, 6, 7, 9, 10, and 13.

The ASI-Lite was administered pretreatment, at months 1, 3, 6, 9, and 12 post-treatment to measure problem severity in seven life areas commonly affected by substance use disorders.

The BDI-II was administered for depression symptoms, the SOWS was administered for opioid withdrawal symptoms, and the ASI was administered to assess subject response during treatment.

Two random urine screens were conducted during the follow-up period, with a third final screen at the time of their last interview. All expenses associated with testing were met.

Statistical methods

Descriptive statistics were used to summarize data, and Friedman’s nonparametric ANOVA was used to test for significant patterns of change over time for the ASI-Lite subscales, BDI-II, and SOWS scores.

Results

Twenty people sought ibogaine treatment with two providers, and 15 were enrolled into the study. One person died during their treatment, and a second person was disqualified from the study. The data reported here describes posttreatment outcomes for 14 participants administered ibogaine for opioid dependence. All participants had moderate comorbid depression symptoms at baseline, and had previously received an average of 4.7 treatments for substance dependence, with 58% of these being detoxification.

During treatment, 10 of 13 subjects received ondansetron, 5 received diazepam, and 1 received zopiclone. One participant died during treatment, and two participants were enrolled via Providers 1 and 2, with one participant subsequently lost to treatment at 11-months.

The SOWS showed a significant reduction in withdrawal symptoms from baseline up to 24 hours post-administration, but did not reach statistical significance at 42 hours.

Only the Drug component of the ASI-Lite showed a statistically significant decrease over time. The remaining composite score categories showed nonsignificant decreases over time, with the notable exception of the Medical component, which actually increased significantly.

Researchers were unable to consistently collect urine drug test data corroborating ASI-Lite reported drug use. However, a majority of participants reported reduced other drug use and alcohol use at three and six months, and a majority of participants reported reduced alcohol use at twelve months.

Discussion

The present study reports treatment outcomes for opioid dependent participants during 12 months following single-dose ibogaine administration. The outcomes are comparable to the success of currently accepted treatments, including those reported from wide-ranging analyses and combined interventions reviewed previously (6).

In a multi-site US study measuring buprenorphine stabilization and tapering to cessation of opioids, there were no differences in abstinence rates between 7-day and 28-day taper groups at 1-month and 3-month follow-ups.

Ibogaine’s attenuation of withdrawal from opioids substantiates earlier experimental research referencing ibogaine’s “significant pharmacologically mediated effect” on opioid withdrawal. This is particularly relevant in a country like New Zealand where methadone is the most commonly injected opioid.

The significant reductions in BDI-II scores (p 0.001) observed in this study support earlier research identifying reductions in depressive symptoms post-ibogaine treatment. Even participants who did not cease opioid use entirely described their ibogaine experience in positive terms.

Five participants reported benzodiazepine use in the 30 days preceding treatment, but at one month, only six participants reported benzodiazepine use.

Despite positive outcomes reported in this study, there are also specific risks associated with ibogaine, the most salient of which is mortality temporally associated with treatment. This issue is of particular significance given the death during treatment of one subject pre-enrolled in the present study.

Ibogaine-related fatalities in treatment have been reported in detail for 19 individuals from 1990 to 2008, and do not appear to be due to a characteristic syndrome of neurotoxicity.

The metabolism of ibogaine by cytochrome P450 enzyme CYP2D6 into noribogaine through the first-pass process has implications for clinical safety, with poor CYP2D6 metabolizers having higher active moiety and longer half-life than individuals having standard metabolic function.

Regarding New Zealand treatments, inquiries revealed that although official reporting on New Zealand treatments is voluntary, two providers collectively reported treating 83 patients. It seems likely that more than 100 treatments occurred during the study period.

Despite the fatality, structural mechanisms exist in New Zealand to reduce ibogaine’s potential risks, and legal access to ibogaine promotes open engagement with the treatment process. Regulation is most likely to occur where there is a will amongst all stakeholders to develop a set of robust clinical guidelines.

This study has provided further evidence supporting ibogaine’s effectiveness in reducing opioid withdrawal, cravings and use over an extended period, but its method is flawed and its sample size is small.

This study has demonstrated that ibogaine treatment can be effective in reducing opioid withdrawal, craving and depressed mood, and reducing or ceasing opioid use in some opioid-dependent individuals.