OPEN Foundation

Iboga / Ibogaine

Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning

Abstract

Background and aims

Very few studies have reported the effectiveness of ibogaine as a treatment for chronic opioid use. Therefore, this study evaluated the acute subjective effects of ibogaine, outcomes on problematic opioid consumption, and the long-term associations with psychological functioning.

Methods

Using online data collection, 88 patients who received ibogaine treatment in Mexico between 2012 and 2015 completed our survey.

Results

Most participants (72%) had used opioids for at least 4 years and 69% reported daily use. Most (80%) indicated that ibogaine eliminated or drastically reduced withdrawal symptoms. Fifty percent reported that ibogaine reduced opioid craving, some (25%) reporting a reduction in craving lasting at least 3 months. Thirty percent of participants reported never using opioids again following ibogaine treatment. And over one half (54%) of these abstainers had been abstinent for at least 1 year, with 31% abstinent for at least 2 years. At the time of survey, 41% of all participants reported sustained abstinence (>6 months). Although 70% of the total sample reported a relapse following treatment, 48% reported decreased use from pretreatment levels and an additional 11% eventually achieved abstinence. Treatment responders had the lowest rates of depressive and anxious symptoms, the highest levels of subjective well-being and rated their ibogaine treatment as more spiritually meaningful compared with treatment non-responders.

Conclusion

The results suggest that ibogaine is associated with reductions in opioid use, including complete abstinence, and has long-term positive psychological outcomes. Future research should investigate the efficacy of ibogaine treatment using rigorous longitudinal and controlled designs.

Davis, A. K., Barsuglia, J. P., Windham-Herman, A. M., Lynch, M., & Polanco, M. (2017). Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short-and long-term outcomes and current psychological functioning. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2017.009
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A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment

Abstract

Objective

This report documents the phenomenology of the subjective experiences of 22 patients with substance-related disorders who were involved in a treatment combining cognitive–behavioral therapy and hospital sessions with ibogaine in Brazil.

Methods

Participants underwent a one-to-one semi-structured interview exploring the subjective effects of ibogaine. We employed interpretative phenomenological analysis to identify relevant phenomenological categories, including physical sensations, perceptual (visual, auditory, and olfactory), emotional, cognitive, and spiritual. Participants also compared ibogaine with other drugs used in life, including psychedelics like ayahuasca, psilocybin mushrooms, and lysergic acid diethylamide.

Results

The findings reveal that the subjective experience with ibogaine has similarities with other psychedelic substances, but also important differences. These include very strong and unpleasant physical effects as well as, at least in this patient population, a very difficult and challenging experience.

Conclusions

Overall, the descriptions involve heightened memory retrieval, specially related to drug abuse and the perception of one’s own future with or without drug use. Strong perceptual phenomena, especially dreamlike visions, were commonly reported. Based on Revonsuo’s evolutionary hypothesis for the function of dreams and of previous suggestions that ibogaine has oneiric properties, we suggest the subjective experience of drug-dependent patients elicited by ibogaine may be framed as simulations of threat and danger.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Tófoli, L. F., Chaves, B. D. R., & da Silveira, D. X. (2017). A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2017.007
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Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes

Abstract

BACKGROUND:
Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine.
OBJECTIVES:
To study outcomes following opioid detoxification with ibogaine.
METHODS:
In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl. Subjects used oxycodone (n = 21; 70%) and/or heroin (n = 18; 60%) in respective amounts of 250 ± 180 mg/day and 1.3 ± 0.94 g/day, and averaged 3.1 ± 2.6 previous episodes of treatment for opioid dependence. Detoxification and follow-up outcomes at 1, 3, 6, 9, and 12 months were evaluated utilizing the Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite (ASIC) scores, respectively.
RESULTS:
SOWS scores decreased from 31.0 ± 11.6 pretreatment to 14.0 ± 9.8 at 76.5 ± 30 hours posttreatment (t = 7.07, df = 26, p < 0.001). At 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. ASIC Drug Use and Legal and Family/Social Status scores were improved relative to pretreatment baseline at all posttreatment time points (p < .001). Improvement in Drug Use scores was maximal at 1 month, and subsequently sustained from 3 to 12 months at levels that did not reach equivalence to the effect at 1 month.
CONCLUSION:
Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful, and may provide a useful prototype for discovery and development of innovative pharmacotherapy of addiction.
Brown, T. K., & Alper, K. (2017). Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse, 1-13. 10.1080/00952990.2017.1320802
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Anxiolytic-like effects of noribogaine in zebrafish

Abstract

Noribogaine is the main psychoactive metabolite of the hallucinogenic drug ibogaine, and is a particularly interesting compound potentially useful to treat dependence and various psychiatric disorders. Here, we report the effects of noribogaine on anxiety and locomotion in zebrafish (Danio rerio), a new promising model organism in neurobehavioral and psychopharmacological research. Adult zebrafish were subjected to the 5min novel tank test (NTT) following an acute, 20-min drug immersion in 1, 5 and 10mg/L noribogaine. Overall, noribogaine produced robust anxiolytic-like behavior in zebrafish (increasing the time spent and transitions to the top half compartment and reducing freezing bouts) without overt effects on fish locomotion. Taken together, these results indicate that noribogaine modulates the components of the acute stress response related to emotionality and anxiety behaviors, implicating this drug as a potentially useful non-sedative anxiolytic agent.
Kalueff, A. V., Kaluyeva, A., & Mailet, E. L. (2017). Anxiolytic-like effects of noribogaine in zebrafish. Behavioural Brain Research330, 63-67. 10.1016/j.bbr.2017.05.008
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Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report

Abstract

Background and aims

Ibogaine is a natural alkaloid that has been used in the last decades as an adjuvant for the treatment of opiate withdrawal. Despite the beneficial results suggested by animal studies and case series, there is a lack of clinical trials to assess the safety and efficacy of ibogaine. Moreover, the majority of reports described cases of heroin-dependent individuals, with and without concomitant use of methadone, using high doses of ibogaine. Therefore, it is not clear if ibogaine at low doses could be used therapeutically in people on methadone maintenance treatments (MMT).

Methods

Case report of a female on MMT for 17 years who performed a self-treatment with several low and cumulative doses of ibogaine over a 6-week period.

Results

The patient successfully eliminated her withdrawals from methadone with ibogaine. Each administration of ibogaine attenuated the withdrawal symptoms for several hours, and reduced the tolerance to methadone until all signs of withdrawal symptoms disappeared at the end of the treatment. No serious adverse effects were observed, and at no point did the QTc measures reach clinically significant scores. Twelve months after the treatment, she was no longer on MMT.

Conclusions

To our knowledge, this is the first case report describing an ibogaine treatment using low and cumulative doses in a person on MMT. Although preliminary, this case suggests that low and cumulative doses of ibogaine may reduce withdrawal symptoms in patients undergoing MMT.

Wilkins, C., dos Santos, R. G., Solá, J., Aixalá, M., Cura, P., Moreno, E., … & Bouso, J. C. (2017). Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report. Journal of Psychedelic Studies1(1), 29-34. 10.1556/2054.01.2017.005
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Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study

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.
Noller, G. E., Frampton, C. M., & Yazar-Klosinski, B. (2017). Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse, 1-10. 10.1080/00952990.2017.1310218
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Examination of the Phenomenology of the Ibogaine Treatment Experience: Role of Altered States of Consciousness and Psychedelic Experiences

Psychedelic drugs have historically been used for ritualistic purposes and to help individuals gain insight. Ibogaine, a naturally occurring psychoactive substance, has been reported to have anti-addictive properties that aid in the treatment of substance use disorders. An online survey obtained retrospective data from individuals who used ibogaine in the past. Individuals who used ibogaine tended to describe thematically similar experiences post-treatment. This study adds to the literature by using the 5d-ASC, a psychometrically sound measure of altered states of consciousness (ASCs), to examine the ASCs induced by ibogaine and discusses the demographic characteristics of those who seek ibogaine treatment (N = 27). The study also examined several aspects of ibogaine treatment experience, including reasons for seeking treatment, course of treatment, and treatment outcome. Results indicated a positive correlation between the various dimensions of the ASCs and the outcome (ability to make changes in one’s life, cravings, and how changed the person was as a result of ibogaine treatment). While this study is limited in generalizability due to high attrition and low sample size, it deepens the understanding of the phenomenological experience of ibogaine and explores the possible utility of ibogaine in the treatment of substance use disorders.

Heink, A., Katsikas, S., & Lange-Altman, T. (2017). Examination of the Phenomenology of the Ibogaine Treatment Experience: Role of Altered States of Consciousness and Psychedelic Experiences. Journal of Psychoactive Drugs, 1-8. 10.1080/02791072.2017.1290855
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Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine

Abstract

BACKGROUND:
Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption.
CASE DETAILS:
The maximum concentration of ibogaine was 1.45 mg/L. Our patient developed markedly prolonged QTc interval of 647ms maximum, several multiple cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and Torsades des Pointes). QTc-prolongation remained present until 12 days after ingestion, several days after ibogaine plasma-levels were low, implicating clinically relevant noribogaine concentrations long after ibogaine had been cleared from the plasma. The ratio k12/k21 for noribogaine was 21.5 and 4.28 for ibogaine, implicating a lower distribution of noribogaine from the peripheral compartment into the central compartment compared to ibogaine.
CONCLUSIONS:
We demonstrated a linear relationship between the concentration of the metabolite and long duration of action, rather than with parent ibogaine. Therefore, after (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite.
Henstra, M., Wong, L., Chahbouni, A., Swart, N., Allaart, C., & Sombogaard, F. (2017). Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine. Clinical Toxicology55(6), 600-602. 10.1080/15563650.2017.1287372
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The Iboga Alkaloids

Abstract

Iboga alkaloids are a particular class of indolomonoterpenes most often characterized by an isoquinuclidine nucleus. Their first occurrence was detected in the roots of Tabernanthe iboga, a sacred plant to the people of Gabon, which made it cult object. Ibogaine is the main representative of this class of alkaloids and its psychoactive properties are well documented. It has been proposed as a drug cessation treatment and has a wide range of activities in targeting opioids, cocaine, and alcohol. The purpose of this chapter is to provide a background on this molecule and related compounds and to update knowledge on the most recent advances made. Difficulties linked to the status of ibogaine as a drug in several countries have hampered its development, but 18-methoxycoronaridine is currently under evaluation for the same purposes and for the treatment of leishmaniasis. The chapter is divided into six parts: an introduction aiming at defining what is called an iboga alkaloid, and this is followed by current knowledge on their biosynthesis, which unfortunately remains a “black box” as far as the key construction step is concerned. Many of these alkaloids are still being discovered and the third and fourth parts of the chapter discuss the analytical tools in use for this purpose and give lists of new monomeric and dimeric alkaloids belonging to this class. When necessary, the structures are discussed especially with regard to absolute configuration determinations, which remain a point of weakness in their assignments. Part V gives an account of progress made in the synthesis, partial and total, which the authors believe is key to providing solid solutions to the industrial development of the most promising molecules. The last part of the chapter is devoted to the biological properties of iboga alkaloids, with particular emphasis on ibogaine and 18-methoxycoronaridine.

Lavaud, C., & Massiot, G. (2017). The Iboga Alkaloids. In Progress in the Chemistry of Organic Natural Products 105 (pp. 89-136). Springer International Publishing. 10.1007/978-3-319-49712-9_2
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Treating drug dependence with the aid of ibogaine: A qualitative study

Abstract

Background: Substance use disorders are important contributors to the global burden of disease, but current treatments are not associated with high rates of recovery. The lack of approved and effective treatments is acutely problematic for psychostimulants like cocaine and crack cocaine. One promising alternative in the treatment of drug dependence in general and psychostimulants in particular is the use of the psychedelic alkaloid ibogaine combined with psychotherapy. This was recently shown to induce prolonged periods of abstinence in polydrug users, including psychostimulants. However, drug dependence treatments cannot be comprehensively evaluated with reductions in consumption alone, with current recommendations including secondary outcome measures like craving, family and social relationship, quality of life, and self-efficacy.

Methods: We therefore employed a directed approach to qualitative content analysis to evaluate the outcomes of a treatment combining ibogaine with cognitive-behavioral therapy based on data gathered from patient’s reports obtained in semi-structured interviews.

Main findings: The results revealed that patients benefited from the treatment in all the secondary outcomes, reporting decreases in craving and improvements in personal relationships, quality of life, and self-efficacy, thus supporting existing notions that treatments combining ibogaine and psychotherapy do have a therapeutic potential in the treatment of substance use disorders.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Chaves, B. D. R., Tófoli, L. F., & da Silveira, D. X. (2016). Treating drug dependence with the aid of ibogaine: A qualitative study. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2016.002

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22 May - Delivering Effective Psychedelic Clinical Trials

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