VeteransAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Neuroimaging & Brain Measures5-MeO-DMTIbogaine

A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder

This case report SPECT imaging study explored the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder (AUD). It reported that the patient felt improvement in mood, cessation of alcohol use, and decreased cravings at 5 days post-treatment, but the patient returned partially to mild alcohol use at 2 months. Also, higher perfusion in multiple brain regions broadly associated with AUD and known pharmacology of both compounds was reported.

Authors

  • Benjamin Kelmendi
  • Joseph Barsuglia
  • Martin Polanco

Published

Progress in Brain Research
individual Study

Abstract

Ibogaine is a plant-derived alkaloid and dissociative psychedelic that demonstrates anti-addictive properties with several substances of abuse, including alcohol. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring psychedelic known to occasion potent mystical-type experiences and also demonstrates anti-addictive properties. The potential therapeutic effects of both compounds in treating alcohol use disorder require further investigation and there are no published human neuroimaging findings of either treatment to date. We present the case of a 31-year-old male military veteran with moderate alcohol use disorder who sought treatment at an inpatient clinic in Mexico that utilized a sequential protocol with ibogaine hydrochloride (1550 mg, 17.9 mg/kg) on day 1, followed by vaporized 5-MeO-DMT (bufotoxin source 50 mg, estimated 5-MeO-DMT content, 5-7 mg) on day 3. The patient received SPECT neuroimaging that included a resting-state protocol before, and 3 days after completion of the program. During the patient's ibogaine treatment, he experienced dream-like visions that included content pertaining to his alcohol use and resolution of past developmental traumas. He described his treatment with 5-MeO-DMT as a peak transformational and spiritual breakthrough. On post-treatment SPECT neuroimaging, increases in brain perfusion were noted in bilateral caudate nuclei, left putamen, right insula, as well as temporal, occipital, and cerebellar regions compared to the patient's baseline scan. The patient reported improvement in mood, cessation of alcohol use, and reduced cravings at 5 days post-treatment, effects which were sustained at 1 month, with a partial return to mild alcohol use at 2 months. In this case, serial administration of ibogaine and 5-MeO-DMT resulted in increased perfusion in multiple brain regions broadly associated with alcohol use disorders and known pharmacology of both compounds, which coincided with a short-term therapeutic outcome. We present theoretical considerations regarding the potential of both psychedelic medicines in treating alcohol use disorders in the context of these isolated findings, and areas for future investigation.

Available with Blossom Pro

Research Summary of 'A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder'

Introduction

Multiple classes of psychedelic compounds have shown preliminary evidence of anti-addictive effects for substances including alcohol, and more effective treatments for alcohol use disorder are needed. Ibogaine, a plant-derived dissociative psychedelic, has been reported in observational studies to interrupt addiction across several substances; 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a short-acting serotonergic tryptamine, is reported to occasion intense mystical-type experiences and has epidemiological and preclinical signals for therapeutic effects in addiction and mood disorders. Despite these lines of evidence, there were no published human neuroimaging data for either compound at the time of this report, and the mechanisms by which they might affect addiction-related brain circuits remained speculative. Barsuglia and colleagues set out to document clinical and regional cerebral blood flow changes associated with a sequential treatment protocol of ibogaine followed by vaporised 5-MeO-DMT in a single patient with alcohol use disorder. The report combines a case description, resting-state single-photon emission computed tomography (SPECT) imaging performed before and after the sequential interventions, and a theoretical rationale for why administering ibogaine and 5-MeO-DMT in sequence might produce complementary or synergistic therapeutic effects.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

Study Details

References (43)

Papers cited by this study that are also in Blossom

Ibogaine: a review

Alper, K. · The Alkaloids Chemistry and Biology (2001)

146 cited
Effect of Iboga Alkaloids on µ-Opioid Receptor-Coupled G Protein Activation

Antonio, T., Childers, S. R., Rothman, R. B. et al. · PLOS ONE (2013)

A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010

Barker, S., McIlhenny, E. H., Strassman, R. J. · Drug Testing and Analysis (2012)

Classic hallucinogens and mystical experiences: phenomenology and neural correlates

Barrett, F. S., Griffiths, R. R. · Current Topics in Behavioral Neurosciences (2017)

Classic hallucinogens in the treatment of addictions

Bogenschutz, M. P., Johnson, M. W. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study

Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)

Ibogaine in the treatment of substance dependence

Brown, T. K. · Current Drug Abuse Reviews (2013)

Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes

Brown, T. K., Alper, K. · The American Journal of Drug and Alcohol Abuse (2017)

The therapeutic potential of psychedelic drugs: past, present, and future

Carhart-Harris, R. L., Goodwin, G. M. · Neuropsychopharmacology (2017)

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)

1174 cited
Show all 43 references
Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

Carhart-Harris, R. L., Bolstridge, &. M., Day, C. M. J. et al. · Psychopharmacology (2017)

Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT

Dakic, V., Nascimento, J. M., Sartore, R. C. et al. · Scientific Reports (2017)

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

Davis, A. K., Barsuglia, J. P., Windham-Herman, A. M. et al. · Journal of Psychedelic Studies (2017)

47 cited
A Mixed-Method Analysis of Persisting Effects Associated with Positive Outcomes Following Ibogaine Detoxification

Davis, A. K., Renn, E., Windham-Herman, A. M. et al. · Journal of Psychoactive Drugs (2018)

Psilocybin for treating substance use disorders?

de Veen, B. T. H., Schellekens, A., Verheij, M. M. et al. · Expert Review of Neurotherapeutics (2016)

Assessment of addiction severity among ritual users of ayahuasca

Fábregas, J. M., González, D., Fondevila, S. et al. · Drug and Alcohol Dependence (2010)

222 cited
Effects of low dose ibogaine on subjective mood state and psychological performance

Forsyth, B., Machado, L., Jowett, T. et al. · Journal of Ethnopharmacology (2016)

Ascending-dose study of noribogaine in healthy volunteers: Pharmacokinetics, pharmacodynamics, safety, and tolerability

Glue, P., Lockhart, M., Lam, F. et al. · Journal of Clinical Pharmacology (2014)

52 cited
Serotonin and serotonin receptors in hallucinogen action

Halberstadt, A. L., Nicholas, C. R. · Handbook of Behavioral Neuroscience (2010)

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)

Psychedelic Drugs in Biomedicine

Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R. et al. · Trends in Pharmacological Sciences (2017)

The iboga alkaloids

Lavaud, C., Massiot, G. · Progress in the Chemistry of Organic Natural Products (2017)

How toxic is ibogaine?

Litjens, R. P. W., Brunt, T. M. · Clinical Toxicology (2016)

64 cited
Therapeutic effects of ritual ayahuasca use in the treatment of substance dependence: qualitative results

Loizaga-Velder, A., Verres, R. · Journal of Psychoactive Drugs (2014)

Psychedelics promote structural and functional neural plasticity

Ly, C., Greb, A. C., Cameron, L. P. et al. · Cell Reports (2018)

Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

Malcolm, B., Polanco, M., Barsuglia, J. P. · Journal of Psychoactive Drugs (2018)

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

Frampton, C. M., Yazar-Klosinski, B., Nollar, G. E. · The American Journal of Drug and Alcohol Abuse (2017)

122 cited
The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network

Palhano-Fontes, F., Andrade, K. C., Tófoli, L.F. et al. · PLOS ONE (2015)

Psychedelics and the human receptorome

Ray, T. S. · PLOS ONE (2010)

265 cited
Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression a SPECT study

Sanches, R. F., Osório, F. L., Dos Santos, R. G. et al. · Journal of Clinical Psychopharmacology (2016)

380 cited
Treating drug dependence with the aid of ibogaine: A retrospective study

Schenberg, E. E., de Castro Comis, M. A., Chaves, T. V. et al. · Journal of Psychopharmacology (2014)

Treating drug dependence with the aid of ibogaine: a qualitative study

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M. et al. · Journal of Psychedelic Studies (2016)

A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M. et al. · Journal of Psychedelic Studies (2017)

35 cited
Why MDMA therapy for alcohol use disorder? And why now?

Sessa, B. · Neuropharmacology (2017)

Can psychedelic compounds play a part in drug dependence therapy?

Sessa, B., Johnson, M. W. · British Journal of Psychiatry (2018)

Cited By (8)

Papers in Blossom that reference this study

5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study

Ragnhildstveit, A., Khan, R., Seli, P. et al. · Frontiers in Psychiatry (2023)

28 cited
Psychedelic therapy in the treatment of addiction: the past, present and future

Zafar, R., Siegel, M., Harding, R. et al. · Frontiers in Psychiatry (2023)

A systematic literature review of clinical trials and therapeutic applications of ibogaine

Köck, P., Frölich, K., Walter, M. et al. · Journal of Substance Abuse Treatment (2022)

46 cited
A narrative synthesis of research with 5-MeO-DMT

Ermakova, A. O., Dunbar, F., Rucker, J. et al. · Journal of Psychopharmacology (2021)

The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020)

Ona, G., Rocha, J. M., Bouso, J. C. et al. · Psychopharmacology (2021)

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.

A case report SPECT study and theoretical... — Research Summary & Context | Blossom