Ibogaine in the Treatment of Alcoholism: a Randomized, Double-blind, Placebo-controlled, Escalating-dose, Phase 2 Trial

Tolerability and Efficacy of Ibogaine in the Treatment of Alcoholism: the First Randomized, Double-blind, Placebo-controlled, Escalating-dose, Phase 2 Trial

Approximately 5% of the world's adult population has some alcohol-related disorder, which in addition is associated with 3% of all deaths in the world. In Brazil, harmful use and dependence on alcohol reach about 10% of the population, with alcohol being one of the main factors of disease and mortality. Although the medications currently used have some efficacy, the adverse effects and relatively long time of treatment are factors that may reduce patients' motivation to continue taking the medication correctly. Therefore, it is necessary to conduct research with new drugs for the treatment of alcoholism. Ibogaine is an alkaloid present in the bush Tabernanthe iboga (iboga), a plant from Central Africa traditionally used in countries such as Gabon and Cameroon. Animal studies and case series suggest that one or a few doses of ibogaine significantly reduce withdrawal symptoms and the intensity of use of various drugs, including opioids, psychostimulants, and alcohol. However, there are no controlled clinical studies that have explored these effects. The aim of the present study is to evaluate the safety, tolerability and efficacy of increasing doses of ibogaine in 12 alcoholic patients. Each patient will be hospitalized for 20 days and receive 3 increasing doses of ibogaine. The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly. The volunteers will also be evaluated 7, 14 and 21 days and 1, 3, 6 and 12 months after leaving the hospital to monitor the consumption of alcohol and other drugs.

Study Overview

• Status: Enrolling by invitation
• Conditions: Alcoholism
• Intervention / Treatment: Drug: Ibogaine Hydrochloride

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rafael dos Santos, PhD; Phone Number: 551636022703; Email: banisteria@gmail.com

Study Locations

• Brazil
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14048900
      • Ribeirão Preto Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Literate people
• Diagnosis of alcoholism assessed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-V)
• History of at least two previous failed treatments for alcoholism (with drug use and / or psychotherapy)
• Signing the Free and Informed Consent Form.

Exclusion Criteria:

• Presence of any psychiatric diagnosis (excluding alcohol / tobacco / nicotine abuse / dependence) assessed by the SCID-V
• Presence of clinical disease (especially cardiovascular and hepatic diseases), based on interview, physical and laboratory examination (hemogram and electrocardiogram, ECG)
• Absence of family or personal history of bipolar disorder and psychotic disorders
• Absence of recent symptoms of hypomania, mania or psychosis
• Non-literate people
• Pregnant or lactating women
• Recent use of illicit drugs (confirmed by examination in urine).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Ibogaine Hydrochloride 240 mg on day 1, placebo on day 4, placebo on day 7	Drug: Ibogaine Hydrochloride; The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly in 3 different groups.; Other Names: Placebo
Experimental: Group 2; Ibogaine Hydrochloride 240 mg on day 1, Ibogaine Hydrochloride 320 mg on day 4, placebo on day 7	Drug: Ibogaine Hydrochloride; The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly in 3 different groups.; Other Names: Placebo
Experimental: Group 3; Ibogaine Hydrochloride 240 mg on day 1, Ibogaine Hydrochloride 320 mg on day 4, Ibogaine Hydrochloride 400 mg on day 7	Drug: Ibogaine Hydrochloride; The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly in 3 different groups.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time without using alcohol	Daily alcohol use	0-1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects	Acute and subacute subjective effects	0-12 hours
Cardiovascular effects	Electrocardiogram	0-72 hours

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Conselho Nacional de Desenvolvimento Científico e Tecnológico; International Center for Ethnobotanical Education, Research, and Service
• Investigators: Principal Investigator: Rafael dos Santos, PhD, Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo; Study Director: Jaime Hallak, PhD, Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo

Publications and helpful links

Helpful Links

• dos Santos RG, Bouso JC, Hallak JEC. The antiaddictive effects of ibogaine: A systematic literature review of human studies. Journal of Psychedelic Studies 1(1): 20-28, 2017.
• Clare W et al. Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report. Journal of Psychedelic Studies 1(1): 29-34.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Hallucinogens; Ibogaine
• Other Study ID Numbers: 72938717.3.0000.5440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No