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

• ClinicalTrials.gov Identifier: NCT03380728
• Recruitment Status: Not yet recruiting
• First Posted: December 21, 2017
• Last Update Posted: May 17, 2022
• 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
• Information provided by (Responsible Party): Rafael Guimarães dos Santos, University of Sao Paulo

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Alcoholism	Drug: Ibogaine Hydrochloride	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Tolerability and Efficacy of Ibogaine in the Treatment of Alcoholism: the First Randomized, Double-blind, Placebo-controlled, Escalating-dose, Phase 2 Trial
• Estimated Study Start Date: October 2022
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

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 Name: 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 Name: 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 Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Time without using alcohol [ Time Frame: 0-12 months ]
   Notebook of daily alcohol use

Secondary Outcome Measures :

1. Subjective effects [ Time Frame: 0-72 hours ]
   Acute and subacute subjective effects
2. Biomarkers [ Time Frame: 0-24 hours ]
   Endocannabinoids, brain-derived neurotrophic factor (BDNF), interleukines
3. Cardiovascular effects [ Time Frame: 0-72 hours ]
   electrocardiogram

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Rafael dos Santos, PhD; 551636022703; banisteria@gmail.com

Locations

Brazil

Ribeirão Preto Medical School

Ribeirão Preto, São Paulo, Brazil, 14048900

Sponsors and Collaborators

University of Sao Paulo

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

More Information

Additional Information:

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. 

• Responsible Party: Rafael Guimarães dos Santos, Postdoctoral Fellow, Principal Investigator, University of Sao Paulo
• ClinicalTrials.gov Identifier: NCT03380728
• Other Study ID Numbers: 72938717.3.0000.5440
• First Posted: December 21, 2017
• Last Update Posted: May 17, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Ibogaine; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action