A Trial to Investigate the Effects of Cannabidiol Plus Naltrexone on Alcohol Craving in Patients With Alcohol Dependence

NCT ID: NCT06845124

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2028-09-30

Brief Summary

Alcohol addiction (AD) is a chronic relapsing disorder with currently limited pharmacological treatment options. Alcohol craving, a hallmark symptom of AD that drives relapse in patients, is only insufficiently treated by existing medication. One promising new compound for the treatment of alcohol craving in AD is Cannabidiol (CBD), which showed beneficial effects on alcohol craving in preliminary clinical studies. Additionally, CBD seems to be a particularly promising candidate for enhancing the effects of established medication, specifically Naltrexone (NTX), an opioid-antagonist, which is approved for AD treatment, due to the synergistic effects of the combination of Cannabidiol plus Naltrexone on alcohol consumption that were shown by preclinical studies. The proposed three-armed, 1:1:1 randomized, double-blind, placebo-controlled parallel group, multicentric phase II trial seeks to test the putative synergistic effects of combined CBD (800mg) + oral NTX (50mg) against CBD (1200mg) + oral NTX (50mg) against Placebo + oral NTX (50mg) on alcohol craving (primary outcome) in male and female patients with AD that suffer from high alcohol craving. The trial seeks to test the effects of the innovative combination of CBD plus NTX against Placebo plus NTX on alcohol craving over a 14-day treatment period, which is embedded in a standardized addiction treatment program according to current treatment guidelines, in order to estimate the added value of treatment with CBD on alcohol craving. Quality of life and neurobiological and biochemical markers for craving will serve as secondary outcomes, because they show strong associations to treatment outcome and relapse risk. Collection and analysis of follow-up data (28 days, 42 days, 105 days, 196 days) will be performed to determine whether treatment effects relate to patient outcome.

Conditions

Alcohol Addiction; Alcoholism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cannabidiol (800mg) + Naltrexone

All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the experimental group of trial arm 1, patients will receive a dose of 800mg Cannabidiol (CBD) daily over the course of 14 days during in-patient treatment.

Group Type: EXPERIMENTAL

Cannabidiol capsules

Intervention Type: DRUG

800mg (trial arm 1) or 1200mg (trial arm 2) Cannabidiol capsules will be administered daily over the course of 14 days.

Naltrexone (drug)

Intervention Type: DRUG

All participants will receive 50mg Naltrexone daily as oral tablet throughout the study.

Cannabidiol (1200mg) + Naltrexone

All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the experimental group of trial arm 2, patients will receive a dose of 1200mg Cannabidiol (CBD) daily over the course of 14 days during in-patient treatment.

Group Type: EXPERIMENTAL

Cannabidiol capsules

Intervention Type: DRUG

800mg (trial arm 1) or 1200mg (trial arm 2) Cannabidiol capsules will be administered daily over the course of 14 days.

Naltrexone (drug)

Intervention Type: DRUG

All participants will receive 50mg Naltrexone daily as oral tablet throughout the study.

Placebo + Naltrexone

All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the comparator group of trial arm 3, patients will receive placebo capsules daily over the course of 14 days during in-patient treatment.

Group Type: ACTIVE_COMPARATOR

Naltrexone (drug)

Intervention Type: DRUG

All participants will receive 50mg Naltrexone daily as oral tablet throughout the study.

Placebo

Intervention Type: DRUG

Placebo capsules matching the cannabidiol capsules will be administered daily.

Interventions

Cannabidiol capsules

800mg (trial arm 1) or 1200mg (trial arm 2) Cannabidiol capsules will be administered daily over the course of 14 days.

Intervention Type: DRUG

Naltrexone (drug)

All participants will receive 50mg Naltrexone daily as oral tablet throughout the study.

Intervention Type: DRUG

Placebo

Placebo capsules matching the cannabidiol capsules will be administered daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 70 years
• Patients meeting the diagnosis of an alcohol dependence according to the ICD-10
• Patients reporting alcohol craving as symptom of AD according to the ICD10 symptom definition
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrollment in the study)
• Consent to random assignment
• For women with childbearing potential (WOCBP) and males with partners with CBP, use of a highly effective birth control method until one month after last IMP administration (see Appendix 1) and negative pregnancy test

Exclusion Criteria

• Current psychotic or bipolar disorder or current severe depressive episode with suicidal ideations
• Current treatment with any of the following substances: Any investigational medicinal product, Opioid-containing Analgesics, Anti-obesity drugs, Anticonvulsants, Opioid-containing Antidiarrheal Agents, Antineoplastics, Antipsychotics (exception: episodic use of melperone, prothipendyl, pipamperone, promethazine and quetiapine are allowed), Antidepressants (exception: allowed, when being taken in stable dose for a minimum of 14 days prior to enrolment and/or doxepine in low doses [max. 75mg daily]), Opioid-containing Cough/cold agents, Systemical Steroids, Other anti-craving (e.g. Acamprosate) or aversive medication (e.g. disulfiram), THC- or CBD-containing medication, Antiretroviral medication (e.g., Efavirenz), Xanthines (e.g., Theophylline), General anesthetics (e.g., propofol), Hypericum perforatum, Antibiotics (e.g., Rifampin, Clarithromycin, Erythromycin)
• Positive drug screening (amphetamines/ecstasy, opiates, cocaine, barbiturates)
• Pregnancy, lactation or breastfeeding
• Current severe somatic comorbidities: severe liver cirrhosis [CHILD B or C] or epilepsy determined by medical history
• Patients with elevated transaminase levels (AST or ALT) above three times the upper limit normal (ULN) value with elevated bilirubin levels above twice the ULN value
• History of hypersensitivity to the investigational medicinal product CBD and/or Naltrexone (trade names: Adepend, Naltrexon-Hcl neuraxpharm, Naltrexonhydrochlorid Accord) or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product CBD and/or Naltrexone
• Participation in other clinical trials or observation period of competing clinical trials, respectively.
• Acute suicidal tendency or acute endangerment of self and others

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University - Institute of Medical Biometry (IMBI)

UNKNOWN

Sponsor Role: collaborator

Heidelberg University - Coordination Centre for Clinical Trials (KKS) of Heidelberg University

UNKNOWN

Sponsor Role: collaborator

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Central Institute of Mental Health, Mannheim

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Bach, Prof. Dr. Dr.

Role: STUDY_DIRECTOR

Central Institute of Mental Health, Mannheim

Locations

Psychiatric Centre North Baden (PZN)

Wiesloch, Baden-Wurttemberg, Germany

Central Institute of Mental Health

Mannheim, , Germany

Countries

Germany

Central Contacts

Patrick Bach, Prof. Dr. Dr.

Role: CONTACT

patrick.bach@zi-mannheim.de

+49-621-1703-0

Sina Vetter, M.Sc.

Role: CONTACT

Sina.Vetter@zi-mannheim.de

+49-621-1703-0

Facility Contacts

Tobias Link, Dr.

Role: primary

sekretariat.sucht@pzn-wiesloch.de

+49 6222 55-2790

Patrick Bach, Prof. Dr. Dr.

Role: primary

patrick.bach@zi-mannheim.de

+496211703

Sina Vetter, M.Sc.

Role: backup

Sina.Vetter@zi-mannheim.de

+496211703

References

Vetter S, Weinberg J, Thomas BC, Kirchner M, Thalmann P, Klose C, Pfisterer M, Kolsch T, Oesterle S, Vollstaedt-Klein S, Koopmann A, Lenz B, Kiefer F, Link T, Bach P. Investigation of the combined effects of cannabidiol plus naltrexone on alcohol craving in alcohol dependence: study protocol of a phase II randomised, double-blind, placebo-controlled, parallel-group trial - ICONICplus Trial. BMJ Open. 2025 Aug 12;15(8):e106348. doi: 10.1136/bmjopen-2025-106348.

Reference Type: DERIVED

PMID: 40803733 (View on PubMed)

Other Identifiers

2024-518164-12-00

Identifier Type: CTIS

Identifier Source: secondary_id

CIMH ICONICplus 25

Identifier Type: -

Identifier Source: org_study_id