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

NCT06845124 | Recruiting Phase 2 DMC

• 2 other identifiers: CIMH ICONICplus 252024-518164-12-00
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Obsessive Compulsive Drinking Scale (OCDS-G)

  The alcohol craving will be assessed at separate time points before and after Cannabidiol administration using the Obsessive Compulsive Drinking Scale. The Obsessive Compulsive Drinking Scale consists of 14 items, each rated on a 5-point Likert scale (0-4), resulting in scores from 0 to 40, with higher scores indicating higher craving.

  The difference of alcohol craving between baseline (visit 2) and 14 days after the first treatment visit (visit 5) will serve as primary endpoint.

Secondary Outcomes (18)

• Obsessive Compulsive Drinking Scale (OCDS-G)

  Differences from baseline (visit 2, day -2) of Obsessive Compulsive Drinking Scale craving scores to visits 4 (day 7, i.e., 7 days after the first treatment visit) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196)

• Subjective quality of life index

  Differences from baseline (visit 2, day -2) of Quality of life (WHO-QOL-BREF scores) to end of treatment (visit 5, day 14) and follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196).

• Beck Depression Inventory (BDI-II)

  Difference from baseline (visit 2, day -2) of depressive symptoms to end of treatment (visit 5, day 14)

• State Trait Anxiety Inventory (STAI)

  Difference from baseline (visit 2, day -2) of depressive symptoms to end of treatment (visit 5, day 14)

• Patient reported outcomes (PRO)

  On visit 3 (day 1 of treatment), visit 4 (day 7 of treatment), visit 5 (day 14, end of treatment) and during follow up visits 6 (day 28), 7 (day 42), 8 (day 105), 9 (day 196)

Study Arms (3)

Cannabidiol (800mg) + Naltrexone

EXPERIMENTAL

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.

Drug: Cannabidiol capsules; Drug: Naltrexone (drug)

Cannabidiol (1200mg) + Naltrexone

EXPERIMENTAL

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.

Drug: Cannabidiol capsules; Drug: Naltrexone (drug)

Placebo + Naltrexone

ACTIVE COMPARATOR

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.

Drug: Naltrexone (drug); Drug: Placebo

Interventions

Cannabidiol capsules DRUG

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

Cannabidiol (1200mg) + Naltrexone; Cannabidiol (800mg) + Naltrexone

Naltrexone (drug) DRUG

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

Cannabidiol (1200mg) + Naltrexone; Cannabidiol (800mg) + Naltrexone; Placebo + Naltrexone

Placebo DRUG

Placebo capsules matching the cannabidiol capsules will be administered daily.

Placebo + Naltrexone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heidelberg University - Institute of Medical Biometry (IMBI): collaborator
• German Federal Ministry of Education and Research: collaborator
• Central Institute of Mental Health, Mannheim: lead
• Heidelberg University - Coordination Centre for Clinical Trials (KKS) of Heidelberg University: collaborator

Study Sites (2)

Psychiatric Centre North Baden (PZN)

Wiesloch, Baden-Wurttemberg, 69168, Germany

NOT YET RECRUITING

Central Institute of Mental Health

Mannheim, 68159, Germany

RECRUITING

Related Publications (1)

• 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.

  PMID: 40803733 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Cannabidiol; Naltrexone; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Patrick Bach, Prof. Dr. Dr.

  Central Institute of Mental Health, Mannheim

  STUDY DIRECTOR

Central Study Contacts

Patrick Bach, Prof. Dr. Dr.

CONTACT

+49-621-1703-0; patrick.bach@zi-mannheim.de

Sina Vetter, M.Sc.

CONTACT

+49-621-1703-0; Sina.Vetter@zi-mannheim.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: February 25, 2025
• Study Start: July 22, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available upon publication of the results until 3 years after that.
• Access Criteria: Individual data will be shared with researchers who provide a methodologically sound proposal (sent to the Principal Investigator/Study Chair of the Trial).

Locations

DE (2)