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
Introduction Alcohol dependence (AD) is highly prevalent and has severe consequences on health and quality of life. However, the efficacy of approved pharmacotherapies such as naltrexone (NTX) remains limited, highlighting the need for novel pharmacotherapeutic approaches. Cannabidiol (CBD) is a pro...
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BMJ Publishing Group
2025-08-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/8/e106348.full |
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| author | Falk Kiefer Christina Klose Bettina C Thomas Sabine Vollstaedt-Klein Marietta Kirchner Anne Koopmann Bernd Lenz Patrick Bach Sina Vetter Julia Weinberg Paul Thalmann Marlen Pfisterer Torsten Kölsch Selma Oesterle Tobias Link |
| author_facet | Falk Kiefer Christina Klose Bettina C Thomas Sabine Vollstaedt-Klein Marietta Kirchner Anne Koopmann Bernd Lenz Patrick Bach Sina Vetter Julia Weinberg Paul Thalmann Marlen Pfisterer Torsten Kölsch Selma Oesterle Tobias Link |
| author_sort | Falk Kiefer |
| collection | DOAJ |
| description | Introduction Alcohol dependence (AD) is highly prevalent and has severe consequences on health and quality of life. However, the efficacy of approved pharmacotherapies such as naltrexone (NTX) remains limited, highlighting the need for novel pharmacotherapeutic approaches. Cannabidiol (CBD) is a promising candidate, which has shown potential to reduce craving and alcohol use by modulating brain circuits involved in craving and addiction. Preclinical studies suggest that CBD may enhance NTX’s therapeutic effects.Methods and analysis This is a three-armed, randomised, double-blind, placebo-controlled parallel group, multicentre phase II clinical trial. A total of 150 patients with AD will be randomised (1:1:1) to receive either 800 mg or 1200 mg CBD plus 50 mg oral NTX or placebo plus 50 mg oral NTX for 14 days. Alcohol craving will be assessed using the Obsessive Compulsive Drinking Scale (OCDS-G) where the primary endpoint is the change from baseline to the end of treatment. Secondary outcomes include craving during the entire study, quality of life, depressive symptoms, anxiety, patient-reported outcomes, neural brain activation, CBD plasma levels, time to relapse, alcohol use and treatment safety. For the comparison of each experimental group to the control group, a strata-adjusted (centre and baseline OCDS-G) van Elteren test is applied with adjustment for multiple testing by Bonferroni-Holm.Ethics and dissemination The trial has been approved by the Ethics Committee and the competent authority (ID: B_03510). All participants will provide written informed consent. An independent Data and Safety Monitoring Board will monitor safety. This trial complies with national and international regulations.Trial registration number NCT06845124; EU Trial Number: 2024-518164-12-00. |
| format | Article |
| id | doaj-art-db32c711ca8a4612a22f01b4be992e34 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-db32c711ca8a4612a22f01b4be992e342025-08-20T03:36:38ZengBMJ Publishing GroupBMJ Open2044-60552025-08-0115810.1136/bmjopen-2025-106348Investigation 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 TrialFalk Kiefer0Christina Klose1Bettina C Thomas2Sabine Vollstaedt-Klein3Marietta Kirchner4Anne Koopmann5Bernd Lenz6Patrick Bach7Sina Vetter8Julia Weinberg9Paul Thalmann10Marlen Pfisterer11Torsten Kölsch12Selma Oesterle13Tobias Link14German Center for Mental Health, Mannheim, GermanyInstitute of Medical Biometry (IMBI), University Hospital Heidelberg, Heidelberg, GermanyCoordination Centre for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyInstitute of Medical Biometry (IMBI), University Hospital Heidelberg, Heidelberg, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyGerman Center for Mental Health, Mannheim, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyInstitute of Medical Biometry (IMBI), University Hospital Heidelberg, Heidelberg, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyDepartment of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University Medical Faculty, Mannheim, GermanyFeuerlein Center on Translational Addiction Medicine (FCTS), Heidelberg University, Heidelberg, GermanyIntroduction Alcohol dependence (AD) is highly prevalent and has severe consequences on health and quality of life. However, the efficacy of approved pharmacotherapies such as naltrexone (NTX) remains limited, highlighting the need for novel pharmacotherapeutic approaches. Cannabidiol (CBD) is a promising candidate, which has shown potential to reduce craving and alcohol use by modulating brain circuits involved in craving and addiction. Preclinical studies suggest that CBD may enhance NTX’s therapeutic effects.Methods and analysis This is a three-armed, randomised, double-blind, placebo-controlled parallel group, multicentre phase II clinical trial. A total of 150 patients with AD will be randomised (1:1:1) to receive either 800 mg or 1200 mg CBD plus 50 mg oral NTX or placebo plus 50 mg oral NTX for 14 days. Alcohol craving will be assessed using the Obsessive Compulsive Drinking Scale (OCDS-G) where the primary endpoint is the change from baseline to the end of treatment. Secondary outcomes include craving during the entire study, quality of life, depressive symptoms, anxiety, patient-reported outcomes, neural brain activation, CBD plasma levels, time to relapse, alcohol use and treatment safety. For the comparison of each experimental group to the control group, a strata-adjusted (centre and baseline OCDS-G) van Elteren test is applied with adjustment for multiple testing by Bonferroni-Holm.Ethics and dissemination The trial has been approved by the Ethics Committee and the competent authority (ID: B_03510). All participants will provide written informed consent. An independent Data and Safety Monitoring Board will monitor safety. This trial complies with national and international regulations.Trial registration number NCT06845124; EU Trial Number: 2024-518164-12-00.https://bmjopen.bmj.com/content/15/8/e106348.full |
| spellingShingle | Falk Kiefer Christina Klose Bettina C Thomas Sabine Vollstaedt-Klein Marietta Kirchner Anne Koopmann Bernd Lenz Patrick Bach Sina Vetter Julia Weinberg Paul Thalmann Marlen Pfisterer Torsten Kölsch Selma Oesterle Tobias Link 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/15/8/e106348.full |
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