Cannabidiol for Reducing Drinking in Alcohol Use Disorder (CARAMEL)

Hôpital le Vinatier

Status and phase: Enrolling; Phase 2

Conditions: Alcohol Use Disorder

Treatments: Drug: Cannabidiol oral oil; Drug: Placebo oral oil

Study type: Interventional

Funder types: Other

Identifiers

NCT05159830

2019-004740-30

Details and patient eligibility

About

The non-psychotomimetic cannabis compound cannabidiol (CBD) has been found effective for reducing alcohol drinking in mice. Moreover, other experimental studies have found that CBD reduced alcohol-induced steatosis in the liver, and reduced alcohol-related injury in the brain. Despite these promising results from animal data, no human study has been conducted yet in alcohol use disorder (AUD).

Full description

CBD has several potential therapeutic prospects in AUD. Preclinical studies now support the potential of CBD for drinking reduction in AUD subjects. Moreover, other experimental studies have found that CBD reverse the alcohol-induced steatosis process in the liver. These two experimental effects need a translational confirmation in humans through an explanatory phase 2 study. In addition, CBD could also exert neuroprotective effects that reduce the deleterious effects of alcohol on the brain. In both the liver and the brain, the idiosyncratic anti-inflammatory effects of CBD could thus strengthen the overall harm reduction allowed by drinking reduction in AUD ± ALD patients.

CBD deserves an exploratory study assessing whether the different therapeutic prospects in AUD are warranted. Moreover, because CBD is extracted from cannabis, and even if it is a CB1 antagonist with no psychotomimetic effects and no reported potential for abuse, the first pieces of evidence in AUD should confirm that CBD is safe in AUD subjects.

The CARAMEL study is a phase-2 clinical trial on 76 subjects, which aims to investigate the efficacy of CBD on reducing alcohol drinking, as well as the potential of CBD for restraining alcohol-induced brain and liver injuries, and confirm the good safety profile of CBD.

Enrollment: 76 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Being aged 18 - 65 years
• Being fluent in French
• Having read the information procedure and signed the informed consent sheet.
• Being affiliated with health insurance.
• DSM-5 criteria for AUD (all stages) (American Psychiatric Association, 2013)
• Average drinking level of at least 12 standard-drinks (120g of ethanol) per day over the month prior to inclusion (i.e., a total alcohol consumption of 336 standard-drinks during the 28-day assessment period prior to inclusion), using the A-TLFB.

Exclusion criteria

• At least one day of abstinence (no alcohol drinking) during the month prior to inclusion
• Criteria for liver cirrhosis (Child-Pugh B or C)
• DSM-5 criteria for schizophrenia, schizoaffective disorder, or bipolar disorder, using the MINI 7.0.2.
• Current suicidality, using the MNI 7.0.2
• Lifelong history of suicide attempts
• Lifelong history or current DSM-5 criteria for substance use disorder (other than alcohol or nicotine) using the MINI 7.0.2.
• Any detected use of cannabis or any other cannabinoid within 60 days prior to screen
• Patients with transaminase elevations greater than 3 times upper the limit of normal and bilirubin greater than 2 times upper the limit of normal.
• Impaired medical condition (investigator's decision)
• Pregnancy, lactation, or insufficient contraceptive measure (precautionary measure) (See 5.2 for acceptable birth control methods)
• Patients with cancer, HIV, pulmonary arterial hypertension, epilepsy and with rifampicin, St. John's wort, Mammalian target of rapamycin (mTOR), calcineurin inhibitors or triazole antifungal agents like posaconazole, fluconazole... .
• History of vascular accident and/or cardiac arrhythmias and/or myocardial infarction
• Patients receiving acamprosate, naltrexone, disulfiram, nalmefene, topiramate, baclofen for AUD within 30 days prior to screening.
• MRI contraindication: pacemaker, insulin pump, heart metal valve, cochlear implant...
• Known hypersensitivity to the active principle (cannabidiol) or excipients (sucralose, menthol, mannitol).
• Person under tutorship or curatorship.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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76 participants in 2 patient groups, including a placebo group

Cannabidiol (CBD)

Experimental group

Description:

CBD Group from 20mg x 2/day up to 600mg/day

Treatment:

Drug: Cannabidiol oral oil

PLACEBO (PCB)

Placebo Comparator group

Description:

PCB Group from 20mg x 2/day up to 600mg/day

Treatment:

Drug: Placebo oral oil