Cannabidiol as an Adjunct Treatment for Alcohol Withdrawal and Craving

Not Applicable

Not yet recruiting

• Conditions: Withdrawal From Addictive Substance; Detoxification; Alcohol Use Disorder (AUD); Craving
• Interventions: Drug: Cannabidiol (CBD); Drug: Placebo

• Registration Number: NCT07148843
• Lead Sponsor: Johns Hopkins University

Brief Summary

Cannabidiol (CBD), one of the most prevalent cannabinoids in cannabis (marijuana) has been shown to reduce alcohol withdrawal symptoms in laboratory animals. In people without alcohol use disorder (AUD), CBD has been show to be effective in reducing anxiety, sleep problems, and seizures; all of these are common symptoms of alcohol withdrawal. This randomized placebo-controlled clinical trial will evaluate the potential of CBD to improve alcohol withdrawal symptoms and reduce craving during acute abstinence among individuals with moderate-to-severe AUD. Adult participants with moderate-to-severe AUD will be admitted to an inpatient research unit at the Johns Hopkins Hospital for a 5-day, 4-night stay that includes alcohol abstinence with management of their alcohol withdrawal. In addition to standard care, participants will receive CBD or placebo (no CBD), complete assessments of withdrawal, sleep quality and provide breath and blood samples.

Detailed Description

Alcohol withdrawal during acute abstinence represents a major health threat to millions of individuals struggling with alcohol use disorder (AUD): it has been associated with complications in patients admitted for medically supervised withdrawal including seizures and delirium tremens (the latter of which can be fatal if not managed appropriately) and can interfere with treatment efforts. Benzodiazepines, such as lorazepam (Ativan) represent the first-line treatments for control of alcohol withdrawal, yet higher doses of benzodiazepines required to manage more complicated withdrawal cases increase risk of respiratory depression and delirium. Furthermore, a growing frequency of benzodiazepine shortages (at least 20 shortages within the previous ten years lasting a median of 244 days) necessitates a need for alternative and adjunctive medications. Preclinical animal trials involving cannabidiol (CBD), one of the most prevalent cannabinoids in cannabis (marijuana) have shown its use is associated with statistically significant reductions in withdrawal symptoms and there is evidence in non-AUD populations that CBD is effective in reducing anxiety, insomnia, and seizures, which are all symptoms of alcohol withdrawal. The capacity for CBD to enhance the effect of the inhibitory neurotransmitter GABA in a manner akin to benzodiazepines has also been demonstrated. Collectively this information suggests that CBD could alleviate signs and symptoms of alcohol withdrawal, and subsequently reduce the need for adjunctive benzodiazepines.

This randomized placebo-controlled clinical trial will enroll adults with moderate-to-severe AUD who will be admitted to an inpatient research unit at the Johns Hopkins Hospital for management of their alcohol withdrawal. Enrolled participants with a history of alcohol withdrawal symptoms will be randomized to receive an oral formulation of either placebo or one of two CBD doses (10 mg/kg or 20 mg/kg). These doses have been well-studied and tolerated in prior studies and clinical trials for other disorders. Alcohol withdrawal symptoms, as defined by Diagnostic and Statistical Manual (DSM-5) criteria, will be assessed by nursing administration of the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) and participant completion of the Alcohol Withdrawal Symptom Checklist (AWSC). The CIWA-Ar scale will be used to guide the administration of symptom-triggered lorazepam (trade name Ativan) for all participants. As insomnia is a DSM-5 criterion for alcohol withdrawal, sleep quality will be assessed by completion of the Consensus Sleep Diary (CSD) and wrist actigraphy. Last, since cravings correlate closely with withdrawal symptoms and CBD has been observed to reduce craving for other substances, we will explore CBD's impact on alcohol craving by having participants complete the Alcohol Urge Questionnaire throughout the study. In short, the goals of this study will be to (1) determine the effect of CBD on physiologic and subjective symptoms of alcohol withdrawal, (2) determine the capacity of CBD to improve insomnia and disordered sleep during withdrawal, and (3) determine if CBD can attenuate alcohol cravings during acute abstinence.

Results from this study can help inform the possible use of CBD as a novel adjunct treatment for alcohol withdrawal and cravings that may reduce benzodiazepine need for alcohol withdrawal treatment. If CBD is shown to be effective, this line of work also points to the potential of the endogenous cannabinoid system playing a mechanistic role in alcohol's withdrawal symptoms. Finally, this study could provide further insights into the efficacy of CBD as a sleep agent for participants with alcohol withdrawal and lay the groundwork for subsequent studies exploring CBD's use in the treatment of alcohol withdrawal in an outpatient setting.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-19
• Study First Submitted QC: 2025-08-26
• Last Update Submitted: 2025-08-26
• Study First Posted: 2025-08-29
• Last Update Posted: 2025-08-29
• Study Start: 2025-12-01
• Primary Completion: 2030-10
• Study Completion: 2030-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
20 mg/kg CBD	Cannabidiol (CBD)	high dose CBD
10 mg/kg CBD	Cannabidiol (CBD)	low dose CBD
placebo	Placebo	Placebo (no CBD)

Primary Outcome Measures

Name	Time	Method
Peak score on the Alcohol Withdrawal Symptom Checklist (AWSC)	Four times daily during inpatient stay (4 nights)	The Alcohol Withdrawal Symptom Checklist (AWSC) is a validated measure in which participants report their own withdrawal symptoms. The scale consists of 17 items. The total possible score is 0-68, with higher scores indicating more severe withdrawal symptoms. The highest score for a participant across the duration of their time on the Clinical Research Unit (CRU) will be included in the analysis.
Average total sleep time (minutes) and wake after sleep onset as measured by wrist actigraphy	4 nights during inpatient stay	Actigraphy will provide a primary assessment of sleep outcomes including total sleep time and wake after sleep onset. The actigraphy devices used will be triaxial accelerometers from GT0X Link Wrist Actigraphy, Actigraph LLC. Values for total sleep time and wake time after sleep onset will be averaged across the study's four nights; this average will be included in the analysis.
Peak alcohol craving as measured by scores on the Alcohol Urge Questionnaire (AUQ)	Four times daily during inpatient stay (4 nights)	The Alcohol Urge Questionnaire (AUQ) is an eight-item self-report questionnaire that has demonstrated validity and discriminative value in identifying and measuring alcohol craving. Each item is ranked on a score of 0 to 7, with a maximum score range of 0- 56. Higher scores indicate greater craving. The highest score for a participant across the duration of their time on the CRU will be included in the analysis.
Peak score on the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar)	4 times daily during inpatient stay (4 nights)	The Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) is a clinically administered measurement that represents the gold standard for assessing the severity of withdrawal symptoms. It consists of 10-items: nausea/ vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation/clouding of sensorium. Each sign and symptom is rated on a Likert scale from 0-7 (with 0=absent and 7 =most severe), except for "clouding of sensorium," which is ranked from 0 to 4. Scores on the CIWA-Ar scale range from 0 to 67, with higher scores indicating more severe withdrawal. The highest score for a participant across the duration of their time on the CRU will be included in the analysis. Clinical staff will use these scores to justify administration of benzodiazepines to treat withdrawal symptoms.

Secondary Outcome Measures

Name	Time	Method
Average Total Sleep Time (minutes) as reported in Consensus Sleep Diary (CSD) results	Upon waking each morning during inpatient stay (4 days)	The Consensus Sleep Diary (CSD) is a standardized subjective sleep rating measure in which participants rate features of their sleep-average total sleep time. Generally higher number is better.
Total Amount of Time (minutes) on Awakenings, as reported in Consensus Sleep Diary (CSD) results	Upon waking each morning during inpatient stay (4 days)	The Consensus Sleep Diary (CSD) is a standardized subjective sleep rating measure in which participants rate features of their sleep- total amount of time on awakenings. Higher number indicating more awakenings (worse).
Sleep Quality as reported in Consensus Sleep Diary (CSD) results	Upon waking each morning during inpatient stay (4 days)	The Consensus Sleep Diary (CSD) is a standardized subjective sleep rating measure consisting of nine items in which participants rate features of their sleep--sleep quality either "Very Poor," "Poor," "Fair," "Good," or "Very Good"
Total amount of time (minutes) spent awake after sleep onset as reported in Consensus Sleep Diary (CSD) results	Upon waking each morning during inpatient stay (4 days)	The Consensus Sleep Diary (CSD) is a standardized subjective sleep rating measure consisting of nine items in which participants rate features of their sleep-- total amount of time spent awake after sleep onset. higher values indicating more time awake (worse).
Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST)	Morning prior to admission, morning of discharge (day 5)	Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes that act as proxies for hepatic function and damage. Elevations in the serum levels (U/L) of these enzymes--particular at levels \>/= 3 times the upper limit of normal--can indicate liver injury.
Sleep Latency (minutes) as reported in Consensus Sleep Diary (CSD) results	Upon waking each morning during inpatient stay (4 days)	The Consensus Sleep Diary (CSD) is a standardized subjective sleep rating measure consisting of nine items in which participants rate features of their sleep - sleep latency (how long it takes one to fall asleep). Higher values would indicate worse sleep latency.
Number of Awakenings as reported in Consensus Sleep Diary (CSD) results	Upon waking each morning during inpatient stay (4 days)	The Consensus Sleep Diary (CSD) is a standardized subjective sleep rating measure consisting of nine items in which participants rate features of their sleep--number of awakenings. Higher number indicating more awakenings (worse).
Total doses of lorazepam administered	Every 4 hours during inpatient stay (4 nights)	Lorazepam (trade name: Ativan) is a benzodiazepine that is frequently used in clinical practice to manage alcohol withdrawal symptoms. Since the decision to administer lorazepam is guided by CIWA scores, it can serve as a proxy for severity of withdrawal symptoms. Every four hours daily as needed for CIWA scores \>/=10 while the participant stays on the inpatient Johns Hopkins Hospital (JHH) CRU

Trial Locations

Locations (1)

Behavioral Pharmacology Research Unit; 🇺🇸 Baltimore, Maryland, United States