Cannabidiol as an Adjunct Treatment for Alcohol Withdrawal and Craving

Project Abstract This project aims to assess the capacity of cannabidiol (CBD) to manage alcohol withdrawal and cravings during detoxification of patients with Alcohol Use Disorder (AUD). AUD is associated with physical and psychiatric consequences as well as exorbitant healthcare costs. Attempts to treat AUD are limited by alcohol withdrawal, which can itself lead to seizures and death if it is not adequately treated. Benzodiazepines have long been the gold standard in the treatment of alcohol withdrawal, but this class of medications has drawbacks including abuse liability that limits its utility in an outpatient setting, adverse effects such as delirium and respiratory depression at high doses, and a susceptibility to shortages. Thus, there is a need to identify novel adjunct treatments for the management of alcohol withdrawal that could reduce benzodiazepine use and further attenuate withdrawal. CBD, one of the main cannabinoids in the Cannabis sativa plant, possesses several attributes that could make it a suitable treatment for alcohol withdrawal: it has a relatively benign side effect profile, lacks abuse liability, and has evidence to manage symptoms seen in alcohol withdrawal, including anxiety, insomnia, and seizures. CBD’s potential to help manage alcohol withdrawal symptoms and craving behaviors has been shown in preclinical studies but there is no data on CBD’s role as a treatment for alcohol withdrawal in human participants. This study will fill this knowledge gap by recruiting individuals with moderate-to-severe AUD to participate in a four-day inpatient study where they will be randomized to receive either placebo solution or CBD solution at a daily dose of 10 mg/kg or 20 mg/kg while undergoing supervised medical detoxification. Withdrawal will be assessed by nursing via the Clinical Institute Withdrawal Assessment, revised (CIWA- Ar) and by participant self-report via Alcohol Withdrawal Symptom Checklist (AWSC). CIWA scores will guide administration of benzodiazepines for the treatment of withdrawal symptoms. We will measure sleep quality through both self-report via the Consensus Sleep Diary (CSD) and objective data collected through wrist actigraphy. Alcohol cravings will also be measured via participant self-report with the Alcohol Urge Questionnaire (AUQ). Additionally, we will measure changes in liver function to verify the hepatic safety of CBD at these doses. Analysis will involve comparison between groups of the scores on the assessments of withdrawal, craving and sleep, wrist actigraphy data, total number of lorazepam doses administered over the course of study, and changes in liver function and vital signs. We hypothesize that CBD will be well-tolerated and attenuate alcohol withdrawal symptoms and cravings in a dose-dependent manner compared to placebo. Results from this study could position CBD as a novel agent for the management of withdrawal, sleep and cravings in early abstinence.