Cannabidiol as an Adjunct Treatment for Alcohol Withdrawal and Craving

Ki vehet részt

• Meets DSM-5 criteria Moderate or Severe Alcohol Use Disorder
• Age 21-65
• Report at least one prior episode of alcohol withdrawal symptoms at least one day in duration that caused significant impairment in functioning (i.e., unable to attend work or engage in typical activities) AND/OR required medications to manage symptoms
• Report at least 21 days of heavy drinking (four or more drinks for women, five or more drinks for men) over the last 28 days
• if female of childbearing potential who has not had a sterilization procedure:
• Negative human chorionic gonadotropin (hCG) on qualitative urine pregnancy screen
• Agree to use a highly effective method of contraception (e.g. hormonal contraception, intrauterine device, double-barrier method) for at least five days prior to administration of the study drug and throughout the duration of the study
• Shipley vocabulary score > 18, corresponding to 5th grade reading level
• Demonstrated understanding of informed consent and ability to consent to participation in the study

Ki nem vehet részt

• Use of gabapentin, benzodiazepines, or other sedative-hypnotic medications within the week prior to admission
• •Urine drug screen indicating the presence of substances other than cannabis at screening
• Mean systolic blood pressure (SBP) >/=160 mm Hg, DBP>/=110 mm Hg, or pulse >/=120 mm Hg during pre-admission at Behavioral Pharmacology Research Unit (BPRU) prior to admission to CRU
• Use of a prescription medication (except for birth control prescriptions) within 14 days of study entry, which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject. This includes any medication in which CYP2C9, CYP2C19, CYP1A2, CYP2B10, or CYP3A4 enzymes are major metabolizers. Participants taking medications that are substrates of UDP-glucuronosyltransferase 1-9 (UGT1A9), UDP-glucuronosyltransferase 2B7 (UGT2B7), CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and/or P-gp wll be allowed into the study but closely monitored for potential adverse events based on the prescribing information of the concomitant medications given CBD's potential to inhibit these enzymes
• Use of prescription medications, OTC medications, herbal medications, and/or dietary supplements that are strong inducers of CYP3A4 or CYP2C19 within 14 days or 5 half-lives (whichever is longer) prior to study drug administration
• Meet DSM-5 criteria for moderate-to-severe substance use disorder (SUD), including moderate-to-severe Cannabis Use Disorder (except for alcohol- and tobacco-related disorders)
• Unstable and/or compromising medical or psychiatric conditions that would interfere with participant safety as determined by study physician
• History of anorexia nervosa or bulimia in the past 2 years
• History of seizures or seizure disorder outside of alcohol-withdrawal related seizures
• History of complicated alcohol withdrawal (e.g. seizures, delirium tremens) as verified by medical record review if available
• Known chronic liver disease or cirrhosis of any etiology (e.g. autoimmune, infections, Metabolic Dysfunction-Associated Steatohepatitis [MASH]]) except in the following cases: 1. Fully resolved hepatitis B infection (HBsAg negative, anti-Hepatitis C core antibody (anti-HBc) and/or anti-Hepatitis B surface antibody (anti-HBs) positive, with normal liver function tests) or 2. Successfully treated hepatitis C infection (HCV RNA negative, with normal liver function tests and no evidence of advanced fibrosis or cirrhosis)
• Recent acute hepatitis of any etiology (e.g. drug-induced hepatitis, hepatitis A infection within the past six months)
• Moderate to severe hepatic impairment (Child-Pugh Class B and C)
• Any of the following laboratory values during screening or upon admission:; AST > 165 U/L (normal range 19-55); ALT > 216 U/L (normal range 19-72); Alkaline phosphatase > 1.5x upper limit of normal (ULN) (normal range 38-126); Total bilirubin >1.5 ULN (normal values=0.3-1.0 mg/dL); Non-fasting glucose > 250 mg/ml (normal range 65-179); Hematocrit < 38 % (normal range 41-53); Hemoglobin < 12 g/dl (normal range 13.5-17.5) or any other laboratory value significantly outside the normal range
• ECG with QT-corrected interval (QTc) > 450 ms and/or presence of clinically significant abnormality
• Current or past alcohol-related medical complications including but not limited to cirrhosis of the liver, esophageal varices, pancreatitis, severe gastritis, hemoptysis, hematochezia, or melena
• Regular use (i.e. twice a week or more) of CBD-dominant products, including Epidiolex®, within the last three months
• Regular use of benzodiazepines (e.g., twice a week or more) within the last three months
• Active suicidal ideation or recent suicide attempts (e.g. within six months)
• Current pregnancy
• BMI <18.5 kg/m2
• Mean systolic blood pressure (SBP) >/= 140 mm Hg, DBP >/= 90 mmHg or pulse >/= 110 mm Hg during screening
• Participation in other clinical trials within the past 60 days
• Court-mandated participation in alcohol treatment or pending incarceration