Cannabidiol as a Treatment for AUD Comorbid With PTSD

In this project, investigators aim to test the hypothesis that CBD will reduce alcohol drinking in individuals with AUD comorbid with PTSD. CBD is currently a medical research focus because it shows promise for treating anxiety and other brain disorders, but does not produce a 'high' like other parts of cannabis, has not been shown to be addictive, and is safe, with few or no side effects. AUD, which is one of the most common and most debilitating psychiatric conditions, is often associated with other comorbid psychiatric disorders - in particular, PTSD: depending on the population studied, 30-60% of individuals with AUD also have PTSD, with high comorbidity rates in military veterans. Evidence from animal models and clinical studies suggests that the negative emotion caused by PTSD symptoms intensifies craving for alcohol during alcohol withdrawal, perpetuating the addictive cycle; further, evidence shows that the brain circuits underlying negative emotion and addiction are linked in a forebrain area called the extended amygdala, which provides a neuropharmacological target to simultaneously treat both negative emotion and alcohol addiction in individuals with AUD and PTSD. CBD is known to inhibit brain activity in the extended amygdala, leading to reduced anxiety in both animal models and humans. CBD also reduces addictive alcohol seeking in animal models.

Inclusion criteria

• Males and females age 18-70
• DSM-5 diagnosis of moderate or severe AUD
• DSM-5 diagnosis of PTSD with Clinician Administered PTSD Scale (CAPS-5) OR subPTSD diagnosis (meeting criterion A, F, G, H and at least 6 symptoms across any criteria B-E) with Clinician Administered PTSD Scale (CAPS-5)
• Able to provide voluntary informed consent
• At least 6 heavy drinking days (4 or more drinks per day for a woman, 5 or more drinks per day for a man) in the 30 days prior to screen
• If of childbearing potential (male or female), are willing to use approved form of contraception from screening for duration of the trial
• Able to provide at least two locators
• Endorse desire to cut down or stop drinking
• Agrees to abstain from all other cannabinoid use for the duration of the study
• Confirms they are reliably domiciled

Exclusion criteria

• Current alcohol withdrawal (CIWA-Ar score >7)
• Exclusionary medical conditions (e.g. current severe alcohol withdrawal requiring medical hospitalization, significantly impaired liver function)
• DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder
• High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process, based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support)
• Exposure to trauma in the last 30 days, including police duty or military service
• Current significant suicidality (assessed using the C-SSRS), any significant suicidal behavior in the past 12 months, or any history of serious suicide attempts requiring hospitalization, or current significant homicidality
• History of Severe Traumatic Brain Injury (TBI; as indicated by Loss of Consciousness > 24 hours)
• DSM-5 diagnosis of current mild cannabis use disorder and/or moderate or severe substance use disorder for a substance other than alcohol or nicotine
• Significant laboratory abnormalities, including significantly impaired liver function, serious abnormalities of complete blood count or metabolic panel
• Active legal problems likely to result in incarceration within 12 weeks of treatment initiation
• Pregnancy or lactation
• Current use of exclusionary medications, including but not limited to cannabinoids; those acting on serotonergic pathways; treatments for addictions including alcohol; moderate to strong inhibitors of CYP3A4 or CYP2C19; medications metabolized primarily by CYP3A4, CYP3A5, or CYP3A7; and medications with a narrow therapeutic index which are substrates of UGT1A9, UGT2B7, CYP2C8, CYP2C9, CYP2C19, CYP1A2, or CYP2B6.
• Current treatment for AUD (with exceptions of: AA/12-step treatment and/or psychosocial treatment initiated more than 3 months prior to the screening visit)
• Psychotherapy for PTSD or other psychiatric condition, if initiated within 3 months of screening
• Inpatient psychiatric treatment in the last 12 months, with the exception of detox and extended Emergency Department stays
• A positive urine drug screen for opioids at screen, baseline, or any later visits. If a participant has a positive drug screen for THC or cocaine at screen, baseline or a later visit- their enrollment will be subject to the clinical judgement of the Principal Investigator.