Cannabidiol as a Treatment for AUD Comorbid With PTSD

• ClinicalTrials.gov Identifier: NCT03248167
• Recruitment Status: Completed
• First Posted: August 14, 2017
• Last Update Posted: May 19, 2022
• Sponsor: NYU Langone Health
• Collaborators: National Institutes of Health (NIH); Tilray
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

This project aims to determine whether cannabidiol (CBD), a compound derived from the cannabis plant, is effective in treating alcohol use disorder (AUD) in individuals with comorbid posttraumatic stress disorder (PTSD). Investigators will test the hypothesis that oral cannabidiol (CBD) will reduce alcohol drinking in individuals with AUD comorbid with PTSD. To test this hypothesis, 48 otherwise healthy adult participants with moderate or severe AUD and PTSD will be randomized to treatment with either CBD (600 mg daily) or placebo, for a period of 6 weeks, such that both participants and study staff are blind to treatment condition. Participants (each treated for 6 weeks) will be continuously recruited over a study period of 14 months until 48 have completed. Baseline and weekly data will be collected on alcohol usage and PTSD symptoms, and investigators will assess whether CBD treatment leads to a greater improvement in these measures relative to placebo, and whether reduction in alcohol drinking is temporally linked to improvement in PTSD symptoms. Subjects will also participate in a task designed to quantify the psychological and physiological links between negative emotion produced by re-experiencing PTSD trauma, and alcohol craving. The task will be administered following 4 weeks of treatment. Treatment-associated reduction in alcohol craving elicited by trauma-associated negative emotion between CBD and placebo groups will be compared. This study will be the first to test whether CBD is effective in treating alcohol addiction and in treating PTSD in humans, and the first to examine the interaction between these treatment effects. Results will serve as proof of concept and provide guidance for a future larger clinical trial. Because CBD is a safe, readily available drug, such a trial would have an immense potential to prevent death, medical illness, and psychological suffering associated with AUD and PTSD. Further, because the brain circuits via which CBD acts to produce hypothesized effects are relatively well-understood, results may substantially advance understanding of the neurobiological basis of alcohol addiction.

Condition or disease	Intervention/treatment	Phase
Alcohol Use Disorder; Post Traumatic Stress Disorder	Drug: Cannabidiol; Drug: Placebos	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Cannabidiol as a Treatment for Alcohol Use Disorder Comorbid With Posttraumatic Stress Disorder
• Actual Study Start Date: September 16, 2019
• Actual Primary Completion Date: April 20, 2022
• Actual Study Completion Date: April 20, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cannabidiol (CBD 600 mg daily); 6 weeks, such that both participants and study staff are blind to treatment condition.	Drug: Cannabidiol; 600 mg daily; Other Name: CBD
Placebo Comparator: Placebo; 6 weeks, such that both participants and study staff are blind to treatment condition.	Drug: Placebos; This project aims to determine whether cannabidiol (CBD) is effective in treating alcohol use disorder (AUD) comorbid posttraumatic stress disorder (PTSD). To address this aim, investigators will conduct a clinical trial in which CBD will be adminstred to 48 individuals with AUD comorbid with PTSD, and assess alcohol intake and PTSD symptoms. The aim is to test the hypothesis that CBD will reduce alcohol drinking in individuals with AUD comorbid with PTSD. To test this hypothesis, 48 otherwise healthy adult participants with moderate or severe AUD and PTSD will be randomized to treatment with either CBD (600 mg daily) or placebo, for a period of 6 weeks, such that both participants and study staff are blind to treatment condition.

Outcome Measures

Primary Outcome Measures :

1. Number of Drinks Per Day [ Time Frame: Baseline ]
   Number of drinks per day will be assessed by the Time Line Follow Back (TLFB) methodology. TLFB is a drinking assessment method that can be administered in various formats: as clinician-administered interview, paper and pencil and computer. TLFB is used to obtain estimates of the quantity of daily drinking.
2. Number of Drinks Per Day [ Time Frame: Week 4 ]
   Number of drinks per day will be assessed by the Time Line Follow Back (TLFB) methodology. TLFB is a drinking assessment method that can be administered in various formats: as clinician-administered interview, paper and pencil and computer. TLFB is used to obtain estimates of the quantity of daily drinking.
3. Number of Drinks Per Day [ Time Frame: Week 6 ]
   Number of drinks per day will be assessed by the Time Line Follow Back (TLFB) methodology. TLFB is a drinking assessment method that can be administered in various formats: as clinician-administered interview, paper and pencil and computer. TLFB is used to obtain estimates of the quantity of daily drinking.
4. PCL-5 Total Score [ Time Frame: Baseline ]
   The PCL-5 is a 20-item self-report measure that assesses the 20 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) symptoms of post-traumatic stress disorder (PTSD). The self-report rating scale is 0-4 for each symptom. Rating scale descriptors are the same: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely." A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items; the higher the score, the more severe the PTSD symptoms.
5. PCL-5 Total Score [ Time Frame: Week 4 ]
   The PCL-5 is a 20-item self-report measure that assesses the 20 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) symptoms of post-traumatic stress disorder (PTSD). The self-report rating scale is 0-4 for each symptom. Rating scale descriptors are the same: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely." A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items; the higher the score, the more severe the PTSD symptoms.
6. PCL-5 Total Score [ Time Frame: Week 6 ]
   The PCL-5 is a 20-item self-report measure that assesses the 20 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) symptoms of post-traumatic stress disorder (PTSD). The self-report rating scale is 0-4 for each symptom. Rating scale descriptors are the same: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely." A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items; the higher the score, the more severe the PTSD symptoms.

Secondary Outcome Measures :

1. Percent Carbohydrate Deficient Transferrin (CDT) [ Time Frame: Baseline ]
   CDT test performed on blood sample
2. Percent Carbohydrate Deficient Transferrin (CDT) [ Time Frame: Week 4 ]
   CDT test performed on blood sample
3. Percent Carbohydrate Deficient Transferrin (CDT) [ Time Frame: Week 6 ]
   CDT test performed on blood sample
4. Percentage of Heavy Drinking Days [ Time Frame: Baseline ]
   Heavy drinking days is defined as 4+ drinks for women or five or more drinks for men per drinking day. This will be averaged for each treatment week.
5. Percentage of Heavy Drinking Days [ Time Frame: Week 1 ]
   Heavy drinking days is defined as 4+ drinks for women or five or more drinks for men per drinking day. This will be averaged for each treatment week.
6. Percentage of Heavy Drinking Days [ Time Frame: Week 2 ]
   Heavy drinking days is defined as 4+ drinks for women or five or more drinks for men per drinking day. This will be averaged for each treatment week.
7. Percentage of Heavy Drinking Days [ Time Frame: Week 3 ]
   Heavy drinking days is defined as 4+ drinks for women or five or more drinks for men per drinking day. This will be averaged for each treatment week.
8. Percentage of Heavy Drinking Days [ Time Frame: Week 4 ]
   Heavy drinking days is defined as 4+ drinks for women or five or more drinks for men per drinking day. This will be averaged for each treatment week.
9. Percentage of Heavy Drinking Days [ Time Frame: Week 5 ]
   Heavy drinking days is defined as 4+ drinks for women or five or more drinks for men per drinking day. This will be averaged for each treatment week.
10. Percentage of Heavy Drinking Days [ Time Frame: Week 6 ]
    Heavy drinking days is defined as 4+ drinks for women or five or more drinks for men per drinking day. This will be averaged for each treatment week.
11. Percentage of Very Heavy Drinking Days [ Time Frame: Baseline ]
    Very heavy drinking days is defined as 8+/10+ drinks per day for women and men respectively. This will be averaged for each treatment week.
12. Percentage of Very Heavy Drinking Days [ Time Frame: Week 1 ]
    Very heavy drinking days is defined as 8+/10+ drinks per day for women and men respectively. This will be averaged for each treatment week.
13. Percentage of Very Heavy Drinking Days [ Time Frame: Week 3 ]
    Very heavy drinking days is defined as 8+/10+ drinks per day for women and men respectively. This will be averaged for each treatment week.
14. Percentage of Very Heavy Drinking Days [ Time Frame: Week 4 ]
    Very heavy drinking days is defined as 8+/10+ drinks per day for women and men respectively. This will be averaged for each treatment week.
15. Percentage of Very Heavy Drinking Days [ Time Frame: Week 5 ]
    Very heavy drinking days is defined as 8+/10+ drinks per day for women and men respectively. This will be averaged for each treatment week.
16. Percentage of Very Heavy Drinking Days [ Time Frame: Week 6 ]
    Very heavy drinking days is defined as 8+/10+ drinks per day for women and men respectively. This will be averaged for each treatment week.
17. Number of Participants with No Heavy Drinking Days [ Time Frame: Baseline ]
18. Number of Participants with No Heavy Drinking Days [ Time Frame: Week 1 ]
19. Number of Participants with No Heavy Drinking Days [ Time Frame: Week 2 ]
20. Number of Participants with No Heavy Drinking Days [ Time Frame: Week 3 ]
21. Number of Participants with No Heavy Drinking Days [ Time Frame: Week 4 ]
22. Number of Participants with No Heavy Drinking Days [ Time Frame: Week 5 ]
23. Number of Participants with No Heavy Drinking Days [ Time Frame: Week 6 ]
24. Number of Participants that are 'Present and Clear' [ Time Frame: Baseline ]
    Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
25. Number of Participants that are 'Present and Clear' [ Time Frame: Week 1 ]
    Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
26. Number of Participants that are 'Present and Clear' [ Time Frame: Week 2 ]
    Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
27. Number of Participants that are 'Present and Clear' [ Time Frame: Week 3 ]
    Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
28. Number of Participants that are 'Present and Clear' [ Time Frame: Week 4 ]
    Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
29. Number of Participants that are 'Present and Clear' [ Time Frame: Week 5 ]
    Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
30. Number of Participants that are 'Present and Clear' [ Time Frame: Week 6 ]
    Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
31. Percentage of Days Abstinent [ Time Frame: Baseline ]
32. Percentage of Days Abstinent [ Time Frame: Week 1 ]
33. Percentage of Days Abstinent [ Time Frame: Week 2 ]
34. Percentage of Days Abstinent [ Time Frame: Week 3 ]
35. Percentage of Days Abstinent [ Time Frame: Week 4 ]
36. Percentage of Days Abstinent [ Time Frame: Week 5 ]
37. Percentage of Days Abstinent [ Time Frame: Week 6 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Males and females age 18-70
2. DSM-5 diagnosis of moderate or severe AUD
3. 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)
4. Able to provide voluntary informed consent
5. 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
6. If of childbearing potential (male or female), are willing to use approved form of contraception from screening for duration of the trial
7. Able to provide at least two locators
8. Endorse desire to cut down or stop drinking
9. Agrees to abstain from all other cannabinoid use for the duration of the study
10. Confirms they are reliably domiciled

Exclusion Criteria:

1. Current alcohol withdrawal (CIWA-Ar score >7)
2. Exclusionary medical conditions (e.g. current severe alcohol withdrawal requiring medical hospitalization, significantly impaired liver function)
3. DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder
4. 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)
5. Exposure to trauma in the last 30 days, including police duty or military service
6. 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
7. History of Severe Traumatic Brain Injury (TBI; as indicated by Loss of Consciousness > 24 hours)
8. 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
9. Significant laboratory abnormalities, including significantly impaired liver function, serious abnormalities of complete blood count or metabolic panel
10. Active legal problems likely to result in incarceration within 12 weeks of treatment initiation
11. Pregnancy or lactation
12. 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.
13. 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)
14. Psychotherapy for PTSD or other psychiatric condition, if initiated within 3 months of screening
15. Inpatient psychiatric treatment in the last 12 months, with the exception of detox and extended Emergency Department stays
16. 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.

Contacts and Locations

Locations

United States, New York

New York University School of Medicine

New York, New York, United States, 10016

Sponsors and Collaborators

NYU Langone Health

National Institutes of Health (NIH)

Tilray

Investigators

• Principal Investigator: Charles Marmar, MD; New York University Grossman School of Medicine

  Study Documents (Full-Text)

Documents provided by NYU Langone Health:

Informed Consent Form  [PDF] October 6, 2021

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT03248167
• Other Study ID Numbers: 17-00949
• First Posted: August 14, 2017
• Last Update Posted: May 19, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by NYU Langone Health:

Cannabidiol

Additional relevant MeSH terms:

Cannabidiol; Disease; Alcoholism; Stress Disorders, Traumatic; Alcohol Drinking; Stress Disorders, Post-Traumatic; Pathologic Processes; Trauma and Stressor Related Disorders; Mental Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Anticonvulsants