Cannabidiol as a Treatment for AUD Comorbid With PTSD

Cannabidiol as a Treatment for Alcohol Use Disorder Comorbid With Posttraumatic Stress Disorder

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03248167

Enrollment

Registered

2017-08-14

Start date

2019-09-16

Completion date

2022-04-20

Last updated

2023-06-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcohol Use Disorder, Post Traumatic Stress Disorder

Keywords

Cannabidiol

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.

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.

Interventions

DRUGCannabidiol

600 mg daily

DRUGPlacebos

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 administered 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Drinks Per Day	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.
PCL-5 Total Score	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.

Secondary

Measure	Time frame	Description
Percentage of Very Heavy Drinking Days	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.
Number of Participants With No Heavy Drinking Days	Baseline	—
Percent Carbohydrate Deficient Transferrin (CDT)	Baseline	CDT test performed on blood sample
Percentage of Days Abstinent	Baseline	—
Number of Participants That Are 'Present and Clear'	Baseline	Present is defined as present to provide breath alcohol levels (BAC). Clear is defined as having a BAC of zero.
Percentage of Heavy Drinking Days	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.

Countries

United States

Participant flow

Pre-assignment details

A total of 95 patients were enrolled in the trial. 65 of those failed screening or were lost to follow-up prior to starting medication. Thus, only 30 participants started medication in the trial.

Participants by arm

Arm	Count
Cannabidiol (CBD 600 mg Daily) 6 weeks, such that both participants and study staff are blind to treatment condition. Cannabidiol: 600 mg daily	17
Placebo 6 weeks, such that both participants and study staff are blind to treatment condition. 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.	13
Total	30

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Institution Mandated COVID-19 Research Pause	2	1
Overall Study	Lost to Follow-up	1	0
Overall Study	Physician Decision	0	1
Overall Study	Withdrawal by Subject	2	2

Baseline characteristics

Characteristic	Cannabidiol (CBD 600 mg Daily)	Total	Placebo
Age, Continuous	38.59 years	38.2 years	37.69 years
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants	12 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants	18 Participants	9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Black or African American	8 Participants	11 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) White	7 Participants	14 Participants	7 Participants
Region of Enrollment United States	17 participants	30 participants	13 participants
Sex: Female, Male Female	12 Participants	19 Participants	7 Participants
Sex: Female, Male Male	5 Participants	11 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 17	0 / 13
other Total, other adverse events	15 / 17	10 / 13
serious Total, serious adverse events	0 / 17	0 / 13

Outcome results

Primary

Number of Drinks Per Day

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.

Time frame: Baseline

Arm	Measure	Value (MEAN)	Dispersion
Cannabidiol (CBD 600 mg Daily)	Number of Drinks Per Day	4.4885 drinks/day	Standard Deviation 2.662
Placebo	Number of Drinks Per Day	5.3623 drinks/day	Standard Deviation 2.7075

Primary

Number of Drinks Per Day

Time frame: Week 6

Arm	Measure	Value (MEAN)	Dispersion
Cannabidiol (CBD 600 mg Daily)	Number of Drinks Per Day	2.4881 drinks/day	Standard Deviation 2.1679
Placebo	Number of Drinks Per Day	2.8175 drinks/day	Standard Deviation 2.2682

Primary

Number of Drinks Per Day

Time frame: Week 4

Arm	Measure	Value (MEAN)	Dispersion
Cannabidiol (CBD 600 mg Daily)	Number of Drinks Per Day	1.9256 drinks/day	Standard Deviation 2.1786
Placebo	Number of Drinks Per Day	2.15 drinks/day	Standard Deviation 2.2792

Primary

PCL-5 Total Score

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.

Time frame: Baseline

Arm	Measure	Value (MEAN)	Dispersion
Cannabidiol (CBD 600 mg Daily)	PCL-5 Total Score	42.0588 score on a scale	Standard Deviation 13.8549
Placebo	PCL-5 Total Score	49.1538 score on a scale	Standard Deviation 13.7739

Primary

PCL-5 Total Score

Time frame: Week 4

Arm	Measure	Value (MEAN)	Dispersion
Cannabidiol (CBD 600 mg Daily)	PCL-5 Total Score	19.9231 score on a scale	Standard Deviation 15.7116
Placebo	PCL-5 Total Score	29.9 score on a scale	Standard Deviation 16.7559

Primary

PCL-5 Total Score

Time frame: Week 6

Arm	Measure	Value (MEAN)	Dispersion
Cannabidiol (CBD 600 mg Daily)	PCL-5 Total Score	26.6364 score on a scale	Standard Deviation 18.4921
Placebo	PCL-5 Total Score	26.8889 score on a scale	Standard Deviation 17.7331

Secondary