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Effects of Cannabidiol in Alcohol Use Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03252756
Recruitment Status : Completed
First Posted : August 17, 2017
Last Update Posted : September 22, 2022
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Tilray
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date  ICMJE August 14, 2017
First Posted Date  ICMJE August 17, 2017
Last Update Posted Date September 22, 2022
Actual Study Start Date  ICMJE September 1, 2019
Actual Primary Completion Date March 16, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2022)
  • Number of Adverse Events [ Time Frame: Up to Week 12 ]
  • Mean Addiction Resource Center Inventory-Short Form (ARCI-SF) Score [ Time Frame: Up to Week 9 ]
    49-item assessment of the subjective effects of acute doses of drugs of abuse. The ARCI-SF measures the subjective effects of a variety of drugs such as alcohol, morphine, LSD, and pentobarbital by a score for each subset. The higher a participant scores on a subset, the more similar the effects of the drug are to the known drug such as alcohol.
  • Rey Auditory Verbal Learning Task (RAVLT) Score [ Time Frame: Week 1 ]
    RAVLT measures verbal learning and declarative memory. During the task, 15 nouns are read aloud for 5 consecutive trials. Each trial is followed by a free recall test in which the participant is asked to recall the words that were just read to them. The raw score is the sum of correctly recalled words across 5 trials. Raw scores are converted to standardized T-scores. T-scores range from 20-100 with a mean of 50; higher scores indicate better performance.
  • Rey Auditory Verbal Learning Task (RAVLT) Score [ Time Frame: Week 5 ]
    RAVLT measures verbal learning and declarative memory. During the task, 15 nouns are read aloud for 5 consecutive trials. Each trial is followed by a free recall test in which the participant is asked to recall the words that were just read to them. The raw score is the sum of correctly recalled words across 5 trials. Raw scores are converted to standardized T-scores. T-scores range from 20-100 with a mean of 50; higher scores indicate better performance.
  • Mental Rotation Task (MRT) Score [ Time Frame: Week 1 ]
    24-item task in which 2D drawings of 3D geometrical figures are compared. Each item comprises a row of five line drawings. The row includes a geometrical target figure in the left-most position, followed by 4 response-choice figures: 2 rotated reproductions of the target and 2 distractors. Participants are asked to indicate which two of the four response choice figures are rotated reproductions of the target figure. The total score is the sum of correct responses and ranges from 0-48; higher scores indicate greater visuospatial ability.
  • Mental Rotation Task (MRT) Score [ Time Frame: Week 5 ]
    24-item task in which 2D drawings of 3D geometrical figures are compared. Each item comprises a row of five line drawings. The row includes a geometrical target figure in the left-most position, followed by 4 response-choice figures: 2 rotated reproductions of the target and 2 distractors. Participants are asked to indicate which two of the four response choice figures are rotated reproductions of the target figure. The total score is the sum of correct responses and ranges from 0-48; higher scores indicate greater visuospatial ability.
  • Time Reproduction Task (TRT) Score [ Time Frame: Week 1 ]
    The TRT asks participants to estimate when 60 seconds has elapsed during five successive trials. Following the trials, the average number of seconds the estimate is off by is calculated as the score.
  • Time Reproduction Task (TRT) Score [ Time Frame: Week 5 ]
    The TRT asks participants to estimate when 60 seconds has elapsed during five successive trials. Following the trials, the average number of seconds the estimate is off by is calculated as the score.
  • Automated Operation Span Task (OSPAN) Score [ Time Frame: Week 1 ]
    OSPAN measures working memory in the presence of distractions. Specifically, the OSPAN sums correctly recalled and ordered items from a memory set in the presence of distractors. The total score is calculated as a sum based on the number of correct answers within a block for the duration of the task. Higher scores indicate better working memory capacity.
  • Automated Operation Span Task (OSPAN) Score [ Time Frame: Week 5 ]
    OSPAN measures working memory in the presence of distractions. Specifically, the OSPAN sums correctly recalled and ordered items from a memory set in the presence of distractors. The total score is calculated as a sum based on the number of correct answers within a block for the duration of the task. Higher scores indicate better working memory capacity.
  • Reading Span (RSpan) Score [ Time Frame: Week 1 ]
    Participants read sets of short sentences consisting of 3, 4, 5, or 6 words per sentence. Half of the sentences are anomalous, and the other half are not. Participants are asked to read each sentence aloud one word at a time and then indicate whether the sentence made semantic sense or not. At the end of each set, participants are asked to remember the last word of each sentence, in order, to the best of their ability. Set sizes increase as the task progresses. Everyone starts with a set size of three words per sentence and ends at a set size of six words per sentence; there are three sentences for each set size. The final score is based on the total number of words recalled. Scores range from 0 to 54, with higher scores indicating better performance.
  • Reading Span (RSpan) Score [ Time Frame: Week 5 ]
    Participants read sets of short sentences consisting of 3, 4, 5, or 6 words per sentence. Half of the sentences are anomalous, and the other half are not. Participants are asked to read each sentence aloud one word at a time and then indicate whether the sentence made semantic sense or not. At the end of each set, participants are asked to remember the last word of each sentence, in order, to the best of their ability. Set sizes increase as the task progresses. Everyone starts with a set size of three words per sentence and ends at a set size of six words per sentence; there are three sentences for each set size. The final score is based on the total number of words recalled. Scores range from 0 to 54, with higher scores indicating better performance.
  • Symmetry Span (SymSpan) Score [ Time Frame: Week 1 ]
    SymSpan consists of 12 trials during which participants assess the symmetry of a series of matrices. After choosing "yes" or "no" for symmetry, a 4 × 4 grid containing a red box appears (the participant's task is to remember the position of the red box). After several combinations, participants view a blank grid and must recall the box positions in correct order from the previous grid screens. Trial length ranges from two to five symmetry-memory matrices per trial. Total scores consist of total number of correct box positions recalled.
  • Symmetry Span (SymSpan) Score [ Time Frame: Week 5 ]
    SymSpan consists of 12 trials during which participants assess the symmetry of a series of matrices. After choosing "yes" or "no" for symmetry, a 4 × 4 grid containing a red box appears (the participant's task is to remember the position of the red box). After several combinations, participants view a blank grid and must recall the box positions in correct order from the previous grid screens. Trial length ranges from two to five symmetry-memory matrices per trial. Total scores consist of total number of correct box positions recalled.
  • Rotation Span (RotSpan) Score [ Time Frame: Week 1 ]
    Working memory assessment. Begins with distractor task asking the participant to judge whether a rotated letter is presented correctly, or is a mirrored image of the letter. Next, to-be-remembered items are presented as arrows of either short or long length and pointing in one of eight different directions. The rotation-arrow sequence is repeated from two to five times per trial. Scores are calculated by summing the number of arrows correctly recalled in the correct order.
  • Rotation Span (RotSpan) Score [ Time Frame: Week 5 ]
    Working memory assessment. Begins with distractor task asking the participant to judge whether a rotated letter is presented correctly, or is a mirrored image of the letter. Next, to-be-remembered items are arrows of either short or long length and pointing in one of eight different directions. Finally, the rotation-arrow sequence is repeated from two to five times per trial. Scores are calculated by summing the number of arrows correctly recalled in the correct order.
Original Primary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
  • Change in Time-line Follow-back (TLFB) assessment of alcohol consumption in Serum [ Time Frame: Baseline to 4 weeks ]
  • Change in Percent carbohydrate deficient transferrin (CDT) assessment of alcohol consumption in Serum [ Time Frame: Baseline to 4 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2022)
  • Change in Penn Alcohol Craving Scale (PACS) Score [ Time Frame: Baseline, Week 9 ]
    5-item questionnaire that measures an individual's craving to drink alcohol in the past week. Items are ranked on a Likert scale from 0-6. Scores range from 0-30; higher scores indicate greater craving to drink alcohol.
  • Change in Beck Anxiety Inventory (BAI) Score [ Time Frame: Baseline, Week 9 ]
    21-item self-report measure of anxiety. Items are ranked on a Likert scale ranging from 0 (Not at all) to 3 (Severely). The total score is the sum of responses and ranges from 0 to 63, where higher scores indicate greater levels of anxiety. Scores are interpreted as follows: 0 - 21 = low anxiety; 22 - 35 = moderate anxiety; 36 and above = potentially concerning levels of anxiety.
  • Change in Beck Depression Inventory-II (BDI-II) Score [ Time Frame: Baseline, Week 9 ]
    21-item self-report inventory designed to measure the severity of depression symptomatology. Participants rank each item on a Likert scale from 0-3. The total score is the sum of responses and ranges from 0-63; higher scores indicate greater severity of depression
  • Change in Alcohol Abstinence Self-Efficacy Scale (AASE): Temptation Subscale [ Time Frame: Baseline, Week 9 ]
    20-item assessment of one's self-confidence in their ability to avoid drinking, with items specifically related to temptation to drink. Responses are rated on a Likert scale from 0-4. The total score is the sum of response and ranges from 0-80; lower overall scores indicate lower temptation to drink.
  • Change in Alcohol Abstinence Self-Efficacy Scale (AASE): Confidence Subscale [ Time Frame: Baseline, Week 9 ]
    20-item assessment of one's self-confidence in their ability to avoid drinking, with items specifically related to confidence to avoid drinking. Responses are rated on a Likert scale from 0-4. The total score is the sum of response and ranges from 0-80; higher overall scores indicate higher confidence in avoiding drinking.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Cannabidiol in Alcohol Use Disorder
Official Title  ICMJE Effects of Cannabidiol in Alcohol Use Disorder
Brief Summary The goal of the proposed project is to begin rigorous study of the clinically relevant effects of non-psychoactive phytocannabinoid cannabidiol (CBD) in patients with severe alcohol use disorder (AUD). This double-blind, randomized proof-of-concept study (n = 40) is designed to assess feasibility and contrast effects of extended (8 weeks) treatment with CBD to those of placebo in AUD patients. Participants with AUD will be randomized to receive either placebo or 600mg CBD/day (PO) for 4 weeks, immediately followed by 1200mg CBD/day (PO) for an additional 4 weeks (8 total weeks). These doses were chosen to reproduce serum CBD levels reported to reduce alcohol-seeking behavior in animal studies. Measures will include circulating levels of CBD, safety measures (THC serum levels, adverse events, cognitive and motoric function), and physiological and psychological domains relevant to AUD (including self-reported craving, depression, and anxiety, and responses to personalized scripts designed to elicit stress- and cue-induced craving and anxiety). Assessments will be conducted following 1 day, 1 week, and 4 weeks of treatment with each dose of CBD vs. placebo, and 1 and 4 weeks after the cessation of treatment. Drinking outcomes across 8 weeks of treatment and 4 weeks of follow-up will also be assessed as an exploratory outcome.
Detailed Description There is increasing recognition of the roles of the endocannabinoid system in neurobiological processes and behavioral domains relevant to addiction. The non-psychoactive phytocannabinoid cannabidiol (CBD) has attracted considerable attention due to its lack of abuse potential, its excellent safety profile, its unique and complex pharmacology, and evidence that it affects anxiety and stress response in animal models and humans. There is a growing body of preclinical data demonstrating that CBD produces marked and persisting decreases in alcohol self-administration and preference for alcohol, and alcohol-, cue- and stress-induced reinstatement of alcohol-seeking behavior, yet there are few studies of the effects of CBD in humans with addictive disorders, and none in alcohol dependent patients.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind, randomized proof-of-concept study
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Alcohol Use Disorder
Intervention  ICMJE
  • Other: Placebo
    600mg Saline (PO) for 4 weeks, immediately followed by 1200mg Saline/ day (PO) for an additional 4 weeks (8 total weeks).
  • Drug: Phytocannabinoid cannabidiol (CBD)
    600mg CBD (PO) for 4 weeks, immediately followed by 1200mg CBD/ day (PO) for an additional 4 weeks (8 total weeks).
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    600mg Saline (PO) for 4 weeks, immediately followed by 1200mg Saline/ day (PO) for an additional 4 weeks (8 total weeks).
    Intervention: Other: Placebo
  • Experimental: Phytocannabinoid cannabidiol (CBD)
    600mg CBD/day (PO) for 4 weeks, immediately followed by 1200mg CBD/day (PO) for an additional 4 weeks (8 total weeks).
    Intervention: Drug: Phytocannabinoid cannabidiol (CBD)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 10, 2022)
61
Original Estimated Enrollment  ICMJE
 (submitted: August 15, 2017)
40
Actual Study Completion Date  ICMJE March 16, 2022
Actual Primary Completion Date March 16, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males and females age 18-65
  • DSM-5 diagnosis of moderate or severe AUD
  • Able to provide voluntary informed consent
  • At least 8 heavy drinking days (4 or more drinks for a woman, 5 or more drinks 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 duration of the study

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 based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support)
  • Current significant suicidality (assessed using the C-SSRS), any 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 (LOC > 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 cannabinoids; 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.
  • Allergy to any ingredient of the study compound.
  • Current treatment for AUD, with exception of AA/12-step treatment
  • No inpatient psychiatric treatment in the last 12 months, with the exception of detox and extended Emergency Department stays
  • A positive urine drug screen for THC, cocaine and/or opioids at screen
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03252756
Other Study ID Numbers  ICMJE 17-01001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: Beginning 3 months and ending 5 years following article publication.
Access Criteria: Researchers who provide a methodologically sound proposal with have access to the data. To gain access, data requestors will need to sign a data access agreement.
Current Responsible Party NYU Langone Health
Original Responsible Party Same as current
Current Study Sponsor  ICMJE NYU Langone Health
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • Tilray
Investigators  ICMJE
Principal Investigator: Michael Bogenschutz, PhD NYU Langone Health
PRS Account NYU Langone Health
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP