Trial Outcomes & Findings for Cannabidiol Effects on Craving and Relapse Prevention in Opioid Use Disorder (NCT NCT03787628)
NCT ID: NCT03787628
Last Updated: 2025-08-01
Results Overview
Number of participants with treatment-emergent adverse events (n/% per treatment group).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
Days 1-56
Results posted on
2025-08-01
Participant Flow
Enrollment was from May 19, 2022 through March 12, 2024. Recruitment was at the Tarzana Treatment Center (TTC), where buprenorphine (as part of their treatment) and CBD (as part of this protocol) were administered. Of 35 enrolled participants, 30 started the study and received CBD or placebo (3 withdrew consent before treatment, 1 was disqualified because opioid use was outside the acceptable window, and 1 was nonmedically discharged prior to receiving the first dose).
Of 170 participants pre-screened, 97 were ineligible. Seventy-one were screened. Of these, 36 were excluded, 35 were enrolled, and 30 started the study and received at least one dose of medication (Safety Population).
Participant milestones
| Measure |
Cannabidiol (CBD) 600 mg
Participants who eligibility criteria were be randomized to receive CBD (ATL5; Ananda Scientific) at a dose of 600 mg.
Cannabidiol (CBD) 600 mg: CBD (300 mg) was administered orally twice daily in the morning and again in the afternoon. The active ingredient in the Ananda investigational new drug, ATL5, is cannabidiol (CBD), extracted from hemp, at a 10% strength (softgel capsules with 100 mg/ml of CBD per capsule). The novel formulation is based on the principle that a water-free mixture of some concentrated inactive ingredients (excipients) self-assemble spontaneously into liquid nanodomains that contain the active component CBD. ATL5 Softgel Capsules was manufactured by Baxco Pharmaceutical Inc. (California, USA) under cGMP conditions.
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Placebo
Up to 30 participants who meet all eligibility criteria were randomized to receive placebo.
Placebo: The placebo softgel capsule formulation had a composition with the same relative proportions as the CBD ATL5 Softgel Capsules. This formulation was manufactured by Baxco Pharmaceutical Inc. under cGMP conditions. The amount (number of softgel capsules) of placebo was administered to match that of the active compound, daily in the morning and afternoon for each of 28 days.
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|---|---|---|
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Overall Study
STARTED
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18
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12
|
|
Overall Study
COMPLETED
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11
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6
|
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Overall Study
NOT COMPLETED
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7
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6
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cannabidiol Effects on Craving and Relapse Prevention in Opioid Use Disorder
Baseline characteristics by cohort
| Measure |
Cannabidiol (CBD) 600 mg
n=18 Participants
Up to 30 participants who meet all eligibility criteria will be randomized to receive CBD (ATL5; Ananda Scientific) at a dose of 600 mg.
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Placebo
n=12 Participants
Up to 30 participants who meet all eligibility criteria will be randomized to receive placebo.
|
Total
n=30 Participants
Total of all reporting groups
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|---|---|---|---|
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Age, Continuous
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36.8 years
STANDARD_DEVIATION 11.34 • n=5 Participants
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35.0 years
STANDARD_DEVIATION 7.98 • n=7 Participants
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36.1 years
STANDARD_DEVIATION 10.01 • n=5 Participants
|
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Sex: Female, Male
Female
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5 Participants
n=5 Participants
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1 Participants
n=7 Participants
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6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
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13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
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24 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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10 Participants
n=5 Participants
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6 Participants
n=7 Participants
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16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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8 Participants
n=5 Participants
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6 Participants
n=7 Participants
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14 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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0 Participants
n=7 Participants
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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0 Participants
n=7 Participants
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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2 Participants
n=5 Participants
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0 Participants
n=7 Participants
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2 Participants
n=5 Participants
|
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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1 Participants
n=7 Participants
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1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
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16 Participants
n=5 Participants
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10 Participants
n=7 Participants
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26 Participants
n=5 Participants
|
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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0 Participants
n=7 Participants
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
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Region of Enrollment
United States
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18 participants
n=5 Participants
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12 participants
n=7 Participants
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30 participants
n=5 Participants
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PRIMARY outcome
Timeframe: Days 1-56Population: The population reported on is the Safety Population, which received at least one dose of active medication or placebo.
Number of participants with treatment-emergent adverse events (n/% per treatment group).
Outcome measures
| Measure |
CBD 600 mg
n=18 Participants
This group reeived the active treatment, CBD at a dose of 600 mg/day.
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Placebo
n=12 Participants
This group received a placebo that was identical in number and appearance of capsules that contained CBD. The excipients in the active formulation were included here.
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|---|---|---|
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The Primary Endpoint Will be Safety and Tolerability of CBD.
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13 participants
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4 participants
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SECONDARY outcome
Timeframe: Before dosing on Day 0 (baseline without CBD) and on Days 7 and 28 after treatment with CBD. The group means below reflect the overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model (GLMM).Population: The analysis populaton was the Safety Population (participants who received at least one dose of test compound).
Cue-induced craving was measured at baseline, Day 7, and Day 28, when participants completed a cue-induced craving task in which they viewed pictures of neutral and opioid-related cues and rated their level of opioid craving on an abbreviated (7-item) version of the Desire for Drug Questionnaire (DDQ). The DDQ is comprised of Likert-style responses ranging from 1 (strongly disagree) to 7 (strongly agree), with total scores on the 7-item scale ranging from 7 to 49, with higher scores reflecting higher craving. The measure of cue-induced craving was derived by subtracting DDQ scores following neutral cues from DDQ scores following opioid cues (range = -42 to 42), with higher scores reflecting greater craving following opioid cues than neutral cues.
Outcome measures
| Measure |
CBD 600 mg
n=18 Participants
This group reeived the active treatment, CBD at a dose of 600 mg/day.
|
Placebo
n=12 Participants
This group received a placebo that was identical in number and appearance of capsules that contained CBD. The excipients in the active formulation were included here.
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|---|---|---|
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The Extent to Which CBD Reduces Cue-induced Craving for Opioids.
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4.45 score on a scale
Standard Deviation 6.54
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7.19 score on a scale
Standard Deviation 6.85
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OTHER_PRE_SPECIFIED outcome
Timeframe: Before dosing (Day 0), daily during treatment period (28 days), and weekly during follow-up (up to 4 weeks). Group means below reflect overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.The Penn Alcohol Craving Scale (PACS) is a brief 4-item self-report measure of spontaneous alcohol craving. In the current study, the items were adapted to measure opioid craving instead of alcohol craving. Responses pertain to opioid craving in the last 24 hours and are measured on a Likert-scale (ranging from 0 to 6), with total scores ranging from 0 to 24. Higher total scores indicate higher levels of spontaneous opioid craving.
Outcome measures
| Measure |
CBD 600 mg
n=18 Participants
This group reeived the active treatment, CBD at a dose of 600 mg/day.
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Placebo
n=12 Participants
This group received a placebo that was identical in number and appearance of capsules that contained CBD. The excipients in the active formulation were included here.
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|---|---|---|
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Spontaneous Opioid Craving Using the Penn Alcohol Craving Scale (PACS), Adapted for Opioid Craving.
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5.11 score on a scale
Standard Deviation 3.97
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5.62 score on a scale
Standard Deviation 4.48
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OTHER_PRE_SPECIFIED outcome
Timeframe: Before dosing (Day 0), daily during treatment period (28 days), and weekly during follow-up (up to 4 weeks). Group means below reflect overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.State anxiety is assessed with the 20-item self-report subscale from the 40-item Spielberger State-Trait Anxiety Inventory (STAI). The state anxiety subscale evaluates how respondents feel "now", in the present moment. All items are rated on a Likert scale from 1 ("not at all") to 4 ("very much so"), with total scores on the state anxiety subscale ranging from 20 to 80. Higher total scores indicate greater state anxiety.
Outcome measures
| Measure |
CBD 600 mg
n=18 Participants
This group reeived the active treatment, CBD at a dose of 600 mg/day.
|
Placebo
n=12 Participants
This group received a placebo that was identical in number and appearance of capsules that contained CBD. The excipients in the active formulation were included here.
|
|---|---|---|
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State Anxiety Subscale of the Spielberger State-Trait Anxiety Inventory (STAI).
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33.25 score on a scale
Standard Deviation 11.18
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36.25 score on a scale
Standard Deviation 8.17
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OTHER_PRE_SPECIFIED outcome
Timeframe: Before dosing (Day 0), daily during treatment period (28 days), and weekly during follow-up (up to 4 weeks). Group means reflect overall group means across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.Negative affect is assessed using the 15-item negative affect subscale from the 30-item Positive and Negative Affect Schedule (PANAS). Each item is rated on a 5-point scale ranging from 1 (not at all) to 5 (extremely), with total scores on the negative affect subscale ranging from 15 to 75. Higher scores reflect greater negative affect.
Outcome measures
| Measure |
CBD 600 mg
n=18 Participants
This group reeived the active treatment, CBD at a dose of 600 mg/day.
|
Placebo
n=12 Participants
This group received a placebo that was identical in number and appearance of capsules that contained CBD. The excipients in the active formulation were included here.
|
|---|---|---|
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Negative Affect Subscale From the Positive and Negative Affect Schedule (PANAS).
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18.97 score on a scale
Standard Deviation 6.70
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19.15 score on a scale
Standard Deviation 5.48
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Adverse Events
Cannabidiol (CBD) 600 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 8 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 3 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cannabidiol (CBD) 600 mg
n=18 participants at risk
Up to 30 participants who meet all eligibility criteria will be randomized to receive CBD (ATL5; Ananda Scientific) at a dose of 600 mg.
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Placebo
n=12 participants at risk
Up to 30 participants who meet all eligibility criteria will be randomized to receive placebo.
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|---|---|---|
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Investigations
Liver function test
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5.6%
1/18 • Number of events 1 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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0.00%
0/12 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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Gastrointestinal disorders
abdominal pain/abdominal cramps or Nausea or Constipation
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33.3%
6/18 • Number of events 7 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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16.7%
2/12 • Number of events 2 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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Nervous system disorders
Headache
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5.6%
1/18 • Number of events 1 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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0.00%
0/12 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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Investigations
Oxygen saturaton decreased
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5.6%
1/18 • Number of events 1 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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0.00%
0/12 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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Reproductive system and breast disorders
Intermenstrual bleeding
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5.6%
1/18 • Number of events 1 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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0.00%
0/12 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
|
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Metabolism and nutrition disorders
Hypoglycemia
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0.00%
0/18 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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8.3%
1/12 • Number of events 1 • Adverse events were recorded over a 28-day treatment perioid and in follow-up sessions through Day 56.
Adverse Events, obtained in self-reports, were recorded dalily. Lab tests and procedures also were performed to monitor safety. Assessment times were during baseline, the treatment period (28 days) and follow up (up to 56 days from the start of treatment): 1. Comprehensive metabolic panel (key tests: AST, ALT, INR) 2. Assessment of Sedation (Observed Observer's Assessment of Alertness/Sedation Scale, pulse oximetry) 3. Electrocardiogram 4. Ovarian hormone battery (females)
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place