Substance Use Disorder
Conditions
Keywords
Marijuana use, Varenicline/Chantix, Motivational enhancement therapy
Brief summary
Marijuana is the most commonly used illicit drug. There is high demand for effective interventions for cannabis use disorder, yet few specific treatments for have been developed. This study will evaluate the efficacy of varenicline for reducing marijuana use in people who use marijuana frequently.
Interventions
DRUGVarenicline
2 mg daily
DRUGPlacebo
2 mg daily
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria * Must meet DSM-5 criteria for cannabis use disorder and use cannabis at least 3 days per week in the last 30 days. * Must be between the ages of 18 and 65 years. * If female and of childbearing potential, must agree to use acceptable methods of birth control for the duration of the trial. * Must consent to random assignment, and be willing to commit to medication ingestion. * Must be able to read and provide informed consent. * Must have body weight \>110lbs (50kg) and have BMI between 18 and 35kg/m2 * Must function at an intellectual level and have knowledge of the English language to sufficiently allow for accurate completion of assessments. Additional Inclusion Criteria for fMRI Eligibility • Must be right-handed. General
Exclusion criteria
* Women who are pregnant, nursing, or plan to become pregnant during the course of the study. * Individuals with severe renal impairment (creatinine clearance less than 30 mL per minute). * Lifetime history of DSM-5 Bipolar I or II Disorder, Schizophrenia or other psychotic disorder. Stably treated MDD, Dysthymia, GAD, Social Phobia, and Specific Phobia diagnoses are acceptable (i.e. same dose of medication has been prescribed for at least 2 months prior to screening and no changes in current medication expected during course of the trial). * Suicidal ideation or behavior within the past 6 months. Subjects who are believed to be at suicidal or homicidal risk (answers 'yes' on questions 4 or 5 of C-SSRS) will be referred for assessment by a qualified mental health professional. * Concomitant use of psychotropic medications, with the exception of stable doses (defined as no dosing adjustments in the past two months) of non-MAO-I antidepressants, non-benzodiazepine anxiolytics, and ADHD medications. * Current use of medications prescribed for mania or psychosis. * Current use of buproprion or nortryptiline. * Moderate or severe non-cannabis substance use disorders within the past 60 days with the exception of tobacco use disorder. * Individuals taking an investigational agent within the last 30 days before baseline visit. * Individuals with clinically significant medical disorders or lab abnormalities. * Any individual at screening with SGOT (AST) or SGPT (ALT) greater than 3 times the upper limit of normal and/or total bilirubin greater than two times the upper limit of normal. * Individuals with clinically significant cardiovascular disease in the past 6 months (e.g., myocardial infarction, CABG, PTCA, severe or unstable angina, serious arrhythmia, or any clinically significant ECG conduction abnormality. * Individuals with clinically significant cerebrovascular disease in the past 6 months such as TIA, CVA, or stroke. * Hypersensitivity to varenicline. * Individuals who have participated in the clinical trial of any investigative compound within the last 60 days. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cannabis Withdrawal Symptoms During Active Treatment | 3 weeks (Week 4-6 of active treatment period) | For this outcome, the negative affect subscale items of The Cannabis Withdrawal Scale (items 5 \[I felt nervous\], 6 \[I had some angry outbursts\], 7 \[I had mood swings\], 8 \[I felt depressed\], 9 \[I was easily irritated\], 15 \[Life seemed an uphill struggle\], 18 \[I felt physically tense\], restlessness (item 11, I felt restless), and/or urge to smoke (items 1 and 10, The only thing I could think about was smoking some cannabis and I had been imagining being stoned) were averaged at Weeks 4, 5, and 6 and for an overall 4-6 week value, with minimum score of the subscale being 0 and maximum score being 100 (higher score indicating worse outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cannabis Abstinence | 3 weeks (Week 4-6 of active treatment period) | Self reported abstinence from Timeline Followback, verified by urine cannabinoid measures |
| Cannabis Use Quantity | 3 weeks (Week 4-6 of active treatment period) | Cannabis use sessions per day measured by Timeline Followback (self-report) at twice weekly visits during Weeks 4, 5 and 6 of the active treatment phase. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline 2 mg daily
Varenicline: 2 mg daily | 35 |
| Placebo 2 mg daily
Placebo: 2 mg daily | 37 |
| Total | 72 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 37 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 34 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 13 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 23 Participants | 42 Participants |
| Region of Enrollment United States | 35 participants | 37 participants | 72 participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Male | 22 Participants | 27 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 37 |
| other Total, other adverse events | 30 / 35 | 32 / 37 |
| serious Total, serious adverse events | 1 / 35 | 0 / 37 |
Outcome results
Primary
Cannabis Withdrawal Symptoms During Active Treatment
For this outcome, the negative affect subscale items of The Cannabis Withdrawal Scale (items 5 \[I felt nervous\], 6 \[I had some angry outbursts\], 7 \[I had mood swings\], 8 \[I felt depressed\], 9 \[I was easily irritated\], 15 \[Life seemed an uphill struggle\], 18 \[I felt physically tense\], restlessness (item 11, I felt restless), and/or urge to smoke (items 1 and 10, The only thing I could think about was smoking some cannabis and I had been imagining being stoned) were averaged at Weeks 4, 5, and 6 and for an overall 4-6 week value, with minimum score of the subscale being 0 and maximum score being 100 (higher score indicating worse outcome).
Time frame: 3 weeks (Week 4-6 of active treatment period)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Cannabis Withdrawal Symptoms During Active Treatment | Overall Week 4-6 average | 2.23 score on a scale | Standard Deviation 4.65 |
| Varenicline | Cannabis Withdrawal Symptoms During Active Treatment | Week 4 | 2.59 score on a scale | Standard Deviation 6.73 |
| Varenicline | Cannabis Withdrawal Symptoms During Active Treatment | Week 5 | 2.15 score on a scale | Standard Deviation 4.84 |
| Varenicline | Cannabis Withdrawal Symptoms During Active Treatment | Week 6 | 1.96 score on a scale | Standard Deviation 4.65 |
| Placebo | Cannabis Withdrawal Symptoms During Active Treatment | Week 6 | 3.47 score on a scale | Standard Deviation 6.07 |
| Placebo | Cannabis Withdrawal Symptoms During Active Treatment | Overall Week 4-6 average | 3.94 score on a scale | Standard Deviation 6.23 |
| Placebo | Cannabis Withdrawal Symptoms During Active Treatment | Week 5 | 4.27 score on a scale | Standard Deviation 7.11 |
| Placebo | Cannabis Withdrawal Symptoms During Active Treatment | Week 4 | 4.07 score on a scale | Standard Deviation 5.81 |
Secondary
Cannabis Use Quantity
Cannabis use sessions per day measured by Timeline Followback (self-report) at twice weekly visits during Weeks 4, 5 and 6 of the active treatment phase.
Time frame: 3 weeks (Week 4-6 of active treatment period)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Varenicline | Cannabis Use Quantity | Week 4 | 0.93 sessions per day |
| Varenicline | Cannabis Use Quantity | Week 5 | 0.89 sessions per day |
| Varenicline | Cannabis Use Quantity | Week 6 | 0.89 sessions per day |
| Placebo | Cannabis Use Quantity | Week 4 | 1.33 sessions per day |
| Placebo | Cannabis Use Quantity | Week 5 | 1.19 sessions per day |
| Placebo | Cannabis Use Quantity | Week 6 | 1.21 sessions per day |
Secondary
Number of Participants With Cannabis Abstinence
Self reported abstinence from Timeline Followback, verified by urine cannabinoid measures
Time frame: 3 weeks (Week 4-6 of active treatment period)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varenicline | Number of Participants With Cannabis Abstinence | Week 4 | 5 Participants |
| Varenicline | Number of Participants With Cannabis Abstinence | Week 5 | 4 Participants |
| Varenicline | Number of Participants With Cannabis Abstinence | Week 6 | 6 Participants |
| Placebo | Number of Participants With Cannabis Abstinence | Week 4 | 3 Participants |
| Placebo | Number of Participants With Cannabis Abstinence | Week 5 | 2 Participants |
| Placebo | Number of Participants With Cannabis Abstinence | Week 6 | 2 Participants |