Cannabis Dependence
Conditions
Brief summary
The primary objective of this study is to evaluate the impact of N-acetylcysteine (NAC) 1200 mg versus matched placebo (PBO) twice daily, added to contingency management (CM), on cannabis use among treatment-seeking cannabis-dependent adults (ages 18-50).
Detailed description
The primary objective of this Phase 3 study is to evaluate the impact of NAC 1200 mg versus matched placebo (PBO) twice daily, added to contingency management (CM), on cannabis use among treatment-seeking cannabis-dependent adults (ages 18-50). After assessment and inclusion into the study, participants will be randomized to receive a 12-week course of NAC 1200 mg or matched placebo twice daily. All participants will concurrently participate in a twice-weekly contingency management (CM) intervention. Medication management will be conducted weekly throughout treatment by the medical clinician. Urine cannabinoid testing will occur at all visits, and will be used as the primary determinant of cannabis use. Participants will return approximately four weeks after treatment conclusion for evaluation of adverse events with medication discontinuation and sustained treatment effects.
Interventions
DRUGN-Acetylcysteine
Study participants randomly assigned to the NAC arm will receive a 12-week course of N-Acetylcysteine (1200mg) twice daily. All participants will concurrently participate in weekly medication management sessions and twice-weekly contingency management interventions.
DRUGPlacebo
Study participants randomly assigned to the placebo arm will receive a matched placebo twice daily. All participants will concurrently participate in weekly medication management sessions and twice-weekly contingency management interventions.
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-50 years * Must be able to understand the study and provide written informed consent * Must meet current DSM-IV criteria for cannabis dependence in the last 30 days * Must express interest in treatment for cannabis dependence * Must submit a positive urine cannabinoid test during screening * Women of child bearing potential must agree to use appropriate birth control methods during study participation: oral contraceptives, contraceptive patch, barrier (diaphragm or condom), levonorgestrel implant, medroxyprogesterone acetate, complete abstinence from sexual intercourse, or hormonal contraceptive vaginal ring
Exclusion criteria
* Allergy or intolerance to N-Acetylcysteine * Women who are pregnant or lactating * Current use of NAC or any supplement containing N-Acetylcysteine (must agree not to take any such supplement throughout study participation) * Use of carbamazepine or nitroglycerin within 14 days of randomization * Current enrollment in treatment for cannabis dependence * Any use of synthetic cannabinoids (such as K2/Spice) in the 30 days prior to screening or during the period between screening and randomization * Current substance dependence, other than cannabis or nicotine * Urine drug screen positive for any drug of abuse other than cannabis or amphetamines at the randomization visit (Only participants who have a valid prescription for amphetamines (e.g., for ADHD) may be included) * Urine drug screen positive for amphetamines at the randomization visit without having a valid prescription for it * Maintenance treatment with buprenorphine or methadone * Recent history of asthma (within the last 3 years) * History of seizure disorder, bipolar disorder, schizophrenia, or other significant or unstable medical or psychiatric illness that may place the participant at increased risk in the judgment of the medical clinician * Significant risk of homicide or suicide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Odds of Negative Urine Cannabinoid Tests During Treatment. | study weeks 2-13 | The primary outcome is the abstinence rate over the 12 weeks of treatment. Abstinence is based on a weekly urine drug screen confirmed by central laboratory testing and defined as a negative cannabinoid result. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred almost exclusively through advertising. Individuals currently in treatment for cannabis dependence were not eligible to participate
Participants by arm
| Arm | Count |
|---|---|
| NAC Plus CM N-acetylcysteine (NAC) plus Contingency Management (CM)
N-Acetylcysteine: Study participants randomly assigned to the NAC arm will receive a 12-week course of N-Acetylcysteine (1200mg) twice daily. All participants will concurrently participate in weekly medication management sessions and twice-weekly contingency management interventions. | 153 |
| Placebo Plus CM Placebo plus Contingency Management (CM)
Placebo: Study participants randomly assigned to the placebo arm will receive a matched placebo twice daily. All participants will concurrently participate in weekly medication management sessions and twice-weekly contingency management interventions. | 149 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 22 | 23 |
| Overall Study | Moved away | 5 | 6 |
| Overall Study | Other reason | 1 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Practical problems | 9 | 5 |
| Overall Study | Withdrawal by Subject | 3 | 7 |
Baseline characteristics
| Characteristic | NAC Plus CM | Total | Placebo Plus CM |
|---|---|---|---|
| Age, Continuous | 29.8 years STANDARD_DEVIATION 8.74 | 30.3 years STANDARD_DEVIATION 9.03 | 30.8 years STANDARD_DEVIATION 9.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 65 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 122 Participants | 237 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 44 Participants | 84 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 13 Participants | 19 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 17 Participants | 7 Participants |
| Race (NIH/OMB) White | 84 Participants | 176 Participants | 92 Participants |
| Region of Enrollment United States | 153 participants | 302 participants | 149 participants |
| Sex: Female, Male Female | 36 Participants | 86 Participants | 50 Participants |
| Sex: Female, Male Male | 117 Participants | 216 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 153 | 45 / 149 |
| serious Total, serious adverse events | 1 / 153 | 6 / 149 |
Outcome results
Primary
The Odds of Negative Urine Cannabinoid Tests During Treatment.
The primary outcome is the abstinence rate over the 12 weeks of treatment. Abstinence is based on a weekly urine drug screen confirmed by central laboratory testing and defined as a negative cannabinoid result.
Time frame: study weeks 2-13
Population: Intent to treat; all participants randomized
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Overall | 410 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 5 | 32 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 2 | 25 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 3 | 30 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 6 | 32 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 7 | 36 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 8 | 40 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 9 | 39 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 10 | 39 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 11 | 38 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 12 | 34 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 13 | 33 cannabis negative urine tests |
| NAC Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 4 | 33 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 12 | 40 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 4 | 36 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 8 | 37 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Overall | 401 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 11 | 36 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 2 | 21 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 9 | 36 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 3 | 22 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 5 | 33 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 13 | 36 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 6 | 30 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 10 | 37 cannabis negative urine tests |
| Placebo Plus CM | The Odds of Negative Urine Cannabinoid Tests During Treatment. | Study Week 7 | 37 cannabis negative urine tests |
Comparison: For the primary outcome measure, a repeated-measures logistic regression model was used to analyze the odds of a negative urine cannabinoid test as an indicator of abstinence across all 12 weeks of treatment. A generalized estimating equations (GEEs) were used to adjust for this correlation with multiple samples per participant. The model for the primary analysis included the main effect of treatment, main effect of time, site effects, effect of smoking tobacco, and timeXtreatment interaction.p-value: 0.98595% CI: [0.63, 1.59]Regression, Logistic