Cannabis Use Disorder
Conditions
Keywords
cannabis, marijuana, youth, adolescent, pharmacotherapy, medication, n-acetylcysteine, trial
Brief summary
This is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups.
Detailed description
Cannabis use is particularly prevalent and problematic among youth. Compared with only one in eleven cannabis-exposed adults, one in six cannabis-exposed youth develops cannabis use disorder. Moreover, youth are more prone than adults to potentially lasting adverse effects of cannabis use, including cognitive impairment, altered brain development, poor educational outcome, and diminished life achievement. Despite this, relatively little work has focused on developing optimally efficacious cannabis use disorder treatments, particularly among youth. Current evidence-based treatments convey generally small to modest effect sizes, and novel approaches are critically needed. Among the most promising approaches is the over-the-counter antioxidant medication N-acetylcysteine (NAC). Our team previously demonstrated superior NAC versus placebo (PBO) abstinence outcomes in youth with CUD who concurrently received the behavioral treatment contingency management (CM). Further work is now needed to test whether NAC is efficacious without a platform of CM. The proposed trial is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups. We will also serially assess cognitive task performance, examining changes in performance among participants who achieve abstinence versus those that do not. This proposed trial is the clear next step in the assessment of NAC as an extremely promising youth CUD treatment modality, and is positioned to inform researchers, clinicians, and the general public, addressing a critical need for optimization of youth CUD treatment.
Interventions
DRUGN-acetyl cysteine
N-acetylcysteine 1200 mg twice daily for 12 weeks (administered orally)
DRUGPlacebo oral capsule
Placebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks (administered orally)
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind placebo-controlled pharmacotherapy trial
Intervention model description
1:1 parallel group allocation randomized placebo controlled trial
Eligibility
Sex/Gender
ALL
Age
14 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Age 14 - 21 years 2. Must be able to understand the study and provide written informed consent (for participants under 18 years old, a parent/legal guardian must be able to provide consent and the participant must be able to provide assent) 3. Must meet current (within last 30 days) DSM-5 criteria for cannabis use disorder 4. Must express interest in treatment for cannabis use disorder 5. Must submit a positive urine cannabinoid test during screening 6. Females 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
1. Allergy or intolerance to N-acetylcysteine 2. Females who are pregnant or lactating 3. Current use of N-acetylcysteine or any supplement containing N-acetylcysteine (must agree not to take any such supplement throughout study participation) 4. Use of carbamazepine or nitroglycerin within 14 days of randomization or expectation of future use during protocol participation 5. Current enrollment in treatment for cannabis use disorder or expectation of other treatment during protocol participation 6. Any use of synthetic cannabinoids (such as K2/Spice) in the 30 days prior to screening or expectation of future use during protocol participation 7. Current moderate or severe substance use disorder, other than cannabis, tobacco, or alcohol 8. Medical history of severe asthma (uncontrolled with medications) 9. History of seizure disorder 10. Any other medical or psychiatric condition or other significant concern that in the Investigator's opinion would impact participant safety or compliance with study instructions, or potentially confound the interpretation of findings
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Urine Tests With Negative Cannabinoid Results During Treatment | Weekly urine cannabinoid tests during 12-week active treatment | Qualitative urine cannabinoid testing, with cutoff of 50 ng/mL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-acetylcysteine N-acetylcysteine 1200 mg twice daily for 12 weeks
N-acetyl cysteine: N-acetylcysteine 1200 mg twice daily for 12 weeks (administered orally) | 98 |
| Placebo Placebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks
Placebo oral capsule: Placebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks (administered orally) | 94 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post-Treatment Follow-Up | Lost to Follow-up | 26 | 21 |
| Treatment Phase | Lost to Follow-up | 28 | 24 |
Baseline characteristics
| Characteristic | N-acetylcysteine | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 19.1 years STANDARD_DEVIATION 1.3 | 19.2 years STANDARD_DEVIATION 1.5 | 19.2 years STANDARD_DEVIATION 1.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 27 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 165 Participants | 83 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 20 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 15 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 78 Participants | 151 Participants | 73 Participants |
| Region of Enrollment United States | 98 participants | 192 participants | 94 participants |
| Sex: Female, Male Female | 55 Participants | 101 Participants | 46 Participants |
| Sex: Female, Male Male | 43 Participants | 91 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 98 | 0 / 94 |
| other Total, other adverse events | 86 / 98 | 73 / 94 |
| serious Total, serious adverse events | 0 / 98 | 0 / 94 |
Outcome results
Primary
Percentage of Urine Tests With Negative Cannabinoid Results During Treatment
Qualitative urine cannabinoid testing, with cutoff of 50 ng/mL
Time frame: Weekly urine cannabinoid tests during 12-week active treatment
Population: Enrolled and randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N-acetylcysteine | Percentage of Urine Tests With Negative Cannabinoid Results During Treatment | 9.4 Percentage |
| Placebo | Percentage of Urine Tests With Negative Cannabinoid Results During Treatment | 14.0 Percentage |