N-Acetylcysteine for Youth Cannabis Use Disorder

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.

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