An Open-Label Trial of N-Acetylcysteine in Cannabis Dependent Adolescents

This project involves investigation of oral N-acetylcysteine (NAC) as a potential
pharmacologic agent for treatment of cannabis dependence in adolescents. Cannabis dependence
continues to be a major problem among adolescents in the United States. To date, psychosocial
interventions have produced only small to modest effect sizes in controlled trials, and
minimal work has been done to investigate the potential role for pharmacotherapy for cannabis
dependence. Translating preclinical research suggesting a role for NAC in cocaine dependent
individuals, our research group has developed preliminary evidence of decreased cocaine use
and cue reactivity in humans taking NAC. Preclinical research has additionally demonstrated
significant parallels in glutamatergic dysfunction in the nucleus accumbens (the proposed
target of NAC treatment) between habitual cocaine and marijuana users. NAC is an inexpensive,
long-available agent with a favorable tolerability profile in adults and children. However,
it has not yet been studied in cannabis dependent adolescents. Hence, we are undertaking an
open-label pilot trial of NAC in adolescents with cannabis dependence.

The primary specific aims of the proposed project are:

1. To assess the feasibility of conducting a trial of NAC in cannabis dependent
adolescents.

2. To assess the safety and tolerability of NAC in cannabis dependent adolescents

The secondary specific aim of the proposed project is:

3. To gather variability information to assist in design of a larger-scale, adequately
powered clinical trial of NAC in cannabis dependent adolescents.

Primary hypotheses

1. It will be feasible to recruit and retain cannabis dependent adolescents in a trial of
NAC.

2. NAC will be well tolerated among cannabis dependent adolescents.

Secondary hypothesis

3. Adequate variability information will be gathered to design a larger-scale, adequately
powered clinical trial of NAC in cannabis dependent adolescents.

Twenty-four adolescents between 12 and 20 years old will be recruited in this study. Results
from this project will be used to design further studies.

Inclusion Criteria:

- Male or female, 12 - 20 years old.

- Participants must be regular smokers of marijuana (on average smoke at least 3 times
per week for at least one year) and meet DSM-IV Criteria for cannabis dependence, with
desire to cut down on marijuana use.

- Participants must understand all oral and written informed consent and give such
consent prior to on-site screening.

- Participants must agree to refrain from marijuana use for 24 hours prior to each cue
reactivity session (Visits 2 and 4).

- Participants must have a person that can be contacted in case of emergency.

- Participants must have had stable residence for the past 30 days.

- Post-menarchal female participants must agree to use birth control to avoid pregnancy.

Exclusion Criteria:

- Allergy or intolerance to N-Acetylcysteine (NAC).

- Pregnancy or lactation.

- History of seizures.

- Current or past history of asthma and/or the occasional or daily use of albuterol or
other beta-agonist inhalers.

- Current use of medications that might affect heart rate or skin conductance.

- Use of carbamazepine or nitroglycerin (or any other medication deemed to be hazardous
if taken with NAC) within 14 days of study.

- History of significant hepatic, renal, endocrine, cardiac (i.e., arrhythmia requiring
medication, angina pectoris, myocardial infarction,), stroke, seizure, neurological,
psychiatric, gastrointestinal, pulmonary, hematologic, metabolic, or other disorders
that may place the participant at increased risk per the judgment of the study
physician.