Nancy A. Melville

June 04, 2012

June 4, 2012 (Phoenix, Arizona) — The antioxidant supplement N-acetylcysteine (NAC) may be effective as an adjunctive therapy in the treatment of marijuana dependence in adolescents, new research suggests.

Results from a randomized controlled trial showed that marijuana-dependent adolescents who received NAC 1200 mg twice daily in addition to brief weekly cessation counseling and a contingency management intervention were twice as likely to have negative cannabinoid urine test results than participants receiving placebo.

"The finding that people who received NAC were more than twice as likely to submit a clean urine sample compared to placebo was statistically significant, and I would argue clinically significant as well," said lead author Kevin M. Gray, MD, an associate professor in the Youth Division of the Medical University of South Carolina's Department of Psychiatry and Behavioral Sciences, in Charleston.

The study results were presented here at the New Clinical Drug Evaluation Unit (NCDEU) 52nd Annual Meeting

A glutamate-modifying agent, NAC is available as an over-the-counter supplement that is commonly known as a mucolytic agent in the management of acetaminophen overdose. It has also been studied in the treatment of cocaine addiction, and a recent study published in Biological Psychiatry and reported by Medscape Medical News also suggests that NAC may help ease some key symptoms of autism.

Effective, Well Tolerated

To evaluate the supplement as a potential marijuana cessation treatment, investigators recruited 166 adolescents seeking treatment for marijuana dependence.

The participants were randomly assigned to receive either NAC 1200 mg or placebo twice daily over the course of 8 weeks. Each group also received brief weekly counselling sessions.

The participants, who were primarily white male adolescents enrolled in school, were described as heavy marijuana users, reporting usage of an average of 23 days in the previous month.

The results showed that patients treated with NAC had more than twice the odds of having negative urine cannabinoid test results during treatment compared with patients receiving placebo (odds ratio, 2.4; 95% confidence interval, 1.1 - 5.4; P = .021).

The treatment was well tolerated, with only mild side effects, Dr. Gray said.

"The tolerability was remarkably good — it was even better than expected," he said. "We expected some mild gastrointestinal upset, but there was very little. Just 1 person had some heartburn."

"The adverse events were mild, including vivid dreams, insomnia, and irritability, but these are relatively classic symptoms of cannabis withdrawal, so by and large, they were benign."

According to the researchers, no other drug therapy has shown similar efficacy in the treatment of marijuana dependence.

"This is the first randomized trial of pharmacotherapy for marijuana dependence in any age group yielding a positive primary cessation outcome via intent-to-treat analysis," they write.

NAC Advantages

Dr. Gray underscored the importance of a potential treatment for adolescents in particular, noting that dependence and abuse rates range from 4% to 6% in adolescents and are 6% in young adults, but that these rates are less than 1% in adults older than 25 years.

"When thinking about trajectory-based treatments, young people are the ones we should be worried about — they are the ones who are particularly likely to be dependent and have a difficult time responding to treatments," he said.

"This is counterintuitive for a lot of people. We tend to think of adults and substance abuse, because they are entrenched in their behaviors, but there are likely some neurobiological underpinnings with adolescents that make them more challenging to deal with clinically."

According to Dr. Gray, NAC offers several advantages.

"NAC has a great appeal because it has been around for a long time, and we have used it in extraordinarily high doses in children and adults, primarily for Tylenol [acetaminophen] overdose," Dr. Gray said.

"In addition, it is inexpensive, and you can actually even buy it in supplement stores," he added.

The research was supported by National Institute on Drug Abuse grant R01DA026777. Dr. Gray has received research support from Supernus Pharmaceuticals.

New Clinical Drug Evaluation Unit (NCDEU) 52nd Annual Meeting. Abstract presented May 20, 2012.

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