N-Acetylcysteine Fails for Cannabis Use Disorder

A recent study involving youth with cannabis use disorder found that N-acetylcysteine is not an effective treatment for the condition. After 12 weeks of treatment, there were no significant differences between the treatment and placebo groups in the proportion of negative urine cannabinoid tests or in self-reported cannabis use. The research was published in Neuropsychopharmacology.

Cannabis use disorder is a medical condition characterized by continued cannabis use despite experiencing significant impairment or distress. Individuals with this disorder often spend a considerable amount of time using cannabis and continue doing so even when it leads to problems at work, school, or in personal relationships. Long-term use in this manner may result in cognitive impairments, reduced motivation, and mental health issues such as anxiety or depression.

Over time, people with cannabis use disorder tend to develop a tolerance, requiring increasing amounts to achieve the same effect. If they abruptly stop using cannabis, they may experience withdrawal symptoms such as irritability, sleep disturbances, and changes in appetite.

Study author Kevin M. Gray and his colleagues aimed to evaluate the efficacy of N-acetylcysteine as a treatment for young people with cannabis use disorder. Participants received this treatment in conjunction with brief, clinician-delivered counseling and medical management of symptoms.

N-acetylcysteine is a supplement and medication derived from the amino acid cysteine. It is known for its antioxidant properties and its ability to replenish intracellular glutathione—a powerful antioxidant found in cells that helps protect them from oxidative stress and supports detoxification.

The study included 192 participants between the ages of 14 and 21 who were seeking treatment for cannabis use disorder. Of these, 140 completed the treatment period, and 93 completed follow-up assessments after treatment concluded.

Participants were randomly assigned to one of two groups. One group received 1200 mg of N-acetylcysteine per day (in the form of two 600 mg capsules), while the other group received identical-looking placebo capsules, both for a duration of 12 weeks.

Throughout the study, participants self-reported their cannabis use through daily mobile surveys. They also provided urine samples at the beginning of the study, during weekly visits, and at post-treatment follow-ups. Researchers used these urine samples to test for cannabinoids, providing an objective measure of cannabis use.

The results showed that participants who used cannabis more frequently before the study were less likely to maintain abstinence during the treatment period. Those who also smoked more tobacco were similarly less likely to remain abstinent. In contrast, participants who expressed greater readiness and confidence to quit were more likely to abstain from cannabis use during the study.

However, there were no significant differences in cannabis use between the N-acetylcysteine and placebo groups—either during treatment or after. This applied to both the proportion of negative urine cannabinoid tests and the participants’ self-reported cannabis use.

“Findings indicate that N-acetylcysteine is not efficacious for youth cannabis use disorder when not paired with contingency management, highlighting the potentially crucial role of a robust behavioral treatment platform in facilitating prior positive efficacy findings with N-acetylcysteine,” the study authors concluded.

This study adds to the growing body of research on N-acetylcysteine’s potential medical applications. However, the researchers acknowledged that the relatively high dropout rate—nearly 30 percent of participants did not complete treatment—may have influenced the results and should be considered when interpreting the findings.

The paper, “N-acetylcysteine for youth cannabis use disorder: randomized controlled trial main findings,” was authored by Kevin M. Gray, Rachel L. Tomko, Nathaniel L. Baker, Erin A. McClure, Aimee L. McRae-Clark, and Lindsay M. Squeglia.

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