N-Acetylcysteine for Cannabis Use Disorder

Overseen By Kevin M Gray, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Medical University of South Carolina

Must not be taking: N-acetylcysteine, Carbamazepine, Nitroglycerin, others

Disqualifiers: Pregnancy, Synthetic cannabinoids, Severe asthma, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N-acetylcysteine can help young people reduce cannabis use. Participants will receive either the medication or a placebo (a pill with no active ingredients) and will also attend weekly counseling sessions to aid in quitting cannabis. The main goal is to determine if those taking N-acetylcysteine have fewer positive urine tests for cannabis over 12 weeks compared to the placebo group. Ideal candidates are young people aged 14 to 21 diagnosed with cannabis use disorder who are interested in stopping their cannabis use. As a Phase 2, Phase 3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use N-acetylcysteine supplements, carbamazepine, or nitroglycerin within 14 days of starting the trial. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that N-acetylcysteine (NAC) is generally safe and well-tolerated. Studies have found that NAC usually causes only mild side effects. In trials with teenagers who use cannabis, NAC was well-tolerated, with most participants experiencing no serious issues. This suggests it is safe for young people dealing with cannabis use problems. For those considering joining a trial, the safety information so far is reassuring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cannabis use disorder, which often include cognitive behavioral therapy and motivational enhancement therapy, N-acetylcysteine (NAC) offers a different approach by targeting the brain's glutamate system. NAC is an antioxidant that helps restore the balance of glutamate, a neurotransmitter that may be dysregulated in individuals with substance use disorders. Researchers are excited about NAC because it represents a novel mechanism of action that could complement or enhance existing behavioral therapies, potentially leading to better outcomes for those struggling with cannabis dependency. Additionally, NAC is already widely used in other medical contexts, suggesting a favorable safety profile.

What evidence suggests that N-acetylcysteine might be an effective treatment for cannabis use disorder?

Research has shown that N-acetylcysteine (NAC), which participants in this trial may receive, can help treat cannabis use disorder. One study found that people taking NAC were more than twice as likely to have negative urine tests for cannabis compared to those taking a placebo, indicating reduced cannabis use. Other studies have found that NAC can help people stop using cannabis and reduce cravings. However, some research suggests that NAC might be most effective when combined with other treatments, such as therapy that rewards positive behavior. Overall, promising evidence indicates that NAC can be effective, but results may vary. ^{1 3 4 5 6}

Who Is on the Research Team?

Kevin M Gray, MD

Principal Investigator

Professor of Psychiatry and Behavioral Sciences

Are You a Good Fit for This Trial?

This trial is for young people aged 14-21 with cannabis use disorder who want treatment. They must understand the study, consent (with guardian consent if under 18), and have used cannabis recently. Females need to follow birth control guidelines. Those with allergies to N-acetylcysteine, severe asthma, seizure disorders, or using certain drugs can't join.

Inclusion Criteria

I can understand the study details and am willing to sign the consent form.

Must meet current (within last 30 days) DSM-5 criteria for cannabis use disorder

Must express interest in treatment for cannabis use disorder

Exclusion Criteria

I am not pregnant or breastfeeding.

I am not taking N-acetylcysteine or supplements containing it, and agree not to take them during the study.

I have not used carbamazepine or nitroglycerin in the last 14 days and do not plan to use them during the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-acetylcysteine or placebo for 12 weeks with weekly cannabis cessation counseling and medication management

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-acetyl cysteine
• Placebo oral capsule

Trial Overview The trial tests if N-acetylcysteine helps youth stop using cannabis over a 12-week period compared to a placebo. Participants will also receive weekly counseling and medication management. Success is measured by urine tests showing no cannabis use.

How Is the Trial Designed?

Group I: N-acetylcysteine Experimental Treatment 1 Intervention

N-acetylcysteine 1200 mg twice daily for 12 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks

N-acetyl cysteine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Cystic fibrosis

Approved in European Union as Acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Cystic fibrosis

Approved in Canada as Acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Cystic fibrosis

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

N-Acetylcysteine is effective as a mucolytic agent for chronic bronchitis and as an antidote for paracetamol poisoning, with peak plasma concentrations achieved within 1 to 2 hours after oral doses of 200 to 400 mg.

While it has significant therapeutic benefits, common side effects include nausea, vomiting, and diarrhea, and it may interact with other drugs, particularly paracetamol and certain anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. Holdiness, MR.[2022]

N-acetylcysteine (NAC) significantly reduced the rate of healthcare resource utilization (HCU) events related to COPD exacerbations by 20% compared to placebo, with an even greater reduction of 23% in current and ex-smokers.

In patients using long-acting bronchodilators without inhaled corticosteroids (ICS), NAC led to a remarkable 60% reduction in exacerbation rates compared to those receiving placebo, suggesting NAC could be a beneficial alternative to ICS in certain COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study. Papi, A., Zheng, J., Criner, GJ., et al.[2020]

In a study involving 302 participants with cannabis use disorder, those taking N-acetylcysteine (NAC) showed a 30% reduction in alcohol consumption compared to a placebo, indicating its potential efficacy in treating alcohol use disorder.

Participants receiving NAC had significantly higher odds of achieving alcohol abstinence and reported fewer drinks and drinking days per week, suggesting NAC could be a promising treatment option for individuals with alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of N-acetylcysteine on alcohol use during a cannabis cessation trial. Squeglia, LM., Tomko, RL., Baker, NL., et al.[2019]

Citations

1. nature.com nature.com/articles/s41386-025-02061-y

N-acetylcysteine for youth cannabis use disorder Findings indicate that N-acetylcysteine is not efficacious for youth cannabis use disorder when not paired with contingency management.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2826714/

N-Acetylcysteine (NAC) in Young Marijuana Users The purpose of this open-label study was to gather tolerability and preliminary efficacy data for NAC in the treatment of cannabis dependence in young people.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306460322000491

N-acetyl cysteine in the treatment of cannabis use disorder NAC has shown to be effective in promoting abstinence, medication adherence and reducing cannabis use and craving among cannabis dependent users.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35189496/

N-acetyl cysteine in the treatment of cannabis use disorder NAC has shown to be effective in promoting abstinence, medication adherence and reducing cannabis use and craving among cannabis dependent users.

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2012.12010055

A Double-Blind Randomized Controlled Trial of N- ... NAC more than doubled the odds of having negative urine cannabinoid tests as compared with placebo, and differences were detectable within a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5993450/

N-acetylcysteine: A potential treatment for substance use ... An open-label, pilot clinical trial found significant reductions in self-reported marijuana use and craving—but not in biomarkers of use—among ...