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

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

192 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if NAC, an over-the-counter antioxidant, can help young people with cannabis use disorder quit using cannabis. NAC works by protecting cells from damage caused by cannabis. The study will test NAC over a period of time.

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.

What data supports the effectiveness of the drug N-acetylcysteine for treating cannabis use disorder?

N-acetylcysteine (NAC) has shown promising results in clinical studies for treating cannabis use disorder, as it may help reduce cravings and use by affecting brain systems involved in addiction. Additionally, NAC has shown potential in reducing cravings and use in other substance use disorders, such as tobacco use. ^{1 2 3 4 5}

Is N-acetylcysteine safe for human use?

N-acetylcysteine (NAC) is generally considered safe and well-tolerated in humans. Common side effects include nausea, vomiting, and diarrhea, but these are not usually serious. It has been used safely for various conditions, including as an antidote for acetaminophen overdose and in chronic obstructive pulmonary disease (COPD). ^{6 7 8 9 10}

How does the drug N-acetylcysteine differ from other treatments for cannabis use disorder?

N-acetylcysteine (NAC) is unique because it is one of the few drugs being studied for cannabis use disorder, a condition with no approved pharmacological treatments. NAC may help reduce cravings and use by affecting the brain's reward system and reducing oxidative stress and inflammation. ^{1 2 4 5 6}

Research Team

Kevin M Gray, MD

Principal Investigator

Professor of Psychiatry and Behavioral Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

N-acetyl cysteine in the treatment of cannabis use disorder: A systematic review of clinical trials. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

N-acetylcysteine for smoking cessation among dual users of tobacco and cannabis: Protocol and rationale for a randomized controlled trial. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

The effect of N-acetylcysteine on alcohol use during a cannabis cessation trial. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Phase I/pharmacodynamic study of N-acetylcysteine/oltipraz in smokers: early termination due to excessive toxicity. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

Evaluating N-acetylcysteine for early and end-of-treatment abstinence in adult cigarette smokers. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. [2022]

7. England 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. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Respiratory paradoxical adverse drug reactions associated with acetylcysteine and carbocysteine systemic use in paediatric patients: a national survey. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease. [2019]

10. England pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. [2022]