Cannabis Use DisorderPhase 2/3NCT03055377
N-Acetylcysteine for Youth Cannabis Use Disorder
A Phase 2/3 study testing N-acetyl cysteine in people with Cannabis Use Disorder, run by Medical University of South Carolina at 1 site in United States.
Trial summary
This is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. Read more about this study
- Who is it for?
- Ages 14 to 21 years
- Conditions the study is for
- Cannabis Use Disorder
- What is being tested?
- N-acetyl cysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2017to 26 Feb 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 14 - 21 years
- Must be able to understand the study and provide written informed consent (for participants under 18 years old, a parent/legal guardian must be able to provide consent and the participant must be able to provide assent)
- Must meet current (within last 30 days) DSM-5 criteria for cannabis use disorder
- Must express interest in treatment for cannabis use disorder
- Must submit a positive urine cannabinoid test during screening
- Females must agree to use appropriate birth control methods during study participation: oral contraceptives, contraceptive patch, barrier (diaphragm or condom), levonorgestrel implant, medroxyprogesterone acetate, complete abstinence from sexual intercourse, or hormonal contraceptive vaginal ring
Who cannot join
- Allergy or intolerance to N-acetylcysteine
- Females who are pregnant or lactating
- Current use of N-acetylcysteine or any supplement containing N-acetylcysteine (must agree not to take any such supplement throughout study participation)
- Use of carbamazepine or nitroglycerin within 14 days of randomization or expectation of future use during protocol participation
- Current enrollment in treatment for cannabis use disorder or expectation of other treatment during protocol participation
- Any use of synthetic cannabinoids (such as K2/Spice) in the 30 days prior to screening or expectation of future use during protocol participation
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- Current moderate or severe substance use disorder, other than cannabis, tobacco, or alcohol
- Medical history of severe asthma (uncontrolled with medications)
- History of seizure disorder
- Any other medical or psychiatric condition or other significant concern that in the Investigator's opinion would impact participant safety or compliance with study instructions, or potentially confound the interpretation of findings
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29403
About this study
This is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups.
Read the detailed description
Cannabis use is particularly prevalent and problematic among youth. Compared with only one in eleven cannabis-exposed adults, one in six cannabis-exposed youth develops cannabis use disorder. Moreover, youth are more prone than adults to potentially lasting adverse effects of cannabis use, including cognitive impairment, altered brain development, poor educational outcome, and diminished life achievement. Despite this, relatively little work has focused on developing optimally efficacious cannabis use disorder treatments, particularly among youth. Current evidence-based treatments convey generally small to modest effect sizes, and novel approaches are critically needed. Among the most promising approaches is the over-the-counter antioxidant medication N-acetylcysteine (NAC). Our team previously demonstrated superior NAC versus placebo (PBO) abstinence outcomes in youth with CUD who concurrently received the behavioral treatment contingency management (CM). Further work is now needed to test whether NAC is efficacious without a platform of CM. The proposed trial is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups. We will also serially assess cognitive task performance, examining changes in performance among participants who achieve abstinence versus those that do not. This proposed trial is the clear "next step" in the assessment of NAC as an extremely promising youth CUD treatment modality, and is positioned to inform researchers, clinicians, and the general public, addressing a critical need for optimization of youth CUD treatment.
- Conditions
- Cannabis Use Disorder
- Being tested
- N-acetyl cysteine, Placebo oral capsule
- Keywords
- cannabis, marijuana, youth, adolescent, pharmacotherapy, medication, n-acetylcysteine, trial
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetyl cysteineDrug
N-acetylcysteine 1200 mg twice daily for 12 weeks (administered orally)
Placebo oral capsuleDrug
Placebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks (administered orally)
| Study group | Role | What they receive |
|---|---|---|
| N-acetylcysteine | Experimental | N-acetylcysteine 1200 mg twice daily for 12 weeks Receives: Drug: N-acetyl cysteine |
| Placebo | Placebo comparator | Placebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Urine Tests With Negative Cannabinoid Results During Treatment
Qualitative urine cannabinoid testing, with cutoff of 50 ng/mL
Measured: Weekly urine cannabinoid tests during 12-week active treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2017
- Study start3 Aug 2017
- Primary completion31 Jan 2024
- Study completion26 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cannabis Use DisorderStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 parallel group allocation randomized placebo controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kevin Gray, Medical University of South Carolina
- Investigators
- Kevin M Gray, MD, Principal investigator, Professor of Psychiatry and Behavioral Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03055377
- Sponsor's protocol ID
- Pro00054499
- Status last verified
- Nov 2024
- First submitted
- 14 Feb 2017
- Last updated
- 17 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gray KM, Tomko RL, Baker NL, McClure EA, McRae-Clark AL, Squeglia LM. N-acetylcysteine for youth cannabis use disorder: randomized controlled trial main findings. Neuropsychopharmacology. 2025 Apr;50(5):731-738. doi: 10.1038/s41386-025-02061-y. Epub 2025 Feb 5.
PubMed 39910268
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-Acetylcysteine for Youth Cannabis Use Disorder
- ClinicalTrials.gov ID
- NCT03055377
- Acronym / sponsor ID
- Pro00054499
- Conditions
- Cannabis Use Disorder
- Keywords
- cannabis, marijuana, youth, adolescent, pharmacotherapy, medication, n-acetylcysteine, trial
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- 3 Aug 2017 (actual)
- Primary completion
- 31 Jan 2024 (actual)
- Study completion
- 26 Feb 2024 (actual)
- First posted
- 16 Feb 2017 (actual)
- Results
- Posted 17 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups.
Detailed description
Cannabis use is particularly prevalent and problematic among youth. Compared with only one in eleven cannabis-exposed adults, one in six cannabis-exposed youth develops cannabis use disorder. Moreover, youth are more prone than adults to potentially lasting adverse effects of cannabis use, including cognitive impairment, altered brain development, poor educational outcome, and diminished life achievement. Despite this, relatively little work has focused on developing optimally efficacious cannabis use disorder treatments, particularly among youth. Current evidence-based treatments convey generally small to modest effect sizes, and novel approaches are critically needed. Among the most promising approaches is the over-the-counter antioxidant medication N-acetylcysteine (NAC). Our team previously demonstrated superior NAC versus placebo (PBO) abstinence outcomes in youth with CUD who concurrently received the behavioral treatment contingency management (CM). Further work is now needed to test whether NAC is efficacious without a platform of CM. The proposed trial is a 12-week randomized, placebo-controlled trial of N-acetylcysteine for cannabis use disorder (CUD) in youth (N=192). Participants will be randomized to double-blind NAC or PBO, yielding two equally-allocated treatment groups. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups. We will also serially assess cognitive task performance, examining changes in performance among participants who achieve abstinence versus those that do not. This proposed trial is the clear "next step" in the assessment of NAC as an extremely promising youth CUD treatment modality, and is positioned to inform researchers, clinicians, and the general public, addressing a critical need for optimization of youth CUD treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 1:1 parallel group allocation randomized placebo controlled trial
| Arm | Type | Receives |
|---|---|---|
| N-acetylcysteine | Experimental | Drug: N-acetyl cysteineN-acetylcysteine 1200 mg twice daily for 12 weeks |
| Placebo | Placebo comparator | Drug: Placebo oral capsulePlacebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks |
Who may qualify
- Ages
- 14 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Age 14 - 21 years
- Must be able to understand the study and provide written informed consent (for participants under 18 years old, a parent/legal guardian must be able to provide consent and the participant must be able to provide assent)
- Must meet current (within last 30 days) DSM-5 criteria for cannabis use disorder
- Must express interest in treatment for cannabis use disorder
- Must submit a positive urine cannabinoid test during screening
Key exclusion criteria (10 listed)
- Allergy or intolerance to N-acetylcysteine
- Females who are pregnant or lactating
- Current use of N-acetylcysteine or any supplement containing N-acetylcysteine (must agree not to take any such supplement throughout study participation)
- Use of carbamazepine or nitroglycerin within 14 days of randomization or expectation of future use during protocol participation
- Current enrollment in treatment for cannabis use disorder or expectation of other treatment during protocol participation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetyl cysteineN-acetylcysteine 1200 mg twice daily for 12 weeks (administered orally) | Drug | N-acetylcysteine |
| Placebo oral capsulePlacebo (matched in appearance to N-acetylcysteine to preserve double-blind) twice daily for 12 weeks (administered orally) | Drug | Placebo |
Primary outcome
Percentage of Urine Tests With Negative Cannabinoid Results During Treatment
Time frame: Weekly urine cannabinoid tests during 12-week active treatment
Qualitative urine cannabinoid testing, with cutoff of 50 ng/mL
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39910268Gray KM, Tomko RL, Baker NL, McClure EA, McRae-Clark AL, Squeglia LM. N-acetylcysteine for youth cannabis use disorder: randomized controlled trial main findings. Neuropsychopharmacology. 2025 Apr;50(5):731-738. doi: 10.1038/s41386-025-02061-y. Epub 2025 Feb 5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin M Gray, MD principal investigator
Professor of Psychiatry and Behavioral Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing N-acetyl cysteine in people with Cannabis Use Disorder, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Urine Tests With Negative Cannabinoid Results During Treatment (time frame: Weekly urine cannabinoid tests during 12-week active treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03055377, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2024.