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CompletedNCT03055377Updated Dec 17, 2024Results posted

N-Acetylcysteine for Youth Cannabis Use Disorder

A Phase 2/3 interventional study of N-acetyl cysteine and Placebo oral capsule in Cannabis Use Disorder, sponsored by Medical University of South Carolina. Completed at 1 site in United States. Open to participants aged 14 Years to 21 Years. Per ClinicalTrials.gov, last updated 2024-12-17.

Sponsored by Medical University of South Carolina · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
192
Allocation
Randomized
Ages
14 Years to 21 Years
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Cannabis Use Disorder

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Keywords

  • cannabis
  • marijuana
  • youth
  • adolescent
  • pharmacotherapy
  • medication
  • n-acetylcysteine
  • trial
03

In context

Marijuana Abuse

530 studies on the registry are indexed under Marijuana Abuse; 114 are open to participants now.

This study's enrollment of 192 is above the median of 60 across 431 interventional studies indexed under Marijuana Abuse.

Browse Marijuana Abuse studies →

Lead sponsor

Medical University of South Carolina is the lead sponsor of 871 studies on the registry; 163 are open to participants now.

Of its 131 completed or terminated interventional studies of FDA-regulated products, 104 (79%) have results posted.

Browse Medical University of South Carolina studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
14 Years to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Age 14 - 21 years
  2. 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)
  3. Must meet current (within last 30 days) DSM-5 criteria for cannabis use disorder
  4. Must express interest in treatment for cannabis use disorder
  5. Must submit a positive urine cannabinoid test during screening
  6. 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

Exclusion criteria

Exclusion Criteria:

  1. Allergy or intolerance to N-acetylcysteine
  2. Females who are pregnant or lactating
  3. Current use of N-acetylcysteine or any supplement containing N-acetylcysteine (must agree not to take any such supplement throughout study participation)
  4. Use of carbamazepine or nitroglycerin within 14 days of randomization or expectation of future use during protocol participation
  5. Current enrollment in treatment for cannabis use disorder or expectation of other treatment during protocol participation
  6. Any use of synthetic cannabinoids (such as K2/Spice) in the 30 days prior to screening or expectation of future use during protocol participation
  7. Current moderate or severe substance use disorder, other than cannabis, tobacco, or alcohol
  8. Medical history of severe asthma (uncontrolled with medications)
  9. History of seizure disorder
  10. 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
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
192 participants (actual)

Study arms

  • Experimental
    N-acetylcysteine

    N-acetylcysteine 1200 mg twice daily for 12 weeks

    Drug: N-acetyl cysteine

  • Placebo comparator
    Placebo

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

    Drug: Placebo oral capsule

Interventions

  • DrugN-acetyl cysteine

    N-acetylcysteine 1200 mg twice daily for 12 weeks (administered orally)

  • DrugPlacebo oral capsule

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

06

What researchers measure

Primary outcomes

  1. Percentage of Urine Tests With Negative Cannabinoid Results During Treatment

    Qualitative urine cannabinoid testing, with cutoff of 50 ng/mL

    Time frame: Weekly urine cannabinoid tests during 12-week active treatment

07

Results

Posted Dec 17, 2024

Participant flow

Treatment Phase
Participant flow — Treatment Phase
MilestoneN-acetylcysteinePlacebo
Started9894
Completed7070
Not completed2824
Withdrew: Lost to follow-up2824
Post-Treatment Follow-Up
Participant flow — Post-Treatment Follow-Up
MilestoneN-acetylcysteinePlacebo
Started7070
Completed4449
Not completed2621
Withdrew: Lost to follow-up2621

Outcome measures

PrimaryPercentage of Urine Tests With Negative Cannabinoid Results During Treatment

Qualitative urine cannabinoid testing, with cutoff of 50 ng/mL

Time frame:
Weekly urine cannabinoid tests during 12-week active treatment
Reported as:
Number · Percentage
Percentage of Urine Tests With Negative Cannabinoid Results During Treatment
PercentageN-acetylcysteinePlacebo
Percentage of Urine Tests With Negative Cannabinoid Results During Treatment9.414.0

Adverse events

Collected over Adverse event data were collected throughout the full 6-month participant enrollment period (includes 12 weeks of study treatment and extended post-treatment follow-up thereafter). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
N-acetylcysteine0/98 (0%)0/98 (0%)86/98 (87.8%)
Placebo0/94 (0%)0/94 (0%)73/94 (77.7%)
Most frequent other events
Showing 10 of 123
Most frequent other events
EventN-acetylcysteinePlacebo
NauseaGastrointestinal disorders32/9816/94
Viral Upper Respiratory Tract InfectionInfections and infestations23/9827/94
HeadacheNervous system disorders25/9816/94
InsomniaPsychiatric disorders18/9814/94
VomitingGastrointestinal disorders16/989/94
Gastroesophageal Reflux DiseaseGastrointestinal disorders14/983/94
AnxietyPsychiatric disorders5/9811/94
DyspepsiaGastrointestinal disorders10/985/94
Decreased AppetiteMetabolism and nutrition disorders9/987/94
DiarrheaGastrointestinal disorders5/988/94

Baseline characteristics

Age, Continuous
Age, Continuous(years)N-acetylcysteinePlaceboTotal
Mean19.1 ± 1.319.2 ± 1.719.2 ± 1.5
Sex: Female, Male
Sex: Female, Male(Participants)N-acetylcysteinePlaceboTotal
Female5546101
Male434891
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)N-acetylcysteinePlaceboTotal
Hispanic or Latino161127
Not Hispanic or Latino8283165
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)N-acetylcysteinePlaceboTotal
American Indian or Alaska Native000
Asian112
Native Hawaiian or Other Pacific Islander000
Black or African American91120
White7873151
More than one race7815
Unknown or Not Reported314
Region of Enrollment
Region of Enrollment(participants)N-acetylcysteinePlaceboTotal
United States9894192
08

Study locations

1 site
  • Medical University of South Carolina
    Charleston, South Carolina 29403, United States
09

References and documents

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 documents

  • Protocol and statistical analysis plan · Apr 14, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Aug 2017 to primary completion in Jan 2024, 77 months.

Results were first posted in Dec 2024, 10 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 14, 2017
First posted
Feb 16, 2017
StartActual
Aug 3, 2017
Primary completionActual
Jan 31, 2024
CompletionActual
Feb 26, 2024
Results first posted
Dec 17, 2024
Last update
Dec 17, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Dec 17, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03055377
Lead sponsor
Medical University of South Carolina
Responsible party
Kevin Gray (Professor of Psychiatry and Behavioral Sciences, Medical University of South Carolina) — Principal investigator
First posted
Feb 16, 2017
Start date
Aug 3, 2017
Primary completion
Jan 31, 2024
Completion
Feb 26, 2024
Results posted
Dec 17, 2024
Last update
Dec 17, 2024

Study contacts

Kevin M Gray, MD
principal investigator · Professor of Psychiatry and Behavioral Sciences

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.

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