for people ages 18 years and up (full criteria)
Healthy Volunteers
healthy people welcome
at San Francisco, California
study started
estimated completion
Principal Investigator
by Ellen Herbst, MD
Photo of Ellen Herbst
Ellen Herbst



Tobacco and cannabis co-use is a common and growing public health problem, especially in states that have legalized cannabis. There are no pharmacologic treatments for co-occurring tobacco and cannabis use. Co-use may make quitting either substance more difficult, given the synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared cues reinforcing co-use. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use.

Official Title

N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use: A Randomized Controlled Trial


N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. NAC has been shown to improve cognition and reduce impulsivity, which in turn may strengthen inhibitory control when presented with contextual cues. To date, no RCT has examined NAC for smoking cessation in the setting of tobacco-cannabis co-use. In a double-blind, placebo-controlled RCT, the investigators will examine a novel pharmacological treatment, NAC, for concurrent tobacco use disorder (TUD) and cannabis use disorder (CUD) in dual users of tobacco and cannabis. Sixty adult daily cigarette smokers who 1) use cannabis regularly and 2) consent to receive interventions to stop smoking cigarettes and using cannabis will be randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups will receive 8 weekly cognitive behavioral therapy sessions addressing both tobacco and cannabis use. Outcomes will be assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette use, nicotine dependence levels, and craving; and cannabis use, CUD severity levels, and craving. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes. NAC SUB-STUDY: Because of the significant clinical and economic burden imposed by tobacco and cannabis use, it is important to understand the mechanism underlying the progression of tobacco (TUD) and cannabis use disorders (CUD) and any potential treatments. TUD and CUD are associated with elevated oxidative stress and chronic inflammation. It has been suggested that patients dependent on these substances have dysregulated markers of oxidation and inflammation, including gluthathione, erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), Interleukin-6 (IL-6). In this sub-study, baseline levels of commonly utilized serum markers of oxidation status and inflammation will be measured in 20 adults recruited under the main study, with the option of being a part of the sub-study who also demonstrate concurrent TUD and CUD. The correlation will be determined between changes in serum markers of oxidative stress and magnitude of use of cigarettes and cannabis. If successful, the investigator will establish regulatory patterns of oxidative stress and inflammation in co-occurring TUD and CUD for the first time, and will implicate oxidative stress and inflammation as playing key roles in the progression and severity of co-occurring TUD and CUD.


Cannabis Use Tobacco Use Disorder Drug Use Disorder Tobacco Cannabis N-acetylcysteine NAC Disease Marijuana Abuse Substance-Related Disorders Acetylcysteine N-monoacetylcystine N-Acetyl cysteine Cognitive behavioral therapy (CBT) N-acetyl cysteine (NAC) & cognitive behavioral therapy


You can join if…

Open to people ages 18 years and up

  • Participants will be male and female daily cigarette smokers ages 18 and over who:
  • Endorse use of smoked cannabis 15 or more of the past 30 days and have positive urine Tetrahydrocannabinol (THC) at Week 0.
  • Meet criteria for Tobacco use disorder (TUD) and Cannabis use disorder (CUD) in the past 12 months per Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and assessed by the Mini International Neuropsychiatric Interview (MINI).
  • Consent to receive interventions to stop smoking cigarettes and using cannabis. Although co-users can use tobacco and cannabis simultaneously (i.e. in "spliffs") and other forms of nicotine and tobacco, participants must smoke combustible cigarettes that are not mixed with cannabis on a daily basis to participate.
  • Female participants 18-55 years old must have a negative urine pregnancy test at the time of screening.

You CAN'T join if...

  1. Psychotic disorders, bipolar disorder, neurocognitive disorder, or other psychiatric or medical conditions judged by the PI to be unstable in the past 30 days, based on MINI.
  2. Concurrent participation in another addiction treatment study or pharmacological study.
  3. Females who are pregnant or lactating.
  4. NAC use at the time of enrollment or at any time during the study period.
  5. Use of medications for TUD (NRT, bupropion, or varenicline) at the time of enrollment or at any time during the study period.
  6. A suicide attempt or suicidal ideation with intent in the 30 days prior to enrollment.


  • San Francisco Veterans Affairs Medical Center
    San Francisco California 94121 United States

Lead Scientist at UCSF

  • Ellen Herbst, MD
    Professor, Psychiatry. Authored (or co-authored) 14 research publications.


not yet accepting patients
Start Date
Completion Date
Ellen Herbst
Phase 4
Study Type
Last Updated