N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use (NAC_CUD-TUD)
N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use: A Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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 in dual users of tobacco and cannabis. Sixty adult regular cigarette smokers who 1) have smoked 2 cigarettes per day in 15 of the past 30 days, or an average of 1 cigarettes per day for the past 30 days and 2) use cannabis regularly and 3) 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, 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 cannabis use. 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 TUD and with concurrent cannabis use 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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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California
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San Francisco, California, United States, 94121
- San Francisco Veterans Affairs Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Participants will be male and female smokers ages 18 and over who: 1) have smoked 2 cigarettes per day in 15 of the past 30 days, or an average of 1 cigarettes per day for the past 30 days; 2) endorse the use of cannabis within the past 30 days, reported by Timeline Follow-Back (TLFB), and have positive urine tetrahydrocannabinol (THC) at Week 0 or up to 30 days prior; 3) meet criteria for tobacco use disorder (TUD) in the past 12 months per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), assessed by medical record review and clinical assessment; and 4) consent to receive interventions to stop smoking cigarettes and reducing cannabis use. 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. Individuals of childbearing potential (ages 18-55) must have a negative urine pregnancy test at the time of screening. Individuals who have been prescribed bupropion for depression, not smoking cessation, are eligible to participate in this study. All participants must be California residents (Veterans enrolled in VA healthcare in another state are eligible).
Exclusion Criteria:
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 screening results and/or medical record review. 2) Concurrent participation in another pharmacological tobacco cessation study. 3) Individuals who are pregnant or lactating. 4) Non-study NAC use at enrollment or at any time during the study period. 5) Use of medications for TUD (NRT, bupropion, or varenicline) at 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. 7) Non-residents of California or Veterans in another state who are not enrolled in VA healthcare.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: N-acetyl cysteine (NAC) & cognitive behavioral therapy
N-acetyl cysteine (NAC) & cognitive behavioral therapy experimental arm consists of 30 regular cigarette smokers and cannabis users with current TUD, who will be randomized to receive N-acetyl cysteine 3600 mg per day over 8 weeks to experimental arm.
Participants will also receive weekly cognitive behavioral therapy for substance use disorders targeting TUD and cannabis use.
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Participants in both groups will receive 8 weekly cognitive behavioral therapy sessions for substance use disorder targeting both tobacco and cannabis use.
Other Names:
The investigators will examine N-acetyl cysteine to treat concurrent tobacco use disorder and cannabis use in a double-blind, placebo-controlled RCT.
Eligible regular cigarette smokers with current tobacco use disorder and cannabis use will be randomized to receive NAC 3600 mg per day over 8 weeks.
Other Names:
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Placebo Comparator: Placebo Comparator: Placebo & cognitive behavioral therapy
Placebo comparator & cognitive behavioral therapy arm consists of 30 regular cigarette smokers and cannabis users with current TUD, who will be randomized to receive placebo over 8 weeks.
Participants will also receive weekly cognitive behavioral therapy for substance use disorders targeting TUD and cannabis use.
|
Participants in both groups will receive 8 weekly cognitive behavioral therapy sessions for substance use disorder targeting both tobacco and cannabis use.
Other Names:
The investigators will examine N-acetyl cysteine to treat concurrent tobacco use disorder and cannabis use in a double-blind, placebo-controlled RCT.
Eligible regular cigarette smokers with current tobacco use disorder and cannabis use will be randomized to receive placebo per day over 8 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Change in the Mean Days of Cannabis Use Over Time
Time Frame: Baseline and 12 weeks
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Days of cannabis use will be determined by weekly self-report use of cannabis assessed with Timeline Follow-back (TLFB) which uses a calendar with specific anchor dates to identify the number of 'use days'.
The change in the mean number of days reported at baseline and at the week 12 visit will be reported by group.
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Baseline and 12 weeks
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Change in the Mean Number of Cigarettes Used Over Time
Time Frame: Baseline and 12 weeks
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Weekly self-report use of cigarettes will be assessed with Timeline Follow-back (TLFB) which uses a calendar with specific anchor dates to identify the quantity of use.
The change in the mean number of cigarettes used reported at baseline and at the week 12 visit will be reported by group.
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Baseline and 12 weeks
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Change in the Mean Number of Days of Cigarette Use Over Time
Time Frame: Baseline and 12 weeks
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Weekly self-report use of cigarettes will be assessed with Timeline Follow-back (TLFB) which uses a calendar with specific anchor dates to identify the frequency of use.
The change in the mean number of days reported at baseline and at the week 12 visit will be reported by group.
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Baseline and 12 weeks
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Percentage of Participants With Biochemically Verified, Point-prevalent Abstinence at Week 8
Time Frame: At Week 8
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Biochemically verified abstinence is defined as a participant self-report of not smoking and a saliva sample to detect the presence or absence of salivary cotinine.
Salivary cotinine tests are an established method to biochemically verify a participant's reported smoking status.
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At Week 8
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Percentage of Participants With Biochemically Verified Point Prevalent Abstinence at Week 12
Time Frame: At Week 12
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Biochemically verified abstinence is defined as a participant self-report of not smoking and a saliva sample to detect the presence or absence of salivary cotinine.
Salivary cotinine tests are an established method to biochemically verify a participant's reported smoking status.
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At Week 12
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Change in Scores on the Fagerstrom Test for Nicotine Dependence (FTND) Over Time
Time Frame: Baseline and 12 weeks
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The Fagerström Test for Nicotine Dependence is a standard instrument for assessing the intensity of physical addiction to nicotine.
It contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence.
In scoring the Fagerstrom Test for Nicotine Dependence, yes/no items are scored from 0 to 1 and multiple-choice items are scored from 0 to 3. The items are summed to yield a total score of 0-10.
The higher the total Fagerström score, the more intense is the patient's physical dependence on nicotine.
The change in the average score by group will be reported.
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Baseline and 12 weeks
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Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Total Over Time
Time Frame: Baseline and 12 weeks
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The QSU-Brief consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire (i.e., right now).
Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree).
The items are summed to yield a total score of 10-70.
Higher total scores indicate stronger current smoking urges.
The change in the average total score between baseline and week 12 will be reported by group.
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Baseline and 12 weeks
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Change in Scores on the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) Over Time
Time Frame: Baseline and 12 weeks
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This questionnaire was designed for self-administration and is scored by adding each of the 8 items relating to cannabis use over the past six months.
Question 1-7 are scored on a 0-4 scale Question 8 is scored 0,2, or 4. Total score is calculated by summing the items for a total score of 0-32.
Total scores of 8 or more indicate hazardous cannabis use, while total scores of 12 or more indicate a possible cannabis use disorder for which further intervention may be required.
The change in the average total score between baseline and week 12 will be reported by group.
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Baseline and 12 weeks
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Change in Total Scores on the Marijuana Craving Questionnaire Short Form (MCQ-SF) Total Over Time
Time Frame: Baseline and 12 weeks
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This 12-item multidimensional measure assesses cannabis craving based on 4 factors: Compulsivity, Emotionality, Expectancy, Purposefulness.
Each item asks about the respondent's feelings and thoughts about smoking marijuana as he or she is completing the questionnaire (i.e., right now).
Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree).
Each of the 4 factors (subscales) consist of 3 items which are scored by taking the total of the responses in that scale for a total possible subscale score of 3-21.
The total score is calculated by summing the total scores for the 4 subscales for a total score range of 12-84 The change in the average total score from baseline to week 12 will be reported by group.
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Baseline and 12 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ellen Herbst, MD, San Francisco Veterans Affairs Medical Center
- Study Director: Madeline Martinez Rivas, PhD, San Francisco Veterans Affairs Medical Center
Publications and helpful links
General Publications
- Schauer GL, Berg CJ, Kegler MC, Donovan DM, Windle M. Assessing the overlap between tobacco and marijuana: Trends in patterns of co-use of tobacco and marijuana in adults from 2003-2012. Addict Behav. 2015 Oct;49:26-32. doi: 10.1016/j.addbeh.2015.05.012. Epub 2015 May 23.
- Davis CN, Slutske WS, Martin NG, Agrawal A, Lynskey MT. Identifying subtypes of cannabis users based on simultaneous polysubstance use. Drug Alcohol Depend. 2019 Dec 1;205:107696. doi: 10.1016/j.drugalcdep.2019.107696. Epub 2019 Oct 28.
- Eisenlohr-Moul TA, Peters JR, Pond RS Jr, DeWall CN. Both trait and state mindfulness predict lower aggressiveness via anger rumination: A multilevel mediation analysis. Mindfulness (N Y). 2016 Jun;7(3):713-726. doi: 10.1007/s12671-016-0508-x. Epub 2016 Mar 9.
- Herbst ED, Pennington DL, Borsari B, Manuel J, Yalch M, Alcid E, Martinez Rivas M, Delacruz J, Rossi N, Garcia B, Wong N, Batki SL. N-acetylcysteine for smoking cessation among dual users of tobacco and cannabis: Protocol and rationale for a randomized controlled trial. Contemp Clin Trials. 2023 Aug;131:107250. doi: 10.1016/j.cct.2023.107250. Epub 2023 Jun 2.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Tobacco Use Disorder
- Marijuana Abuse
- Amino Acids, Peptides, and Proteins
- Sulfur Compounds
- Organic Chemicals
- Amino Acids
- Behavior Therapy
- Psychotherapy
- Behavioral Disciplines and Activities
- Cysteine
- Amino Acids, Sulfur
- Acetylcysteine
- Cognitive Behavioral Therapy
Other Study ID Numbers
- 20-31475
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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