N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use

NCT04627922 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 20-31475
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cannabis Use; Tobacco Use Disorder; Drug Use Disorder

Keywords

Tobacco; Cannabis; N-acetylcysteine; NAC

Outcome Measures

Primary Outcomes (11)

• Change in the mean days of cannabis use over time

  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 of use over time will be reported by group.

  Up to Week 12

• Change in the mean number of cigarettes used over time

  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 over time will be reported by group.

  Up to Week 12

• Change in the mean number of days of cigarette use over time

  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 of cigarette use by group over time will be reported.

  Up to Week 12

• Percentage of participants with biochemically verified, point prevalent abstinence at week 8

  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.

  At Week 8

• Percentage of participants with Biochemically verified point prevalent abstinence at week 12

  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.

  At Week 12

• Change in Scores on the Fagerstrom Test for Nicotine Dependence (FTND) over time

  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.

  Up to 12 weeks

• Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Desire to smoke over time

  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) and scores are calculated by summing the item scores. The change in the average score by group will be reported.

  Up to 12 weeks

• Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Nicotine withdrawal over time

  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) and scores are calculated by summing the item scores. The change in the average score by group will be reported.

  Up to 12 weeks

• Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Total over time

  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) and total scores are calculated by summing the item scores. The change in the average score by group will be reported.

  Up to 12 weeks

• Change in Scores on the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) over time

  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. Scores of 8 or more indicate hazardous cannabis use, while scores of 12 or more indicate a possible cannabis use disorder for which further intervention may be required. The change in the average score by group will be reported.

  Up to 12 weeks

• Change in Scores on the Marijuana Craving Questionnaire Short Form (MCQ-SF) Total over time

  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) and scores are using the mean to the corresponding item. Total Scores are the sum of the means for the 4 subscales. The change in the average score by group will be reported.

  Up to 12 weeks

Study Arms (2)

N-acetyl cysteine (NAC) & cognitive behavioral therapy

EXPERIMENTAL

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.

Drug: N-Acetyl cysteine; Behavioral: Cognitive behavioral therapy (CBT)

Placebo Comparator: Placebo & cognitive behavioral therapy

PLACEBO COMPARATOR

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.

Other: Placebo comparator; Behavioral: Cognitive behavioral therapy (CBT)

Interventions

N-Acetyl cysteine DRUG

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.

Also known as: NAC

N-acetyl cysteine (NAC) & cognitive behavioral therapy

Placebo comparator OTHER

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.

Placebo Comparator: Placebo & cognitive behavioral therapy

Cognitive behavioral therapy (CBT) BEHAVIORAL

Participants in both groups will receive 8 weekly cognitive behavioral therapy sessions for substance use disorder targeting both tobacco and cannabis use.

Also known as: CBT

N-acetyl cysteine (NAC) & cognitive behavioral therapy; Placebo Comparator: Placebo & cognitive behavioral therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 TLFB, and have positive urine THC at Week 0 or up to 30 days prior; 3) meet criteria for TUD in the past 12 months per 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).

You may not qualify if:

• \) 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.

Sponsors & Collaborators

• Ellen Herbst: lead
• Tobacco Related Disease Research Program: collaborator

Study Sites (1)

San Francisco Veterans Affairs Medical Center

San Francisco, California, 94121, United States

Location

Related Publications (4)

• 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.

  PMID: 26036666 BACKGROUND

• 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.

  PMID: 31726429 BACKGROUND

• 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.

  PMID: 27429667 BACKGROUND

• 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.

  PMID: 37271412 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder; Substance-Related Disorders; Marijuana Abuse

Interventions

Acetylcysteine; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Ellen Herbst, MD

  San Francisco Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

• Madeline Martinez Rivas, PhD

  San Francisco Veterans Affairs Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 13, 2020
• Study Start: August 25, 2021
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)