Clinical trial NCT04627922: N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use
Official title: N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Cannabis Use
Tobacco Use Disorder
Drug Use Disorder
Keywords: Tobacco
Cannabis
N-acetylcysteine
NAC
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Tobacco Related Disease Research Program
First posted: 2020-11-13
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 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 the Mini International Neuropsychiatric Interview140-141 (MINI), 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 MINI. 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.

Primary outcomes:
measure: Number of participants with reported drug usage
timeFrame: Baseline
measure: Number of participants with reported drug usage
timeFrame: 4 weeks
measure: Number of participants with reported drug usage
timeFrame: 8 weeks
measure: Number of participants with reported drug usage
timeFrame: 12 weeks
measure: Mean Salivary Cotinine Levels
timeFrame: 4 weeks
measure: Mean Salivary Cotinine Levels
timeFrame: 8 weeks
measure: Mean Salivary Cotinine Levels
timeFrame: 12 weeks
measure: Change in Percentage of Participants with Point Prevalent Abstinence
timeFrame: Up to 12 weeks
measure: Changes in Score on the Contemplation Ladder
timeFrame: Up to 12 weeks
measure: Change in Scores on the Fagerstrom Test for Nicotine Dependence (FTND)
timeFrame: Up to 12 weeks
measure: Change in Scores on the Minnesota Tobacco Withdrawal Scale-Revised (MTWS-R)
timeFrame: Up to 12 weeks
measure: Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Desire to smoke
timeFrame: Up to 12 weeks
measure: Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Nicotine withdrawal
timeFrame: Up to 12 weeks
measure: Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Total
timeFrame: Up to 12 weeks
measure: Change in Scores on the Cannabis Use Disorder Identification Test - Revised (CUDIT-R)
timeFrame: Up to 12 weeks
measure: Change in Scores on the Marijuana Craving Questionnaire Short Form (MCQ-SF) Total
timeFrame: Up to 12 weeks
measure: Change in Scores on the Cannabis Withdrawal Scale
timeFrame: Up to 12 weeks
measure: Change in Scores on the Beck Depression Inventory (BDI)
timeFrame: Up to 12 weeks
measure: Change in Scores on the Beck Anxiety Inventory (BAI)
timeFrame: Up to 12 weeks
measure: Change in Scores on the Emotion Regulation Questionnaire (ERQ)
timeFrame: Up to 12 weeks
measure: Change in Scores on the Mindful Attention Awareness Scale (MAAS)
timeFrame: Up to 12 weeks
measure: Change in Scores on the Client Satisfaction Questionnaire (CSQ-8)
timeFrame: Up to 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco Veterans Affairs Medical Center
state: California
Study officials:
affiliation: San Francisco Veterans Affairs Medical Center
name: Ellen Herbst, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Francisco Veterans Affairs Medical Center
name: Madeline Martinez Rivas, PhD
role: STUDY_DIRECTOR
References:
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citation: 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.
citation: 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.