N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use (NAC_CUD-TUD)

Ellen Herbst

Status and phase: Active, not recruiting; Phase 4

Conditions: Tobacco Use Disorder; Cannabis Use; Drug Use Disorder

Treatments: Behavioral: Cognitive behavioral therapy (CBT); Other: Placebo comparator; Drug: N-Acetyl cysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT04627922

20-31475

Details and patient eligibility

About

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.

Full 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.

Enrollment: 59 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Parallel Assignment

Masking: Double Blind

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59 participants in 2 patient groups, including a placebo group

N-acetyl cysteine (NAC) & cognitive behavioral therapy

Experimental group

Description:

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.

Treatment:

Drug: N-Acetyl cysteine

Behavioral: Cognitive behavioral therapy (CBT)

Placebo Comparator: Placebo & cognitive behavioral therapy

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo comparator

Behavioral: Cognitive behavioral therapy (CBT)