What side effects are associated with this type of intervention?

Common treatments for Tobacco Use Disorder include varenicline, bupropion, and nicotine replacement therapy (NRT). Varenicline may cause neuropsychiatric side effects such as anxiety, depression, agitation, and hostility, particularly in individuals with pre-existing mental disorders. Bupropion can lead to insomnia, dry mouth, and an increased risk of seizures. Nicotine replacement therapy, available in forms such as patches, gum, and lozenges, may cause local irritation, nausea, and insomnia. While N-acetylcysteine (NAC) is being studied for its potential to reduce cravings and use, its side effects are generally mild and include gastrointestinal discomfort and rare allergic reactions.

What prior FDA approvals exist?

The FDA has approved several pharmacologic treatments for Tobacco Use Disorder that modulate neurobiological systems related to reward and craving. These include varenicline, which acts as a partial agonist at the nicotinic acetylcholine receptors, and bupropion, an atypical antidepressant that inhibits the reuptake of norepinephrine and dopamine. Additionally, various forms of nicotine replacement therapy (NRT), such as patches, gum, and lozenges, are approved to help reduce withdrawal symptoms and cravings. These treatments aim to support smoking cessation by targeting the neurobiological pathways involved in addiction.

What other types of research exist?

Promising novel alternatives to N-acetylcysteine (NAC) for Tobacco Use Disorder include: 1) Varenicline, which acts as a partial agonist at nicotinic acetylcholine receptors, reducing cravings and withdrawal symptoms. 2) Combination Nicotine Replacement Therapy (NRT), using both a long-acting form (patch) and a short-acting form (gum or lozenge) to manage cravings and withdrawal. 3) Bupropion, an atypical antidepressant that inhibits the reuptake of norepinephrine and dopamine, reducing cravings and withdrawal symptoms. These treatments have shown efficacy in clinical trials and are recommended based on patient preference and clinical discussion.

← Back to Search

Mucolytic Agent

N-Acetylcysteine for Substance Use Disorder (NAC_CUD-TUD Trial)

Phase 4

Recruiting

Led By Ellen Herbst, MD

Research Sponsored by Ellen Herbst

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must 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

Participants will be male and female smokers ages 18 and over who have smoked 2 cigarettes per day in 15 of the past 30 days, or an average of 1 cigarette per day for the past 30 days

Must not have

Non-study NAC use at enrollment or at any time during the study period

Use of medications for TUD (NRT, bupropion, or varenicline) at enrollment or at any time during the study period

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 weeks

Awards & highlights

Pivotal Trial

Drug Has Already Been Approved

Summary

This trial tests NAC, a medication and supplement, to help adults who use both tobacco and cannabis reduce their cravings. NAC works by calming overactive brain signals and reducing stress, making it easier to control cravings. N-acetylcysteine (NAC) has been tested in previous trials for cannabis use disorder, showing mixed results in efficacy.

Who is the study for?

This trial is for adult smokers in California who smoke cigarettes daily and have used cannabis in the last 30 days. They must want to quit smoking, not be using other cessation drugs or participating in another cessation study, and can't have certain psychiatric conditions or be pregnant.

What is being tested?

The trial tests N-Acetylcysteine (NAC) against a placebo while participants also receive Cognitive Behavioral Therapy (CBT). It aims to see if NAC helps reduce cravings and use of both tobacco and cannabis compared to just CBT alone.

What are the potential side effects?

While not specified here, common side effects of NAC may include nausea, vomiting, rash, and headache. Side effects from CBT are rare but can include discomfort from discussing past experiences related to substance use.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with tobacco use disorder in the last year.

Select...

I am a smoker, 18 or older, and have smoked regularly for the past month.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am not using non-study chemotherapy now or during the study.

Select...

I am using or will use medication to quit smoking during the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Percentage of Participants with Point Prevalent Abstinence

Change in Scores on the Beck Anxiety Inventory (BAI)

Change in Scores on the Beck Depression Inventory (BDI)

+14 more

Side effects data

From 2024 Phase 2 trial • 13 Patients • NCT03499249

62%

GGT 400 IU/L >pre-KP value

46%

AST 400 IU/L >pre-KP value

31%

Loss of an IV

23%

Emesis with feeds

15%

Febrile illness

15%

Conjugated bilirubin 3 mg/dL >pre-KP value

Tachycardia

ALT 700 IU/L >pre-KP value

INR >2.0

Total bilirubin 5 mg/dL >pre-KP value

100%

80%

60%

40%

20%

Study treatment Arm

N-Acetylcysteine Treatment

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: N-acetyl cysteine (NAC) & cognitive behavioral therapyExperimental Treatment2 Interventions

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.

Group II: Placebo Comparator: Placebo & cognitive behavioral therapyPlacebo Group2 Interventions

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

First Studied

Drug Approval Stage

How many patients have taken this drug

N-Acetyl cysteine

2022

Completed Phase 4

~190

Cognitive behavioral therapy (CBT)

2002

Completed Phase 3

~2020

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Tobacco Use Disorder include pharmacologic therapies such as varenicline, nicotine replacement therapy (NRT), and bupropion, as well as behavioral interventions. Varenicline works by partially stimulating nicotine receptors in the brain, reducing cravings and withdrawal symptoms while also blocking the rewarding effects of nicotine. NRT provides a controlled dose of nicotine to ease withdrawal symptoms and reduce cravings. Bupropion, an atypical antidepressant, affects neurotransmitters like dopamine and norepinephrine, which are involved in the reward pathways. Behavioral therapies, including counseling and support groups, help patients develop coping strategies and modify behaviors associated with smoking. These treatments are crucial as they address both the physiological and psychological aspects of addiction, improving the chances of successful cessation.

Smoking cessation in chronically ill medical patients.Combination treatment for nicotine dependence: state of the science.