What side effects are associated with this type of intervention?

The most common treatments for tobacco smoking cessation include nicotine replacement therapy (NRT), varenicline, and bupropion. NRT can cause side effects such as skin reactions (with patches), insomnia, and headaches. Varenicline is associated with nausea, insomnia, abnormal dreams, and potential neuropsychiatric effects like anxiety and depression, particularly in individuals with pre-existing mental health conditions. Bupropion may cause insomnia, dry mouth, and an increased risk of seizures. While ketamine's NMDA receptor antagonism is not a common mechanism in these treatments, the side effects of these smoking cessation therapies are well-documented and should be discussed with a healthcare provider.

What prior FDA approvals exist?

FDA-approved treatments for tobacco smoking cessation include varenicline, a selective nicotinic acetylcholine receptor agonist, bupropion, an antidepressant, and various forms of nicotine replacement therapy (NRT) such as patches, gums, and lozenges. These treatments have been shown to be effective in increasing quit rates among smokers. While NMDA receptor antagonists like ketamine are being studied for their potential effects on smoking behavior, they are not yet approved for this purpose. Current research is exploring their efficacy and safety in this context.

What other types of research exist?

Promising alternatives to Ketamine for treating tobacco smoking include Varenicline, which has shown efficacy in perioperative smoking cessation programs, and Nicotine Replacement Therapy (NRT), which is considered safe and effective in the perioperative period. Additionally, behavioral interventions such as counseling and referral to telephone quitlines have demonstrated long-term quit rates.

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NMDA Receptor Antagonist

Ketamine vs Midazolam for Tobacco Use Disorder (SED-TUD2 Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for tobacco smoking include nicotine replacement therapy (NRT), bupropion, and varenicline. NRT works by providing a controlled dose of nicotine to reduce withdrawal symptoms and cravings, aiding in gradual cessation. Bupropion, an atypical antidepressant, inhibits the reuptake of norepinephrine and dopamine, which helps reduce cravings and withdrawal symptoms. Varenicline, a selective nicotinic acetylcholine receptor agonist, reduces cravings and withdrawal by partially stimulating nicotine receptors and blocking nicotine from binding. NMDA receptor antagonists like ketamine are being studied for their potential to disrupt the neural pathways associated with addiction and craving, offering a novel approach to smoking cessation. Understanding these mechanisms is crucial for tailoring treatments to individual patients, potentially improving quit rates and reducing relapse.

Phase < 1

Recruiting

Led By Merideth A Addicott, MD

Research Sponsored by Wake Forest University Health Sciences

Eligibility Criteria Checklist

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

Must have

Be between 18 and 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24-hours post infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial tests how different drugs affect smoking habits and cravings in people who are not trying to quit. Participants receive an injection of either ketamine, midazolam, dexmedetomidine, or a saltwater solution. The study aims to see if these drugs can help reduce cravings and withdrawal symptoms.

Who is the study for?

This trial is for daily cigarette smokers of at least 2 years, with specific levels of carbon monoxide or cotinine in their breath/urine and no recent use of psychoactive drugs. It excludes those with serious head trauma, certain mental health conditions, unstable medical issues, pregnant or breastfeeding women, extreme obesity, poor vision not correctable to 20/40, severe hypertension or liver/kidney dysfunction.

What is being tested?

The study tests the effects of sedatives (ketamine, midazolam, dexmedetomidine) versus a placebo (saline) on smoking behavior and cravings. Participants are randomly assigned to receive one treatment intravenously without knowing which one they get—a method known as double-blind.

What are the potential side effects?

Potential side effects from the sedatives may include drowsiness, changes in blood pressure and heart rate; mood alterations; nausea; potential for abuse with ketamine; memory impairment particularly with midazolam; dry mouth and possible withdrawal symptoms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24-hours post infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24-hours post infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24-hours post infusion for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Difference in cigarette demand

Pharmaceutical Preparations

Difference in tobacco withdrawal symptoms

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: Saline first injection; midazolam second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion midazolam at the second injection visit

Group II: Saline first injection; ketamine second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion ketamine at the second injection visit.

Group III: Saline first injection; dexmedetomidine second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of placebo at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.

Group IV: Midazolam first injection; ketamine second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion ketamine at the second injection visit.

Group V: Midazolam first injection; dexmedetomidine second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.

Group VI: Midazolam first injection; Saline second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of midazolam at the first injection visit and a single intravenous infusion placebo at the second injection visit.

Group VII: Ketamine first injection; midazolam second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.

Group VIII: Ketamine first injection; dexmedetomidine second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion dexmedetomidine at the second injection visit.

Group IX: Ketamine first injection; Saline second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of ketamine at the first injection visit and a single intravenous infusion placebo at the second injection visit.

Group X: Dexmedetomidine first injection; midazolam second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion midazolam at the second injection visit.

Group XI: Dexmedetomidine first injection; ketamine second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion ketamine at the second injection visit.

Group XII: Dexmedetomidine first injection; Saline second injectionExperimental Treatment2 Interventions

Subjects in this arm will receive a single intravenous infusion of dexmedetomidine at the first injection visit and a single intravenous infusion placebo at the second injection visit.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Saline

2013

Completed Phase 4

~2130

Midazolam

2018

Completed Phase 4

~1910

Dexmedetomidine

2015

Completed Phase 4

~2050

Ketamine

2011

Completed Phase 4

~1120

Do I qualify?Apply below to find out

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 smoking include nicotine replacement therapy (NRT), bupropion, and varenicline. NRT works by providing a controlled dose of nicotine to reduce withdrawal symptoms and cravings, aiding in gradual cessation. Bupropion, an atypical antidepressant, inhibits the reuptake of norepinephrine and dopamine, which helps reduce cravings and withdrawal symptoms. Varenicline, a selective nicotinic acetylcholine receptor agonist, reduces cravings and withdrawal by partially stimulating nicotine receptors and blocking nicotine from binding. NMDA receptor antagonists like ketamine are being studied for their potential to disrupt the neural pathways associated with addiction and craving, offering a novel approach to smoking cessation. Understanding these mechanisms is crucial for tailoring treatments to individual patients, potentially improving quit rates and reducing relapse.

Exploring Potential for a Personalized Medicine Approach to Smoking Cessation With an American Indian Tribe.Combination treatment for nicotine dependence: state of the science.