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Ketamine-enhanced psychotherapy for smoking cessation: A pilot study of feasibility, safety, and clinical outcomes.

Jennifer Jones, Joseph Redding, Emily Amador

Journal of Psychopharmacology September 25, 2026 DOI: 10.1177/02698811261488486 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Open-label pilot study Peer reviewed
Sample size 7
Population Cigarette smokers aged 29-64 with tobacco use disorder and a history of unsuccessful quit attempts
Interventions Ketamine motivational enhancement therapy (MET)
Dose 0.71 mg/kg
Duration Three weekly sessions
Topics Ketamine Neuroplasticity Esketamine
Keywords Glutamate receptor antagonist Smoking cessation Tobacco use disorder
Key points All seven participants completed three weekly intramuscular ketamine sessions combined with motivational enhancement therapy, and the treatment was well tolerated with no adverse events beyond expected transient psychoactive effects. Cigarette consumption and nicotine craving decreased, while withdrawal symptoms, nicotine dependence severity, and motivation to quit remained stable. The authors conclude that ketamine-enhanced psychotherapy for tobacco use disorder was feasible and call for further trials.

Abstract

Tobacco use remains a leading preventable cause of morbidity and mortality. Although several pharmacotherapies and behavioral treatments for tobacco use disorder (TUD) exist, their overall efficacy is modest, underscoring the need for innovative treatment approaches. Ketamine, a rapid-acting glutamate receptor antagonist with neuroplasticity-enhancing properties, has shown promise in the treatment of other substance use disorders. Combining ketamine with motivational enhancement therapy (MET) may complement behavioral treatment in TUD by facilitating cognitive and psychological flexibility while strengthening individuals' ability to quit smoking. The primary aim of this open-label pilot study was to evaluate the feasibility and preliminary clinical outcomes of ketamine treatments delivered in conjunction with MET for smoking cessation in individuals with TUD. Seven cigarette smokers (ages 29-64) with a history of unsuccessful quit attempts underwent three weekly intramuscular ketamine sessions (0.71 mg/kg) combined with MET. Feasibility, the primary outcome, was assessed by study completion rates. Secondary outcomes included changes in smoking patterns, craving, nicotine dependence, withdrawal, and motivation to quit. All participants completed the interventional sessions. Ketamine sessions were well-tolerated, and no adverse events other than the expected transient psychoactive effects were observed. Cigarette consumption decreased, accompanied by reductions in nicotine craving. Withdrawal symptoms, nicotine dependence severity, and motivation to quit remained stable. Ketamine-enhanced psychotherapy for TUD was feasible and was associated with reductions in smoking and craving. These preliminary findings support further trials investigating ketamine's potential to enhance behavioral interventions for addiction.

Comparable studies

Other non-randomized and open-label trials on ketamine, most cited first.

Study Year Design Participants
Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder 2010 Open-label trial n = 33
Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression 2020 Open-label pilot trial n = 7
A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... 2024 Open label study n = 17
Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research Alcoholic patients 1997 Controlled clinical trial n = 211
Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... 2014 Pooled analysis of three clinical trials n = 97

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