{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T12:06:31Z","timestamp":1778846791096,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH NIDA","award":["R21 DA053393"],"award-info":[{"award-number":["R21 DA053393"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: A sub-anesthetic dose of ketamine has shown promise in reducing craving, withdrawal symptoms, and use of drugs such as alcohol, cocaine, and opioids among individuals with substance use disorders. Ketamine\u2019s therapeutic potential for tobacco use is unknown. Here, we investigated a single sub-anesthetic dose among adults with tobacco use disorder who were not interested in changing their smoking behavior. Methods: Utilizing a randomized, within-subject crossover, double-blinded, counter-balanced, midazolam-controlled design, participants (n = 18) received a 0.71 mg\/kg infusion of ketamine and a 0.025 mg\/kg infusion of midazolam (i.e., active placebo) at least two weeks apart. Participants were asked to abstain from smoking after the infusions until the post-infusion sessions, 1 day following infusion, where participants completed measures of smoking behavior, craving, and withdrawal symptoms. Participants continued to record their smoking behavior over the 7 days following infusion. Participants also completed a semi-structured qualitative interview regarding their experiences. Results: Compared to midazolam, ketamine infusion led to a non-significant reduction (p = 0.10, \u03b7p2 = 0.153) in the number of cigarettes smoked during the requested abstinence period. Following this period, there were no significant differences in ad lib smoking. Ketamine showed no effect on craving or withdrawal symptoms. Participants reported more intense psychological experiences following ketamine infusion (p &lt; 0.001, \u03b7p2 = 0.830) and about half reported it felt easier to abstain from smoking after the ketamine infusion. Conclusions: While well tolerated, these findings suggest ketamine has little to no direct effect on quantitative measures of cigarette smoking, craving, or withdrawal. However, the qualitative measures suggest ketamine improves mood and reduces craving in some individuals for several days. Future studies should investigate whether ketamine can indirectly support smoking cessation among individuals with comorbid psychiatric indications for ketamine treatment.<\/jats:p>","DOI":"10.3390\/brainsci16050496","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:33:17Z","timestamp":1777627997000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of a Single Sub-Anesthetic Dose of Ketamine in Tobacco Use Disorder: An Active-Placebo, Randomized Crossover Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Nathan R.","family":"Luzum","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia H.","family":"McCall","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5005-8599","authenticated-orcid":false,"given":"Charlotte Talley","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Columbano","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Ip","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0327-9193","authenticated-orcid":false,"given":"Santiago","family":"Saldana","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-230X","authenticated-orcid":false,"given":"Alison H.","family":"Oliveto","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merideth","family":"Addicott","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","unstructured":"U.S. Department of Health and Human Services (2014). 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