Provided herein are methods of treating
alcohol use disorder (AUD),
opioid use disorder (OUD), and other
substance use disorders (SUDs) in a subject, for example by administering an oral transmucosal
dosage form of esketamine, such as an oral thin film (OTF) form of esketamine, sublingually or buccally. Disclosed methods may combine one or more therapy modalities provided before, during, and / or after
drug administration. In some aspects, the methods comprise administering a
dose of esketamine that is sufficient to produce dissociative effects in a subject. In some further aspects, the methods comprise the use of specific therapy modalities or
ketamine-assisted psychotherapy (KAP) protocols, including manualized
relapse prevention cognitive behavioral therapy (CBT). In yet further aspects, the methods comprise ongoing support, including additional psychotherapy and / or adjunct medication, such as
naltrexone,
buprenorphine,
buprenorphine-naloxone,
disulfiram, naloxone, and others.