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ObjectiveAssess changes in symptoms of anxiety, depression, and psychosocial or spiritual distress before and after ketamine-assisted psychotherapy (KAP) in individuals with problematic substance use (PSU).MethodsA retrospective chart review was performed on participant data from two five-year prospective outcomes studies: the AIMS Medical Outcomes Study (AMOS) and the AIMS Cancer Outcomes Study (ACOS). The efficacy of KAP for anxiety, depression, and psychosocial or spiritual well being was assessed in patients with current, past, or high risk of substance use disorder. Validated psychometrics utilized were Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and the National Institute of Health - Healing Experiences of All Life Stressors (NIH-HEALS) questionnaires.ResultsBetween November 1, 2020 and October 31, 2022, a total of 18 patients identified with problematic substance use completed at least one KAP session and at least one baseline and post-KAP metric questionnaire. The PSU subpopulation average score changes were as follows: GAD-7 (-6.71 ± 9.15, n = 14); PHQ-9 (-7.44 ± 5.42, n = 16); and NIH-HEALS (5.13 ± 13.64, n = 15). The average score changes for the KAP population of enrolled subjects were as follows: GAD-7 (-2.45 ± 6.01, n = 104); PHQ-9 (-3.02 ± 6.01, n = 111); and NIH-HEALS (2.93 ± 11.91, n = 86). A comparison of average score changes (p