{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:58:18Z","timestamp":1785351498136,"version":"3.55.0"},"reference-count":65,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA054700"],"award-info":[{"award-number":["R01DA054700"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The mechanisms underlying pharmacological treatments for stimulant use disorders are poorly understood. This study examined whether changes in craving, depressive symptoms, and\/or impulsivity mediate treatment effect in pharmacotherapy with combined naltrexone and bupropion for methamphetamine use disorder (MUD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The study was based on secondary analysis of data from the Accelerated Development of Additive Pharmacotherapy Treatment for methamphetamine disorder (ADAPT-2) trial which randomized adults with MUD to combined treatment with injectable naltrexone (380\u2009mg every 3\u2009weeks) plus oral bupropion (450\u2009mg daily) versus placebo. A total of 403 adults with MUD participated in the first stage; 225 of first stage participants in the placebo arm who did not respond to treatment were re-randomized in the second stage. Mediation effects were examined using longitudinal multi-level structural equation modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Naltrexone-bupropion treatment was associated with decreases in drug use, craving, depressive symptoms, and impulsivity. The indirect effect of treatment through change in craving was significant (self-reported use\u2009=\u2009\u22120.21, 95% credible interval (CrI)\u2009=\u2009\u22120.35, \u22120.09; drug screen-ascertained use\u2009=\u2009\u22120.36, 95% CrI\u2009=\u2009\u22120.63, \u22120.16). Change in craving mediated 56% of the treatment effect on self-reported drug use and 45% of the effect on drug screen-ascertained use. Estimates for mediated effects for depressive symptoms and impulsivity were smaller in magnitude and nonsignificant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Reduction in craving mediates the effect of naltrexone-bupropion pharmacotherapy in MUD. Craving may serve as a surrogate measure of treatment efficacy in short-term trials and help identify promising candidate medications to be tested in larger and longer-term trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration:<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      number: NCT03078075.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811261464533","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:45:00Z","timestamp":1785131100000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mediators of treatment response in a clinical trial of naltrexone and bupropion for methamphetamine use disorder: A longitudinal mediation analysis"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-4043","authenticated-orcid":false,"given":"Ramin","family":"Mojtabai","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Tulane University School of Medicine, New Orleans, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Susukida","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Farokhnia","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA"},{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang Quynh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Leggio","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8183-1273","authenticated-orcid":false,"given":"Cecilia","family":"Bergeria","sequence":"additional","affiliation":[{"name":"Kahlert Institute for Addiction Medicine, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Tulane University School of Medicine, New Orleans, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-3108","authenticated-orcid":false,"given":"Kelly E.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Kahlert Institute for Addiction Medicine, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Amin-Esmaeili","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Ahmadi J Sahraian A Biuseh M (2019) A randomized clinical trial on the effects of bupropion and buprenorphine on the reduction of methamphetamine craving. 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