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Many datasets collected to investigate a specific SUD include participants with comorbid SUDs. Although most studies treat comorbid SUDs as covariates of no interest, these covariates also contain untapped information. This is particularly relevant as cannabis use disorder (\n                    <jats:bold>CanUD<\/jats:bold>\n                    ) has become increasingly prevalent and comorbid with other SUDs that have been more thoroughly studied. While pharmacotherapies have been established for multiple SUDs, none have been approved for CanUD, although naltrexone (\n                    <jats:bold>NTX<\/jats:bold>\n                    ) has been associated with reduced use. Here, we conducted a retrospective secondary analysis of functional magnetic resonance imaging (\n                    <jats:bold>fMRI<\/jats:bold>\n                    ) data from individuals with primary opioid use disorder (\n                    <jats:bold>OUD\u2010only<\/jats:bold>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200925 pre\u2010NTX,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200920 on\u2010NTX) with comorbid CanUD (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200910), alcohol use disorder (\n                    <jats:bold>AUD<\/jats:bold>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20096) or cocaine use disorder (\n                    <jats:bold>CocUD<\/jats:bold>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20097). All participants underwent imaging prior to receiving a therapeutic dose of long\u2010acting intramuscular NTX (Vivitrol), an approved treatment for OUD and AUD but not for CocUD, and again 2\u2009weeks postadministration. At baseline, OUD individuals with comorbid CanUD, AUD or CocUD exhibited distinct functional connectivity (\n                    <jats:bold>FC<\/jats:bold>\n                    ) alterations compared to those with OUD\u2010only. These differences were greater in younger participants and primarily involved the default mode network. Following NTX administration, FC differences between the comorbid CanUD and OUD\u2010only groups globally diminished. A similar FC response to NTX was observed in the comorbid AUD group, whereas little change in FC was observed in comorbid CocUD. These findings, combined with prior evidence that NTX reduces cannabis use by dampening reward, suggest NTX may hold promise as a treatment for CanUD.\n                  <\/jats:p>","DOI":"10.1111\/adb.70159","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:37:42Z","timestamp":1779082662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long\u2010Acting Naltrexone Restores Network Connectivity in Subjects With Comorbid Cannabis and Opioid Use Disorder"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1831-4935","authenticated-orcid":false,"given":"Lindsey M.","family":"Brier","sequence":"first","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Langleben","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-8794","authenticated-orcid":false,"given":"Corinde E.","family":"Wiers","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Radiology, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhao","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21073"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2018.01.035"},{"issue":"2","key":"e_1_2_12_4_1","article-title":"Cocaethylene: When Cocaine and Alcohol Are Taken Together","volume":"14","author":"Pergolizzi 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