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Many datasets collected to investigate a specific SUD include participants with co-morbid SUDs. While 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 co-morbid with other SUDs that have been more thoroughly studied. While treatments 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<\/jats:bold>\n                  ) with co-morbid CanUD, alcohol use disorder (\n                  <jats:bold>AUD<\/jats:bold>\n                  ), or cocaine use disorder (\n                  <jats:bold>CocUD<\/jats:bold>\n                  ), while controlling for opioid use. All participants underwent imaging prior to receiving a therapeutic dose of long-acting intramuscular NTX (Vivitrol\n                  <jats:sup>\u00ae<\/jats:sup>\n                  ), an approved treatment for OUD and AUD but not for CocUD, and again two weeks post-administration. At baseline, OUD individuals with co-morbid CanUD, AUD, or CocUD exhibited distinct functional connectivity (\n                  <jats:bold>FC<\/jats:bold>\n                  ) alterations compared to those with OUD-only. These differences were greater in younger participants and primarily involved the default mode network. Following NTX administration, FC differences between the co-morbid CanUD and OUD-only groups globally diminished. A similar FC response to NTX was observed in the parietal, subcortical, sensory, and cerebellar networks in the co-morbid AUD group. In contrast, little change in FC was observed in co-morbid CocUD. These findings, combined with prior evidence that NTX reduces cannabis use by dampening the experience of reward, suggest NTX may hold promise as a treatment for CanUD.\n                <\/jats:p>","DOI":"10.1101\/2025.09.18.676931","type":"posted-content","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T23:55:14Z","timestamp":1758326114000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-acting naltrexone restores network connectivity in subjects with co-morbid cannabis and opioid use disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1831-4935","authenticated-orcid":false,"given":"Lindsey M.","family":"Brier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Langleben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-8794","authenticated-orcid":false,"given":"Corinde 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