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Dexmedetomidine (sublingual film formulation\u2014BXCL501; IGALMI) is a highly potent, selective \u237a2\u2010adrenergic receptor agonist and may be superior to other pharmacotherapeutic approaches. A within subjects, phase 1b safety laboratory study was conducted to evaluate adverse effects of BXCL501 when combined with alcohol; BXCL501's potential efficacy was also explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Heavy drinker participants with a diagnosis of or who were at risk for PTSD participated in three separate test days which included pretreatment with BXCL501 (40\u2009\u00b5g, 80\u2009\u00b5g or placebo) administered in a randomized, double\u2010blind fashion, followed by three testing conditions: alcohol cue reactivity, trauma\u2010induced reactivity, and IV ethanol administration. Safety outcomes included blood pressure (BP) and sedation. Exploratory outcomes included alcohol craving, trauma\u2010induced anxiety and craving and subjective effects of alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten of twelve randomized participants competed the entire study. BXCL501 (80\u2009\u00b5g) was associated with expected mild changes in BP and sedation; administration with alcohol did not affect those parameters. There were no clinically significant adverse effects. BXCL501 attenuated trauma\u2010induced anxiety and attenuated subjective effects of alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussions and Conclusions<\/jats:title><jats:p>BXCL501 is safe for use in humans who may drink alcohol while undergoing treatment. BXCL501 may be explored as a potential treatment for PTSD and AUD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Scientific Significance<\/jats:title><jats:p>This is the first study to provide scientific support for BXCL501's potential to treat PTSD and comorbid AUD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ajad.13637","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T02:05:06Z","timestamp":1723860306000},"page":"7-14","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo\u2010controlled crossover laboratory study"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6894-5946","authenticated-orcid":false,"given":"Ismene L.","family":"Petrakis","sequence":"first","affiliation":[{"name":"Department of Veterans Affairs VA Connecticut Healthcare System West Haven Connecticut USA"},{"name":"Department of Psychiatry Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Nolen","sequence":"additional","affiliation":[{"name":"Social, Statistical, &amp; Environmental Sciences RTI International Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Vandergrift","sequence":"additional","affiliation":[{"name":"Social, Statistical, &amp; Environmental Sciences RTI International Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Social, Statistical, &amp; Environmental Sciences RTI International Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Krystal","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs VA Connecticut Healthcare System West Haven Connecticut USA"},{"name":"Department of Psychiatry Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"De Vivo","sequence":"additional","affiliation":[{"name":"BioXcel Therapeutics Inc. 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