Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo-controlled crossover laboratory study.

Autor: Petrakis IL; Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, Connecticut, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA., Nolen T; Social, Statistical, & Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA., Vandergrift N; Social, Statistical, & Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA., Hirsch S; Social, Statistical, & Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA., Krystal JH; Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, Connecticut, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA., De Vivo M; BioXcel Therapeutics Inc., New Haven, Connecticut, USA., Sabados J; BioXcel Therapeutics Inc., New Haven, Connecticut, USA., Pisani E; Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, Connecticut, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA., Newcomb J; Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, Connecticut, USA.; Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA., Kosten TR; Baylor College of Medicine, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: The American journal on addictions [Am J Addict] 2024 Aug 16. Date of Electronic Publication: 2024 Aug 16.
DOI: 10.1111/ajad.13637
Abstrakt: Background and Objectives: Noradrenergic dysregulation is important in the pathophysiology of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD); pharmacotherapies targeting adrenergic function have potential as treatment for comorbidity. Dexmedetomidine (sublingual film formulation-BXCL501; IGALMI) is a highly potent, selective ⍺2-adrenergic 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.
Methods: 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 µg, 80 µg or placebo) administered in a randomized, double-blind fashion, followed by three testing conditions: alcohol cue reactivity, trauma-induced reactivity, and IV ethanol administration. Safety outcomes included blood pressure (BP) and sedation. Exploratory outcomes included alcohol craving, trauma-induced anxiety and craving and subjective effects of alcohol.
Results: Ten of twelve randomized participants competed the entire study. BXCL501 (80 µg) 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-induced anxiety and attenuated subjective effects of alcohol.
Discussions and Conclusions: 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.
Scientific Significance: This is the first study to provide scientific support for BXCL501's potential to treat PTSD and comorbid AUD.
(Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)
Databáze: MEDLINE
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