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Article History

Received: 26 May 2025

Accepted: 1 November 2025

First Online: 8 December 2025

Competing interests

: J.G., B.Q., M.T., C.C., and P.L. are employed by NetraMark Corp. J.G. declares that he owns substantial shares in NetraMark Holdings, which funded a major portion of this study. L.P. and L.A. are also shareholders in this company. C.A.Z.J is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. E.D.B. and C.A.Z.J. are employees of the United States Government, and this work was completed as part of their official duties as Government employees. The views expressed do not necessarily reflect the views of the NIH, the Department of Health and Human Services, or the United States Government. Funding for this work was provided in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIAMH002927). L.P. disclosures (Last 2 years): AbbVie, USA; Acumen, USA; Aicure, USA; Alexion, Italy; BCG, Switzerland; Astra-Zeneca, Italy; Boehringer Ingelheim International GmbH, Germany; EDRA-LSWR Publishing Company, Italy; GH-Pharma, Ireland; GLG-Institute, USA; Immunogen, USA; Johnson & Johnson USA; LB-Pharmaceuticals, USA; Magdalena BioSciences, USA; MSD, Italy; Sanofi-Aventis-Genzyme, France and USA; Lundbeck, Denmark and Italy; NapoPharma, USA and EU; NetraMark, Canada; Pfizer Global, USA; Relmada Therapeutics, USA; Takeda, USA. Shares/Options: Relmada, NetraMark.