{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:51:26Z","timestamp":1792651886661,"version":"4.5.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30 DK020541"],"award-info":[{"award-number":["P30 DK020541"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK105015"],"award-info":[{"award-number":["R01 DK105015"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK128242"],"award-info":[{"award-number":["R01 DK128242"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Harmine is a component of the hallucinogenic brew, Ayahuasca, which also contains the psychoactive compound, N, N-dimethyltryptamine. Whether pharmaceutical-grade harmine hydrochloride (HCl) has psychoactive effects, the doses at which these might occur, and the dose-response relationship to side effects and safety in humans are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We conducted a Phase 1, open-label single ascending dose trial in healthy adults with normal body mass index and no prior psychiatric illness. The primary goal was to determine the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine HCl and to characterize safety and tolerability. A secondary goal was to ascertain whether any oral dose has psychoactive effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Thirty-four adult participants, aged 18\u201355\u2009years, were screened for study eligibility. Twenty-five participants met eligibility criteria and were randomized to a single dose of 100, 200, 300, or 500\u2009mg of harmine HCl, respectively, using a continuous reassessment method. The most common adverse events (AEs) observed were gastrointestinal and\/or neurological, dose-related, and of mild to moderate severity. The MTD was determined to be between 100 and 200\u2009mg and is weight-based, with 90% of those participants receiving &gt;2.7\u2009mg\/kg experiencing a dose-limiting toxicity. No serious AEs of harmine HCl were identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Harmine HCl can be orally administered to healthy participants in doses &lt;2.7\u2009mg\/kg with minimal or no AEs. Doses &gt;2.7\u2009mg\/kg are associated with vomiting, drowsiness, and limited psychoactivity. This study is the first to systematically characterize the psychoactive effects of pharmaceutical quality harmine in healthy participants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811241273772","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T07:20:39Z","timestamp":1726816839000},"page":"911-923","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1818-3506","authenticated-orcid":false,"given":"Jessica L","family":"Ables","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Department of Medicine, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Israel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha","family":"Govindarajulu","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy, Center for Biostatistics, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel T","family":"Fremont","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronjon","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geming","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, CA, 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