{"abstract":"The Food and Drug Administration (FDA or the Agency) is describing the approaches it is considering for the design of early- phase clinical trials of ibogaine drug products and is opening a public docket to receive comments. The Department of Health and Human Services (HHS) is funding clinical development of ibogaine, and the first federally supported trials are expected to study ibogaine in adults with opioid use disorder (OUD) and adults with post-traumatic stress disorder (PTSD). FDA is building on the guidance for industry entitled \"Psychedelic Drugs: Considerations for Clinical Investigations\" by seeking comments, data, and information from the public on protocol elements relevant to ibogaine development--including dose selection and escalation, care setting, safety monitoring, eligibility criteria, stopping rules, and safety oversight, in part, because the Federal Government is funding work in this area. FDA will consider all information provided in response to this Request for Information (RFI) to inform whether and how these specific elements should be considered in its review of Investigational New Drug Applications (INDs) involving ibogaine.","action":"Notice; request for information; establishment of a public docket.","agencies":[{"raw_name":"DEPARTMENT OF HEALTH AND HUMAN SERVICES","name":"Health and Human Services Department","id":221,"url":"https://www.federalregister.gov/agencies/health-and-human-services-department","json_url":"https://www.federalregister.gov/api/v1/agencies/221","parent_id":null,"slug":"health-and-human-services-department"},{"raw_name":"Food and Drug Administration","name":"Food and Drug Administration","id":199,"url":"https://www.federalregister.gov/agencies/food-and-drug-administration","json_url":"https://www.federalregister.gov/api/v1/agencies/199","parent_id":221,"slug":"food-and-drug-administration"}],"body_html_url":"https://www.federalregister.gov/documents/full_text/html/2026/10/06/2026-20427.html","cfr_references":[],"citation":"91 FR 63563","comment_url":"http://www.regulations.gov/commenton/FDA-2026-N-10429-0001","comments_close_on":"2026-11-20","correction_of":null,"corrections":[],"dates":"Submit either electronic or written comments, data, or information by November 20, 2026.","disposition_notes":null,"docket_ids":["Docket No. FDA-2026-N-10429"],"dockets":[{"supporting_documents":[{"title":"Reference 8 - Rocha, J.M., Reis, J.A.S., Bouso, J.C., Hallak, J.E.C., and R.G. Dos Santos, ‘‘Identifying setting factors associated with improved ibogaine safety: a systematic review of clinical studies,’’ Eur. Arch. Psychiatry Clin. Neurosci., 273(7):1527–1542 (2023), available at doi:10.1007/s00406-023-01590-1.","document_id":"FDA-2026-N-10429-0009"},{"title":"Reference 7 - Roden, D.M., ‘‘Drug-induced prolongation of the QT interval,’’ N. Engl. J. Med., 350(10):1013–1022 (2004), available at doi:10.1056/NEJMra032426.","document_id":"FDA-2026-N-10429-0008"},{"title":"Reference 6. - Ona, G., Rocha, J.M., Bouso, J.C., Hallak, J.E.C., Borra`s, T., et al., ‘‘The adverse events of ibogaine in humans: an updated systematic review of the literature (2015–2020),’’ Psychopharmacology, 239(6):1977–1987\n(2022), available at doi:10.1007/s00213-021-05964-y.","document_id":"FDA-2026-N-10429-0007"},{"title":"Reference 5 - Kock, P., Froelich, K., Walter, M., Lang, U., and K.M. Du¨ rsteler, ‘‘A systematic literature review of clinical trials and therapeutic applications of ibogaine,’’ J. Subst. Abuse Treat., 138:108717 (2022), available at doi:10.1016/j.jsat.2021.108717.","document_id":"FDA-2026-N-10429-0006"},{"title":"Reference 4 - Knuijver, T., ter Heine, R., Schellekens, A.F.A., Heydari, P., Lucas, L., et al., ‘‘The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients,’’ J. Psychopharmacol., 38(5):481–488 (2024),\navailable at doi:10.1177/02698811241237873.","document_id":"FDA-2026-N-10429-0005"},{"title":"Reference 3 - Knuijver, T., Schellekens, A., Belgers, M., Donders, R., van Oosteren, T., et al., ‘‘Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study,’’ Addiction, 117(1):118–128 (2022), available at doi:10.1111/add.15448.","document_id":"FDA-2026-N-10429-0004"},{"title":"Reference 2 - Brunt, T.M., ‘‘Rare but relevant: ibogaine and cardiovascular complications— prolonged QT interval and ventricular arrhythmias,’’ Addiction, 121(6):1616– 1621 (2026), available at doi:10.1111/add.70319.","document_id":"FDA-2026-N-10429-0003"},{"title":"Reference 1 - Alper, K.R., Stajic´, M., and J.R. Gill, ‘‘Fatalities temporally associated with the ingestion of ibogaine,’’ J. Forensic Sci., 57(2):398–412 (2012), available at doi:10.1111/j.1556-4029.2011.02008.x.","document_id":"FDA-2026-N-10429-0002"}],"agency_name":"FDA","documents":[{"comment_count":34,"comment_start_date":"2026-10-06","updated_at":"2026-11-04T00:56:33.710-05:00","comment_url":"https://www.regulations.gov/commenton/FDA-2026-N-10429-0001","allow_late_comments":false,"id":"FDA-2026-N-10429-0001","comment_end_date":"2026-11-21","regulations_dot_gov_open_for_comment":true}],"supporting_documents_count":8,"id":"FDA-2026-N-10429","title":"Design and Safety Considerations for Clinical Trials Involving Ibogaine Drug Products; Request for Information"}],"document_number":"2026-20427","effective_on":null,"end_page":63569,"executive_order_notes":null,"executive_order_number":null,"full_text_xml_url":"https://www.federalregister.gov/documents/full_text/xml/2026/10/06/2026-20427.xml","html_url":"https://www.federalregister.gov/documents/2026/10/06/2026-20427/design-and-safety-considerations-for-clinical-trials-involving-ibogaine-drug-products-request-for","images":{},"images_metadata":{},"json_url":"https://www.federalregister.gov/api/v1/documents/2026-20427?publication_date=2026-10-06","mods_url":"https://www.govinfo.gov/metadata/granule/FR-2026-10-06/2026-20427/mods.xml","not_received_for_publication":null,"page_length":7,"page_views":{"count":1158,"last_updated":"2026-11-04 04:15:04 -0500"},"pdf_url":"https://www.govinfo.gov/content/pkg/FR-2026-10-06/pdf/2026-20427.pdf","presidential_document_number":null,"proclamation_number":null,"public_inspection_pdf_url":"https://public-inspection.federalregister.gov/2026-20427.pdf?1791204314","publication_date":"2026-10-06","raw_text_url":"https://www.federalregister.gov/documents/full_text/text/2026/10/06/2026-20427.txt","regulation_id_number_info":{},"regulation_id_numbers":[],"regulations_dot_gov_info":{"supporting_documents":[{"title":"Reference 8 - Rocha, J.M., Reis, J.A.S., Bouso, J.C., Hallak, J.E.C., and R.G. Dos Santos, ‘‘Identifying setting factors associated with improved ibogaine safety: a systematic review of clinical studies,’’ Eur. Arch. Psychiatry Clin. Neurosci., 273(7):1527–1542 (2023), available at doi:10.1007/s00406-023-01590-1.","document_id":"FDA-2026-N-10429-0009"},{"title":"Reference 7 - Roden, D.M., ‘‘Drug-induced prolongation of the QT interval,’’ N. Engl. J. Med., 350(10):1013–1022 (2004), available at doi:10.1056/NEJMra032426.","document_id":"FDA-2026-N-10429-0008"},{"title":"Reference 6. - Ona, G., Rocha, J.M., Bouso, J.C., Hallak, J.E.C., Borra`s, T., et al., ‘‘The adverse events of ibogaine in humans: an updated systematic review of the literature (2015–2020),’’ Psychopharmacology, 239(6):1977–1987\n(2022), available at doi:10.1007/s00213-021-05964-y.","document_id":"FDA-2026-N-10429-0007"},{"title":"Reference 5 - Kock, P., Froelich, K., Walter, M., Lang, U., and K.M. Du¨ rsteler, ‘‘A systematic literature review of clinical trials and therapeutic applications of ibogaine,’’ J. Subst. Abuse Treat., 138:108717 (2022), available at doi:10.1016/j.jsat.2021.108717.","document_id":"FDA-2026-N-10429-0006"},{"title":"Reference 4 - Knuijver, T., ter Heine, R., Schellekens, A.F.A., Heydari, P., Lucas, L., et al., ‘‘The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients,’’ J. Psychopharmacol., 38(5):481–488 (2024),\navailable at doi:10.1177/02698811241237873.","document_id":"FDA-2026-N-10429-0005"},{"title":"Reference 3 - Knuijver, T., Schellekens, A., Belgers, M., Donders, R., van Oosteren, T., et al., ‘‘Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study,’’ Addiction, 117(1):118–128 (2022), available at doi:10.1111/add.15448.","document_id":"FDA-2026-N-10429-0004"},{"title":"Reference 2 - Brunt, T.M., ‘‘Rare but relevant: ibogaine and cardiovascular complications— prolonged QT interval and ventricular arrhythmias,’’ Addiction, 121(6):1616– 1621 (2026), available at doi:10.1111/add.70319.","document_id":"FDA-2026-N-10429-0003"},{"title":"Reference 1 - Alper, K.R., Stajic´, M., and J.R. Gill, ‘‘Fatalities temporally associated with the ingestion of ibogaine,’’ J. Forensic Sci., 57(2):398–412 (2012), available at doi:10.1111/j.1556-4029.2011.02008.x.","document_id":"FDA-2026-N-10429-0002"}],"comments_count":34,"agency_id":"FDA","comments_url":"https://www.regulations.gov/docketBrowser?rpp=50&so=DESC&sb=postedDate&po=0&dct=PS&D=FDA-2026-N-10429","supporting_documents_count":8,"docket_id":"FDA-2026-N-10429","document_id":"FDA-2026-N-10429-0001","regulation_id_number":null,"title":"Design and Safety Considerations for Clinical Trials Involving Ibogaine Drug Products; Request for Information","checked_regulationsdotgov_at":"2026-11-04T09:55:04Z"},"regulations_dot_gov_url":"http://www.regulations.gov/commenton/FDA-2026-N-10429-0001","significant":null,"signing_date":null,"start_page":63563,"subtype":null,"title":"Design and Safety Considerations for Clinical Trials Involving Ibogaine Drug Products; Request for Information","toc_doc":"Design and Safety Considerations for Clinical Trials Involving Ibogaine Drug Products","toc_subject":"Request for Information","topics":[],"type":"Notice","volume":91}