{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:19:05Z","timestamp":1792448345851,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) can result in prolonged post-concussive syndrome and chronic hypoxic-ischemic brain injury (HIBI) sequelae remains therapeutically challenging with the persistence of significant neurological and cognitive impairments. While conventional treatments often provide limited relief, emerging research explores alternative therapeutic interventions, including psychedelic compounds combined with therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This naturalistic case series examines clinical observations following an integrative, participant-directed iboga-containing microdosing protocol paired with Accelerated Experiential Dynamic Psychotherapy (AEDP) in three individuals with persistent neurologic symptoms after traumatic brain injury (TBI) or hypoxic-ischemic brain injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three participants completed a 6\u00a0week protocol using Tabernanthe iboga root bark biomass (participant-directed titration 0.1\u20131.0\u00a0g\/day, 4\u00a0days-on\/3\u00a0days-off). Quantitative qNMR\/HPLC analysis (University of Cape Town) demonstrated approximately 3.845% ibogaine content by mass, yielding estimated ibogaine-equivalent exposure of 3.8\u201338.5\u00a0mg\/day. All administration utilized whole root bark biomass only. Weekly AEDP psychotherapy and supportive nutraceuticals were provided concurrently.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patient one<\/jats:title>\n                    <jats:p>A 43\u00a0year-old man with TBI sustained in a motorcycle accident. Patient Two: A 40-year-old woman with chronic hypoxic brain injury sustained during an avalanche burial event. Patient Three: A 19\u00a0year old woman with TBI sustained in a motor vehicle accident.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All three patients demonstrated progressive neurological recovery over the 6-week microdosing iboga protocol with two of the patients declaring complete symptom remission at a long term follow up assessment. Initial reported symptoms included a constellation of daily headaches, episodic migraines, disequilibrium, irritability, mood swings, fatigue, brain fog, sleep disruptions, and loss of interest in typical life activities. At the conclusion of the protocol, and at long term follow-up visits, patients felt able to discontinue all prescription medications for symptomatic treatment, reporting absence of severe migraine headaches, resolution of brain fog, fatigue, irritability, and stabilized mood, with the ability to return all regular activities with a renewed enthusiasm for life. All patients provided consent to share their significant clinical and therapeutic improvement journey in this publication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Safety considerations<\/jats:title>\n                    <jats:p>The microdosing protocol was carefully implemented with rigorous screening to mitigate potential cardiac and neurological risks associated with iboga administration, including medical background screening for potential drug interactions, and past medical history contraindications including heart conditions and\/or the concomitant administration of selective serotonin reuptake inhibitors (SSRIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This naturalistic case series provides hypothesis-generating observations regarding possible clinical improvement following an integrative iboga-containing intervention paired with psychotherapeutic and supportive care. The findings do not establish causality or iboga-specific efficacy and should be interpreted within the context of multimodal therapeutic exposure and substantial methodological limitations. These preliminary observations suggest that an integrative iboga microdosing protocol, in association with psychotherapeutic and supportive care, may be linked to meaningful improvements in prolonged post-concussive symptoms. As a hypothesis-generating case series, these findings warrant further investigation in controlled trials to establish causality and specificity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1840956","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:11:18Z","timestamp":1780474278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical improvement following an integrative iboga microdosing protocol in post-concussive and hypoxic brain injury syndromes: a case series"],"prefix":"10.3389","volume":"17","author":[{"given":"Burton J.","family":"Tabaac","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Nevada Reno School of Medicine","place":["Reno, NV, United States"]},{"name":"Department of Neurology, Carson Tahoe Health","place":["Carson City, NV, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L.","family":"Carhart-Harris","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Psychiatry, University of California San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Yung","sequence":"additional","affiliation":[{"name":"Department of Psychology, Meridian University","place":["Petaluma, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e77262","DOI":"10.1371\/journal.pone.0077262","article-title":"Effect of iboga alkaloids on \u00b5-opioid receptor-coupled G protein activation","volume":"8","author":"Antonio","year":"2013","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/j.1749-6632.2000.tb05210.x","article-title":"Noribogaine (12-hydroxyibogamine): a biologically active metabolite of the antiaddictive drug ibogaine","volume":"914","author":"Baumann","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1594307","DOI":"10.3389\/fpsyt.2025.1594307","article-title":"Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat","volume":"16","author":"Blest-Hopley","year":"2025","journal-title":"Front. Psychiatry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/s41591-023-02759-w","article-title":"An ancient psychedelic for traumatic brain injury","volume":"30","author":"Brody","year":"2024","journal-title":"Nat. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1080\/00952990.2017.1320802","article-title":"Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes","volume":"44","author":"Brown","year":"2018","journal-title":"Am. J. Drug Alcohol Abuse"},{"key":"B6","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s41586-020-3008-z","article-title":"A non-hallucinogenic psychedelic analogue with therapeutic potential","volume":"589","author":"Cameron","year":"2021","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.neuropharm.2018.03.010","article-title":"The entropic brain - revisited","volume":"142","author":"Carhart-Harris","year":"2018","journal-title":"Neuropharmacology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1124\/pr.118.017160","article-title":"REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics","volume":"71","author":"Carhart-Harris","year":"2019","journal-title":"Pharmacol. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e133","DOI":"10.1097\/MJT.0000000000001723","article-title":"Psychedelic therapy: a primer for primary care clinicians-ibogaine","volume":"31","author":"Cherian","year":"2024","journal-title":"Am. J. Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/s41591-023-02705-w","article-title":"Magnesium-ibogaine therapy in veterans with traumatic brain injuries","volume":"30","author":"Cherian","year":"2024","journal-title":"Nat. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"724606","DOI":"10.3389\/fpsyt.2021.724606","article-title":"Psychedelics and neuroplasticity: a systematic review unraveling the biological underpinnings of psychedelics","volume":"12","author":"de Vos","year":"2021","journal-title":"Front. Psychiatry"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1096\/fj.06-6394fje","article-title":"Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, ibogaine","volume":"20","author":"He","year":"2006","journal-title":"FASEB J."},{"key":"B12","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/7854_2022_366","article-title":"Psilocybin for trauma-related disorders","volume":"56","author":"Khan","year":"2022","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1111\/add.15448","article-title":"Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study","volume":"117","author":"Knuijver","year":"2022","journal-title":"Addiction"},{"key":"B14","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1177\/02698811241237873","article-title":"The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients","volume":"38","author":"Knuijver","year":"2024","journal-title":"J. Psychopharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.3390\/molecules20022208","article-title":"The anti-addiction drug ibogaine and the heart: a delicate relation","volume":"20","author":"Koenig","year":"2015","journal-title":"Molecules"},{"key":"B16","doi-asserted-by":"publisher","first-page":"984","DOI":"10.3390\/medicina44120123","article-title":"Acute toxicity of ibogaine and noribogaine","volume":"44","author":"Kubiliene","year":"2008","journal-title":"Med. Kaunas."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2045125320950567","DOI":"10.1177\/2045125320950567","article-title":"The therapeutic potential of microdosing psychedelics in depression","volume":"10","author":"Kuypers","year":"2020","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1038\/s44220-025-00463-x","article-title":"Magnesium\u2013ibogaine therapy effects on cortical oscillations and neural complexity in veterans with traumatic brain injury","volume":"3","author":"Lissemore","year":"2025","journal-title":"Nat. Ment. Health"},{"key":"B19","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3109\/15563650.2016.1138226","article-title":"How toxic is ibogaine?","volume":"54","author":"Litjens","year":"2016","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15288\/jsad.23-00011","article-title":"Traditional medicine, culture, and psychedelic science: new pathways for recovery from substance use disorders","volume":"85","author":"Loizaga-Velder","year":"2024","journal-title":"J. Stud. Alcohol Drugs"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1080\/17425255.2021.1944099","article-title":"Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse","volume":"17","author":"Luz","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.3390\/ijms24021329","article-title":"The bright side of psychedelics: latest advances and challenges in neuropharmacology","volume":"24","author":"Mastinu","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1177\/0960327107087802","article-title":"Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review","volume":"27","author":"Maciulaitis","year":"2008","journal-title":"Hum. Exp. Toxicol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3389\/fphar.2019.00193","article-title":"Ibogaine administration modifies GDNF and BDNF expression in brain regions involved in mesocorticolimbic and nigral dopaminergic circuits","volume":"10","author":"Marton","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1111\/j.1749-6632.1998.tb08242.x","article-title":"Medication development of ibogaine as a pharmacotherapy for drug dependence","volume":"844","author":"Mash","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/j.1749-6632.2000.tb05213.x","article-title":"Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures","volume":"914","author":"Mash","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"529","DOI":"10.3389\/fphar.2018.00529","article-title":"Ibogaine detoxification transitions opioid and cocaine abusers between dependence and abstinence: clinical observations and treatment outcomes","volume":"9","author":"Mash","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.2174\/1570159X21666221017085612","article-title":"Ibogaine\/noribogaine in the treatment of substance use disorders: a systematic review of the current literature","volume":"21","author":"Mosca","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1080\/00952990.2017.1310218","article-title":"Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study","volume":"44","author":"Noller","year":"2018","journal-title":"Am. J. Drug Alcohol Abuse"},{"key":"B30","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/0306-4522(93)90500-f","article-title":"Degeneration of purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline","volume":"55","author":"O'Hearn","year":"1993","journal-title":"Neuroscience"},{"key":"B31","doi-asserted-by":"publisher","first-page":"572","DOI":"10.3390\/brainsci15060572","article-title":"The potential role of psilocybin in traumatic brain injury recovery: a narrative review","volume":"15","author":"Palmer","year":"2025","journal-title":"Brain Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"111448","DOI":"10.1016\/j.pnpbp.2025.111448","article-title":"Examining the potential of psilocybin and 5-MeO-DMT as therapeutics for traumatic brain injury","volume":"141","author":"Plummer","year":"2025","journal-title":"Prog. Neuro-Psychopharmacology Biol. Psychiatry"},{"key":"B33","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0099-9598(08)60027-9","article-title":"Chapter 3 - pharmacology of ibogaine and ibogaine-related alkaloids","volume":"52","author":"Popik","year":"1999","journal-title":"Alkaloids Chem. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"111624","DOI":"10.1016\/j.pnpbp.2026.111624","article-title":"Psychedelics for the management of symptoms of traumatic brain injury: findings from the global psychedelic survey","volume":"145","author":"VanderZwaag","year":"2026","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B35","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/j.1749-6632.1997.tb46187.x","article-title":"Assessment of neurotoxicity from potential medications for drug abuse: ibogaine testing and brain imaging","volume":"820","author":"Vocci","year":"1997","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2174\/1874473708666150107120011.PMID:25563446","article-title":"Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, peyote, ibogaine and ayahuasca","volume":"7","author":"Winkelman","year":"2014","journal-title":"Curr. Drug Abuse Rev."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1840956\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:11:22Z","timestamp":1780474282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1840956\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":37,"alternative-id":["10.3389\/fphar.2026.1840956"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1840956","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"article-number":"1840956"}}