Editing N,N-Dimethyltryptamine (section)

==Research==
Existing research on clinical use of DMT mostly focuses on its effects when exogenously administered as a drug. Although the scientific consensus is that DMT is a naturally occurring molecule in humans, the effects of endogenous DMT in humans (and more broadly in mammals) are still not well understood.<ref>{{cite journal | vauthors = Jiménez JH, Bouso JC | title = Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate | journal = Journal of Psychopharmacology | volume = 36 | issue = 8 | pages = 905–919 | date = August 2022 | pmid = 35695604 | doi = 10.1177/02698811221104054 }}</ref> 

Dimethyltryptamine (DMT), an endogenous ligand of [[sigma-1 receptor]]s (Sig-1Rs), acts against systemic hypoxia. Research demonstrates DMT reduces the number of apoptotic and ferroptotic cells in mammalian forebrain and supports astrocyte survival in an ischemic environment. According to these data, DMT may be considered as adjuvant [[pharmacological therapy]] in the management of acute [[cerebral ischemia]].<ref>{{cite journal | vauthors = Szabó Í, Varga VÉ, Dvorácskó S, Farkas AE, Körmöczi T, Berkecz R, Kecskés S, Menyhárt Á, Frank R, Hantosi D, Cozzi NV, Frecska E, Tömböly C, Krizbai IA, Bari F, Farkas E | title = ''N'',''N''-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain | journal = Neuropharmacology | volume = 192 | page = 108612 | date = July 2021 | pmid = 34023338 | doi = 10.1016/j.neuropharm.2021.108612 | s2cid = 235169696 | doi-access = free }}</ref>

DMT is studied as a potential treatment for [[Parkinson's disease]] in a [[Phases of clinical research|Phase 1/2 clinical trial]].<ref>{{Cite web |vauthors=Pinto V |title=Akome Developing Psychedelic Parkinson's Therapy, Seeks US Patent |date=30 July 2021 |url=https://parkinsonsnewstoday.com/news/akome-developing-psychedelic-parkinsons-therapy-ako004-seeks-us-patent/ |access-date=2022-09-11 |language=en-US |archive-date=2022-09-11 |archive-url=https://web.archive.org/web/20220911123705/https://parkinsonsnewstoday.com/news/akome-developing-psychedelic-parkinsons-therapy-ako004-seeks-us-patent/ |url-status=live }}</ref><ref>{{Cite web |vauthors=Jai |title=Hallucinogenics |date=30 July 2021 |url=https://hallucinogenics.store/product-category/dmt/ |access-date=2022-09-11 |language=en-US |archive-date=2024-05-26 |archive-url=https://web.archive.org/web/20240526041615/https://hallucinogenics.store/product-category/dmt/ |url-status=live }}</ref>

SPL026 (DMT fumarate) is currently undergoing [[Phase II Clinical Trials|phase II clinical trials]] investigating its use alongside supportive psychotherapy as a potential treatment for [[major depressive disorder]].<ref>{{ClinicalTrialsGov|NCT04673383|A Double-blind, Randomised, Placebo-controlled Study of Intravenous Doses of SPL026 (DMT Fumarate), a Serotonergic Psychedelic, in Healthy Subjects (Part A) and Patients With Major Depressive Disorder (Part B) }}</ref> Additionally, a safety study is underway to investigate the effects of combining [[SSRI]]s with SPL026.<ref>{{ClinicalTrialsGov|NCT05553691|An Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics & Exploratory Efficacy of Intravenous SPL026 Drug Product (DMT Fumarate) Alone or in Combination With SSRIs in Patients With Major Depressive Disorder}}</ref>

A small phase 2a [[open-label study|open-label]] [[pilot study]] of [[vaporization|vaporized]] DMT for [[treatment-resistant depression]] has been conducted and published.<ref name="Ramaekers2025">{{cite journal | vauthors = Ramaekers JG | title = Less is more? Antidepressant effects of short-acting psychedelics | journal = Neuropsychopharmacology | volume = 50 | issue = 6 | pages = 875–876 | date = May 2025 | pmid = 40258989 | doi = 10.1038/s41386-025-02103-5 | pmc = 12032289 | pmc-embargo-date = May 1, 2026 }}</ref><ref name="RamaekersReckwegMason2025">{{cite journal | vauthors = Ramaekers JG, Reckweg JT, Mason NL | title = Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression | journal = The American Journal of Psychiatry | volume = 182 | issue = 1 | pages = 33–46 | date = January 2025 | pmid = 39741439 | doi = 10.1176/appi.ajp.20230890 }}</ref><ref name="Falchi-CarvalhoPalhano-FontesWießner2025">{{cite journal | vauthors = Falchi-Carvalho M, Barros H, Bolcont R, Laborde S, Wießner I, ((Ruschi B Silva S)), Montanini D, Barbosa DC, Teixeira E, Florence-Vilela R, Almeida R, de Macedo RK, Arichelle F, Pantrigo ÉJ, Costa-Macedo JV, Arcoverde E, Galvão-Coelho N, Araujo DB, Palhano-Fontes F | title = Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression | journal = Neuropsychopharmacology | volume = 50 | issue = 6 | pages = 895–903 | date = May 2025 | pmid = 40258990 | doi = 10.1038/s41386-025-02091-6 | pmc = 12032144 | pmc-embargo-date = May 1, 2026 }}</ref><ref name="Falchi-CarvalhoBarrosBolcont2025">{{cite journal | vauthors = Falchi-Carvalho M, Barros H, Bolcont R, Laborde S, Wießner I, ((Ruschi B. Silva S)), Montanini D, Barbosa DC, Teixeira E, Florence-Vilela R, Almeida R | title = The Antidepressant Effects of Vaporized <i>N</i>,<i>N</i>-Dimethyltryptamine: An Open-Label Pilot Trial in Treatment-Resistant Depression | journal = Psychedelic Medicine | volume = 3 | issue = 1 | pages = 48–52 | date = March 2025 | pmid = 40337754 | pmc = 12054606 | doi = 10.1089/psymed.2024.0002 | pmc-embargo-date = February 27, 2026 }}</ref> In this study, at day 7 post-dosing, the [[response rate (medicine)|response rate]] was 85.7% and the [[remission rate]] was 57.1%.<ref name="Ramaekers2025" /><ref name="RamaekersReckwegMason2025" /><ref name="Falchi-CarvalhoPalhano-FontesWießner2025" /> The improvements in depressive symptoms persisted for at least 3{{nbsp}}months in most patients, with a response rate of 57.1% and a remission rate of 35.7% at that time point.<ref name="Ramaekers2025" /><ref name="RamaekersReckwegMason2025" /><ref name="Falchi-CarvalhoPalhano-FontesWießner2025" />

Ultra-short-acting psychedelics like DMT and [[5-MeO-DMT]] may be advantageous to longer-acting psychedelics like [[psilocybin]] in terms of practicality for use as therapeutic interventions in clinical settings.<ref name="Ramaekers2025" /><ref name="RamaekersReckwegMason2025" />