Editing Dimethyltryptamine (section)

==Research==
Short-acting psychedelics like DMT and 5-MeO-DMT show rapid and sustained antidepressant effects in treatment-resistant depression, potentially offering a more scalable alternative to psilocybin, though larger controlled trials are needed to confirm efficacy.<ref name="Ramaekers2025">{{cite journal |vauthors=Ramaekers JG |date=May 2025 |title=Less is more? Antidepressant effects of short-acting psychedelics |journal=Neuropsychopharmacology |volume=50 |issue=6 |pages=875–876 |doi=10.1038/s41386-025-02103-5 |pmc=12032289 |pmid=40258989 |pmc-embargo-date=May 1, 2026}}</ref><ref name="RamaekersReckwegMason2025">{{cite journal |vauthors=Ramaekers JG, Reckweg JT, Mason NL |date=January 2025 |title=Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression |url=https://cris.maastrichtuniversity.nl/en/publications/fb3d3cba-472c-42bf-b665-bf9607461199 |journal=The American Journal of Psychiatry |volume=182 |issue=1 |pages=33–46 |doi=10.1176/appi.ajp.20230890 |pmid=39741439}}</ref>

A recent Phase 1/2 clinical trial evaluated the safety, tolerability, pharmacokinetics, and antidepressant effects of SPL026, an intravenous formulation of DMT [[Fumaric acid|fumarate]], in both healthy volunteers and patients with moderate-to-severe major depressive disorder, using randomized, placebo-controlled and open-label dosing protocols.<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>  It found that inhaled 5-MeO-DMT (GH001) was well tolerated and produced rapid antidepressant effects in treatment-resistant depression, with individualized dosing showing the highest remission rates.<ref>{{cite journal | vauthors = James E, Erritzoe D, Benway T, Joel Z, Timmermann C, Good M, Agnorelli C, Weiss BM, Barba T, Campbell G, Baker Jones M, Hughes C, Topping H, Boyce M, Routledge C | title = Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial | journal = Frontiers in Psychiatry | volume = 14 | pages = 1305796 | date = 2023 | pmid = 38274414 | pmc = 10810248 | doi = 10.3389/fpsyt.2023.1305796 | doi-access = free }}</ref>

A Phase 1 open-label study assessed the safety, tolerability, pharmacokinetics, and preliminary efficacy of intravenous SPL026  alone or combined with SSRIs in patients with major depressive disorder whose symptoms were not fully relieved by [[Selective serotonin reuptake inhibitor|SSRIs]].<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>

In a phase 2a open-label trial, inhaled DMT produced rapid, well-tolerated, and sustained antidepressant effects in patients with treatment-resistant depression, showing high response and remission rates within 7 days and lasting up to 3 months.<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>

A single-day, open-label trial found that vaporized DMT produced rapid and sustained antidepressant effects in treatment-resistant depression, with up to 50% of participants maintaining remission one month post-dose.<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>

DMT exists naturally in humans and other animals; it may play significant roles in mammalian physiology—potentially as a neurotransmitter, [[hormone]], and immunomodulator—despite longstanding skepticism based on outdated or flawed evidence.<ref>{{cite journal |vauthors=Jiménez JH, Bouso JC |date=August 2022 |title=Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate |journal=Journal of Psychopharmacology |volume=36 |issue=8 |pages=905–919 |doi=10.1177/02698811221104054 |pmid=35695604}}</ref>