Recent studies have demonstrated rapid antidepressant effects of inhaled N,N-dimethyltryptamine (DMT); however, long-term effects, including broader well-being dimensions, are sparsely explored across populations.
Aims:
Investigating whether DMT produces sustained improvements in anxiety, life satisfaction, and quality of life, in both healthy individuals and patients with treatment-resistant depression (TRD).
Methods:
In 2 open-label clinical trials, 27 healthy individuals and 14 patients with TRD, respectively, received inhaled DMT in a supportive clinical setting. Repeated assessments were conducted from baseline up to 12 months (only patients), including state anxiety (State-Trait Anxiety Inventory State, STAI-S), life satisfaction (Satisfaction with Life Scale, SWL), and quality of life (World Health Organization Quality of Life Instrument – Abbreviated Version, WHOQOL-BREF, and Spirituality, Religion and Personal Beliefs Module, WHOQOL-SRPB).
Results:
All volunteers showed reduced state anxiety after inhalation up to 1 day afterward. Healthy volunteers reported increased life satisfaction up to 14 days post-administration. Beyond symptom reduction, patients reported increased life satisfaction after 12 months and sustained improvements in quality of life over that period, including Physical Health, Psychological Health, Social Relationships, and Environment (WHOQOL-BREF), and partially Inner Peace and Hope & Optimism (WHOQOL-SRPB).
Conclusion:
These findings suggest that inhaled DMT, combined with psychological support, is associated with recovery of daily functioning and health domains in patients with depression. Although limited by open-label design, lacking placebo control, and modest sample size, this exploratory study highlights the value of incorporating multidimensional outcomes in psychedelic research and DMT’s potential relevance in both clinical and public health contexts.
AdayJSMitzkovitzCMBloeschEK, et al. (2020) Long-term effects of psychedelic drugs: A systematic review. Neuroscience and Biobehavioral Reviews113: 179–189.
2.
AmorimP (2000) Mini International Neuropsychiatric Interview (MINI): Validação de entrevista breve para diagnóstico de transtornos mentais. Brazilian Journal of Psychiatry22(3): 106–115.
3.
Baig-WardKMJhaMKTrivediMH (2023) The individual and societal burden of treatment-resistant depression: An overview. The Psychiatric Clinics of North America46(2): 211–226.
4.
BarbosaPCMizumotoSBogenschutzMP, et al. (2012) Health status of ayahuasca users. Drug Testing and Analysis4(7–8): 601–609.
5.
BarrosHFalchi-CarvalhoMMaiaLO, et al. (2025) Expressive resource in a clinical psychedelic study: Art as an integration tool. Progress in Brain Research296: 131–146.
6.
Carhart-HarrisRLFristonKJ (2019) REBUS and the anarchic brain: Toward a unified model of the brain action of psychedelics. Pharmacological Reviews71(3): 316–344.
7.
CarneiroAMFernandesFMorenoRA (2015) Hamilton depression rating scale and Montgomery-Asberg Depression Rating Scale in depressed and bipolar I patients: Psychometric properties in a Brazilian sample. Health and Quality of Life Outcomes13(1): 42.
8.
CunhaJA (2001) Manual da versão em português das Escalas Beck. Casa do Psicólogo.
9.
De AlmeidaRNGalvãoACMDa SilvaFS, et al. (2019) Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca: Observation from a randomized controlled trial. Frontiers in Psychology10: 1234.
10.
De SousaGMDe Oliveira TavaresVDDe Menezes GalvãoAC, et al. (2022) Moderators of ayahuasca’s biological antidepressant action. Frontiers in Psychiatry/Frontiers Research Foundation13: 1033816.
11.
Dos SantosRGOsórioFLCrippaJAS, et al. (2016) Antidepressive and anxiolytic effects of ayahuasca: A systematic literature review of animal and human studies. Revista Brasileira de Psiquiatria38(1): 65–72.
12.
D’SouzaDCSyedSAFlynnLT, et al. (2022) Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. Neuropsychopharmacology47(10): 1854–1862.
13.
EarleywineMLowFLauC, et al. (2022) Integration in psychedelic-assisted treatments: Recurring themes in current providers’ definitions, challenges, and concerns. Journal of Humanistic Psychology 002216782210858.
14.
Falchi-CarvalhoMWießnerISilvaSRB, et al. (2023) Safety and tolerability of inhaled N,N-Dimethyltryptamine (BMND01 candidate): A phase I clinical trial. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology80: 27–35.
15.
Falchi-CarvalhoMPalhano-FontesFWießnerI, et al. (2025) Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: A phase 2a clinical trial in treatment-resistant depression. Neuropsychopharmacology50(6): 895–903.
16.
Fioravanti-BastosaACMCheniauxELandeira-FernandezJ (2011) Development and validation of a short-form version of the Brazilian State-Trait Anxiety Inventory. Psicologia: Reflexão e Crítica24(3): 485–494.
17.
FleckMPALouzadaSXavierM, et al. (2000) Aplicação da versão em português do instrumento abreviado de avaliação da qualidade de vida ‘WHOQOL-bref’ [Application of the Portuguese version of the abbreviated instrument of quality life WHOQOL-bref]. Revista de Saúde Pública34(2): 178–183.
18.
GoodwinGMAaronsonSTAlvarezO, et al. (2023) Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life. Journal of Affective Disorders327: 120–127.
19.
GouveiaVVMilfontTLDa FonsecaPN, et al. (2009) Life satisfaction in Brazil: Testing the psychometric properties of the satisfaction with life scale (SWLS) in five Brazilian samples. Social Indicators Research90(2): 267–277.
20.
GriffithsRRJohnsonMWCarducciMA, et al. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology30(12): 1181–1197.
21.
HuttenNRPWMasonNLDolderPC, et al. (2021) Low doses of LSD acutely increase BDNF blood plasma levels in healthy volunteers. ACS Pharmacology & Translational Science4(2): 461–466.
22.
Jiménez-GarridoDFGómez-SousaMOnaG, et al. (2020) Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination. Scientific Reports10(1): 4075.
23.
KesslerRCBerglundPDemlerO, et al. (2003) The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R). JAMA: The Journal of the American Medical Association289(23): 3095–3105.
24.
KeyesCLM (2007) Promoting and protecting mental health as flourishing: A complementary strategy for improving national mental health. The American Psychologist62(2): 95–108.
25.
KoolenMWirschingAKredietE, et al. (2025) Assessing the attitudes of Dutch mental health care professionals toward psychedelic-assisted psychotherapy: A cross-sectional exploratory study assessing the attitudes of Dutch mental health care professionals toward. Journal of Psychoactive Drugs1–11. https://doi.org/10.1080/02791072.2025.2508156
26.
LawrenceDWCarhart-HarrisRGriffithsR, et al. (2022) Phenomenology and content of the inhaled N, N-dimethyltryptamine (N, N-DMT) experience. Scientific Reports12(1): 8562.
27.
LoweMXKettnerHJollyDRP, et al. (2024) Long-term benefits to psychological health and well-being after ceremonial use of Ayahuasca in Middle Eastern and North African immigrants and refugees. Frontiers in Psychiatry15: 1279887.
28.
MaiaLODaldegan-BuenoDTófoliLF (2021) The ritual use of ayahuasca during treatment of severe physical illnesses: A qualitative study. Journal of Psychoactive Drugs53(3): 272–282.
29.
MarseilleEMitchellJ (2025) Inappropriate comparator and high pricing in MDMA-assisted therapy for PTSD: A critique of the lykos cost-effectiveness analysis. Psychedelics2: 100002.
30.
MizumotoSDa SilveiraDXBarbosaPCR, et al. (2011) [Hallucinogen Rating Scale (HRS) – A Brazilian version: Translation and cross-cultural adaptation]. Revista de Psiquiatria Clinica38(6): 231–237.
31.
NunesDFaroA (2022) Estrutura Fatorial, Análise de Invariância e Distribuição Social do Patient Health Questionnaire-9 (PHQ-9). Revista Iberoamericana de Diagnóstico y Evaluación–e Avaliação Psicológica62(1): 37.
32.
Palhano-FontesFBarretoDOniasH, et al. (2018) Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: A randomized placebo-controlled trial. Psychological Medicine49(4): 655–663.
33.
PallaviciniCCavannaFZamberlanF, et al. (2021) Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings. Journal of Psychopharmacology35(4): 406–420.
34.
PanziniRGMaganhaCDa RochaNS, et al. (2011) Brazilian validation of the quality of life instrument related to spirituality, religion and personal beliefs. Revista de Saude Publica45(1): 153–165.
35.
Pronovost-MorganCGreenwayKTRosemanL, et al. (2025) An international Delphi consensus for reporting of setting in psychedelic clinical trials. Nature Medicine31(7): 2186–2195.
36.
RaisonCLSanacoraGWoolleyJ, et al. (2023) Single-dose psilocybin treatment for major depressive disorder: A randomized clinical trial. JAMA: The Journal of the American Medical Association330(9): 843–853.
37.
RodriguesRSWießnerIDaldegan-BuenoD, et al. (2025) OAV and 5D-ASC for Brazilian Portuguese: A validation and adaptation study. Journal of Psychopharmacology (Oxford, England)39(9): 990–1006.
38.
RosemanLNuttDJCarhart-HarrisRL (2017) Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Frontiers in Pharmacology8: 974.
39.
RossSBossisAGussJ, et al. (2016) Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial. Journal of Psychopharmacology30(12): 1165–1180.
40.
RuffellSGDCrosland-WoodMPalmerR, et al. (2023) Ayahuasca: A review of historical, pharmacological, and therapeutic aspects. PCN Reports: Psychiatry and Clinical Neurosciences2(4): e146.
41.
RushAJTrivediMHWisniewskiSR, et al. (2008) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. Focus (American Psychiatric Publishing)6(1): 128–142.
42.
RyffCD (2014) Psychological well-being revisited: Advances in the science and practice of eudaimonia. Psychotherapy and Psychosomatics83(1): 10–28.
43.
SanchesRFDe Lima OsórioFDos SantosRG, et al. (2016) Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A SPECT study. Journal of Clinical Psychopharmacology36(1): 77–81.
44.
SarrisJPerkinsDCribbL, et al. (2021) Ayahuasca use and reported effects on depression and anxiety symptoms: An international cross-sectional study of 11,912 consumers. Journal of Affective Disorders Reports4: 100098.
45.
SchenbergEETófoliLFRezinovskyD, et al. (2017) Translation and cultural adaptation of the States of Consciousness Questionnaire (SOCQ) and statistical validation of the Mystical Experience Questionnaire (MEQ30) in Brazilian Portuguese. Archives of Clinical Psychiatry (São Paulo)44(1): 1–5.
46.
SchimmersNBreeksemaJJSmith-ApeldoornSY, et al. (2022) Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: A systematic review. Psychopharmacology239(1): 15–33.
47.
SchrankBBirdVRudnickA, et al. (2012) Determinants, self-management strategies and interventions for hope in people with mental disorders: Systematic search and narrative review. Social Science & Medicine (1982)74(4): 554–564.
48.
SforziniLWorrellCKoseM, et al. (2022) A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials. Molecular Psychiatry27(3): 1286–1299.
49.
SloshowerJZeifmanRJGussJ, et al. (2024) Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: Results from an exploratory placebo-controlled trial. Scientific Reports14(1): 8833.
50.
StrassmanRJQuallsCR (1994) Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Archives of General Psychiatry51(2): 85–97.
51.
StroudJBFreemanTPLeechR, et al. (2018) Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression. Psychopharmacology235: 459–466.
52.
ThomsonSThomacosN (2025) Utilizing psychedelics to enhance well-being: A systematic review. Journal of Psychoactive Drugs1–17.
53.
TimmermannCRosemanLSchartnerM, et al. (2019) Neural correlates of the DMT experience assessed with multivariate EEG. Scientific Reports9(1): 16324.
54.
UthaugMVLancelottaRVan OorsouwK, et al. (2019) A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology236(9): 2653–2666.
55.
Van ElkMYadenDB (2022) Pharmacological, neural, and psychological mechanisms underlying psychedelics: A critical review. Neuroscience and Biobehavioral Reviews140: 104793.
56.
Van OorsouwKToennesSWRamaekersJG (2022) Therapeutic effect of an ayahuasca analogue in clinically depressed patients: A longitudinal observational study. Psychopharmacology239(6): 1839–1852.
57.
ViolAViswanathanGMSoldatkinaO, et al. (2023) Information parity increases on functional brain networks under influence of a psychedelic substance. Journal of Physics: Complexity4(1): 01LT02.
58.
VollenweiderFXPrellerKH (2020) Psychedelic drugs: Neurobiology and potential for treatment of psychiatric disorders. Nature Reviews. Neuroscience21(11): 611–624.
59.
WießnerIFalchiMMaiaLO, et al. (2022a) LSD and creativity: Increased novelty and symbolic thinking, decreased utility and convergent thinking. Journal of Psychopharmacology36(3): 348–359.
60.
WießnerIFalchiMPalhano-FontesF, et al. (2022b) Low-dose LSD and the stream of thought: Increased discontinuity of mind, deep thoughts and abstract flow. Psychopharmacology239(6): 1721–1733.
61.
WießnerIFalchiMPalhano-FontesF, et al. (2023) LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model. Psychological Medicine53(4): 1151–1165.
62.
WießnerIFalchi-CarvalhoMLabordeS, et al. (2025) Safety, tolerability and subjective effects of vaporized N,N-dimethyltryptamine: A randomized double-blind clinical trial. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology97: 16–27.
63.
YangHaoGaoSLiJ, et al. (2022) Remission of symptoms is not equal to functional recovery: Psychosocial functioning impairment in major depression. Frontiers in Psychiatry13: 915689.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
