DMT and harmine responses in monocyte-derived microglia- like cells from patients with treatment-resistant depression
Francisco Cid Coelho Pinto, Fátima Cássia Evangelista Oliveira, Hilda Tahim Souza, José Brito Vieira Neto, Isabelle de Fátima Vieira Camelo Maia, Sérgio André Souza Júnior, Fábio Oliveira Silva Ribeiro, Alyne Rodrigues Araujo Nobre, Claudio Costa Dos Santos, Islay Lima Magalhães, Caio Andrade Oliveira, Deysi Viviana Tenazoa Wong, Claudia Do Ó Pessoa, David Freitas Lucena, Maria Francilene Souza Silva, Danielle S. Macêdo
preprint DOI: 10.21203/rs.3.rs-11516239/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Exploratory in vitro laboratory study |
|---|---|
| Sample size | 11 |
| Population | Monocyte-derived microglia-like cells (iMGs) from four healthy controls and seven patients with treatment-resistant depression |
| Interventions | DMT Harmine |
| Dose | DMT 90 µg/mL; harmine 35 µM |
| Duration | LPS 24 h; DMT or harmine 3 h |
| Measures | IL10, IL6, CD86, CD200, high-content imaging |
| Topics | Depression DMT |
| Key points | DMT increased IL10 expression in TRD-derived iMGs relative to LPS alone (mean difference 0.4088; 95% CI 0.1546–0.6629), while neither DMT nor harmine significantly reduced LPS-induced IL6 after adjustment. CD86 and CD200 positivity showed no significant condition effects, and process number showed an overall condition effect without significant drug-versus-LPS contrasts after correction. The authors propose IL10 transcription as a candidate response measure for replication, cautioning that small samples and other limitations preclude inference about disease specificity or clinical efficacy. |
Abstract
Abstract Purpose To examine cytokine, surface-marker, and morphological responses to N, N-dimethyltryptamine (DMT) and harmine in lipopolysaccharide (LPS)-challenged monocyte-derived microglia-like cells (iMGs) from patients with treatment-resistant depression (TRD).
Methods: This exploratory study used assay-specific subsets of a cohort of four healthy controls and seven patients with TRD. The principal pharmacological assays used TRD-derived iMGs. Parallel cultures were compared under control conditions, LPS alone (100 ng/mL, 24 h), or LPS followed by DMT (90 µg/mL) or harmine (35 µM) for 3 h. Cytokine transcripts and surface-marker positivity were evaluated in four donors, and high-content imaging in three.
Results: DMT increased IL10 expression relative to LPS alone (mean difference, 0.4088; 95% confidence interval, 0.1546–0.6629; Tukey-adjusted p = 0.0134). LPS increased IL6 relative to control (adjusted p = 0.0305), whereas neither compound significantly reduced IL6 after adjustment. CD86 and CD200 positivity showed no significant condition effects. Process number showed an overall condition effect (exact Friedman p = 0.017), without significant drug-versus-LPS contrasts after Holm correction.
Conclusion: IL10 transcription is a candidate response measure for replication. Small donor samples, the absence of matched healthy-control pharmacological assays, and concentration-selection limitations prevent inference about disease specificity, generalized anti-inflammatory activity, or clinical efficacy.
Comparable studies
Other preclinical and animal studies on DMT for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Immunomodulatory and behavioral effects of ayahuasca and N, N-dimethyltryptamine in a rat model of lipopolysaccharide-induced depression. Wistar rats | 2025 | Randomized controlled trial | n = 126 |
| Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model. Male mice exposed to chronic unpredictable mild stress | 2026 | Preclinical animal study | |
| N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine. Male helpless mice (single-housed and group-housed) | 2026 | Animal study | |
| 5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines. Beagle dogs | 2026 | Preclinical animal study | n = 11 |
Citations in the library
Cites 10
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PLoS One 2014
- Metabolism and disposition of N,N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca Drug Testing and Analysis April 19, 2012
- Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression. Neuropsychopharmacology May 1, 2025
- Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca Frontiers in Pharmacology May 2, 2022
and 5 more in the library