DMT and harmine responses in monocyte-derived microglia- like cells from patients with treatment-resistant depression

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.