Frontiers in Neuroscience
September 14, 2016
Attila Szabó, A. Kovács, Jordi Riba et al.
18 citations
N,N-dimethyltryptamine (DMT), an endogenous hallucinogen found in the human brain, activates the sigma-1 receptor (Sig-1R), an intracellular chaperone that helps manage cellular stress. This study tested whether DMT protects brain cells from hypoxia by activating Sig-1R. In cultured human cortical neurons, macrophages, and dendritic cells exposed to severe hypoxia (0.5% O2), DMT robustly increased cell survival through Sig-1R activation. This effect was linked to decreased expression and function of hypoxia-inducible factor 1 alpha (HIF-1α), suggesting DMT alleviates hypoxic stress independently of HIF-1. The results indicate DMT may be endogenously produced during stress to protect the brain from hypoxic or ischemic damage.
Science advances
August 15, 2025
Marcell J László, Judit P Vigh, Anna E Kocsis et al.
9 citations
In a rat stroke model, DMT reduces brain damage by decreasing swelling, restoring the blood-brain barrier, and shifting the body toward an anti-inflammatory state. DMT also suppresses inflammatory signals from brain and immune cells via the sigma-1 receptor. These effects suggest DMT could complement existing stroke therapies.
bioRxiv (Cold Spring Harbor Laboratory)
April 12, 2026
Ibrahim A. Akkouh, Jordi Requena Osete, N. W. Steen et al.
Activating GABA-A receptors with muscimol, a non-classic psychedelic, suppresses inflammatory signaling and promotes neuroplasticity in human cortical spheroids and astrocytes derived from patients with schizophrenia. Inflammatory stimulation triggered interferon-responsive gene programs, with astrocytes acting as key mediators. Muscimol reduced proinflammatory cytokine secretion, attenuated interferon signaling, and upregulated neuroplasticity-related genes such as NTRK2 and ELK1. It also restored impaired glutamate uptake in schizophrenia-derived astrocytes. These effects depended on GABA-A receptor activation. Proteomic analyses of spheroids and human brain tissue confirmed baseline dysregulation of GABAergic and neurotrophin signaling in schizophrenia, supporting the therapeutic potential of targeting astrocyte GABAergic signaling to restore neural homeostasis.