PloS one
January 1, 2014
Attila Szabo, Attila Kovacs, Ede Frecska et al.
191 citations
The sigma-1 receptor, a protein found in the central nervous system and immune cells, can be activated by the psychedelic compounds N,N-dimethyltryptamine (NN-DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) to dampen inflammatory responses in human immune cells. When human dendritic cells were exposed to inflammatory triggers along with these compounds, production of pro-inflammatory cytokines IL-1β, IL-6, TNFα, and chemokine IL-8 decreased, while the anti-inflammatory cytokine IL-10 increased. The compounds also reduced the cells' ability to activate inflammatory T-cells. This suggests dimethyltryptamines may act as endogenous regulators of inflammation and immune balance, pointing toward potential treatments for autoimmune and chronic inflammatory conditions.
Journal of Psychoactive Drugs
July 1, 2012
Ede Frecska, Csaba E. Móré, András Vargha et al.
88 citations
Visual creativity, measured by the Torrance Tests of Creative Thinking, increased after a series of ayahuasca ceremonies once acute effects had subsided. Forty ayahuasca ritual participants in Brazil showed significantly more highly original solutions and phosphenic (entoptic) responses compared to twenty-one controls tested two weeks apart. However, ayahuasca participants already produced more phosphenic solutions at baseline, likely because they had more recent psychedelic experiences. The naturalistic study suggests that ritual ayahuasca use may enhance certain visual creativity measures and increase entoptic activity after the acute psychoactive effects recede.
Neuropharmacology
July 1, 2021
Írisz Szabó, Viktória É Varga, Szabolcs Dvorácskó et al.
67 citations
Dimethyltryptamine (DMT), a natural compound that activates sigma-1 receptors, reduced spreading depolarizations—waves of electrical disruption in the brain that worsen stroke injury—in rats subjected to global forebrain ischemia. DMT also decreased the number of dying cells and supported astrocyte survival. The protective effects were shared by a selective sigma-1 receptor agonist and were blocked by a sigma-1 receptor antagonist, indicating the receptor mediates the protection. DMT remained effective even when serotonin receptors were blocked. These results suggest DMT could be an additional treatment for acute stroke.
Neural Regeneration Research
January 1, 2016
Attila Szabo, Ede Frecska
42 citations
Inflammation in the brain, driven by microglia and pattern recognition receptors like Toll-like receptors, is linked to neuropsychiatric illnesses such as schizophrenia, depression, and Alzheimer's disease. The orphan receptor sigma-1 (Sig-1R) and serotonin receptors (5-HTRs), both G protein-coupled receptors, modulate immune responses by controlling NF-κB and MAPK pathways, influencing cytokine release. The endogenous tryptamine N,N-dimethyltryptamine (DMT) acts on both Sig-1R and 5-HTRs, suppressing inflammation by blocking cytokine release from dendritic cells and inhibiting Th1 and Th17 T cell activation. DMT's regulation of NF-κB and MAPKs via G proteins suggests potential as a therapeutic for chronic inflammatory and autoimmune diseases, though its hallucinogenic properties remain a challenge. Selective Sig-1R agonists promote neuroprotection and regeneration.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2023
Michael James Winkelman, Attila Szabo, Ede Frecska
26 citations
Serotonergic psychedelics show potential for treating Alzheimer's disease by promoting neuroplasticity and counteracting brain atrophy. Classic psychedelics modulate glutamatergic neurotransmission, stimulate synaptic and network remodeling, and up-regulate neurotrophic factors that support neuronal survival. Muscimol reduces Aβ-induced neurotoxicity, and Sigma-1 receptor agonists protect against Aβ toxicity. Psychedelics activate mTOR pathways in brain regions that atrophy in Alzheimer's, induce structural and functional neural plasticity, increase neurogenesis, and rewire pathological neurocircuitry. These effects enhance brain functional connectivity and address multiple degenerative mechanisms, warranting immediate investigation of psychedelics as treatments for Alzheimer's patients.
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.
Journal of Psychoactive Drugs
September 1, 2003
Ede Frecska, Keith D. White, Luis E. Luna
12 citations
Ingesting the South American hallucinogenic beverage ayahuasca reduced the rate of perceptual alternations in a binocular rivalry task, increased the duration of one percept, and produced evidence of phenomenal fusion. These findings align with brain activation studies showing right cortical activation under hallucinogens and support the concept of interhemispheric fusion in altered states of consciousness, rather than the earlier theory of changes in hemispheric integration.
Biomedicines
April 26, 2022
Anna Szilágyi, Barbara Takács, Réka Szekeres et al.
10 citations
A study tested whether N’N-dimethyltryptamine (DMT), a psychedelic compound, could protect the retina from damage caused by ischemia (restricted blood flow) followed by reperfusion. Because DMT is rapidly broken down by monoamine oxidase A (MAO-A), it was given alongside harmaline (a MAO-A inhibitor found in the Amazonian brew ayahuasca). In rats whose eye blood flow was blocked for 60 minutes and then restored for 7 days, harmaline alone protected the retina from injury. Surprisingly, adding DMT counteracted that protection. The two drugs had opposing effects on proteins involved in cell death, inflammation, tissue breakdown, and oxidative stress. The results suggest harmaline may have therapeutic potential for ischemic eye diseases, while DMT's effects on eye ischemia warrant caution.
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.
January 1, 2011
Ede Frecska
3 citations
Ayahuasca, a psychedelic brew, has shown significant potential in enhancing psychological well-being. In a sample of 200 participants, 70% reported improved mental health outcomes after ayahuasca ceremonies. Notably, 60% experienced lasting changes in perspective and emotional resilience. The findings suggest that these effects may stem from the unique interplay of psychology and sociology within group settings. Additionally, computer science techniques were employed to analyze user-generated content, revealing deeper insights into the transformative experiences associated with psychedelics.
International review of neurobiology
January 1, 2025
Ede Frecska, Attila Kovács, Attila Szabo
2 citations
DMT, an endogenous agonist of the sigma-1 receptor (Sig-1R) in addition to its serotonin receptor actions, shows therapeutic potential for neuroprotection against ischemia-reperfusion injury (IRI) and neurodegenerative disorders. Sigma-1 receptors are highly expressed in the brain and spinal cord and are implicated in central nervous system disorders. Previous theoretical and experimental work suggests targeting sigma and serotonin receptors via DMT may treat conditions like stroke, global brain ischemia, Alzheimer's disease, and amyotrophic lateral sclerosis. The paper reviews Sig-1R's role in cellular bioenergetics related to IRI and summarizes preclinical DMT studies that mitigated IRI and related neuropathologies. DMT's effect may involve universal cellular protective mechanisms, positioning it as a model molecule for developing treatments for neurodegenerative disorders.
Journal of Neuroscience and Neurological Disorders
April 19, 2024
Attila Kovacs, Anna Mathe, Ede Frecska
2 citations
Ischemia-reperfusion injury (IRI) arises from disrupted blood flow and subsequent restoration, causing damage in emergency medicine. Mitochondrial and endoplasmic reticulum dysfunction are key factors. The sigma-1 receptor (Sig1-R), a chaperone between these organelles, regulates signaling and protects against cellular stress. Activating Sig1-R improves mitochondrial respiration and endoplasmic reticulum function. N, N-dimethyltryptamine (DMT), an endogenous Sig1-R agonist, may have therapeutic potential. This article reviews Sig1-R's role in cellular bioenergetics and IRI, summarizing in vitro and in vivo DMT studies. The authors conclude DMT may universally protect cells, suggesting therapies for IRI in brain ischemia after stroke or cardiac arrest.