5-MeO-DMT Modulates the Immune System Showing Promise for Mood and Neuroinflammatory Conditions
Exploring the Intersection of Psychedelics, Inflammation, and Healing
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), sometimes called the GOD molecule, has been described as a compound of dissolution and renewal. Originally isolated from the Sonoran Desert Toad, it has been found to occur naturally in humans and other organisms. It has gained the interest of researchers in neuroscience, psychiatry, and psychedelic medicine due to its ability to cause rapid and profound imrpovements in measures of depression, anxiety, and stress. It is known to be an intense but short-acting tryptamine psychedelic, with new research showing it may be a potent regulator of the immune system with anti-inflammatory properties.
Psychedelics and the Immune Response
Preclinical studies show that 5-MeO-DMT interacts with the sigma-1 receptor, a molecular chaperone involved in protecting cells from stress, oxidative damage, and inflammation. When this receptor is activated, it regulates calcium signaling, mitochondrial resilience, and cytokine production, which are key processes for immune homeostasis.
In human monocyte-derived dendritic cells, 5-MeO-DMT and its analogue DMT suppress pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8) and increase the anti-inflammatory cytokine IL-10 [1]. This shift leads to reduced T-cell activation and less differentiation into inflammatory Th1 and Th17 effector cells, suggesting a broad, immunosuppressive effect that may be protective in autoimmune and chronic inflammatory states.
Human Evidence: Stress, Inflammation, and Affect
While human studies are still in early trials, findings are compelling. In a 2020 study of healthy volunteers, inhaled 5-MeO-DMT led to a reduction in salivary IL-6 and an increase in cortisol, the body’s own anti-inflammatory hormone. While the participants reported improved mood, reduced anxiety, and reduced stress immediately following the session, the immunological changes occurred independently of the psychedelic intensity and mental health ratings, suggesting that 5-MeO-DMT’s immune effects likely operate through direct biochemical mechanisms.[2]
Mechanisms: Serotonin and Sigma-1 Receptor Pathways
5-MeO-DMT acts on 5-HT1A and 5-HT2A serotonin receptors, both expressed on immune cells [3]. While serotonin signaling at 5-HT2A can sometimes promote inflammation, certain psychedelics can exert anti-inflammatory effectsthrough these same receptors, depending on the cellular context [4].
Proteomic studies in human cerebral organoids reinforce this dual activity. 5-MeO-DMT downregulates inflammatory proteins while enhancing neuroplasticity-related pathways involved in structural repair and resilience [5].
Clinical Implications
Clinically, 5-MeO-DMT has shown promise in rapidly relieving depression and anxiety, with early trials reporting remission within hours after a single session [6]. While most studies focus on mental health, its ability to lower inflammatory markers and modulate stress hormones may also give it potential benefits beyond mood disorders.
Because chronic inflammation underlies many psychiatric and systemic conditions, including autoimmune disease and neurodegeneration, 5-MeO-DMT’s immunomodulatory profile could become a bridge between psychoneuroimmunology and psychedelic medicine.
The Future of Immunopsychedelics
We are only beginning to understand how compounds like 5-MeO-DMT influence immune regulation, stress physiology, and emotional processing. Yet the evidence so far points toward an integrated framework where mind, brain, and immunity are a unified system.
As research continues, 5-MeO-DMT may help illuminate new therapeutic frontiers for autoimmune, neuroinflammatory, and mood disorders, leading to a future where immune modulation and integrated mind-body healing are part of the same treatment plan.
These multi-system effects may help explain the physiological underpinnings of some extraordinary healing accounts reported in shamanic traditions [7]. Case reports of remission in cancer, autoimmune, and trauma-related illnesses following ceremonial healing, suggest that profound psychophysiological shifts, potentially involving immune and sigma-1 receptor pathways, may underlie these outcomes, offering a biological explanation for some of these accounts. While research into this phenomenon is extremely preliminary, it provides a scientific basis for understanding what has been previously regarded as unexplainable, and makes future research into immunopsychedelic mechanisms extremely promising.
References
Szabo A, Kovacs A, Frecska E, Rajnavolgyi E. 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;9(8):e106533. doi:10.1371/journal.pone.0106533.
Uthaug MV, Lancelotta R, Szabo A, et al. Prospective Examination of Synthetic 5-Methoxy-N,N-Dimethyltryptamine Inhalation: Effects on Salivary IL-6, Cortisol Levels, Affect, and Non-Judgment.Psychopharmacology. 2020;237(3):773–785. doi:10.1007/s00213-019-05414-w.
Nichols CD, Foster TP. Serotonin, Immune Function, and Psychedelics as Potent Anti-Inflammatories.International Review of Neurobiology. 2025;181:45–76. doi:10.1016/bs.irn.2025.04.011.
Warren AL, Lankri D, Cunningham MJ, et al. Structural Pharmacology and Therapeutic Potential of 5-Methoxytryptamines. Nature. 2024;630(8015):237–246. doi:10.1038/s41586-024-07403-2.
Dakic V, Minardi Nascimento J, Costa Sartore R, et al. Short Term Changes in the Proteome of Human Cerebral Organoids Induced by 5-MeO-DMT. Scientific Reports. 2017;7(1):12863. doi:10.1038/s41598-017-12779-5.
Reckweg JT, van Leeuwen CJ, Henquet C, et al. A Phase 1/2 Trial to Assess Safety and Efficacy of a Vaporized 5-Methoxy-N,N-Dimethyltryptamine Formulation (GH001) in Patients With Treatment-Resistant Depression.Frontiers in Psychiatry. 2023;14:1133414. doi:10.3389/fpsyt.2023.1133414.
Frecska E, Bokor P, Winkelman MJ. The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization. Frontiers in Pharmacology. 2016;6:35. doi:10.3389/fphar.2015.00035.