Experimental neurology • September 1, 2026 • Javier Calleja-Conde, Víctor Echeverry-Alzate, Marina Sanz-sancristobal et al.
In a preclinical model of Parkinson's disease, the compound N,N-dimethyltryptamine (DMT), the main psychoactive ingredient in ayahuasca, reduced neuroinflammation and preserved neurons in the nigrostriatal pathway. Treated animals also showed improvements in behavior. These results suggest DMT may have disease-modifying potential for Parkinson's disease, a progressive neurodegenerative disorder marked by loss of dopaminergic neurons and chronic inflammation, for which current treatments only relieve symptoms.
Psychopharmacology • July 14, 2026 • Helena D Aicher, Joëlle Dornbierer, Luzia Caflisch et al.
A combination of harmine and DMT, the active ingredients in ayahuasca, reduces feelings of embarrassment and shame in healthy men. In a randomized trial with 28 participants, those who received the combination reported significantly less embarrassment when listening to recordings of their own singing compared to those who received a placebo. The treatment also lowered overall shame scores. Harmine alone did not produce these effects. The findings suggest that this compound may help treat psychiatric disorders where negative self-focused emotions play a key role.
ACS Medicinal Chemistry Letters • July 10, 2026 • Anna C. Renner, Robert B. Kargbo
The psychedelic therapeutics field is moving beyond classical hallucinogens to integrated treatment platforms that combine optimized pharmacology, drug delivery, and clinical implementation. Recent patent applications describe selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds, and structured 5-MeO-DMT treatment regimens for depression. These innovations represent a convergence toward scalable, safer, and clinically practical neuropsychiatric therapies that may reshape the future of serotonergic medicine.
Figshare • July 10, 2026 • José Alexandre Salerno, Elizabeth R. Dominguez, Karina Karmirian et al.
A brief 24-hour exposure to the serotonergic psychedelic DMT increases proliferation of human neural stem cells derived from induced pluripotent stem cells. The effect was concentration-dependent, with half-maximal effect at 59.7 nM. DMT treatment also altered trophic gene expression, decreasing neurotrophin-3 while increasing nerve growth factor and brain-derived neurotrophic factor (BDNF) transcripts and intracellular BDNF protein. After DMT was removed, the primed stem cells formed larger neurospheres, with progenitor and early neuronal marker composition matching controls by day 10. These findings demonstrate that brief DMT exposure engages proliferative and neurotrophin-associated responses in human neural stem cells at concentrations consistent with those reported for DMT-induced plasticity in other systems.
ACS chemical neuroscience • July 9, 2026 • José Alexandre Salerno, Elizabeth R Dominguez, Karina Karmirian et al.
Brief exposure to the psychedelic N,N-dimethyltryptamine (DMT) increases proliferation of human neural stem cells derived from induced pluripotent stem cells. A 24-hour DMT treatment boosted cell division in a concentration-dependent way, with half-maximal effect at 59.7 nM, and raised levels of G1 cell-cycle regulators. DMT also altered expression of trophic genes, decreasing neurotrophin-3 while increasing nerve growth factor and brain-derived neurotrophic factor (BDNF) transcripts and intracellular BDNF protein. After DMT was removed, treated stem cells formed larger neurospheres, with progenitor and early neuron markers matching controls by day 10. The findings indicate DMT can engage proliferative and neurotrophin-related responses in human neural stem cells at concentrations linked to plasticity in other systems.
Journal of Psychopharmacology • July 8, 2026 • Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros et al.
Inhaled DMT, combined with psychological support, is associated with reduced state anxiety up to one day after administration in both healthy individuals and patients with treatment-resistant depression. Healthy volunteers reported increased life satisfaction up to 14 days. Patients showed increased life satisfaction after 12 months and sustained improvements in quality of life over that period, including physical health, psychological health, social relationships, and environment, as well as inner peace and hope and optimism. The study is limited by an open-label design, lack of placebo control, and modest sample size.
Zenodo (CERN European Organization for Nuclear Research) • July 2, 2026 • Eugene Catrambone
A unified framework links psychedelic neuropharmacology, microtubule biophysics, and spacetime information theory. It proposes that DMT alters subjective time by modulating microtubule vibrational coherence through 5-HT2A and sigma-1 receptor pathways. A coherence parameter Q scales an informational awareness tensor that couples to a scalar clock field, slowing it and producing time dilation and timelessness. The model integrates biophysical, computational, and field-theoretic levels, generating falsifiable predictions across scales: shifts in microtubule spectra under DMT, entropy and traveling-wave changes in EEG/MEG, and behavioral timing distortions. It expands the connection to the Orch-OR tradition and introduces a mathematical treatment of microtubule coherence within the scalar-clock framework, with status tags marking claims as established, hypothesis, or speculative.
Neuropharmacology • July 1, 2026 • Anne Nathalia De Sousa-silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al. • 1 citation
In helpless mice, the psychedelic compound N,N-dimethyltryptamine (DMT) produced rapid and long-lasting antidepressant effects comparable to the fast-acting antidepressant S-ketamine. DMT at 10 mg/kg reversed escape deficits and reduced immobility in several behavioral tests, with effects lasting up to 8 days, whereas S-ketamine's effects lasted up to 30 hours. DMT also showed anxiolytic-like effects, reversing stress-induced hypolocomotion and increasing open-arm exploration, while S-ketamine did not. Neither drug altered behavior in the novelty-suppressed feeding test. These findings suggest DMT has transdiagnostic therapeutic potential for stress-related disorders.
Zenodo (CERN European Organization for Nuclear Research) • July 1, 2026 • Schüller Thomas
DMT is the fourth classical psychedelic in a series and has five distinguishing features: oral inactivity without an MAO inhibitor; ultra-short duration (minutes) when smoked or injected; ayahuasca as a plant combination (DMT source plus β-carboline MAOI); endogenous occurrence in mammals; and the unique religious legal ruling Gonzales v. O Centro (2006). Chemically, DMT is a tryptamine (like psilocybin and LSD), contrasting with the phenethylamine mescaline. This bilingual full work provides a transdisciplinary scientific overview of DMT and ayahuasca across eight disciplines, with explicit labeling of levels of certainty (confirmed / probable / open).
Clinical pharmacology and therapeutics • July 1, 2026 • Tijana Stojanović, Kent W Nilsson, Robert Fredriksson et al.
The clinical trial landscape for ayahuasca and DMT expanded rapidly after 2020-2021, dominated by early-stage development. Most trials are phase I, primarily sponsored by academic or hospital institutions, and focus on DMT-only administration. Eligibility criteria are conservative, enrolling medically and psychiatrically healthy adults with extensive cardiovascular and psychiatric exclusions. Primary outcomes prioritize acute safety, physiological monitoring, and characterization of subjective altered-states, while disorder-specific symptom endpoints are less common. Publications from depression-focused trials provide preliminary evidence of potential clinical effects, but the field remains constrained by a limited number of indication-specific programs beyond depression.
Proceedings of the National Academy of Sciences of the United States of America • March 28, 2023 • Christopher Timmermann, Leor Roseman, Sharad Haridas et al. • 217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
The International journal on drug policy • January 1, 2021 • Liridona Gashi, Sveinung Sandberg, Willy Pedersen • 170 citations
Bad trips—frightening experiences of losing oneself or going crazy—are common among users of psychedelics. Based on interviews with 50 Norwegian users, most described such episodes but said they could be avoided by following rules based on tacit subcultural knowledge. This knowledge served as symbolic boundary work distinguishing insiders from outsiders. Some rejected the term bad trip entirely, arguing the experience reflected a lack of competence. Crucially, most participants said these unpleasant experiences had been beneficial, sometimes yielding deep existential and life-altering insights. Storytelling transforms bad trips into valuable experiences, serving as a coping mechanism that helps users make sense of frightening episodes and integrate them into their life stories, enabling continued psychedelic use.
Neuropharmacology • May 1, 2020 • Adam L Halberstadt, Muhammad Chatha, Adam K Klein et al. • 274 citations
Serotonergic hallucinogens like LSD cause head twitches in rodents through 5-HT2A receptor activation. This study tested whether the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm correlates with their potencies in rats and humans. Dose-response experiments with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice expanded HTR potency data to 41 compounds. For 36 agents with human data, a strong positive correlation (r = 0.9448) was found between mouse HTR potencies and human hallucinogenic potencies. HTR potencies also correlated with drug discrimination ED50 values in rats trained with LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). These three behavioral effects show consistent potencies linked to 5-HT2A receptor activation, supporting the HTR assay as a predictive preclinical model for hallucinogen potency in humans.
Sci Rep • November 19, 2019 • 325 citations
Intravenous DMT, a fast-acting psychedelic, markedly reduces alpha and beta brain wave power and increases spontaneous signal diversity in the human brain, as measured by EEG. The emergence of delta and theta oscillatory activity correlates with the peak of the subjective experience, especially its eyes-closed visual component. Relationships between changes in subjective experience and brain activity were observed across time, linking specific brain changes to specific aspects of the experience.
PLoS ONE • April 23, 2019 • Roland R. Griffiths, Ethan Hurwitz, Alan K. Davis et al. • 249 citations
Experiences interpreted as personal encounters with God, whether occurring naturally or after taking psychedelic drugs, share striking similarities. In an online survey of over 4,200 people, those who had a nondrug encounter most often called it God, whereas those who had a psychedelic encounter most often called it Ultimate Reality. Regardless of origin, most participants vividly remembered the encounter as involving a conscious, benevolent, intelligent, sacred, eternal, and all-knowing presence. About half of all encounters met criteria for a complete mystical experience. More than two-thirds of self-identified atheists no longer identified as atheist afterward.
Psychopharmacology (Berl) • April 13, 2019 • 198 citations
A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is associated with sustained improvements in life satisfaction and mindfulness-related capacities, along with a reduction in psychopathological symptoms.
Frontiers in Psychology • August 15, 2018 • Christopher Timmermann, Leor Roseman, L. Williams et al. • 228 citations
Near-death experiences (NDEs) share striking phenomenological similarities with the effects of the psychedelic drug DMT. In a placebo-controlled, within-subjects study, 13 healthy participants received DMT and placebo, then completed a standard NDE measure. DMT significantly increased NDE-like features compared to placebo. NDE scores were linked to DMT-induced ego-dissolution and mystical experiences, as well as baseline traits of absorption and delusional ideation. Nearly all NDE features overlapped between DMT-induced experiences and a matched group of actual NDE experiencers. These results indicate a remarkable similarity between the DMT state and NDEs, warranting further research.
Frontiers in Neuroscience • August 6, 2018 • 174 citations
This report reviews historical research on the endogenous hallucinogen N,N-dimethyltryptamine (DMT), covering its biosynthesis and metabolism in the brain and peripheral tissues, detection methods in body fluids and brain, new sites of action, and possible physiological and therapeutic roles. It also addresses evidence for DMT as a putative neurotransmitter. The authors propose future directions: brain mapping of DMT biosynthesis enzymes, further studies of its presence and role in the pineal gland, reconsideration of binding site data, and new administration and imaging studies. They emphasize the need to distinguish the natural role of an endogenous hallucinogen from effects of peripheral administration.
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.
Current drug metabolism • October 1, 2010 • Hong-wu Shen, Xi-ling Jiang, Jerrold C Winter et al. • 171 citations
5-MeO-DMT, a naturally occurring psychoactive drug, is metabolized by the enzyme CYP2D6 into the active metabolite bufotenine and is mainly inactivated by MAO-A. When taken with MAO-A inhibitors like harmaline, deamination is reduced, leading to prolonged exposure to both 5-MeO-DMT and bufotenine. These compounds act together on serotonin systems, potentially causing serotonin toxicity. CYP2D6 also metabolizes harmaline, and genetic variations in this enzyme may alter drug interactions and risks. This review covers the metabolism, pharmacokinetics, and drug-drug interactions of 5-MeO-DMT with harmaline, along with risks of intoxication.
Science • February 13, 2009 • Dominique Fontanilla, Molly Johannessen, Abdol R. Hajipour et al. • 528 citations
The sigma-1 receptor, once mistaken for an opioid receptor, binds many synthetic compounds but not opioid peptides and is now considered an orphan receptor. Its pharmacophore includes an alkylamine core also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion channels in both native cardiac myocytes and heterologous cells expressing sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.
Addiction • December 20, 2006 • Robert S. Gable • 240 citations
A systematic review and interviews with ceremony participants assessed the acute toxicity and psychological risks of ayahuasca, a brew containing dimethyltryptamine (DMT) and β‐carbolines used in religious ceremonies. No animal models tested ayahuasca's acute toxicity or abuse potential, but separate studies of DMT and harmala alkaloids suggest a lethal human dose is probably over 20 times a typical ceremonial dose. Adverse effects may occur with casual use, especially alongside serotonergic substances. DMT can cause aversive reactions or transient psychotic episodes that resolve within hours. There is no evidence of substantial abuse potential, and long-term psychological benefits are documented when used in a well-established social context. The safety margin is comparable to codeine, mescaline, or methadone.
Pharmacopsychiatry • November 1, 2005 • 198 citations
Two classes of hallucinogenic drugs model different aspects of schizophrenia-like symptoms. In a double-blind crossover study, fifteen healthy volunteers received both the serotonin 5-HT2A agonist DMT and the glutamate NMDA antagonist (S)-ketamine. Nine subjects completed both sessions. DMT produced stronger positive symptoms resembling schizophrenia, such as formal thought disorder and inappropriate affect. (S)-ketamine produced stronger negative symptoms, attention deficits, body perception disturbances, and catatonia-like motor phenomena. The findings suggest neither drug model is overall superior; rather, each models distinct symptom profiles: DMT models paranoid-type psychoses, while (S)-ketamine models psychoses with prominent negative and catatonic features.
Archives of General Psychiatry • February 1, 1994 • Ruck J. Strassman • 454 citations
Intravenous DMT produces rapid, intense hallucinogenic effects that peak within two minutes and resolve within half an hour, closely tracking blood levels. At higher doses (0.2 and 0.4 mg/kg), volunteers experienced brightly colored, rapidly moving visual images, a dissociative state with alternating euphoria and anxiety, and a complete replacement of ongoing mental experience. Lower doses (0.05–0.1 mg/kg) primarily caused emotional and bodily sensations, with 0.1 mg/kg producing the least desirable effects. A new Hallucinogen Rating Scale captured dose-related differences better than biological measures, offering a tool for comparing DMT with other agents affecting brain receptors.