We propose a three-phase experimental protocol testing whether the radical pair mechanism (RPM) operates during N,N-dimethyltryptamine (DMT)-induced psychedelicstates at the 5-HT2A receptor. Position-specific isotopic substitution of the ligand (13C at C3a, 15N on indole nitrogen) modifies nuclear spin content without altering molecular geometry, receptor affinity, or metabolic...
Background: Conventional psychological and pharmacological substance abuse treatments are limited to moderate effect sizes and fail to magnify outcomes when combined. Analog psychedelic agents N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) show therapeutic potential for treatment-resistant psychiatric disorders including substance addictions. Methods: This...
Alamia et al. (2020) reported that N,N-dimethyltryptamine (DMT) significantly increases forward (bottom-up) cortical travelling waves, based on surrogate-normalized 2D FFT analysis. We reanalyze the same publicly available EEG dataset (N = 12) using the same method, supplemented by absolute power analysis. Absolute forward wave power decreases under DMT in all 12 subjects at alpha (8–13 Hz) and...
Understanding the toxicity of serotonergic tryptamines is becoming increasingly important from both clinical and forensic perspectives, yet experimental data for these compounds remain extremely limited. Despite their growing medical relevance and widespread non-medical use, there is still no systematic evaluation of their toxicological risks. This study presents the first comprehensive in...
N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that produces short-lived peak effects when administered intravenously as a bolus dose. Initial trials suggested therapeutic effects of DMT in depressive disorders. However, systematic data on dose-dependent pharmacokinetics and acute effects of intravenous bolus DMT administration are currently lacking. We used a double-blind,...
While the limitations of existing treatment options have spurred investigations into the applicability of psychedelic therapies for chronic and treatment-resistant psychological disorders, there remain significant unresolved issues pertaining to how these treatments should be regulated and the implementation of an ethical framework for their widespread delivery in practice. Research...
To our knowledge, this is the first fMRI characterization of 5-MeO-DMT in any species, and it reveals a previously unreported sex difference in psychedelic response. The rapid onset and brief duration of peak effects align with 5-MeO-DMT's unique pharmacological profile and clinical reports.
PsychedelicsMarch 1, 2026A.m Ortiz Bernal, C L Raison, A.m Vargas Prieto et al.
5-methoxy- N,N -dimethyltryptamine (5-MeO-DMT) is a potent, short-acting psychedelic compound found in several South American plant species and in the glandular secretions of Incilius alvarius, a toad native to the Sonoran Desert. While plant-based snuff preparations containing 5-MeO-DMT have documented use in Indigenous Caribbean and South American contexts, recent claims that toad-derived...
Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, suggesting BPL-003 could be beneficial in TRD, warranting investigation in larger controlled trials.
Bufotenin (also spelt as bufotenine) and its methylated derivative, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychedelics that are found in many plants but also excreted by some species of toads. The compounds are regulated differently around the world, and although used in traditional medicine, 20th-century prohibition culture has slowed research into their utility for...
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics as breakthrough therapies for mental disorders. Psychedelics can influence cognitive and emotional processes, showing solid therapeutic potential, particularly in treatment-resistant psychiatric disorders. Amongst the most promising compounds,...
Summarizes preclinical and clinical evidence on ayahuasca—a traditional Amazonian brew combining N, N-Dimethyltryptamine (DMT) and β-carbolines—in treating depression, anxiety, post-traumatic stress disorder, substance use, eating, and personality disorders. Preclinical work shows enhanced neuroplasticity, reduced inflammation, and oxidative stress. Human neuroimaging reveals decreased default...
Emerging evidence supports 5-MeO-DMT as a promising, ultra-short-acting psychedelic for treatment-resistant depression and other psychiatric conditions, warranting larger RCTs.
We carried out a systematic review of modern-era (1990-2025) placebo-controlled studies assessing the acute and post-acute effects of lysergic acid diethylamide, dimethyltryptamine and psilocybin on cognitive and psychological functions. From February 28 to March 19, 2025, PubMed and APA PsychINFO were systematically searched for placebo-controlled studies examining the influence of...
Multiple lines of neuroscientific evidence have converged on a set of closely related findings: the mammalian brain endogenously synthesizes N,N-dimethyltryptamine (DMT) at neurotransmitter-comparable concentrations (Dean et al., 2019); psychedelic compounds suppress the default mode network (DMN) and dissolve ego boundaries (Carhart-Harris et al., 2012; Tagliazucchi et al., 2016); the brain...
Mammalian brain may contain an endogenous pool of the psychedelic substance N,N-dimethyltryptamine (DMT), which may act as a co-transmitter with serotonin (5-HT). We tested the joint hypotheses. We tested the joint hypotheses that endogenous DMT would accumulate in rat brain after inhibiting monoamine oxidase with pargyline, whereas its acidic metabolite 3-indoleacetic acid (3-IAA) would...
Mammalian brain may contain an endogenous pool of the psychedelic substance N,N-dimethyltryptamine (DMT), which may act as a co-transmitter with serotonin (5-HT). We tested the joint hypotheses. We tested the joint hypotheses that endogenous DMT would accumulate in rat brain after inhibiting monoamine oxidase with pargyline, whereas its acidic metabolite 3-indoleacetic acid (3-IAA) would...
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and other psychiatric disorders. A critical safety concern for serotonergic compounds is their potential to induce seizures, as a severe manifestation of serotonin toxicity. The objective of this study was to evaluate the seizure liability of 5-MeO-DMT in a...