Renewed clinical interest in psychedelics has drawn attention to their challenging effects, yet most phenomenological and psychometric work derives from psilocybin, leaving cross-substance variation underexplored. This thesis employed codebook thematic analysis to examine challenging experiences across DMT, psilocybin, MDMA, and ketamine, utilising 146 naturalistic accounts collected from...
Abstract Background Serotonergic psychedelics show promise for treating psychiatric disorders, with symptom improvements lasting for weeks after a single dose. Clarifying the neural basis of these effects would benefit from an identification of empirical biomarkers of such lasting shifts in brain function. Resting state EEG offers a rapid (<5 minute), low-cost window into functional brain...
This paper examines dimethyltryptamine (DMT) as one of the most unusual and scientifically provocative psychoactive substances ever studied. It traces DMT’s history from Indigenous Amazonian ayahuasca traditions and Richard Spruce’s nineteenth-century observations to twentieth-century psychedelic science, countercultural fascination, prohibition, and the modern revival of clinical research. The...
Abstract N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) are structurally related tryptamine psychedelics with emerging therapeutic potential, yet their comparative acute pharmacology and longer-term neuroplastic effects remain incompletely defined. Here we show that DMT produces a bell-shaped dose–response curve in the mouse head-twitch response (HTR) assay,...
ABSTRACT N,N -dimethyltryptamine (DMT) is an endogenous psychedelic tryptamine that has recently emerged as a promising therapeutic candidate for acute ischemic stroke. Although DMT consistently reduces infarct size, attenuates neuroinflammation, and improves functional outcome in experimental stroke, the cellular and receptor mechanisms underlying these effects remain poorly understood....
BACKGROUND AND AIMS: This study qualitatively explored psychological change processes as described by participants and therapists within a phase 2a clinical trial evaluating the safety, tolerability, and preliminary efficacy of a single dose of intranasal 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; BPL-003) administered alongside psychological support and manualised cognitive behavioural...
Abstract Adult dentate gyrus neurogenesis and cell proliferation are regulated by multiple physiological inputs, including experience-dependent signals that have been linked to the DNA glycosylase NEIL3. Whether NEIL3 also gates psychedelic-induced proliferation is unknown. Here we tested the effect of a single dose of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), a serotonergic agonist with...
Negative self-referential emotions such as embarrassment and shame play a key role in the psychopathology of psychiatric disorders but are often insufficiently addressed by standard treatments. Psychedelics such as ayahuasca - an Amazonian plant decoction containing the psychedelic N,N-dimethyltryptamine (DMT) and harmala alkaloids, have been proposed to positively modulate self-referential...
High Resolution Image Download MS PowerPoint Slide The psychedelic therapeutics field continues to evolve beyond classical hallucinogens toward integrated treatment platforms that combine optimized pharmacology, drug delivery, and clinical implementation. Recent patent applications disclose selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds,...
The serotonergic psychedelic N,N-dimethyltryptamine (DMT) produces rapid antidepressant effects in preclinical and early clinical studies. Therapeutic benefits have been linked to sustained neural plasticity, including adult neurogenesis in rodents. Whether brief DMT exposure engages proliferative responses in human neural stem cells (NSCs) remains unresolved. Using human iPSC-derived NSCs, we...
BACKGROUND: -dimethyltryptamine (DMT); however, long-term effects, including broader well-being dimensions, are sparsely explored across populations. AIMS: Investigating whether DMT produces sustained improvements in anxiety, life satisfaction, and quality of life, in both healthy individuals and patients with treatment-resistant depression (TRD). METHODS: In 2 open-label clinical trials, 27...
N,N-dimethyltryptamine (DMT) is a bioactive indole alkaloid that could greatly benefit from scalable, fermentation-based production for research and pharmaceutical applications. In this study, we reconstructed a two-step bacterial pathway converting L-tryptophan to DMT via tryptamine. This involved combining a pyridoxal 5'-phosphate (PLP)-dependent tryptophan decarboxylase from the bacterium...
NeuropharmacologyJuly 1, 2026Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.1 citation
N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...
Interest in ayahuasca and its main component, N,N-Dimethyltryptamine (DMT), has currently moved from historical and experimental use into modern clinical development. Yet, current evidence is fragmented, and systematic mapping of trial methods and design choices remains limited. We therefore systematically examined registered interventional trials of DMT, ayahuasca, and DMT combined with...
In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and...
The brain’s ability to rewire itself, neuroplasticity, declines dramatically with age. Children learn faster; adults get stuck in patterns; older adults struggle to adapt. The reasons for this decline remain unclear. In a companion paper (Solis, 2026a), I critically evaluated the broad hypothesis that N,N-dimethyltryptamine (DMT) has endogenous physiological functions. The evidence was found to...
Future PharmacologyJune 23, 2026Gabriella de Souza Gomes Ribeiro, Pieter Annaert, Frederico Severino Martins et al.
Background/Objectives: In this study, we present an analysis of ayahuasca, a psychedelic preparation containing N,N-dimethyltryptamine (DMT) and β-carbolines, such as harmine (HRM), a reversible monoamine oxidase A (MAO-A) inhibitor that enables the oral bioavailability of DMT. CYP2D6 is a highly polymorphic enzyme associated with interindividual variability in drug exposure, but its influence...
-dimethyltryptamine (DMT). Overall, the data indicate that 4-Br-DMT has a serotonergic profile without psychedelic-like effects in mice but has a reduced safety profile compared to psilocin and DMT.
The ongoing psychedelic renaissance has prompted a renewed search for novel drugs based on modifying existing psychedelic motifs. In this study, a synthesis of 4-bromo-N,N-dimethyltryptamine (4-Br-DMT) was achieved and used as a late-stage intermediate for analog development. Specifically, we were able to synthesize and access novel molecules by forming carbon–carbon bonds at the C4 position...
The human body possesses enzymatic machinery to both synthesize and rapidly degrade N,N-dimethyltryptamine (DMT). This coexistence raises a question: does DMT serve an endogenous function, or is it a metabolic byproduct with no physiological role? DMT is structurally almost identical to serotonin and binds to the same serotonin receptors. Serotonin is universally accepted as a neurotransmitter...