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...
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...
Metabolic EngineeringJune 14, 2026Zachary N. Abrahms, Mohammad Majdi, Siena M. Madsen et al.
Stable, high-level biosynthesis of complex natural products requires precise control of heterologous pathway expression, yet transcriptional architectures optimized on plasmids often fail when transferred to the chromosome. Here, we present ePathIntegrate, a genome-centric pathway engineering strategy that leverages CRISPR-associated transposases (CASTs) to integrate and rebalance multigene...
Approximately 30% of patients treated for major depressive disorder develop treatment-resistant depression (TRD). The STAR*D study demonstrated remission rates decline progressively with each antidepressant failure (37%, 31%, 14%, and 13%, respectively). A single-day individualized dosing regimen of GH001 (synthetic mebufotenin for inhalation) produced rapid, large improvements in depressive...
Classical psychedelics such as N,N -dimethyltryptamine (DMT) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine—mimicking the pharmacological profile of ayahuasca—oral DMT induces a psychedelic experience lasting 4–5 h. While some neuroimaging...
Classical psychedelics such as N,N-dimethyltryptamine (DMT) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine-mimicking the pharmacological profile of ayahuasca-oral DMT induces a psychedelic experience lasting 4-5 h. While some neuroimaging...
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a potent, short-acting psychedelic, induces profound shifts in cognition, affect, and self-awareness. Because language explicitly expresses these domains and voice implicitly conveys them, both may serve as potential 'biomarkers' of behavioural change. This study introduces a novel framework for analysing baseline language and vocal features, pre-...
Parkinson's disease is a progressive neurodegenerative disorder with increasing global prevalence, primarily driven by population ageing. A hallmark of the disease is the degeneration of nigrostriatal dopaminergic neurons, accompanied by marked activation of glial cells and a sustained neuroinflammatory response. Current pharmacological treatments are limited to symptomatic relief and do not...
Parkinson's disease is a progressive neurodegenerative disorder with increasing global prevalence, primarily driven by population ageing. A hallmark of the disease is the degeneration of nigrostriatal dopaminergic neurons, accompanied by marked activation of glial cells and a sustained neuroinflammatory response. Current pharmacological treatments are limited to symptomatic relief and do not...
World FuturesApril 29, 2026Azul Delgrasso, Jay Monger
This article explores how council practice, men’s work, and low-dose 5-MeO-DMT can support the cultivation of transformative leadership in complex, transdisciplinary contexts. Drawing on transformative leadership, integrative transdisciplinarity as an approach to inquiry, and research on transdisciplinary leadership learning, we argue that well-designed relational “containers” can deepen...
Over the past 25 years, the use of 5-MeO-DMT in informal and underground settings has contributed a substantial, yet underrecognized, body of knowledge relating to the efficacy of 5-MeO-DMT in alleviating depressive symptoms. Traditional models of drug development, typically characterized by structured trials and regulatory milestones, rarely consider findings from these alternative routes. The...
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...
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,...
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...
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,...
Emerging evidence supports 5-MeO-DMT as a promising, ultra-short-acting psychedelic for treatment-resistant depression and other psychiatric conditions, warranting larger RCTs.