Abstract Recent studies have sparked renewed interest in the therapeutic potential of psychedelics for treating depression and other mental health conditions. Simultaneously, the novel psychoactive substances (NPS) phenomenon, with a huge number of NPS emerging constantly, has changed remarkably the illicit drug market, being their scientific evaluation an urgent need. Thus, this study aims to...
Psychedelics are being increasingly examined for their therapeutic potential in mood disorders. While the acute effects of ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) last over several hours, inhaled N,N-Dimethyltryptamine (DMT) effects last around 10 min, which might provide a cost- and time-effective alternative to the clinical application of oral psychedelics. We aimed at...
A recent report by Chen et al. describes the discovery of RmNMT, a highly active and promiscuous tryptamine N-methyltransferase from the cane toad, Rhinella marina. N,N-dimethyltryptamine derivatives produced by this enzyme were then evaluated for their potential to serve as next-generation treatments for mental health disorders.
PsychoactivesFebruary 26, 2024Frankie A. Colosimo, Philip Borsellino, Reese I. Krider et al.8 citations
The human brain is an extraordinarily complex organ responsible for all aspects of cognition and control. Billions of neurons form connections with thousands of other neurons, resulting in trillions of synapses that create a vast and intricate network. This network is subjected to continuous remodeling that adapts to environmental and developmental changes. The resulting neuroplasticity is...
World FuturesFebruary 17, 2024Azul Delgrasso4 citations
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychedelic and entheogenic compound that has been used for centuries by Indigenous Peoples in the Amazon, Caribbean, and more recently in communities in Northern Mexico in ceremonial practices and to connect with nature. In recent years, there has been growing interest in 5-MeO-DMT to treat mental health conditions such as depression, anxiety...
Ayahuasca is a beverage used in Amazonian traditional medicine and it has been part of the human experience for millennia as well as other different psychoactive plants. Although Ayahuasca has been proposed as potentially therapeutic as an anxiolytic and antidepressant, whilst no studies have been carried out so far investigating their direct effect on brain emotional processing. This study...
ACS Medicinal Chemistry LettersFebruary 8, 2024Navoda Jayakodiarachchi, Mallory A Maurer, Daniel C Schultz et al.6 citations
Herein, we report the synthesis and characterization of a novel set of substituted indazole-ethanamines and indazole-tetrahydropyridines as potent serotonin receptor subtype 2 (5-HT2) agonists. Specifically, we examine the 5-HT2 pharmacology of the direct indazole analogs of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and related serotonergic tryptamines, and highlight the need for rigorous...
Abstract Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin’s acute effects (4–6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting...
Abstract The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description of their acute effects. We used a time-dependent whole-brain model to reproduce large-scale brain dynamics measured with fMRI from 15 volunteers under 20 mg intravenous N,N-Dimethyltryptamine (DMT), a short-acting psychedelic. To capture its transient effects, we...
There is a growing interest in the medical use of psychedelic substances, as preliminary studies using them for psychiatric disorders have shown positive results. In particular, one of these substances is N, N-dimethyltryptamine (DMT), an agonist serotonergic psychedelic that can induce profound alterations in the state of consciousness. In this work, we use an exploratory tool to reveal...
According to the opponent-process theory of drug addiction, the intake of an addictive substance initiates two processes: a rapid primary process that results in the drug's rewarding effects, and a slower opponent process that leads to the aversive motivational state of drug aftereffects. This aversive state is integral in the desire, pursuit, and maintenance of drug use, potentially leading to...
Abstract Introduction N,N-Dimethyltryptamine (DMT), a naturally occurring psychedelic tryptamine contained in the indigenous ayahuasca brew has shown antidepressant effects. This Phase 2a clinical trial investigates for the first time the efficacy of isolated DMT in treatment-resistant depression (TRD). Methods Six TRD patients participated in an open-label, fixed-order, dose-escalation study,...
In recent years, policymakers have proposed and implemented regulatory changes promoting the deprioritization, decriminalization, or state-level legalization of one or more psychedelic substances, usually referencing data from clinical trials as reasons to support liberalizing drug control policies. As psychedelic policies continue to be drafted, personal possession limits may be considered for...
This study investigated the sense of familiarity attributed to N, N-dimethyltryptamine (DMT) experiences. 227 naturalistic inhaled-DMT experiences reporting a sense of familiarity were included. No experiences referenced a previous DMT or psychedelic experience as the source of the familiarity. A high prevalence of concomitant features discordant from ordinary consciousness were identified:...
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that induces a rapid and transient altered state of consciousness when inhaled or injected via bolus administration. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions. In a within-subjects,...
Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences,...
The knowledge that brain functional connectomes are unique and reliable has enabled behaviourally relevant inferences at a subject level. However, whether such "fingerprints" persist under altered states of consciousness is unknown. Ayahuasca is a potent serotonergic psychedelic which produces a widespread dysregulation of functional connectivity. Used communally in religious ceremonies, its...
The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of...
Psychedelic agents have regained the attention of pharmaceutical companies as promising treatments for depressive episodes. 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), an atypical psychedelic, is emerging as a potentially effective, novel rapid-acting antidepressant. In this systematic review, we analyze the safety and tolerability evidence from clinical trials. Following the Preferred...
The modulation of social cognition is suggested as a possible mechanism contributing to the potential clinical efficacy of psychedelics in disorders involving socio-emotional and reward processing deficits. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) can be used to detect changes in brain connectivity during psychedelic-induced states. Thus, this pharmacoimaging study...