Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea,...
Abstract N,N -dimethyltryptamine (DMT) is a serotonergic psychedelic that is known for its short-lasting effects when administered intravenously. Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking. We...
5-methoxy-N,N-dimethyltrytpamine (5-MeO-DMT) analogs are used as recreational drugs, but they are also being developed as potential medicines, warranting further investigation into their pharmacology. Here, we investigated the neuropharmacology of 5-MeO-DMT and several of its N-alkyl, N-allyl, and 2-methyl analogs, with three major aims: 1) to determine in vitro receptor profiles for the...
This dissertation explores the lasting impact of psychedelic use on brain networks, ranging from basic sensory processing to abstract mystical experiences. Recent research has highlighted the potential of these substances for treating psychiatric disorders, with therapeutic effects persisting weeks after a single dose. We focus on serotonergic psychedelics such as psilocybin and LSD, which are...
Recent advancements in the therapeutic use of psychedelic compounds, particularly 5-MeO-DMT and DMT, have demonstrated significant potential in treating various mental health disorders. This Patent Highlight evaluates findings from multiple recent patents that explore novel applications of these compounds, including their use in severe psychiatric conditions such as depression, anxiety, and...
The "wine of jurema", used in ancient Brazilian shamanic rituals, is rich in N,N-dimethyltryptamine (DMT), a naturally occurring tryptamine like serotonin and melatonin. Widely found in plants and animals, DMT is the main component of some botanical tisanes used for centuries as a channel of communication with the otherworld (1, 2). Despite being classified as a "classical psychedelic” (2-4),...
The first sentence in the Limitations section of the abstract for “Psychedelic Therapy: A Primer for Primary Care Clinicians - N,N-Dimethyltryptamine and Ayahuasca” stated:“There has only been a single published double-blind randomized controlled trial on ayahuasca and 2 on DMT.” The end of this sentence is incorrect. There are no published, double-blind randomized controlled trials on DMT as...
Abstract 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychedelic drug known for its uniquely profound effects on subjective experience, reliably eradicating the perception of time, space, and the self. However, little is known about how this drug alters large-scale brain activity. We collected naturalistic electroencephalography (EEG) data of 29 healthy individuals before and after...
RSC Medicinal ChemistryOctober 7, 2024Andreas Simoens, Andreas Dejaegere, Marthe Vandevelde et al.2 citations
Herein, we describe the continuous flow synthesis and in-line extraction of N,N-dimethyltryptamine (DMT) and several of its analogues using a Fischer indole reaction, along with a larger gram scale synthesis (4.75 g) of the model compound. These products could then be quickly transformed into their respective fumarate salts, making them easier to handle and stable for long time storage using a...
The potent hallucinogen N,N-dimethyltryptamine (DMT) has garnered significant interest in recent years due to its profound effects on consciousness and its therapeutic psychopotential. DMT is an integral (but not exclusive) psychoactive alkaloid in the Amazonian plant-based brew ayahuasca, in which admixture of several β-carboline monoamine oxidase A (MAO-A) inhibitors potentiate the activity...
Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain...
Novel Psychoactive Substances (NPS) derived from tryptamines has been detected in aquatic environments, leading to environmental toxicology concerns. However, the specific toxicological mechanism, underlying these NPS, remains unclear. In our previous work, we used 5-Methoxy-N-isopropyl-N-methyltryptamine (5-MeO-MiPT) as the representative drug for NPS, and found that, 5-MeO-MiPT led to obvious...
To investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), in healthy participants. In all, 44 psychedelic-naïve participants enrolled in the double-blind, placebo-controlled single ascending dose study (1-12 mg BPL-003). Concentrations of 5-MeO-DMT and its...
There is considerable evidence from the literature that psychedelics, such as N,N-dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in...
We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification...
The original version of this Article contained an error in Affiliation 6, which was incorrectly given as ‘Brain Network Dynamics Unit, University of Oxford, Oxford, UK.’ The correct affiliation is listed below:
5-MeO-DMT is a psychedelic substance with a short duration of action and intensive effects. Its therapeutic efficacy and practicality may significantly surpass those of classical psychedelics such as ayahuasca and LSD. This retrospective ethnographic inquiry features a woman in her mid-thirties who witnessed her mother's violent suicide and its bloody aftermath at the age of three. Before and...
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding...
Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. 3×TG-AD transgenic mice were administered with...
The human brain is a complex system, whose activity exhibits flexible and continuous reorganization across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states...