Since depression is a common mental illness affecting an estimated 5% of people worldwide, investigators are encouraged to develop effective antidepressants. According to the monoamine-deficiency hypothesis, the underlying pathophysiology of depression is a deficiency of some neurotransmitters (serotonin, norepinephrine, or dopamine) in the central nervous system. The neurotransmitter serotonin...
The psychedelic N,N- dimethyltryptamine (DMT) is in clinical development for the treatment of major depressive disorder. However, when administered via intravenous infusion, its effects are short-lived due to rapid clearance. Here we describe the synthesis of deuterated analogues of DMT with the aim of prolonging the half-life and decreasing the clearance rate while maintaining similar...
Tetrahedron LettersSeptember 13, 2023Karen Ichikawa, Jessica C. Neville, Yihan Yu et al.3 citations
Herein we report the results of a synthetic strategy toward the marine alkaloid convolutindole A, a structurally remarkable derivative of the hallucinogen N,N-dimethyltryptamine (DMT). While attempts to forge an advanced tryptamine intermediate using the Fischer reaction were unsuccessful, an iterative C-H functionalisation strategy proved more fruitful. Subjecting 6-bromoindole to an...
Background: Research in psychedelic medicine has focused primarily on civilian populations. Further study is needed to understand whether these treatments are effective for Veteran populations.Objectives: Here, we examine the effectiveness of psychedelic-assisted therapy among trauma-exposed Special Operations Forces Veterans (SOFV) seeking treatment for cognitive and mental health problems in...
Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase...
The sigma-1 receptor S1R is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum ER membrane MAM, it is considered a “pluripotent modulator” in living systems, plays a critical role in maintaining neuronal homeostasis and acts as a dynamic pluripotent modulator in living systems. Given its specific localization at the MAM, S1R plays a major role regulating...
N,N-dimethyltryptamine (DMT) is the simplest psychedelic tryptamine and is produced naturally by many plant and animal species, including humans. While classical psychedelics, such as lysergic acid diethylamide, or psilocybin, are gaining interest because of their therapeutic potential, DMT has yet to be fully investigated. However, preliminary clinical evidence suggests that DMT and/or...
Background Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD. Methods The Phase 1 part ( n = 8) of the trial investigated two single...
N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-hydroxy-N,N-dimethyltryptamine (bufotenine) are psychedelic tryptamines found naturally in both plants and animals and have shown clinical potential to help treat mental disorders, such as anxiety and depression. Advances in both metabolic and genetic engineering make it possible to engineer microbes as cell...
N,N-dimethyltryptamine (DMT) is a psychedelic compound under development for the treatment of major depressive disorder (MDD). This study evaluated the preclinical and clinical pharmacokinetics and metabolism of DMT in healthy subjects. The physiochemical properties of DMT were determined using a series of in vitro experiments and its metabolic profile was assessed using monoamine oxidase (MAO)...