Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT

Abstract

As with all drugs, the route, form, and/or dose of a substance administered or applied can play a defining role in its overall pharmacology and use as a therapeutic. This review will focus on these factors as they relate to the psychedelic N,N-dimethyltryptamine (DMT). It will examine the positive and negative aspects of different formulations and routes of administration of DMT and the observed effects from such administrations in the form of ayahuasca teas; oral “pharmahuasca”; injections by intravenous (IV) and intramuscular (IM) routes; inhalation, insufflation; and other routes; and high-dose, low-dose, and “micro-dose” effects. The review will consider possible oral route of administration alternatives that would not require concomitant use of a monoamine oxidase inhibitor. The review will then address the current research findings for DMT from in vivo and in vitro studies as well as the possibility that these findings may be revealing the role of endogenous DMT in normal brain function.

New Paradigms of Old Psychedelics in Schizophrenia

“…Emerging hypotheses suggest that psychedelic drugs work through a brain resetting mechanisms and could cure the underlying pathology of neuronal circuitry, which could benefit psychiatric disorders including schizophrenia. Hence, psychedelics currently offer an exciting scientific tool for researchers around the globe to explore new neuropsychiatric approaches for treating a wide range of psychiatric maladies including schizophrenia [ 123 ].…”

“…In recent studies, DMT has been found to be well-tolerated, providing ample opportunities to investigate the potential of DMT. In a recent review, it was proposed that DMT and other psychedelics could play substantial roles in the development, growth, maintenance, and repair of the brain [ 123 ].…”

Application of Deuterated N,N-Dimethyltryptamine in the Potential Treatment of Psychiatric and Neurological Disorders

“…The table below shows results from human hepatocytes assays conducted with D 6 -DMT and D 8 -DMT, which indicated that intrinsic clearance of D 8 -DMT displayed a 2.1 change from that of DMT (SPL026). …”

Classic psychedelics do not affect T cell and monocyte immune responses

“…The so-called "classic psychedelics" comprise tryptamines, such as N,N-dimethyltryptamine (DMT), and psilocybin, lysergamides, such as lysergic acid diethylamide (LSD), and phenethylamines, such as mescaline. A growing body of evidence shows that psychedelics have therapeutic potential for the treatment of various psychiatric disorders such as major depression, anxiety, post-traumatic stress disorder (PTSD) as well as depression and anxiety due to terminal illnesses (4)(5)(6)(7)(8). Moreover, recent in vivo studies in rodents suggest that psychedelics may also exert positive effects on neuropsychiatric diseases and neuronal damage, 10.3389/fpsyt.2023.1042440 such as Alzheimer's Disease and traumatic brain injury (9,10).…”