Depressive DisordersPTSDSubstance Use Disorders (SUD)Medicinal Chemistry & Drug DevelopmentDMT

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

This comprehensive review (2022) explores the positive and negative aspects of different formulations and routes of administration of DMT. Alternative routes to oral administration in tandem with a monoamine oxidase inhibitor (ayahuasca/pharmahuasca) are discussed as well as the role of endogenous DMT in normal brain function.

Authors

  • Barker, S. A.

Published

Psychopharmacology
meta Study

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 the 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.

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

Introduction

Barker frames the review within the recent resurgence of interest in psychedelics as therapeutics for conditions such as depression, post‑traumatic stress disorder, and substance use disorders, and notes experimental evidence for neuroplastic and neuroprotective effects in vitro and in vivo. The introduction emphasises that route, formulation, and dose critically shape a drug's pharmacology and therefore the therapeutic and research utility of N,N‑dimethyltryptamine (DMT). Prior uncertainty arises from the multiplicity of administration modes (ayahuasca teas, pharmahuasca, IV/IM injection, inhalation, insufflation, transdermal and others) and from the complex pharmacology added by monoamine oxidase inhibitors (MAOIs) present in ayahuasca. This review sets out to examine those formulation and route variables, summarise observed effects across high, low and “micro‑dose” regimens, consider strategies to enable oral DMT without co‑administered MAOIs, and integrate recent in vivo and in vitro findings that bear on the role of endogenous DMT in normal brain function. The scope is broad, spanning ethnobotanical history, clinical and experimental reports of effects, medicinal chemistry approaches to alter metabolism, and evidence regarding endogenous synthesis and concentration in brain tissue.

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