Effects of Dimethyltryptamine in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in
      recreational and spiritual settings. DMT can be used as a tool to induce an altered state of
      consciousness of interest in psychological and psychiatric research. DMT is rapidly
      metabolized by monoamine oxidase (MAO) A. Therefore, it is inactive when administered orally
      and has a very short duration of action when administered parenterally (<20 min).Therefore,
      an intravenous administration regime including a bolus and maintenance perfusion has been
      proposed to induce a stable and prolonged DMT experience allowing to study the psychological
      and autonomic acute effects of DMT. This administration allows to induce and end an altered
      state safely and quickly. The goal of the present study is to experimentally test different
      intravenous DMT administration schedules to investigate the subjective and autonomic effects
      of DMT in healthy subjects.
    

Detailed description: 
      N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in
      recreational and spiritual settings in the form of Ayahuasca. Similar to lysergic acid
      diethylamide (LSD) or psilocybin, DMT is considered a tool to induce an altered state of
      consciousness of interest in psychological and psychiatric research. Pharmacologically, DMT
      interacts with the serotonin 5-HT2A receptor similar to other classic hallucinogens including
      LSD and psilocybin. The main difference of DMT in comparison with LSD or psilocybin is
      inactivity when administered orally without monoamine oxidase (MAO) A inhibition and its
      short action when administered intravenously or by inhalation. In Ayahuasca, DMT is consumed
      iin combination with harmala alkaloids that inhibit MAO to increase the oral bioavailability
      of DMT and to prolong its action after oral use. Alternatively, an intravenous administration
      regime including a bolus and a one hour maintenance perfusion has been proposed to induce a
      stable and prolonged DMT experience, allowing to study the psychological and autonomic acute
      effects of DMT. Also, the maintenance perfusion administration allows to end an altered state
      of consciousness quickly. In the present study this model will be tested using four modified
      administration schemes. The goal of this study is to experimentally test different
      intravenous DMT administration schedules to investigate the subjective and autonomic effects
      of DMT in healthy subjects. The study is expected to inform researchers on dosing regimes of
      intravenous DMT as a tool to examine alterations of the mind and is of interest for
      psychology and psychiatry. This study does not intend to provide any therapeutic benefit for
      the participants. Currently, no study has validly determined the elimination half-life of DMT
      and other pharmacokinetic parameters. The key aim is to test the dose-response of DMT as well
      as the difference between the loading dose bolus and no-bolus perfusion conditions regarding
      pharmacokinetic, subjective, and autonomic effects including psychological and physical
      tolerability.
    

Intervention name(s): Dimethyltryptamine (DMT); Saline
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous DMT bolus and/or DMT maintenance perfusion over 90 min; Intravenous saline bolus and/or saline maintenance perfusion over 90 min
Intervention MeSH terms: N,N-Dimethyltryptamine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double-blind, placebo-controlled, 5-period cross-over design with 4 different doses of DMT and placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science