MedPath

Effects of Dimethyltryptamine in Healthy Subjects

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT04353024
Lead Sponsor
University Hospital, Basel, Switzerland
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
31
Inclusion Criteria
  • Age between 25 and 65 years old
  • Sufficient understanding of the German language
  • Understanding of procedures and risks associated with the study
  • Willing to adhere to the protocol and signing of the consent form
  • Willing to refrain from the consumption of illicit psychoactive substances during the study
  • Abstaining from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
  • Willing not to operate heavy machinery within 6 h of DMT administration
  • Willing to use double-barrier birth control throughout study participation
  • Body mass index between 18-29 kg/m2
Exclusion Criteria
  • Chronic or acute medical condition
  • Current or previous major psychiatric disorder
  • Psychotic disorder or bipolar disorder in first-degree relatives
  • Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
  • Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
  • Pregnancy or current breastfeeding
  • Participation in another clinical trial (currently or within the last 30 days)
  • Use of medication that may interfere with the effects of the study medication
  • Tobacco smoking (>10 cigarettes/day)
  • Consumption of alcoholic beverages (>20 drinks/week)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Low doseDimethyltryptamine (DMT)Intravenous bolus of 0 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 54 mg DMT.
High dose with bolusDimethyltryptamine (DMT)Intravenous bolus of 25 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 115 mg DMT.
PlaceboSalineBolus of 0 mg DMT + perfusion of 0 mg/min DMT over 60 min, resulting in a total dose of 0 mg DMT.
High doseSalineIntravenous bolus of 0 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 90 mg DMT.
Low doseSalineIntravenous bolus of 0 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 54 mg DMT.
Low dose with bolusDimethyltryptamine (DMT)Intravenous bolus of 15 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 69 mg DMT.
High doseDimethyltryptamine (DMT)Intravenous bolus of 0 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 90 mg DMT.
Primary Outcome Measures
NameTimeMethod
Altered states of consciousness profile150 minutes

Assessed once on each study day via 5 Dimensions of Altered States of Consciousness (5D-ASC) scale consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects

Subjective effect ratings over time150 minutes

Assessed 22 times on each study day via Subjective Effect Scale (SES), consisting of 4 questions to be rated on a Likert scale ranging from 1 to 10, with higher ratings indicating stronger effects

Secondary Outcome Measures
NameTimeMethod
Plasma levels of oxytocin60 minutes

Assessed twice on each study day via blood samples

Renal clearance of DMT3 hours

Collected once per study day via one-time interval urine recovery

Effect moderation through personality traits IBaseline

Assessed via NEO-Five-Factor-Inventory (NEO-FFI)

Autonomic effects I150 minutes

Assessed 22 times on each study day via systolic and diastolic blood pressure, Emax

Plasma levels of blood-derived neurotrophic factor (BDNF)150 minutes

Assessed 21 times on each study day via blood samples

Adverse effects150 minutes

Assessed via the List of Complaints (LC) which covers the emergence of 66 complaints in a yes/no format

Mystical-type experiences150 minutes

Assessed once on each study day via States of Consciousness Questionnaire (SCQ) which measures the emergence and intensity of phenomenons occurring in altered states of consciousness on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely")

Effect moderation through personality trait VBaseline

Assessed via Jankowski Humility Scale (JHS) which measures the personality trait humility through 18 items on a 5-point Likert scale ranging from "not at all" to "strongly"

Effect moderation through personality trait VIIBaseline

Assessed via Defense Style Questionnaire (DSQ-40)

Plasma levels of DMT150 minutes

Assessed 21 times on each study day via blood samples

Effect moderation through personality traits IIIBaseline

Assessed via Saarbrücker Personality Questionnaire (SPF)

Effect moderation through personality trait VIBaseline

Assessed via Arnett Inventory of Sensation Seeking (AISS-d)

Subjective mood ratings150 minutes

Assessed twice on each study day via the Adjective Mood Rating Scale (AMRS) consisting of 60 items to be rated on a 4-point Likert scale, with higher ratings indicating stronger identification with the specific mood

Autonomic effects II150 minutes

Assessed 22 times on each study day via heart rate, Emax

Effect moderation through personality traits IIBaseline

Assessed via Freiburger Personality Inventory (FPI)

Effect moderation through personality trait IVBaseline

Assessed via Elliot Humility Scale (EHS) which measures the personality trait humility through 13 items on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree"

Trial Locations

Locations (1)

University Hospital Basel

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Basel, Basel-Stadt BS, Switzerland

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