Effects of Dimethyltryptamine in Healthy Subjects

DMT

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.

Intervention / Treatment

Double-blind, placebo-controlled, 5-period cross-over design with 4 different doses of DMT and placebo
  • Dimethyltryptamine (DMT) (DRUG)
    Intravenous DMT bolus and/or DMT maintenance perfusion over 90 min
  • Saline (DRUG)
    Intravenous saline bolus and/or saline maintenance perfusion over 90 min

Condition or Disease

  • Healthy

Phase

  • Phase 1

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 25 Years to 65 Years
    Enrollment: 31 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Basic Science

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Jun 18, 2021 ACTUAL
    Primary Completion: Aug 29, 2022 ACTUAL
    Completion Date: Sep 22, 2022 ACTUAL
    Study First Posted: Apr 20, 2020 ACTUAL
    Results First Posted: Aug 30, 2020
    Last Updated: Oct 10, 2022

    Sponsors / Collaborators

    Lead Sponsor: University Hospital, Basel, Switzerland
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Basel, Basel-Stadt, Switzerland

    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.

    Participant Groups

    • Bolus of 0 mg DMT + perfusion of 0 mg/min DMT over 60 min, resulting in a total dose of 0 mg 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.

    • 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.

    • Intravenous bolus of 0 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 90 mg 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.

    Eligibility Criteria

    Sex: All
    Minimum Age: 25
    Maximum Age: 65
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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)

    Primary Outcomes

    • 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

    • 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 Outcomes

    • 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

    • 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")

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

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

    • Assessed 21 times on each study day via blood samples

    • Assessed 21 times on each study day via blood samples

    • Assessed twice on each study day via blood samples

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

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

    • Assessed via Freiburger Personality Inventory (FPI)

    • Assessed via Saarbrücker Personality Questionnaire (SPF)

    • 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"

    • 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"

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

    • Assessed via Defense Style Questionnaire (DSQ-40)

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

    More Details

    NCT Number: NCT04353024
    Acronym: DMT
    Other IDs: BASEC 2020-00376
    Study URL: https://clinicaltrials.gov/study/NCT04353024
    Last updated: Sep 29, 2023