Acute Dose-dependent Effects of DMT in Healthy Subjects (DMT DR)

Acute Dose-dependent Effects of DMT in Healthy Subjects: A Placebo-controlled Cross-over Study

N,N-dimethyltryptamine (DMT) is a psychoactive substance with similar effects such as LSD or psilocybin. However, DMT is less well characterized than the latter substances. The present study is a modern randomized cross-over trial, investigating different continuous intravenous DMT dose rates over a broad dose range. Thus, different doses will be tested and related to subjective and autonomic effects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: N,N-Dimethyltryptamine (54 mg); Drug: N,N-Dimethyltryptamine (108 mg); Drug: N,N-Dimethyltryptamine (162 mg); Drug: N,N-Dimethyltryptamine (216 mg); Drug: Placebo; Drug: N,N-Dimethyltryptamine (108 mg) + dose titration

Detailed Description

N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in recreational and spiritual settings (Ayahuasca). DMT is considered 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). In Ayahuasca, DMT is consumed together with harmala alkaloids that inhibit MAO to increase the oral bioavailablitity of DMT and to prolong its action after oral use. Alternatively, an intravenous administration regime including a bolus and maintenance perfusion has been proposed to induce a stable and prolonged DMT experience and is currently being investigated. However, to date no clinical study has investigated dose-response effects over a broad range of different doses of DMT within the same patient. The aim of the present study is to experimentally test different intravenous DMT doses over a broad dose range and investigate the related subjective and autonomic effects in order to establish a precise dose-response relationship of DMT in healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Matthias E Liechti, MD; Phone Number: +41 61 328 68 68; Email: matthias.liechti@usb.ch
• Study Contact Backup: Name: Severin B Vogt, MD; Phone Number: +41 61 328 68 66; Email: severinbenjamin.vogt@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4056
    • Universtity Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age between 25 and 65 years old
2. Sufficient understanding of the German language
3. Understanding of procedures and risks associated with the study
4. Willing to adhere to the protocol and signing of the consent form
5. Willing to refrain from the consumption of illicit psychoactive substances during the study
6. Abstaining from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
7. Willing not to operate heavy machinery within 6 h of DMT administration
8. Willing to use double-barrier birth control throughout study participation
9. Body mass index between 18-29 kg/m2

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
3. Psychotic disorder or bipolar disorder in first-degree relatives
4. Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
5. Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
6. Pregnancy or current breastfeeding
7. Participation in another clinical trial (currently or within the last 30 days)
8. Use of medication that may interfere with the effects of the study medication
9. Tobacco smoking (>10 cigarettes/day)
10. Consumption of alcoholic beverages (>20 drinks/week)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; A Placebo (saline infusion) will be administered.
Experimental: DMT 0.6 mg/min	Drug: N,N-Dimethyltryptamine (54 mg); A dose rate of 0.6 mg/min will be administered
Experimental: DMT 1.2 mg/min	Drug: N,N-Dimethyltryptamine (108 mg); A dose rate of 1.2 mg/min will be administered
Experimental: DMT 1.8 mg/min	Drug: N,N-Dimethyltryptamine (162 mg); A dose rate of 1.8 mg/min will be administered
Experimental: DMT 2.4 mg/min	Drug: N,N-Dimethyltryptamine (216 mg); A dose rate of 2.4 mg/min will be administered
Experimental: DMT 1.2 mg/min + dose titration	Drug: N,N-Dimethyltryptamine (108 mg) + dose titration; A dose rate of 1.2 mg/min will be administered with subsequent patient-guided dose titration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Altered states of consciousness profile (5D-ASC)	5 Dimensions of Altered States of Consciousness (5D-ASC) consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects with higher scores representing more intense effects. Assessed once on each study day	12 months
Subjective effect ratings over time	Participants will be asked by the investigator to repeatedly rate their subjective effects verbally on a Likert scale from 0 to 10 for: "any drug effect", "good drug effect", "bad drug effect", and "fear". Ratings will be performed before and repeatedly after substance administration and will take approximately 30 sec complete.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NEO-Five-Factor-Inventory (NEO-FFI)	The NEO-FFI is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".	Baseline
States of consciousness questionnaire (SCQ)	Assesses 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") once on each study day	12 months
Spiritual Realms Questionnaire	Assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered 100mm visual analog scales once on each study day	12 months
Blood pressure	Assessed 20 times on each study day via systolic and diastolic blood pressure	12 months
heart rate	Assessed 20 times on each study day via heart rate	12 months
body temperature	Assessed 20 times on each study day via tympanic body temperature	12 months
Plasma level DMT	Assessed 22 times on each study day	12 months
Plasma level of oxytocin	Assessed 3 times on each study day	12 months
Plasma level of cortisol	Assessed 3 times on each study day	12 months
Plasma level of BDNF	Assessed 3 times on each study day	12 months
Plasma level of Prolactin	Assessed 3 times on each study day	12 months
Urine recovery of DMT	Assessed once on each study day	12 months
Saarbrücker Personality Questionnaire (SPF)	The SPF defines empathy as the "reactions of one individual to the observed experiences of another." It assesses 28- items on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales (Perspective Taking, Fantasy, Empathic Concern, Personal Distress) each made up of 7 different items.	Baseline
Elliot Humility Scale (EHS)	The Elliot Humility Scale (EHS) is a validated 13-item self-rating measure assessing four subscales, i.e. openness, self-forgetfulness, accurate self-assessment, and focus on others on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree"	Baseline

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E Liechti, MD, University Hospital Basel, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Actual): March 8, 2024
• Study Completion (Actual): March 13, 2024

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; N,N-Dimethyltryptamine
• Other Study ID Numbers: BASEC 2022-00378

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No