Clinical trial NCT04353024: Effects of Dimethyltryptamine in Healthy Subjects
Official title: Effects of Dimethyltryptamine (DMT) in Healthy Subjects: A Placebo-controlled Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2020-04-20
Enrollment: 31
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, placebo-controlled, 5-period cross-over design with 4 different doses of DMT and placebo
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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:
measure: Altered states of consciousness profile
timeFrame: 150 minutes
measure: Subjective effect ratings over time
timeFrame: 150 minutes
Secondary outcomes:
measure: Subjective mood ratings
timeFrame: 150 minutes
measure: Mystical-type experiences
timeFrame: 150 minutes
measure: Autonomic effects I
timeFrame: 150 minutes
measure: Autonomic effects II
timeFrame: 150 minutes
measure: Plasma levels of DMT
timeFrame: 150 minutes
measure: Plasma levels of blood-derived neurotrophic factor (BDNF)
timeFrame: 150 minutes
measure: Plasma levels of oxytocin
timeFrame: 60 minutes
measure: Renal clearance of DMT
timeFrame: 3 hours
measure: Effect moderation through personality traits I
timeFrame: Baseline
measure: Effect moderation through personality traits II
timeFrame: Baseline
measure: Effect moderation through personality traits III
timeFrame: Baseline
measure: Effect moderation through personality trait IV
timeFrame: Baseline
measure: Effect moderation through personality trait V
timeFrame: Baseline
measure: Effect moderation through personality trait VI
timeFrame: Baseline
measure: Effect moderation through personality trait VII
timeFrame: Baseline
measure: Adverse effects
timeFrame: 150 minutes
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt BS
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, Prof. Dr. MD
role: PRINCIPAL_INVESTIGATOR
References: