Clinical trial NCT05384678: Acute Dose-dependent Effects of DMT in Healthy Subjects
Official title: Acute Dose-dependent Effects of 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: 2022-05-20
Enrollment: 24
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: 5-period random order, placebo-controlled, double-blind cross-over study with four active substance conditions and placebo: 1. 0.6 mg/min, 2. 1.2 mg/min, 3. 1.8 mg/min, 4. 2.4 mg/min, 5. Placebo. Additionally, a patient-guided titration will be performed at the sixth and last session (not randomized).
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Altered states of consciousness profile (5D-ASC)
timeFrame: 12 months
measure: Subjective effect ratings over time
timeFrame: 12 months
Secondary outcomes:
measure: States of consciousness questionnaire (SCQ)
timeFrame: 12 months
measure: Spiritual Realms Questionnaire
timeFrame: 12 months
measure: Blood pressure
timeFrame: 12 months
measure: heart rate
timeFrame: 12 months
measure: body temperature
timeFrame: 12 months
measure: Plasma level DMT
timeFrame: 12 months
measure: Plasma level of oxytocin
timeFrame: 12 months
measure: Plasma level of cortisol
timeFrame: 12 months
measure: Plasma level of BDNF
timeFrame: 12 months
measure: Plasma level of Prolactin
timeFrame: 12 months
measure: Urine recovery of DMT
timeFrame: 12 months
measure: NEO-Five-Factor-Inventory (NEO-FFI)
timeFrame: Baseline
measure: Saarbrücker Personality Questionnaire (SPF)
timeFrame: Baseline
measure: Elliot Humility Scale (EHS)
timeFrame: Baseline
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Universtity Hospital Basel
Study officials:
affiliation: University Hospital Basel, Basel, Switzerland
name: Matthias E Liechti, MD
role: PRINCIPAL_INVESTIGATOR
References: