Acute Effects of Intravenous 5-MeO-DMT in Healthy Participants

Phase 1RecruitingNCT07444788

University Hospital, Basel, Switzerland40 enrolled

Overview

Participation in this study lasts approximately two weeks and includes three on-site study visits: a screening visit (approximately 2 hours), a study drug administration visit (approximately 4 hours), and a follow-up visit approximately one week later (approximately 2 hours). If participants decide to take part in the study and meet the inclusion and exclusion criteria, they will be randomly assigned to one of two groups: an experimental group or a control group. Participants will not be informed of your group assignment. Participants in the experimental group will receive the investigational substance 5-MeO-DMT at a dose of 0.2, 0.4, 0.6, or 0.8 mg/min for a total infusion duration of 30 min. Participants in the control group will receive a placebo that is indistinguishable in appearance from the investigational substance. Following substance administration, participants will be repeatedly asked to describe their subjective experiences. Blood pressure and heart rate will be monitored regularly, and blood samples will be collected via an intravenous catheter.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

Conditions

5-methoxy-dimethyltryptamine (5-MeO-DMT)

Interventions

Eligibility

Sex: ALLMin age: 25 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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. Willing not to operate heavy machinery for 48 hours after the study session. 7. Willing to use effective birth control throughout study participation 8. Body mass index between 18-29 kg/m2 Exclusion Criteria: 1. Chronic or acute medical condition 2. Current or previous major psychiatric disorder 3. Psychotic disorder or bipolar disorder in first-degree relatives 4. Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg) 5. Hallucinogenic and/or dissociative 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 (\>15 drinks or \>180g alcohol per week)

Outcomes

Primary Outcomes

Change in subjective effects over time (assessed with subjective effect scales (SES))

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 to complete.

Time frame: Up to 245 minutes at the substance administration session (Session 2): 1 hour and 5 minutes before and 5, 10, 15, 20, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 min after substance administration.

Secondary Outcomes

Treatment-emergent adverse events (TEAEs)

A TEAE is an adverse event (AE) that emerges during treatment (having been absent before treatment) or that worsens after treatment. Spontaneously reported AEs, AEs in response to questioning or observed AEs by the investigators will be recorded at the substance administration session (Session 2) and at the end of study visit (EOS, Session 3). Clinically significant abnormalities in the results of a laboratory test, on the ECG or on suicidal ideation (C-SSRS) may also be recorded as TEAE. TEAEs will be summarized and tabulated by treatment (5-MeO-DMT vs. placebo).

Time frame: Up to one week (from substance administration session (Session 2) to end of study visit (EOS, Session 3))

Change in Safety lab parameters

A routine safety laboratory blood test is performed at the screening (Session 1) and at the end of study visit (Session 3) including creatinine, alanine aminotransferase (ALAT), aspartate transaminase (ASAT), hemoglobin, hematocrit, white blood cell count, red blood cell count, and platelet cell count (total of 7.3 ml blood).

Time frame: Up to 14 days (from Screening (Session 1) until end-of-study-visit (EOS, Session 3))

Change in Vital Signs

Blood pressure, heart rate, and body temperature will be recorded at baseline and repeatedly throughout the drug administration session (Session 2). Blood pressure (systolic and diastolic) and heart rate will be measured with an automatic oscillometric device. Measurements will be taken in supine position. For blood pressure, duplicate measurements will be performed.

Change in Adverse effects list (Beschwerdenliste (BL-R)

The Adverse effects list (= Beschwerdenliste) is a self-reporting tool to assess physical and general discomfort. We will use the 2011 revised version, which consists of a 40-item list to assess physiological complaints throughout the study sessions. The BL-R covers a wide variety of symptoms and complaints that are answered with a four-point Likert scale ranging from "not at all" to "strong". We added several items that have been frequently observed in previous research with psychedelics by the several research groups. The scale will be administered at baseline and at the end of the substance administration session (Session 2).

Time frame: Up to 4 hours at substance administration session (Session 2) (at baseline and after substance administration)

Swiss Psychedelic Side Effects Inventory (SPSI)

The Swiss Psychedelic Side Effects Inventory (SPSI) has recently been developed and validated by an expert panel, leveraging insights from previous research to enhance the assessment of clinically relevant side effects in studies of psychedelic-assisted therapy. The SPSI assesses 32 potential side effects, along with standardized follow-up questions about their severity, impact, treatment-relatedness, and duration. The scale provides total scores for the number, severity, and impact of side effects, as well as an overall score representing the burden of side effects within a specified timeframe. The scale will be administered at the end of study visit (EOS, Session 3).

Time frame: One time assessment at End-of-study-visit (EOS, Session 3 = 7 days after substance administration)

Change in Columbia-Suicide-Severity-Rating-Scale (C-SSRS)

The C-SSRS is a suicide risk assessment tool that assesses suicidal ideation and behavior and has repeatedly been shown to accurately predict suicide risks across different populations. The C-SSRS includes the two main domains suicidal ideation and suicidal behaviour. The suicidal ideation domain will be rated based on "Yes"/"No" responses to each of the following types of ideation: 1) wish to be dead, 2) non-specific ideal active suicidal thoughts, 3) active suicidal ideation with any methods (no plan) without intent to act, 4) active suicidal ideation with some intent to act without a specific plan, and 5) active suicidal ideation with a specific plan and intent. The highest numbered item rated "yes" will be scored to assess the suicidal ideation score. If suicidal ideation is present, the intensity of suicidal ideation will be measured (frequency, duration, controllability, deterrents, and reasons for suicidal ideation).

Time frame: Up to 14 days (from Screening (Session 1) to Substance administration session (Session 2) until End-of-study-visit (EOS, Session 3))

5-Dimensions of Altered States of Consciousness Scale (5D-ASC)

Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.