Acute Effects of MDMA Co-administration on the Response to Psilocybin in Healthy Subjects

NCT06884514 | Recruiting Phase 1

• 1 other identifier: BASEC 2024-00893
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The acute subjective effects of serotonin (5-HT)2A receptor stimulation with psilocybin in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking, or loss of trust towards other people are common effects, depending on the dose administered, the personality traits of the person consuming it (set), or the environment in which psilocybin is taken (setting). Negative psychedelic effects may cause acute distress to the subject and acute anxiety has been linked to less favorable long-term outcomes in patients experimentally treated with psilocybin or similar substances for the treatment of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA) reliably induces positive mood, euphoria, comfort, empathy, and feelings of trust. If administered in combination with psilocybin, MDMA may increase positive subjective drug effects including positive mood, empathy, and trust and reduce negative emotions and anxiety associated with psilocybin and overall produce a more positive over negative experience. The present study will assess subjective and autonomic effects of psilocybin alone and in combination with MDMA.

Conditions

Healthy

Outcome Measures

Primary Outcomes (7)

• Acute Subjective effects I

  The Visual Analog Scales (VAS) assesses the intensity and duration of the subjective effect on a scale from 0 - 100 percent with higher scores representing more intense effects. Assessed 12 times on each study day

  through study completion, an average of 18 months

• Acute Subjective effects II

  The Adjective Mood Rating Scale (AMRS) assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely".

  through study completion, an average of 18 months

• Acute Subjective effects III

  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.

  through study completion, an average of 18 months

• Acute autonomic effects I (blood pressure)

  Blood pressure (systolic and diastolic) will be measured with an automatic oscillometric device.

  through study completion, an average of 18 months

• Acute autonomic effects I (heart rate)

  Heart rate will be measured with an automatic oscillometric device.

  through study completion, an average of 18 months

• Acute autonomic effects III (body temperature)

  Body temperature will be measured with an ear thermometer.

  through study completion, an average of 18 months

• Acute autonomic effects IV (ECG QT-time)

  An ECG will be performed twice: once before and once after substance administration.

  through study completion, an average of 18 months

Secondary Outcomes (23)

• Peak plasma concentration (Cmax) of MDMA and metabolites

  through study completion, an average of 18 months

• Time to peak plasma concentration (Tmax) of MDMA and metabolites

  through study completion, an average of 18 months

• Area under the plasma concentration vs. time curve (AUC) of MDMA and metabolites

  through study completion, an average of 18 months

• Elimination half-life values of MDMA and metabolites

  through study completion, an average of 18 months

• Peak plasma concentration (Cmax) of Psilocybin and metabolites

  through study completion, an average of 18 months

Study Arms (4)

20 mg Psilocybin + MDMA placebo

EXPERIMENTAL

20 mg Psilocybin + MDMA placebo

Drug: Psilocybin; Drug: 3,4-Methylenedioxymethamphetamine placebo

Psilocybin placebo + 100 mg MDMA

EXPERIMENTAL

Psilocybin placebo + 100 mg MDMA

Drug: 3,4-Methylenedioxymethamphetamine; Drug: Psilocybin placebo

20 mg Psilocybin + 100 mg MDMA

EXPERIMENTAL

20 mg Psilocybin + 100 mg MDMA

Drug: Psilocybin; Drug: 3,4-Methylenedioxymethamphetamine

Psilocybin placebo + MDMA placebo

PLACEBO COMPARATOR

Psilocybin placebo + MDMA placebo

Drug: Psilocybin placebo; Drug: 3,4-Methylenedioxymethamphetamine placebo

Interventions

Psilocybin DRUG

A moderate dose of 20 mg psilocybin will be administered.

20 mg Psilocybin + 100 mg MDMA; 20 mg Psilocybin + MDMA placebo

3,4-Methylenedioxymethamphetamine DRUG

A moderate dose of 100 mg MDMA will be administered.

20 mg Psilocybin + 100 mg MDMA; Psilocybin placebo + 100 mg MDMA

Psilocybin placebo DRUG

Mannitol capsules instead of capsules containing psilocybin.

Psilocybin placebo + 100 mg MDMA; Psilocybin placebo + MDMA placebo

3,4-Methylenedioxymethamphetamine placebo DRUG

Mannitol capsules instead of capsules containing MDMA.

20 mg Psilocybin + MDMA placebo; Psilocybin placebo + MDMA placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 25 and 65 years.
• Understanding of the German language.
• Understanding the procedures and the risks that are associated with the study.
• Participants must be willing to adhere to the protocol and sign the consent form.
• Participants must be willing to refrain from taking illicit psychoactive substances during the study.
• Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
• Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
• Willing to use effective birth control throughout study participation.
• Body mass index between 18-29 kg/m2.

You may not qualify if:

• Chronic or acute medical condition
• Current or previous major psychiatric disorder
• Psychotic disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain.
• Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
• Illicit substance use (not including cannabis) more than 20 times or any time within the previous month
• Pregnant or nursing women.
• Participation in another clinical trial (currently or within the last 30 days).
• Use of medications that may interfere with the effects of the study medications.
• Tobacco smoking (\>10 cigarettes/day).
• Consumption of alcoholic drinks (\>15 drinks/week).

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Interventions

Psilocybin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Matthias E Liechti, Prof. Dr. MD

  University Hospital Basel, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthias E Liechti, Prof. Dr. MD

CONTACT

+41 61 328 68 68; matthias.liechti@usb.ch

Isabelle Straumann, PhD

CONTACT

isabelle.straumann@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo-controlled, 4-period cross-over design with three active substance conditions and placebo: 1. 20 mg Psilocybin + MDMA placebo 2. Psilocybin placebo + 100 mg MDMA 3. 20 mg Psilocybin + 100 mg MDMA 4. Psilocybin placebo + MDMA placebo

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: March 19, 2025
• Study Start: April 3, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

CH (1)