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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-03

Study Completion Date

2026-07-01

Brief Summary

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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.

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Detailed Description

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Psilocybin is a classic serotonergic psychedelic. Clinically, the acute effects of psilocybin last shorter than those of lysergic acid diethylamide (LSD) but are qualitatively very similar. Currently, psilocybin is the most investigated psychedelic substance among the classic psychedelics including LSD, psilocybin, mescaline, and dimethyltryptamine (DMT). Psilocybin is capable of inducing exceptional subjective effects such as a dream-like alteration of consciousness, affective changes, psychological insight, visual imagery, pseudo-hallucinations and ego-dissolution. The acute subjective effects elicited by psilocybin are mostly positive in humans. However, psychedelic substances like psilocybin may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of psilocybin used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize the effects of psilocybin by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.

Conditions

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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20 mg Psilocybin + MDMA placebo

Group Type EXPERIMENTAL

Psilocybin

Intervention Type DRUG

A moderate dose of 20 mg psilocybin will be administered.

3,4-Methylenedioxymethamphetamine placebo

Intervention Type DRUG

Mannitol capsules instead of capsules containing MDMA.

Psilocybin placebo + 100 mg MDMA

Group Type EXPERIMENTAL

3,4-Methylenedioxymethamphetamine

Intervention Type DRUG

A moderate dose of 100 mg MDMA will be administered.

Psilocybin placebo

Intervention Type DRUG

Mannitol capsules instead of capsules containing psilocybin.

20 mg Psilocybin + 100 mg MDMA

Group Type EXPERIMENTAL

Psilocybin

Intervention Type DRUG

A moderate dose of 20 mg psilocybin will be administered.

3,4-Methylenedioxymethamphetamine

Intervention Type DRUG

A moderate dose of 100 mg MDMA will be administered.

Psilocybin placebo + MDMA placebo

Group Type PLACEBO_COMPARATOR

Psilocybin placebo

Intervention Type DRUG

Mannitol capsules instead of capsules containing psilocybin.

3,4-Methylenedioxymethamphetamine placebo

Intervention Type DRUG

Mannitol capsules instead of capsules containing MDMA.

Interventions

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Psilocybin

A moderate dose of 20 mg psilocybin will be administered.

Intervention Type DRUG

3,4-Methylenedioxymethamphetamine

A moderate dose of 100 mg MDMA will be administered.

Intervention Type DRUG

Psilocybin placebo

Mannitol capsules instead of capsules containing psilocybin.

Intervention Type DRUG

3,4-Methylenedioxymethamphetamine placebo

Mannitol capsules instead of capsules containing MDMA.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age between 25 and 65 years.
2. Understanding of the German language.
3. Understanding the procedures and the risks that are associated with the study.
4. Participants must be willing to adhere to the protocol and sign the consent form.
5. Participants must be willing to refrain from taking illicit psychoactive substances during the study.
6. 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.
7. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
8. Willing to use effective 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
3. 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.
4. Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
5. Illicit substance use (not including cannabis) more than 20 times or any time within the previous month
6. Pregnant or nursing women.
7. Participation in another clinical trial (currently or within the last 30 days).
8. Use of medications that may interfere with the effects of the study medications.
9. Tobacco smoking (\>10 cigarettes/day).
10. Consumption of alcoholic drinks (\>15 drinks/week).

Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes