AzTrials
AzTrials

HealthyPhase 1MDMA-PsiloNCT06884514

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

A Phase 1 study testing Psilocybin and 3,4-Methylenedioxymethamphetamine in people with Healthy, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 25 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Psilocybin and 3,4-Methylenedioxymethamphetamine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteSwitzerland
Study dates
3 Apr 2025to 28 May 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country.

Switzerland1 site
  • University Hospital Basel

    Basel, 4031

Other trials in Switzerland

About this study

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.

Read the detailed description

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
Healthy
Being tested
Psilocybin, 3,4-Methylenedioxymethamphetamine, Psilocybin placebo, 3,4-Methylenedioxymethamphetamine placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PsilocybinDrug

    A moderate dose of 20 mg psilocybin will be administered.

  • 3,4-MethylenedioxymethamphetamineDrug

    A moderate dose of 100 mg MDMA will be administered.

  • Psilocybin placeboDrug

    Mannitol capsules instead of capsules containing psilocybin.

  • 3,4-Methylenedioxymethamphetamine placeboDrug

    Mannitol capsules instead of capsules containing MDMA.

Study groups in NCT06884514
Study groupRoleWhat they receive
20 mg Psilocybin + MDMA placeboExperimental20 mg Psilocybin + MDMA placebo
Receives: Drug: Psilocybin; Drug: 3,4-Methylenedioxymethamphetamine placebo
Psilocybin placebo + 100 mg MDMAExperimentalPsilocybin placebo + 100 mg MDMA
Receives: Drug: 3,4-Methylenedioxymethamphetamine; Drug: Psilocybin placebo
20 mg Psilocybin + 100 mg MDMAExperimental20 mg Psilocybin + 100 mg MDMA
Receives: Drug: Psilocybin; Drug: 3,4-Methylenedioxymethamphetamine
Psilocybin placebo + MDMA placeboPlacebo comparatorPsilocybin placebo + MDMA placebo
Receives: Drug: Psilocybin placebo; Drug: 3,4-Methylenedioxymethamphetamine placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: through study completion, an average of 18 months

  2. 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".

    Measured: through study completion, an average of 18 months

  3. 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.

    Measured: through study completion, an average of 18 months

  4. Acute autonomic effects I (blood pressure)

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

    Measured: through study completion, an average of 18 months

  5. Acute autonomic effects I (heart rate)

    Heart rate will be measured with an automatic oscillometric device.

    Measured: through study completion, an average of 18 months

  6. Acute autonomic effects III (body temperature)

    Body temperature will be measured with an ear thermometer.

    Measured: through study completion, an average of 18 months

  7. Acute autonomic effects IV (ECG QT-time)

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

    Measured: through study completion, an average of 18 months

Secondary outcomes (23)
  1. Peak plasma concentration (Cmax) of MDMA and metabolites

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

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

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

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

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

  4. Elimination half-life values of MDMA and metabolites

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

  5. Peak plasma concentration (Cmax) of Psilocybin and metabolites

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

  6. Time to peak plasma concentration (Tmax) of Psilocybin and metabolites

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

  7. Area under the concentration vs. time curve (AUC) of Psilocybin and metabolites

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

  8. Elimination half-life values of Psilocybin and metabolites

    Assessed via blood samples. Findings will be described descriptively.

    Measured: through study completion, an average of 18 months

  9. Plasma concentration of Oxytocin

    Assessed via blood samples.

    Measured: through study completion, an average of 18 months

  10. States of Consciousness Questionnaire

    Assesses the emergence and intensity of phenomenons occurring in altered states of consciousness on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely")

    Measured: through study completion, an average of 18 months

  11. Spiritual Realms Questionnaire

    Assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered 100mm visual analog scales once on each study day

    Measured: through study completion, an average of 18 months

  12. Subacute effects on general and mental well-being I (WEMWBS)

    The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) is a 14-item questionnaire, that covers different concepts associated with positive mental health, including both hedonic and eudaimonic aspects, positive affect, satisfying interpersonal relationships and positive functioning. For each item an ordinal five point frequency answer format, ranging from 1 = none of the time" to 5 = "all of the time" is applied.

    Measured: through study completion, an average of 18 months

  13. Subacute effects on general and mental well-being II (GHQ-12)

    The General Health Questionnaire (GHQ-12) consists of a 12-item questionnaire with a four-point response scale assessing general psychological discomfort.

    Measured: through study completion, an average of 18 months

  14. Subacute effects on general and mental well-being III (SPANE)

    The Scale of Positive and Negative Experience (SPANE) is a 12-item questionnaire to capture the affective component of subjective well-being. The SPANE includes six items to assess positive feelings and six items to assess negative feelings. The feelings are reported on a 5-point scale ranging from "very rarely" to "very often or always".

    Measured: through study completion, an average of 18 months

  15. Subacute effects on general and mental well-being IV (BFW/E)

    The "Positive Attitude towards Life" is an 8-item subscale of the 39-item Bern Subjective Well-Being Questionnaire for adults. A six-point rating scale ranging from 1 ('strongly disagree') to 6 ('strongly agree') is used to rate the attitude towards life.

    Measured: through study completion, an average of 18 months

  16. Subacute effects on general and mental well-being V (GLS)

    Global life satisfaction is assessed based on a single item life satisfaction measure which is a simple, yet widespread approach. The question is answered on a 11-point scale: "In general, how satisfied are you with your life if 0 means 'not at all satisfied' and 10 means 'completely satisfied'?".

    Measured: through study completion, an average of 18 months

  17. Adverse effects (acute and subacute)

    The 2011 revised Beschwerden-Liste (B-LR) consists of a 40-item list covering a wide variety of symptoms and complaints that are answered with a four-point intensity-scoring ranging from "not at all" to "strong".

    Measured: through study completion, an average of 18 months

  18. Effects on Appreciation

    The Appreciation Scale (AS) comprises 57 items used to measure aspects of appreciation. Subjects are asked to rate themselves on a scale from 1 to 7 in terms of either attitude intensity ('strongly disagree' to 'strongly agree') or frequency ('never' to 'more than once a day'). Scores on the subscales are summed up to yield a score representing the overall degree of appreciation (or level of appreciativeness), with higher scores indicating more of the positive construct.

    Measured: through study completion, an average of 18 months

  19. Effect moderation by personality traits I (NEO-FFI)

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The NEO Five Factor Inventory (NEO-FFI) is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".

    Measured: Baseline

  20. Effect moderation by personality traits II (FPI-R)

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Freiburger Personality Inventory (FPI-R) version comprises 138 items and covers 12 dimensions of personality: life satisfaction, social orientation, performance orientation, inhibition, excitability, aggressiveness, stress, physical complaints, health concerns, openness, as well as the secondary factors according to Eysenck's Extraversion and Emotionality (Neuroticism). It uses a 2-point scale ("true" and "not true").

    Measured: Baseline

  21. Effect moderation by personality traits III (SPF)

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Saarbrücker Persönlichkeitsfragebogen (SPF) defines empathy as the "reactions of one individual to the observed experiences of another." It assesses 28-items on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales (Perspective Taking, Fantasy, Empathic Concern, Personal Distress) each made up of 7 different items.

    Measured: Baseline

  22. Effect moderation by personality traits IV (HEXACO)

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The HEXACO personality inventory is a six-dimensional model of human personality with 100 items.The six factors are: Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness and Openness to Experience.

    Measured: Baseline

  23. Effect moderation by personality traits V (DSQ-40)

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Defense Style Questionnaire (DSQ-40) can provide scores for 20 individual defenses, and scores for the three factors "mature", "neurotic", and "immature". Each item is evaluated on a scale from 1 to 9, where "1" indicates "completely disagree" and "9" indicates "fully agree".

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2025
  2. Study start3 Apr 2025
  3. Primary completion13 May 2026
  4. Study completion28 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
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
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06884514
Sponsor's protocol ID
BASEC 2024-00893
Acronym
MDMA-Psilo
Status last verified
May 2025
First submitted
31 Jan 2025
Last updated
25 Jun 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Psilocybin and 3,4-Methylenedioxymethamphetamine in people with Healthy, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Acute Subjective effects I (time frame: through study completion, an average of 18 months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in