HealthyPhase 1NCT03912974
Effects of SERT Inhibition on the Subjective Response to Psilocybin in Healthy Subjects
A Phase 1 study testing Escitalopram in people with Healthy, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
Psilocybin is a classic serotonergic hallucinogen acting on the 5-HT2A receptor. It is used recreationally and in psychiatric research. Selective serotonin reuptake inhibitors (SSRIs) like escitalopram are first-line treatments for depression. They inhibit the serotonin transporter (SERT). 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?
- Escitalopram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteSwitzerland
- Study dates
- 4 Jul 2019to 26 Nov 2020
- 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.
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- Participants must be willing not to drive a traffic vehicle or to operate machines within 24 h after substance administration.
- Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
- Women of childbearing potential must be willing to use double-barrier birth control.
Who cannot join
- Chronic or acute medical condition, including a history of seizures.
- Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders, and substance abuse).
- 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.
- Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.
- History of an angle closure glaucoma.
- Pregnant or nursing women.
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- 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 (any psychiatric medications and any medication with known pharmacokinetic or pharmacodynamic interactions with escitalopram).
- A corrected QT time (QTc), calculated by Bazett's formula, of over 450 milliseconds in males and over 470 milliseconds in females.
- Tobacco smoking (>10 cigarettes/day).
- Consumption of alcoholic drinks (>10 drinks / week).
- Bodyweight < 45 kg.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel, Clinical Trial Unit
Basel, Canton of Basel-City, 4056
About this study
Official title: Effects of Serotonin Transporter Inhibition on the Subjective Response to Psilocybin in Healthy Subjects
Psilocybin is a classic serotonergic hallucinogen acting on the 5-HT2A receptor. It is used recreationally and in psychiatric research. Selective serotonin reuptake inhibitors (SSRIs) like escitalopram are first-line treatments for depression. They inhibit the serotonin transporter (SERT). This might cause a possible downregulation of postsynaptic 5-HT receptors, e.g. the 5-HT2A receptor. The aim of the study is to investigate the effects of psilocybin after escitalopram and Placebo pretreatment. Subjective and physiological effects as well as effects on gene expression will be assessed.
Read the detailed description
Psilocybin (the active substance in "magic mushrooms") is a classic serotonergic hallucinogen acting on the serotonin 5-HT2A receptor. Psilocybin is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression. SSRIs like escitalopram are currently among the first-line treatments of this disorder. Escitalopram acts as a serotonin transporter (SERT) inhibitor. However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to psilocybin.
Participants will be treated with escitalopram (10 mg in the 1st and 20 mg in the 2nd week) or placebo for 14 days. Pretreatment is followed the first study day. A single dose of psilocybin (25 mg) will be administered. Primary study endpoint are the subjective effects on consciousness (measured by the 5D-ASC total score). Secondary study endpoints include additional psychological measurements, plasma concentrations of psilocybin and escitalopram, hydroxytryptamine receptor (HTR) gene expression, as well as some safety measures (autonomic effects, ECG). The washout between the first study day and the second pretreatment will be at least 2 days. In the second pretreatment period, participants will be treated with placebo or escitalopram (cross-over) for another 14 days. This is followed by the second study day and administration of psilocybin (25 mg).
Based on a power analysis the sample size is 24 participants (12 female and 12 male).
- Conditions
- Healthy
- Being tested
- Escitalopram, Placebo oral capsule
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
see 'arm description'
Placebo oral capsuleDrug
see 'arm description'
| Study group | Role | What they receive |
|---|---|---|
| Pretreatment with escitalopram | Active comparator | Pretreatment with escitalopram (10 mg for 7 days orally, 20 mg for another 7 days orally), followed by administration of psilocybin (25 mg orally) on the study day Receives: Drug: Escitalopram |
| Pretreatment with placebo oral capsule | Placebo comparator | Pretreatment with placebo, followed by administration of psilocybin (25 mg orally) on the study day Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
5 dimensions of altered state of consciousness (5D-ASC) profile total score
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.
Measured: 20 Months
Secondary outcomes (13)
Visual Analog Scales (VAS)
VAS will be repeatedly used to assess subjective alterations in consciousness over time. VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS will be used: "any effect", "good effect", "bad effect","liking", "high", "happy", "fear", "stimulated", "feeling close to others", "concentration", "thinking", "open", "trust", "want to be with other people", "loss of sense of time", and "the boundaries between myself and my surroundings seemed to blur". Subjects will mark the scale with vertical lines.
Measured: 20 Months
Adjective mood rating scale (AMRS)
The adjective mood rating scale (AMRS or EWL60S) is a 60-item Likert scale that allows repeated assessment of mood in 6 dimensions: activation, inactivation, well-being, anxiety/depressed mood, extroversion and introversion, and emotional excitability.The AMRS consists of subscales measuring "activation", "positive mood", "extroversion", "introversion", "inactivation", and "emotional excitability.
Measured: 20 Months
States of consciousness questionnaire (SCQ)
This 100-item questionnaire is rated on a six-point scale. Forty-three items embedded into this questionnaire comprise the Mystical Experience Questionnaire (MEQ). which is sensitive to the effects of psilocybin. The 43 items provide scale scores for each of seven domains of mystical experiences: internal unity (pure awareness, a merging with ultimate reality), external unity (unity of all things, all things are alive, all is one), sense of sacredness (reverence, sacred), noetic quality (encounter with ultimate reality, more real than everyday reality), transcendence of time and space, deeply felt positive mood (joy, peace, love), paradoxicality/ineffability (claim of difficulty in describing the experience in words). We will also derived the four scale scores of the newly validated revised 30-item MEQ: mystical, positive mood, transcendence of time and space, and ineffability.
Measured: 20 Months
Mysticism scale (MS)
The MS is a 32-item questionnaire that was developed to assess primary mystical experiences. The items are rated on a 9-point Likert scale. The scale consists of 16 positively worded statements and 16 negatively worded statements.
Measured: 20 Months
Eppendorf Schizophrenia Inventory (ESI)
The ESI yields four schizophrenia-specific dimensions: attention and speech impairment (AS), ideas of reference (IR), auditory uncertainty (AU), and deviant perception (DP).
Measured: 20 Months
Blood pressure
Repeatedly measured using blood pressure / pulse apparatus (mmHg scale)
Measured: 20 Months
Heart rate
Repeatedly measured using blood pressure / pulse apparatus (beats per minute scale)
Measured: 20 Months
Body temperature
Repeatedly measured using ear thermometer (degree Celsius scale)
Measured: 20 Months
Pupil diameter
Repeatedly measured using pupil distance meter (millimeter scale)
Measured: 20 Months
Plasma concentrations of escitalopram
Escitalopram plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)
Measured: 20 Months
Plasma concentrations of psilocin
Escitalopram plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)
Measured: 20 Months
HTR gene expression
Messenger ribonucleic acid (mRNA) expression levels in whole blood as a peripheral marker of spiny neuronal gene (CNS) expression will be used to measure expression of HTR genes as well as expression of the SERT gene.
Measured: 20 Months
Changes in the electrocardiogram (ECG)
12-lead electrocardiogram will be measured twice on the study days (baseline and at peak drug effect) as well as on the screening exam to examine possible drug-induced changes in the ECG as well as a safety measure (millisecond scale).
Measured: 20 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2019
- Study start4 Jul 2019
- Primary completion26 Nov 2020
- Study completion26 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 2-period cross-over, randomized, double-blinded (escitalopram vs. placebo)study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthias E Liechti, MD, MAS, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03912974
- Sponsor's protocol ID
- BASEC 2019-00223
- Status last verified
- Nov 2020
- First submitted
- 6 Mar 2019
- Last updated
- 1 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Holze F, Becker AM, Kolaczynska KE, Duthaler U, Liechti ME. Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants. Clin Pharmacol Ther. 2023 Apr;113(4):822-831. doi: 10.1002/cpt.2821. Epub 2022 Dec 31.
PubMed 36507738Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, Duthaler U, Varghese N, Eckert A, Grunblatt E, Liechti ME. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clin Pharmacol Ther. 2022 Apr;111(4):886-895. doi: 10.1002/cpt.2487. Epub 2021 Nov 22.
PubMed 34743319
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Serotonin Transporter Inhibition on the Subjective Response to Psilocybin in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03912974
- Acronym / sponsor ID
- BASEC 2019-00223
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 4 Jul 2019 (actual)
- Primary completion
- 26 Nov 2020 (actual)
- Study completion
- 26 Nov 2020 (actual)
- First posted
- 12 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Psilocybin is a classic serotonergic hallucinogen acting on the 5-HT2A receptor. It is used recreationally and in psychiatric research. Selective serotonin reuptake inhibitors (SSRIs) like escitalopram are first-line treatments for depression. They inhibit the serotonin transporter (SERT). This might cause a possible downregulation of postsynaptic 5-HT receptors, e.g. the 5-HT2A receptor. The aim of the study is to investigate the effects of psilocybin after escitalopram and Placebo pretreatment. Subjective and physiological effects as well as effects on gene expression will be assessed.
Detailed description
Psilocybin (the active substance in "magic mushrooms") is a classic serotonergic hallucinogen acting on the serotonin 5-HT2A receptor. Psilocybin is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression. SSRIs like escitalopram are currently among the first-line treatments of this disorder. Escitalopram acts as a serotonin transporter (SERT) inhibitor. However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to psilocybin.
Participants will be treated with escitalopram (10 mg in the 1st and 20 mg in the 2nd week) or placebo for 14 days. Pretreatment is followed the first study day. A single dose of psilocybin (25 mg) will be administered. Primary study endpoint are the subjective effects on consciousness (measured by the 5D-ASC total score). Secondary study endpoints include additional psychological measurements, plasma concentrations of psilocybin and escitalopram, hydroxytryptamine receptor (HTR) gene expression, as well as some safety measures (autonomic effects, ECG). The washout between the first study day and the second pretreatment will be at least 2 days. In the second pretreatment period, participants will be treated with placebo or escitalopram (cross-over) for another 14 days. This is followed by the second study day and administration of psilocybin (25 mg).
Based on a power analysis the sample size is 24 participants (12 female and 12 male).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 2-period cross-over, randomized, double-blinded (escitalopram vs. placebo)study
| Arm | Type | Receives |
|---|---|---|
| Pretreatment with escitalopram | Active comparator | Drug: EscitalopramPretreatment with escitalopram (10 mg for 7 days orally, 20 mg for another 7 days orally), followed by administration of psilocybin (25 mg orally) on the study day |
| Pretreatment with placebo oral capsule | Placebo comparator | Drug: Placebo oral capsulePretreatment with placebo, followed by administration of psilocybin (25 mg orally) on the study day |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- Chronic or acute medical condition, including a history of seizures.
- Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders, and substance abuse).
- 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.
- Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.
- History of an angle closure glaucoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Escitalopramsee 'arm description' | Drug | Pretreatment with escitalopram |
| Placebo oral capsulesee 'arm description' | Drug | Pretreatment with placebo oral capsule |
Primary outcome
5 dimensions of altered state of consciousness (5D-ASC) profile total score
Time frame: 20 Months
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.
13 secondary outcomes
Visual Analog Scales (VAS)
Time frame: 20 Months
Adjective mood rating scale (AMRS)
Time frame: 20 Months
States of consciousness questionnaire (SCQ)
Time frame: 20 Months
Mysticism scale (MS)
Time frame: 20 Months
Eppendorf Schizophrenia Inventory (ESI)
Time frame: 20 Months
Blood pressure
Time frame: 20 Months
Heart rate
Time frame: 20 Months
Body temperature
Time frame: 20 Months
Pupil diameter
Time frame: 20 Months
Plasma concentrations of escitalopram
Time frame: 20 Months
Plasma concentrations of psilocin
Time frame: 20 Months
HTR gene expression
Time frame: 20 Months
Changes in the electrocardiogram (ECG)
Time frame: 20 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2020.
- Derived from this study: PubMed 36507738Holze F, Becker AM, Kolaczynska KE, Duthaler U, Liechti ME. Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants. Clin Pharmacol Ther. 2023 Apr;113(4):822-831. doi: 10.1002/cpt.2821. Epub 2022 Dec 31.
- Derived from this study: PubMed 34743319Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, Duthaler U, Varghese N, Eckert A, Grunblatt E, Liechti ME. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clin Pharmacol Ther. 2022 Apr;111(4):886-895. doi: 10.1002/cpt.2487. Epub 2021 Nov 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias E Liechti, MD, MAS principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Escitalopram 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 12 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 1 Dec 2020. 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?
5 dimensions of altered state of consciousness (5D-ASC) profile total score (time frame: 20 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03912974, which also lists 2 linked publications.
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 1 Dec 2020.