Effects of SERT Inhibition on the Subjective Response to Psilocybin in Healthy Subjects
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03912974|
Recruitment Status : Recruiting
First Posted : April 12, 2019
Last Update Posted : March 2, 2020
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Drug: Escitalopram Drug: Placebo oral capsule||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||2-period cross-over, randomized, double-blinded (escitalopram vs. placebo)study|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||Pretreatment condition is double-blinded (escitalopram 10 mg x 7 days, then 20 mg orally x 7 days vs. placebo (mannitol) orally x 14 days) On each of the 2 study days, participants will receive psilocybin 25 mg orally (no placebo control on the study days)|
|Primary Purpose:||Basic Science|
|Official Title:||Effects of Serotonin Transporter Inhibition on the Subjective Response to Psilocybin in Healthy Subjects|
|Actual Study Start Date :||July 4, 2019|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Active Comparator: Pretreatment with escitalopram
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
see 'arm description'
Placebo Comparator: Pretreatment with placebo oral capsule
Pretreatment with placebo, followed by administration of psilocybin (25 mg orally) on the study day
Drug: Placebo oral capsule
see 'arm description'
- 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.
- Visual Analog Scales (VAS) [ Time Frame: 20 Months ]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.
- Adjective mood rating scale (AMRS) [ Time Frame: 20 Months ]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.
- States of consciousness questionnaire (SCQ) [ Time Frame: 20 Months ]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.
- Mysticism scale (MS) [ Time Frame: 20 Months ]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.
- Eppendorf Schizophrenia Inventory (ESI) [ Time Frame: 20 Months ]The ESI yields four schizophrenia-specific dimensions: attention and speech impairment (AS), ideas of reference (IR), auditory uncertainty (AU), and deviant perception (DP).
- Blood pressure [ Time Frame: 20 Months ]Repeatedly measured using blood pressure / pulse apparatus (mmHg scale)
- Heart rate [ Time Frame: 20 Months ]Repeatedly measured using blood pressure / pulse apparatus (beats per minute scale)
- Body temperature [ Time Frame: 20 Months ]Repeatedly measured using ear thermometer (degree Celsius scale)
- Pupil diameter [ Time Frame: 20 Months ]Repeatedly measured using pupil distance meter (millimeter scale)
- Plasma concentrations of escitalopram [ Time Frame: 20 Months ]Escitalopram plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)
- Plasma concentrations of psilocin [ Time Frame: 20 Months ]Escitalopram plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)
- HTR gene expression [ Time Frame: 20 Months ]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.
- Changes in the electrocardiogram (ECG) [ Time Frame: 20 Months ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03912974
|Contact: Matthias E Liechti, MD, MAS||613286868 ext +firstname.lastname@example.org|
|Contact: Anna Becker, MSc||613286861 ext +email@example.com|
|University Hospital Basel, Clinical Trial Unit||Recruiting|
|Basel, BS, Switzerland, 4056|
|Contact: Matthias E Liechti, MD, MAS|
|Principal Investigator:||Matthias E Liechti, MD, MAS||University Hospital, Basel, Switzerland|