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Effects of SERT Inhibition on the Subjective Response to Psilocybin in Healthy Subjects

NCT ID: NCT03912974

Last Updated: 2020-12-01

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

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-04

Study Completion Date

2020-11-26

Brief Summary

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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

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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

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

2-period cross-over, randomized, double-blinded (escitalopram vs. placebo)study
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
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)

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Escitalopram

Intervention Type DRUG

see 'arm description'

Pretreatment with placebo oral capsule

Pretreatment with placebo, followed by administration of psilocybin (25 mg orally) on the study day

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

see 'arm description'

Interventions

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Escitalopram

see 'arm description'

Intervention Type DRUG

Placebo oral capsule

see 'arm description'

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 24 h after substance administration.
8. Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
9. Women of childbearing potential must be willing to use double-barrier birth control.

Exclusion Criteria

1. Chronic or acute medical condition, including a history of seizures.
2. Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders, and substance abuse).
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. Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.
5. History of an angle closure glaucoma.
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 (any psychiatric medications and any medication with known pharmacokinetic or pharmacodynamic interactions with escitalopram).
9. A corrected QT time (QTc), calculated by Bazett's formula, of over 450 milliseconds in males and over 470 milliseconds in females.
10. Tobacco smoking (\>10 cigarettes/day).
11. Consumption of alcoholic drinks (\>10 drinks / week).
12. Bodyweight \< 45 kg.
Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthias E Liechti, MD, MAS

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

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University Hospital Basel, Clinical Trial Unit

Basel, Canton of Basel-City, Switzerland

Site Status

Countries

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Switzerland

References

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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.

Reference Type DERIVED
PMID: 36507738 (View on PubMed)

Becker 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.

Reference Type DERIVED
PMID: 34743319 (View on PubMed)

Other Identifiers

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BASEC 2019-00223

Identifier Type: -

Identifier Source: org_study_id