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.
Topic Healthy Subjects
Compound Placebo
Psilocybin
Country Switzerland
Visit trial
Status
Completed
Results Published
Yes
Start date
04 July 2019
End date
26 November 2020
Chance of happening
100%
Phase
Phase I
Design
Blinded
Type
Interventional
Generation
First
Participants
27
Sex
All
Age
25- 65
Therapy
No
Trial Details
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)NCT Number NCT03912974
Sponsors & Collaborators
University of BaselThe University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.
Papers
Pharmacokinetics and pharmacodynamics of oral psilocybin administration in healthy participantsThis study analysed data from three clinical trials (n=79) to characterize the pharmacokinetic-pharmacodynamic relationship of orally administered psilocybin (15-30 mg). Maximal psilocin concentrations were 11 ng/ml, 17 ng/ml, and 21 ng/ml after the administration of 15, 25, and 30 mg psilocybin, respectively, and maximal levels were reached after an average of 2 hours. The duration and intensity of subjective effects were dose-dependent.
Acute effects of psilocybin after escitalopram or placebo pretreatment in a randomized, double-blind, placebo-controlled, cross-over study in healthy subjects
In this double-blind, cross-over, the effects of psilocybin (25mg) were assessed in healthy volunteers (n=23) who had been taking the antidepressant escitalopram (10-20mg, 14 days) or placebo before psilocybin treatment. Pretreatment with escitalopram had no relevant effect on positive mood but significantly reduced bad drug effects and adverse cardiovascular effects.
Measures Used
5-Dimensional Altered States of Consciousness QuestionnaireThe 5D-ASC scale measures altered states of consciousness and contains 94 items (visual analog scales).
States of Consciousness Questionnaire
The States of Consciousness Questionnaire (SOCQ) was developed to assess the occurrence features of the change in consciousness induced by psilocybin and includes the Mystical Experience Questionnaire (MEQ). The SOCQ consists of 100 items, 43 of which are from the MEQ.