Effects of SERT Inhibition on the Subjective Response to Psilocybin in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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). 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).
    

Intervention name(s): Escitalopram; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): see 'arm description'; see 'arm description'
Intervention MeSH terms: Escitalopram
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 2-period cross-over, randomized, double-blinded (escitalopram vs. placebo)study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science