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The present study used a double\u2010blind, placebo\u2010controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25\u00a0mg) in healthy subjects after pretreatment with escitalopram or placebo. The treatment order was random and counterbalanced. Pretreatment consisted of 10\u00a0mg escitalopram daily for 7\u00a0days, followed by 20\u00a0mg daily for 7\u00a0days, including the day of psilocybin administration, or 14\u00a0days of placebo pretreatment before psilocybin administration. Psilocybin treatments were separated by at least 16\u00a0days. The outcome measures included self\u2010rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain\u2010derived neurotrophic factor (BDNF) levels, electrocardiogram QTc time, whole\u2010blood <jats:italic>HTR2A<\/jats:italic> and <jats:italic>SCL6A4<\/jats:italic> gene expression, and pharmacokinetics. Escitalopram pretreatment had no relevant effect on positive mood effects of psilocybin but significantly reduced bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects of psilocybin compared with placebo pretreatment. Escitalopram did not alter the pharmacokinetics of psilocin. The half\u2010life of psychoactive free (unconjugated) psilocin was 1.8\u00a0hours (range 1.1\u20132.2\u00a0hours), consistent with the short duration of action of psilocybin. Escitalopram did not alter <jats:italic>HTR2A<\/jats:italic> or <jats:italic>SCL6A4<\/jats:italic> gene expression before psilocybin administration, QTc intervals, or circulating BDNF levels before or after psilocybin administration. Further studies are needed with a longer antidepressant pretreatment time and patients with psychiatric disorders to further define interactions between antidepressants and psilocybin.<\/jats:p>","DOI":"10.1002\/cpt.2487","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T13:04:05Z","timestamp":1636290245000},"page":"886-895","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double\u2010Blind, Placebo\u2010Controlled, Crossover Study in Healthy Subjects"],"prefix":"10.1111","volume":"111","author":[{"given":"Anna M.","family":"Becker","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Toxicology Department of Biomedicine University Hospital Basel University of Basel Basel Switzerland"},{"name":"Department of Clinical Research University Hospital Basel University of Basel 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