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Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects

Summary

This study examined whether taking the antidepressant escitalopram before using psilocybin affects the drug’s effects. Twenty-three healthy participants took either escitalopram or placebo for two weeks, then received a dose of psilocybin. Surprisingly, escitalopram did not reduce the positive mood effects of psilocybin and actually reduced some negative side effects like anxiety and bad feelings. The combination appeared safe with no increased cardiovascular risks.

Background

Psilocybin is being investigated for treatment of depression and anxiety. Case reports suggest antidepressants may reduce psychedelic effects, leading clinical trials to require discontinuation of antidepressant treatment before psilocybin administration. However, stopping antidepressants can cause withdrawal symptoms and relapse of depression.

Objective

To investigate whether escitalopram pretreatment alters the acute subjective and adverse effects of psilocybin in healthy subjects using a randomized, double-blind, placebo-controlled, crossover design.

Results

Escitalopram pretreatment had no effect on positive mood effects of psilocybin but significantly reduced bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects compared with placebo. Escitalopram did not alter psilocin pharmacokinetics, with a half-life of 1.8 hours. No changes in QTc intervals, HTR2A or SCL6A4 gene expression, or BDNF levels were observed.

Conclusion

Escitalopram pretreatment does not reduce the positive mood effects of psilocybin and may reduce adverse effects. The combination appears safe to administer together. Further studies in patients and with longer antidepressant pretreatment are needed to clarify therapeutic interactions.
  • Published in:Clinical Pharmacology & Therapeutics,
  • Study Type:Randomized Controlled Trial,
  • Source: PMID: 34743319, DOI: 10.1002/cpt.2487
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