Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study in Healthy Subjects
Anna M Becker, Friederike Holze, Tanja Grandinetti, Aaron Klaiber, Vanja E. Toedtli, Karolina E. Kolaczynska, Urs Duthaler, Nimmy Varghese, Anne Eckert, Edna Grünblatt, Matthias E. Liechti
Clinical Pharmacology & Therapeutics November 7, 2021 DOI: 10.1002/cpt.2487 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, crossover study Randomized Peer reviewed |
|---|---|
| Population | Healthy subjects |
| Interventions | Escitalopram Psilocybin |
| Dose | 25 mg psilocybin; 10 mg escitalopram daily for 7 days, then 20 mg daily for 7 days |
| Duration | 14-day pretreatment, psilocybin sessions separated by at least 16 days |
| Topics | Psilocybin |
| Keywords | Escitalopram Placebo Crossover study Pharmacology Antidepressant Adverse effect Anesthesia Hallucinogen |
| Citations | 177 |
| Key points | Escitalopram pretreatment reduced adverse effects of psilocybin without diminishing its positive mood effects. |
Abstract
The psychedelic psilocybin is being investigated for the treatment of depression and anxiety. Unclear is whether antidepressant treatments interact with psilocybin. The present study used a double‐blind, placebo‐controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25 mg) in healthy subjects after pretreatment with escitalopram or placebo. The treatment order was random and counterbalanced. Pretreatment consisted of 10 mg escitalopram daily for 7 days, followed by 20 mg daily for 7 days, including the day of psilocybin administration, or 14 days of placebo pretreatment before psilocybin administration. Psilocybin treatments were separated by at least 16 days. The outcome measures included self‐rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain‐derived neurotrophic factor (BDNF) levels, electrocardiogram QTc time, whole‐blood HTR2A and SCL6A4 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‐life of psychoactive free (unconjugated) psilocin was 1.8 hours (range 1.1–2.2 hours), consistent with the short duration of action of psilocybin. Escitalopram did not alter HTR2A or SCL6A4 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.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 164
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology February 25, 2022
- Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology September 1, 2023
- Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology October 1, 2023
- Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis. Psychiatry Research May 1, 2024
and 159 more in the library
Cites 37
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
and 32 more in the library