Two weeks of escitalopram left psilocybin's positive effects intact and reduced its bad ones, in a crossover trial
After escitalopram 20 mg or placebo, "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".
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Healthy volunteers, 14 days of pretreatment, one psilocybin dose in a laboratory; partly funded by a psychedelic drug developer. The Gukasyan 2023 survey in this wave reports blunting in ordinary use that this design could not detect.
The controlled experiment on the antidepressant plus psilocybin question, run by the same Basel group that studied MDMA and citalopram twenty years earlier.
Significant findings
Becker and colleagues (Clinical Pharmacology and Therapeutics, 2022) 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." Pretreatment was escitalopram 10 mg daily for 7 days then 20 mg for 7 days, including the psilocybin day, against 14 days of placebo.
"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." Nor did it change QTc intervals, BDNF levels or the expression of the serotonin receptor and transporter genes measured.
The authors' own limit: "Further studies are needed with a longer antidepressant pretreatment time and patients with psychiatric disorders to further define interactions between antidepressants and psilocybin."
Worth asking
Fourteen days of escitalopram in healthy people is not years of sertraline in someone with depression, and the survey row beside this one found half of such people report weaker effects. Read together: an SSRI does not appear to make psilocybin dangerous, may soften its worst moments, and may blunt it for some people, especially with longer use. What the trial does not test is the thing people actually do, which is take mushrooms of unknown dose outside a clinic. Funding note: this study was supported in part by Mind Medicine, a psychedelic drug developer, and the senior author consults for it.
Source
Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects — Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, Duthaler U, Varghese N, et al (2022)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1002/cpt.2487
DOI: 10.1002/cpt.2487
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Mixed public and industry funding
- Published in
- Reputable peer-reviewed journal
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 64 out of 100 on our published rubric. One caveat travels with that badge: Healthy volunteers, 14 days of pretreatment, one psilocybin dose in a laboratory; partly funded by a psychedelic drug developer. The Gukasyan 2023 survey in this wave reports blunting in ordinary use that this design could not detect. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects — Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, Duthaler U, Varghese N, et al (2022). Published in: Reputable peer-reviewed journal. DOI: 10.1002/cpt.2487. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Mixed public and industry funding. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.