Escitalopram mostly dampens the nastiness of psilocybin, but not the positive experience

There is a scientific article that investigates whether escitalopram, a widely used SSRI, alters the acute effects of psilocybin.

In it, we discuss:

The researchers conducted a randomized, double-blind, placebo-controlled crossover study in healthy volunteers. Participants received 25 mg of psilocybin twice, escitalopram once after 14 days, and placebo once after 14 days. The escitalopram pretreatment consisted of 10 mg per day for 7 days, followed by 20 mg per day for 7 days, including the day of psilocybin administration.

The real focus of this article lies on the question of whether an SSRI weakens the psilocybin experience or makes it more dangerous. This is important because antidepressants are tapered off beforehand in many psilocybin studies, whereas it was not entirely clear whether that is always necessary.

The results show that escitalopram barely altered the positive subjective effects of psilocybin. Total scores on scales for altered states of consciousness remained largely comparable. However, escitalopram did specifically reduce anxious and unpleasant aspects of the experience, such as anxious ego dissolution and anxiety.

Physically, too, escitalopram appeared to make the experience slightly milder. According to the authors, the pretreatment reduced adverse cardiovascular effects and other side effects of psilocybin. At the same time, escitalopram did not alter the pharmacokinetics of psilocin, suggesting that the effect is primarily pharmacodynamic and not due to a reduced level of active substance in the blood.

In addition, the researchers found no change in QTc interval, no marked change in circulating BDNF levels, and no change in HTR2A or SCL6A4 gene expression prior to psilocybin administration. The half-life of free psilocin averaged 1.8 hours, which is consistent with the relatively short duration of action of psilocybin.

It is important to note, however, that this study was conducted in healthy subjects and with only two weeks of escitalopram pretreatment. Therefore, this article does not automatically prove that long-term use of antidepressants has exactly the same effect in patients. The authors themselves indicate that follow-up research is needed with longer pretreatment and in psychiatric populations.

In one sentence: this article shows that escitalopram hardly weakens the positive effects of psilocybin, but primarily seems to reduce the anxious and unpleasant aspects of the experience.