Clinical Pharmacology & Therapeutics
November 7, 2021
A. Becker, Friederike Holze, Tanja Grandinetti et al.
177 citations
In healthy volunteers, taking the antidepressant escitalopram for two weeks before a 25 mg dose of psilocybin did not reduce the positive mood effects of the psychedelic, but it significantly lessened bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects compared to placebo pretreatment. Escitalopram did not alter psilocin's pharmacokinetics; the half-life of free psilocin was 1.8 hours. It also did not change HTR2A or SCL6A4 gene expression, QTc intervals, or BDNF levels. Longer antidepressant pretreatment and studies in patients are needed to further define interactions between antidepressants and psilocybin.
Clinical Pharmacology & Therapeutics
February 28, 2025
Lorenz Mueller, Alen Jelusic, Avram Tolev et al.
15 citations
In a double-blind, placebo-controlled crossover study with 23 healthy participants, daily paroxetine (an SSRI antidepressant) did not reduce the pleasant subjective effects of a single 100 μg dose of LSD, but it significantly lessened negative effects such as 'bad drug effect,' anxiety, and nausea. Paroxetine increased LSD's peak concentration and total exposure by 40% and 50%, respectively, by inhibiting the CYP2D6 enzyme, indicating this enzyme is involved in LSD metabolism. The interaction was strongest in normal CYP2D6 metabolizers and weakest in poor metabolizers. The findings suggest LSD can be safely added to SSRI treatment without dose adjustment when the SSRI inhibits CYP2D6, but no definitive recommendation can be made for other SSRIs.
Frontiers in Pharmacology
June 28, 2017
Patrick C. Dolder, Edna Grünblatt, Felix Müller et al.
12 citations
A single 100 μg dose of LSD did not change the expression of the serotonin 5-HT2A receptor gene (HTR2A) or the early growth response genes EGR1, EGR2, and EGR3 in the whole blood of 15 healthy subjects, measured 1.5 and 24 hours after administration. This null finding contrasts with rodent studies showing that LSD acutely increases EGR1 and EGR2 expression in the brain and that repeated use reduces 5-HT2A receptor binding. Whether chronic LSD administration alters gene expression in humans remains unknown.