10:00am - 10:30am
Track 2: Bernhard von Langenbeck Room
Effects of Serotonin Reuptake Inhibitor (SSRI) Pretreatment on the Subjective Response to Psilocybin in Healthy Subjects
Psilocybin is investigated as a treatment for a variety of psychiatric disorders, including mood and anxiety disorders. Psilocybin is a prodrug that is activated to psilocin in the body. Its effects are primary mediated by partial agonism at the serotonin ﴾5‐HT﴿ 2A receptor. First-line therapy for patients with mood and anxiety disorders are serotonin reuptake inhibitors ﴾SSRls﴿, which acutely increase 5‐HT levels in the synapses in the brain, however, the mood‐elevating effects generally occur after several weeks of repeated daily treatment and are likely associated with adaptive changes of the brain. For example, chronic administration of SSRIs decreases the number of 5‐HT2 receptors in various brain regions due to receptor downregulation. An SSRI treatment is therefore expected to reduce the acute responses to psilocin. However, the exact extent of the interaction of these two substances has not yet been studied. For phase two studies and compassionate use programs, which use psilocybin it will be important to know whether patients need to stop their SSRI treatment before psilocybin administration. Hence, the aim of the present study was to evaluate interactions of psilocybin and the commonly used SSRI escitalopram.
Methods: A double‐blind, randomized, placebo‐controlled, crossover trial pretreating 23 healthy volunteers with escitalopram or placebo for 14 days ﴾10 mg in the 1st and 20 mg in the 2nd week﴿, followed by a single administration of 25 mg psilocybin was carried out. Psychometric tools, such as the five‐dimensions of Altered States of Consciousness ﴾5D‐ASC﴿, Mystical effects questionnaire ﴾MEQ﴿ and visual analogue scales ﴾VASs﴿ were assessed, as well as autonomic effects, plasma concentrations and concentration-effect relationships using PK‐PD modeling.