Naturalistic Study of Microdosing With Psilocybin

Sub-threshold doses of serotonergic psychedelics are frequently consumed as cognitive enhancers, and due to their purported positive effects on mood, energy and creativity ("microdosing").

The acute and short-term effects of psilocybin (the psychoactive compound of Psilocybe cubensis mushrooms) on several variables will be investigated, comprising spontaneous and evoked electrophysiological brain activity, perception and cognitive function (cognitive flexibility, attention, inhibitory control, conscious access, visual perception), creativity (problem solving, divergent and convergent thinking), behavior (actigraphy and sleep patterns, natural language production) and several domains related to well-being and mental health of the participants.

This study is simultaneously naturalistic (i.e. recruited subjects are intrinsically motivated to microdose, as they have decided to embark in a microdosing protocol) and controlled by expectations, following a double-blind placebo-controlled design. Participants will microdose according to the following schedule:

Two sessions (0.5 g dried Psilocybin mushrooms vs. dried edible mushroom material without psychoactive effects as a placebo condition) will be conducted. A third party will be in charge of generating their active dose and placebo capsules, and they will also implement a blinding procedure.

Each session will span one week of measurements. Subjects will be given a smartwatch to monitor activity and sleeping patterns at the beginning of the week. At days 3 and 5, subjects will take capsules with active mushroom material or placebo, and then several variables will be recorded. Experiments will be conducted in a setting that is natural and comfortable for the participants, e.g. their homes.

The main outcome measures consist of resting state activity recorded with EEG, evoked response potentials and performance during cognitive tasks, behavioral variables obtained with actigraphy and automated sleep scoring, natural language analysis, and several measurs self-reported via standarized questionnaires.

After completion, this study will provide direct evidence concerning the efficacy of microdosing for cognitive enhancement under natural conditions, i.e. those most frequently used by individuals who microdose, as well as provide information concerning the potential underlying neurobiological mechanisms.