Naturalistic Study of Microdosing With Psilocybin (NATMICRO)

Double-blind Placebo-controlled Naturalistic Study of Microdosing With Psilocybin: Effects on Brain Activity, Behavior, Cognition, Creativity, and Mental Health

This study seeks to understand the neural, cognitive and behavioral effects of low doses of psilocybin administered in the form of dried mushroom material (0.5 g of Psilocybe cubensis) consumed in natural settings following a placebo-controlled double-blind experimental design.

Study Overview

• Status: Completed
• Conditions: Sleep; Cognitive Change; Mood Change; Creativity
• Intervention / Treatment: Drug: Psilocybin; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1428
    • Instituto de Fisica de Buenos Aires (IFIBA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and woman with more than 21 years.
2. Participans are planning to microdose using their own dried mushroom material and adhere to the experimental protocol.
3. No active psychiatric conditions requiring treatment with psychotropic medications.
4. Able to provide informed consent.

Excusion Criteria:

1. Use of psychotropic medication during the study, including stimulants such as caffeine.
2. Prior adverse reactions to psychedelics according to the Challenging Experiences Questionnaire administered during initial screening.
3. Pregnant women or women during lactation
4. History of high or low blood pressure or other cardiovascular risks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Psilocybe cubensis; 0.5 g dried and powdered P. cubensis in gel capsules, dosing on two separate days, separated by one week from the placebo, randomized order.	Drug: Psilocybin; 0.5 g dried Psilocybe cubensis mushroom material, 0.8 mg psilocybin.
Placebo Comparator: Inactive placebo; Same weight of inactive placebo in gel capsules, dosing on two separate days, separated by one week from the placebo, randomized order.	Drug: Placebo; 0.5 g dried edible non-psychoactive mushroom material.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting state oscillations measured with EEG	Our goal is to study changes in spectral content before and during the acute effects with the purpose of comparing changes with those observed under higher doses of psilocybin.	1 week
Attention	Measured performance in the attentional blink paradigm	1 week
Inhibitory control	Measured using the go/no go experimental paradigm	1 week
Conscious access	Measured using the backward masking paradigm	1 week
Visual perception	Measured using the binocular rivalry paradigm	1 week
Physical activity	Measured using wrist actigraphy using a smartwach	1 week
Divergent thinking	Measured using the Alternative Uses Task (AUT)	1 week
Attention	Measured using the hiearchical mismatch negativity paradigm combined with EEG	1 week
Cognitive flexibility	Measured using the stroop task	1 week
Convergent thinking	Measured using the Remote Associations Task (RAT)	1 week
Convergent thinking	Measured using the Wallach-Kogan test (WK)	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect positive/negative affect and well-being	Measured using the Positive and Negative Affect Schedule (PANAS)	1 week
Effects on anxiety	Measured using State Trait Anxiety Inventory (STAI)	1 week
Effects on personality	Measured using the Big Five inventory (BFI)	1 week
Concentration of psilocybin in the dried material	To be measured using high performance liquid chromatography	1 week

Collaborators and Investigators

• Sponsor: National Council of Scientific and Technical Research, Argentina
• Investigators: Principal Investigator: Enzo Tagliazucchi, PhD, National Council of Scientific and Technical Research, Argentina

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2021
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): December 16, 2021
• Last Update Submitted That Met QC Criteria: December 3, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: sleep; cognition; behavior; EEG; psilocybin; microdosing; creativity; psychedelics; nootropics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: 001 (NavyGHB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All raw data will be made available online through a data sharing webside (e.g. Zenodo) upon publication of the pre-pring containing the results of our study.
• IPD Sharing Time Frame: After publication, indefinite.
• IPD Sharing Access Criteria: Public
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No