The Effects of Psilocybin in Healthy Volunteers: Psychological, Biochemical and Electrophysiological Biomarkers. (PSILOBIOMARKER)

In this study, participants will received either psilocybin (the active ingredient found in certain mushrooms) or an inactive placebo (a look-alike tablet with no active drug). The psilocybin is supplied by Filament Health (Burnaby, British Columbia).

After psilocybin ingestion, the body quickly converts it into psilocin, which is the form that produces the temporary psychological effects. Psilocin mainly works by interacting with serotonin receptors in the brain, especially a type called the 5-HT2A receptor.

This study will be done in healthy volunteers using a single oral dose of 25 mg (one tablet by mouth), consistent with doses used in previous clinical research.

The goal is to understand the biological, psychological, and high-density EEG (hd-EEG) changes that can happen after a one-time dose of psilocybin.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Participants; Psilocybin; Placebo - Control
• Intervention / Treatment: Drug: Psilocybin (drug); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Maryam Oraei, MD; Phone Number: +1-514-3984650; Email: maryam.oraei@mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or Female adults ages 21-65 at the time of screening.
• Females of childbearing potential must have a negative pregnancy test at all designated visits.
• Have a self-reported interest in psychedelic drugs and altered states of consciousness.
• Never have used a classic, serotonergic psychedelic (such as psilocybin, psilocybin, LSD, or ayahuasca) or a dissociative anesthetic such as ketamine or PCP), or maximum one experience 5 years before the study starting without untoward effects.
• Participants must be free of current or past substance use dependence or disorders, as determined by a semi-structured clinical interview for DSM-5 diagnoses (SCID-DSM-5).
• Have a Body Max Index (BMI) 18-34 kg/m2 and an abdomen circumference ≤ 90 for women and 97 for men.
• In the investigator's opinion, participants are reliable and willing and able to comply with the protocol requirements and procedures.
• In addition to meeting the inclusion criteria outlined, it is important to develop a positive rapport between all individuals both participating in and coordinating the study.

Exclusion Criteria:

• Any psychiatric, cardiovascular, neurological, or other disorders that may be aggravated by participation in the study, or complicate interpretation of the study's results.
• Any substance use disorder.
• For women, a positive pregnancy test, or not using a reliable method of birth control.
• Personal or family history of severe psychiatric disorders (schizophrenia, bipolar disorder, addiction, ASD) and/or psychosis in the first and second degree.
• During the interview family history is asked in detail. Example: Did your parents or grandparents received a diagnosis of schizophrenia, bipolar disorder, depression.... Did somebody die by suicide? ...Did somebody was hospitalized in a psychiatric hospital? Did somebody in the family was judged "strange"? Different? Even if 40 years ago the diagnosis of depression or bipolar disorder was less precise, do you have the impression that somebody was sick?
• A resting blood pressure > 140 systolic and 90 diastolic (mmHg).
• Cardiovascular diseases including valvulopathy.
• Current tricyclic antidepressant, lithium, SSRIs, first- and second-generation ketamine antipsychotics, or MAOI prescription regimen.
• Current dietary supplementation of 5-hydroxytryptophan and St. John's Wort.
• Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure e.g. CLRC < 30 ml/min etc.).
• History of serious suicide attempts requiring hospitalization.
• Significant history of mania (determined by study psychiatrist and medical records).
• Psychiatric condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin, e.g. borderline personality disorder.
• Blood or needle phobia.
• Participants who do not agree to use an acceptable contraceptive method throughout their participation in study.
• Use of contraindicated medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Psilocybin	Drug: Psilocybin (drug); One arm will receive psilocybin 25 mg; Other Names: Placebo
Placebo Comparator: Placebo; Psilocybin vs Placebo	Drug: Placebo; One group will receive a placebo pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 AG (pmol/mL) , 2 OG (pmol/mL) , AEA (pmol/mL) , OEA (pmol/mL) , PEA (pmol/mL)	Plasmatic Endocannabinoids	Baseline to 7 days post-dose
Trp (μg/mL) , Kyn (ng/mL) , Kyn/Trp*1000 , 5 HT (ng/mL)	Tryptophan Pathways	Baseline to 7 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interpersonal Reactivity Index (IRI)	Interpersonal Reactivity Index (IRI, 28 items): A multidimensional assessment of empathy. There are 4 subitems measuring Perspective Taking, the tendency to spontaneously adopt the psychological point of view of others; Fantasy, one's tendency to transpose themselves imaginatively into the feelings and actions of fictitious characters; Empathic Concern, feelings of sympathy and concern for unfortunate others; and Personal Distress, feelings of personal anxiety and unease in tense interpersonal settings.	Baseline to 7 days post-dose
Multifaceted Empathy Test (MET) Scores	The Multifaceted Empathy Test (MET) is used to measure empathy competence. It consists of a series of photorealistic images showing people in emotionally charged situations. The test yields two primary sub-scores: 1) Cognitive Empathy: Participants infer the mental state of the person in the image; 2) Emotional Empathy: Participants rate their own emotional reaction to the image (e.g., "How much do you feel for this person?"). Responses are typically recorded on a Likert scale (e.g., 1-9), where 1 represents "not at all" and 9 represents "very strong." Scores are summed for each component, with higher scores indicating higher levels of empathy.	Baseline to 7 days post-dose
Profile of Mood States (POMS)	POMS is a 65 item scales which assesses transient mood states in individuals 18 and older. The scale has been widely used within clinical psychiatric and psychotherapeutic environments for the purpose of assessing individuals' mood-related treatment responses. There are 6 subscales, including Tension-Anxiety, Depression, Anger-Hostility, Fatigue, Confusion-Bewilderment, and Vigour-Activity. The scale has been validated widely and possesses test-retest reliability.	From Baseline to 1 week after treatment
High Density Electroecephalogram (hd-EEG)	High-density electroencephalography (hd-EEG) is a non-invasive method used to record electrical brain activity from multiple electrodes placed on the scalp. This technique provides detailed information about brain function and neural activity. In this study, hd-EEG will be used to assess changes in brain activity following study drug administration. The procedure is painless and involves wearing an electrode cap for approximately 20-40 minutes.	Before the administration of psilocybin or placebo and during the effect of the drug (about 6 hours).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA methylation	DNA methylation and histone modification) analysis of genes involved in spirituality and resilience	Baseline and 1 week after treatment

Collaborators and Investigators

• Sponsor: Gabriella Gobbi

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: biomarkers; psychdelics; hd-EEG
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin; Pharmaceutical Preparations
• Other Study ID Numbers: PSILO-2026-11722

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No