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

NCT07433452 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: PSILO-2026-11722
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy Participants; Placebo - Control; Psilocybin

Keywords

psychdelics; biomarkers; hd-EEG

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Interpersonal Reactivity Index (IRI)

  Baseline to 7 days post-dose

• Multifaceted Empathy Test (MET) Scores

  Baseline to 7 days post-dose

• Profile of Mood States (POMS)

  From Baseline to 1 week after treatment

• High Density Electroecephalogram (hd-EEG)

  Before the administration of psilocybin or placebo and during the effect of the drug (about 6 hours).

Other Outcomes (1)

• DNA methylation

  Baseline and 1 week after treatment

Study Arms (2)

Psilocybin

ACTIVE COMPARATOR

Drug: Psilocybin (drug)

Placebo

PLACEBO COMPARATOR

Psilocybin vs Placebo

Drug: Placebo

Interventions

Psilocybin (drug) DRUG

One arm will receive psilocybin 25 mg

Also known as: Placebo

Psilocybin

Placebo DRUG

One group will receive a placebo pill

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gabriella Gobbi: lead

MeSH Terms

Interventions

Psilocybin; Pharmaceutical Preparations

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Central Study Contacts

Maryam Oraei, MD

CONTACT

+1-514-3984650; maryam.oraei@mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 25, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: February 25, 2026

Record last verified: 2026-02