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Psilocybin

Phase 3

Major Depressive Disorder | Small molecule | Psychiatry |COMPASS Pathways Plc - American Depository Shares|Last Updated: Aug 10, 2026

Target and mechanism

Molecular targetHTR2A
Target classAgonist
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment122

FDA Designations

No designations recorded

Clinical trial landscape

Psilocybin · 10 trials · 5 indications

Phase 3 3Phase 2 7
NCT06247839The Effects of Psilocybin on Self-Focus and Self-Related Processing in Major Depressive DisorderMajor Depressive Disorder
RECRUITING20 Analytics
NCT05711940Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRDTreatment Resistant Depression
ACTIVE NOT_RECRUITING572 Analytics
NCT05624268Efficacy, Safety, and Tolerability of COMP360 in Participants With TRDTreatment Resistant Depression
COMPLETED258 Analytics
PHASE3RECRUITING
The Effects of Psilocybin on Self-Focus and Self-Related Processing in Major Depressive Disorder
Major Depressive DisorderUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRD
Treatment Resistant DepressionUnlock trial analytics
PHASE3COMPLETED
Efficacy, Safety, and Tolerability of COMP360 in Participants With TRD
Treatment Resistant DepressionUnlock trial analytics

Study Endpoints

Primary Endpoints

Change in Massachusetts General Hospital Rumination Questionnaire (MGH-RQ)
Baseline, and 3 weeks, 6 weeks, 9 weeks, and 12 weeks after psilocybin administration.

A transdiagnostic state measure of rumination over the previous two weeks consisting of 9 items on a 5 point Likert scale from 0 (Never/Rarely) to 4 (All The Time).

Change in Resting-State Functional Connectivity
Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

Changes in resting-state activity during functional magnetic resonance imaging(fMRI) scans.

Change in Self-Attribution Task performance
Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

Participants are shown words one at a time and asked to answer if each of the words apply to 'Self' or 'Other'.

Change in Task-Based Activity during Self-Attribution Task
Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

Changes in activity in the default mode network during functional magnetic resonance imaging(fMRI) scans while participants perform a self-attribution task.

COMP360 25 mg versus COMP360 1 mg for the change from baseline in MADRS total score.
Week 6

Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician rated scale measuring depression severity

COMP360 25 mg versus placebo for the change from baseline in MADRS total score
Week 6

Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician rated scale measuring depression severity

Incidence and occurrence of changes in AEs
Baseline to Day 28
Incidence of clinically important changes in ECG parameters
Baseline to Day 1
Incidence of clinically important changes in laboratory tests
Baseline to Day 1
Incidence of clinically significant changes in vital signs
Baseline to Day 1
Incidence of changes in the Columbia-Suicide Severity Rating Scale (C-SSRS) at each post-Baseline visit
Baseline to Day 28

The C-SSRS will be used to assess suicide potential or tendency as a study entry criteria and monitored throughout the study.

Body Dysmorphic Disorder Modification of the Yale-Brown Obsessive Compulsive Disorder Scale
From baseline (day -1) up to 3 months post-dose

The Yale-Brown Obsessive Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS) is a 12-item, semi-structured, rater-administered measure that assesses body dysmorphic disorder severity during the past week. Scores for each item range from 0 (no symptoms) to 4 (extreme symptoms); the total score ranges from 0 to 48, with higher scores reflecting more severe symptoms.

Safety and tolerability of COMP360 Psilocybin
Up to Week 6

Proportion of patients with adverse events (AEs)

Change from baseline in the Eating Disorder Examination (EDE) global score
Week 4

The EDE is a structured clinical interview (investigator rated) used to measure severity of the characteristic psychopathology of eating disorders

Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Up to 12 weeks

A TEAE is defined as an adverse event (AE) that has an onset on or after the dose of study drug, or any pre-existing AE condition that has worsened on or after the dose of study drug.

Improvement in Depressive Symptoms
3 weeks

Change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to 3 weeks post psilocybin administration. The minimum and maximum MADRS total score values are 0 and 60 and a higher score means a worse outcome.

Montgomery Asberg Depression Rating Scale (MADRS) Change From Baseline to Week 3
Change from Baseline to Week 3

MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response \>= 50% decrease and remission \<= 10 total score.

MADRS Change From Baseline to Week 3, Sensitivity Analysis
Change from Baseline to Week 3

MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response \>= 50% decrease and remission \<= 10 total score.

Secondary Endpoints

Change in Montgomery-Asberg Depression Rating Scale(MADRS)
Baseline, the day before psilocybin administration and at 1 day, 1 week, 2 weeks, 3 weeks, 6 weeks, 9 weeks and 12 weeks after psilocybin administration.
Change in Quick Inventory of Depressive Symptomatology Self Report - 16 item (QIDS-SR-16)
Baseline, the day before psilocybin administration and at 1 day, 1 week, 2 weeks, 3 weeks, 6 weeks, 9 weeks and 12 weeks after psilocybin administration.
Change in Positive and Negative Affect Schedule (PANAS)
Baseline, the day of psilocybin administration and at 3 weeks and 12 weeks after psilocybin administration.
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PsilocybinEXPERIMENTAL25mg Psilocybin
25 mg COMP360 PsilocybinEXPERIMENTAL25 mg COMP360 Psilocybin
10 mg COMP360 PsilocybinEXPERIMENTAL10 mg COMP360 Psilocybin
1 mg COMP360 PsilocybinACTIVE_COMPARATOR1 mg COMP360 Psilocybin, active comparator
PlaceboPLACEBO_COMPARATORMatched placebo
Safety, Tolerability, and TreatmentEXPERIMENTALOn dosing day, each participant will receive 1 x 25 mg treatment bottle containing 5 x 5 mg oral capsules of psilocybin. The administration session will last approximately 4-6 hours and will be supported by a lead therapist and an assisting therapist.
COMP360 PsilocybinEXPERIMENTAL25 mg COMP360 Psilocybin
Low doseEXPERIMENTALLow dose Psilocybin
Medium doseEXPERIMENTALMedium dose Psilocybin
High doseEXPERIMENTALHigh dose Psilocybin

Interventions

NameTypeDescription
PsilocybinDRUGCOMP360 (Brand name of psilocybin to be used)
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Eligibility Criteria

Age Range18 Years to 55 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: 1. Must be able to sign the informed consent form (ICF). Participants will demonstrate capacity to provide informed consent by demonstrated understanding of the protocol and what their involvement in the study requires from them. 2. Be 18-55 years of age at screening. 3. At leas...

Countries:United StatesCanadaCzechiaDenmarkFranceGermanyIrelandNetherlandsPolandSpainSwedenUnited KingdomPortugal
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Recent Changes (Last 90 Days)

LOWAug 11, 2026NCT05711940primaryCompletionDate: changed
HIGHAug 11, 2026NCT05624268Status: ACTIVE_NOT_RECRUITING → COMPLETED
LOWAug 11, 2026NCT05711940primaryCompletionDate: changed
HIGHAug 11, 2026NCT05624268Status: ACTIVE_NOT_RECRUITING → COMPLETED
LOWAug 11, 2026NCT05711940primaryCompletionDate: changed
HIGHAug 11, 2026NCT05624268Status: ACTIVE_NOT_RECRUITING → COMPLETED

Frequently asked questions about Psilocybin

What is Psilocybin used for?

Psilocybin is an investigational small molecule being developed by COMPASS Pathways for several psychiatric conditions, including Post Traumatic Stress Disorder, Body Dysmorphic Disorders, Anorexia Nervosa, Major Depressive Disorder, and Treatment Resistant Depression. It is currently in Phase 2 clinical trials and is not yet approved by the FDA.

What does Psilocybin target?

Psilocybin targets the HTR2A receptor, acting as an agonist. This means it binds to and activates the serotonin 2A receptor, which is thought to modulate mood and perception. This mechanism is being studied for its potential therapeutic effects in various psychiatric disorders.

Who makes Psilocybin?

Psilocybin is being developed by COMPASS Pathways Plc, a biopharmaceutical company traded on the NASDAQ under the ticker symbol CMPS. The company is conducting clinical trials to evaluate the safety and efficacy of psilocybin for multiple psychiatric indications.

What phase is Psilocybin in?

Psilocybin is currently in Phase 2 clinical development. It is being studied in multiple Phase 2 trials for conditions such as Post Traumatic Stress Disorder, Anorexia Nervosa, and Major Depressive Disorder. Psilocybin is an investigational drug and has not received FDA approval.

What clinical trials is Psilocybin in?

Psilocybin is being evaluated in several clinical trials, including NCT05312151 for Post Traumatic Stress Disorder, NCT05481736 for Anorexia Nervosa, and NCT05733546 for Major Depressive Disorder. These trials are Phase 2 studies with active or completed status, involving adult participants.

Is Psilocybin the same as COMP360?

Psilocybin is the active ingredient in COMP360, which is the investigational drug product developed by COMPASS Pathways. Clinical trials such as NCT05312151 and NCT05733546 refer to COMP360, indicating that COMP360 contains psilocybin as its active pharmaceutical ingredient.