A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 in Healthy Participants

A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 (Psilocybin) in Healthy Participants

MLS101 is being developed as a low dose psilocybin, that can be administered to treat neurological and psychiatric conditions.

The purpose of this clinical trial is to assess how safe and tolerated MLS101 is; to see how MLS101 is distributed and cleared by the body (pharmacokinetics); and to assess the psychedelic effects of MLS101 in healthy, adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Psilocybin; Drug: Placebo

Detailed Description

In recent years, high-dose psilocybin has gained attention for it potential therapeutic benefit in many psychiatric conditions, however existing clinical data for low psilocybin doses are limited.

Microdoses are generally considered to be those absent of profound sensory and cognitive effects that would interfere with normal everyday functioning, but only a small number of prospective studies have evaluated microdoses and/or low doses in a controlled manner.

As a foundational study of the therapeutic use of psilocybin microdoses, this study will assess the safety, tolerability, pharmacokinetics and sensorial effects using a prospective, controlled, multiple dose regimen in healthy volunteers.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males or females aged 18 to 65 years old (inclusive) at the time of signing the informed consent form. Standard contraception measures are required for this clinical trial.
2. Healthy, in the opinion of the Investigator, based on prior (history of) or current (ongoing) medical and psychiatric screening assessments.
3. Participants with no clinically significant findings on physical examination, laboratory tests, and cardiac assessment.
4. Body mass index (BMI) within the range 18-32 kg/m2, inclusive.
5. Normal blood pressure.
6. Capable of giving signed informed consent which includes the requirements and restrictions as per the approved study protocol.

Exclusion Criteria:

1. Prior known exposure to psilocybin within the past 5 years.
2. Prior (history of) or current (ongoing) diagnosis, or first-degree relatives with clinically significant medical or psychiatric condition or disease.
3. History of or presence of cardiovascular disease.
4. Abnormal and clinically significant ECG.
5. History or presence of a neurodegenerative disorder such Alzheimer's disease or Parkinson's disease.
6. Use of medications that have CNS effects or affect performance.
7. Use of medications with serotonergic activity.
8. History or presence of hypersensitivity or idiosyncratic reaction to psilocybin or related compounds.
9. History of substance or alcohol abuse disorder in the last 1 year.
10. Participant who, for any reason, is deemed by the Investigator to be inappropriate for this study; or has any condition which would confound or interfere with the evaluation of the safety, tolerability, or PK of the investigational drug; or is unable to comply with the study protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MLS101; MLS101 capsule(s) administered orally as a once a day dose	Drug: Psilocybin; Capsule containing active ingredient, psilocybin; Other Names: MLS101
Placebo Comparator: Placebo; Active treatment matching capsules will be administered orally as a once a day dose	Drug: Placebo; Capsule with no active ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and seriousness of treatment-emergent adverse events (TEAEs)	Physical examinations, safety laboratory tests, ECGs	Screening (Day -28) to end of study visit (Cohort 1: Day 15; Cohort 2: Day 23)
Occurrence of clinically significant changes in physical examination, vital signs, ECGs, clinical laboratory tests, the Columbia-Suicide Severity Rating Scale (C-SSRS).	The Columbia Suicide Severity Rating Scale (C-SSRS) is a short questionnaire. If there is a positive result for suicidality on the C-SSRS after Screening (defined by a participant answering "yes" to questions 4 or 5 on the suicidal ideation portion of the C-SSRS), the participant will be evaluated by an Investigator or medically qualified Sub-investigator for continuation in the study. Participants with suicidal ideation or behaviour (a "yes" answer at any time during treatment to any one of the ten suicidal ideation and behaviour questions (Categories 1-10) on the C-SSRS) at any time during the study will be withdrawn from the study. If a participant becomes suicidal during the study, an Investigator or medically qualified Sub-investigator should provide the appropriate treatment to the participant.	Screening (Day -28) to end of study visit (Cohort 1: Day 15; Cohort 2: Day 23)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of MLS101: maximum observed serum concentration (Cmax)	Blood sample collections	Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
Pharmacokinetics of MLS101: area under the plasma concentration-time curve (AUC)	Blood sample collections	Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
Pharmacokinetics of MLS101: time corresponding to the occurrence of Cmax (Tmax)	Blood sample collections	Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
Pharmacokinetics of MLS101: apparent terminal elimination half-life (t½)	Blood sample collections	Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
Pharmacokinetics of MLS101: apparent total systemic clearance after oral administration (CL/F)	Blood sample collections	Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
Pharmacokinetics of MLS101: apparent volume of distribution during the terminal phase (Vz/F)	Blood sample collections	Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
Sensorial effects of MLS101	Using validated questionnaires, the nominal sensorial threshold dose of MLS101 will be identified. The nominal sensorial threshold dose is defined as the highest dose studied that is absent of clinically significant sensorial effects, and which would not interfere with the participant's ability to carry on with routine activities of daily living. Higher scores indicate presence of sensorial effects.	Day 1 to Day 8 pre- and post-dose (Cohort 1); Day 1 to Day 16 pre- and post-dose (Cohort 2)
Cognitive function: Digit Symbol Substitution Test (DSST)	The test taker's score is the number of correct symbol-to-number matches they complete within the allotted time.	Pre-dose (Day -1), Day 1, Day 4 and Day 8 (Cohort 1); Pre-dose (Day -1), Day 1, Day 4 and Day 16 (Cohort 2)
Cognitive Function: Stroop Color and Word Test (SCWT)	Participants read tables of words and colors as quickly as possible.	Pre-dose (Day -1), Day 1, Day 4 and Day 8 (Cohort 1); Pre-dose (Day -1), Day 1, Day 4 and Day 16 (Cohort 2)
Cognitive function: Trail Making Test A (TMT-A)	The participant draws lines to connect circled numbers in an ascending pattern (i.e., in numerical sequence 1-2-3, etc.) as rapidly as possible. The score is the time it takes the participant to complete the task in seconds.	Pre-dose (Day -1), Day 1, Day 4 and Day 8 (Cohort 1); Pre-dose (Day -1), Day 1, Day 4 and Day 16 (Cohort 2)

Collaborators and Investigators

• Sponsor: MycoMedica Life Sciences PBC

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2024
• Primary Completion (Actual): March 12, 2025
• Study Completion (Actual): March 12, 2025

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: October 13, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: June 9, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: 24-MLS101-102

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