A Study Assessing Brain Activity, Safety, Tolerability, and Pharmacokinetics Following Multiple Doses of MLS101 (Psilocybin) in Healthy Volunteers

A Phase 1 Translational Study to Assess Brain Activity Using Functional Magnetic Resonance Imaging (fMRI) and to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 (Psilocybin) in Healthy Volunteers

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

The purpose of this trial is to investigate brain activity, safety, tolerability, and PK of multiple doses of MLS101 in healthy participants.

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.

The multiple-dose regimen proposed in this study is designed to optimize the pharmacology of MLS101 and elucidate whether it provides a longer period of positive effects, which could be used in future studies in chronic indications such as PMDD, obsessive compulsive disorder and opioid use disorder. Translational functional magnetic resonance imaging (fMRI) imaging will confirm the central nervous system (CNS) activity of priming and repeat low-dose psilocybin, which will serve as a computational evaluation of efficacy and complement the cognitive and perceptual scales and questionnaires.

Inclusion Criteria:

• Males or females aged 18 to 55 years old (inclusive) at the time of signing the informed consent form.
• Standard contraception measures are required for this clinical trial.
• Healthy, in the opinion of the Investigator, based on prior (history of) or current (ongoing) medical and psychiatric screening assessments.
• Participants with no clinically significant findings on physical examination, laboratory tests, and cardiac assessment.
• Body mass index (BMI) within the range 18-32 kg/m2, inclusive.
• Normal blood pressure.
• Willing to not operate heavy machinery, including driving a vehicle at least 36 hours post Day 1 dose administration and 24 hours post all other dose administrations.
• Capable of giving signed informed consent which includes the requirements and restrictions as per the approved study protocol

Exclusion Criteria:

• Prior known exposure to psilocybin, LSD, ayahuasca, N, N-Dimethyltryptamine, and related tryptamines, within the past 5 years.
• Prior (history of) or current (ongoing) diagnosis, or first-degree relatives with clinically significant medical or psychiatric condition or disease.
• History of non-hospitalized but medicated Major Depressive Disorder (MDD), Generalized Anxiety Disorder or Panic Disorder ≤ 5 years prior to Screening.
• History of or presence of cardiovascular disease.
• Abnormal and clinically significant ECG.
• Known personal or family history of congenital long QT syndrome or sudden death.
• Current or a history of orthostatic hypotension or postural orthostatic tachycardic syndrome, multiple syncopes, or unresolved/ongoing clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness.
• History or presence of a neurodegenerative disorder such Alzheimer's disease or Parkinson's disease or other behavioral disturbances resulting from other neurological disorders.
• Use of medications that have CNS effects or affect performance.
• Use of medications with serotonergic activity.
• History or presence of hypersensitivity or idiosyncratic reaction to psilocybin or related compounds or microcrystalline cellulose
• History of substance or alcohol abuse disorder in the last 10 years.
• Participant who, for any reason, is deemed by the Investigator to be inappropriate for this study.
• Contraindications to magnetic resonance imaging (MRI) or fMRI.