Bioavailability Study of Psilocybin in Normal Adults

Study Overview
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Brief Summary
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The purpose of this research study is to compare an oral dose of psilocybin and an intravenous (IV) infusion of psilocybin to assess differences in how the drug is absorbed by the body, the psychedelic experience, and any side effects when taken by healthy adult participants. Participants can expect to be in the study for approximately 12 weeks.

Detailed Description
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Psilocybin, when delivered to screened and prepared participants in a controlled environment, has shown strong evidence of positive effects in treating cancer-related psychiatric distress, depression and anxiety, treatment-resistant depression, and nicotine or alcohol addiction. Psilocybin therapy is generally safe and well-tolerated when conducted under controlled conditions. Psilocybin is very rapidly transformed to the active metabolite psilocin, which is considered the active agent from psilocybin administration. Oral and IV psilocybin are expected to have similar pharmacokinetic and psychedelic effects, as well as safety profiles, while IV psilocybin will achieve more consistent blood levels than are possible with oral psilocybin.

Official Title
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A Phase 1 Study Comparing the Pharmacokinetics and Safety of Intravenous and Oral Psilocybin

Conditions
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Healthy

Intervention / Treatment
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* Drug: Oral Psilocybin
* Drug: IV Psilocybin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overall healthy and medically stable, as determined by screening Capable of giving signed informed consent Negative urine pregnancy test in persons of childbearing potential Exclusion Criteria: Have any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, prior myocardial infarction, tachycardia, artificial heart valve, corrected QT interval (QTc) >450 msec at screening, any other clinically significant screening ECG abnormality, or any other significant cardiovascular condition Presence of a gastrointestinal disease that could interfere with absorption of an orally administered drug Have epilepsy Positive urine drug test Prior adverse effects from psilocybin or other psychedelics that required hospitalization Currently taking on a regular basis (e.g., daily) any medications having a primary centrally acting serotonergic effect, including selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), or serotonin-acting dietary supplements (such as 5-hydroxy-tryptophan or St. John's wort) Currently taking prohibited medications, including antihypertensive medications, UGT1A9 or 1A10 inhibitors (e.g., regorafenib, rifampicin, phenytoin, eltrombopag, mefenamic acid, diflunisal, niflumic acid, sorafenib, isavuconazole, deferasiroxor, ginseng), and aldehyde or alcohol dehydrogenase inhibitors (e.g,, disulfiram) Participation in another concurrent clinical study; or use of investigational drugs, biologics, or devices within 30 days prior to assignment of study drug administration order Anyone who is pregnant, lactating, or planning on becoming pregnant during the study Unwilling to withhold prohibited concomitant medications

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral and IV psilocybin<br>Psilocybin with psychological support: Psilocybin will be administered in the form of capsules, taken orally with water, at one visit. Psilocybin will be administered through IV at the other visit. | Drug: Oral Psilocybin<br>* 25mg orally<br>Drug: IV Psilocybin<br>* 5mg intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum concentration of psilocin following oral and IV administrations of psilocybin | Determine the maximum plasma concentration of psilocin in plasma following a single IV dose as compared to that following a single oral dose. | Day 8, Day 22 | 
| Determine the concentration of psilocin following oral and IV administrations of psilocybin | Determine the time to maximum plasma concentration of psilocin in plasma following a single IV dose as compared to that following a single oral dose. | Day 8, Day 22 | 
| Determine the concentration of psilocin following oral and IV administrations of psilocybin | Determine the half-life of psilocin in plasma following a single IV dose as compared to that following a single oral dose. | Day 8, Day 22 | 
| Determine the concentration of psilocin following oral and IV administrations of psilocybin | Determine the AUC of psilocin in plasma following a single IV dose as compared to that following a single oral dose. | Day 8, Day 22 | 
| Difference in the area under plasma concentration-time curve (AUC) between psilocybin administration methods. | AUC will be determined after oral and IV psilocybin doses to assess for more consistent blood concentration. | Day 8, Day 22 | 
| Difference in the maximum concentration (Cmax) between psilocybin administration methods. | Cmax will be determined after oral and IV psilocybin doses to assess for more consistent blood concentration. | Day 8, Day 22 | 
| Difference in the time to maximum plasma concentration (Tmax) between psilocybin administration methods. | Tmax will be determined after oral and IV psilocybin doses to assess for more consistent blood concentration. | Day 8, Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the incidence and severity of adverse events associated with doses of psilocybin in healthy adults | The incidence and severity of expected and unexpected adverse events will be collected using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials | 12 weeks | 
| Suicidal ideation | Assessed using the Columbia - Suicide Severity Rating Scale (C-SSRS) at every in-person visit | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psilocybin, psychedelics