Assessing the Efficacy of Micro-dosed Psilocybin on Reducing Anxiety & Depression Levels in Adults

Randomized Double Blind Placebo Controlled Assessing the Efficacy of Micro-dosed Psilocybin in Reducing Anxiety and or Depression Levels in Adults

To investigate the efficacy of a 16 week treatment with PSIL428 patient reported anxiety levels in otherwise healthy individuals suffering from depression and or anxiety symptoms.

Study Overview

• Status: Withdrawn
• Conditions: Anxiety and Depression
• Intervention / Treatment: Drug: PSIL428; Drug: PSIL428; Dietary supplement: Oyster mushroom

Detailed Description

Randomized, double-blind, placebo-controlled study assessing the efficacy of micro-dosed psilocybin on reducing anxiety and/or depression levels in adults

Study summary:

The Institute for Health Metrics and Evaluation reported that Anxiety disorders currently affect an estimated 275 million people worldwide, about one in 13 people (7.3 percent).

COVID-19 has accelerated the rate of new anxiety diagnoses and exacerbated pre-existing diagnoses of anxiety in individuals worldwide.

The effectiveness of full dose psilocybin for treatment of anxiety and depression has been shown in a number of clinical trials. While there is a significant evidence of clinical efficacy of full dose psilocybin, acute effects of the dose result in a significant impairment - perceptual and sensory distortions incapacitating the patient for the duration of drug activity. Recent work suggests while not producing perceptual changes, micro-dosing may indeed be associated with improved mood and enhanced well-being. The practice of micro-dosing is gaining popularity in the general population, while clinical data on its safety and efficacy is lacking.

This will be a novel randomized, double-blind, placebo-controlled study aimed at establishment of safety and anxiolytic efficacy of psilocybin PSIL428 administered in a micro-dosing regimen (2-5% of a full therapeutic dose) to adults suffering from depression or anxiety.

The primary outcome of this study is the change in anxiety and/or depression levels from screening to week 16. Participant anxiety levels will be monitored through Beck Anxiety inventory, depression levels - through Beck Depression Inventory forms on a bi-weekly basis across the course of the study.

Study Drug PSIL428 is an experimental intervention and the active ingredient psilocybin is botanically derived. Similar interventions are currently undergoing Phase IIb/III clinical trials in international jurisdictions. It is being assessed for treatment of depressive disorders. Typically psilocybin used in full therapeutic doses associated with significant acute adverse effects. The proposed trial would utilize psilocybin in different dosing regimen - as micro-dosing - ingesting of sub-perceptual doses of the drug equal to 2-10% of the full dose. The micro-dosing practice is gaining significant popularity world-wide, however evidence-based data around it is minimal. Risks and benefits associated with the trial are not definitively established, however existing pre-clinical and clinical data around full-dose use of the drug carries a favorable risk-benefit potential.

The trial will be conducted in accordance with the most recently acceptable version of the Declaration of Helsinki, Good Clinical Practice (GCP) according to International Conference on Harmonization (ICH) guidelines, and applicable Standard Operating Procedures (SOPs). The trial will be conducted under a protocol reviewed and approved by an IRB; the trial will be conducted by scientifically and medically qualified persons; the benefits of the study are in proportion to the risks; the rights and welfare of the subjects will be respected; each subject will give his or her written informed consent before any protocol-driven tests or evaluations are performed.

The investigators are responsible for obtaining informed consent in adherence to GCP and according to applicable regulations prior to entering the subject into the trial.

A positive change in Beck Anxiety and/or Beck Depression numeric levels between PSIL428 and placebo groups will mark our primary outcome achievement of confirming beneficial effects of micro-dose-administered psilocybin on study participants' overall anxiety and/or depression levels

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Jamaica
  • Kingston, Jamaica
    • FMS Department of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Experiencing persistent anxiety and/or depression symptoms
• Scoring between 10-20 on BAI and/or between 15-25 on BDI-II
• Females and males with the minimum age of 18 at screening;
• Not of child bearing potential, which is defined as females who have had hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with 1 year since last menstruation)

OR

• Female participants of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result, prior to enrollment. All hormonal birth controls require a minimum stability of three months and remain consistent throughout the study. Acceptable methods of birth control include:
• Hormonal contraceptives; oral, hormone patch (Ortho Evra), vaginal ring (NuvaRing), injectable (Depo-Provera, Lunelle), or hormone implant (Norplant System)
• Double-barrier method
• Intrauterine devices
• Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
• Vasectomy of partner (shown successful as per appropriate follow-up);
• Willing to maintain current levels of activity throughout the study;
• Healthy as determined by self-report and medical history;
• Willingness to complete all study visits and requirements associated with the study;
• Has access to a computer, tablet, or smart phone with internet connection; sufficiently comfortable with using app-based technology for data gathering;
• Has given voluntary, written, informed consent to participate in the study.

Exclusion Criteria

• Individuals who are pregnant, breastfeeding, or planning to become pregnant.
• Individuals with psychotic disorders including schizophrenia; bipolar disorder. personality disorder. Participants with 1st-degree relatives with related psychotic disorders.
• Alcohol or drug abuse within the last 6 months that meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
• Participation in a clinical research study within 30 days of enrollment.
• Allergy or sensitivity to study product ingredients.
• Clinically significant abnormal laboratory results at screening.
• Unstable medical conditions as assessed by the Principal Investigator.
• Individuals who are cognitively impaired and/or unable to give informed consent.
• Any other condition which in the Principal Investigator's opinion may adversely affect the participant's ability to complete the study or its measures or which may pose significant risk to the participant.
• Individuals who have taken a psychedelic drug (Psilocybin, DMT, Peyote, Ayahuasca, Ibogaine, LSD, Ketamine) within 60 days of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention arm; participants will take the active intervention PSIL428	Drug: PSIL428; 1 mg of psilocybin; Drug: PSIL428; 1 mg psilocybin
EXPERIMENTAL: placebo arm; participants will take the intervention 1 mg Oyster mushrooms	Dietary supplement: Oyster mushroom; 1 mg of oyster mushroom
EXPERIMENTAL: open label; all participants will take the active intervention PSIL428	Drug: PSIL428; 1 mg of psilocybin; Drug: PSIL428; 1 mg psilocybin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Beck Anxiety Inventory BAI	Measures 21 items in physical and cognitive anxiety ranges 0-7 mild, to 26-63 severe Questionnaire BDI-11	Screening to week 16
Changes in Beck Depression Inventory 02 - BDI-II	Measures 21 items in the presence and severity of depressive symptoms 0-9 no depression, 10 -18 mild depression, 19-29 moderate to severe depression	screening to week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the European Quality of life 5 dimensions- EQ-5D	changes between the intervention PSIL-428 and placebo groups for mobility, self-care, pain & discomfort, usual activities and anxiety & depression	screening to week 16
Cognitive flexibility, using the Stroop Color & Word Test (SCWT)	Changes in cognition between the PSIL-428 and placebo groups in the reading of words as compared to identifying & naming colors. A stopwatch is used and the test-taker reads color words or names ink colors from different pages as quickly as possible. An interference score, cognitive flexibility, creativity and reaction to cognitive pressure are measured	Screening to week 16
Changes in resilience using the Brief Resiliency Scale	assesses the ability of the individual to bounce back or recover from stress a score of one means low resiliency and a score of 5 means high resiliency	Screening to 16 weeks
Measurement of higher level cognitive processes using the Wisconsin Card Sorting Test	Uses two card packs, having 4 stimulus cards and 64 response cards measures attention, perseverance , abstract thinking and set shifting.	screen to 16 weeks
The incidence of adverse events	The number of reported cases of adverse events	Screening to 16 weeks
The severity of adverse events	Adverse events which range from mild,moderate, severe and lethal	Screening to 16 weeks
Incidence of abnormal blood pressure	Blood pressure which is consistently above and below120/80	Screening to 16 weeks
Incidence of abnormal heart rate	The incidence of atrial fibrillation, supraventricular tachycardia or bradycardia	Screening to 16 weeks
incidence of irregular heart rate	incidence of arrhythmias	Screening to 16 weeks
incidence of suicidal ideation using the Columbian Suicide Severity Rating Scale	Measures Suicidal Ideation items 1-5; Suicidal Behavior 6-10 and both Suicidal Ideation and Behavior Items 1-10	Screening to 16 weeks
Change in the number of steps	Wearable and or mobile devices	Screening to Week 16
Changes in concomitant medication	Recently prescribed medication	Screening to 16 weeks
Changes in volume of Alcohol	self reports	screening to 16 weeks
Changes in the number of cigarettes	self reports	screening to 16 weeks
Changes in the number of cannabis joints	Self reports	Screening to 16 weeks
Changes in other over the counter medication	Self Reports	Screening to 16 weeks
Changes in Estradiol	Salivary panel profile values	Screening to 16 weeks
Changes in Testosterone	Salivary panel profile vales	Screening to 16 weeks
Changes in Cortisol	Salivary panel profile values	Screening to 16 weeks
Changes in Progesterone	Salivary panel profiles values	Screening to 16 weeks
Changes in Melatonin	Salivary panel profile values	Screening to 16 weeks
Changes in DHEA (Dehydroepiandrosterone)	Salivary panel profile values	Screening to 16 weeks
Changes in DHT(Dihydrotestosterone)	Salivary panel profile values	Screening to 16 weeks
Changes in Androstenedione	Salivary panel profile values	Screening to 16 weeks
Changes in Estrone	Salivary panel profile values	Screening to 16 weeks

Collaborators and Investigators

• Sponsor: Wake Network, Inc.
• Collaborators: Professor Roger Gibson Section of Psychiatry Faculty of Medical Sciences UWI
• Investigators: Principal Investigator: Roger Gibson, Faculty of Medical Sciences UWI Mona; Study Director: Sharon White, Wake Network, Inc.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 15, 2022
• Primary Completion (ANTICIPATED): June 20, 2023
• Study Completion (ANTICIPATED): August 31, 2023

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (ACTUAL): August 4, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 25, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Anxiety Disorders
• Other Study ID Numbers: ECP242-19/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data will be made available through publications and conference presentations

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No