Psilocybin and Depression (Psilo101)

Psilocybin and Depression - Assessing the Long-term Effects of a Single Administration of Psilocybin on the Psychiatric Symptoms and Brain Activity of Patients With Severe Depression

The main aim of the study is to investigate the possible long-term therapeutic effects of psilocybin on the symptoms of severe depression, as well as the brain mechanisms underlying these changes. Depression severity is assessed before and after (i.e., 1 week, 3 months and 6 months after) a single dose of psilocybin and compared to respective scores of a group receiving an active placebo, ketamine. Brain activity (using functional magnetic resonance imaging) is measured before and one week after drug administration in order to determine whether changes in brain networks related to emotional and self-referential processing correlate with any observed changes in depression scores. Further, blood samples will be obtained from the participants and analyzed in order to reveal gene expression and molecular level correlates underlying rapid antidepressant effects, and to identify biomarkers that predict treatment outcome.

Study Overview

• Status: Unknown
• Conditions: Severe Depression
• Intervention / Treatment: Drug: Psilocybin; Drug: Ketamine (Ketalar)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Major depression of a moderate to severe degree (17+ on the 21-item HAM-D).
2. No health-related contraindications.

Exclusion Criteria:

1. Current or previously diagnosed psychotic disorder.
2. Immediate family member with a diagnosed psychotic disorder.
3. Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure etc.).
4. History of suicide attempts.
5. History of mania.
6. Current 5-HT2A antagonist antidepressant medication.
7. Blood or needle phobia.
8. Positive pregnancy test.
9. Current drug or alcohol dependence.
10. Lack of appropriate use of contraception.
11. Breast-feeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin group; This group will receive a single oral 25mg dose of psilocybin under surveilled and safe conditions.	Drug: Psilocybin; Psilocybin ingested orally
Active Comparator: Ketamine group; This group will receive a single intranasal 125mg dose of ketamine under surveilled and safe conditions.	Drug: Ketamine (Ketalar); Ketamine administered intranasally
No Intervention: No-treatment group; This group will be included in the study as a no-treatment group, so that natural time-dependent changes in depressive symptoms can be controlled for and thus the antidepressive effects of ketamine and psilocybin treatment can be verified

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 16-Item Quick Inventory of Depressive Symptomatology (QIDS)	The primary outcome measures in this study will be the mean change in QIDS scores from pre-administration baseline at day 1 to Follow-up 2 at day 103 (3 months after the administration session). Additionally, an electronic version of the QIDS will be performed 6 months after the administration session. The criteria for determining response will be a reduction of 25% in the (QIDS; Rush et al., 2003) scores from baseline (screening), and remission will be scores of ≤5 on the QIDS.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Montgomery and Asberg Depression Rating Scale	The Montgomery and Asberg Depression Rating Scale will be carried out at screening ( day 1), Follow-up 1 (day 18) and Follow-up 2 (day 103, 3 months after the administration session).	3 months
Hamilton Depression Rating Scale	The Hamilton Depression Rating Scale will be carried out at screening ( day 1), Follow-up 1 (day 18) and Follow-up 2 (day 103, 3 months after the administration session).	3 months

Collaborators and Investigators

• Sponsor: University of Helsinki
• Collaborators: Dr. Tomi Rantamäki, Laboratory of Neurotherapeutics, Department of Biosciences, University of Helsinki; Dr. Robin Carthart-Harris and Prof. David Nutt, Imperial College London, UK

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (Actual): December 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 21, 2017
• Last Update Submitted That Met QC Criteria: December 15, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: biomarker; fMRI; ketamine; psilocybin; rapid-acting antidepressants
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Hallucinogens; Ketamine; Psilocybin
• Other Study ID Numbers: 2016-004195-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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