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Psilocybin in Adults With and Without Autism Spectrum Disorder (PSILAUT)

Primary Purpose

Autism Spectrum Disorder

Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Psilocybin 5 mg
Psilocybin 2 mg
Placebo
Sponsored by
King's College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Autism Spectrum Disorder focused on measuring Autism Spectrum Disorder, Psilocybin, Serotonin, Pharmacological Imaging, MRI, EEG, Psychedelics

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: For all participants: Calendar age above 18 years Working knowledge of English Able to give informed consent Not pregnant or breastfeeding Individuals should be in good physical health, prescription medication free during the 2-week period preceding a study visit. However, occasional use of over-the-counter medication (e.g. painkillers) on an as needed basis (and not on the day of study visit) may be permitted. In addition, regular prescription medication (use of a stable dose over the two months preceding participation) with a drug that does not affect 5HT directly may be permitted. Also permitted is topical medication without systemic exposure For individuals with ASD: Diagnosis of ASD by recognised clinical service supported by the Autism Diagnostic Interview-Revised (ADI-R) if a relative is available. Current symptom level assessed using the Autism Diagnostic Observation Schedule (ADOS-2) Exclusion Criteria: For all participants: History of allergy/idiosyncrasy to psilocybin or chemically related compounds or excipients which may be employed in the study or to any other drug used in the past Clinically relevant history or presence of any medical disorder, potentially interfering with this study Clinically relevant abnormality at screening as judged by the investigator History of or current abuse of drugs (including prescription medication) or alcohol or solvents Participation in a research study involving a pharmacological probe or drug trial within last month Subjects with current epilepsy, seizures or episodes of unexplained and unprovoked loss of consciousness Anyone with a history or examination which indicates laboratory testing is needed will be excluded from the study Intelligence Quotient below 70 Currently taking prescription medications of propranolol or pindolol Individuals with major mental illness Individuals who have a current or past history of meeting diagnostic criteria for schizophrenia or other psychotic disorders or bipolar I or II disorder Reproductive safety: Pregnancy or breastfeeding (is a routine exclusion for research MRI scanning) Female study participants must be willing to use one form of highly effective non-hormonal contraception for one week after study drug administration. This would include a vasectomised partner (sole partner), tubal occlusion, intrauterine system [IUS]/hormonal coil or copper containing intrauterine device or copper containing IUD, or true abstinence (when this is in line with the preferred and usual lifestyle of the subject). Women should have been stable on their chosen method of birth control for a minimum of 2 months before entering the study. Participants must agree to undergo a pregnancy test prior to each administration of study drug For individuals with ASD: ASD caused by a known genetic syndrome, e.g. Fragile X, 22q11 deletion syndrome. Currently treated for epilepsy

Sites / Locations

  • King's College LondonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Placebo, Psilocybin_2, Psilocybin_5

Psilocybin_2, Placebo, Psilocybin_5

Psilocybin_2, Psilocybin_5, Placebo

Arm Description

Dose order: Placebo, Psilocybin 2mg, Psilocybin 5mg

Dose order: Psilocybin 2mg, Placebo, Psilocybin 5mg

Dose order: Psilocybin 2mg, Psilocybin 5mg, Placebo

Outcomes

Primary Outcome Measures

Brain activation and connectivity response to serotonergic stimulation as assessed by functional magnetic resonance imaging.
Comparing whole brain blood-oxygen-level-dependent (BOLD) activation (institutional units) during the resting state in cases and controls when the serotonin system is activated by a single oral dose of psilocybin (COMP360) versus the placebo condition.
Brain electrophysiological activity task-free electroencephalography (EEG)
Case-control comparison of task-free EEG by time-frequency analysis during placebo and when serotonin system is activated with psilocybin.
Brain electrophysiological activity electroencephalography (EEG) during visual stimulation
Case-control comparison of EEG Evoked Potentials in response to visual stimulation during placebo and when serotonin system is activated with psilocybin.
Brain electrophysiological activity electroencephalography (EEG) during auditory stimulation
Case-control comparison of EEG Event Related Potentials in response to auditory tones during placebo and when serotonin system is activated with psilocybin.

Secondary Outcome Measures

Brain excitation and inhibition response to serotonergic stimulation as assessed by magnetic resonance spectroscopy.
Quantification and case-control comparison of brain metabolites relevant to regulation of excitation and inhibition (focus on Glx, GABA, GSH) using proton magnetic resonance spectroscopy when serotonin system is 'at rest' (placebo) and when activated by psilocybin.

Full Information

First Posted
November 11, 2022
Last Updated
December 6, 2022
Sponsor
King's College London
Collaborators
University of Cambridge
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1. Study Identification

Unique Protocol Identification Number
NCT05651126
Brief Title
Psilocybin in Adults With and Without Autism Spectrum Disorder
Acronym
PSILAUT
Official Title
Modulation of Serotonin Pathways Using Psilocybin in Adults With and Without Autism Spectrum Disorder (ASD)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2022 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
King's College London
Collaborators
University of Cambridge

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will test the hypothesis that brain systems are differentially regulated by serotonin in individuals with and without Autism Spectrum Disorder.
Detailed Description
To do this, the brain response to two single acute doses of partial serotonin (5HT)1A/2A receptor agonist psilocybin (COMP360) relative to a single dose of placebo (baseline serotonin activity) will be compared in healthy autistic and non-autistic adults. Brain function will be assessed using a range of MRI (fMRI and MRS), EEG and sensory tasks. Unimodal and multimodal analyses will be conducted. Please note that this study uses psilocybin as a probe of the serotonin system in a Case-Control science study and, following Scope protocol review, the U.K. MHRA confirmed that it is not a 'Clinical Trial of an Investigational Medicinal Product' (IMP) as defined by the EU Directive 2001/20/EC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder
Keywords
Autism Spectrum Disorder, Psilocybin, Serotonin, Pharmacological Imaging, MRI, EEG, Psychedelics

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Case-Control comparison using repeated-measures cross-over design. Each participant receives each one of the three pharmacological probes in separate visits (i.e., placebo, psilocybin low dose and psilocybin higher dose), with the order of administration being pseudorandomized (to prevent order effects).
Masking
ParticipantInvestigator
Masking Description
Participants and investigators are blinded to the drug condition
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo, Psilocybin_2, Psilocybin_5
Arm Type
Experimental
Arm Description
Dose order: Placebo, Psilocybin 2mg, Psilocybin 5mg
Arm Title
Psilocybin_2, Placebo, Psilocybin_5
Arm Type
Experimental
Arm Description
Dose order: Psilocybin 2mg, Placebo, Psilocybin 5mg
Arm Title
Psilocybin_2, Psilocybin_5, Placebo
Arm Type
Experimental
Arm Description
Dose order: Psilocybin 2mg, Psilocybin 5mg, Placebo
Intervention Type
Drug
Intervention Name(s)
Psilocybin 5 mg
Other Intervention Name(s)
COMP360
Intervention Description
Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin
Intervention Type
Drug
Intervention Name(s)
Psilocybin 2 mg
Other Intervention Name(s)
COMP360
Intervention Description
Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inactive placebo
Primary Outcome Measure Information:
Title
Brain activation and connectivity response to serotonergic stimulation as assessed by functional magnetic resonance imaging.
Description
Comparing whole brain blood-oxygen-level-dependent (BOLD) activation (institutional units) during the resting state in cases and controls when the serotonin system is activated by a single oral dose of psilocybin (COMP360) versus the placebo condition.
Time Frame
Data collected on up to 3 visit days per participant.
Title
Brain electrophysiological activity task-free electroencephalography (EEG)
Description
Case-control comparison of task-free EEG by time-frequency analysis during placebo and when serotonin system is activated with psilocybin.
Time Frame
Data collected on up to 3 visit days per participant.
Title
Brain electrophysiological activity electroencephalography (EEG) during visual stimulation
Description
Case-control comparison of EEG Evoked Potentials in response to visual stimulation during placebo and when serotonin system is activated with psilocybin.
Time Frame
Data collected on up to 3 visit days per participant.
Title
Brain electrophysiological activity electroencephalography (EEG) during auditory stimulation
Description
Case-control comparison of EEG Event Related Potentials in response to auditory tones during placebo and when serotonin system is activated with psilocybin.
Time Frame
Data collected on up to 3 visit days per participant.
Secondary Outcome Measure Information:
Title
Brain excitation and inhibition response to serotonergic stimulation as assessed by magnetic resonance spectroscopy.
Description
Quantification and case-control comparison of brain metabolites relevant to regulation of excitation and inhibition (focus on Glx, GABA, GSH) using proton magnetic resonance spectroscopy when serotonin system is 'at rest' (placebo) and when activated by psilocybin.
Time Frame
Data collected on up to 3 visit days per participant.
Other Pre-specified Outcome Measures:
Title
Exploratory: Subjective effects intensity
Description
5-Dimensional altered states of consciousness (5D-ASC) used for Case-control comparison of subjective effects intensity at placebo and when serotonin system activated with psilocybin
Time Frame
Data collected on up to 3 visit days per participant.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: For all participants: Calendar age above 18 years Working knowledge of English Able to give informed consent Not pregnant or breastfeeding Individuals should be in good physical health, prescription medication free during the 2-week period preceding a study visit. However, occasional use of over-the-counter medication (e.g. painkillers) on an as needed basis (and not on the day of study visit) may be permitted. In addition, regular prescription medication (use of a stable dose over the two months preceding participation) with a drug that does not affect 5HT directly may be permitted. Also permitted is topical medication without systemic exposure For individuals with ASD: Diagnosis of ASD by recognised clinical service supported by the Autism Diagnostic Interview-Revised (ADI-R) if a relative is available. Current symptom level assessed using the Autism Diagnostic Observation Schedule (ADOS-2) Exclusion Criteria: For all participants: History of allergy/idiosyncrasy to psilocybin or chemically related compounds or excipients which may be employed in the study or to any other drug used in the past Clinically relevant history or presence of any medical disorder, potentially interfering with this study Clinically relevant abnormality at screening as judged by the investigator History of or current abuse of drugs (including prescription medication) or alcohol or solvents Participation in a research study involving a pharmacological probe or drug trial within last month Subjects with current epilepsy, seizures or episodes of unexplained and unprovoked loss of consciousness Anyone with a history or examination which indicates laboratory testing is needed will be excluded from the study Intelligence Quotient below 70 Currently taking prescription medications of propranolol or pindolol Individuals with major mental illness Individuals who have a current or past history of meeting diagnostic criteria for schizophrenia or other psychotic disorders or bipolar I or II disorder Reproductive safety: Pregnancy or breastfeeding (is a routine exclusion for research MRI scanning) Female study participants must be willing to use one form of highly effective non-hormonal contraception for one week after study drug administration. This would include a vasectomised partner (sole partner), tubal occlusion, intrauterine system [IUS]/hormonal coil or copper containing intrauterine device or copper containing IUD, or true abstinence (when this is in line with the preferred and usual lifestyle of the subject). Women should have been stable on their chosen method of birth control for a minimum of 2 months before entering the study. Participants must agree to undergo a pregnancy test prior to each administration of study drug For individuals with ASD: ASD caused by a known genetic syndrome, e.g. Fragile X, 22q11 deletion syndrome. Currently treated for epilepsy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Grainne McAlonan
Phone
00442078480002
Email
mrs@kcl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Tobias Whelan
Phone
00442078480002
Email
mrs@kcl.ac.uk
Facility Information:
Facility Name
King's College London
City
London
ZIP/Postal Code
SE5 8AF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Professor Grainne McAlonan

12. IPD Sharing Statement

Plan to Share IPD
No

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Psilocybin in Adults With and Without Autism Spectrum Disorder

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