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

Modulation of Serotonin Pathways Using Psilocybin in Adults With and Without Autism Spectrum Disorder (ASD)

This study will test the hypothesis that brain systems are differentially regulated by serotonin in individuals with and without Autism Spectrum Disorder.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Psilocybin 5 mg; Drug: Psilocybin 2 mg; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 8AF
    • King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo, Psilocybin_2, Psilocybin_5; Dose order: Placebo, Psilocybin 2mg, Psilocybin 5mg	Drug: Psilocybin 5 mg; Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin; Other Names: COMP360; Drug: Psilocybin 2 mg; Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin; Other Names: COMP360; Drug: Placebo; Inactive placebo
Experimental: Psilocybin_2, Placebo, Psilocybin_5; Dose order: Psilocybin 2mg, Placebo, Psilocybin 5mg	Drug: Psilocybin 5 mg; Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin; Other Names: COMP360; Drug: Psilocybin 2 mg; Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin; Other Names: COMP360; Drug: Placebo; Inactive placebo
Experimental: Psilocybin_2, Psilocybin_5, Placebo; Dose order: Psilocybin 2mg, Psilocybin 5mg, Placebo	Drug: Psilocybin 5 mg; Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin; Other Names: COMP360; Drug: Psilocybin 2 mg; Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin; Other Names: COMP360; Drug: Placebo; Inactive placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Data collected on up to 3 visit days per participant.
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.	Data collected on up to 3 visit days per participant.
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.	Data collected on up to 3 visit days per participant.
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.	Data collected on up to 3 visit days per participant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Data collected on up to 3 visit days per participant.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Subjective effects intensity	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	Data collected on up to 3 visit days per participant.

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: University of Cambridge

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Actual): August 23, 2024
• Study Completion (Actual): August 23, 2024

Study Registration Dates

• First Submitted: November 11, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 23, 2025
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MRI; EEG; Serotonin; Autism Spectrum Disorder; Psilocybin; Psychedelics; Pharmacological Imaging
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autism Spectrum Disorder; Autistic Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: IRAS: 292281; REC: 21/LO/0795

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
• product manufactured in and exported from the U.S.: No