Psilocybin in Adults With and Without Autism Spectrum Disorder

NCT05651126 | Completed

• 1 other identifier: IRAS: 292281; REC: 21/LO/0795
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Autism Spectrum Disorder

Keywords

Autism Spectrum Disorder; Psilocybin; Serotonin; Pharmacological Imaging; MRI; EEG; Psychedelics

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Brain excitation and inhibition response to serotonergic stimulation as assessed by magnetic resonance spectroscopy.

  Data collected on up to 3 visit days per participant.

Other Outcomes (1)

• Exploratory: Subjective effects intensity

  Data collected on up to 3 visit days per participant.

Study Arms (3)

Placebo, Psilocybin_2, Psilocybin_5

EXPERIMENTAL

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

Drug: Psilocybin 5 mg; Drug: Psilocybin 2 mg; Drug: Placebo

Psilocybin_2, Placebo, Psilocybin_5

EXPERIMENTAL

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

Drug: Psilocybin 5 mg; Drug: Psilocybin 2 mg; Drug: Placebo

Psilocybin_2, Psilocybin_5, Placebo

EXPERIMENTAL

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

Drug: Psilocybin 5 mg; Drug: Psilocybin 2 mg; Drug: Placebo

Interventions

Psilocybin 5 mg DRUG

Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin

Also known as: COMP360

Placebo, Psilocybin_2, Psilocybin_5; Psilocybin_2, Placebo, Psilocybin_5; Psilocybin_2, Psilocybin_5, Placebo

Psilocybin 2 mg DRUG

Partial Serotonin (5HT) 1A/2A Receptor Agonist Psilocybin

Also known as: COMP360

Placebo, Psilocybin_2, Psilocybin_5; Psilocybin_2, Placebo, Psilocybin_5; Psilocybin_2, Psilocybin_5, Placebo

Placebo DRUG

Inactive placebo

Placebo, Psilocybin_2, Psilocybin_5; Psilocybin_2, Placebo, Psilocybin_5; Psilocybin_2, Psilocybin_5, Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• 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:

Sponsors & Collaborators

• King's College London: lead
• University of Cambridge: collaborator

Study Sites (1)

King's College London

London, SE5 8AF, United Kingdom

Location

Related Publications (1)

• Whelan TP, Daly E, Puts NA, Smith P, Allison C, Baron-Cohen S, Malievskaia E, Murphy DGM, McAlonan GM. The 'PSILAUT' protocol: an experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin. BMC Psychiatry. 2024 Apr 25;24(1):319. doi: 10.1186/s12888-024-05768-2.

  PMID: 38658877 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators are blinded to the drug condition
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Head of Department

Model Details: 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).

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: December 14, 2022
• Study Start: December 12, 2022
• Primary Completion: August 23, 2024
• Study Completion: August 23, 2024
• Last Updated: July 28, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)