PSILAUT: Psilocybin in Adults With and Without Autism Spectrum Disorder

Sponsor

King's College London (Other)

Overall Status

Recruiting

CT.gov ID

NCT05651126

Collaborator

University of Cambridge (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder	Drug: Psilocybin 5 mg Drug: Psilocybin 2 mg Drug: Placebo	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention 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).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:

Double (Participant, Investigator)

Masking Description:

Participants and investigators are blinded to the drug condition

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Brain activation and connectivity response to serotonergic stimulation as assessed by functional magnetic resonance imaging. [Data collected on up to 3 visit days per participant.]
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) [Data collected on up to 3 visit days per participant.]
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 [Data collected on up to 3 visit days per participant.]
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 [Data collected on up to 3 visit days per participant.]
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. [Data collected on up to 3 visit days per participant.]
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.

Other Outcome Measures

Exploratory: Subjective effects intensity [Data collected on up to 3 visit days per participant.]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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