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

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.

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

Participants and investigators are blinded to the drug condition