Psilocybin in Adults With and Without Autism Spectrum Disorder

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 duringthe 2-week period preceding a study visit. However, occasional use ofover-the-counter medication (e.g. painkillers) on an as needed basis (and not on theday 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 thatdoes not affect 5HT directly may be permitted. Also permitted is topical medicationwithout systemic exposure

For individuals with ASD:

• Diagnosis of ASD by recognised clinical service supported by the Autism DiagnosticInterview-Revised (ADI-R) if a relative is available. Current symptom level assessedusing the Autism Diagnostic Observation Schedule (ADOS-2)

Exclusion Criteria:

For all participants:

• History of allergy/idiosyncrasy to psilocybin or chemically related compounds orexcipients 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, potentiallyinterfering with this study

• Clinically relevant abnormality at screening as judged by the investigator

• History of or current abuse of drugs (including prescription medication) or alcoholor solvents

• Participation in a research study involving a pharmacological probe or drug trialwithin last month

• Subjects with current epilepsy, seizures or episodes of unexplained and unprovokedloss of consciousness

• Anyone with a history or examination which indicates laboratory testing is neededwill 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 forschizophrenia 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 effectivenon-hormonal contraception for one week after study drug administration. This wouldinclude a vasectomised partner (sole partner), tubal occlusion, intrauterine system [IUS]/hormonal coil or copper containing intrauterine device or copper containingIUD, or true abstinence (when this is in line with the preferred and usual lifestyleof the subject). Women should have been stable on their chosen method of birthcontrol for a minimum of 2 months before entering the study. Participants must agreeto 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