Psilocybin in Adults With and Without Autism Spectrum Disorder

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

Inclusion Criteria:For all participants:Calendar age above 18 yearsWorking knowledge of EnglishAble to give informed consentNot pregnant or breastfeedingIndividuals 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 exposureFor 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 pastClinically relevant history or presence of any medical disorder, potentially interfering with this studyClinically relevant abnormality at screening as judged by the investigatorHistory of or current abuse of drugs (including prescription medication) or alcohol or solventsParticipation in a research study involving a pharmacological probe or drug trial within last monthSubjects with current epilepsy, seizures or episodes of unexplained and unprovoked loss of consciousnessAnyone with a history or examination which indicates laboratory testing is needed will be excluded from the studyIntelligence Quotient below 70Currently taking prescription medications of propranolol or pindololIndividuals with major mental illnessIndividuals who have a current or past history of meeting diagnostic criteria for schizophrenia or other psychotic disorders or bipolar I or II disorderReproductive 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 drugFor individuals with ASD:ASD caused by a known genetic syndrome, e.g. Fragile X, 22q11 deletion syndrome.Currently treated for epilepsy