The 'PSILAUT' protocol: an experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin.
Tobias P. Whelan, Eileen Daly, Nicolaas A.j. Puts, Paula Smith, Carrie Allison, Simon Baron-Cohen, Ekaterina Malievskaia, Declan G M Murphy, Grainne M McAlonan
BMC Psychiatry April 25, 2024 DOI: 10.1186/s12888-024-05768-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Randomized Double-blind Peer reviewed |
|---|---|
| Population | Autistic and non-autistic adults |
| Intervention | Psilocybin |
| Dose | 2 mg and 5 mg |
| Topics | Psilocybin Serotonin |
| Keywords | Brain imaging Pharmacology Psychedelics hallucinogens Entheogens Psychoactive compounds Autism asd Autism spectrum disorder Neurodevelopmental disorder Neuroimaging brain scanning FMRI |
| Citations | 8 |
| Registration | NCT05651126 |
| Key findings | The study will test the hypothesis that serotonergic targets of psilocybin function differently in autistic and non-autistic adults. |
Abstract
The underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT2A receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that serotonergic signalling is involved in a candidate brain function our approach is to change it and observe a shift in that function. We will use psilocybin as a pharmacological probe of the serotonin system in vivo. We will directly test the hypothesis that serotonergic targets of psilocybin - principally, but not exclusively, 5HT2A receptor pathways-function differently in autistic and non-autistic adults. The 'PSILAUT' "shiftability" study is a case-control study autistic and non-autistic adults. How neural responses 'shift' in response to low doses (2 mg and 5 mg) of psilocybin compared to placebo will be examined using multimodal techniques including functional MRI and EEG. Each participant will attend on up to three separate visits with drug or placebo administration in a double-blind and randomized order. This study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain. We will also examine individual differences in serotonin system function. This work will inform our understanding of the neurobiology of autism as well as decisions about future clinical trials of psilocybin and/or related compounds including stratification approaches. NCT05651126.
Comparable studies
Other observational and cohort studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Dynamic coupling of whole-brain neuronal and neurotransmitter systems Healthy humans | 2020 | Observational study | |
| The Serotonin System and Spiritual Experiences Normal male subjects, ages 20-45 years | 2003 | Observational cohort | n = 15 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cited by 8
- The Emergence of Psilocybin in Psychiatry and Neuroscience Pharmaceuticals April 9, 2025
- Perceived changes in mental health and social engagement attributed to a single psychedelic experience in autistic adults: results from an online survey. Psychopharmacology February 1, 2025
- Psilocybin Use in the Autism Spectrum Disorder: A Scoping Review Clinical Neuropharmacology September 1, 2025
- Psychedelics and autism spectrum disorder: Mechanistic insights, translational evidence and ethical challenges Journal of Psychiatric Research June 23, 2026
- Serotonergic psychedelics for Autism spectrum disorder: Neurobiological mechanisms and translational prospects. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 20, 2026
and 3 more in the library
Cites 19
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder The Journal of Clinical Psychiatry November 15, 2006
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
and 14 more in the library