Research tells us that the autistic brain responds differently to medications,
so that's where development should begin.
Support tailored to individual biology, as a person is more than just their diagnosis.
Success defined by what helps you thrive.
Thirty-seven autistic and thirty non-autistic adults each had three visits, receiving a placebo on one and a low dose of psilocybin (2 mg or 5 mg) on the others. About 70 minutes after taking it, they had an MRI scan to test how strongly different brain networks were communicating with each other.
After placebo, the two groups' brains looked the same. However, after 5 mg psilocybin, they did not: connectivity between networks involved in attention, mood and cognition increased in autistic adults and decreased in non-autistic adults. If a person had a greater extent of autistic traits, the increase in connectivity between these networks was bigger. Responses to psilocybin also varied a lot between autistic individuals, which suggests that brain measures may help identify who is likely to respond clinically in future.
Overall, our findings show that autistic people can be more sensitive to low doses of psilocybin and that the distinct response of their brain should be considered moving forward.
This paper sets out the plan for our study of low dose psilocybin with autistic adults ('PSILAUT'), before any results were collected — it also explains why psilocybin was chosen and why low doses were used.
Thirty-seven autistic and thirty non-autistic adults, matched for age and sex, attended three visits. On each visit they received either a placebo or a single low dose of psilocybin (2 mg or 5 mg), in an order that neither they nor the researchers knew. Each visit included an MRI scan, EEG recordings and sensory tasks.
The community engagement that we did prior to the study is described too, in which 331 autistic adults were asked for their views.
Studies comparing autistic and non-autistic brains at rest often disagree with each other. This paper suggests that the difference may not be in how the brain looks when nothing is happening, but in how it responds when something changes it — a drug, for example.
This paper brought together several MRI studies that used drugs acting on three different chemical messenger systems in the brain — the GABA, serotonin and opioid systems. Each drug changed the connectivity of brain networks differently in autistic adults, sometimes in the opposite direction to non-autistic adults. There was also a generalised response of the autistic brain to drugs, as across all the drugs investigated, the difference was mainly due to increased connectivity between brain networks that are usually more distinct, rather than within them.
These same systems are the targets of medications commonly prescribed to autistic people for co-occurring mental health difficulties. This may help explain why those medications are often less effective, and why autistic people can experience more side effects.
Rather than extrapolating from trials in populations assumed to be non-autistic, drug development needs a deliberate effort that considers autism specifically from the start to provide better support options.
Trials of drugs that target the core features of autism have largely failed. One reason may be the 'one size fits all' approach to autism, that considers only diagnosis. Another is that biological measurements collected at rest assume the brain is static, when actually it is a dynamic system that responds to your environment.
The 'shiftability' concept introduced here addresses this. Instead of comparing brains as they are, a chemical system is deliberately changed with a single low dose of a drug and the resulting 'shift' is recorded — using an MRI, EEG or sensory task, for example. If a system behaves differently in autistic people, that difference should show up in the response.
The paper explains the thinking behind the approach and how it is put into practice, as we have done in our 'PSILAUT' study to investigate the distinct brain mechanisms of low dose psilocybin in the autistic brain specifically. We aim for an 'individual biology first' approach to pharmacological support: one that starts with how a person's brain actually responds, rather than just the diagnosis they were given.
Ekaterina received her medical degree from St Petersburg Medical Academy in St Petersburg, Russia, and then moved to the US where she completed her Internal Medicine residency training. She worked in private practice, academic medicine and public health for more than 15 years in the greater New York area. She was a Clinical Instructor of Medicine at Mount Sinai School of Medicine, as well as a Research Professor at City University of New York.
Ekaterina worked in global health and medical philanthropy, focusing on improving outcomes in maternal and child health. She founded Compass Pathways in 2016, having experienced at first hand the challenges in accessing evidence-based and effective mental health care for a family member.
Tobias completed his PhD in Neuroscience at King's College London, where he investigated how autistic people respond differently to medications and led the first experimental medicine study ('PSILAUT') of low dose psilocybin with autistic adults. He has won European and international awards for this work, including the 2026 International Society for Autism Research's Dissertation Award.
Tobias is a post-doctoral researcher at King's, and previously he was an early employee at Compass Pathways, initially as an intern and most recently as a Research Scientist.
George is a psychiatrist and neuroscientist with more than 30 years of experience leading global CNS and neurodevelopmental drug development at Roche, Novartis and Janssen, where he oversaw the development of breakthrough treatments including Ocrevus® for primary progressive and relapsing remitting multiple sclerosis and Exelon® for Alzheimer's disease and Parkinson's disease dementia. Trained in child and adolescent psychiatry in Paris, he brings a lifelong focus on neurodevelopmental conditions to n1 bio's mission of developing better support options in autism. Known for his commitment to empowering patients and families, George has published more than 100 peer-reviewed articles and has developed widely used clinician- and patient-reported outcome measures.
He co-founded Noema Pharma and StutterSenseAI Therapeutics and is a co-founder and past president of the International Society for CNS Clinical Trials and Methodology.
Diego is Founding Director of the Noel Drury, M.D. Institute for Translational Depression Discoveries at the University of California, Irvine, where he is a Distinguished Professor in the Department of Psychiatry and Human Behavior and the Department of Neurobiology and Behavior, and holds the Noel Drury MD Endowed Chair. He is also Center Director for a Silvio O. Conte Center for Basic Translational Mental Health Research focused on the neurobiology of depression and novel treatment targets.
Until December 2024 he was a Professor of Psychiatry at Harvard Medical School. He was recruited to McLean Hospital in 2010 as Founding Director of the Center for Depression, Anxiety and Stress Research, and as Director of the McLean Imaging Center. From 2002 to 2010 he was a faculty member in the Department of Psychology at Harvard University, where he served as the John and Ruth Hazel Associate Professor of the Social Sciences.
Diego received his M.A. (1995) and Ph.D. (1998) from the University of Zurich, Switzerland, and did post-doctoral work at the University of Wisconsin, Madison.
Professor Gráinne McAlonan is a translational neuroscientist and consultant psychiatrist whose work has moved autism science from descriptive diagnosis towards mechanism-led approaches. She is Director of the NIHR Maudsley Biomedical Research Centre, where she leads a £41m infrastructure award that has recruited over 12,000 participants and generated more than 1,200 publications.
She holds senior leadership roles in AIMS-2-TRIALS, the world's largest autism research award, and will co-lead TOAST, a Horizon Europe multicentre platform testing pharmacological, behavioural and combination therapeutics in autism. She was chief investigator on 'PSILAUT', the first study of low dose psilocybin brain-mechanism engagement in autism.
Her research spans the life course, from early structural neuroimaging that reshaped understanding of autism neuroanatomy to experimental medicine targeting excitation-inhibition balance and sensory processing. As an honorary consultant psychiatrist she keeps clinically committed time in specialist NHS services, and embeds lived experience and co-production across her research.
Professor Murphy is Professor of Translational Neurodevelopment and Director of the Institute of Translational Neurodevelopment at the Institute of Psychiatry, Psychology & Neuroscience, King's College London. He was formerly Head of the Department of Forensic and Neurodevelopmental Sciences, and Director of the Behavioural and Developmental Psychiatry Clinical Academic Group at King's Health Partners.
His work focuses on translating research from bench to bedside: understanding the mechanisms behind risk and resilience, and developing new diagnostic approaches, treatments and services. He established the MRC UK AIMS imaging network, the first of its kind in Europe, and from it developed EU-AIMS and its successor EU-AIMS-2-TRIALS, which brings together 48 partners across 14 European countries.
Declan trained in medicine at University College London and Westminster Medical School, and subsequently in psychiatry at the Maudsley Hospital. His research training was at the Institute of Psychiatry in London and at the Laboratory of Neurosciences at the National Institutes of Health in the United States.