Bridging the translational neuroscience gap: Development of the ‘shiftability’ paradigm and an exemplar protocol to capture psilocybin-elicited ‘shift’ in neurobiological mechanisms in autism
Tobias P. Whelan, Eileen Daly, Nicolaas A.j. Puts, Ekaterina Malievskaia, Declan G M Murphy, Grainne M McAlonan
medRxiv May 26, 2023 preprint DOI: 10.1101/2023.05.25.23290521 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Protocol for an experimental study using a pharmacological probe |
|---|---|
| Population | Autistic and non-autistic adults |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Neurochemical Autism |
| Citations | 3 |
| Key findings | The authors propose a 'shiftability' paradigm using psilocybin to directly test the hypothesis that the serotonin system functions differently in autistic and non-autistic adults. |
Abstract
Abstract Clinical trials of pharmacological approaches targeting the core features of autism have failed. This is despite evidence from preclinical studies, genetics, post-mortem studies and correlational analyses linking peripheral and central markers of multiple candidate neurochemical systems to brain function in autism. Whilst this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is very little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. As a result, our understanding of how neurochemical differences contribute to neurodiversity is limited and impedes our ability to translate findings from animal studies into humans. Here, we begin by introducing our “shiftability” paradigm, an approach to bridge the translational gap in autism research. We then provide an overview of the methodologies used and explain our most recent choice of psilocybin as a pharmacological probe of the serotonin system in vivo . Finally, we provide a summary of the protocol for ‘PSILAUT’, an exemplar “shiftability” study which uses psilocybin to directly test the hypothesis that the serotonin system functions differently in autistic and non-autistic adults.
Comparable studies
Other experimental studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... | 2015 | Validation study using pooled data from five laboratory experiments | n = 184 |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... | 2020 | Long-term within-subjects follow-up analysis | n = 15 |
| Enzymatic Synthesis of Psilocybin | 2017 | Laboratory study |
Citations in the library
Cites 18
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- 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
- Broadband Cortical Desynchronization Underlies the Human Psychedelic State Journal of Neuroscience September 18, 2013
and 13 more in the library