BMC Psychiatry
April 25, 2024
Tobias P. Whelan, Eileen Daly, Nicolaas A.j. Puts et al.
8 citations
The serotonin system, particularly the 5HT2A receptor, may differ in autistic and non-autistic brains, but previous studies only show correlations. This registered clinical trial (NCT05651126) will directly test whether serotonergic signaling functions differently by using low doses (2 mg and 5 mg) of psilocybin as a pharmacological probe. In a double-blind, randomized, placebo-controlled case-control design, autistic and non-autistic adults will undergo functional MRI and EEG to measure how neural responses shift with psilocybin. The study aims to provide the first direct evidence of differential serotonin system function in autism and inform future clinical trials.
bioRxiv (Cold Spring Harbor Laboratory)
September 10, 2020
Irene Mollinedo-Gajate, Chenchen Song, Marcos Sintes-Rodriguez et al.
6 citations
preprint
In a mouse model of autism spectrum disorder (ASD) created by prenatal exposure to valproic acid, the acute response to the serotonergic psychedelic psilocybin was reduced compared to controls. However, psilocybin treatment reversed the social behavior deficits that are characteristic of the ASD model. These findings suggest that psilocybin may have therapeutic potential for improving social interaction in ASD.
medRxiv
May 26, 2023
Tobias P. Whelan, Eileen Daly, Nicolaas A.j. Puts et al.
3 citations
preprint
Clinical trials for drugs targeting core autism features have failed, despite evidence linking various neurochemical systems to brain function in autism. The field has relied on association studies, but the only way to directly establish a neurotransmitter's role in a brain function is to experimentally change it and observe a shift. There is little direct experimental evidence on how neurochemical systems modulate information processing in the living human brain, limiting translation from animal studies. The authors introduce a "shiftability" paradigm to bridge this gap, using psilocybin as a pharmacological probe of the serotonin system in vivo. They present the protocol for 'PSILAUT', a study testing whether the serotonin system functions differently in autistic and non-autistic adults.
Psychedelic Medicine
February 3, 2026
Anton T. Gregersen, Tobias P. Whelan, Caroline T. Golden et al.
2 citations
Psilocybin, a serotonergic psychedelic, impaired short-term learning and unlearning speeds in rats performing a three-choice visual reversal learning task, though exploratory analysis suggested possible long-term enhancements in learning dynamics. Only five of sixteen Long-Evans rats (31%) successfully completed all six reversal protocols, demonstrating significant learning and unlearning over time. Computational modeling showed low learning rates with no significant differences between psilocybin and placebo conditions on any parameters. The findings indicate a nuanced effect of psilocybin on cognitive flexibility, with potential relevance for its use in neuropsychiatric disorders, but further research is needed on long-term outcomes.
Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Psilocybin and ketamine acutely increased reward responsiveness in rats, and the effect persisted 24 hours after dosing. The increase from psilocybin, but not ketamine, was blocked by a 5-HT2A receptor antagonist. Other psychedelics, DMT and DOI, also acutely increased reward responsiveness but the effect did not last 24 hours. The non-psychedelic 5-HT2A agonist lisuride and the SSRI fluoxetine had no positive effects. These results suggest psychedelics can produce acute and enduring increases in reward responsiveness, partly through the 5-HT2A receptor, though the time course varies and clinical implications require further validation.
February 27, 2025
Anton T. Gregersen, Tobias P. Whelan, Caroline T. Golden et al.
preprint
In a visual reversal learning task with rats, psilocybin temporarily impaired the speed of learning and unlearning, but exploratory analyses suggested possible long-term improvements in learning dynamics. Five out of sixteen rats completed all six reversal protocols, showing significant decreases in sessions needed to meet learning criteria and in reaction time over successive reversals. Computational modeling revealed low learning rates overall, with no significant differences between psilocybin and placebo on any modeled parameter. The findings indicate a nuanced, time-dependent effect of psilocybin on cognitive flexibility, with short-term impairment and hints of later enhancement, warranting further study of long-term outcomes.