Evaluating the Potential Use of Serotonergic Psychedelics in Autism Spectrum Disorder
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Recent clinical and preclinical evidence points towards empathogenic and prosocial effects elicited by psychedelic compounds, notably the serotonin 5-HT 2A agonists lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), and their derivatives. These findings suggest a therapeutic potential of psychedelic compounds for some of the behavioural traits associated with autism spectrum disorder (ASD), a neurodevelopmental condition characterized by atypical social behaviour. In this review, we highlight evidence suggesting that psychedelics may potentially ameliorate some of the behavioural atypicalities of ASD, including reduced social behaviour and highly co-occurring anxiety and depression. Next, we discuss dysregulated neurobiological systems in ASD and how they may underlie or potentially limit the therapeutic effects of psychedelics. These phenomena include: 1) synaptic function, 2) serotonergic signaling, 3) prefrontal cortex activity, and 4) thalamocortical signaling. Lastly, we discuss clinical studies from the 1960s and 70s that assessed the use of psychedelics in the treatment of children with ASD. We highlight the positive behavioural outcomes of these studies, including enhanced mood and social behaviour, as well as the adverse effects of these trials, including increases in aggressive behaviour and dissociative and psychotic states. Despite preliminary evidence, further studies are needed to determine whether the benefits of psychedelic treatment in ASD outweigh the risks associated with the use of these compounds in this population, and if the 5-HT 2A receptor may represent a target for social-behavioural disorders.
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LSD showed potential efficacy in ASD during the 'first wave' of psychedelic research.
“LSD showed potential efficacy in ASDduring the ' first wave ' of psychedelic research. 103”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [103]
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Perez, N., Langlest, F., Mallet, L., De Pieri, M., Sentissi, O., Thorens, G., Seragnoli, F., Zullino, D., Kirschner, M., Kaiser, S., et al. (2023) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2023.07.011 · Cited by 88 · see citing works
“…of 9 mg/70 kg) – in most disorders where anxiety of psychotic symptoms might occur (e.g.; anxiety disorders; schizoaffective disorders ( Arnovitz et al., 2022 ); bipolar depression ( Gard et al., 2021 ); autism spectrum disorders ( Markopoulos et al., 2022 ); borderline personality (NCT05399498).”
Pepe, M., Hesami, M., de la Cerda, K. A., Perreault, M. L., Hsiang, T., & Jones, A. M. P. (2023) · Biotechnology Advances · doi:10.1016/j.biotechadv.2023.108247 · Cited by 36 · see citing works
Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome
Buzzelli, V., Carbone, E., Manduca, A., Schiavi, S., Feo, A., Perederiy, J. V., Ambert, K. H., Hausman, M., & Trezza, V. (2023) · Psychopharmacology · doi:10.1007/s00213-022-06286-3 · Cited by 22 · see citing works
Scala, M., Fabbri, C., Fusar-Poli, P., Di Lorenzo, G., Ferrara, M., Amerio, A., Fusar-Poli, L., Pichiecchio, A., Asteggiano, C., Menchetti, M., et al. (2024) · CNS Spectrums · doi:10.1017/s1092852924002268 · Cited by 9 · see citing works
“103 Psilocybin ’ s empathogenic effects may alleviate social anxiety, and depression, as well as rigid cognitive and behavioral patterns associated with ASD while increasing emotional empathy and sociability.”
- Authors
- Markopoulos, A., Inserra, A., De Gregorio, D., & Gobbi, G.
- Affiliations
- McGill University (CA)
- McGill University Health Centre (CA)
- Corresponding author
- Gobbi, Gabriella
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2022-01-27
- Volume
- 12
- Pages
- 749068-749068
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC8846292
- OpenAlex
- W4210379385
- Cited by
- 46
- References
- 28
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 14 · 2023: 11 · 2022: 5
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Fonds de Recherche du Québec - Santé
- Canadian Institutes of Health Research
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- autism spectrum disorder, psychedelics, serotonergic psychedelics, 5-HT2A receptor, LSD, psilocybin, DMT, social behavior, anxiety, depression, synaptic function, prefrontal cortex
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