Evaluating the Potential Use of Serotonergic Psychedelics in Autism Spectrum Disorder
This review evaluates evidence that serotonergic psychedelics (5‑HT2A agonists such as LSD, psilocybin and DMT) may ameliorate social deficits and co‑occurring anxiety and depression in autism spectrum disorder. It highlights neurobiological constraints (synaptic, serotonergic, prefrontal and thalamocortical dysfunction), mixed and sometimes adverse outcomes in historical paediatric trials, and concludes that rigorous contemporary studies are needed to determine whether benefits outweigh risks and whether 5‑HT2A is a viable therapeutic target.
Authors
- Danilo De Gregorio
- Gabriella Gobbi
Published
Abstract
Recent clinical and preclinical evidence points towards empathogenic and prosocial effects elicited by psychedelic compounds, notably the serotonin 5-HT2A 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-HT2A receptor may represent a target for social-behavioural disorders.
Research Summary of 'Evaluating the Potential Use of Serotonergic Psychedelics in Autism Spectrum Disorder'
Introduction
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition affecting an estimated 1-2% of the global population, characterised chiefly by atypical social communication and restricted, repetitive behaviours. Currently there are no medications that selectively target the core social and communicative features of ASD; instead clinicians use antipsychotics, antidepressants, mood stabilisers and stimulants to treat associated symptoms such as irritability, anxiety and depression. Against this background, serotonergic or "classical" psychedelics—compounds that produce their principal effects via agonism at the serotonin 5-HT2A receptor (for example LSD, psilocybin and DMT)—have re-emerged in research because of reported empathogenic and prosocial effects in preclinical and clinical studies of neurotypical adults. Markopoulos and colleagues set out to review the evidence bearing on whether serotonergic psychedelics could have therapeutic value for some behavioural atypicalities in ASD. The review outlines (1) behavioural findings that suggest psychedelics increase sociability and reduce co-occurring anxiety and depression; (2) neurobiological systems implicated in ASD that might mediate or limit psychedelic effects (synaptic function, serotonergic signalling, prefrontal cortex function and thalamocortical circuits); and (3) early clinical trials from the 1960s–70s that tested psychedelics in children with what was then called "autistic schizophrenic" or severely emotionally disturbed presentations. The authors emphasise both the preliminary promise and the risks identified historically, arguing for careful contemporary research before clinical application in ASD.
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Markopoulos, A., Inserra, A., De Gregorio, D., & Gobbi, G. (2022). Evaluating the Potential Use of Serotonergic Psychedelics in Autism Spectrum Disorder. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.749068
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