Classic psychedelics and autism spectrum disorder: preclinical evidence, mechanistic insights and unresolved challenges.
Fabrizio Ascone, Diletta Giangiacomo, Viviana Trezza
Neuroscience & Biobehavioral Reviews August 1, 2026 DOI: 10.1016/j.neubiorev.2026.106761 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Preclinical studies on animal models and behavioral domains relevant to autism spectrum disorder |
| Topics | Neuroplasticity |
| Keywords | 5-ht2a signaling Autism spectrum disorder Classic psychedelics Neurobiological mechanisms Preclinical models |
| Key findings | Classic psychedelics affect behavioral domains overlapping with ASD phenotypes through neurobiological mechanisms that converge with alterations implicated in ASD, but direct evidence from validated animal models of ASD is scarce. |
Abstract
Classic psychedelics have re-emerged as compelling probes of neural plasticity, raising interest in their potential relevance for behavioral and circuit-level features associated with autism spectrum disorder (ASD). Although only a limited number of studies have examined these compounds in validated animal models of ASD, a growing body of preclinical work has investigated their effects on behavioral and neurobiological processes relevant to ASD. In this context, this review adopts a domain-based perspective, discussing studies that examine the effects of classic psychedelics on behavioral domains overlapping with ASD phenotypes, including social interaction, communication, repetitive behaviors, anxiety-like traits, and cognitive function. We critically evaluate the neurobiological mechanisms underlying these effects, focusing on serotonergic signaling, glutamatergic neurotransmission, neuroinflammatory processes, BDNF/TrkB pathways, oxytocinergic and dopaminergic modulation. Across these domains, we identify points of mechanistic convergence with neurobiological alterations implicated in ASD, and integrate emerging preclinical findings that may guide future hypothesis-driven research. At the same time, we highlight significant gaps that constrain interpretation. We conclude by outlining key conceptual and methodological limitations, including the scarcity of studies in established animal models of ASD, reliance on simplified behavioral assays, and uncertainty regarding how ASD-specific circuit alterations may influence responses to psychedelics. Addressing these issues will be essential to determine whether psychedelic-induced plasticity can provide meaningful insights into ASD pathophysiology or inform future translational efforts.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cites 59
- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
and 54 more in the library