Therapeutic potential of classic and non-classic psychedelics in neurodevelopmental disorders: Opportunities and challenges
Mattia Giovenzana, Noemi Nicosia, Stefano Spinosa, Laura Musazzi, Jessica Mingardi
Pharmacological Research August 26, 2026 DOI: 10.1016/j.phrs.2026.108366 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Neuroplasticity |
| Keywords | Psychedelics Neurodevelopmental disorders |
| Key findings | Argues that available evidence on psychedelics for NDDs is limited, with most data from small adult clinical studies of low-dose ketamine and scarce observational reports on classic psychedelics, yet findings are promising, especially for cognitive and social improvements. |
Abstract
Neurodevelopmental disorders (NDDs) comprise a heterogeneous group of conditions arising from altered brain development and leading to impairments in social, cognitive, emotional, and motor domains. Clinical manifestations are highly variable in severity and symptom profile, reflecting the complex and multifactorial etiology of NDDs. Available treatments are limited to early behavioral interventions, eventually combined with symptomatic pharmacotherapies, but remain largely unsatisfactory. Among possible new therapeutic strategies for NDDs, classic psychedelics, such as LSD or psilocybin, and non-classic psychedelics including ketamine have recently received interest due to their potential in enhancing neuroplasticity and restoring social and cognitive deficits. Classic psychedelics are a group of psychoactive substances sharing agonistic activity on serotonergic 5-HT2A receptors while ketamine is a dissociative anesthetic acting as N-methyl-D-aspartate (NMDA) receptor non-competitive antagonist. Although the literature about the potential of psychedelics in the treatment of NDDs is still scarce and heterogeneous, we revised here available clinical and preclinical data to discuss the opportunities and challenges associated with the use of these drugs in NDDs. We found that most of the evidence comes from small clinical studies on adult subjects mainly evaluating the therapeutic potential of low dose ketamine, while reports with classic psychedelics are scarce and primarily observational. Overall, despite further research being needed before any conclusions can be drawn regarding the efficacy and safety of classic and non-classic psychedelics in the management of NDDs, most findings are promising and report significant behavioral improvements especially in cognitive and social domains.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Argues that available evidence on psychedelics for neurodevelopmental disorders is limited, with most data from small adult clinical studies of low-dose ketamine and scarce observational reports on classic psychedelics, yet findings are promising, especially for cognitive and social improvements.
Synthesized
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 72
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
and 67 more in the library