Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders.
Uriel Heresco-Levy, Bernard Lerer
Molecular Psychiatry 2024 DOI: 10.1038/s41380-023-02312-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Interventions | Psilocybin D-serine D-cycloserine |
| Topics | Neuroplasticity |
| Keywords | Mental health treatment Pharmacology Psychedelics |
| Citations | 17 |
| Key points | Proposes that the synchronous administration of a psychedelic and an NMDAR modulator may increase therapeutic impact and improve safety. |
Abstract
Modern research data suggest a therapeutic role for serotonergic psychedelics in depression and other neuropsychiatric disorders, although psychotomimetic effects may limit their widespread utilization. Serotonergic psychedelics enhance neuroplasticity via serotonin 2 A receptors (5HT2AR) activation and complex serotonergic-glutamatergic interactions involving the ionotropic glutamate receptors, tropomyosin receptor kinase B (TrkB) and the mammalian target of rapamycin (mTOR). N-methyl-d-aspartate receptors (NMDAR) channel antagonists, i.e. ketamine, and glycine modulatory site full and partial agonists, i.e., D-serine (DSR) and D-cycloserine (DCS), share some of these mechanisms of action and have neuroplastic and antidepressant effects. Moreover, procognitive effects have been reported for DSR and DCS and 5HT2AR-NMDAR interactions modulate neuronal excitability in prefrontal cortex and represent a target for new antipsychotics. We hypothesize that the synchronous administration of a psychedelic and a NMDAR modulator may increase the therapeutic impact of each of the treatment components and allow for dose adjustments and improved safety. We propose to initially focus research on the acute concurrent administration of psilocybin and DSR or DCS in depression.
Comparable studies
Other theoretical and historical papers on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic Potential? | 2021 | Theoretical or philosophical paper | |
| A complex systems perspective on psychedelic brain action. | 2023 | Theoretical or philosophical paper | |
| Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy | 2021 | Theoretical or philosophical paper | |
| Therapeutic mechanisms of psychedelics and entactogens. | 2023 | Theoretical or philosophical paper |
Citations in the library
Cited by 8
- Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies. Molecular Psychiatry March 1, 2025
- Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming Molecular Psychiatry October 11, 2024
- Psilocybin as Transformative Fast‐Acting Antidepressant: Pharmacological Properties and Molecular Mechanisms Fundamental and Clinical Pharmacology July 16, 2025
- Synergistic behavioral and neuroplastic effects of psilocybin-NMDAR modulator administration Translational Psychiatry June 13, 2025
- Is there a place for psychedelics in sports practice? Acta Neuropsychiatrica 2025
and 3 more in the library
Cites 22
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
and 17 more in the library