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Related Experiment Video

Updated: Jan 16, 2026

Microtransplantation of Synaptic Membranes to Reactivate Human Synaptic Receptors for Functional Studies
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Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.

Jacopo Sapienza1,2, Marco Spangaro1, Stefano Comai1,3,4,5

  • 1IRCCS San Raffaele Scientific Institute, 20127 Milan, Italy.

International Journal of Molecular Sciences
|September 27, 2025
PubMed
Summary
This summary is machine-generated.

Psychedelics may help treat schizophrenia by promoting neuroplasticity and synaptogenesis, counteracting synaptic loss. Microdoses are recommended for initial trials in patients with deficit schizophrenia.

Keywords:
LSDSV2Acognitioncomplement 4microglianegative symptomsneuroplasticitypsilocybinpsychosissynaptogenesis

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Schizophrenia is a polygenic disorder linked to altered synaptic homeostasis.
  • Complement component 4 (C4) gene variants strongly associate with schizophrenia, impacting synaptic pruning via microglia.
  • Overactive microglia and reduced synaptic density in the prefrontal cortex (PFC) are hallmarks of schizophrenia.

Purpose of the Study:

  • To explore the potential of psychedelics in treating schizophrenia.
  • To investigate if psychedelics can counteract synaptic loss and promote neuroplasticity in schizophrenia.

Main Methods:

  • Review of preclinical evidence (in vitro and animal models) on psychedelic effects on neuroplasticity.
  • Consideration of in vivo studies using SV2A radioligands to assess synaptic density in schizophrenia patients.

Main Results:

  • Preclinical studies show psychedelics promote neuroplasticity and synaptogenesis.
  • Lower synaptic density in the PFC of schizophrenia patients confirmed by SV2A imaging.
  • Potential for psychedelics to restore volume loss and improve negative/cognitive symptoms.

Conclusions:

  • Psychedelics show promise for schizophrenia treatment by enhancing synaptic connections.
  • Microdosing psychedelics should be explored first in deficit schizophrenia patients.
  • Further research with varying doses may reveal broader therapeutic applications.