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Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia

Summary

Schizophrenia involves excessive loss of connections between brain cells in areas responsible for emotion and thinking, leading to negative symptoms and cognitive problems. Research shows that small doses of psychedelics like psilocybin can promote the growth of new brain connections and reduce inflammation. The authors suggest that microdosing psychedelics alongside standard treatments might help restore these lost connections and improve symptoms that don’t respond well to current medications.

Background

Schizophrenia is characterized by reduced synaptic density in the prefrontal cortex (PFC), particularly due to excessive complement-mediated synaptic pruning. Recent PET imaging with SV2A radioligands has confirmed in vivo synaptic loss in individuals with schizophrenia. Psychedelics have demonstrated neuroplasticity-promoting properties in preclinical studies that could potentially counteract this synaptic deficit.

Objective

This perspective paper examines the theoretical basis for using microdoses of psychedelics to restore synaptic density and treat negative and cognitive symptoms in schizophrenia. The authors propose that psychedelics’ synaptogenic and anti-inflammatory properties could address the underlying synaptic pathology of the disease.

Results

Evidence shows reduced synaptic density in schizophrenia correlates with negative and cognitive symptoms. Psychedelics promote synaptogenesis and have anti-inflammatory properties that could reduce excessive pruning. Historical studies reported improvements in negative symptoms and social interactions with low-dose LSD (25-50 µg), suggesting potential therapeutic benefit.

Conclusion

Carefully designed clinical trials exploring microdosing of psychedelics in patients with deficit schizophrenia and prominent negative symptoms are justified. The authors recommend starting with microdoses combined with ongoing antipsychotic treatment, under medical supervision, with [11C] UCB-J PET imaging to assess synaptic density changes.
  • Published in:International Journal of Molecular Sciences,
  • Study Type:Perspective/Review,
  • Source: PMID: 41009515, DOI: 10.3390/ijms26188949
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