ArticleMolecular psychiatry2024
Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Naturally Derived Psilocybin for Therapeutic Use: A Six-Criterion Framework for Evidence, Safety, and Benefit-Risk Considerations in Policy and Clinical Development.Biomolecules · 2026Review
- Surprising Variability in Tryptamine Profiles ofJournal of fungi (Basel, Switzerland) · 2026Article
- Specific and Multi-Product Clade I and Clade IV Sesquiterpene Synthases Contribute to the Psilocybe cubensis Volatilome.Chembiochem : a European journal of chemical biology · 2026Article
- Electrocorticographic Changes and Neuronal Maturation in the Antidepressant-like and Anxiolytic Effects of Micro- or Macrodosing ofMolecules (Basel, Switzerland) · 2026Article
- Review
- Network pharmacology and molecular simulation reveal the entourage effect mechanisms of psilocybin-producing mushrooms on the brain.Scientific reports · 2026Article
- Community engagement as a foundation for implementation research for group psilocybin assisted therapy in New Mexico.Frontiers in public health · 2026Article
- An exploration of the relationships between the effects of psilocybin on behavior, 5-HTJournal of psychopharmacology (Oxford, England) · 2026Article
- Electroacupuncture alleviates comorbid obesity and depression via the gut-brain axis: orchestrating SCFA-producing bacteria and hippocampal synaptic plasticity.Frontiers in microbiology · 2026Article
- The Neuroimmunology of Autism.Molecular neurobiology · 2025Review
- Anti-P antibodies that impair memory perturb hippocampal glutamatergic receptor trafficking, synapse structure and microglia.Molecular medicine (Cambridge, Mass.) · 2025Article
- ASTROGLIA: Molecular Mechanisms, Functional Roles, and Neurophysiological Implications in the Central Nervous System.Life (Basel, Switzerland) · 2025Review
- Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.International journal of molecular sciences · 2025Review
- Letter to the editor: Comments on 'Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming' by Brownstien et al. (2024).Molecular psychiatry · 2025Article
- Clade III Synthases Add Cyclic and Linear Terpenoids to the Psilocybe Metabolome.Chembiochem : a European journal of chemical biology · 2025Article
- Premorbid characteristics of the SAPAP3 mouse model of obsessive-compulsive disorder: behavior, neuroplasticity, and psilocybin treatment.The international journal of neuropsychopharmacology · 2025Article
- Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters.Scientific reports · 2025Article
- 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 · 2025Article
- ExploringJournal of fungi (Basel, Switzerland) · 2025Review
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications.Brain sciences · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice. HTR measurement showed similar effects of PSIL and PME over 20 min. Brain specimens (frontal cortex, hippocampus, amygdala, striatum) were assayed for the synaptic proteins, GAP43, PSD95, synaptophysin and SV2A, using western blots. These proteins may serve as indicators of synaptic plasticity. Three days after treatment, there was minimal increase in synaptic proteins. After 11 days, PSIL and PME significantly increased GAP43 in the frontal cortex (p = 0.019; p = 0.039 respectively) and hippocampus (p = 0.015; p = 0.027) and synaptophysin in the hippocampus (p = 0.041; p = 0.05) and amygdala (p = 0.035; p = 0.004). PSIL increased SV2A in the amygdala (p = 0.036) and PME did so in the hippocampus (p = 0.014). In the striatum, synaptophysin was increased by PME only (p = 0.023). There were no significant effects of PSIL or PME on PSD95 in any brain area when these were analyzed separately. Nested analysis of variance (ANOVA) showed a significant increase in each of the 4 proteins over all brain areas for PME versus vehicle control, while significant PSIL effects were observed only in the hippocampus and amygdala and were limited to PSD95 and SV2A. Metabolomic analyses of the pre-frontal cortex were performed by untargeted polar metabolomics utilizing capillary electrophoresis - Fourier transform mass spectrometry (CE-FTMS) and showed a differential metabolic separation between PME and vehicle groups. The purines guanosine, hypoxanthine and inosine, associated with oxidative stress and energy production pathways, showed a progressive decline from VEH to PSIL to PME. In conclusion, our synaptic protein findings suggest that PME has a more potent and prolonged effect on synaptic plasticity than PSIL. Our metabolomics data support a gradient of effects from inert vehicle via chemical psilocybin to PME further supporting differential effects. Further studies are needed to confirm and extend these findings and to identify the molecules that may be responsible for the enhanced effects of PME as compared to psilocybin alone.
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