Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.
Orr Shahar, Alexander Botvinnik, Amit Shwartz, Elad Lerer, Peretz Golding, Alex Buko, Ethan Hamid, Dani Kahn, Miles Guralnick, Karin Blakolmer, Gilly Wolf, Amit Lotan, Leonard Lerer, Bernard Lerer, Tzuri Lifschytz
Molecular Psychiatry July 1, 2024 DOI: 10.1038/s41380-024-02477-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male C57Bl/6j mice |
| Intervention | chemically synthesized psilocybin (PSIL) |
| Duration | Single dose, with measurements at 3 days and 11 days post-treatment |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Psychedelics Medicinal mushrooms |
| Citations | 37 |
| Key findings | Psilocybin-containing mushroom extract produced more potent and prolonged effects on synaptic plasticity proteins and distinct metabolomic profiles compared to chemically synthesized psilocybin alone. |
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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 32
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 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 for the treatment of Alzheimer’s disease Frontiers in Neuroscience July 10, 2024
- Concurrent stress modulates the acute and post-acute effects of psilocybin in a sex-dependent manner Neuropharmacology December 24, 2024
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
and 27 more in the library
Cites 44
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Structure-based discovery of nonhallucinogenic psychedelic analogs Science January 27, 2022
and 39 more in the library