Molecular psychiatry
July 1, 2024
Orr Shahar, Alexander Botvinnik, Amit Shwartz et al.
37 citations
Psilocybin-containing mushroom extract (PME) may have stronger and longer-lasting effects on synaptic plasticity than chemically synthesized psilocybin (PSIL) alone. In male mice, both PME and PSIL increased synaptic proteins GAP43 and synaptophysin in brain regions linked to learning and memory, but PME increased more proteins across more brain areas after 11 days. Metabolomic analysis of the frontal cortex revealed a distinct metabolic profile for PME, with a progressive decline in purines associated with oxidative stress from vehicle to PSIL to PME. These findings suggest that other compounds in the mushroom extract contribute to enhanced neuroplasticity, though further research is needed to identify them.
Molecular Psychiatry
October 11, 2024
Michal Brownstien, Michal Lazar, Alexander Botvinnik et al.
23 citations
In mice lacking the SAPAP3 gene, which display excessive self-grooming and anxiety similar to human obsessive-compulsive disorder, a single injection of psilocybin or psychedelic mushroom extract reduced self-grooming by about 15-19% over 21 days, while vehicle-treated mice showed a 119% increase. The effects lasted up to 7 weeks in responsive mice, and non-responsive mice later treated with psilocybin also improved. The mushroom extract was superior for reducing head-body twitches and anxiety. These results support clinical trials of psilocybin for OCD.
Frontiers in Pharmacology
April 18, 2024
Elad Lerer, Alexander Botvinnik, Orr Shahar et al.
14 citations
Psilocybin and a psilocybin-containing mushroom extract, but not the serotonin precursor 5-hydroxytryptophan, increased expression of immediate early genes cfos and egr1 in the somatosensory cortex of male mice. The head twitch response, a behavioral measure, did not correlate with gene expression changes. Blocking the 5-HT2C receptor enhanced psilocybin-induced egr2 expression, but other serotonergic modulators had no effect. These findings suggest that cfos and egr1 expression may be linked to psychedelic effects.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2023
Leonard Lerer, Eric Reynolds, Jeet Varia et al.
6 citations
A cell line derived from the parotoid gland of the endangered Sonoran Desert toad (Incilius alvarius) can biosynthesize 5-MeO-DMT, a psychedelic compound with therapeutic potential for psychiatric disorders. The toad's secretions also contain other molecules such as bufotenine, bufagenins, bufotoxins, and indole alkylamines, which may have individual clinical utility or act as entourage molecules. The species faces ecological pressure from demand for natural 5-MeO-DMT and habitat loss. Cell-based biosynthesis offers a potentially cruelty-free and sustainable source of naturally derived 5-MeO-DMT for research and drug development.
bioRxiv (Cold Spring Harbor Laboratory)
June 29, 2024
Michal Brownstien, Michal Lazar, Alexander Botvinnik et al.
5 citations
preprint
In mice with a genetic deletion that causes excessive self-grooming and anxiety—behaviors resembling aspects of obsessive-compulsive disorder (OCD)—a single dose of psilocybin or psychedelic mushroom extract reduced self-grooming over 21 days, while vehicle-treated mice showed a 118.7% increase. Psilocybin and the extract both decreased self-grooming by about 15–19%, and improvements in secondary measures like twitches and anxiety were also significant. In responsive mice, benefits lasted up to 7 weeks. The extract was superior for alleviating head-body twitches and anxiety. These results support clinical trials of psilocybin for OCD.
Research Square
July 20, 2023
Orr Shahar, Alexander Botvinnik, Amit Shwartz et al.
3 citations
Psilocybin-containing mushroom extract (PME) produces more potent and prolonged effects on synaptic plasticity in the mouse brain than chemically synthesized psilocybin alone. In male C57Bl/6j mice, both PME and psilocybin triggered similar head twitch responses, but PME increased four synaptic proteins (GAP43, PSD95, synaptophysin, SV2A) across all brain areas studied after 11 days, whereas psilocybin only increased two proteins in the hippocampus and amygdala. Metabolomic analysis of the prefrontal cortex showed a gradient of metabolic changes from vehicle to psilocybin to PME, with declines in purines linked to oxidative stress and energy production. The findings suggest that additional compounds in the mushroom extract may enhance psilocybin's effects on brain plasticity.
The International Journal of Neuropsychopharmacology
February 1, 2025
Leonard Lerer, Kathleen Spear, Jeet Varia et al.
In a zebrafish model of depression, both synthetic psilocybin and an extract from psychedelic mushrooms reversed stress-induced behavioral changes, making the fish behave similarly to non-stressed controls. The mushroom extract produced more neurotransmitter precursors in the brain than synthetic psilocybin, though no significant behavioral differences between the two treatments were observed. Whole-brain metabolomics revealed increases in GABA, vitamin B6, glutamine, and NADH, along with a decrease in xanthosine, suggesting possible neuroplastic effects. This work demonstrates the potential of zebrafish models for studying psychedelic compounds.
bioRxiv (Cold Spring Harbor Laboratory)
May 22, 2022
Leonard Lerer, Eric C. Reynolds, Jeet Varia et al.
preprint
A sustainable source of 5-MeO-DMT, a promising compound for psychiatric treatment, has been developed using a cell line from the parotoid gland of the endangered Incilius alvarius toad. This innovative approach demonstrated successful biosynthesis of 5-MeO-DMT through chemical processes in vitro. Given that natural populations are under ecological threat due to habitat loss and demand, this method offers a cruelty-free alternative for producing 5-MeO-DMT, potentially supporting future psychedelics and drug studies while preserving biodiversity.