Set and setting, and psilocin binding to 5HT2A receptors are the two domgas of how magic mushrooms work. To the point it feels that's all we think matters to dictate a psilocybin experience from magic mushrooms. Let's think back a couple of million years to before mammals were on the scene. Under a clock-like rate of speciation, species are between 500K to 5 million years old. Genera are somewhat older, and Basidiomycota are an anomaly compared to other organisms. Genera of Basidiomycota are usually 20–100 million years old. (Check out this paper if you want to read more: https://academic.oup.com/mbe/article/32/4/835/1078218). Psilocybe could be anywhere from 20 to 100 million years old. We assume that the most recent common ancestor of all species of Psilocybe could produce psilocybin (because all except one produce it), and likely psilocybin is the same age as Psilocybe. All species of Psilocybe, extant and extinct, have forged their way in niches of leaf litter, wood, grass, moss, and dung. We don't know the exact purpose of psilocybin, whether to repel, control, or attract, but we can be certain it targets metazoans with serotonin receptors. Whatever metazoans dominate the different niches of Psilocybe, we can be sure over an evolutionary time scale the genes that produce psilocybin in 200 or so species are refined to best target species of slug, arthropod, nematode, or whatever was eating it for whatever reason in whatever niche. This has happened time and again with co-evolved relationships, especially those with metabolites governing the symbiosis. If you accept that there are different predators across 200 species of Psilocybe, you may be on the way to understanding why I think different magic mushrooms give different psychedelic experiences. Different effects from different species given an evolutionary time scale is hopefully palatable, but to say that allelic variation in one species changes an experience is more difficult to swallow, especially with the dogmas of how trips work. We showed that populations of P. subaeruginosa maintain genetic diversity in the alleles that produce psilocybin rather than just one becoming dominant (balancing selection to be fancy). This is probably why WLP can be in some, but not all genotypes and is maintained in populations. What the blazes is the benefit of all this diversity? Diversity to the extent that psilocybin alleles are barely shared by closely related populations and there is reason to suspect recombination within the locus itself that would ensure that the same alleles in the pathway are not linked (or not always inherited together).
Long story short, our work on subs shows an evolutionary process of maintaining allelic diversity in the psilocybin pathway (or balancing selection). Cubes have a solid 5–6 alleles at the psilocybin locus in the entire population of cultivated mushrooms and a bunch more in naturalised populations. I've grown most of these and am in the process of testing the tryptamine landscape in homozygous genotypes. I've crossed different alleles to see what happens when the psilocybin locus is heterozygous. I've never been more convinced that there are phenotypic impacts from genotypic diversity, and I hope to hold hard evidence soon. Rest assured, if the time comes, the people will be able to decide if there are differences themselves. In the meantime, do me a favour next sub season: don't combine harvests from different patches. Experience them separately and share whether there is a difference (given a consistent set and setting). Expect there to be different psilocybin alleles at different mushroom sites, unless the mushrooms are harvested from mulch/woodchips that have been spread artificially (wild harvests will guaranteed be different alleles). More on all this soon.
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Designer Shrooms @ Funky Fungus on 1st July 2023
I started a gig at Funky Fungus as Chief Scientific Officer to make designer shrooms Our research on Psilocybe
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