Mushrooms of the genus Psilocybe appear to have begun producing the psychedelic compound psilocybin roughly 67 million years ago, right around the time of the dinosaurs’ demise, according to a newly published study led by researchers from the University of Utah and the Natural History Museum of Utah.
The results also suggested that wood decomposition—as opposed to other preferred niches like dung or soil—as “the ancestral ecology of Psilocybe,” though the ability to produce psilocybin seems to have later jumped from some types of fungi to others over tens of millions of years.
Authors noted that some past research has speculated that interaction with termites “may have provided the selective force for the evolution of psilocybin as a modulator of the symbiosis.”
The new report represents the largest-ever genomic diversity study for the genus Psilocybe, according to a University of Utah announcement, and involved analyzing dozens of specimens—including 39 species that had never before been genetically sequenced.
Researchers then “bioinformatically mined the primary psilocybin [biosynthetic gene cluster] and mapped the core genes on the phylogeny to investigate the tempo, mode, and patterns of its evolution,” says the team’s dense, nine-page research article published in the journal PNAS (Proceedings of the National Academy of Sciences) earlier this month.
The project essentially allowed researchers to trace psilocybin-related gene patterns back through an even more detailed family tree. The work helps shed light on the evolutionary history of psychedelic fungi, including when psilocybin production may have arisen and spread.
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The authors wrote that physical interaction between wood-dwelling mushrooms and other fungi “may be one way the psilocybin [biosynthetic gene cluster] could be transferred horizontally. However, the true vector of these [horizontal gene transfers] is unknown.”
That’s the beauty of it,” said Alexander Bradshaw, a postdoctoral researcher at the University of Utah and the study’s lead author. “No one has really sequenced type specimens at this scale, and now we get to produce molecular and genomic data to the gold standard of Psilocybe types for people to compare against.”
Type specimens, the study explains, “are the ultimate authority for applying names to other collections and are therefore essential references for accurately naming and describing diversity.” But “outside of a handful of common species,” it says, Psilocybe species “are not commonly collected, and many specimens are represented by a single collection, making research with them tremendously difficult.”
“This work represents a big step in the understanding of the evolutionary relationships in Psilocybe because it is the first to include a broad species sampling and is based on type specimens,” said Virginia Ramírez-Cruz, a mycologist at the Universidad de Guadalajara and co-lead author of the study.
According to the university release, the study helps establish that psilocybin was first synthesized in Psilocybe, “with four or five possible horizontal gene transfers to other mushrooms from 40 [million] to 9 million years ago.”
The analysis further revealed “two distinct gene orders within the gene cluster that produces psilocybin,” it says. “The two gene patterns correspond to an ancient split in the genus, suggesting two independent acquisitions of psilocybin in its evolutionary history. The study is the first to reveal such a strong evolutionary pattern within the gene sequences underpinning the psychoactive protein synthesis.”
Despite the strong likelihood of some horizontal transfers, authors wrote that the presence of the psilocybin gene cluster in all the study’s Psilocybe specimens— ”suggests that the [gene cluster] is primarily inherited vertically within the genus, although some patterns suggest this may not be the only mechanism.”
The study’s senior author, Bryn Dentinger, curator of mycology at the National History Museum of Utah, said the findings could help fuel future therapeutic research.
“There’s a wealth of diversity of these compounds out there. To understand where they are and how they’re made, we need to do this kind of molecular work to use biodiversity to our advantage,” he said. “If psilocybin does turn out to be this kind of wonder drug, there’s going to be a need to develop therapeutics to improve its efficacy. What if it already exists in nature?”
The study doesn’t attempt to provide a definitive answer for the ecological role of psilocybin. Disorientation or altered behavior in some animals, including humans, might be either a deterrent (to protect the fungus) or an attractant (to help spread spores), although authors note that because some species are scarce and pharmacological effects may be delayed, it’s “difficult to imagine how animals could learn to recognize them.”
Psilocybin may also be a historical defense against insect pests, although “anecdotes and personal observations confirm that psilocybin-containing mushrooms regularly have living insect larvae in them and they can be reared to adults,” suggesting that any chemical defense properties “may be ineffective against insects or that some insects may have evolved detoxifying capabilities in response.”
Others hypothesize that it’s some sort of “inducible chemical defense system” associated with the blue pigment that forms when psilocybin-containing mushrooms are damaged. At that point, psilocybin is converted into psilocin, which forms polymer chains that “produce reactive oxygen molecules that can damage gut tissue.”
“They propose the ‘polymer hypothesis,’” the study’s authors explained of the theory’s proponents, “where the psilocin oligo/polymers may be an inducible defense against fungivory and psilocybin is simply the artillery and psilocybin is simply the artillery kept in reserve for the true chemical weaponry.”
They note that “the formation of the blue psilocin oligo/polymers is invariably connected to psilocybin biosynthesis throughout the multiple independent inheritances and convergent evolution.”
One possibility might be slugs—a hypothesis authors aim to test in future research, according to the University of Utah:
“The authors are preparing experiments to test an alternative theory that they call the Gastropod Hypothesis. The timing and divergence dates of Psilocybe coincide with the KPg boundary, the geological marker of the asteroid that threw Earth into a brutal, prolonged winter and killed 80% of all life. Two lifeforms that thrived during the darkness and decay were fungi and terrestrial gastropods. Evidence, including the fossil record, shows that gastropods had a massive diversification and proliferation just after the asteroid hit, and it’s known that terrestrial slugs are heavy predators of mushrooms. With the study’s molecular dating of Psilocybe to around 65 million years ago, it’s possible that psilocybin evolved as a slug deterrent.”
Institutions worldwide sent specimens to be sequenced as part of the study, the university’s release said, including some that were collected more than 150 years ago.
“It’s impossible to overstate the importance of collections for doing studies like this,” Bradshaw said. “We are standing on the shoulders of giants, who spent thousands of people-power hours to create these collections, so that I can write an email and request access to rare specimens, many of which have only ever been collected once, and may never be collected again.”
As far as human use of psilocybin mushrooms goes, separate research suggests humans have been ingesting them for potentially millions of years. The use of marijuana, by contrast, is believed to be more recent.
Studies published last year and in 2019 suggest that humans first began using plants of the genus Cannabis about 10,000 years ago, initially using hemp for fibers and nutrition.
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Consuming cannabis for its experiential effects, meanwhile, seems to date back roughly 3,000 years. A Chinese emperor from about 2,700 B.C.E. described the plant as “a first-class herb.”
Cannabis and the genus that contains hops—marijuana’s closest living relative—diverged about 28 million years ago, according to a 2018 study.
Another study suggests the rise of cannabinoids like THC and CBD may have been the result of genetic mischief at the hands of ancient viruses.
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