Psychedelic Mushrooms Existed Millions of Years Before Humans, Largest-Ever Study Reveals

Scientists have completed the largest genomic study of magic mushrooms to date, laying the groundwork for new therapeutics and providing new tools for biotechnologists.

In a study published Tuesday in Proceedings of the National Academy of Sciences, researchers from the US, UK and Mexico analyzed the genomes of more than 50 mushrooms from the Psilocybe genus—the group whose members almost all contain the psychedelic compounds psilocybin and psilocin.

Despite the flurry of attention psilocybin has received due to its promising potential as a drug for treating mental illness or for end of life care, very few of the roughly 165 species that make up this group have been studied before. 

“Genomics is what you need to really investigate all of the unique properties of these different species,” co-author and curator of mycology at the Natural History Museum of Utah, Bryn Dentinger, told Motherboard. “We pushed this as far as we possibly could with as many species and as many specimens as we could.”

Dentinger and his team found that psilocybin-making in Psilocybe sprung up in evolutionary history around 65 million years ago. To put that in perspective, the earliest human species appeared on the scene roughly 2 million years ago, with modern Homo sapiens evolving 300,000 years ago. Before this study, scientists had no definitive estimate of when this trippy ability evolved. What’s more, they found that the mushrooms evolved two independent ways of making psilocybin, one of which was previously undiscovered.

Most fungi make psilocybin using four core enzymes that work in a particular sequence, or pathway. How those enzymes are made and in what order they work is controlled by a specific cluster of genes. This study found that these genes could appear in a different order to the one researchers had previously identified. Of the mushrooms they studied, more than 65 percent had genes that were arranged in this non-typical way.

The finding could be a boon for biotechnology companies looking to make synthetic versions of the hallucinogenic compound. “If you’re looking for a way to express the genes to produce the psilocybin and related compounds, you no longer have to rely on only one set of gene sequences to do that,” said Dentinger. “We’ve greatly expanded the ingredients that are available for developing these kinds of tools.”

One gene in particular—the PsiH or P450 monooxegynase gene—was a lot more variable across the genus than the others. Alexander Bradshaw, lead author of the study, says they’re not sure yet why but it could be one for researchers and biotech scientists to keep an eye on. “There’s probably a lot more going on with that gene, and we don’t know exactly what that is at this point,” the postdoctoral researcher said.

As well as identifying specific genes of interest, the study as a whole lays the groundwork for researchers to uncover new therapeutic compounds by documenting the diversity of these mushrooms. 

In 2020, the researchers gave themselves a goal to sequence every Psilocybe species. While they’ve made a substantial dent in that goal, Detinger says they’ve been held back by regulation, stigma, and confusion surrounding the ‘shrooms. 

“The research has been stifled quite a bit," he said. "Even some of the stuff we’re working on now has been done in other groups of fungi that don’t have these social and political issues.” 

Some potential-collaborators wouldn’t lend them their samples for analysis because they had a blanket rule against providing the material, Detinger added. 

Alistair McTaggart, a prominent mycologist from The University of Queensland who wasn't involved in the study, has called the rules around Psilocybe research “draconian." McTaggart says we need to understand how genetic diversity contributes to how people experience a trip, but that that isn’t possible without looking at as many genomes as possible.

Detinger adds that the long-held stigma turned sudden interest for the mushrooms means there’s been a boom in the amount of “underground secondary scientific” research that’s, in some cases, yielded misinformation. Plus, it’s still difficult to get funding from big agencies for this kind of work, despite the potential positive scientific and therapeutic outcomes.