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How Psychedelic Mushrooms Evolved Their Magic

Two distantly related groups of mushrooms take radically different routes to producing psilocybin, a mind-bending molecule.

Researchers were surprised to see how profoundly the two mushroom’s paths to making psilocybin diverged. Credit...Alana Paterson for The New York Times

No one knows why magic mushrooms evolved to produce psilocybin, a powerful psychedelic molecule. But this trait was apparently so beneficial for fungi that it independently evolved in two distantly related types of mushrooms.

An even greater surprise to biologists was that rather than arriving at the same solution for producing psilocybin, the two groups pursued completely different biochemical pathways, according to a study published last month in the journal Angewandte Chemie International Edition.

“This finding reminds us that nature finds more than one way to make important molecules,” said Dirk Hoffmeister, a pharmaceutical microbiologist at Friedrich Schiller University Jena in Germany and an author of the study. He added that it was also evidence that mushrooms were “brilliant chemists.”

Practically speaking, Dr. Hoffmeister said, the research also suggested a possible new path for synthesizing psilocybin for use in scientific research and therapies. “We can expand our toolbox,” he said.

Psilocybe and Inocybe mushrooms occur in some of the same habitats, but they follow different lifestyles. Psilocybe, the group that includes what are traditionally called magic mushrooms, thrives on decaying material such as decomposing organic matter or cow dung. Inocybe, commonly known as fiber caps, are symbiotic organisms that form intimate, mutually beneficial relationships with trees.

In 1958, Albert Hofmann, the Swiss chemist who discovered LSD, became the first researcher to isolate psilocybin from Psilocybe mushrooms. Some scientists later suspected that a few Inocybe mushrooms also produced the compound. Since then, psilocybin has been identified in around half a dozen Inocybe species. (The other species tend to produce a potent neurotoxin.)

Some researchers hypothesized, however, that the enzymatic formula magic mushrooms use to make psilocybin might not be the only way nature has found to create the molecule. The new study offers biochemical evidence supporting that hunch.

Dr. Hoffmeister and his colleagues produced and analyzed the enzymes responsible for psilocybin biosynthesis in both magic mushrooms and fiber caps. They used computer models to predict the molecular structures of new enzymes they found along the way.

When the researchers compared the two routes the fungi took to make psilocybin, they were surprised to see just how profoundly they diverged. “We definitely hadn’t expected that the two pathways would be so radically different,” Dr. Hoffmeister said.

Psilocybe and Inocybe both use the same amino acid starting point to produce psilocybin. But from there, the mushrooms follow separate road maps of genes and enzymes. Midway through, they meet at an intermediate molecular point before parting ways once again — only to converge on a shared end product.

“It’s like meandering through New York City and taking different roads to get to the same destination,” Dr. Hoffmeister said. “You can go this way or that way, but at a certain point, you meet at Central Park.”

Jon Thorson, a chemist at the University of Kentucky who was not involved in the work, pointed out that psilocybin was already “a fairly simple molecule” to make.

But he added that the new study “expands our molecular level of understanding” of the biosynthetic steps involved in the process. He agreed that this could pave the way for new methods of producing psilocybin in more “user-friendly formats.”

The findings did not bring evolutionary biologists much closer to explaining why some mushrooms evolved to produce psilocybin, said Jason Slot, a mycologist at Ohio State University who was not involved in the research. But he said the findings did add evidence for the belief that psilocybin was not an evolutionary accident, but rather a “solution to a particular challenge faced by mushroom-forming fungi” that helped them thrive.

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