Psilocybin, the active ingredient in “magic mushrooms”, is one of the most famous molecules in modern culture. Humans have ingested it for thousands of years in ritual and recreation, and today scientists are testing it as a powerful treatment for depression, anxiety, addiction, and PTSD.
A new and intriguing study shows that psilocybin didn’t emerge from a single evolutionary sequence. Instead, two completely unrelated groups of mushrooms independently evolved to make the exact same psychedelic compound.
It’s as if nature ran the same strange experiment twice and came to the same trippy conclusion.
Two Paths, Same Trip
Most people know psilocybin from Psilocybe mushrooms, the so-called magic mushrooms that thrive on manure and decaying wood. Its pathway has been mapped out in detail, starting from the amino acid tryptophan and involving four specialized enzymes: PsiD, PsiH, PsiM, and PsiK. These enzymes work in a precise order to build the compound while avoiding the unstable intermediate psilocin, which could damage cells.
But another, less famous group — fiber caps, part of the Inocybe genus — also make psilocybin. Until now, scientists assumed they must have inherited the ability from a common ancestor.
That assumption just got upended.
Researchers at the Leibniz Institute in Jena recreated the enzymes of Psilocybe and Inocybe mushrooms in the lab. They found none of the reactions in Psilocybe occur in the same way in Inocybe.
“It was like looking at two different workshops, but both ultimately delivering the same product,” said Tim Schäfer of the Leibniz Institute for Natural Product Research and Infection Biology, lead author of the new paper in Angewandte Chemie International Edition. His team found that Psilocybe and fiber caps use totally different sets of enzymes. Yet both routes end up with psilocybin.
The researchers confirmed this by analyzing fungal genomes and running enzyme reactions in the lab. “Here, nature has actually invented the same active compound twice,” Schäfer said.
This is convergent evolution — when unrelated organisms develop the same feature independently, usually because it helps them survive in similar ways. Birds, bats, and insects all evolved wings separately. Now it seems mushrooms have done the same with psychedelics.
Why Make Psychedelics at All?
The bigger mystery is why.
“This concerns the biosynthesis of a molecule that has a very long history with humans,” explained Professor Dirk Hoffmeister, senior author of the study, in a press release. “However, why two such different groups of fungi produce the same active compound remains unclear.”
He added bluntly: “The real answer is: we don’t know.”
There are theories. Psilocybin may deter predators. Psilocybe mushrooms, for instance, bruise blue when injured. That color comes from chemical breakdown products of psilocybin, which could be a warning signal aimed at insects or other organisms trying to eat them.
“Nature does nothing without reason,” Hoffmeister said. “So, there must be an advantage to both fiber cap mushrooms in the forest and Psilocybe species on manure or wood mulch producing this molecule — we just don’t know what it is yet.”
Biotech Dreams from Mushroom Mysteries
While scientists scratch their heads over evolution’s motives, biotech is thrilled.
“Now that we know about additional enzymes, we have more tools in our toolbox for the biotechnological production of psilocybin,” Hoffmeister said.
Psilocybin is hard to make at scale using chemical synthesis. Pharmaceutical companies want a reliable, efficient source, especially as clinical trials point to its potential against therapy-resistant depression.
Schäfer and his team even demonstrated multi-enzyme reactions in vitro, showing that the Inocybe enzymes can churn out psilocybin outside of a living mushroom. Fiber cap mushrooms could thus offer a new biochemical toolkit that could make industrial production easier.
“We hope that our results will contribute to the future production of psilocybin for pharmaceuticals in bioreactors without the need for complex chemical syntheses,” Schäfer explained.
