Why do plants and fungi produce psychedelics? 5 Questions for evolutionary biology and genetics professor Noah Whiteman

Whiteman discusses how insects’ behavior may have given rise to plants and fungi with psychoactive properties.

Noah Whiteman grew up 50 miles northeast of Duluth, Minnesota, an area he calls “the middle of nowhere” — and he credits that rural experience for developing his love of nature. That fascination with the natural world turned into academic interest, and Whiteman became the first person in his family to go to college — and to earn a Ph.D. in entomology. Whiteman has always been interested in interactions between species; early in his academic career, Whiteman studied the coevolution of hawks and parasites in the Galapagos. He went on to probe dynamics between fruit flies and mustard plants growing in parking lots near Harvard, where he completed a postdoctoral fellowship. 

Now an evolutionary biology and genetics professor at the University of California, Berkeley, Whiteman is turning his attention towards psychedelics-producing plants and fungi. The Microdose spoke with him about how insects’ behavior may have given rise to plants and fungi with psychoactive properties.

How might psychedelics have evolved?

Plants and fungi produce structures that are really valuable for animals and insects to eat. But plants can’t move! So, most have evolved barriers to being eaten. In some cases, they have physical barriers, like a thick epidermis. But insects can evolve adaptations to get through those; for instance, there’s a fly that eats mustard plants and it’s evolved a cool adaptation to get into the plant: vaginal teeth that they can use to get into a leaf. 

Plants also have what are called secondary chemicals, many of which are toxins or prototoxins that can turn into a toxin if it’s disturbed — it’s like a fuse that hasn’t been lit yet. Each set of plants makes a different set of toxins; for instance, plants in the mustard family — broccoli, canola, horseradish, wasabi, Brussels sprouts, kale, kohlrabi — all produce mustard oils, which are really potent insecticides, and have a peppery taste. 

For years, people didn’t really know what purpose those served: why would a plant use precious amino acids to make, say, cyanide in apple seeds? In the case of mustard plants, we now know that if you knock the genes out that encode the enzymes that make mustard oil, plants suffer in the presence of insects. They get eaten more, they have lower fitness, they produce fewer seeds. It makes complete sense in hindsight: these evolved as toxic shields. 

So, why might a mushroom have made psilocybin? It could just be a waste product, and have nothing to do with plant defense. But it could have evolved because it protected the plant; mushrooms that evolved with this defense were protected from attack.

What evidence is there that psychedelics might be a plant defense mechanism?

A big hint is that this ability has evolved and spread across the plant, mushroom, and animal lineages independently. Psilocybin is in psilocybe mushrooms, but many other mushrooms produce it too — some of those are very distantly related evolutionarily, like millions of years from having a common ancestor. One big finding in the last five years was that hallucinogenic mushrooms’ DNA contains a set of genes that encode enzymes which turn amino acid into psilocybin; that set of genes are all found together, next to each other in the genetic code. In 15 different mushroom species, they all have this set of genes, but different species had that set of genes in different places in the genome, so we know it’s not inherited from a common ancestor. So how did it get there? It moved horizontally between lineages, in a process called horizontal gene transfer; bacteria use this process all the time, too, and that’s how antibiotic resistance evolves. Basically, species share genes and if those genes are beneficial, they keep them. 

What kinds of studies are you interested in doing to further flesh out this evolutionary theory?

What we would need to do is knock those genes out to see what function they serve. Would those mushrooms then be more susceptible to fungivores? Another experiment that you could do is to put those genes into a species that doesn't have them, and see if it protects them from fungivores. The former would be a loss of function study; the latter, a gain of function. 

You can also feed these substances to insects and see what happens to them. Do they stop eating? Do they stumble over? Do they die? Do they avoid it? Or do they go to it? 

If psychedelics evolved as a result of this arms race between insects and plants or fungi, have humans had any role?

By design, we’re not the beneficiaries. Plants evolved to make just enough toxin to protect itself; given that making those toxins comes at the cost of making pollen or seeds, it’s costly to make more than what would be enough to knock out an insect. Yet, we share the same brains as these insects. The brain machinery necessary to operate a fly brain is similar to ours. Of course, we’re bigger, so we can handle toxins at doses that would be lethal to a small insect. 

But plants did not evolve with us in mind; they evolved to kill animals and pathogens that are attacking plants, not to help us. The fact that they do is just luck. They target important proteins in our bodies and that can be coaxed into a therapeutic benefit, or even a recreational benefit. And now there’s coevolution occurring as humans select for plants and fungi, too. 

In clinical trials where participants are directly given psychedelic drugs, researchers must go through a rigorous process to receive authorization to conduct research. In the research you described, you’d be studying plants and fungi that naturally produce these drugs, and how insects respond to them. What has the approval process been like for that work?

It’s interesting to consider that it’s a little open to interpretation what a psychedelic is. Technically, I’ve got a psychedelic in my kitchen cabinet; it’s called nutmeg. You’d have to eat a lot of it to feel the effects and people absolutely should not do that, because it’s very toxic, but these molecules, in their refined form, are incredibly powerful, so I completely understand why they’re regulated.

Since some of the chemicals these organisms are making are Schedule I drugs, we do have to get approvals from DEA and from the state, so we’re in the process of applying for those. I estimate it could take another six months to a year before we have all approvals — and in the next several years we’ll know more about what functions psychoactive chemicals serve.

This interview has been edited and condensed for clarity and length.