February 22, 2024

The evolutionary origins of psychedelics

HHumans depend on a host of strange natural chemicals to spice up our food and drink, tolerate pain, and change our perspective. We use caffeine from coffee, tea and yerba mate to stimulate our bodies and minds, capsaicin from red pepper flakes or isothiocyanates in horseradish or wasabi to enliven our food with spices, and codeine or morphine to tolerate the pain of injuries and surgeries .

Lately, however, some have also turned to psychedelics like psilocybin to change their perspectives. Researchers are even beginning to test whether they could serve as new treatments for mental disorders.

That said, the bigger question is Why plants, mushrooms, microbes and even some animals make these types of chemicals with life-saving, life-enhancing and even life-ending properties. My job as an evolutionary biologist who studies the age-old battle between plants and herbivores is to help answer this question. By doing this, we can gain important information about the potential risks, as well as the potential benefits, of harnessing evolved chemicals for our own devices.

Just take these five examples: Botulinum toxin, made by some bacteria to paralyze their hosts, is both one of the deadliest of all natural toxins known to science and the active ingredient in the anti-wrinkle drug Botox. A chemical used by bread molds to ward off competing bacteria is also the miracle drug penicillin. A powerful insecticide produced by distantly related plants is also the most widely used psychoactive drug in the world: caffeine. A poison produced by yew trees to slow the growth of caterpillars is also the powerful anti-cancer drug known as Taxol, which prevents the growth of rapidly dividing cells, such as those in malignant tumors. The poison cone snails that paralyze fish also contain the powerful painkiller ziconotide.

It seems like these chemicals are tailor-made for us. Yet humans weren’t around when the organisms that produced the chemicals first developed the ability to make them. A closer look reveals that in many cases we appear to have simply intercepted chemical weapons deployed in what naturalist Charles Darwin called “nature’s war.” Quite simply, many of the baroque chemicals we use and abuse have appeared on the planet because they increase the chances of survival of the organisms that make them or absorb them through their diet or microbiome.

People have been the unwitting beneficiaries of this war, and sometimes its victims. My father’s death from alcohol addiction in 2017 fell squarely into the latter category. He died because he couldn’t stop drinking a poison made by brewer’s yeast called ethanol, the alcohol in beer, wine and spirits. Brewer’s yeast produces ethanol to prevent other microbes from competing for sugar in fruit and to store the energy for later use, as a toxic private reserve.

The yeasts aren’t the only ones creating protective chemical shields for themselves. Consider the monarch butterfly, whose caterpillars chew milkweed plants and ingest the cardiac glycoside poisons found in the sap. When they turn into butterflies, the recycled plant poisons provide a chemical shield against hungry birds and other predators. In 2019, my collaborators and I used CRISPR gene editing to discover how the butterflies evolved to resist the powerful heart poisons in their own bodies. Similar chemicals made by Digitalis Foxglove plants were among the first medications used to treat heart failure.

Illustrations by Julie Johnson

When my father died, I began to see more clearly that my research into the evolution of toxins was also a mirror to my father’s demise. And in the wake of both his death from a yeast poison and our research into poisonous butterflies, natural psychedelic chemicals were also having a moment. Psychedelics are chemicals that bind to and activate serotonin receptors in our brains. They include serotonin-mimicking psilocybin from ‘magic mushrooms’, DMT from the Psychotry plants used by shamans in the Amazon to prepare ayahuasca, the 5-Meo-DMT found in the venom glands of the toads of the Colorado River or the Sonoran Desert, mescaline in peyote and San Pedro cacti, and LSD-like ergot -alkaloids such as lysergic acid hydroxyethylamide produced by some fungi for example that live in the seeds of some morning glory plants.

Illustrations by Julie Johnson

Just as natural psychedelics evolved independently in many different organisms, so too did their cultural use time and time again by indigenous peoples around the world, who employed them as medicine, spiritual practice, and more. Although long taboo in modern “Western” societies, psychedelic chemicals are increasingly emerging as transformative therapies for a wide range of mental disorders resistant to treatment, from alcohol use disorder to post-traumatic stress disorder.

Why do some organisms make psychedelic chemicals? Perhaps because what’s good for the goose is good for the goose: Like botulinum toxin, penicillin, caffeine, Taxol and ziconotide, natural psychedelics can serve as chemical weapons that plants, fungi and animals use to defend against enemies

While we are still trying to understand the origins and functions of natural psychedelics in the organisms that create them, it is clear that their evolution has nothing to do with us. Given that the ability to produce them evolved millions of years ago before humans lived, we would do well to study and scrutinize their natural functions as our society begins a rapprochement with these powerful compounds. Basic research into their evolution is as crucial as the clinical trials conducted to assess their potential as medicine. By examining both sides of these double-edged swords, we can learn more about how they can act like drugs and how they can harm us.

5-Meo-DMT, DMT, psilocybin, mescaline, and ergot alkaloids are extremely bitter, so most animals likely avoid them in nature, which in itself can serve as a defense. Among the plants that make 5-Meo-DMT and DMT are grasses of the genus Phalaris are protected from grazing mammalian herbivores such as sheep, which find these and related but non-psychedelic chemicals such as gramine distasteful. When eaten, a condition known as ‘phalaris staggers’ has been reported, reflecting the potentially neurotoxic effects of these alkaloids in the grasses.

Likewise, a clue to why magic mushrooms evolved to produce high levels of psilocybin comes from the fact that these fungi turn blue when injured. In that case, two enzymes chemically convert psilocybin into a chain of psilocin molecules that become linked together. These chains are very similar to indigo or some tannins, which also turn blue when oxidized, and can disrupt the digestive tract. Although psilocin produces psychedelic experiences after being converted from psilocybin, these experiences may be unintended consequences of its ultimate function for mushrooms.

Read more: What psychedelics can teach us about playing

Considering their potential as medicine, I am a strong advocate of testing psychedelics to assess their safety and efficacy and subjecting them to double-blind, placebo-controlled clinical trials, the gold standard in medicine. I am convinced that psychedelics have great potential as a therapy for a wide range of mental disorders. Maybe they could even have helped my father.

Still, psychedelics are not a foolproof cure. The clinical trials so far are small and the volunteers are highly motivated to seek treatment. While illegal, clinically uncontrolled and recreational use of these drugs is ubiquitous, there is much more we don’t know about how they affect us and the risks they can pose, especially to the most vulnerable people in our society.

Lessons from nature suggest that natural psychedelic chemicals evolved to keep enemies at bay. Although Taxol works by stopping cancer cells from dividing, it can stop any cell from dividing, including the cells that grow our hair. Therefore, hair loss is a side effect. Clearly, the idea that what is “natural” is inherently good for us is a fallacy about appealing to nature. Such faulty reasoning has permeated the wellness industry, is perpetuated by the mass media and even in the scientific literature. It also rears its head as we try to understand the origins and functions of natural psychedelics for the organisms that make these chemicals. Despite their obvious promise as a therapy, we should not forget that the organisms that produce these and all the other so-called drugs in nature’s pharmacopoeia are also desperate to live. Living requires fighting in nature’s crushing and brutal war.

Leave a Reply

Your email address will not be published. Required fields are marked *