The peyote cactus tastes terrible. Bite into one and your mouth fills with a bitterness that seems engineered to make you stop, and in a sense it was. The compound responsible, mescaline, is the same molecule that has sent generations of seekers into kaleidoscopic visions. A team of Chinese researchers now thinks those two facts are not a coincidence at all. The bitterness came first. The visions are an accident.
That, broadly, is the argument running through a Perspective published in the Proceedings of the National Academy of Sciences on 24 June. The work, led by Wang Xiaohui at the Changchun Institute of Applied Chemistry, asks a question that the psychedelic renaissance has mostly skipped over.
Why does nature keep inventing these things? Psilocybin in fungi, mescaline in cacti, DMT seemingly everywhere, the toxic brew oozing from a desert toad. These organisms are not related. They sit on wildly distant branches of the tree of life, and yet they have all, independently, hit upon molecules that reach into an animal brain and rearrange it. The team’s answer is that hallucinogens are not chemical oddities or evolutionary noise. They are tools. Ecological tools, shaped by the grubby business of survival, defence and manipulation.
A Limited Toolbox, Used Again and Again
Here is the part that makes the convergence less mysterious and, oddly, more impressive. Life works with a small kit. To build a psychoactive molecule, an organism reaches for a handful of starting materials, an amino acid like tryptophan, say, and runs them through a familiar set of chemical edits: hydroxylation, methylation, phosphorylation, prenylation. Tweak the order, swap a group here, and you get structurally different compounds that all converge on the same trick. It is rather like different cuisines arriving at the dumpling without ever comparing notes.
The recipes themselves are now being read in detail. In psilocybin-producing fungi, the researchers note, a tight cluster of genes encoding the enzymes PsiD, PsiH, PsiM and PsiK does the work of turning tryptophan into the finished psychedelic. And comparative genomics hints that this cluster has hopped between fungal lineages through horizontal gene transfer, the biological equivalent of one species photocopying another’s blueprint. Mescaline biosynthesis in cacti is yielding up its steps too.
So if the chemistry is borrowed and reborrowed, what is it actually for? The team’s wager is defence, manipulation, and communication across the boundaries that usually keep species apart.
The Toad’s Argument
Consider the Sonoran Desert toad, Incilius alvarius, which has become a minor celebrity of the smokable-psychedelic scene. The animal does not secrete 5-MeO-DMT for anyone’s enlightenment. It secretes a cocktail: 5-MeO-DMT, bufotenine, bufadienolides, cardiotonic steroids, the lot, a layered chemical defence that a predator learns to regret. The hallucinogenic component sits inside a package built to say, in the only language a coyote understands, leave me alone. Peyote’s bitter mescaline plausibly does similar work against anything inclined to graze on it. The drug effect we prize is, on this reading, the by-product of a warning label.
The reason any of this works at all comes down to a deep accident of shared ancestry. Animals, from worms to whales, run on a few very old neurotransmitter systems, and serotonin signalling is among the oldest. The 5-HT2A receptor, the lock that classic psychedelics fit, appeared early and spread across the animal kingdom; it turns up in invertebrates and vertebrates alike. A plant or fungus that can nudge serotonin can, in principle, tilt the feeding, movement, learning or avoidance behaviour of an enormous range of creatures with one small molecule. Conserved targets, conserved leverage. That is the engine the authors think has driven the same chemistry to evolve over and over.
Not every tryptamine story fits the defence frame, mind you, and the paper is careful here. The endogenous tryptamines found in mammals, including ourselves, have long tempted people toward grand claims about built-in psychedelia.
The authors push the other way. The weight of evidence, they argue, points to those internal compounds acting through the sigma-1 receptor in a protective, stress-buffering role for cells, rather than serving any innate hallucinatory purpose. It is a deflationary note in a field prone to mysticism, and probably a healthy one.
From Wild Harvest to Fermenter
If the framework holds, it changes where you go looking. Treat hallucinogens as chemical ecology and the question becomes predictive: which organisms face the kinds of pressure, herbivores to deter, pollinators to court, symbionts to keep in line, that might have selected for a serotonin-bending molecule? That is a map for bioprospecting, and a sharper one than trawling folklore. The same logic points toward the lab. Advances in synthetic biology, microbial fermentation and pathway engineering could let these compounds be brewed in a vat rather than stripped from wild peyote or hunted from toads, which matters when the renaissance threatens to love some of these species to death. The authors are blunt about the need to fold conservation, ethical sourcing and benefit-sharing into the boom now, not after.
Most of this remains hypothesis, it should be said, and the paper reads as a call for fieldwork rather than a verdict: behavioural trials, more genomes, the patient business of catching a molecule in the act of doing its ecological job. But the reframing has a certain elegance. The trip, it suggests, was never meant for us. We just happen to carry the ancient hardware these molecules were built to exploit, and stumbled, late and delighted, into a conversation that plants and fungi started a very long time ago.
DOI / Source: https://doi.org/10.1073/pnas.2535785123
Frequently Asked Questions
Why would a plant or fungus evolve a molecule that affects the human brain?
It almost certainly did not evolve it for us. The researchers argue these compounds were shaped to deter predators, discourage grazing, or manipulate the behaviour of insects and other animals an organism actually interacts with. Because humans share very old neural machinery, particularly serotonin receptors, with those target animals, the same molecules happen to work on us too. Our experience of them is a side effect.
How can unrelated species end up making such similar drugs?
This is convergent evolution: distant organisms arriving at similar solutions because they face similar problems. Life builds these molecules from a small set of common ingredients and a recurring kit of chemical reactions, so the same psychoactive scaffolds keep emerging independently. In fungi, the genes for making psilocybin even appear to have jumped between lineages through horizontal gene transfer.
Is it true that our own bodies make psychedelics?
Humans do produce small amounts of tryptamine compounds, which has fuelled speculation about built-in psychedelia. The authors are skeptical. They contend the best evidence suggests these internal molecules mainly act through the sigma-1 receptor to protect cells under stress, rather than to alter consciousness.
Could this change how psychedelic medicines are made?
Potentially, in two ways. Understanding the ecological logic could guide scientists toward new compounds worth investigating. And brewing these molecules through microbial fermentation and engineered biosynthetic pathways could supply them without harvesting wild cacti, fungi or toads, which the surge of interest is already putting under pressure.
