New Evolutionary Framework Views Psychedelic Compounds as Crucial Ecological Tools

Natural hallucinogens, such as psilocybin, mescaline, N,N-dimethyltryptamine (DMT), and related compounds, have generally received attention for their effects on human perception, emotion, and cognition. Recently, interest in these compounds has expanded to include their potential roles in psychiatric treatment, neuroplasticity research, and the study of consciousness.

Yet their ecological origins remain poorly understood. Why have unrelated plants, fungi, and animals repeatedly evolved molecules capable of strongly modulating animal nervous systems?

Now, researchers led by Prof. WANG Xiaohui from the Changchun Institute of Applied Chemistry of the Chinese Academy of Sciences have proposed that natural hallucinogens may have primarily evolved as ecological tools that help organisms survive, defend themselves, and interact with other species.

The research was discussed in a Perspective published in PNAS on June 24.

The study integrates chemical ecology, comparative genomics, biosynthesis, neuropharmacology, and evolutionary biology to create an ecological and evolutionary framework for understanding psychoactive natural products. The researchers argue that natural hallucinogens should be viewed as products of chemical ecology-the study of how organisms use chemicals to interact with one another and with their environment-and of convergent evolution, in which similar traits evolve independently in unrelated organisms because they face similar environmental challenges.

According to the study, these hallucinogenic compounds are not accidental "chemical anomalies." Rather, they may represent ecological tools shaped by interactions among producer organisms and their consumers, predators, competitors, or symbiotic partners. Across biological kingdoms, organisms repeatedly use a limited set of metabolic building blocks and enzymatic transformations, including hydroxylation, methylation, phosphorylation, and prenylation, to generate structurally diverse psychoactive molecules.

These molecules may contribute to predator defense, feeding deterrence, symbiotic regulation, cross-kingdom communication, and responses to environmental stress. Because animals share ancient and highly conserved neurotransmitter systems, particularly serotonin signaling pathways, organisms may be able to influence the behavior of other species by producing small amounts of such compounds that target these pathways.

The Perspective highlights examples from plants, fungi, and animals. For example, peyote (Lophophora williamsii) accumulates mescaline, which has a bitter taste and physiological activity that suggest possible defensive functions. Psilocybin-producing fungi possess a core biosynthetic module that encodes the enzymes PsiD, PsiH, PsiM, and PsiK, which together convert tryptophan into psilocybin. Comparative genomics suggests that related gene clusters may have spread through genomic rearrangement and horizontal gene transfer. The Sonoran Desert toad (Incilius alvarius) secretes 5-MeO-DMT, bufotenine, bufadienolide, and cardiotonic steroids, forming a multi-component chemical defense system that may promote predator avoidance.

The researchers further suggest that the repeated emergence of hallucinogenic chemistry in these organisms represents convergent evolution driven by shared ecological pressures and conserved neural targets. The serotonin signaling system, particularly the 5-HT2A receptor, emerged early in animal evolution and is widespread among invertebrates and vertebrates. By modulating serotonin signaling, producer organisms may influence feeding, movement, learning, avoidance, and orientation in other organisms.

The researchers emphasized that many ecological hypotheses remain to be tested through field ecology, genetics, behavioral biology, comparative genomics, and chemical biology. They also discussed conservation and sustainability related to this research. They noted that advances in biosynthetic studies, synthetic biology, microbial fermentation, and pathway engineering could enable these compounds to be produced in laboratories or industrial systems, thereby reducing the need to harvest wild plants, fungi, and animals.

Overall, the study suggests that viewing natural hallucinogens through an ecological and evolutionary lens could provide new clues about where to look for related compounds, how to produce them sustainably, and how to develop and apply them responsibly.