Chemical ecology and convergent evolution of natural hallucinogens: From ecological defense to conserved neural targets

Summary

Natural hallucinogenic compounds have evolved independently in plants, fungi, and animals, serving as potential defensive agents or manipulators of behavior. These compounds, including mescaline and psilocybin, are linked through a biosynthetic logic that connects primary metabolism to psychotropic effects. The study suggests that human psychoactivity may be an evolutionary by-product of these molecules, which interact with conserved neural targets across species. This perspective emphasizes the importance of conservation and ethical sourcing in the use of hallucinogens.

Study at a glance

Abstract

Natural hallucinogenic compounds have arisen independently across plants, fungi, and animals, evolving into a diverse chemical arsenal that includes phenethylamines, indolealkylamines, and terpenoid scaffolds. Beyond clinical and cultural frameworks, their ecological origins and evolutionary trajectories may help explain why such potent modulators of perception, emotion, and cognition persist in nature. Here, integrating chemical ecology, comparative genomics, biosynthetic logic, and evolutionary biology, we propose that these molecules may function as defensive agents or symbiosis-associated manipulators of herbivore and pollinator behavior. A "building-block" biosynthetic logic links primary metabolism to convergent psychotropic scaffolds via a recurrent set of tailoring reactions, including decarboxylations and methylations. Recent advances illuminate mescaline biosynthesis in cacti, horizontal gene transfer of psilocybin clusters in fungi, and symbiont-derived alkaloids in grasses. We also assess the debate surrounding endogenous mammalian tryptamines, arguing that the leading hypothesis points toward sigma-1 receptor-mediated cytoprotection and stress responses, supported by convergent pharmacological and cellular evidence, rather than inherent hallucinogenic functions. Across kingdoms, natural hallucinogens appear to converge on conserved neural targets, including serotonergic and other neuromodulatory systems that are shared across phyla. From this perspective, human psychoactivity is likely an evolutionary by-product of molecules selected for ecological interactions with animals possessing deeply conserved receptor architectures. Framing hallucinogens through chemical ecology not only clarifies their origins but also highlights translational opportunities in target discovery, pathway engineering, and sustainable production, while emphasizing the need to integrate conservation, ethical sourcing, and benefit-sharing into the current hallucinogenic renaissance.

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