Engineering the Perfect Psychedelic

Nature is always performing chemistry experiments, and in the dark and sticky corners of its forests and jungles, it creates compounds that have hyper-specific effects on the human mind. In China’s Yunnan province, a yellow mushroom with a droopy cap sprouts up in the mountains, usually in the shade of long-needled pines. Many people of different ages and cultural backgrounds have eaten this mushroom and experienced the same hallucination. They report seeing elf-like figures that parkour around on clothes, on furniture, and on walls. These little people seem to like dancing and performing acrobatics. Large groups of them will march in formation. This “lilliputian hallucination” can last for a day, and closing your eyes is no escape. The tiny humans sometimes linger in the blank space of your mind, staring back at you in a teasing way.For thousands of years, humans have searched nature for mind-altering substances through a process of trial and (sometimes fatal) error. People have choked down foul roots, boiled woody vines, and scraped bitter bark off of tree trunks. They’ve milked toad glands and chugged the urine of reindeer that were themselves tripping on fungi. These experiments have revealed hundreds of plants and fungi that contain psychedelic compounds.Now that psychedelic research has been legitimized, scientists at university labs and biotech start-ups are wondering whether they can create a better one. It’s a seductive idea, that some new and perfect drug might be hiding in the near-limitless parameter space of synthetic chemistry. Who wouldn’t want to take a little pill that could help you slough off your old self and see the world anew, a half-day therapy that would leave you with a feeling of enlightenment, if not in the exalted state itself?“Nature’s compounds aren’t always optimal,” Manoj Doss, a professor of psychiatry at the University of Texas at Austin, told me. Take ibogaine, a naturally occurring psychedelic derived from an African shrub. A sing