The High-Stakes Race to Engineer New Psychedelic Drugs

“This is my life,” Wallach says. “There is nothing else I’d rather be doing. If I was given a billion dollars, today, the first thing I would do is build a superlab.” When Compass came calling, he finally got the golden opportunity to pursue that dream. Maybe not a full-blown, billion-dollar superlab. But a lab of his own.

In pop culture, psychedelia is a Day-Glo tapestry of mandalas, black-light inks, tie-dye, and phat pants embossed with lime-green alien heads. In their various states of synthesis and manufacture, psychoactive drugs are decidedly unkaleidoscopic: brownish, yellowish, and vaguely gross, like plaque scraped off nicotine-stained teeth. The labs where these drugs are synthesized smell as if someone were burning a Rotten Eggs Yankee Candle.

Last fall, I visited Wallach in his lab, where he was preparing some N,N-dipropyltryptamine—a legal, and extremely potent, hallucinogen. Dressed in a faded maroon polo, khakis, and chunky desert boots, Wallach sets up a reaction in a round-bottom flask while explaining that in the ’70s, scientists investigated DPT for use in psychotherapy. He flits around the lab, blasting out moisture from glassware, sealing tubes with argon gas, dissolving reagents in methanol, and advising me to keep my distance as he fiddles with substances that are, he warns, “fairly toxic.” It’s like watching a chef show off at a teppanyaki restaurant, slicing and dicing by pure reflex.

The fall semester is in session, and Wallach has returned, after the pandemic disruption, to in-class teaching. His lab—and its work for Compass—presses on. Wallach and his squad of mostly twentysomethings weave among a few different offices, testing compounds for purity, sketching out molecules in grid-lined notebooks, and preparing potentially mind-expanding substances in discreetly marked mailers to be sent for mouse-twitch tests at a partner lab at UC San Diego.

The job is to develop drugs that tickle the 5-HT2A receptor, a cellular protein involved in a range of functions—appetite, imagination, anxiety, sexual arousal. The receptor has proven crucial to understanding the neuropharmacology of the psychedelic experience induced by classical hallucinogens. LSD, mescaline, psilocybin—they all interact with 5-HT2A. (In certain circles, the phrase “5-HT2A agonist” has supplanted “psychedelic,” which still carries faint whiffs of hippie-era hedonism.) “If you’re designing a new version of a classical hallucinogen,” Wallach says, “the first thing you’re doing is looking at its interaction with that receptor.”

One of Wallach’s goals is to hack how long a psychedelic’s effect lasts. Full-dose psilocybin trips usually run in excess of six hours. Hand-me-down hippie wisdom dictates three full days for a proper LSD experience: one to prepare, one to trip, and one for reacclimating yourself to the world of waking, non-wiggly consciousness. From a clinical perspective, such epic sessions are expensive and may not be necessary. Meanwhile, drugs like DMT are acute and intense, with effects lasting only minutes (sometimes called “the businessman’s trip” because it can be enjoyed within a typical lunch hour). Finding what Compass cofounder Lars Wilde calls “the sweet spot” between the length of a trip and clinical efficacy is just one of Wallach’s many challenges. If he and his team of researchers happen upon a concoction that’s particularly potent or experientially unique—“cool” is a word that gets tossed around a lot—well, all the better.