A Chapter In Psychedelics History: Alexander Shulgin's 'Blending' Of Sensory Experiences With Science And Chemistry

The Alexander Shulgin Research Institute (ASRI), the organization advancing the renowned chemist’s scientific work and legacy, presented novel psychoactive compounds at the MAPS' Psychedelic Science 2023 last month in Denver.  

ASRI co-founder and president Dr. Nicholas Cozzi spoke to Benzinga about Alexander ‘Sasha’ Shulgin’s contributions to the field and how it all began. (See part one of the conversation.)

“Shulgin was really the first to recognize the value of MDMA, first exploring it as a psychotherapeutic agent, but also for understanding brain function,” Cozzi told Benzinga.

Working with his wife and therapist Ann, they tested the substances he created together with a small group of people to start building consensus around its effects and whether they held value.

When MAPS's founder Rick Doblin began working toward federal approval of MDMA, he recalls both Ann and Shasha Shulgin being mainly supportive of his work.

“There was a faction that thought this was never gonna go anywhere, but then there were other folks that wanted to develop it. I believe that Sasha and Ann Shulgin were in that second group, they wanted the research to continue and do it.”

Research In The 80s And 90s And Roland Griffiths’ Opening The Field

Cozzi says that back in the 80s, “psychedelics had this air of scandal or shame associated” and,  with the still close War on Drugs, “you really couldn’t speak about them.” 

In that scenario and trying to figure out a way to study the substances, he entered the field through other psychoactive drugs like opioids, anxiolytics or antidepressants. He joined the American Chemical Society where the medicinal chemistry branch designed and synthesized drugs to understand the relationship between their chemical structure and effects. 

“That’s kind of a systematic way to go about it, you alter the structure in certain ways and then test it and see what that chemical change did to the response you're getting,” done today with computer-assisted drug design and even AI. 

Interested in structure-activity, or ”taking a completely inert molecule and then adding a piece of a structure onto it and all of a sudden it becomes active,” Cozzi joined a scientific journal where he found an article by Shulgin on psychoactive tryptamines. 

“And there were like a dozen or so of the likes, in a hard-core journal, describing some human effects of the substances that they’ve taken themselves. And I thought, ‘Wow, this is really what I want to do, and here's a way to do it, upfront, and they’re publishing this’.” 

Cozzi says Shulgin's work was about blending sensorial, psychedelic experiences with science and chemistry. “And so, he became kind of a role model for me.” 

Shulgin directed him to Dave Nichols, who had an ongoing psychedelics research program at Purdue. Nichols, who became one of Cozzis' Ph.D. advisors, was close with Shulgin and together they published what Cozzi recalls as the first paper on MDMA pharmacology that suggested its potential as a therapeutic agent.

Cozzi holds a from UW-Madison, where he worked as a professor until his recent retirement. Following undergrad studies, Cozzi earned a Ph.D. and a postdoc. And after 10 or 12 years of lab work and publishing, he started working with Shulgin long-distance. 

“He would send me compounds and I would test them in vitro, and we wrote some papers together. But at that time (the 1990s,) it was still not something you wanted to talk about,” Cozzi said. 

But what really broke the field open, said Cozzi, was Roland Griffiths’ 2006 publication in the Psychopharmacology journal. The article was titled "Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance."

“Because Roland is just an A scientist. I mean, very rigorous," Cozzi said. "Anything that he publishes, you can have confidence that it's true, and within Johns Hopkins, a world-class historical institution. So this lent credibility to the work and it allowed other people who weren't at Hopkins to come out and say, ‘Oh, we're studying this too.’ People were more accepting.”

Part 3 on the field’s recognition of Shulgin's work and ASRI’s plans coming up next.

Photo: Benzinga edit with photo by Zolnierek on Shutterstock and Charlie Llewellin on Wikipedia.