How Yale researchers helped create the ketamine industry — and their own psychedelics startup.

The clinical trial that set the stage for today’s fast-growing ketamine industry runs just three pages long and involved only eight patients. It was published, not in the New England Journal of Medicine or The Lancet, but in a specialized journal called Biological Psychiatry.

Psychiatrists at the Yale School of Medicine did the research. They were seeking to understand the basic biology of depression, and in particular the role of glutamate, a chemical that carries electrical impulses in the brain. Knowing that ketamine, an anesthetic, triggers glutamate production, they gave ketamine to patients with major depression.

To the amazement of the researchers and the patients, patients given ketamine felt better right away. The study, titled Antidepressant Effects of Ketamine in Depressed Patients, was published in 2000.

Nothing much happened, for a time.

“There was an enormous amount of skepticism in the field,” says Dr. John Krystal, an author of the study and pioneering ketamine researcher who is now chair of psychiatry at the Yale medical school.

The study “definitely needed replication,” says Dr. Robert Berman, its lead author. Only after scientists at the National Institute of Mental…