Hidden Valley Road - Inside the Mind of an American Family - Robert Kolker Page 0,124

this receptor needs in order to function, and smokers—or the α7 receptors in their brains—like it when their acetylcholine is turbocharged. This is the feeling cigarettes can give smokers—that way nicotine has of focusing their minds for short periods, or calming them. Could it just be a coincidence, Freedman wondered, that many schizophrenia patients—Peter Galvin among them—can’t get enough cigarettes? For very brief moments, nicotine may offer them at least some relief from their delusions. If Freedman could amplify that effect—mimic it in a lab, bottle it, and send it out to everyone diagnosed with schizophrenia—could it treat the symptoms of the illness more effectively and less harmfully than Thorazine?

First, he needed more proof. In 1997, Freedman devised an experiment: He gave nicotine to people with schizophrenia, usually many pieces of Nicorette chewing gum, and then measured their brain waves with his double-click test. Sure enough, people with schizophrenia who chewed three pieces of Nicorette passed the test with flying colors. They responded to the first sound and didn’t respond to the second, just like people without schizophrenia. The effects didn’t last after the nicotine wore off, but Freedman still was stunned.

His study won applause from a lot of his colleagues, including Richard Wyatt, Lynn DeLisi’s old boss at NIMH, who called the Nicorette experiment “important and exciting” and the promise of nicotine “intuitively very strong.” Freedman went all-in on nicotine. He made plans to develop a drug that did what nicotine did to the α7 receptor, only better—so well that schizophrenia patients could find relief from their delusions not for minutes but hours, or even days. He secured funding for a drug trial from NARSAD, the National Association for Research on Schizophrenia and Depression (now known as the Brain and Behavior Research Foundation), a donor-supported group that serves as the American Cancer Society for mental illness. “We thought perhaps we could make a better nicotine,” he said.

He found a natural substance called anabaseine that mimicked the function of nicotine. A researcher in Florida had been cultivating a synthetic version with no solid idea of what use the drug might have. He told Freedman he’d been waiting for ten years for someone like him to call. Freedman cultivated the drug, called DMXBA (short for 3-2,4 dimethoxybenzylidene anabaseine), and started testing it. The drug had the same effects as nicotine in the double-click test. And when, in 2004, he tested the drug on a group of schizophrenia patients in a double-blind controlled study, the results seemed miraculous. One subject who got the real drug, not the placebo, told Freedman that she had been having trouble finishing a short story she’d been writing, but now she was able to concentrate enough to do it. Another said, “I’m not noticing my voices.” The mother of a third told Freedman that for the first time, her son was able to take in the scenery around him—to be amused by watching rabbits in the yard, undistracted by his own hallucinations.

Within a year several different pharmaceutical companies were hard at work creating versions of his drug. They couldn’t just buy his because its patent, owned by the University of Florida, had been in existence too long: No company wanted to buy a patent that was just a few years away from expiring. “There isn’t much financial incentive for using the drug that we’ve gotten to work in clinical trials,” Freedman said, “so they had to go out and make their own.”

As an unpaid advisor, Freedman told each company the properties of the drug, hoping they would design their versions using the principles he suggested. A few companies made it pretty far. One company, Forum Pharmaceuticals, worked on trials that were halted after too many subjects experienced constipation. Another company, AbbVie, the research division of Abbott Laboratories, made it to the third phase of clinical trials with a drug based on DMXBA with mixed results, and then stopped their research. The problem, as Freedman saw it, was that they insisted on a once-a-day dose. Freedman’s team had tried that, but found that his drug only worked when administered in three or four small doses over the course of a day. Abbott thought it would never be able to market a drug that had to be taken that frequently, on such a rigorous schedule. (Think of Peter Galvin, skipping out on his drug regimen constantly, only to have yet