Can Fear Be Forgotten?

Making the Fear Pill

Beginning this fall, in Orangeburg, New York, LeDoux will direct a new research lab, the Emotional Brain Institute, where scientists will comb the brain's molecular networks to search for biochemical clues that might ultimately be used to develop fear-quashing therapies. He won't have any trouble finding test patients. LeDoux gets frequent e-mails and letters from people pleading for relief. "They have phobias, panic disorders, schizophrenia, PTSD-you name it," he says.

Some of research at the Emotional Brain Institute will involve human subjects, and so LeDoux won't be able to use U0126, because it needs to be injected directly into the brain. But there's another compound, an antibiotic called d-cycloserine, or DCS, that already has FDA approval (in higher doses, it's prescribed to treat tuberculosis). The strange thing about DCS is that it works in nearly the opposite way U0126 does-instead of shunting off old memories, it helps the brain to form new ones-but it produces similar results.

DCS stimulates a protein in the brain called the N-methyl-D-aspartate (NMDA) receptor, which facilitates memory formation. When the amygdala is actively embedding a new memory or evoking an old one, NMDA receptors switch on. DCS is like Red Bull for NMDA receptors: It makes them hyperactive, facilitating the formation of new memories. The idea is to create new memories of a given stimulus-a view from a great height, for instance-that lack the traumatic associations of the old memory.

Michael Davis, a professor of psychiatry and behavioral science at Emory University, has conducted some of the first experiments using DCS on humans. Davis gave DCS to patients who had a fear of heights and then outfitted them with virtual-reality (VR) goggles that played a digital video clip simulating the inside of an ascending glass elevator. "The higher they got, the more anxious they got," he says. But over time, their old traumatic memories were overwhelmed by new memories of a benign virtual-reality glass elevator. Compared with those who took the placebo, the DCS patients conquered their fear at a rate of almost 4 to 1.

Davis's latest project is a 300-patient trial that will examine if DCS can alleviate post-traumatic stress disorder in soldiers returning from war. "We have a virtual Iraq, where soldiers are driving their Humvees down the road and there are [explosives] going off," he says. Wearing VR goggles, soldiers are assaulted with the sights and sounds of battle. Before the memories are rekindled, the patients are given DCS in pill form. Neuroscientist Jacek Debiec is running a similar trial in association with LeDoux's lab for PTSD-afflicted vets. "Our VR software has visual, audio and tactile components. We also added smells, like smoke," he says. "It's quite realistic, very intense."

But perhaps the most ambitious endeavor is in Atlanta, at Tikvah Therapeutics. Its CEO, Harold Shlevin, a pharmaceutical-company executive who founded the firm in 2006, tells me that Tikvah (Hebrew for "hope") is conducting clinical trials to get FDA approval to use DCS to treat panic disorders, PTSD, obsessive-compulsive disorder (OCD) and "a general catchall category for fears such as snakes, spiders and heights." Shlevin has enlisted a company called Virtually Better to create virtual-reality simulations, and he plans to release a DVD that will be packaged with DCS capsules. The DVD would feature simulations to address a variety of fears-the interior of a jetliner, for example, for fear of flying, or a crowded auditorium with the patient on center stage, for fear of public speaking. For OCD, Shlevin says, "we'd emphasize cleanliness, so we will have them touching a toilet seat." He expects to market the medication and DVDs to consumers in late 2009 or early 2010; it will available on a prescription-only basis from a psychiatrist.