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No Fear: Memory Adjustment Pills Get Pentagon Push

By Katie Drummond

December 19, 2011 "Wired" --  The Pentagon hasn’t come close to solving the PTSD crisis plaguing the current generation of troops. And the top brass looks like it’s ready to try anything — like a major push into a cutting-edge, controversial realm of treatment. One that’d see military personnel popping a pill to wipe away the fear they associate with traumatic memories.

The Pentagon this week announced an $11 million grant doled out to three research institutions, all of them long-time hubs for the military’s ongoing PTSD investigations. Experts at Emory University, the University of Southern California and New York-Presbyterian/Weill Cornell Medical Center will study the effectiveness of D-Cycloserine (DCS). DCS is a pharmaceutical thought to help extinguish fearful memories. It’s usually taken right before exposure therapy, a process that involves recalling traumatic experiences in an effort to nullify the menacing associations that accompany them.

“We already know that exposure therapy is an effective [therapy] for PTSD, and we want to figure out how to optimize it,” Dr. Barbara Rothbaum, who will lead the Emory team’s research, told Danger Room. “I really think that this study will move beyond the theoretical. We can rescue people.”

Exposure therapy is thought to work by allowing patients to revisit traumas in safe settings. Every time the mind remembers an event, it “rewrites” that recollection. By helping a patient rewrite traumatic memories to be less frightening, studies suggest that exposure therapy can significantly improve symptoms like nightmares and flashbacks.

Adding DCS seems to hasten that process, targeting the precise brain pathways responsible for regulating fear responses.

Researchers will look at two different kinds of exposure therapy: Virtual reality, where a patient is fully immersed in digital combat scenarios, and prolonged imaginal exposure therapy, which asks them to simply remember and recount fearful memories. A total of 300 patients, all of them veterans from Iraq and Afghanistan, will partake. They’ll undergo seven individual weekly sessions of one of the therapies. Before each session, half will receive DCS, and the rest will get a placebo.

Experts have already spent plenty of time figuring out how DCS works. It’s been around since the 1960s, when it was used to treat tuberculosis. Now, however, researchers are more excited about the drug’s potential ability to alleviate symptoms of depression, schizophrenia, obsessive-compulsive disorder and, of course, PTSD — without a lifetime of pill-popping.

“Most drugs, you dose every day,” Rothbaum says. “But DCS is only useful during exposure therapy, so you’re taking the drug right before the session. And when your series of sessions end, the medication ends too.”

DCS seems to enhance the brain’s learning process. For PTSD treatment, the drug could, ostensibly, help patients more quickly internalize that, say, driving down a suburban American highway is far different — and less dangerous — than driving on a Baghdad street. The drug also binds to receptors in the amygdala, the region of the brain that governs fear response. So by blocking out fearful reactions while a patient revisits trauma, experts think DCS can, literally, “extinguish” fear right at the source.

Emory researchers have already tried using DCS and virtual reality in humans with PTSD, fear of heights and obsessive compulsive disorder. Since 2006, Rothbaum and a team of experts have been comparing exposure therapy, used along with DCS, Xanax or placebo, in patients. “Results so far are positive,” Rothbaum says, though they haven’t finished analyzing the data.

That said, results from other human studies on DCS aren’t encouraging. Just last year, several disappointing trials using DCS were presented by researchers assembled at the International Society for Traumatic Stress Studies conference. “The early results are not as positive as we [had] hoped,” noted Dr. Charles Marmar, head of the psychiatry department at NYU, of his team’s study that combined DCS with cognitive behavioral therapy.

But even a glimmer of hope seems to be enough for the Pentagon. So far, what they’ve tried to treat PTSD — which afflicts at least 250,000 of this generation’s soldiers — isn’t working. Conventional approaches, like antidepressants and behavioral therapy, have been a massive failure. So it makes sense that military officials are increasingly open to out-there ideas: They’re already funding research into yoga and acupuncture, neck injections and “digital dream” computer programs — although promising approaches taking advantage of “illicit” substances, like marijuana and ecstasy, have thus far been nixed.

Of course, this latest study will be bigger and more thorough than its failed predecessors. It also builds on years of animal research suggesting that DCS has potential. And there’s no doubt the project is calling on some of the Pentagon’s top civilian scientists. Dr. Rothbaum has been evaluating PTSD treatments, including preliminary studies on DCS, for decades. And Dr. Albert “Skip” Rizzo, from the University of Southern California, pioneered the use of virtual reality therapy to mitigate PTSD symptoms.

Not to mention that this research team will also be conducting genetic tests on every patient. In particular, they’ll be looking at a gene dubbed “BDNF.” Experts already know that a variant of the BDNF gene can make fear extinction tougher. By comparing patient results to genes, Rothbaum says they hope to “figure out what’s the best treatment approach, and whether DCS can really rescue those patients, where maybe therapy alone can’t.”

Of course, the idea of using drugs to tweak memories isn’t without controversy: An online debate flared last year among two camps of neurologists and neuroethicists, arguing over whether the existence of such drugs would “alter something that makes us all human,” or open a Pandora’s Box of illicit use “by people doing things they’d like to forget themselves, or that they would like others to forget.”

Then again, those debates hinge on DCS, or some other memory extinguisher, actually working. DCS’s efficacy is far from proven. And earlier research efforts that tested supposed “fear-extinguishing” drugs, most notably a series of much-touted, Pentagon-funded studies on Propanolol at Harvard, have all been disappointments.

 

 

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