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The Memory Pill

November 26, 2006 – Original Source: 60 minutes, CBS

(CBS)  This segment was originally broadcast on Nov. 26, 2006. It was updated on June 14, 2007.

If there were something you could take after experiencing a painful or traumatic event that would permanently weaken your memory of what had just happened, would you take it? As correspondent Lesley Stahl first reported last fall, it’s an idea that may not be so far off, and that has some critics alarmed, and some trauma victims filled with hope.

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“I couldn’t get my body to stop shaking. I was trembling, constantly trembling. Memories of it would just come back, reoccurring over and over and over,” subway conductor Beatriz Arguedas recalls.

A year ago September, Beatriz was driving her normal route on the Red Line in Boston when one of her worst fears came to pass: “Upon entering one of the busiest stations, a man jumped in front of my train, to commit suicide,” she explains.

Beatriz saw the man jump. “We sort of made eye contact and then I felt the thud from him hitting the train and then the crackling sound underneath the train and, then, of course, my heart starts thumping,” she recalls.

“She came into our emergency room afterwards, very upset. No physical injury. Entirely a psychological trauma,” says Dr. Roger Pitman, a psychiatrist at Harvard Medical School who has studied and treated patients with post-traumatic stress disorder, or PTSD, for 25 years.

“They’re caught up so much with this past event that it’s constantly in their mind,” Pitman explains. “They’re living it over and over and over as if it’s happening again. And they just can’t get involved in real life.”

When Beatriz arrived in the emergency room, Pitman enrolled her in an experimental study of a drug called propranolol, a medication commonly used for high blood pressure … and unofficially for stage fright. Pitman thought it might do something almost magical – trick Beatriz’s brain into making a weaker memory of the event she had just experienced.

In the study, which is still under way, half the subjects get propranolol; half get a placebo.

Asked whether he knows if Beatriz got the drug or the placebo, Dr. Pitman says he has no idea and neither does she, and that the research team won’t know for another two years.

If Pitman is right, the results could fundamentally change the way accident victims, rape victims, even soldiers are treated after they experience trauma.

The story begins with some surprising discoveries about memory. It turns out our memories are sort of like Jello – they take time to solidify in our brains. And while they’re setting, it’s possible to make them stronger or weaker. It all depends on the stress hormone adrenaline.

The man who discovered this is James McGaugh, a professor of neurobiology at the University of California, Irvine.

(CBS)  McGaugh studies memory in rats, and he invited Stahl to watch the making of a rat memory – in this case how a rat who’s never been in this tank of water before learns how to find a clear plastic platform just below the surface.

“He’ll swim around randomly,” McGaugh explains. The rat cannot see the platform, since his eyes are on the top of his head.

The rat will swim around the edge for a long time, until eventually he ventures out and by chance bumps into the platform. The next day, he’ll find the platform a little bit faster.

But another rat, who had learned where the platform was the day prior, and then received a shot of adrenaline immediately afterwards, today swam instantly to the platform.

Adrenaline actually made this rat’s brain remember better, and McGaugh believes the same thing happens in people. “Suppose I said to you, ‘You know, I’ve watched your programs a lot over the years, and although it pains me to have to tell you this, I think you’re one of worst people I’ve ever seen on … now don’t take it, don’t take it personally,'” McGaugh says.

“So, my stress system would go into overdrive, no question,” Stahl says.

“Even with my telling you that it’s not true, there’s nothing to keep you from blushing, from feeling warm all over,” McGaugh points out. “That’s the adrenaline. And I dare say that you’re gonna remember my having said that long after you’ve forgotten the other details of our discussion here. I guarantee it.”

McGaugh says that’s why we remember important and emotional events in our lives more than regular day-to-day experiences. The next step in his research was to see what would happen when adrenaline was blocked; he started experimenting with propranolol.

“Propranolol sits on that nerve cell and blocks it, so that, think of this as being a key, and this is a lock, the hole in the lock is blocked because of propranolol sitting there. So adrenaline can be present, but it can’t do its job,” McGaugh explains.

McGaugh showed Stahl a third rat that had learned where the platform was on the previous day and then received an injection of propranolol. The next day, the rat swam around the edge, as if he had forgotten there ever was a platform out there.

Across the country at Harvard, Roger Pitman read McGaugh’s studies and a light bulb went on. “When I read about this, I said, ‘This has got to be how post-traumatic stress disorder works.’ Because think about what happens to a person. First of all, they have a horribly traumatic event, and they have intense fear and helplessness. So that intense fear and helplessness is gonna stimulate adrenaline,” Pitman says. “And then what do we find three months or six months or 20 years later? Excessively strong memories.”

(CBS)  Pitman figured he could block that cycle by giving trauma victims propranolol right away … before adrenaline could make the memories too strong. He started recruiting patients for a small pilot study. One of the first was Kathleen Logue, a paralegal who had been knocked down in the middle of a busy Boston street by a bicyclist.

“He just hit the whole left side of my body. And it seemed like forever that I was laying in the middle of State Street, downtown Boston,” Logue remembers.

She says she was terrified that she was just going to get run over.

As part of the study, Logue took propranolol four times a day for 10 days. Like the others who got the drug, three months later she showed no physiological signs of PTSD, while several subjects who got a placebo did. Those results got Pitman funding for a larger study by the National Institutes of Health.

But then the President’s Council on Bioethics condemned the study in a report that said our memories make us who we are and that “re-writing” memories pharmacologically … risks “undermining our true identity.”

“This is a quote. ‘It risks making shameful acts seem less shameful or terrible acts less terrible than they really are,'” Stahl reads to Logue.

“A terrible act,” she replies. “Why should you have to live with it every day of your life? It doesn’t erase the fact that it happened. It doesn’t erase your memory of it. It makes it easier to remember and function.”

David Magnus, director of Stanford University’s Center for Biomedical Ethics, says he worries that it won’t be just trauma victims trying to dull painful memories.

“From the point of view of a pharmaceutical industry, they’re going to have every interest in having as many people as possible diagnosed with this condition and have it used as broadly as possible. That’s the reality of how drugs get introduced and utilized,” Magnus argues.

He’s concerned it will be used for trivial reasons. “If I embarrass myself at a party Friday night and instead of feeling bad about it I could take a pill then I’m going to avoid – not have to avoid making a fool of myself at parties,” Magnus says.

“So you think that that embarrassment and all of that is teaching us?” Stahl asks.

“Absolutely,” Magnus says. “Our breakups, our relationships, as painful as they are, we learn from some of those painful experiences. They make us better people.”

But while the ethicists debate the issue, the science is moving forward. Researchers have shown in rat studies that propranolol can also blunt old memories.

Pitman wondered: Could it work in humans? He teamed up with Canadian colleague Alain Brunet, who searched for people with long-standing PTSD, like Rita Magil. She had suffered for three years from nightmares after a life-threatening car accident.

Another study subject is Louise O’Donnell-Jasmin, who was raped by a doctor at the age of 12. “He raped me on his desk, on a chair, and on the floor. It, for me, it was like I was dying inside,” she remembers. “The world had ended.”

O’Donnell-Jasmin was haunted by the rape for more than 30 years. She never felt comfortable undressing in front of her husband and suffered from recurrent flashbacks and nightmares.

The study was simple: Subjects came in and were asked to think about and write down every detail they could remember about their trauma; in Magil’s case, her car accident, reactivating the memory in her brain. She was then given propranolol.

Rita says she suffered no side effects.

A week later, electrodes measured her body’s stress response as she listened to a retelling of her trauma. Asked what happened, Magil says, “No reaction.”

And she says she had no more nightmares.

The patient who made the most dramatic recovery turned out to be O’Donnell-Jasmin, but there’s a catch, because she was in a control group and therefore wasn’t supposed to improve at all.

(CBS)  O’Donnell-Jasmin was given propranolol, but unlike Magil, she took the drug while watching a pleasant movie, not after telling every detail about her rape. And yet, a week later, she noticed a change. “I wake up. And I find myself undressing. And my husband is there. And I realize I’m undressing, and I’m not feeling as though I need to hide under the bed anymore,” she explains.

Asked if it is gone, O’Donnell-Jasmin says, “Yes. The link, what held the emotions to the memories, it’s like the umbilical cord has been cut. And there is no way I can access the emotions anymore. And furthermore, every day it gets better.”

“Louise got a great result. But, scientifically, it confused things,” Pitman says.

He speculates that despite the pleasant movie, O’Donnell-Jasmin may have been thinking about the rape when she took the propranolol, and that’s why it worked. “The only way we’re going to know is to study another 10 or a hundred patients like Louise and see how it pans out,” Pitman says.

That this drug could actually alter and weaken old memories means we’re talking about a potentially revolutionary advance in treating post traumatic stress disorder.

“Are you at all concerned that since propranolol is already out there available for doctors to prescribe for heart conditions, for stage fright, that some soldier who’s come back and is having terrible nightmares can go to his doctor and get it right now? Is that a concern for you, or not a concern?” Stahl asks McGaugh.

“No. Not a concern for me. Not a concern,” he replies. “If it helps, why not.”

“Let me tell you something that you told us before. I’m quoting you. ‘It’s like they went in and altered my mind,'” Stahl tells Louise.

O’Donnell-Jasmin admits it’s very creepy. “This study has taken away a part of me that’s been in me for so long, and that I find very weird,” she says.

“It’s not normal to have gone through a rape and feel nothing. Or to have gone through something traumatic … and feel as though it happened to somebody else,” Stahl tells Pitman.

“Let’s suppose you have a person who comes in after a physical assault and they’ve had some bones broken, and they’re in intense pain. Should we deprive them of morphine because we might be taking away the full emotional experience? Who would ever argue that?” Pitman replies.

“No,” Stahl says.

“Why should psychiatry be different? I think that somehow behind this argument lurks the notion that mental disorders are not the same as physical disorders. That treating them or not is more of an optional thing,” Pitman says.

The studies are still in their early stages, so O’Donnell-Jasmin’s apparent positive result isn’t conclusive, though to her, it’s absolutely real.

Asked if there is any sense that she has lost any of her identity, O’Donnell-Jasmin says, “I have regained my identity. What was broken when I was 12 was fixed. They have given me back myself.”

* * *

And now the U.S. military has taken note. Dr. Pitman will be receiving Army funding later this summer to try the same propranolol experiment done with Rita and Louise to treat American soldiers returning from Afghanistan and Iraq. He cautions that the studies are still in the experimental stage and not yet ready for general use.

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