A drug to take away the bad times

Blocking a hormone involved in the body's stress response may change the way people remember negative memories, according to a new study.

But it's still unclear exactly how the drug involved works, and whether the finding has implications for treating conditions like post-traumatic stress disorder (PTSD).

The drug, metyrapone, blocks cortisol and has been used to treat people with diseases related to cortisol production. But cortisol is also involved in storing and retrieving memories, leading researchers to wonder if altering its levels in the body could change how people recall past events.

"We know that (cortisol) is important for memory," Marie-France Marin, the study's lead author from the University of Montreal, said. "Very high levels are bad for your memory, and very low levels are bad for your memory."

The research

In their research, Marin and her colleagues went for the very low levels, using metyrapone to stop healthy volunteers from producing cortisol.

Those volunteers, 33 young men, were first shown a narrated slide show that had both "neutral" and "emotionally negative" slides.

The slides told the story of a young girl who goes to her grandparents' house. There, she and her grandparents try to build a birdhouse, and the girl gets badly injured, with scenes showing lots of blood and a trip to the operating room. In the end, viewers know that the girl will be okay.

Three days after watching the video, the men took a single 750-mg dose of metyrapone, a double dose, or a placebo. Then the researchers asked them to recall as much information as possible from the story.

Another four days after that, they brought the participants in once more, and without giving them any drugs asked them to recall the story again.

No difference

There was no difference in how men who had taken a single dose of metyrapone and those given a placebo remembered the story either time. But on both occasions, those given a double dose remembered significantly less of the negative emotional components of the story.

For example, men in the placebo group scored between 40% and 50% on their second memory test for negative emotional information in the story, whereas men given a double dose scored about 30% on average.

"The fact that the effects of metyrapone were still evident for four days after, that's pretty remarkable," said Tony Buchanan, who studies stress and memory at Saint Louis University and was not involved in the study.

Both metyrapone groups scored just as well as the placebo group on recall of "neutral" information.

The investigators who determined how much participants remembered didn't know whether they had taken metyrapone or the placebo, according to an article published in the Journal of Clinical Endocrinology & Metabolism.

Marin and her colleagues believe that once participants were asked to retrieve the memory of the story, those taking the high dose of metyrapone re-stored that memory in a different, less-emotional way, probably because cortisol levels were lower at that time.

Though they predicted that people would remember the story differently while under the effects of the drug, they didn't know the memory would still be changed once hormone levels returned to normal.

Memory modification

"What was really surprising is that once the memory was sorted in the brain we were able to modify it in a long-lasting manner," Marin said.

Researchers still aren't sure why metyrapone might affect how negative memories, but not neutral ones, are recalled and re-stored, Marin said.

The ultimate goal from this and other studies that have tried to use drugs to alter negative memories is to treat people who are overwhelmed by these memories, such as war veterans suffering from PTSD, an idea that still makes some uncomfortable.

According to the National Institute of Mental Health, about 3.5% of US adults suffer from PTSD, but that rate may be as high as 20% in veterans of the Iraq and Afghanistan wars.

It's not clear yet that a drug that helps people without PTSD remember fewer ugly details in a story will also work for those who experienced the trauma first-hand and have been profoundly affected by that trauma.

"We need to see if autobiographical memories are sensitive (to metyrapone) in the same way or not," Marin said.

What's more, "only a small fraction of people exposed to traumatic events experience PTSD," Buchanan said. It's hard to tell if any of those 33 volunteers might have had certain characteristics that would predispose them to PTSD or not, he said.

In people with that predisposition, he said, "you'd imagine there's something different about their brains before the trial," which could affect how they recall negative memories.

Researchers also can't be sure that women would have the same reaction to the drug as men, since only men were used in the study.

Metyrapone is currently not on the market, the authors note, so it's important also to study other drugs that may have the same effect.

More research is needed before metyrapone, or similar drugs that block cortisol, can be tested in PTSD patients. But according to Buchanan, the new study "is a great step in that direction."

(Reuters Health, Genevra Pittman, May 2011)

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