A drug that seems to dampen bad memories, while leaving other memories intact, may one day be used to treat post-traumatic stress disorder.
Previously, scientists knew that a stress hormone called cortisol affects people's ability to form new memories and decrease negative emotions that might have been associated with them. But they thought once memories had solidified, they could no longer be affected by cortisol.
A new study led by researchers at the Centre for Studies on Human Stress, affiliated with the University of Montreal, shows that in fact, metyrapone, a drug that temporarily alters cortisol levels can be used to dampen an old, negative memory for days and possibly the long term.
"It gives us a second chance, basically, to act on the memory," said Marie-France Marin, lead author of the study published in the Journal of Clinical Endocrinology and Metabolism.
What is PTSD?
Post-traumatic stress disorder is the constellation of symptoms such as depression, flashbacks and nightmares that can be brought on by any type of trauma.
It's most often associated with military service, among soldiers who return from battle only to suffer the after-effects of what was once called "shell shock."
Psychotherapy may be an effective treatment. Drugs such as antidepressants, antipsychotics, anticonvulsants and beta blockers may also help with some of the symptoms.
That makes it potentially very useful, because most memories that cause problems are older rather than newly formed.
"Soldiers, for example, or rape victims, are not going to go to the emergency room within an hour, obviously," Marin said Thursday.
She added that many people who experience traumatic events don't necessarily go on to develop post-traumatic stress disorder, and the fact that the drug works long after the memory was formed means it can be selectively given to people who have suffered long-term effects from a traumatic experience.
The study involved 33 men who were asked to watch a story in the form of slides with audio narration. The story starts off as an emotionally neutral tale of a little girl who visits her grandparents and builds a birdhouse. The middle three slides show an accident where the girl's hand gets mutilated and bloodied with a saw. The final four slides are also neutral, as the girl gets medical care and is expected to be fine.
Three days later, the volunteers were given a placebo or one or two doses of a drug called metyrapone, which dramatically decreases levels of cortisol, which is normally present at a certain level in the blood.
They were then asked to recall the story.
Those who received two doses of metyrapone had significantly more trouble remembering the negative parts of the story compared to the rest of the story. That effect was not seen among those who had taken the single dose or the placebo.
What is cortisol?
Cortisol is a hormone produced by the adrenal gland in the kidneys. It is always present at low levels in the body, but more is produced when the body is under stress. Cortisol affects many systems in the body, including metabolism and the immune system.
What is metyrapone?
Metyrapone is a drug that lowers levels of cortisol to far beneath normal levels — low levels that cannot be achieved without drugs, researcher Marie-France Marin says. It was originally used to treat an uncommon disorder called Cushing's disease, in which people secrete too much cortisol. However, other treatments for Cushing's have been developed, and metyrapone is no longer on the market. The drug does have some side-effects, such as dizziness. However, Marin believes that since it only needs to be taken once to affect memories, the side-effects are minimal compared to the potential benefit.
Four days later, when their cortisol levels were back to normal, the participants came back into the lab and were asked to recall the story again.
Those who had taken two doses of metyrapone still had trouble remembering the negative parts of the story.
That result surprised the researchers.
It seems to show that contrary to what scientists previously believed, "at the time of retrieving the memory, you open an opportunity for the memory to be changed," Marin said. "And by lowering the cortisol levels, you change it in a lasting manner."
Marin said the researchers believe the double dose had an effect where the single one didn't because the two doses were separated by three hours, lowering cortisol levels for a longer time.
Potential use during psychotherapy
She foresees that the drug may one day be given to people with serious cases of post-traumatic stress disorder during psychotherapy, when they are asked to describe their traumatic experiences.
However, before that happens, the researchers must do more work to figure out whether the technique will work on memories that are years old instead of days old, and just how long-lasting the effects are.
"A lot of studies are needed to get to the perfect treatment, obviously," she said.
She also emphasized that the drug should only be used in cases of people with very serious cases of PTSD.
"It's really, really to help people who could not recover, who could not live a normal life, basically," she said.
"You can't start giving this to everyone who has a bad day…. Memories are important. They define who you are."