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from the CCLE.

Blanks for the memories:

Someday you may be able to take a pill to forget painful recollections

By Scott LaFee,  (c) San Diego Union Tribune  Feb. 11, 2004

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There’s a scene in Shakespeare’s “Macbeth” where the protagonist implores a doctor to treat Lady Macbeth, who is wracked by memories of past bad acts.

“Canst thou not minister to a mind diseas’d,

Pluck from the memory a rooted sorrow,

Raze out the written troubles of the brain,

And with some sweet oblivious antidote

Cleanse the stuff’d bosom of that perilous stuff

Which weighs upon the heart?”

The doctor, of course, can offer no real salvation. Lady Macbeth is condemned to live with her bad memories. Recalling our past is a part of the human condition. But what if that reality changed? What if people – 400 years after Shakespeare asked – could take a pill to purposefully dim – perhaps erase – our most painful and unwanted memories?

The notion has long been a favorite of fiction writers, from Shakespeare to fantasists like the late Philip K. Dick, but serious people – scientists and scholars – now believe it might be possible.

“The burgeoning field of neuroscience is providing new, more specific, and safer agents to help us combat all sorts of psychic distress,” wrote the authors of “Beyond Therapy,” a recently released report by the President’s Council on Bioethics.

“Soon, doctors may have just the ‘sweet oblivious antidote’ that Macbeth so desired: drugs that numb the emotional sting typically associated with our intensely bad memories.”

The authors do not think this is necessarily a good thing.

Think it with feelings

Memory isn’t a single entity. There are different kinds and types.

Short-term memory lasts just a few seconds. It’s the ability to recall a phone number long enough to dial it. Capacity is limited. It’s no coincidence that phone numbers are just seven numbers long. That’s the working limit for most people’s short-term memory.

Long-term memories come in two broad categories. Explicit memories are general knowledge, facts of life, conscious recollections, the sort of stuff most people think of as memory.

Implicit memories are perceptual abilities, motor skills, conditioned or instinctive responses that operate outside of consciousness, such as instantly recognizing an object or knowing how to ride a bike.

Researchers focus on long-term memory because it is the primary driver of behavior. Much about how long-term memories are formed or function is fuzzy or unknown, but some fundamentals are well-understood.

To wit: Strong emotions make strong memories.

Most daily events are quickly forgotten. They are memories writ in pencil, never made permanent. But some events provoke an emotional response. In these moments of joy or sadness, terror or surprise, the body is flooded with stress hormones released by the adrenal glands, which are located above the kidneys. This is part of the ancient “fight or flight” response. Hormones like adrenaline wash over the amygdala – an almond-shaped portion of the brain that processes emotion, most notably fear. Adrenaline tells the amygdala that what’s happening at that moment is worth remembering, that this is a memory to be writ in neurological ink.

Here’s where many neuroscientists think there’s an opportunity to act, to perhaps dilute a potentially traumatic memory before it dries hard and fast.

“We’ve learned that if you can prevent the system from working, give a drug that blocks the action of stress hormones (upon the amygdala and brain), then you may be able to prevent the influence of making stronger memories,” said James L. McGaugh, director of UC Irvine’s Center for the Neurobiology of Learning and Memory and author of “Memory & Emotion: The Making of Lasting Memories.”

Memory-altering drug research is currently focused on propranolol, one of several so-called beta blockers widely used to reduce blood pressure, treat abnormal heart rhythms and prevent migraines. The brand name for propranolol is Inderal. Other beta blocker brand names are Inderide, Innopran XL, Betachron E-R, Kerlone, Lopressor, Tenormin, Toprol XL, Visken and Zebeta.

Beta blockers work by “blocking” the stimulative influence of stress hormones – specifically adrenaline – upon the body, relaxing blood vessels and slowing nerve impulses inside the heart.

Experiments indicate propranolol also blocks the effect of adrenaline upon areas of the brain involved in memory formation, including the amygdala. It seems to disconnect emotion from memory.

In a study conducted by Larry Cahill, a neurobiologist at UC Irvine, McGaugh and others in the late 1990s, test subjects were told an emotionally neutral, comparatively boring story illustrated by 12 slides. A second group of subjects was then shown the same 12 slides. The related story, however, was much more emotional, involving a severely injured boy.

When later asked what they remembered seeing in the pictures, subjects in the second group recalled much greater detail about the story than the first group did about theirs.

Cahill and McGaugh then presented the second, emotionally upsetting story with slides to a third group of volunteers who were given a standard dose of propranolol or endurol (another beta blocker). Their memories, when tested three weeks later, were “just like that of subjects who had received the boring story,” said McGaugh.

Subjects remembered the story, but without any emotional depth.

Such findings suggest an obvious potential therapeutic benefit: If people who have just experienced a traumatic event could be given a memory-dampening drug like propranolol, they might avoid suffering later psychic damage, such as post-traumatic stress disorder or PTSD.

Roughly 5 million Americans between the ages of 18 and 54 suffer from PTSD at any given time. Almost 8 percent of Americans will experience PTSD at some point in their lives, women twice as likely as men. Clearly, McGaugh and others said, there are times when blocking the formation of traumatic memories would be beneficial.

“Let me give you an example from the 1978 PSA (plane) crash in San Diego where they made the horrible mistake of sending out desk people and baggage handlers to clean up body parts after the crash. Later, there was a follow-up report that said a very high percentage of those people were never able to work again. They had been permanently disabled because of the trauma.

“Now, that’s PTSD to the nth degree, that would be a case in which something like (a memory-blunting drug) would be of value.”

Two subsequent studies reinforce the potential efficacy of using beta blockers to blunt memory. In a 2002 pilot study, Roger Pitman, a professor of psychiatry at Harvard University, recruited 31 people from the emergency room of Massachusetts General Hospital who had just been involved in a traumatic event, typically an automobile accident.

Some of the study volunteers were treated with propranolol for 10 days after the trauma; some received a placebo. Evaluated one month later, none of the subjects treated with propranolol had a stressful physical reaction to re-creations of their traumatic event, while six of the 14 subjects treated with a placebo did.

A similar 2003 study, conducted at two French hospitals, produced analogous results. Larger studies are being planned.

A need to remember

Despite its therapeutic potential, some people are wary of memory-altering drugs. Chief among them: the President’s Council on Bioethics, an advisory group of doctors and scholars formed in 2001.

In its report, the council worries that dampening painful memories – or in the future, erasing them altogether – may disconnect people from reality or their true selves.

“The use of memory-blunters at the time of traumatic events could interfere with the normal psychic work and adaptive value of emotionally charged memory,” the council wrote. “A primary function of the brain’s special way of encoding memories for emotional experiences would seem to be to make us remember important events longer and more vividly than trivial events.”

In other words, emotional memories, however painful, serve a purpose. We remember memories linked to emotions longer and better because they help us learn, adapt, survive. Early hominids needed to know and remember that lions were dangerous. Modern children burn their fingers on a match and learn that fire hurts. We all learn to avoid bad things by remembering bad experiences.

Council members fret that dampening traumatic memories with beta blockers may short-circuit “the normal process of recovery,” that in some way it may diminish our character or our personal development.

Blocking emotional memories, the council asserted, risks “falsifying our perception and understanding of the world. It risks making shameful acts seem less shameful, or terrible acts less terrible, than they really are.”

“It’s the morning-after pill for just about anything that produces regret, remorse, pain, or guilt,” said Dr. Leon Kass, who chaired the President’s Council, to the Village Voice last year. (Kass noted he was speaking as an individual, not on behalf of the council.)

The council expressed a host of concerns and troubling scenarios.

For example, the council posited, what if somebody committed an act of violence and then took propranolol to dull the emotional impact. Would they come to think of violence as more tolerable than it really is?

Would rape victims, having taken memory-altering drugs to ease their trauma, forget key details vital to the prosecution of their attackers?

More broadly, is there a social obligation for people to remember the past events for the communal good, such as victims of the Holocaust?

“The impulse is to help people to not fall apart. You don’t want to condemn that,” said Kass. “But that you would treat these things with equanimity, the horrible things of the world, so that they don’t disturb you … you’d cease to be a human being.”

Long-term effect

Such talk dismays researchers like McGaugh. Partly because they believe it overstates current scientific realities; partly because it seems a moot point. Society, suggests McGaugh, decided decades ago that the benefits of certain drugs outweighed any memory-altering side effects.

“We made that decision with the advent and use of psychoactive drugs. Valium is a memory-impairing drug, but I don’t hear people raising memory issues about it.”

More to the point, the influence of propranolol seems to be limited to new, emotional memories – and only if taken during or shortly after a traumatic event.

“The (memory-dampening) effects (of beta blockers) are rather weak,” said Larry Squire, a neurobiologist at UCSD and the Veterans’ Administration Medical Center in La Jolla. “And no one can imagine possibly tinkering with memory that represents our personal identities, memories of childhood, our connections to people and the past. Those are transformed over time. They’re hard-wired in our brains and can’t be fooled with.”

But some researchers aren’t so sure. In animal studies, neuroscientists like Joseph Ledoux at New York University say they have found evidence that there is a window of opportunity to alter a memory each time it is recalled.

Specifically, lab rats were trained to expect an electric shock when they heard a particular tone. The rats soon froze in fear whenever they heard the tone, even if no shock followed. Then the NYU researchers backed off, allowing the rats’ brains to consolidate the memory, to embed it long-term. Days later, they played the tone again, eliciting the fearful response. But this time, some of the rats were given a drug that prevented the amygdala from making proteins necessary for memory storage. These rats stopped being fearful of the tone, apparently forgetting their earlier emotional response to it.

Other studies, blocking protein production in the hippocampus of crabs and chicks, produced similar results.

Karim Nader, an assistant professor of psychology at Montreal’s McGill University who participated in the NYU rat research, believes there may be a human corollary to these animal studies and a potential opportunity to influence deeper, older memories when they are recalled, and then laid back down.

But the idea is highly controversial, with many skeptics.

“It’s likely that any effects are reversible, temporary,” said Squire. “You may be able to bring up a memory, weaken it, but eventually the memory comes back. The effect is more like interference than real change.”

“I simply do not believe the (NYU) research is valid,” added McGaugh. “Human studies have shown no such effect. They show human memory doesn’t work that way.”

Fact and fiction

McGaugh and similarly minded researchers doubt science will ever be able to probe an individual’s mind, precisely plucking and altering specific memories like they do in movies. The brains of real people are far too complex. Memories aren’t single molecules or neurons, but intricate patterns of biochemical and electrical energy occurring in various parts of the brain and different levels of the mind.

Take, for example, new findings from Michael Anderson and John Gabrieli, psychology professors at the University of Oregon and Stanford, respectively. Last month, they reported identifying the brain mechanism that allows humans to voluntarily block unwanted memories.

“Often in life we encounter reminders of things we’d rather not think about,” Anderson said. “We have all had that experience at some point – the experience of seeing something that reminds us of an unwanted memory, leading us to wince briefly – but just as quickly to put the recollection out of mind. How do human beings do this?”

Anderson and Gabrieli discovered that when people consciously determine not to think about something they do not want to remember, their ability to recall that memory gradually weakens. Call it motivated forgetting.

The effect, said McGaugh, is not unlike what propranolol does biochemically and it fits neatly into what’s known about how PTSD can progressively worsen with each recurrence of the traumatic memory.

How Anderson and Gabrieli’s work can be exploited therapeutically, if at all, remains to be seen.

Currently, the pursuit of memory-altering drugs is limited, both in terms of the numbers of researchers involved and in what they are trying to do or learn. Prospects of a pill-to-forget hitting the market anytime soon are nil.

But even the existence of that prospect raises profound questions that demand answers, said Dr. William B. Hurlbut, a consulting professor in biology at Stanford University and a member of the President’s Council on Bioethics.

“The pattern of our personality is like a Persian rug,” Hurlbut said. “It is built one knot at a time, each woven into the others. There’s a continuity to self, a sense that who we are is based upon solid, reliable experience. We build our whole interpretation and understanding of the world based upon that experience or on the accuracy of our memories.

“If you disrupt those memories, remove continuity, what you have is an erosion of personhood.”

See Also: Cognitive Liberty in the Age of Memory-management Drugs


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