From the archive, originally posted by: [ spectre ]


Scientists find drug to banish bad memories
BY Richard Gray  /   01/07/2007

It failed to bring Jim Carrey happiness in the award-winning film
Eternal Sunshine of the Spotless Mind, but scientists have now
developed a way to block and even delete unwanted memories from
people’s brains.

Researchers have found they can use drugs to wipe away single,
specific memories while leaving other memories intact. By injecting an
amnesia drug at the right time, when a subject was recalling a
particular thought, neuro-scientists discovered they could disrupt the
way the memory is stored and even make it disappear.

The research has, however, sparked concern among parliamentary
advisers who insist that new regulations are now needed to control the
use of the drugs to prevent them becoming used by healthy people as a
“quick fix”.

But the US scientists behind the research insist that amnesia drugs
could be invaluable in treating patients with psychiatric disorders
such as post-traumatic stress.

In a new study, revealed in the Journal of Psychiatric Research,
psychiatrists at McGill University, in Montreal, and Harvard
University, in Boston, used an amnesia drug to “dampen” the memories
of trauma victims.

Prof Karim Nader, of McGill University, said: “When you remember old
memories they can become ‘unstored’ and then have to be ‘restored’.

“As the memory is getting restored, we gave patients a drug that turns
down the emotional part of the memory. It left the conscious part of
the memory intact, so they could still remember all the details but
without being overwhelmed by the memory.”

The research suggests memories can be manipulated because they act as
if made from glass, existing in a molten state as they are being
created, before turning solid. When the memory is recalled, however,
it becomes molten again and so can be altered before it once more

The drug used by the scientists is thought to disrupt the biochemical
pathways that allow the memory to “harden” after it is recalled.

The researchers used propranolol, a drug normally used to treat
hypertension in heart disease patients but also known to cause memory
problems. They treated 19 accident or rape victims for 10 days with
the drug or with dummy pills, while they asked to describe their
memories of a traumatic event that happened 10 years earlier.

A week later, they found that the patients given the drug suffered
fewer signs of stress such as raised heart rate when recalling their

The technique echoes scenes from Eternal Sunshine of the Spotless
Mind, where the characters played by Jim Carrey and Kate Winslet both
undergo treatment to delete each other from their memories.

In the film, scientists ask the characters to remember their unwanted
memories in order to target them with small electric shocks. But the
treatment goes drastically wrong, when the characters discover they in
fact wanted to hold on to the memories after all.

Scientists at New York University have published another new study
where they claim to have erased a single memory from the brains of
rats while leaving the rest of the animals’ memories still intact.

The rats were trained to associate two musical tones with a mild
electrical shock so that when they heard either of the tones they
would brace themselves for a shock.

The researchers then gave half the rats a drug, called U0126 and known
to cause limited amnesia, when playing one of the musical tones.

After the treatment, the rats that had been given the drug no longer
associated that particular tone with an imminent shock but still
braced themselves upon hearing the second tone, demonstrating only one
memory had been deleted.

Prof Joseph LeDoux, who led the New York team, said: “Such treatments
may have highly specific and potentially permanent effects.”

The research has alarmed some experts, however, who fear that memory
altering drugs could be abused by healthy individuals to delete
unwanted memories on a whim.

A new report published by the Parliamentary Office of Science and
Technology, which advises MPs about scientific advances, warned that
regulations need to be put in place to restrict the use of any memory-
blocking drugs, imposing strict limits on their prescription.

Dr Peter Border, who edited the report, said: “There has been a
deafening silence from the regulators about whether or not they might
consider licensing pharmaceuticals for use in individuals where there
is no medical benefits. There is a need for someone to consider how to
regulate these things.”


Effect of post-retrieval propranolol on psychophysiologic responding
during subsequent script-driven traumatic imagery in post-traumatic
stress disorder

Received 28 March 2007;  accepted 1 May 2007.  Available online 22
June 2007.


The β-adrenergic blocker propranolol given within hours of a
psychologically traumatic event reduces physiologic responses during
subsequent mental imagery of the event. Here we tested the effect of
propranolol given after the retrieval of memories of past traumatic
events. Subjects with chronic post-traumatic stress disorder described
their traumatic event during a script preparation session and then
received a one-day dose of propranolol (n = 9) or placebo (n = 10),
randomized and double-blind. A week later, they engaged in script-
driven mental imagery of their traumatic event while heart rate, skin
conductance, and left corrugator electromyogram were measured.
Physiologic responses were significantly smaller in the subjects who
had received post-reactivation propranolol a week earlier. Propranolol
given after reactivation of the memory of a past traumatic event
reduces physiologic responding during subsequent mental imagery of the
event in a similar manner to propranolol given shortly after the
occurrence of a traumatic event.

Keywords: Stress disorders, post-traumatic; Memory; Conditioning;
Propranolol; Imagery; Psychophysiology

Drs. Brunet, Nader, and Pitman designed the study. Drs. Brunet and
Pitman wrote the protocol. Dr. Tremblay served as study physician. Ms.
Robertson served as study coordinator and data manager. Dr. Orr
performed the statistical analyses. Drs. Brunet and Pitman wrote the
first draft of the manuscript. All authors contributed to and have
approved the final manuscript.

Corresponding Author Contact : Address: Massachusetts General Hospital-
East, Room 2616, Building 149, 13th Street, Charlestown, MA 02129,
USA. Tel.: +1 617 726 5333; fax: +1 617 726 4078.

Alain Bruneta, Scott P. Orrb, c, Jacques Tremblaya, Kate Robertsona,
Karim Nadernext termd and Roger K. Pitmanc,Corresponding Author
Contact Information, E-mail The Corresponding Author
a Department of Psychiatry, McGill University and Douglas Hospital
Research Center, Montreal, QC, Canada
b VA Medical Center, Manchester, NH, USA
c Department of Psychiatry, Massachusetts General Hospital and Harvard
Medical School, Boston, MA, USA
d Department of Psychology, McGill University, Montreal, QC, Canada


Is every memory worth keeping?

Pills to reduce mental trauma raise controversy
By Rob Stein, The Washington Post, Oct 19, 2004

Kathleen Logue was waiting at a traffic light when two men smashed her
car’s side window, pointed a gun at her head and ordered her to drive.
For hours, Logue fought off her attackers’ attempts to rape her, and
finally she escaped. But for years afterward, she was tormented by
memories of that terrifying day.

So years later, after a speeding bicycle messenger knocked the Boston
paralegal onto the pavement in front of oncoming traffic, Logue jumped
at a chance to try something that might prevent her from being haunted
by her latest ordeal.

“I didn’t want to suffer years and years of cold sweats and nightmares
and not being able to function again,” Logue said. “I was prone to it
because I had suffered post-traumatic stress from being carjacked. I
didn’t want to go through that again.”

Logue volunteered for an experiment designed to test whether taking a
pill immediately after a terrorizing experience might reduce the risk
of post-traumatic stress disorder (PTSD). The study is part of a
promising but controversial field of research seeking to alter, or
possibly erase, the impact of painful memories — a concept dubbed
“therapeutic forgetting” by some and taken to science fiction extremes
in films such as this summer’s “Eternal Sunshine of the Spotless

Proponents say it could lead to pills that prevent or treat PTSD in
soldiers coping with the horrors of battle, torture victims recovering
from brutalization, survivors who fled the World Trade Center on Sept.
11, 2001, and other victims of severe, psychologically devastating

“Some memories can be very disruptive. They come back to you when you
don’t want to have them — in a daydream or nightmare or flashbacks —
and are usually accompanied by very painful emotions,” said Roger K.
Pitman, a professor of psychiatry at Harvard Medical School who is
studying the approach. “This could relieve a lot of that suffering.”

Skeptics, however, argue that tinkering with memories treads into
dangerous territory because memories are part of the very essence of a
person’s identity, as well as crucial threads in the fabric of society
that help humanity avoid the mistakes of the past.

“All of us can think of traumatic events in our lives that were
horrible at the time but made us who we are. I’m not sure we’d want to
wipe those memories out,” said Rebecca S. Dresser, a medical ethicist
at Washington University in St. Louis who serves on the President’s
Council on Bioethics, which condemned the research last year. “We
don’t have an omniscient view of what’s best for the world.”

Some fear anything designed for those severely disabled by psychic
damage will eventually end up being used far more casually — to,
perhaps, forget a bad date or a lousy day at work.

“You can easily imagine a scenario of ‘I was embarrassed at my boss’s
party last night, and I want to take something to forget it so I can
have more confidence when I go into the office tomorrow,’ ” said David
Magnus, co-director of Stanford University’s Center for Biomedical
Ethics. “It’s not hard to imagine that it will end up being used much
more broadly.”

So far, only a handful of small studies have been conducted in people
in the United States and France, most testing a drug called
propranolol, which blocks the action of stress hormones that etch
memories in the brain. The results suggest drugs may be able to
prevent traumatic memories from being stored with such disturbing
intensity in the first place, or perhaps deaden effects of old
memories if taken shortly after they have been reawakened. The results
have been promising enough that researchers are planning larger
studies in several countries, including the United States, Canada,
France and Israel, testing propranolol and other drugs, including the
active components of marijuana.

“You always have the ability to misuse science,” said Joseph E.
LeDoux, a New York University memory researcher planning one of the
studies. “But this isn’t going to be radical surgery on memory. All
we’d like to do is help people have better control of memories they
want or prevent intrusive memories from coming into their minds when
they don’t want them.”

The ability to manipulate memory has long been the stuff of science
fiction, inspiring fears of government mind control and films such as
the 1962 classic “The Manchurian Candidate.” No one is anywhere near
having the power to extract the memory of a love affair or implant
complex new memories, as depicted in “Eternal Sunshine” and a 2004
“Manchurian Candidate” remake.

But scientists have started taking the first tentative steps toward
developing treatments based on new insights into why emotionally
charged events — whether it be President John F. Kennedy’s
assassination, Sept. 11 or a first kiss — create such indelible

“Whatever is being learned at the time of emotional arousal is learned
much more strongly,” said James L. McGaugh of the University of
California at Irvine. McGaugh demonstrated that strong emotions —
fear, love, hate, panic — trigger stress hormones such as adrenalin
and cortisol, which activate a part of the brain called the amygdala,
creating unusually vivid, emotionally charged memories. “Any strong
emotion will have that effect. It could be winning a Nobel Prize. It
could be a very faint whisper in the ear, ‘I love you,’ at the right

Propranolol, widely used for heart patients, blocks the action of
stress hormones on the amygdala, which led researchers to start
testing whether it could prevent PTSD. The study Logue was in, along
with a similar one in France, found that people who took propranolol
immediately after a traffic accident or some other traumatic
experience had fewer physical symptoms of PTSD months later.

“I really think it helped,” said Logue, 35. “It helped not bring back
my earlier bout with post-traumatic stress and made it easier to cope
with this new incident. I look both ways before I cross a one-way
street now, but I’m not in a panic.”

So far, the research has suggested only that the emotional effects of
memories may be blunted, not that the memories themselves are erased.

“I think it’s an unfortunate misconception that it’s blotting out
memories,” said Charles R. Marmar of the San Francisco Veterans
Affairs Medical Center, who helped conduct the French study. “What it
does is help people manage the memories so they can tolerate them.”

But other researchers are trying to go further, possibly deadening or
even obliterating any effects of old memories.

“People had thought that once a memory was stored or consolidated it
stays that way. People thought, it’s there for life — it’s fixed,”
said Karim Nader, a neuroscientist at McGill University in Montreal.
“We showed that wasn’t the case.”

Laboratory rats trained to fear a tone completely lost that fear when
scientists injected into their brains a drug that blocked formation of
proteins necessary for memory storage while the animals were prompted
to reexperience fear and store the memory again.

“When you activate a memory, it comes back up in a dynamic state and
has to be restabilized using the same mechanisms that stored it in the
first place. You can interfere with that,” Nader said.

A small preliminary study being presented next week at a Society for
Neuroscience meeting in San Diego tested for the first time whether
propranolol can affect old memories in people.

“We have no idea whether it’s erasing memory or putting a fence around
the memory,” LeDoux said. “But from the point of view of the PTSD
patient, it doesn’t matter as long as the effects are gone.”

But some ethicists question this whole line of research.

“Our experiences and our memories in a lot of ways define us and
define who we are,” Magnus said. “And so that’s a scary step to go
down. We should be very careful about going down a path that could
lead to a serious alteration of the core essence of our identities.”

Beyond the personal impact, ethicists also worry about the societal

“Consider the case of a person who has suffered or witnessed
atrocities that occasion unbearable memories: for example, those with
firsthand experience of the Holocaust,” the President’s Council on
Bioethics wrote. “The life of that individual might well be served by
dulling such bitter memories, but such a humanitarian intervention, if
widely practiced, would seem deeply troubling: Would the community as
a whole — would the human race — be served by such a mass numbing of
this terrible but indispensable memory?”

The researchers acknowledge the prickly ethical questions but argue
that the research should go forward because of its potential to
alleviate suffering.

“I approach it from a medical standpoint — that PTSD is as much a
medical disorder as a broken leg,” Pitman said. “I don’t say they
don’t have legitimate concerns, but it’s hard to argue we shouldn’t
pursue this just because of ethical speculations.”

Psychiatrists at the University of California at San Diego are
finishing a follow-up pilot study on accident victims. Pitman and the
French team are starting bigger studies to confirm their initial
emergency room findings. And Nader and colleagues in Montreal, and
LeDoux and his colleagues in New York, are beginning studies in PTSD
patients who will take propranolol immediately after reliving their
traumatic memories to see if it can affect memory re-storage, known as
“reconsolidation.” Researchers at Hebrew University in Jerusalem are
planning a similar study involving the active ingredient in marijuana.

Marmar and Pitman are working on identifying those most prone to PTSD,
with the idea that they could receive propranolol immediately after a
terrorist attack or some other traumatizing disaster.

“If this is safe and effective, it’s one of the few tools we’d have in
the case of a mass disaster,” Marmar said. “What are you going to do
if there’s a dirty bomb? You’ll have widespread panic. Do you want
these poor people to be haunted by this searing memory?”


Entonox instead of Conscious Sedation


Do you think Entonox(50%Nitrous Oxide/50%Oxygen) is a good
alternative for people who do not want the side effects associated
with amnesia causing drugs used in conscious sedation especially in
non-surgical out-patient procedures? It`s been used at the Mayo Clinic
apparently with good results for procedures like colonoscopy.


The effects of anesthetic drugs on memory, cognition, and sedation
is an active and complex area of study. Although neuroscientists
believe that sedation and amnesia are separate processes, in reality
the drugs used in everyday clinical practice are usually both sedative
and “amnestic” agents. The benzodiazepines, like midazolam (Versed),
have prominent effects on memory acquisition and retention as well as
being useful sedatives. The inhalational agents (gases) have similar
effects on memory.

Amnesia during a surgical procedure is considered by most doctors
and patients to be a desirable state. In fact, “awareness” during
general anesthesia is a feared event. However a number of people,
including several who write in to this forum, seem to be concerned
about this, looking for ways to avoid amnesia and retain memory
acquisition during the procedure, while at the same time being
comfortably sedated. I am not sure that this is possible. Nitrous
oxide causes loss of consciousness at levels above 70% concentration.
Entonox (50% nitrous oxide, 50% oxygen) causes sedation, usually
without loss oc consciousness.

Does Entonox cause amnesia? The short answer is YES. In fact, a
very careful recent animal study, in a model that seems to correlate
well with the effects in humans, showed that nitrous oxide, compared
to the equivalent sedative dose of other gases (halothane, isoflurane,
desflurane) is the MOST potent amnestic drug in this class! The
effects of nitrous oxide on memory have been recognized since 1799,
described in Britain by Humphrey Davy! Propofol, often used for
patients undergoing colonoscopy, causes amnesia too.

Just about the only drugs commonly used in anesthesia that do not
affect memory are the opioids – drugs such as fentanyl, meperidine and
morphine. Unfortunately you get sedation only as a side-effect of
opioids, and you also get respiratory (breathing) depression.


Joseph E. LeDoux
Memory and Emotion

My lab’s research is aimed at understanding the biological mechanisms
of emotional memory. We are particularly interested in how the brain
learns and stores information about danger. Using classical fear
conditioning as way of inducing emotional memories in rats, we have
mapped the neural pathways by which sensory stimuli enter and flow
through the brain in the process of fear learning. This work
implicated specific circuits in within the amygdala as essential for
the formation of memories of the fear conditioning experience. It is
now clear that the same brain system underlies fear learning in and
humans. The detailed mechanisms of fear, which can only be uncovered
through animal studies, are thus applicable to understanding fear
processing in the human brain.

With the neural system mediating fear learning now understood in
considerable detail, we are pursuing the cellular and molecular
mechanisms involved. This is being done by performing studies in which
we compare the effects of pharmacological manipulations of the brain
on fear learning in behaving animals and on long-term potentiation in
vitro. Through such studies the neural plasticity underlying fear
conditioning has been shown to involve elevation of calcium in
amygdala cells through NMDA receptors and L-type voltage gated calcium
channels. The elevated calcium activates protein kinases, which
initiate gene expression and protein synthesis, leading to the
consolidation of the memory, and its reconsolidation after retrieval.

Some of the techniques we use to explore emotional memory in the brain
include brain lesions, neuroanatomical tract tracing at the light and
electron microscopic level, pharmacological and viral manipulation of
brain chemistry, single unit and field recordings of neural activity
in awake and anesthetized animals, whole cell recordings in in vitro
brain slices, and fMRI in healthy human volunteers and in patients
with fear/anxiety disorders.

Conceptual issues being explored include the following. Is the same
basic system that has been uncovered for the conditioning of reflexive
responses also apply to voluntary behavioral responses in dangerous
situations or do other networks become involved? How does the brain
regulate fear, as in extinction or other processes? Are other emotions
mediated by similar or different circuits? What are the mechanisms
through which conscious emotional feelings, as opposed to behavioral
or autonomic responses, come about?

E-mail: ledoux [at] cns [dot] nyu [dot] edu

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