
A Drug to Cure Fear - sharp11
http://www.nytimes.com/2016/01/24/opinion/sunday/a-drug-to-cure-fear.html?_r=0
======
tokenadult
I feared that many participants here would react to this interesting article's
headline rather than to its content, and it appears that that fear is
warranted. But, seriously, this is a thoughtful article and well worth reading
for better understanding of debilitating phobias and how they are currently
treated. It is also good to read the whole fine article to see what the
medical doctor author has to say about the trade-offs of the proposed drug
treatment suggested as an addition to the currently standard exposure therapy.
I don't know anyone among my close friends who has a phobia as disabling as
those described in the article. There is a big difference between such phobias
and the everyday caution and avoidance of rash behavior that helps keep us all
safe.

AFTER EDIT, AFTER OTHER COMMENTS TO THE THREAD: I remember that back in the
1980s propranolol (a beta-blocker originally prescribed to prevent heart
disease) was investigated for anxiety conditions like stage fright. (The cases
of stage fright among performers I know best largely resolved as the
performers gain in performance competence from more coaching and practice and
reduced fear of performing by performing in public more often.) So this line
of research about propranolol has been going on for a long time.

~~~
spangry
This article seems a little inaccurate to me, or at least incomplete.

On phobias, it's not quite as simple as a 'fear memory', although certainly a
part of it when we're discussing 'conditioned fear' (e.g. PTSD). There's a
part of your brain called the amygdala that is implicated in modulation of
memory formation and emotional processing. It's part of the limbic system,
which is tied in to the body's autonomic nervous system. This controls your
'fight or flight' response, essentially a sudden release of adrenaline into
your system which causes 'anxiety symptoms': increased heart rate, increased
perspiration, butterflies in stomach (due to diversion of blood flow to large
muscles in your limbs).

The amygdala is sort of like a 'heuristic co-processor' that receives sensory
input earlier than other parts of the brain. If the input matches a heuristic,
the body's fight or flight response is activated. If the amygdala is
dysfunctional, is 'pre-programmed' with heuristics now considered maladaptive,
or you've had experiences that have 'programmed' inappropriate heuristics, it
will activate your fight or flight response in response to non-threatening
stimuli.

Drugs like propranolol, which I take daily for a panic disorder, antagonise
(i.e. block) beta-adrendergic receptors, blocking the action of adrenaline and
noradrenaline, which dampens the fight or flight response. This reduces or
eliminates panic/anxiety like symptoms, and alters how memories are encoded
while under its effects (however I'm not clear on whether this interferes with
memory formation, or whether it causes the memories to be encoded in a
different way).

The part I find most interesting is the 'pre-programmed maladaptive
heuristics' still present in our heuristic database. Evolution is a slow
process, and has not caught up to our rapidly changing context. For instance,
if you've ever given a public speech, you've probably experienced a 'fight-or-
flight' response. It's not because you've had some bad past experience with
public speaking that has conditioned a 'fear response'; it's because of a left
over heuristic in your amygdala that may have been adaptive a thousands of
years ago.

Humans used to live in small tribes or groups with maybe a dozen other humans,
and the only other humans they might have contact with in their life would be
when fighting other groups for resources. If you publicly humiliated yourself
in this context, it would have likely meant elimination from the gene pool or
possibly even death. In a modern context, where you're giving a speech to a
room full of people in another country, this isn't even mildly the case. But
evolution is a slow process, so many of us still experience a fight or flight
response anyway, which is maladaptive.

~~~
sridca
In your experience taking this drug, does propranolol have any effect on 'pre-
programmed maladaptive heuristics'?

~~~
spangry
I'm not 100% sure. I think so, possibly in the same way that exposure therapy
can be helpful.

On rare occasions when I've forgotten to take my propranolol dose, I think I
experienced less severe panic reactions to provoking stimuli compared to in
the past. This might be due to higher levels of 'exposure' when taking
propranolol without a concurrent onset of panic symptoms, leading to a partial
reversal of 'fear conditioning' (perhaps better characterised as 're-
conditioning'?)

In my case I've found it to be very effective at treating the symptoms of my
panic disorder, which are mostly physical/autonomic nervous system mediated. I
think beta-blockers wouldn't be as effective for anxiety disorders where the
symptoms are mostly 'mental' (e.g. catastrophic thinking, irrational anxious
beliefs etc.).

tl;dr - Propranolol is great for 'physical' anxiety, possibly not as effective
for 'mental' anxiety

~~~
taurath
Wonderful description - thank you very much. Sounds very promising as a
treatment for post-CBT resistant anxiety, which is a simple word for what I
have. I can feel a physical fear response coming on and a large drain in my
willpower resources based on very small stimuli that aren't cognatively fear-
inducing. Sounds like this could help calm my overactive fight or flight
system - its been on my list to try for a long while.

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dawnbreez
Title is misleading; article is about PTSD, phobias, and other mental
disorders, rather than fear.

~~~
return0
Phobias and PTSD are pathological fear conditions. The title is not
misleading.

~~~
lifeisstillgood
I agree with the OP - getting rid of fear is foolish. Most of us are fearful
of rattlesnakes.

This is about managing the memories of fearful situations. PTSD sufferers were
right to be fearful in the original case - it's just the repeating of that
fear in other situations is less helpful.

~~~
sridca
> getting rid of fear is foolish

Name one instance of sensibility in retaining fear-response in this modern
world.

~~~
lukas099
You need to cross a busy street. You could cross in the middle and get to your
destination faster, but your fear of getting hit impels you to go to the
crosswalk instead. That wasn't even hard.

~~~
sridca
Is that an excuse for a chipmunk crossing the road? Seriously, as a member of
intelligent species you don’t _need_ fear to inhibit yourself from doing such
a senseless and risky act of crossing in the middle of a busy street. A
rephrasing of Hanlon’s razor is appropriate here: “Never attribute to lack-of-
fear that which is adequately explained by stupidity.” Indeed, normal people
with fear intact perform such risky acts on a daily basis (i.e., despite being
fully capable of fear); I was raised in India, where busy streets with erratic
traffic patterns are usual, so I should know.

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sharp11
What I found fascinating here are the implications for the neurobiology of
memory. Here it is limited to highly emotional fear-based memories, but
nonetheless the idea that a memory gets rewritten immediately after recall, as
saving a file after edit, and that that is an opportunity to completely
redefine the memory, is quite striking.

~~~
xkcd-sucks
There's some evidence that recalling a memory makes it labile, and that
interrupting memory reconsolidation processes during this labile period can
'erase' them, much like not getting sleep after initially forming a memory can
prevent it from becoming permanent.

Emotional/fear associated memories are a really easy model to work with, and
are also the most clinically compelling application of memory extinction.

See Cristina alberini's work, and others, as well as reviews like
[http://www.nature.com/nrn/journal/v8/n4/abs/nrn2090.html](http://www.nature.com/nrn/journal/v8/n4/abs/nrn2090.html)

~~~
sharp11
Thank you for the incisive suggestions! This is remarkable stuff. Here's a
good one not behind a paywall:
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056265/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056265/)

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mcphilip
I've been using extended release propanelol daily for the past couple years as
part of the treatment for chronic mixed tension migraines. I'd been struggling
with migraines leaving half of my body feeling extreme muscular tension 2-3
times a week. I can't comment on beta blockers effectiveness in treating
anxiety, but it does seem to have a powerful effect on soothing the nervous
system without the damaging side effects of addiction and impaired memory when
I was taking Xanax or Valium.

~~~
sridca
> [using extended release propanelol daily for the past couple years] seem to
> have a powerful effect on soothing the nervous system

If you don't mind me asking could you comment on what effect this drug has
had, over the past couple years, on your fear-responses? Not talking about
phobias, but normal fear-responses.

~~~
mcphilip
I seem to have less nervous tics associated with stressful situations, but
anxiety related racing thoughts don't seem to have changed. E.G. Propanelol
doesn't seem to impact problems like laying in bed worrying about the upcoming
day

~~~
sridca
Thank you for the response.

Could the difference, in those two kinds of situations, be due to the
presence/lack of awareness of the _trigger_ of fear response?

To explain my thinking: it appears that you are normally aware of the fear-
triggers on those "stressful situations" (i.e., _what_ triggers the fear),
which awareness of trigger in combination with propanelol's inhibitiveness,
leads to you have less nervous tics than usual (and less fear-responses).
Whereas, it appears that on other kinds of situations, such as laying in bed
running through dispersed thoughts about the upcoming day, there is no well-
defined trigger (or so it seems) that can be pin-pointed in time, leading to
propanelol not being as effective, thus resulting in racing thoughts.

The original study[1] involved a 2-minute exposure prior to administration of
propanelol for it to be effective in eliminating the fear-conditioning. And
this 2-minute exposure implicitly includes awareness of the fear-trigger.

[1]
[http://www.biologicalpsychiatryjournal.com/article/S0006-322...](http://www.biologicalpsychiatryjournal.com/article/S0006-3223%2815%2900313-3/abstract?showall=true=)

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lifeisstillgood
tl;dr this is about phobias and anxiety not "fear" we seem to have Discovered
a drug that when a subject relieves the trigger emotion (sees a spider) the
drug inhibits the reconciliation of the memory into long term storage.
Something previously not thought possible

It clearly has some value for phobias, but it's big value might be in PTSD
treatment _but_ from family experience this is a big difficult area and silver
bullets are rare.

US and UK need to do much more for long term expensive treatment of the
veterans we have made - and if governments complain about the cost, we should
very loudly point out they can save money in the future by simply stopping
creating new veterans of wars.

~~~
sridca
I don't think your summary is accurate.

It is more than _relieving_ "the trigger emotion". According to the linked
study, there is an _ending_ of the conditioned fear-response itself:

"Disrupting reconsolidation of fear memory transformed avoidance behavior into
approach behavior in a virtual binary fashion—an effect that persisted at
least 1 year after treatment"

... which ending naturally segues into approaching.

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Mandatum
It's common practice amongst professional poker players/gamblers to use beta
blockers.

[http://www.pokernewsdaily.com/poker-players-take-
performance...](http://www.pokernewsdaily.com/poker-players-take-performance-
enhancing-substances-12074/)

------
kmicklas
Weren't they having good success in clinical trials using MDMA in a similar
manner?

~~~
Synaesthesia
Indeed, and MDMA really can help you in a transformative, psychological
manner, but it's not a drug which can be taken with regularity, and it can
have major side effects. It requires careful monitoring and therapeutic
assistance.

This drug is much more side effect free and can be used regularly so not
exactly in a similar manner.

~~~
kmicklas
Right, that's why this research is so exciting. I just found it interesting
because MDMA is a stimulant which probably has the opposite effects of beta
blockers. But I guess that is overridden by the serotonergic effects with
respect to anxiety.

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DenisM
[...] the arachnophobes who were exposed to the spider and given the drug were
able to touch the tarantula within days and, by three months, many felt
comfortable holding the spider with their bare hands [...]

Meditation in a pill?! Where do I sign up?

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davesque
Attention grabbing headline aside, a very interesting read. A good reminder
that there are viable treatment options for severe anxiety.

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marincounty
Interesting small study of 45 people. It seems like it could be investigated
quickly in the military today. Propanol is still used to treat high blood
pressure. Most doctors have switched their patents to metoprolol(longer half
life, and doesn't cross blood/brain barrier as easily), but propanol is still
an effective way to reduce high blood pressure. It also helps a bit with
anxiety-- maybe?

I know a bit about it because I have taken these drugs. I also had a nervous
breakdown with symptomology very similar to those that have PTSD.

I took propanol for 15 years. I didn't have any complaints with the drug. I
actually think beta blockers are healthy for patients high blood pressure, and
prone to anxiety. I said healthy--in my case I think they might be healthy. I
can't explain it, just have a feeling?

That said the fear title threw me; I call it anxiety. Ever since that
breakdown, I have never been the same. My fears were random. I was scared of
heights on one week, and was fine/better the following week. Some months I was
scared of being around people; other times I seeked out crowds of people.
There was no reason to my fears. My brain just went bezerk, and I didn't get
better for years. I'm still not the guy I used to be. Yes, I'm still
employable, but barely. I hide my problems pretty well, or I think I do? My
anxiety didn't affect my ability to learn new things--thank god!

When I was younger I had consistent fears, actually only public speaking. I
got through college with only one oral report, but it took a lot of planning.

After that breakdown, I was fearful almost everything. I felt like I reverted
back to being a child, or worse. I wasn't a fearful child. When I blew a
gasket, the world became difficult, and I was scared of it. There was no
rhyme, or reason to my fears. The stuff I was scared of before, like public
speaking, and a slight fear of snakes--completely vanished.

I guess what I'm trying to say is they still don't know much about
anxiety(o.k. Fear).

When I took propanol I developed new fears. Repeat--when I took a beta blocker
I developed new fears. My fears would come, and go away. They weren't
consistent. Yes, this is all antidotal, and I'm probally not the best subject;
I don't think I'm like you guys anymore, but who knows?

That said, I was hoping they would have found treatments for anxiety related
disorders by now. In my case, heterocyclic, and tricyclics dugs did nothing
for my anxiety. Addictive drugs, and alcohol are the only drugs that helped.

I hope a beta blocker will help those with PTSD, and guys who have been hit
with whatever hit me. I didn't have a bad childhood, or wasn't more nervous as
a child as the other kids. I just Blew a gasket in my twenties. If you are
reading this and are slightly dizzy, slightly anxious, just don't feel like
you did; you have my complete sympathy. All I can say is it gets better with
age. Most of you will be better a a few weeks. I have never met someone like
myself, but my doctor like to say, "All my patients are different." He's
right! That's why we need to study mental disorders more carefully.

Right now they treat us like cattle when they set up these studies. "Oh, you
have this, and this out of twenty symptoms. I'll put you in this category." No
wonder we have low efficacy treatments. And yes, I know it's expensive to do
quality studies.

Sorry, about rambling on. I just kinda tense up with new cures for anxiety. I
took so many drugs that didn't work. And the therapy--well give it a shot, I
guess. You will never quite know if you don't give it a test drive.

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newman314
Not being snarky but it would be nice to have a drug that cures the sort of
fear associated with FUD.

