A Drug to Cure Fear
nytimes.com
nytimes.com
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.
The idea that someone exposed to a traumatic event (e.g. rape, child abuse) could immediately given a single dose of a drug that would prevent a possible 30-40 years of painful PTSD is, honestly, pretty compelling.
I think it's important to note that a fear or anxiety reaction may not, as you say, keep us safe. When I'm calm and rational, I make better decisions than when I'm gripped by fear.
As an avid hiker and explorer, occasionally my fear of heights interferes with my enjoyment of my hobby. I try to push past it as much as possible, but when my heart is racing and my legs are shaking, a situation which would otherwise be safe can become dangerous.
Also, unlike you, I do have two friends who suffer from PTSD (it's common enough that one may be surprised to find that a friend one has known for years wrestles with PTSD in some aspect of life but doesn't advertise that fact). One of those friends has gotten off an elevator early because being in an enclosed situation with a stranger gave her a panic attack. Another called me on the phone nearly in tears because she had to stay late at work and walking across the deserted, dark carpark to her car was almost more than she could handle.
I think it would be great if a drug could help people like these two friends of mine go through life without feeling controlled by anxiety in situations like these. I also think it would be great if people like me whose day-to-day lives are unmarred by fear can do more things -- safely; the drug does not impair reason -- through this therapy. The tradeoffs are important to know (and as you say, the article does a great job exploring them), but to me this sounds really promising.
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.
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
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.
Name one instance of sensibility in retaining fear-response in this modern world.
If curiously approaching a deadly creature is what it takes to be labelled "pathological", I would gladly allow myself to be pathological if it means the ending of fear.
Yup, life is certainly way more fun without fear around.
> you can play with [that hungry, pissed-off tiger] all you want.
I can also choose to not play with it. That is the beauty of intelligently responding (free choice) instead of affectively responding (limited choice).
The point is that the fear-response tells you to not play with the tiger, you astounding idiot.
Last I checked, the fear-response "tells" more than not to play with the tiger. For example, it tells (via moral conditioning) not to kill or maim or wound (not to mention insult as you evidently are doing here) one's fellow humans - yet reading the daily news will confirm that such violence does happen on a regular basis (despite fear "telling" them not to do it). Therefore, is there something new you can contribute to aid human understanding?
I'm starting to wonder about your mental state, as well. You seem to be very focused on direct connections between emotion and full-on mental illness--all anger is violence, all fear is crippling phobia, all sadness is unending depression, at least to you. I can only guess at what led to these conclusions.
> I'm starting to wonder about your mental state, as well.
Your beating around the bush, via rephrasing that "you astounding idiot" insult, this time isn't going to change the fact that you'd rather go ad hominem than engage with rational discussion ... speaking of which, it may be apposite to point out that it was you who deemed human intelligence to be insufficient when it comes to such a simple act of not recklessly fooling around with dangerous creatures, to wit:
<quote> dawnbreez: The point is that the fear-response tells you to not play with the tiger, you astounding idiot. <endquote>
> You seem to be very focused on direct connections between emotion and full-on mental illness--all anger is violence, all fear is crippling phobia, all sadness is unending depression, at least to you. I can only guess at what led to these conclusions.
Guess and wonder what you will ... meanwhile the original query, asked 22 hours ago, is yet to be answered:
<quote> sridca: Name one instance of sensibility in retaining fear-response in this modern world. <endquote>
A large fire. An angry tiger. A busy street.
All of these are situations where a particular response--namely, distancing oneself from the threat--makes survival much more likely. Fear happens to produce that response, in a much faster way than higher-level cognitive processes, even in children who haven't got enough experience to reason about the danger.
Also, seriously, get a therapist. It's been shown in psychological studies that trying to suppress emotions (of any kind) tends to lead to depression.
Furthermore, fear in such instances more often than not introduces more harm than otherwise as it hampers clear thinking that is essential to successfully come out of those dangers. The list of accidents and deaths caused by human stampedes and crushes should surely give you a pause before you reach for the keyboard once again to defend the much-cherished fear and introduce ever more carefully crafted denigrations.
Lastly, there is a distinction between fear itself (the emotion/passion) and the reflex action, and that being without fear doesn't necessarily get rid of the reflex action which is indeed useful in avoiding danger, especially on those situations you mention. As for "children who haven't got enough experience to reason about the danger" - that is besides the point as this discussion is pertaining to adults.
> Also, seriously, get a therapist. It's been shown in psychological studies that trying to suppress emotions (of any kind) tends to lead to depression.
As suppression and repression (a hallmark of such practices as Vipassana and Stoicism, which HN is known to be fond of) are at much lower levels than normal in this body, your ill-informed and unsolicited suggestion to "get a therapist," stemming as it does from your "you astounding idiot" insult, is cast aside in the waste bin where it rightfully belongs.
Meanwhile here is an useful word for you:
<quote> projection |prəˈjekSH(ə)n| noun • the unconscious transfer of one's own desires or emotions to another person: we protect the self by a number of defense mechanisms, including repression and projection. <endquote>
Edit: Also, this book by a threat assessment specialist talks about problems faced by women in particular who have the fear response in mild form, but suppress it. His conclusion is that the emotional response can actually be a lot clearer and more accurate than the intellectual one in a dangerous situation and it is wise to listen to it. If that man chatting you up is making you nervous, it's a sign you ought to be careful.
http://www.amazon.co.uk/Gift-Fear-Survival-Signals-Violence/...
The lesson from the book is that fear is a second signal (in addition to reasoning) that may heighten perception of a dangerous situation and should not be ignored.
One example: a girl is being chatted up by a guy. He seems nice, says all the right things. Intellectually everything seems fine. But there's a feeling nagging at her that something isn't right. A feeling of fear.
Mr De Becker is saying that in all the cases he's examined, the women went on to ignore their fear - eg by the socially expected action of returning reciprocated trust. Someone tells you a bit of information, you return it. Someone reveals a bit more, you do the same. Ultimately, these women put themselves in danger by not listening to their fear.
Now I'm not sure what you mean by the difference between "no fear" and "ignored fear." Plainly they have ignored their fear. But if a situation seems off due to a feeling of fear, not having that feeling isn't going to help in any sense. Its a signal that is no longer available, so you lose one data point to make a decision. Decisions with less data tend to be less reliable.
It is one thing to regurgitate a widely believed aphorism, but an entirely another thing to justify it with facts.
Primordial instinctive fear is not required for the human species. Name one example where it is required (where an intelligent response is deemed insufficient).
1. Here is an example of reckless behavior associated with a lack of fear as it pertains to humans taking anti-fear drugs.
[1] http://news.nationalpost.com/news/there-was-no-fear-anymore-...
And then there are studies of animals changing their behavior to be more reckless. I am curious to see your thoughts on correlation of animal and human testing.
[2] https://med.stanford.edu/news/all-news/2011/03/scientists-di...
If one is going about life "without thinking or caring about the consequences of an action", that is more a sign of being unintelligent (quite often a case of native intelligence being hampered by such strong emotions as ideological feelings) than merely being fearless.
Animals (especially early primate ancestors of humans) do not have fully developed intelligence, so it not unsurprising that they unlike us require primitive emotions such as fear to survive as a species.
When one considers ill effects of fear, often stuff like PTSD and phobias come to mind. But normal people too are adversely affected by fear on a daily basis. As this documentary shows the masses are easily influenced (via fear) by propaganda/ public relations to make decisions that are not in their own best interest.
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
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.
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...
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.
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.
http://www.pokernewsdaily.com/poker-players-take-performance...
This drug is much more side effect free and can be used regularly so not exactly in a similar manner.
As you point out in another comment, MDMA actually increases norepinephrine levels, which I suppose would enhance the strength of the new associations.
As for neurotoxicity, limiting use to less than once a month is quite effective at reducing it, I've heard. This is probably not much of a problem for theraputic use, but if it needs to be administered more frequently, there's some evidence that taking an SSRI before taking MDMA will reduce toxicity (don't do this, you might risk seratonin syndrome). DXM too has been shown effective at reducing amphetamine toxicity, so it might also help (also don't do this). If MDMA is ever rescheduled to allow for research, though, these techniques might allow more frequent use in theraputic settings.
Meditation in a pill?! Where do I sign up?
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.