
Ketamine’s effect bolsters a new theory of mental illness - pmcpinto
http://nautil.us/issue/31/stress/a-vaccine-for-depression
======
astazangasta
I have been depressed a significant fraction of my adult life. I am also a
biologist who abhors the medical description of this problem. I don't even
like the word 'mental illness'. This shit is not an illness, its a normal
response to a fucked up life! Can I get at least some acknowledgment of this
fact?

The sine qua non for me was an issue of Nature a few years back that focused
on depression, talked about how prevalent it is, how it is a 'drain on
productivity', etc. Included therein was a graph of the worst affected
populations, topping the list was Afghanistan. This passed without comment.
How about: 'hey, the cause of depression seems to be human misery, like war,
unemployment, alienation, etc.'

But you can't sell a fucking pill to cure war and alienation, so ...

~~~
slapshot
I am close to somebody who has been strongly affected by depression. She has,
in any material respect, a perfect life. She has food, clothes, a supportive
family, a great job, plenty of money, etc. There is nothing "wrong" with her
life.

But she suffers off-and-on depression. Not just "I feel bad" depression.
Crippling, "can't get out of bed" depression. Periodic suicidal ideation.
Occasional suicide attempts.

She knows she has depression. She talks about it. And she wants to be done
with it. She knows how she feels when her brain is "in balance" and how it
feels when she's depressed. One of these states is much more preferable to the
other.

She's tried drugs, ECT, talk therapy, etc. And, yes, she's tried ketamine.
Anything that will put her back to a state where she is able to get out of bed
and function, and reduce the odds of her killing herself when she's depressed.

I'm sure there are a lot of people who are depressed due to outside factors --
poverty, oppression, war, etc. But I can tell you quite certainly that there
are people who have "perfect" lives who find themselves clinically depressed.
And at least some of those people want to get back to a non-depressed state.
This research helps them.

TL;DR: Not all people are depressed because their life sucks, nor is
depression something that all people can "cure" by thinking harder or trying
harder. Some people have a brain imbalance and would like to fix it so they
can have a life. Literally.

~~~
spangry
I'm very much in this category of depression. I have what is unfortunately
termed 'melancholic depression'. I should note that I'm very sceptical of the
DSM 'disease model' of mental illness, and am glad to see psychiatry and
neuroscience beginning to converge. 'Discrete disease' is a poor abstraction
for most mental illnesses. A better term for my kind of depression would be
'endogenous depression' (i.e. depression that comes from within). I have an
objectively good life: I have a family that loves me, friends that care about
me, and a job that I enjoy with colleagues I respect.

Yet I still have episodes where I sometimes can't get out of bed, or can't
bring myself to leave the house. A couple of months ago I spent three days
just sitting (and occasionally sleeping) in a chair, not even getting up to
eat or shower. I just simply couldn't do it.

While it's true that people can experience temporary depressive episodes due
to 'exogenous' factors (e.g. the death of a loved one), it is very different
to 'endogenous' depression, and requires different types of treatment. While
talk therapy and time can be very helpful for people to work through difficult
and temporary 'adverse circumstances', it is of little help for
endogenous/biological depression.

No amount of 'talk therapy' can convince my pre-frontal cortex to operate
within 'normal' parameters or to get my brain to produce appropriate
quantities of neurotransmitters like serotonin, dopamine and noradrenaline.
I'm reasonably sure this is a chronic illness that I will never be rid of (as
I've learned from 15 years of failed treatment attempts). On the upside,
there's a good chance that there is some treatment out there, coupled with
sustained lifestyle changes, that will allow me to stave off the symptoms so
that I can live a relatively 'normal' life. In some ways it's similar to how
type 1 diabetics can survive and live normal lives with regular injections of
insulin.

~~~
Abraln
It does get pretty tiring explaining the difference between them. Mine is
definitely biologically based, although stress exacerbates it like it does
many other things like acne. My "eureka" moment came in high school (when
brain chemistry changes from puberty can cause such issues). I was at home
playing video games online with friends when I noticed my vision was blurry. I
went to the bathroom and saw tears streaming down my face, which baffled me as
my conscious thoughts were in no way sad/negative at the time. There was just
an underlying feeling of heartache. Over the next 4-5 years I worked with a
professional and finally managed to find a drug combo that balances me out. I
still get sad, but only for logical reasons, and only as much as I used to
before my symptoms developed. It has been a full year for me now without any
"episodes", something I had not thought possible previously. I just figured I
would share this in case someone else might benefit from reading it.

~~~
cpncrunch
A lot of the time with depression there is no logical "reason" for it, and no
negative thoughts at the time. For example:

\- running multiple ultramarathons with too little rest can cause depression,
even if you love it. \- working very hard in a job you like with too little
sleep for a long time can cause depression.

In both cases it's likely your brain it just telling you that you're pushing
too hard.

Some people -- like me -- find it easier to get into these mental overdrive
situations, and some people might be more likely to suffer depression from the
same stressors, but ultimately it seems to be the same factors at work.

------
DanBC
Ketamine is an exciting experimental approach for depression (especially with
suicidal thinking) and anhedonia.

[http://www.thelancet.com/journals/lanpsy/article/PIIS2215-03...](http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366\(15\)00392-2/fulltext)

Researchers seem to be using an infusion of 5 mg per kg of body weight. That
means you don't give a bunch of pills to a patient, which in itself helps a
bit to reduce risk.

There's a bit of a web-based discussion here:
[https://www.youtube.com/watch?v=5b6zrpd1trk](https://www.youtube.com/watch?v=5b6zrpd1trk)

~~~
bigbugbag
Is ketamine some sort of wonder-drug for depression?

Probably not, at least not according to most of the research conducted on it
so far. Like many treatments for depression — including psychotherapy — it
appears to change the way the brain processes certain information and effects
the connections between neurons. But it’s not clear how long these changes
last, or whether chronic ketamine treatment would be needed, similar to a
diabetic taking insulin.

[http://psychcentral.com/blog/archives/2012/12/01/should-
you-...](http://psychcentral.com/blog/archives/2012/12/01/should-you-try-
ketamine-for-depression/)

Ketamine has been tested in treatment-resistant bipolar disorder, major
depressive disorder, and people in a suicidal crisis in emergency rooms.[26]
Benefit is often of a short duration.[27] The quality of the evidence
supporting benefit is generally low.[27]

The drug is given by a single intravenous infusion at doses less than those
used in anesthesia, and preliminary data indicate it produces a rapid (within
2 hours) and relatively sustained (about 1–2 weeks long) reduction in symptoms
in some people.

[https://en.wikipedia.org/wiki/Ketamine#Depression](https://en.wikipedia.org/wiki/Ketamine#Depression)

Ketamine may have its use for treatment resistant depression and dealing with
emergencies caused by suicidal bouts because it can make depression symptoms
disappear for few days, but this is only temporary as better ketamine based
drugs are developed.

~~~
kruhft
Most (illegal) drugs are a wonder-drug for depression.

At least until they wear off.

------
altonzheng
It doesn't surprise me one bit that we have a very poor understanding of how
to treat depression. I think we often have a reductionist view of it. The fact
that a whole constellation of causes is referred to as just 'depression' bugs
me.

~~~
johndevor
Well put. I find it troubling that we spend so much on research when it's a
very -- dare I say -- wholistic problem with a _myriad_ number of causes, some
subtle and some more obvious. We may never understand fully the depth of the
problem and shining a light on things like certain drugs, while helpful as
short-term fixes for certain individuals, may just be masking those other
issues.

------
LesZedCB
I'm excited for there to be alternatives to SSRIs. I've never been diagnosed
with depression, but my partner has and takes an SSRI. It certainly seemed to
have a generally positive affect (totally subjectively), and relatively few
negative side affects. That being said, having to take it every day sucks, and
when she runs out, having forgotten to get it refilled, the mood affects are
pretty terrible for us both. Hopefully this branch of research will continue
and develop into a more positive alternative.

~~~
bigbugbag
I recently read that the theory behind serotonin reuptake inhibitors might
actually be wrong and possibly cause more harm than good. The actual
neurotransmitter mechanism behind depression would be dopamine.

I'm sorry that I can't recall the source, but you should look into this.

~~~
meowface
There is no consensus on what the root causes of major depression are; there
are probably many causes. Dopamine can definitely affect happiness, but giving
a chronically depressed patient L-DOPA once per day generally won't treat
their depression for very long.

On that same note, people with ADHD are often missing dopamine in many parts
of the brain, but ADHD isn't necessarily correlated strongly with depression.
And quick dopamine-releasing drugs like amphetamine
(Adderall/Dexedrine/Vyvanse), or dopamine reuptake inhibitors like
methylphenidate (Ritalin/Concerta), tend not to be great treatments for
depression, either. They can be a short term treatment by giving you a
euphoric high the first few times you take them, or if you take big doses, but
that's not a good long term treatment strategy.

~~~
MrBra
And then are better results achievable with SSRIs instead?

~~~
meowface
Compared to taking amphetamine? On average, yes, of course.

SSRIs don't work very well for many people, but they do work well for many
other people.

------
c3534l
Personal experience here. My depression has been an unending struggle since my
tweens. I've been on every medication, spent fortunes in therapy. I also
abused dissociatives like Ketamine. Ketamine's antidepressant effects seemed
very real after the initial high and it was qualitatively different from
SSRIs. SSRIs seemed _more_ like a drug than Ketamine which felt more like
relief (again, for the days following the high - the actual high was, you
know, psychedelic and stuff). I think for some people research into this area
would be a real boon. Not everyone responds well to traditional treatments.
I'm not sure what's different about my brain that makes even high doses of
SSRIs ineffective or even unpleasant, but I don't think we understand all that
well how depression actually works at all, other than SSRIs and similar seem
to kind of work.

If you think depression is about just increasing serotonin in the brain, let
me point out that "serotonin syndrome" is a very real risk of using
antidepressants. It's essentially an overdose on serotonin. It's clear that
messing with serotonin in the brain, you can give a sort of neurochemcial
nudge that can help you overcome depression, but happiness is not itself the
amount of serotonin in your system.

Either way, I quit using drugs and alcohol many years ago and regular exercise
with exercise, tons of CBT, and lots of vigilance has helped the best. But it
would be nice to have a drug on the market that would make keeping depression
at bay so effortful and so much hard, consistent work.

Anecdote isn't worth much in medicine, but there really is something special
about Ketamine.

~~~
wdmeldon
I've responded fairly well to SSRIs, but I think it might be significantly
influenced by how bad I had gotten without them. The side-effects I endure are
objectively terrible (I hit almost all of the common ones and most of the
uncommon ones) but the change for me has been night and day. I've always
wanted to try Ketamine because of what I've heard about its effects on
depression, but I've never gotten the opportunity. I do hope this starts a
broader conversation about people like us.

------
onga5v
I see several people in this thread welcoming the fact that there is "finally
an alternative to SSRIs". I don't want to discuss whether Ketamine is or is
not a good alternative to SSRIs -- instead, I'd like to point out that there
are already a great number of alternatives to SSRIs.

For one, there are tricyclics (TCAs), which were the first antidepressants on
the market, and generally are not prescribed nowadays. Another category of
older antidepressants includes MAOIs, which were the first mass-market
antidepressants. These are also not generally prescribed nowadays due to
interactions with common types of food, although modern MAOIs such as
moclobemide [1] require far less diatary restrictions than the older MAOIs
did. The final major category I'll mention are SNRIs, which along with SSRIs
are the most commonly prescribed first-line antidepressants.

Apart from these major categories, there are a bunch of atypical
antidepressants on the market. There's bupropion, which I personally take, and
which has far less side effects than SSRIs and SNRIs but may not be as
effective for all patients. There's St. John's wort, which is available off
prescription in many countries. There's lithium, which has recently gained
popularity. In total, I would guess there are about a hundred different types
of antidepressants in production around the world (including old Soviet
concoctions that are not available in the West due to the huge price of
getting just one of them to market).

If you're unhappy with the side effects of SSRIs, I would encourage you to
look up other types of antidepressants, as they have very widely varying side
effects, and most atypicals have far _fewer_ common side effects than SSRIs
and SNRIs do. In particular, I would like to point out that bupropion usually
_increases_ sex drive instead of lowering it like SNRIs and SSRIs tend to do.

[1]:
[https://en.wikipedia.org/wiki/Moclobemide](https://en.wikipedia.org/wiki/Moclobemide)

~~~
DanBC
Depression is a major risk factor in suicide.

Tricyclics are frequently used in attempted and completed suicide.

Being more careful with prescribing tricyclics to people with suicidal
ideation would probably reduce the numbers of attempted and completed suicide.

------
throwaway439853
A warning to those considering experimenting with Ketamine. It may help
alleviate depression, but the flip side is can reduce the 'technical ability'
part of the brain to such an extent that you will no longer be able to code.

This will wear off in a few days, but it is not side-effect free drug - there
are still many unknowns.

~~~
meowface
Ketamine has a lot of mechanisms of action, but one of its big ones is that
it's a major NMDA receptor antagonist. This prevents glutamate from affecting
cells very well. A major decrease in glutamic activity may reduce depression,
but it can effectively drop your IQ by quite a lot. People generally report
feeling "very stupid" and "brain foggy" after taking strong NMDA antagonists.

I don't know if ketamine has high risk of causing general intelligence
reduction in the long term, but there are reports of that from people who
abuse the drug in recreational doses for a long period of time. So, it's
definitely something to be wary about.

------
siyer
On the mechanistic side of things,
[http://www.pnas.org/content/112/26/8106.short](http://www.pnas.org/content/112/26/8106.short)
is one of the more interesting papers to come out recently on ketamine's mode
of action.

------
drharvey
I think some of these posts might be inadvertently debating _dualism_ , "the
philosophical position that mental phenomena are non-physical." You're arguing
whether depression is caused by emotions and thoughts vs biology (mind vs
brain), when Neuroscience doesn't make a distinction. Emotions and thoughts
_are_ biology - serotonin and glutamate and neurons are not considered to be
separate from behavior, they are how behavior is encoded. In Neuroscience, the
mind is usually considered an emergent property of the brain.

It's like arguing that a bug is a problem with the UI, not the code...

[https://en.wikipedia.org/wiki/Dualism_(philosophy_of_mind)](https://en.wikipedia.org/wiki/Dualism_\(philosophy_of_mind\))

------
atomical
There are other drugs in the pipeline that have a faster onset of action than
what is currently available, including GLYX-13 and NSI-189. I have taken
NSI-189 and I can confirm that it works fast.

~~~
rbinv
How did you happen to take NSI-189? Were you part of the phase 1 trial?

~~~
comrh
Google suggests you can buy it as a research chemical (here have this random
white power...).

~~~
cypherpunks01
Not sure about above, but I used to (~1yr ago) buy NSI-189 from THT.CO and
other sources compiled/tested by the reddit r/nootropics community. Apparently
since then, Neuralstem has sent cease & desist letters to all of the companies
selling it, and sources have since been spotty. Also I know that some group
buys/syntheses have been coordinated on Longecity.

~~~
comrh
Did it work for you? Any side effects?

~~~
cypherpunks01
I used it for a couple months at the oral dose that the early phase NIH
clinical trial found to be effective. I did feel like i got a positive benefit
from it with no side effects, though didn't do any extensive blind testing
myself so it's purely anecdotal. I found it to lift some constant anxieties a
bit, and help guide my overall outlook on life more positively.

That said, I did find ketamine to be an extremely effective anti depressant
with the primary effects being immediately noticeable and positive. I
currently re-dose on ketamine every couple months and take bupropion daily--
between all of these I've been able to greatly reduce fairly severe depression
that went untreated and worsened over a 10+ yr period.

~~~
nether
Might I ask how you self-administer your ketamine? And where do you acquire
it? You can email me at nodus3 at google mail.

~~~
cypherpunks01
Unfortunately I have to administer it, um, insufflated. Which I am really not
a fan of but it's the only route that I've found workable. Wasn't able to
administer sufficient quantity for intranasal spray, and oral is out as it
tastes absolutely horrid. Sources, nothing that you couldn't find off reddit.

------
openasocket
I'm skeptical of the long term benefits of Ketamine. It seems odd to give an
anesthetic, a depressant, to someone with depression. They claim it reduces
the risk of suicide and works quickly, but is that due to a curative
neurological effect or is it just because you've given them a sedative? Not to
mention the side effects: memory loss, delusions, psychosis, even
schizophrenia-like symptoms. Sure, these tend to happen at higher doses, but
the long term effects of low doses have not been studied thoroughly.

~~~
cjhveal
While a moderately high dosage of Ketamine does have anesthetic effects,
through it's antagonism of the NMDA receptor at dosages (which suppresses
activity required for signals to cross spine/brain), inhibition of nitric
oxide production, and weak agonism of opioid receptors, it also has a slew of
other interactions at various affinities.

Ketamine inhibits the reuptake of all three major monoamines. Thus it mimics
to some degree both the mechanisms of action of SNRIs
(serotonin/norepinephrine reuptake inhibitor) such as venlafaxine (effexor),
used to treat depression/anxiety and DNRIs (dopamine/norepinephrine) such as
bupropion (wellbutrin)/methylphenidate (ritalin), which are used to treat
depression/ADHD. Ketamine also impacts the acetylcholine receptors, which have
been linked to anti-depressant effects, and the less-well-researched sigma
receptor.

While the above interactions may contribute to the reported anti-depressant
effects, some of those same interactions make it undesirable as a medication.
Dopamine reuptake inhibitors and mu-opioid antagonists are notoriously abused
for their euphoric effects. However, those effects are contrasted with
psychotomimetic effects of ketamine's interaction with NMDA, kappa-opioid,
muscarinic acetylcholine, and simga receptors.

Ultimately, it's incorrect to simply categorize ketamine as a depressant or a
sedative. The body is an exceptionally complex chemical network, and you're
right to be skeptical. But I think it's important that we not dismiss the
positive reported effects of the drug because of the side effects that occur
at various points on the dose-response curve. We may find out that by
controlling dosage we can tune a beneficial level of antidepressant response
without psychosis, dissociation, or amnesic effects due to hormetic effects.
Or it might work exceptionally well for some otherwise treatment-resistant
cases. Even if not, we'll be able to use that data to tweak the binding
affinities to investigate drugs that have a better therapeutic use.

------
walmartian
I am surprised at the number of anecdotal experiences people are using here to
describe depression as a non-disorder. It's unbelievable that people cannot
distinguish between depression caused by environment factors and depression
caused by physiological differences.

------
lilcarlyung
What with the pro-drug posts here all the time. I'm guessing that most of the
HN audience is American. Is it common among techies in the U.S. to experiment
with psychoactive drugs, hence the interest and knowledege? Please, do not
mention Steve Jobs acid experiences.

------
lilcarlyung
What with the pro-drug posts here all the time. I'm guessing that most of the
HN audience is American. Is it common among techies in the U.S. to experiment
with psychoactive drugs, hence the interest and knowledge? Please, do not
mention Steve Jobs acid experiences.

~~~
Igglyboo
It is very common in my experience. Google, Microsoft, Apple, and every tech
company I've ever applied to (even small midwestern shops) do not drug test.

The FBI has a problem hiring good security experts because of their strict
drug testing policies.

[http://www.wsj.com/articles/SB100014240527023044227045795743...](http://www.wsj.com/articles/SB10001424052702304422704579574374286817550)

~~~
kaybe
Are employer drugtests common in the US, even for non-critical work?

~~~
rconti
The crappier the job, the more likely that it drug tests.

And, of course, safety-reliant jobs like truck drivers, warehouse staff, etc.

~~~
chillwaves
This. The only jobs I ever got tested for where the ones not worth having.

------
NickHaflinger
'Either a green unicorn just raced across the lab, or I accidentally took some
LSD.', Dr. Walter Bishop

------
tcj_phx
Having observed my girlfriend's "mental illness" [1], I can say, with
confidence, that Psychiatry is the problem with America's approach to mental
health. As Dr. McHugh observes [2], conventional Psychiatrists "diagnose"
their patients' symptoms, and treat the diagnosis without much concern about
the actual causes thereof.

One of my girlfriend's problems is that she has low energy levels - certainly
caused by previous stimulant use, and her body's inability to efficiently
produce energy (ATP) by burning glucose/fructose. Before she met me, she
treated this symptom (low cellular energy levels) by drinking alcohol
regularly. Alcohol is an energy-rich molecule, the metabolites of which are
easily burned by the insulin-resistant brain cells which have become insulin-
resistant. She started drinking a month after starting methadone, a drug which
is known to cause sugar cravings.

Deciding to quit methadone was easy once she realized that she hated it. But
when she lost access to alcohol, her brain went into a sort of 'survival'
mode, which led to her being taken to the hospital [1]...

The causes behind my girlfriend's condition are fairly obvious to me, having
observed her for months now. But the hospital staff had no context for why
their patient was acting the way she was, so they just treated her symptoms.
The doctors at the inpatient facilities she's been at don't care about
physiology either, they just reach into the pharmacy and try new drugs with
the proper label ("anti-depressant", "anti-psychotic", "mood-stabilizer" \-
these are marketing terms, imho). She's still exhausted, but at least they're
giving her the coconut oil capsules I dropped.

There is another way. My grandfather, a dentist with an interest in hypnosis,
didn't remember much of his one class with psychiatrist Milton Erickson, M.D.,
except that Dr. Erickson was always "bitching" \- about having to go to
medical school, having to learn anatomy, physiology and pharmacology, etc etc,
when all he really wanted to do was hypnosis (this was Dr. Erickson's method
of conversational hypnosis, applied to an audience of medical professionals).
The Erickson Foundation released a really cool documentary [3] last year...

[1]
[https://news.ycombinator.com/item?id=10639657](https://news.ycombinator.com/item?id=10639657)
[2] [https://www.commentarymagazine.com/articles/how-
psychiatry-l...](https://www.commentarymagazine.com/articles/how-psychiatry-
lost-its-way/) [3]
[http://wizardofthedesertfilm.com/](http://wizardofthedesertfilm.com/)

~~~
chillingeffect
Yes, it's shame, but medicine has a mainstream, industrial aspect as well as
it has a high-quality, focused aspect. I hope it gets well for the two of you.
Remember good old exercise, nutrition, sunlight and everything else. Success
creates new realities!

And most especially, thank you for pointing out that amazing documentary on
Erickson! I've read the NLP foundation's first two books on him and they're
incredible. I just picked up a copy of the DVD.

BTW, have you tried any NLP of the therapy variety with your gf? How surprised
would you be to find it working as well as you can imagine? ;)

~~~
tcj_phx
The documentary is really cool - I heard about the premiere on NPR one
morning, and went that afternoon.

> BTW, have you tried any NLP of the therapy variety with your gf? How
> surprised would you be to find it working as well as you can imagine? ;)

She's come a long way since I met her. I recently found a copy of /UnHypnosis/
at a local thrift store, which she's going through:
[http://stevetaubman.com/unhypnosis/](http://stevetaubman.com/unhypnosis/) \-
seems like it's basically applied NLP. I have most of the old NLP books, and
some of the newer ones too.

 _My Voice Will Go With You_ \-
[https://books.google.com/books?id=AEo9acmCFNUC](https://books.google.com/books?id=AEo9acmCFNUC)

------
escape_goat
The full article title is "A Vaccine for Depression?: Ketamine's effect
holsters a new theory of mental illness." I have mixed feelings about posts
being required to suffer from the title, as this is often an editorial rather
than an authorial decision, but the submerged gist of the article, the novel
content, is indeed the suggestion that Ketamine could be used as a "vaccine"
for post-traumatic stress disorder.

A few words about new theories. All new theories that can garner such
enthusiasm for their presentation are invariably bolstered by something. No-
one writes magazine articles about ambiguous signals from an exciting new
theory. If the evidence presented is not in some way definitive, then it
should be viewed as a precondition for the propagation of the theory, not
evidence in favour of it. Few of us are expert judges of neurological
theories, and we are not able to tell if there is anything substantial beyond
the _feeling_ that we experience that something valuable has been learned.

I know that the effects of Ketamine in treating serious episodic depression
are very exciting. I feel that I understand enough to suggest that
neuroplasticity is not an especially 'new' theory, or a 'theory' by itself.
The neuroplastic response is real, well documented, and undisputed. What _is_
a theory, and had not been established as fact, the last time I discussed it
with someone, is that idea that the neuroplastic response is the central
intermediary between the physical effect of the drug and the clinical effect
of the drug. It occurs, but it had not been established that it is causal.

The central suggestion regarding the 'vaccine' effect seemed to be buried a
bit in the article (unless I missed something in skimming), but it is the
actual new information, which is interesting and heartening. Soldiers coming
to a forward operating medical station with severe burns were treated with
Ketamine rather than another anaesthetic because of its relative safety. They
subsequently developed PTSD half as often as all soldiers and civilians
treated for less or equally severe burns with other anaesthetics.

On the basis of the theory that PTSD and depression emerge an erosion of
neurosynaptic connections, the leap is made from there to the idea that
Ketamine might perhaps serve as a true 'vaccine' when people were going into
high-stress situations. From my relatively uneducated perspective, this seems
a bit irresponsible in two separate ways.

Firstly, the evidence is that the soldiers were 'vaccinated' against
psychological disturbances associated with extreme trauma... after the initial
extreme trauma had occurred. There is evidence from studies with mice that a
Ketamine treatment changes their response to stressors in a way that seems
both dramatic and positive. Ketamine is a common recreational drug. If we
should be excited about the prospect of this response being replicated in
humans, then why is there not already ample evidence that this response is
replicated in humans?

Secondly, there is absolutely no reason that we should conclude that the
effect of the Ketamine on the burn victims has anything to do with
neuroplastic response. Ketamine is _an anesthetic_. It limits pain, which is
traumatic. Anesthetics operate in different ways. Ketamine seems to inhibit
the transmission of pain signals in the spinal cord. This prevents them from
reaching the limbic system. Other forms of anesthesia may not. Ketamine is,
infamously, _an amnesic and a dissociative_. Stress disorders require memory
formation. Ketamine prevents memory formation. Other forms of anesthesia may
not. And so on. In the context of the surfeit of plausible explanations for
this effect, to suggest that the effect is particular evidence supporting a
theory that PTSD is cured by neuroplastic regeneration of synaptic connections
is not particularly responsible. It might not be terrible journalism, but it
is definitely bad science, and almost certainly not something that was
presented as science to the journalist.

~~~
drharvey
"The central suggestion regarding the 'vaccine' effect seemed to be buried a
bit in the article (unless I missed something in skimming), but it is the
actual new information, which is interesting and heartening."

You are correct, this is a new finding. It does not, however, come from the
study looking at soldiers. In that study, ketamine was actually given after
stress (not as a 'vaccine'). Those researchers also failed to replicate that
effect when they looked a larger group of soldiers. The first study was done
in 2008 and the second one was done in 2014. Believe me, if they had found a
protective effect in humans 7 years ago, you would have heard about it by now.

The research that actually shows the ketamine might be a 'vaccine' has all
come out this year (2015). And, so far, _it 's all only in mice._ The
scientific publication referred to in the Nautilus article is "Ketamine as a
Prophylactic Against Stress-Induced Depressive-Like Behavior":
[http://www.biologicalpsychiatryjournal.com/article/S0006-322...](http://www.biologicalpsychiatryjournal.com/article/S0006-3223\(15\)00360-1/abstract).
At least two other research teams at other universities (FSU & UC-Boulder)
have independently also found similar effects, but none of that is published
yet (though it was presented this year at the national Society for
Neuroscience conference). In other words: yes, it's new.

Additionally, neuroscientists at Mt. Sinai, the NIMH, and UC-Boulder (among
others) have found that bacteria and immune cells might also be used to
'vaccinate' against stress. Again, most of that research--though not all of it
--is still not published yet, and has only been presented at conferences so
far.

~~~
drharvey
\-- As an aside, it's a textbook example of multiple discovery/simultaneous
invention:
[https://en.wikipedia.org/wiki/Multiple_discovery](https://en.wikipedia.org/wiki/Multiple_discovery)
\--

I also completely agree that the sedative-level dose given to soldiers after
stress might have worked by blocking traumatic memory formation. It has
already been established that blocking or "erasing" stress memories may
prevent PTSD (here's just one example:
[http://www.medscape.com/viewarticle/819452](http://www.medscape.com/viewarticle/819452)).

In the studies in mice, ketamine was no longer in the animals' systems by the
time they were stressed. So they were not sedated. And the researchers tested
memory formation to confirm it was not affected. Thus, it seems that
ketamine's protective effect in mice _isn 't_ just because memory is
disrupted. That said, it is always possible they missed something.

From what I can find, it doesn't seem like anyone has even _looked_ yet to see
how this ketamine-vaccine strategy effects neuroplasticity. At this stage,
it's probably best to consider the post-stress effect of ketamine in soldiers
(1), the pre-stress protection in mice (2), and the neuroplastic effects of
ketamine (3) as three separate things.

------
spotman
This makes me nervous. Ketamine has major issues with bladder damage when
taken repetitively.

Possibly with a low enough dosage this would be manageable, but speaking from
experience from watching people that have been on the wrong end of the stick
with this one. it can do some really serious long term damage in that
department.

~~~
civilian
The depression-fixing threshold is smaller that most recreational use, and it
would only be once every two weeks. That side effect trivial to rule it out.
Educate yourself and stop being a pawn of the drug war.

I watched two documentaries in short succession: Drugs Inc's episode on
Ketamine, and a few episodes of Combat Medic. Drug Incs' played up the bladder
damage, the persistant dissociative feeling with abusers, and how it's just
_horse_ and _cat_ tranquilizer that's no longer used on humans.

Combat Medic non-challantly showed medics giving ketamine to US soldiers in
Afghanistan, because it's an effective and immediate anesthetic. They were
subtle about it, but it was there. Our the dissonance in the media about drugs
like this is indicative of fear mongering and propaganda.

~~~
tptacek
This would have been a better comment without the "educate yourself and stop
being a pawn of the drug war." Please remain civil.

