
Ketamine and Depression: A Breakthrough? - DiabloD3
http://blogs.discovermagazine.com/neuroskeptic/2016/05/07/ketamine-depression-breakthrough/
======
cubano
Back in my raver days, when this was still doable, one of my boys started
driving to Mexico and buying K there and bringing it back in cheap water
bottles to get by the border DEA.

One day he shows up at the club and says, "hey, check out my car trunk" and
was like "uhhh ok that's kinda weird" but I went out and presto, there was 4
one-liter water bottles full of ketamine.

Thats a shitload of K, considering a vial is 50ml and costs around $100. So I
started selling it for him, and man did it go fast. Almost everyone loved it,
including myself. Oddly enough, even people who did too much the first time
and had a really wack k-hole experience would try it again.

It was rather miraculous to me, and surely did some sort of transformative
rearranging of my brain while I was dosing it. I think what I remember best
was that it became my self-described "drug of choice", which, honestly, was a
pretty huge achievement in my life.

I liked it because it removed my desire to do other, much darker and
destructive drugs somehow, and it wasn't just a matter of typical
substitution, but something much more fundamental, so studies like this are
very unsurprising to me, and I really hope these researchers keep at it.

~~~
DanBC
Recreational use is large doses.

The studies I've seen for medical psychiatric use were about 5 mg per kg of
body weight.

~~~
lumpypua
0.5 mg/kg. 5 mg/kg will be a hell of a ride.

~~~
DanBC
Ah, yes. Max dose used in this study was 80 mg.
[http://www.oxfordhealth.nhs.uk/news/first-uk-study-of-
ketami...](http://www.oxfordhealth.nhs.uk/news/first-uk-study-of-ketamine-for-
people-with-severe-depression/)

[http://www.oxfordhealth.nhs.uk/service_description/ketamine-...](http://www.oxfordhealth.nhs.uk/service_description/ketamine-
clinic-for-depression/)

I don't know where I got 5 mg/kg from.

------
tshtf
This article misses the second part of the study, as elucidated by Derek Lowe
here
[http://blogs.sciencemag.org/pipeline/archives/2016/05/06/it-...](http://blogs.sciencemag.org/pipeline/archives/2016/05/06/it-
isnt-ketamine):

 _In a rather elegant experiment, the authors deuterated ketamine at the
methylene next to its carbonyl group, and showed that this compound (as
expected) displayed the same NMDA activity as the parent compound – but that
it was far slower at producing the metabolite, and had no activity in the
antidepressant screens._

~~~
simonster
The "antidepressant screens" referred to here are in mice, not humans. The
Nature paper is an amazing set of experiments that provide very compelling
evidence that (2R,6R)-HNK is responsible for the antidepressant effects of
ketamine in mouse models of depression, but Neuroskeptic is right that it's
not clear that (2R,6R)-HNK is also responsible for the antidepressant effects
of ketamine in humans. We know that mouse models of depression are not
necessarily great; SSRIs seem to be more effective in mouse models than they
are in humans.

~~~
zcarter
Per Neuroskeptic's due diligence, human effects don't look promising.

>>> This is a citation to one of their own papers, from 2012. There’s just one
problem – as far as I can see that paper didn’t find the correlation that
Zanos et al. say it did.

------
mabbo
Has there been any increase in illegal use of ketamine since research on its
use as a depression treatment first started being published?

Having dealt with those issues for many years, and recovered, I can see a real
danger in those who suffer from depression saying "K will fix this? I'll try
anything". I would have.

I'm a firm believer in drug law reform and decriminalization of drug use but
from what I've seen of it Ketamine isn't something you want people taking out
of desperation, with little knowledge of how crazy it just might get. Or
worse, developing a dependency on. It's pretty serious stuff.

~~~
lumpypua
I've used ketamine to self-medicate depression. I decided to out of
desperation. It was extremely effective for me.

Several provisos for potential users:

\- Read the papers. If you can't read the papers on K as a depression
treatment and come up with your own dosing protocol, you probably shouldn't
try K.

\- Probably don't try it if you have an addictive personality.

\- Make sure you're aware of potential side effects such as memory and urinary
issues. That said, doses used in treatment protocols shouldn't come anywhere
near that.

I waited forever to just get some goddamn K and treat myself, because
everybody on the internet is like "don't do it, you'll fuck yourself up". I'm
smart and do my homework, and I regret not trusting myself and suffering for
longer than needed.

~~~
pmiller2
I wouldn't even know where to get it, and I don't want to get caught and go to
jail, due to our stupid drug laws. :(

~~~
a2m
it's a schedule 3 drug, so a misdemeanor. i don't think you'd get any jail
time if you got caught (assuming you're a first time offender in CA). if
you're that desperate and you've read up on it and consider it a viable escape
from that hell i know too well, give it a shot. (i have not used it).

shame i had to make a new account to speak freely about this.

~~~
cubano
No..in fact hell no.

Ketamine is schedule 1 or 2 I believe everywhere in the US, so that is
definitely a felony.

~~~
nefitty
It's Schedule III:
[https://en.m.wikipedia.org/wiki/Ketamine#Legal_status](https://en.m.wikipedia.org/wiki/Ketamine#Legal_status)

"Ketamine is a "core" medicine in the World Health Organization's Essential
Drugs List, a list of minimum medical needs for a basic healthcare system."

~~~
cubano
"...flunitrazepam, ketamine, or any other Schedule I or Schedule II CDS is a
Class 6 felony."

[http://www.criminaldefenselawyer.com/resources/criminal-
defe...](http://www.criminaldefenselawyer.com/resources/criminal-defense/drug-
charges/possession-controlled-substance-colorado)

~~~
nefitty
Well, that's wrong.

"Schedule III drugs, substances, or chemicals are defined as drugs with a
moderate to low potential for physical and psychological dependence. Schedule
III drugs abuse potential is less than Schedule I and Schedule II drugs but
more than Schedule IV. Some examples of Schedule III drugs are:

Products containing less than 90 milligrams of codeine per dosage unit
(Tylenol with codeine), _ketamine_ , anabolic steroids, testosterone"

[http://www.dea.gov/druginfo/ds.shtml](http://www.dea.gov/druginfo/ds.shtml)

[https://www.erowid.org/ask/ask.php?ID=2972](https://www.erowid.org/ask/ask.php?ID=2972)

~~~
cubano
Ok fair enough and a great link...but here is the twist to this.

That page describes Xanax as a schedule 4, and yet I have been charged not
once but twice with felony possession of Alprazolam and was adjudicated guilty
both times, so perhaps we are both correct in this case, and that yes its a
schedule 3 but its also a felony.

------
tominous
The blog says that HNK (the purported antidepressant) is a known metabolite of
ketamine, but then claims:

> However, getting regulatory approval for such a study, which would
> technically (as far as I know) be a first-in-man trial of HNK, might take a
> long time.

I don't understand this. We already know that when we give ketamine to
patients they are exposed to HNK. Is there a real risk that it is more
dangerous in isolation?

Even if caution is required in the first patients, why do we accept as normal
that developing treatments like this should involve years of waiting for
bureaucratic approval?

------
YngwieMalware
Disassociatives have been used for a while in the treatment of opiate
addiction, including the usage of higher doses of dextromethorphan to treat
heroin addicts. To me it comes with little surprise that this could also be an
effective treatment for depression, despite the fact that depression isn't
necessarily something that can just be treated away. I've personally done more
than my fair share of recreational ketamine and it seemed to aid my coping
with some major life issues I've had, though I suppose this could also be
placebo. Regardless, I'm glad these types of studies are being done and hope
to see some more concrete evidence of positive effect.

------
superobserver
Ketamine is still far too drastic and probably only really necessary when the
depression is acute and prolonged. I would rather advise a non-SSRI like
tianeptine. At least that is currently O.C. without an Rx required.

Edit: looks like HN has been down this very same road before[0] when Ketamine
was brought up; and I'm smiling to see that I'm not the only one to think of
Tianeptine in contrast to the drastic use of Ketamine. Psychopharmacology is
the tried and true drug pusher of our times.

[0]:
[https://news.ycombinator.com/item?id=4615750](https://news.ycombinator.com/item?id=4615750)

~~~
pizza
Well, afaik antidepressant doses of ketamine seem to be lower than 100 mg -
which is quite a bit less than the most drastic of recreational doses - I
don't know (but would love to see research conducted on) whether that's
actually that risky.

Tianeptine is a mu-opioid receptor agonist, so it has abuse & addiction
potential above therapeutic doses. It's also rx-only in many countries,
according to Wikipedia.

Additionally, ketamine works for a week whereas it's not uncommon for people
who use tianeptine to split their daily regimen into something like 3 separate
doses throughout the course of the day.

At least neither require several weeks to reach efficacy while initially
potentially increasing the severity of depression...

~~~
slfnflctd
> It's also rx-only in many countries, according to Wikipedia

Those countries include parts of Europe, Asia and Latin America.

On the same Wikipedia page, "not available [as in, at all, even with a
prescription] in Australia, Canada, New Zealand, the U.K. or the U.S."

Kind of a bummer, I was starting to think I might have something new to look
into. Not surprised, though.

~~~
pizza
You can order it online no problem in the U.S. I'm not gonna source anything
for you b/c I don't want to seem like a shill or anything, but this type of
info is easily acquired on r/nootropics - just use your common sense and
ignore all the BS medical advice on that subreddit, lol.

------
daodedickinson
So this is what Nature has come to? Following up on a study where people took
Ketamine once and felt good for a while? Nobody was doubting that people could
get high on Ketamine. Isolating the most intoxicating metabolite is a bit
useful, but it really bothered me that "studies" looking at a single dose of
Ketamine and labeling the rather short effect "sustained" get so much press.

~~~
simonster
The Nature paper was about isolating a metabolite of ketamine that _is not_
responsible for the intoxicating aspects, but _is_ responsible for the
antidepressant activities (at least in mice).

------
alfonsoperez
From my limited comprehension of the matter, what about:

[http://jneuroinflammation.biomedcentral.com/articles/10.1186...](http://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-8-94)

------
KaiserPro
However, one of the nasty side effects of long term K use is having a tiny
bladder.

~~~
DanBC
Yes, but these newer therapeutic uses have much lower dosing than recreational
use. Recreational users take doses of about a gram or more. These thereutic
doses tend to be on the order of 5 mg per kg of body weight.

(If you have any information about problems caused by long term low dosing I'd
be really interested to read it).

------
droithomme
We need to drown more mice to be sure.

~~~
mookerific
It would be interesting to see how the various research chemicals out there -
deschloroketamine, ephenidine, and others - would fare. There are anecdotal
reports of varying levels of the antidepressant effect and they shouldn't be
left unacknowledged.

------
dschiptsov
Depression, like obesity, is acquired, habitual change due to environmental
factors. Non fraudulent CBT (active traveling in a unfamilar environment as a
simplest example) is enough to introduce persistent changes (that is why there
are so many stories about profound changes people undergo after visiting the
East - radical behavioral change will lead, through conditioning, to change in
biochemistry - body is a dynamic, adaptive system).

There is, of course, no way to change one's physical or mental conditions
without introducing changes to habits, daily routines and environment.

~~~
pfarnsworth
This is, of course, bullshit. I know two friends who acquired their depression
genetically from their parents, and it manifested itself in them, and their
siblings as well. At times they were extremely suicidal, and they described it
as waking up and wanting to kill themselves every day, and not killing
themselves was the biggest struggle they ever faced.

~~~
dschiptsov
Genetic depression is really bullshit.) These "genes" would have been wiped
out in a few generations.

Genetics does not work that way.) Behavior straight out of genes, without
social and environmental conditioning is bullshit. Behavior is product of
training and acquired habits, guided by hard-wired instincts and emotions.

There might be some predispositions - mutations which introduce minor changes
(there cannot be major ones - changes must be small and gradual enough for the
organizm to cope with) into some locations, which affect sensitivity to
certain chemical compound (hormones, neurotransmitters) or minor structural
changes which affects metabolism, but _all this could be easily compensated by
behavioral patterns_ on a higher level.

Animals and people with sudden traumas leading to disability are doing this,
but way too sophisticated, self-obsessed hipstes and couch potatoes cannot.

~~~
mabbo
Right, just like all other diseases. If any disease had a genetic origin, it
would be wiped out within a few generations.

Oh, except for all of these:
[https://en.wikipedia.org/wiki/List_of_genetic_disorders](https://en.wikipedia.org/wiki/List_of_genetic_disorders)

There are even lots of diseases that provide strange benefits that protect the
sufferer from other illnesses. Having half the genes for sickle-cell trait
will give you strong resistance to malaria. Having both is a terrible illness.
Huntington's Disease seems to provide resistance to certain types of cancers,
but when you turn 35 or 40 your life becomes a real nightmare.

The point is that the purpose of genetics is not to promote healthy humans,
it's to promote the reproduction of the group of genes in question. Genes will
use all kinds of tricky methods to duplicate themselves, including all kinds
of things that are awful for the person with them.

~~~
dschiptsov
What is the genetic basis of depression, according to which set of
successfully replicated experiments?

What is the experimentaly supported cause of depression, what are the
pathological changes, in which areas, caused by which genes?

~~~
mabbo
Truthfully? I don't know. That's why I didn't state depression was genetic or
provided any benefit to those who suffer from it.

My point is merely that stating depression can't be genetic because of its
negative effects misunderstands genetics, evolution. I'm not saying your
conclusion is incorrect- there may not be a genetic component to depression at
all- but I am saying your methodology for coming to that conclusion is wrong.

