S-Ketamine injected through the ear drum, into the middle ear, is currently undergoing phase III trials as a treatment for noise or infection induced tinnitus.

Chronic tinnitus is currently a condition which if one were to go to the doctor and ask for a cure one would be told to get used to it as there is not much that can be done.

The pace of medical and biotech advancement is increasing as the FDA has relaxed a bit and better understanding of human biology is creating cures for what once were incurable diseases. Exciting times, but not fast enough for me.

The most interesting question for me these days: How can we 10x the number of dollars and scientists engaged in medical research, and then 10x that?

Dammit, I got my hopes up... :(

"The treatment, delivered directly into the inner ear via three injections over three days, must catch the disorder while the problem is still within the ear, before the brain has begun overcompensating for the loss of hearing. Once that happens, no amount of adjustment to the receptors on the auditory nerves will do any good.

Because it is not known when that transition from ear to brain occurs, one of the current trials, of 300 European patients, is specifically testing tinnitus sufferers who have developed the condition no more than three months prior to treatment. The other, a study of 330 North American patients, is investigating a therapy within one year post-trauma. Preliminary results suggest that S-ketamine is effective beyond three months, but declines in effectiveness within a year of the initial trauma, so later stages of the trial are being refocused on the four- to six-month time frame. The trials will be completed at the end of this year, and Auris hopes to submit to the US Food and Drug Administration (FDA) for approval in the summer of 2016."

Connecting the whole world to internet brings the best returns.

I wish there was a good program advocating the effectiveness of Electroconvulsive therapy (and maybe some studies around harmful effects on long term usage). I've taken basically every drug on the spectrum (benzos, SSRIs, et.al.) for most of my life since I was a teenager and nothing helped as much as ECT.

Bit tangential but I think this can be informative for some sufferers - I've been taking zoloft for a few years now as I have (or had I should say) panic/anxiety attacks and co-morbid depression which went untreated for decades ... I inquired from my doctor about ECT, and although ECT is the cadillac of treatments, in some patients that it has not worked, to my great surprise, nicotine has had a really great effect on reducing or eliminating depression.

I'm not advocating taking up smoking, although it is something worthwhile to consider if things like ECT don't help. There's probably ways nicotine can be therapeutically administered without the negative side-effects of burning tobacco.

I had a similar experience, suffered for years with severe depression. Tried every type of drug, nothing was working. But stimulants significantly helped.

Turns out it wasn't depression, but type 2 bipolar. If stimulants are providing relief, you need to see a psychiatrist if you haven't already.

There is, unfortunately, a social stigma associated with the non-tobacco-smoking form of nicotine ingestion and the components to those devices (e-cigarettes) are not regulated enough for us to be fully sure of their effects.

You mean batteries and heating elements? No, to be less obtuse, I must infer: Clearly you mean the fluids.

Let me get this straight...you are actually claiming that regulation increases knowledge? The mind boggles.

That is a shocking and novel epistemological formula - although obviously it has been the implicit subtext of public education in the u.s. for over a century.

No, I'm talking about the heating elements.

'Our results demonstrate that overall electronic cigarettes seem to be less harmful than regular cigarettes, but their elevated content of toxic metals such as nickel and chromium do raise concerns," said Constantinos Sioutas, professor at the USC Viterbi School of Engineering, and corresponding author of the study, which was published online on August 22 by the Journal of Environmental Science, Processes and Impacts.

The metal particles likely come from the cartridge of the e-cigarette devices themselves - which opens up the possibility that better manufacturing standards for the devices could reduce the quantity of metals in the smoke," said Arian Saffari, a PhD student at USC Viterbi and lead author of the paper. "Studies of this kind are necessary for implementing effective regulatory measures. E-cigarettes are so new, there just isn't much research available on them yet.'

http://www.eurekalert.org/pub_releases/2014-08/uosc-ses08281...

But now that you mention it, the vapor does emit alarming levels of formaldehyde when the devices are used at high voltage:

http://www.nejm.org/doi/full/10.1056/NEJMc1413069

The methodology of that NEJM study was flawed and naive, at best. Look into it.

You can choose from the whole palette of Nicotine Replacement Therapy devices: Adhesive patches, chewing gums, lozenges, nose sprays, and inhalers. :)

I'm on Zoloft now as well (who isn't). But its done wonders for me even with the side effects. I suffered from actual psychosomatic dizziness and vertigo which was making life hell and it totally got rid of it.

You can try an e-cigarette

I do :).

Doesn't even modern ECT have serious problems with memory loss side effects?

I think it varies from patient to patient. In my case, 2 separate courses of 6 treatments resulted in almost no short term memory loss.

It does. That's why it should be considered as a last resort if all else fails.

The recent emergence of studies suggesting psychedelics as a novel means of treating depression and other mental illnesses is a double-edged blade: the sheer capability of drugs like LSD and psilocybin and ketamine to hard-reset the brain's pathways is a huge leap from the accepted style of treatment that often boils down to "Take these pills, check in each week, maybe you'll feel better in a month or two."

However, it also gives people the false impression that all they need to do is chew on some shrooms and listen to the Grateful Dead for a couple of hours and suddenly they will be free of all addiction and depression forever.

Every time a study like this comes out there is a predictable pattern in patients' depression scores: immediately after psychedelic treatment, depression signs plunge, wade around the low end for a while, then steadily creep back up.

With the exception of people whose brains simply do not work as they should (I have a friend who is chronically depressed because his body can't produce enough serotonin even with antidepressants), depression is often as influenced by external factors as internal ones. A spectacular drug trip won't change the reality of having a death in the family, not being able to find a job after being laid off at 45, or simply the stress of the modern, always-on world.

Discoveries like these are always helpful towards understanding the brain and how to formulate effective treatment, but in the end, mental health will always be vastly more complex and harder to cure than any physical ailment. There will never be anything close to an ibuprofen for the brain.

#1) The serotonin theory of depression has seen way better days. There's simply no way you (or anyone) can say with such reductive certainty that your friend is "not producing enough serotonin"

http://bigthink.com/devil-in-the-data/the-chemical-imbalance...

#2) The novel method of ketamine doesn't really appear to be related to the psychedelic trip itself -- indeed many people are using regular sub-threshold doses of ketamine in their self-designed regimens and seem to be getting good results. LSD and psilocybin treatment seems to be mostly about insights gained during the experience -- much like a supercharged therapy session. Ketamine on the other hand, appears to have some sort of mode of action that isn't about insight and is more about a "brain reset" of sorts.

#3) I do agree with you that mental health issues defy reductivity simply because they encompass biological, psychological, and sociological systems that all interact.

All good points, although I would supplement that "microdosing" tiny amounts of powerful hallucinogens (with doses so low that psychoactive effects can barely be registered) has also gained traction in recent years. Proponents of microdosing argue that taking 1/20th of a tab of acid every few days allows them to remain productive while under the influence, and that the effects are more positive and profound than they have experienced with traditional antidepressants. It's no silver bullet but it is an option that merits further study.

http://motherboard.vice.com/read/a-brief-history-of-microdos...

> With the exception of people whose brains simply do not work as they should

Exactly the people these treatments target. I'm on of those people and I have never thought I could "chew on some shrooms and listen to the Grateful Dead for a couple of hours." Quite the opposite. Depression makes you think nothing will work. When I'm in a depressed state it takes a tremendous amount of will to do anything, including taking medication of any sort or even getting out of bed for that matter.

Fortunately SSRIs work for me, as well as tight control of my diet and exercise. Exercise alone has never made a difference for me, though. One of the worst episodes I ever had came at a time when I was in the best shape of my life, working out everyday.

that mirrors my experience w/depression prior to having it diagnosed. I knew something was up, and tried to self medicate in a number of ways, among which dieting, exercising and long term fasting was present. Everything seemed to help a bit, kind of mask the turmoil of the anxiety and panic that was going on, but eventually my 'nature' took over and I'd go back to feeling like doomsday's around the corner...

SSRI seems to have done the trick. Apparently we all produce "normal amounts" of serotonin, but with depressed folk like myself, the serotonin doesn't hang on the synapse long enough ...i.e. our specific biology depletes it faster.

Looking at my wider family, this condition is so pervasive ... and inherited, it's not even funny in all the ways it wreaked havoc on people's lives in many ways. Glad I caught a break.

Based on your description it seems like we suffer (or in your case 'suffered') from the same condition. I've been suffering from panic-disorder since my mid-teens and it is only recently when I tried an MAOI that my doctor recommended that I've seen the condition lift a bit. There is some co-morbid depression but I believe that is a result of the anxiety and not the reverse. The MAOI is effective but my anxiety still flares up from time to time, and I've been thinking of other ways I can try to improve my state of mind. I'm not even sure how I would broach the subject of ECT, as I haven't experimented with enough drugs to know if they are all ineffective. However, these trials give me hope that in the future we will have better ways of dealing with anxiety / panic disorders.

> Looking at my wider family, this condition is so pervasive ... and inherited, it's not even funny in all the ways it wreaked havoc on people's lives in many ways. Glad I caught a break.

I agree, it is quite sad. Like right now I'm certain that my father is depressed although the reasons for this are somewhat interconnected with real life events like unemployment, loss of loved ones, etc ...

> A spectacular drug trip won't change the reality of having a death in the family, not being able to find a job after being laid off at 45, or simply the stress of the modern, always-on world.

It's true that drugs won't change reality, but our interpretation and reaction to reality is what's important, and therapy/drugs can certainly change that.

One of the more interesting properties of ketamine that underscores your statement is its effectiveness in treating PTSD...[1]

...as well as lowering the incidence of PTSD among people who had been treated with ketamine as an anesthetic prior to a traumatic experience. [2] [3]

[1] - https://www.ncbi.nlm.nih.gov/pubmed/24740528

[2] - http://www.biologicalpsychiatryjournal.com/article/S0006-322...

[3] - http://www.dtic.mil/get-tr-doc/pdf?AD=ADA480518

"depression is often as influenced by external factors as internal ones. A spectacular drug trip won't change the reality of having a death in the family, not being able to find a job after being laid off at 45, or simply the stress of the modern, always-on world."

Have you ever taken hallucinogens? You don't experience a "spectacular drug trip" and suddenly feel better, you actively work on your problems and have a seemingly raw, uncompromising perspective on the external/internal factors that affect your life.

It's a bit like expedited therapy. It's a trying, intentional experience that you have to put effort into in order to get any benefit.

Doesn't a finding like this move us a big step away from that double-edged problem? I would dispute your claim that people think all they need to do is chew on some shrooms, etc. – I've never seen an article that suggested anything of the sort. But even if that were the case, discovering that the psychedelic effects may be separable from the antidepressant effect moves us away from that idea. Yet you seem to treat this news negatively.

Sadly, you seem to have missed my point, which is not to say that there is anything wrong with the science, but rather folks who would read the same article and think "maybe all I need is a good trip and I don't need no stinkin' doctor to tell me what to do or how much to take."

At a guess, the majority would be correct. In general, physicians, like all humans, are incompetent and self-interested. Absolving yourself of personal responsibility by ceding your autonomy to an authority figure rarely works out. This is why I hate compulsory government healthcare: Physicians cease to be employees or voluntary servants who help, and become police (or tax farmers) who control and exploit. It is human nature.

> In general, physicians, like all humans, are incompetent and self-interested

Self-interested, perhaps. But assuming that physicians are representative of the broader population when it comes to incompetence is really poorly-grounded.

I have had close friends killed by grossly incompetent diagnosticians, and seen numerous botched and often superfluous surgeries. Completely anecdotal, but evidently typical of rural environs.

> stress of the modern, always-on world

There was stress in the old world too. Also, we work less than historically. I'd argue today's world is less stressed.

We work less than people did during the industrial revolution, yes. But not less than before the industrial revolution.

http://groups.csail.mit.edu/mac/users/rauch/worktime/hours_w...

Ketamine is quite different than psychedelics, so the two can't be compared. It's also important to note that the recent study of psilocybin in treatment-resistant depression was extremely preliminary and not of good quality. The sample size was very small (n=12), there was no placebo control group (huge red flag in any depression study), and nearly half of the patients indicated previous psilocybin use.

Placebo control groups are absolutely critical in depression studies because the placebo response rate for depression is incredibly high. Moreover, placebo response rates are actually rising in recent years for unknown reasons. It's not uncommon for the placebo control group in a depression study to have response rates upwards of 60%, at least in the short-term timeframes of clinical studies. When you read sensational news articles about how SSRIs are barely better than placebo, remember that placebo is pretty damn good (again, in the short-term) at producing a response in depression studies. The story changes in clinical practice over the long-term, of course, but the point is that separating placebo response from actual treatment effects is critical for assessing anti-depressant efficacy, and psychedelic (not ketamine) studies lately have omitted placebo control groups completely, which is unfortunate.

It gets more complicated, though. In the case of psychedelics, the placebo effect may actually play a central role in the anti-depressant effects. Psychedelics are known to induce suggestibility and create a false sense of enlightenment. If that suggestibility and sense of enlightenment is deliberately framed in the context of depression treatment and actively guided by clinicians, as in the studies, then perhaps it's possible that the psychedelics are at least partially acting as an instrument for amplifying the placebo effect. To the depressed patient, it doesn't matter if the result is placebo effect or not, as long as the end result is the same. At that point, the real question is whether or not the end result is the same.

> However, it also gives people the false impression that all they need to do is chew on some shrooms and listen to the Grateful Dead for a couple of hours and suddenly they will be free of all addiction and depression forever.

I completely agree that public and media perception of these experimental depression treatments is completely off base. There is a lot of interesting potential in here, but many people are walking away with an idea that they can self-medicate their problems away by themselves in their basements. There are many people in forums and subreddits chasing ill-conceived plans to treat themselves with psychedelics or NMDA antagonists in ways that don't match the study protocols at all, and it's all very concerning.

> Every time a study like this comes out there is a predictable pattern in patients' depression scores: immediately after psychedelic treatment, depression signs plunge, wade around the low end for a while, then steadily creep back up.

Unfortunately, the same pattern is observed in placebo control groups for depression studies. That's why it's so critical to have a placebo control group such in depression studies.

> With the exception of people whose brains simply do not work as they should (I have a friend who is chronically depressed because his body can't produce enough serotonin even with antidepressants), depression is often as influenced by external factors as internal ones.

Your comments on external factors are spot-on. Training the brain to have healthy responses and coping mechanisms, as in CBT, is critical to depression treatment.

However, the comments about your friend's brain not producing enough serotonin is more pseudo-science than real science. I don't doubt that doctors have told your friend that, but it's a metaphor at best. SSRIs don't cause the brain to produce more serotonin, they modify the dynamics of serotonin transmission. The anti-depressant effects come from downstream changes that result from that alteration in serotonin dynamics, which are complex and multi-faceted.

But depression isn't simply a function of serotonin levels or balances like the over-simplified explanations would suggest. It's entirely possible to increase extra-synaptic serotonin functions well beyond normal, healthy ranges with medications without making the patient "feel" good. Depression is massively complex, and we modulate serotonin because it's one of the easiest and safest paths to manipulate brain function, not necessarily because patients don't have "enough" of it.

> mental health will always be vastly more complex and harder to cure than any physical ailment.

You're absolutely right that effective mental health treatment requires more than just a pill. But having effective medications to augment healthy mental habits, coping mechanisms, and CBT-type treatments makes it a whole lot easier.

> Ketamine is quite different than psychedelics,

I can't really agree with this. I was given ketamine in a surgical setting. The result could really only be described as what the cool kids call "tripping balls". Totally out-of-body experience.

To counter your anecdote, I've also received ketamine sedation for procedures, and never have I experienced any sort of "tripping"-like effects. It certainly can be used without those effects, at least in some portion of the population.

It's a dosage thing. I was given a relatively high dose, apparently.

There are similarities in the general quality of the mental state. The BIG difference is that ketamine is dissociative. Perceptions on LSD and shrooms are still strongly correlated with real sensory input. You're hyperconscious of your real surroundings. Ketamine is more like a lucid dream where you're having a rich, strange experience, but not very conscious of your real surroundings.

Yes, that's very much how I'd describe it.

> How can we 10x the number of dollars and scientists engaged in medical research, and then 10x that?

Have you considered multiplying by 100? Note that the preceding sentence also has the advantage of having a real actual verb in it.

Though I suppose it's pointless to rail against insufferable tech buzzword-speak, or typical valley-style nonsensical 10x statements at this point. Oh well.

This breaks the HN guidelines by calling names. It's also needless nitpicking. Please don't comment like this, even when someone else's use of English bugs you.

We detached this subthread from https://news.ycombinator.com/item?id=11903404 and marked it off-topic.

1) "Nx" is a widely-understood, abbreviated way to write "multiply by N". You certainly understood it. Do you have an issue with abbreviations?

2) It seems like he said "10x...and then 10x" instead of "100x" as either A) an allusion to a multi-staged process, or B) a rhetorical device to emphasize the magnitude of the changes needed. Either way, it isn't exactly the same as just saying "100x".

3) Your comment has no substance and is just an attack. That's against HN rules.

Exponential growth doesn't happen in one discrete operation, friend.

Here's some more interesting info about the trials for s-ketamine as a tinnitus treatment.

The vision for the company that is trying to bring intratympanic s-ketamine to market as a tinnitus treatment was very interesting to me.

The founder was looking for new uses for drugs that are currently approved and with long safety records, that could be tested on animals.

I thought it was interesting criteria for a low-hanging fruit search of the problem space in medicine, considering regulatory realities as well as financial ones.

> Exponential growth doesn't happen in one discrete operation, friend.

Correct. In fact, it simply doesn't happen at all in a category like medical research spending.

Even if it did it's not likely the returns to that spending would grow exponentially.

But to humor you, by what mechanism do you think medical spending in the U.S. will grow from its current $95bn per year amount to $9.5 trillion?

Is your assumption that basic medical research will grow to consume 57% of the country's GDP, or do you anticipate growing the size of our nation's economy by approximately 50% to accomplish this feat?

Assuming you've got that sorted, who do you think should get the $9.4 trillion dollars in additional medical research spending you propose?

Sounds fanciful, right? Only if you impose the constraint of this being an effort by ~4% of the human population, the population of the United States.

The U.S once spent 75% of global research dollars, it's share has now dropped to below 50% as Asia has come online in this sphere.

If current spending is just 95 billion in the US, that has been quite a drop from previous years, but for a thought experiment, if US level research spending was the same per capita for the rest of the 96% of the human population, we would be somewhere around 2.3 Trillion globally.

There are billions of people outside the U.S, some with minds as sharp as WSU's Joe Harding, who as of right now are left out. But where do we find the money to lift them out of poverty?

One answer, we discover cures for some really expensive ailments, like diabetes, heart and respiratory disease.

What is the cost of disease? It is terrible. With an aging population, it has the capacity to ruin developed nations.

While we tinker around the edges, and manage chronic disease like diabetes with insulin, or Parkinson's with carbidopa, we spend large fortunes and get poor outcomes.

SENS is moving in the right direction. We need the ability to repair ourselves at the cellular level, and we are making progress in this regard.

What is the prize of discovering how to repair the inner workings of the molecular machinery that make us up?

> First, Non communicable diseases already pose a substantial economic burden and this burden will evolve into a staggering one over the next two decades. For example, with respect to cardiovascular disease, chronic respiratory disease, cancer, diabetes and mental health, the macroeconomic simulations suggest a cumulative output loss of US$ 47 trillion over the next two decades. This loss represents 75% of global GDP in 2010 (US$ 63 trillion). It also represents enough money to eradicate two dollar-a-day poverty among the 2.5 billion people in that state for more than half a century. [1]

So yes, $9.4 trillion is a good global goal, but I believe there is opportunity for tremendous cost savings.

Open source drug discovery, open source cancer treatment, that is what I am interested in these day. I would like to see an army of pro-amateurs collaborating online and performing experiments on mice in their garage, a hacker movement for biotech.

We are on the cusp of fantastic gains in health and longevity. We have only just begun to understand the molecular processes that age us and make us sick. Lets pick up the pace.

[1] http://www3.weforum.org/docs/WEF_Harvard_HE_GlobalEconomicBu...

And PS:

I checked out your page, you did some work for my favorite band, The Hold Steady. Awesome :)

Thank you so much for taking the time to give a level-headed response to GP. While many seem to disapprove of their tone, I actually found GP's questions to be rather good ones, and was wondering the same things myself. And as I keep reading, rather than the usual name-calling I've come to expect from Web fora, I see nothing but very good, detailed answers in reply. Thank you for that.

Mmm, pointless internet hostility

Without conflict, there can be no drama.

If you were unaware, ketamine and similar drugs have been used in humans for their incidental antidepressant effects, which has been getting some level of traction for investigation of late.

Discovering which metabolite was responsible for this in mice is a useful step toward trying said metabolite in humans, since the cognitive effects of attempting some of the things that they did to the mice would be...unpleasant, to say the least, if not outright unethical.

In addition, finding the component responsible will permit them to utilize it as a treatment without any of the concerns , difficulties, or stigma associated with being given an IV of a psychedelic addictive substance periodically.

People who know that ketamine is "horse tranquilizer" uniformly also know that it's used in humans. That's simply a troll comment.

Ketamine is an extraordinarily safe anesthetic and so is often used in vulnerable human populations as well.

I wonder, if you had to for some reason do field surgery at a rave, whether you could go round grabbing baggies off of people in order to dose them enough to operate.

depends on how quick you can operate I guess ;) There's a reason that stuff is on a continuous drip while operating. But I've seen people accidentally hit an anesthetic dose before when using recreationally and be knocked out for 20 min or so.

Yeah I'd prefer to be patched up whilst in a k hole than sober, in all fairness. Could the ketamine complicate it with ODs and other stuff, though?

Ketamine is consumed by humans too.

OK, I've been skeptical in the past about studies suggesting drugs like ketamine and MDMA could be used to treat depression. Ketamine especially would not be a good anti-depressant pill, because it is highly addictive, not to mention you're giving a _depressant_ to a depressed person.

However, this result is promising. This study has claimed to have isolated the anti-depressant effect to a particular product of ketamine metabolism, and that this compound contains none of the anesthetic and addictive properties. Obviously, this is just a single study, performed on mice, but it is a promising first step towards the potential development of a new anti-depressant.

"not to mention you're giving a _depressant_ to a depressed person"

Heh, these concepts are unrelated to the point that this statement could make a decent joke. As a rough example, it's on the level of "not to mention that you're installing a clock application on a computer that's already overclocked".

Love the example. In reminded of snopes' take on the "the car called Nova failed to sell in Mexico because 'no va' means 'it doesn't go' in Spanish" myth. Their example was of Americans not wanting to buy a car called "Notable" because it had no table.

Or was "not able".

Like the mindset that eating fat directly makes a person increase fat percentage. Similarly to the idea around cholesterol.

At the risk of making an appeal to authority, I got that quote from a clinical psychologist, referring to the effect of alcohol on clinical depression. See my other comment for an explanation.

I see, it makes more sense when you make it more explicit. But then I also have an appeal to authority: the majority of drugs prescribed against depression also happen to be depressants. And sometimes it works, though they all tend to have addiction and habituation potentials as well. I would say the psychologist you're quoting is raising a point that goes against the mainstream, which is not necessarily bad of course, but the phrase in itself remains a (somewhat misleading) play on words.

>the majority of drugs prescribed against depression also happen to be depressants

Can you give a source for that, and some examples? I couldn't find anything (googling "antidepressant depressant" is about as helpful as you'd think).

I'd still argue that the effects of depressants (the inhibition of neurotransmission) are in and of themselves not helpful for people depression.

I agree my phrasing was a bit confusing, I tend to value poignancy over explicitness :)

>Can you give a source for that

I guess it depends on how strict you are with your definition of a depressant, but looking at this list:

http://www.webmd.com/drugs/condition-1022-depression.aspx

If you establish a depressant <-> stimulant axis, the major drugs here are very much on the depressant side. As for their effectiveness, depressants generally feature a euphoric, "feel good" component. From there it's easy to see how some members of this class might be helpful against depression. It seems paradoxical that you might be worsening the lethargic aspect, but basically the treatment concentrates on the negative mood, loss of pleasure aspect, which appears to be a more effective way of approaching the problem (if you take for granted that chemicals are a good approach at all).

> Ketamine especially would not be a good anti-depressant pill, because it is highly addictive

SSRI withdrawl effects last up to a month whereas Ketamine once a month produces no such effects.

So the current therapy for depression is more addictive, by design, than Ketamine.

Just a note: in English, “by design” is an idiomatic construction that means “deliberately”. You probably want something like “by nature”.

By design seems more correct, given the pecuniary interests of the designers.

Why are you reasoning from the words used to describe it?

"depressant" has also never meant "induces long term state of depression".

depressants inhibit neurotransmission, and the prevailing theory as to the biologic foundations of depression is decreased availability of certain neurotransmitters. I'm not saying depressants can cause or induce depression, but they certainly don't help.

On a more practical level, many people with clinical depression suffer from reduced affect, lethargy, and general lack of energy. Depressants will make those symptoms worse.

> I'm not saying depressants can cause or induce depression, but they certainly don't help.

Studies say otherwise.[1][2]

> On a more practical level, many people with clinical depression suffer from reduced affect, lethargy, and general lack of energy. Depressants will make those symptoms worse.

Reduced affect is brought up all the time when talking about various things and people go "Oh noes! Reduced affect!" which only goes to show that they have no idea what the phrase means. It's not particularly negative in itself; it's only a diagnostic criteria of underlying disorders which have negative effects.

Lethargy and general lack of energy are the same thing.

So basically you have one negative symptom you claim ketamine will cause because it's a depressant. Given that it's a party drug taken in much-higher-than-clinical doses at raves where people dance for hours on it, you should maybe consider the idea that you don't know what you're talking about and stop talking.

To be clear, I'm not particularly in favor of ketamine in treatment. If you knew what you were talking about, you might have, for example, cited the most obvious side effect of ketamine which is bladder damage. Ketamine needs to be studied more, in my opinion, to find out whether the positives outweigh the negatives.

But your ignorant opinion based on the etymology of "depression" is actually detracting from this conversation and doesn't help us to study it. You're just spreading misinformation for no reason except your own ego.

[1] https://www.clinicaltrials.gov/ct2/show/NCT00088699

[2] https://www.nimh.nih.gov/about/director/2014/ketamine.shtml

I'd so try a ketamine based product, despite the fact that its regular use is for general anesthesia ... If I remember correctly even SSRIs were "accidentally" discovered by observing metabolizing effects of - and I hope someone corrects me here if I'm off - cough syrup.

Dicking around with the chemistry of ketamine to make it safe and therapeutic as well as pre-cursory enough for consumption to generate the desired effect could take years though, and there still might be issues even then that would prevent it from general use....

Bit off topic - if there's one place where I am for patents, it's for pharma - takes years to find something that works, and when they finally do, it's only natural that they would want to recoup the money.

There are clinics in the US using it to treat depression.

Who knows how much scientific justification they have to do so, but they are taking patients and so on.

I think you make some good points, though I think some of your remarks are a tad too aggressive. Some rebuttal: Your first link is to a trial on ketamine that is currently ongoing, so hasn't reported any results. The second mentions some promise in ketamine for clinical usage, but that doesn't dispute my point that depressants will exacerbate many of the symptoms of clinical depression.

> Given that it's a party drug taken in much-higher-than-clinical doses at raves where people dance for hours on it ...

You can make the same point about alcohol: people routinely ingest large amounts of alcohol and can still engage in lots of physical activity, despite it being a depressant.

> I think you make some good points, though I think some of your remarks are a tad too aggressive.

If you decide to share your opinions on things you don't know about as if you do know about them, then I'm not sure what you're expecting. Warmth and acceptance?

> You can make the same point about alcohol: people routinely ingest large amounts of alcohol and can still engage in lots of physical activity, despite it being a depressant.

Yes and I will, because that's the entire point of what I'm saying. Just because something falls in the broad category of "depressant" doesn't mean it's going to make you lethargic.

>Depressants will make those symptoms worse.

Ketamine is used in a very small dose. There's plenty of research showing some beneficial effect.

"Some" is a gross understatement of the treatment's efficacy and import in the cases where it is effective.

I think you're oversimplifying the concepts in service of a category error vis-a-vis depressants and depression.

It is right to be skeptical of using the actual compound with its negatives (for instance, the hallucinogenic / dissociative properties of ketamine and the neurotransmitter depletion of MDMA.)

However, it is possible that illegal recreational compounds can shed some light on body chemistry, and I think that's what happened here. The "ketamine is an antidepressant" story has been around for a while. It was considered kind of a deal because everything about depression previously dealt with serotonin, and ketamine clearly has nothing to do with serotonin.

Consequently there's people working on compounds with similar actions, but without ketamine's ill effects. The closest one I know to production is this one:

https://en.wikipedia.org/wiki/Rapastinel

Which, as a Phase III "breakthrough candidate", still has a long way to go, of course.

This new study is significant, though, if it is not the NMDA receptor that is really creating ketamine's anti-depressant effects. It may allow for alternate compounds to be explored beyond even what is being worked on now.

highly addictive is a pretty serious stretch don't you think. It is definitely possible do develop a psychological dependency, but nothing like morphine, nicotine, or even caffeine.

Like the drugs you've listed, it builds a physical dependence if used frequently enough. Someone who is physically dependent will experience withdrawals in the absence of ketamine. Like those drugs, it induces a desire to consume more of the substance in many users in such a way that something like codeine does and ibuprofen doesn't.

Ketamine is a dopamine reuptake inhibitor, possibly leading to some of the euphoric and reinforcing effects of the drug. Cocaine, methylphenidate and methamphetamine are examples of addictive and abused dopamine reuptake inhibitors. Addictive drugs have direct or downstream effects on the dopamine system. It also stimulates the D2 subtype of dopamine receptors.

Edit: reply was meant for GP

Ketamine primarily acts on glutamate, one of the reasons it's such an "effective" anesthetic, as the specific glutamate receptor (NMDA) it acts on is involved both in memory formation and the rather complex neurological process that leads to experiencing chronic pain. Its effect on dopamine reuptake (along with norepinephrine and serotonin), GABA potentiation, and opioid receptors means, roughly, it affects much more of the brain's chemistry than the "unwashed masses" using it are aware of.

They think it's relatively safe because it wears off faster than PCP (it does) or other depressants (it does) but in reality it dramatically affects multiple systems in their bodies, with some effects building up over time to ultimately cause physical damage (like bladder wall thickening, or damage to cardiac tissues). And in the meantime, they come to relish the escape of the K-hole. At least, until they have a bad trip, because the hallucinations they have are still controlled by their own brains, and if they're having a bad time in life, their hallucinations aren't going to be helpful. What's worse, because they think it's like any other depressant, they freely combine it with Adderall. Ketamine is a cardiovascular stimulant, and mixing with Adderall has a very real risk of proving fatal.

Psychological addiction causes users to disregard all these risks, even the ones the users know about, and pursue taking the drug regardless, and is no less dangerous than physical addiction. In fact, because of its effects on dopaminergic modulation and opioid receptors, there is an easy argument to be made for the addictive potential of ketamine. Further, it's important to understand: rats will self-dose with it, humans rate the high they get from low doses of it as being likable and causing them to want more, daily users often go through withdrawal symptoms and experience cravings after they stop using, and users rapidly develop a tolerance for it - all of these are metrics used to determine how addictive something is. Which is to say, in the case of Ketamine, quite.

So, no, it's not a stretch at all.

That doesn't limit its usefulness in clinical settings, but do not fool yourself or anyone else that it's not addictive.

Thank you for the detailed explanation! I've often wanted to try K to help battle my nastier depressive episodes, but your comment definitely gave me pause. It's very tempting to look around at all the party usage of K and forget how dangerous it could potentially be.

> not to mention you're giving a _depressant_ to a depressed person

That's about as terrible as giving _ham_ to a hamster.