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Comment by openasocket | Hacker News Reader

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.

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"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".

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).

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

> 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.

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

>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.

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.

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