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Ketamine’s effect bolsters a new theory of mental illness

nautil.us

61–70 of 156 posts

Re: Ketamine’s effect bolsters a new theory of mental illness

#61
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.

Re: Ketamine’s effect bolsters a new theory of mental illness

#62

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 happ…

Ketamine, unaltered, would probably never a good treatment for depression except in some extreme cases. I think people are more interested in understanding how Ketamine can have this unexpected effect so that they can develop classes of drugs that are designed from the ground-up to treat depression. Kind of like how understanding how MAOIs led to tricyclics and then SSRIs. I think that's the direction research is going in.

Re: Ketamine’s effect bolsters a new theory of mental illness

#63
post #58

Earlier quoted context omitted.

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...

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

Yes, very much so. Aside from fast food, pretty much all jobs I've ever had required them (including retail and grocery.)

Re: Ketamine’s effect bolsters a new theory of mental illness

#64

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 prev…

Even before selling the current pills, I've seen mentions from the mid-1800s of how something horrible would happen to someone and it would be lamented in mere economic terms, lost productivity.

Re: Ketamine’s effect bolsters a new theory of mental illness

#65
post #54

Earlier quoted context omitted.

> 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? Well, no you can't because it seems a lot of people with really good life are just struck by it. Although I believe the environment (physical, emotional, relational [edit: in recovery or/and prevention]) plays a huge role there still seems to be something extra going on.

Many people who believe they are just being struck randomly by depression are simply not aware of the reasons they are feeling depressed. That doesn't mean there aren't emotional/psychological reasons for what they're experiencing---only that they don't see those things as the cause. For the first decade or so after being diagnosed with depression I believed it could only be explained by brain chemistry or something…

I also didn't realize how much I was shaped by my awful upbringing. I just thought I'd get away and that I was a rational person and everything would be all right.

Re: Ketamine’s effect bolsters a new theory of mental illness

#66
post #61

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…

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.

Re: Ketamine’s effect bolsters a new theory of mental illness

#67
post #58

Earlier quoted context omitted.

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...

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

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

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

Re: Ketamine’s effect bolsters a new theory of mental illness

#68

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 prev…

Maybe its useful to discern between 'rational depression' and 'medical depression' .. by firstly labeling them as such ?

I don't know how you'd differentiate between this formally, but it seems there is a massive difference - and they need different solutions.

[ edit readability ]

Re: Ketamine’s effect bolsters a new theory of mental illness

#69
post #68

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 prev…

Maybe its useful to discern between 'rational depression' and 'medical depression' .. by firstly labeling them as such ? I don't know how you'd differentiate between this formally, but it seems there is a massive difference - and they need different solutions. [ edit readability ]

I believe the medical terminology is exogenous and endogenous depression, where exogenous is due to external factors and endogenous is independent of them.

Re: Ketamine’s effect bolsters a new theory of mental illness

#70

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 happ…

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.

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