[Sometimes psychotic]

Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses

Ok so I ran across this abstract but I can't access the paper until it's indexed on pubmed. It's about a drug called ketamine that some people have been promoting as a rapid treatment for depression but it has always freaked me out because it's used to induce psychosis in mice...they use it to model schizophrenia so to me it doesn't seem like a drug you'd want to take.

Anyway they are trying to figure out why it causes psychosis but not another nmda receptor antagonist which is interesting in and of itself because you would expect them to do the same thing. Thing is the second drug also has no impact on depression. So whatever is promoting psychosis is actually beneficial when it comes to depression. Well one of the things it alters is bdnf which is often referred to as brain fertilizer.

This is totally speculative now but I'm wondering if psychosis is the brains attempt to evolve and change to something more suited to the current often stressful environment. Can you imagine if the brain could actually adapt more fluidly during a persons lifetime whenever they were under pressure it would try to enhance itself.

To be honest I have no idea how closely the ketamine effect mirrors actual human psychosis or if something similar could be going on in other typical people but never progress to the psychosis level. I just think it would be neat if psychosis or early pathways involved in psychosis could induce growth, change and adaptation to the environment rather than being entirely detrimental. We only hear about the negative outcomes because only those people end up at the pdoc but what of the 5% of the population that hear voices...what if they are more adaptable being on the cusp of it, not in full psychosis.

Anyway this is just random thought but what if we are the beginning of the next wave of evolution? That would be cool...

[junkDNA]

ketamine is scary. i did a lot of drugs, most all of them, with the exception of dissociative drugs like ketamine and PCP. i was scared of those drugs, which doesnt make much sense cuz i was smoking heroin in restaurant bathrooms at my worst. im completely sober now. its been a long journey, but im glad to say that i am sober. i wouldnt trust using ketamine as a medicine. there are some bad effects from that drug such as going into a k-hole. idk. seems risky.

[Sometimes psychotic]

Thanks junk I wasn't saying ketamine was good I find it scary too because it can induce psychosis but this was more of a conceptual thing----what if the pathways that lead up to psychosis are really about adaptive change in a person and its a matter of degree---a little bit can be beneficial but too much leads to this out of control psychosis. What if we all got thrown into psychosis because our minds were trying to correct an issue and just went a little bit too far. It was much more of an out there philosophical wandering about the basis for psychosis for me than anything realistic...

[nbritton]

Originally Posted by Sometimes psychotic

We only hear about the negative outcomes because only those people end up at the pdoc but what of the 5% of the population that hear voices...what if they are more adaptable being on the cusp of it, not in full psychosis.

Evolutionarily speaking, there must be some benefit, because otherwise evolution would take it out.

You're talking about the NMDA PCP/ketamine binding site, yeah it's scary stuff because basically it induces schizophrenia in regular people... this is entirely the reason why people go batsh*t crazy on PCP, and to see it used to treat depression leaves me scratching my head. The NMDA receptor is a complicated structure...

[Secretum]

Interesting! One thing that I've read before, though-the dose of ketamine given to treat depression is much lower than the dose needed to induce hallucinations. So it may not be exactly the same pathway. But I could see psychosis as being neuroprotective in it's own weird, paradoxical way, providing a way to escape when reality gets to be too painful. As someone with a psychotic mood disorder, I've noticed that my mood symptoms are less severe than most people with mood disorders. But I'm only one person...

[Sometimes psychotic]

Great nmda receptor diagram...it really is a complicated and super cool structure. On an evolutionary level though it could just be all a roll of the dice some genes are beneficial in some combinations but not so awesome in others like for COMT you have to be heterozygous either met/met or val/val have increased risk of sz. Still I like the idea that there could be an evolutionary advantage much like there is for sickle cell albeit in that case as well it's the heterozygous who win against malaria but don't get sickle cell.

But yeah regarding the dose of ketamine being low, that's why I think the process that leads to psychosis might be a beneficial process but that can go into overdrive in some people and became deleterious but if it's a normal biological say repair/remodeling pathway there should be an off switch for when it's not needed. So stress/depression is the on switch but what triggers the feedback process that says OK we're doing great now brain is at 100% optimal function time to shut of the remodeling. I just wonder because some people have one break and then get better and it's like their off switch kicks in and some people have long remissions which is the same theoretical process. I mean we could forget about long term dopamine blockade if we could just find the normal mechanism to shut this process down, well maybe but it would be cool if we could