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Long Term Effects of NMDA Antagonist Abuse

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bjznoviskey

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Oct 17, 2013
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Can someone point me to a possible article on the topic or have sufficient knowledge themselves?

Been thinking about my use, which is two-three times a week, usually on my weekends to chill. I use a variety, MXE, 3-MeO-PCP, O-PCE, O-PCM and Ketamine. Been using dissociatives like this for probably a few years now, am I setting myself up for long term damage of some kind? I don't notice any issues at the moment.

Any solid, fact based info would be awesome. Please don't even bring up the Olney's lesions thing.

Thanks
 
This is my theoretical opinion, but I think the main fallout of abusing an NMDA antagonist will be related to a negation of long term potentiation and normal NMDA function, possibly resulting in some (mild) intellectual difficulties depending on if it's abused enough. I have a feeling that use solely on the weekends will not be enough to do serious harm in this way, it would probably require every day use. I think regarding the deficits of DXM abusers, this makes sense - because I assume there is no "toxic" action of DXM, it must be something about its mechanism of action that results in deficits. I can't say I know whether or not any of your substances of choice may be toxic as far as the compound itself goes.

The other possibility explaining DXM users deficits is that they are experiencing rebound glutamate on the comedown - I think adding a little bit of a dose on the comedown to smooth things out will help with this.

I have heard one person mention concern of weakening of the NMDA input to the suprachiasmatic nucleus - the circadian rhythms center.

I suggest learning about the process of long term potentiation if you want to know how NMDA antagonism might treat you long term, I think I remember dendritic spines get stronger with LTP so some NMDA antagonism might be okay but a weakening of NMDA circuits with chronic abuse could be bad.
 
I think if you can mange to keep yourself out of the mental wards, NMDA antagonists can be useful tools.
 
bjznoviskey said:
Can someone point me to a possible article on the topic or have sufficient knowledge themselves?

Been thinking about my use, which is two-three times a week, usually on my weekends to chill. I use a variety, MXE, 3-MeO-PCP, O-PCE, O-PCM and Ketamine. Been using dissociatives like this for probably a few years now, am I setting myself up for long term damage of some kind? I don't notice any issues at the moment.

Any solid, fact based info would be awesome. Please don't even bring up the Olney's lesions thing.

Thanks
Click to expand...

Why do you mention not to bring up the topic of Olney's lesions?
 
aced126 said:
Why do you mention not to bring up the topic of Olney's lesions?
Click to expand...
Good point, its not like they have been disproven in humans, and human ketamine lesions are visible on MRI http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713393/ - "The damage on the nervous system included neuronal loss, synaptic changes, changes in functional magnetic resonance imaging (fMRI) activities, and the formation of mutated tau protein in neurons as described in models of rodents and monkeys". The Tau protein worries me. I really hope some of these effects are compound specific and would not apply to say 5mg of Memantine for life.

"These lesions appeared as minute patches in the first year and became larger sites of atrophy by 4 years of addiction. The majority of the addicts was on dosage of 1 g per day and used ketamine daily for several years. Medical histories indicated that addicts over 4 year of ketamine addiction displayed memory deficits and anxiety depression while those from the 5 to 7 years developed definitive ataxia and by 7 years and above, dyskinesia became obvious"
 
Sorry, I may have misspoke on the first entry. I mean that, I'm aware of Olney's lesions but I don't think my abuse is at a level to cause this but, what could happen in terms other long term effects.

Thank you for your answers thus far
 
Probably mildly lowered IQ due to hypo-excitability (Hypo-excitability except for the olney's part ofcourse which is excitotoxicity to specific neurons) similar to GABAergic drugs. Furthermore HPPD is a risk.

I think the biggest source of damage remains olneys lessions though.
 
Olney's lesions don't occur in humans as far as anyone can tell.

And the unfortunate part about this debate is that there just haven't been many comparative MRI studies of a varied cross section of dissociative users. I mean, if you think about it, even a study on the brains of PCP abusers would help here. Instead all we have is one study about ketamine, and that could mean a few things.

1a. All NMDA antagonists cause this stuff at any dose.
1b. All NMDA antagonists cause this stuff at high enough dosages.
1c. 1b, except "only in some people, sometimes".
1d. 1c, except "only in some people, sometimes".

2. Only high trapping NMDA antagonists cause this.

3. Only ketamine-type keto aryl cyclohexylamines cause this.

4. Only ketamine causes this.

5. There is an additional, unknown, exacerbating factor that everyone has missed.

For now, the best I can say is that regular moderate to high dose usage of NMDA antagonists at the very least isn't good for one's mental state (been there, done that, see also FastNBulbous). Partly because the person taking them often isn't keeping track of their dosages as they should be, partly because they tend to be self-reinforcing, etc., but mostly because eventually people just... snap. And do ridiculous shit, and then they end up hospitalized. Or jailed, institutionalized. Worst case, shot by police. Sometimes they undertake gratuitous acts of disfiguring self-harm (up to removing one's own eye with a spoon.) Or they just end up dead through their own ridiculous actions.

Most of the "urban legends" about PCP do have some basis of truth to them. And I'm sure this extends to stuff like MXE, diphenidine, and the like.

So take it easy and if you're going to use these drugs, keep track of your dosages. Keep it to once a week or even less.

Do these drugs negatively effect the structure of the brain? If a sample size of one means anything (it doesn't), I had been a really high dose, high frequency user of a bunch of dissociatives (DXM, Ketamine, MXE, 3-MeO-PCP) for a long time (years) up until I got hospitalized (which was to be expected), got a pair of CT scans, and my brain looks fine. No holes, nothing different from baseline.

But I do keep my mind active, and lead a pretty good lifestyle. (aerobic exercise, good diet). So maybe that saved me. I don't know.

So yeah, some words of wisdom and insight into sekio's personal life for y'all. I'm off the NMDA antagonists now.
 
Very interesting sekio, intramuscular haloperidol sounds like a blast.

I wonder what role negation of LTP is playing in the brain atrophy of the K users, I have heard that LTP can strengthen and enlarge dendritic spines. So you might have a factor 6. This only happens if you use often enough to significantly negate LTP.

It sounds like those ketamine users were every day users. I'd be very curious to see how taking a couple days off every week would have changed things. If we could apply what we know about muscle atrophy then I think even 2-3 days of good brain/LTP/NMDA "exercise" will help prevent a lot of the atrophy seen in K users.
 
Yeah I mean I know very little about NMDA receptors and the effects that the various ligands of it produce.

Until recently with all the hype surrounding ketamine I don't think that NMDA/AMPA receptors haven't been much studied. That said, in the next ten or so years, there will be a lot more research into glutamate. It seems to be largely responsible for plasticity.

No doubt though that there are stories of people being permanently fucked up due to DXM abuse over a decent period of time.

At the very least, if I were you and were dead set on using recreational NMDA antagonists, I'd keep it to drugs that have a semblance of verified safety to them.

And some people do entirely lose it under the influence of hallucinogens and end up incarcerated as a criminal or a convict.

HPPD is definitely a possibility.
 
Ho-Chi-Minh said:
Until recently with all the hype surrounding ketamine I don't think that NMDA/AMPA receptors haven't been much studied. That said, in the next ten or so years, there will be a lot more research into glutamate. It seems to be largely responsible for plasticity.
Click to expand...

AMPA and NMDA receptors are two of the most highly studied neurotransmitter receptors.
 
Serotonin, what do you think is responsible for the Ketamine abuser's abnormal MRIs? Anything to do with negation of LTP or do you think it might be something compound specific to ketamine?
 
Ho-Chi-Minh said:
Hmmm bizarre, not monoamine receptors?
Click to expand...

The monoamine receptors have certainly been studied. But AMPA and NMDA receptors play a fundamental role in neural processing, learning, memory, etc., as well as in a wide range of disease states. As an example, many electrophysiologists work on projects unrelated to monoamine systems but glutamate receptors tend to be involved in everything because glutamate is one of the main ways that excitatory cells communicate.
 
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