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Ketamine: loss of effects means brain damage?

~_Hiss_~

~_Hiss_~

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This was taken from erowid, in an article called "This is your brain on dissociatives". I know the validity of this article is probably small, but here is an interesting part I've been wondering about:

Many of the peculiar effects of dissociatives seem to correspond with their effects in animals (including damage). DXM users often report that their upper-plateau trips rapidly lose the interesting effects, perhaps because the cells that are going haywire (and making the whole temporal lobes function unusually, thus the effects) are burning out.
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I have used ketamine many times at high doses over the past 4 years. I've noticed a 50% increase in tolerance as well as less memory of the experiences and less "mystical" effects like I once had. Does this mean the brain cells that caused the interesting experiences are dead? Or could they have learned to ignore the K?

I have noticed memory problems following using K for a while then stopping. I don't remember how long it lasted or if it ever went away though. Hopefully us K-heads and ex-K-heads will be fine and our wonderful grey chunks of magic will continue on like nothing happened. Or not much at least.
 
Wouldn't this be due to NMDA receptor upregulation?
(No, not downregulation, since Ket is an antagonist, not an agonist...).

It is //possible// that you coudl get some excitotoxicity from prolonged and intense K use, but I haven't seen the evidence to show that recreational-level use can do this.

More likely than not however i'd sugegst you've simply become used to K's effects so it just doesn't seem all that interesting anymore.
 
Many of the peculiar effects of dissociatives seem to correspond with their effects in animals (including damage). DXM users often report that their upper-plateau trips rapidly lose the interesting effects, perhaps because the cells that are going haywire (and making the whole temporal lobes function unusually, thus the effects) are burning out
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1) Effects in animals do not automatically equate to identical effects in humans. Rat's can eat MPTP with impunity, let a human ingest a tiny amount and they have severe, permanant Parkinson's disease.

2)DXM is not ketamine. DXM acts at may more receptors than ketamine and is basically a much more toxic drug to use in dissociative doses (eg it can cause hyperthermia which is known to cause neuron death if prolomged

3)'cells going haywire... and burning out' is hardly a scientific observation. Memory loss does not equate to neural deaths etc as NMDA receptors in the hippocampus are integral to LTP & memory formation, so it would be expected, not a sign of damage.
 
I've never really understood how NMDA antagonism could cause brain damage. Atrophy of neurites maybe, (which would fit in with an impairment of memory formation) but not damage?
 
~_Hiss_~ said:
Hopefully us K-heads and ex-K-heads will be fine and our wonderful grey chunks of magic will continue on like nothing happened. Or not much at least.
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I don't mean to be a dick here, but if your K is grey chunks thats really not a great sign. You should first be concerned about what is making your K grey and the possible problems associated with this cut (whatever it may be). Unless there is something I am missing, it was my impression that decently pure K is always shards of somewhat opaque crystals when dried out.
 
:) .

Thanks for the replies, I feel better but I wish I knew why the effects aren't like they used to be. Hopefully that doesn't also mean my imagination got weakened, if the two are related. That question may be a mystery for some time to come.
 
Altered prefrontal dopaminergic function in chronic recreational ketamine users.Narendran R, Frankle WG, Keefe R, Gil R, Martinez D, Slifstein M, Kegeles LS, Talbot PS, Huang Y, Hwang DR, Khenissi L, Cooper TB, Laruelle M, Abi-Dargham A. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. [email protected]

... In chronic ketamine abusers, limited studies suggest the persistence of neurocognitive deficits up to 3 days after use, but these studies are compromised by the polysubstance use in these samples (12, 13). ... The animal literature suggests that repeated exposure to noncompetitive NMDA antagonists leads to sustained impairment of performance in numerous cognitive domains, such as working memory tasks (reviewed by Jentsch and Roth [14]). These deficits induced by NMDA antagonists have been linked to reduced function of the prefrontal dopaminergic system, which plays a critical role in sustaining working memory and executive functions (15–19). ... Thus, in experimental animals, chronic exposure to NMDA antagonists has led to deficits in presynaptic dopaminergic function in the prefrontal cortex, which are associated with a compensatory up-regulation of postsynaptic dopamine D1 receptors.

... In contrast to the ketamine users studied previously, who were polydrug abusers (12, 13), subjects included in this cohort did not exhibit neurocognitive alterations on a battery of tests administered after 2 days of monitored abstinence.
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So this study says that the D1 receptor upregulation in the dorsolateral prefrontal cortex as a result of ketamine use is true for humans as well. It reports no cognitive deficits at two days abstinence (vs. three days for the previous polydrug abuser study). The imaging for D1 receptor, however, was done at least three days post use so apparently it persists somewhat, but doesn't significantly impact cognitive performance. I think it would be interesting to see if the D1 receptor levels return to normal after a month or so of abstinence. From what I can tell, this study didn't report "damage" per se, but instead it pointed to a seemingly reversible mechanism (I could be wrong about this). I thought it was also interesting to read that D1 receptor upregulation in the dorsolateral region of the prefrontal cortex is a hallmark of schizophrenia.

Still no evidence of damage.
 
No, but I've induced it in myself before (not on purpose...) from overdoing amphetamine & sleep deprivation. OK it only models for paranoid schizophrenia, but I think that's the most commonly diagnosed form. My only 'defect' in that sense is manic-depression and not severe at that!
 
I, like F&B, have (or "am?" just doesn't sound right!) bipolar. I don't know about F&B's reactions, but for me, Ketamine was (and still is, whenver I have access to it) more mood-stabelizing than any other drug I've taken. When I have K available to me, I take daily 10mg-ish doses and never get unreasonable dips or jumps that way. The effect remains for a while afterwards. Also, while the state of dissociative is anything but smart, the after-effects of a high-dose ketamine trip are very nootropic, especially when it comes to linguistic skills.

As for the similarities in my experience between schizophrenia (also amphetamine/sleep deprivation-induced here) and dissociatives, of the ones I've tried, I'd say that only PCP of all the dissociatives I tried comes close to it. Though I suppose psychosis is even more subjective than drugs, so it would be hard to compare my case to F&B's or others'.
 
Sorry if this post is inappropriate in this thread but would anyone care to comment on the damage potential when contrasting user a:

A) Never encounters the K-hole but consumes huge quantities of ketamine over the course of 24-72 hours, bumping away to maintain a consistent level of intoxication (3 grams perhaps).

and user b:

B) Takes either a sufficient singular IM dose or intranasal dose (100-250mg perhaps) to enter the K-hole. Maintains a multiple day gap (3 days) between dosing, where consumption is restricted to a two week period (consumption last for no longer than 14 days in both cases, user A is assumed to take 3 days break between 24-72 hour dosing, user b takes a similar break but doses only once every 3 days).
 
^ User A is doing a lot worse to himself. And by not going to the K hole is missing out on the best part. Repeated doses don't give the brain time to recover at all, it keeps shutting off more brain cells, some of which cause overstimulation by switching off inhibitory neurons. Thats my opinion though, probably not exactly scientific.
 
Matt the Raver said:
I've never really understood how NMDA antagonism could cause brain damage. Atrophy of neurites maybe, (which would fit in with an impairment of memory formation) but not damage?
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Neurotoxicity..overexcitability of the neurotransmitter leads to cell death and therefore brain damage.
 
fastandbulbous said:
^Well from what I've read & experienced, the dissociative state and schizophrenia have more in common that any other drug intoxication, so it's not too surprising
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i don't think a 'state' of schizophrenia can really be acheived..like i mean it takes years and years to develop, stages of social withdrawal coupled with many other factors and also genetic susceptibility for the disease to kick in..im not sure whether a temporary state occurs? Possibly just you get one or two of the symptoms but then again Schizo is "the most characteristic plague of the twentieth century" so its easy to get a few.
 
Symmetrical Daze said:
^ User A is doing a lot worse to himself. And by not going to the K hole is missing out on the best part. Repeated doses don't give the brain time to recover at all, it keeps shutting off more brain cells, some of which cause overstimulation by switching off inhibitory neurons. Thats my opinion though, probably not exactly scientific.
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Well, 'not exactly scientific' or not, that was the answer I was hoping someone would come back with.

Totally agree about 'he who will no hole, loses' - the handful of k-hole experiences I can draw from, outrank the one-time bumping (never been a bumper myself) by ooh, a hundred-million-billion to one. Nah, I'm a little off - the figure is far higher than that.
 
Vid P said:
Neurotoxicity..overexcitability of the neurotransmitter leads to cell death and therefore brain damage.
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I'm aware of the connection between excessive neural activity, glutamate release, oxidative stress and cell death.

My point was that an NMDA receptor antagonist (such as ketamine) works by blocking calcium ion influx, thereby reducing neural activity and cell death.

So if ketamine reduces neural activity it must surely be causing cell death by another process. But how?
 
I use ketamine almost daily (with psychedelics recently) and I haven't seen any lost of effects.
 
almost- said:
I use ketamine almost daily (with psychedelics recently) and I haven't seen any lost of effects.
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You'll start to notice memory problems if you keep up the daily dosing regeime as NMDA antagonism reduces LTP (long term potentiation), which is essential for the storage of memories. It does this by buggering about with the hippocampus, which is effectively the Heathrow airport/Grand Central station when it comes to memory formation. I'm not sure if it's irreversible, but either way, you're going to potentially have large vague gaps in your memory as you get older and the most insideous thing is that because your memory is buggered, you can't remember what having a fully functioning memory is like.

Far better to rearrange your dosing to prevent it getting to the point where your memory is in big danger of suffering. It'll also slow the development of a monster ketamine tolerance
 
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