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Non-neurotoxic drugs.

Unfortunately I'm still a 'Greenlighter' and thus cannot PM you. My address is the same as my username; it's a g-mail account. Someone edit my post if it's against the rules to solicit personal information publicly, though.

How safe are the z-hypnotics in relation to cognitive effects? Are those the hypnotics you were referring to, theWorldWithin? Or were you talking about GHB and the like? What of their safety, too?
 
Benzo's and tropanes aren't as directly toxic as amphetamines and such but cause down regulation of receptors I think . Xanax for example will leave you with lesser GABA density. As stated in an above post though the risks are low for occasional use
 
rocknroll714 said:
That being said, here are the relatively few mainstream neurotoxic drugs I'm aware of:

  • Dissociatives [NMDA receptor antagonists] (alcohol, DXM, ketamine, PCP, nitrous oxide, etc).
[/LIST]
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References would be nice.

To my knowledge, all allegation of at least Ketamine's "toxicity" are theoretical at best (if not just plain mythical). On the other hand, most of the NMDA-antagonists mentioned above are actually proven neuroprotective.

Example: http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
 
Jamshyd said:
References would be nice.

To my knowledge, all allegation of at least Ketamine's "toxicity" are theoretical at best (if not just plain mythical). On the other hand, most of the NMDA-antagonists mentioned above are actually proven neuroprotective.

Example: http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
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Yes, there is a bevy of studies which demonstrate the neuroprotective effects of dozens of NMDA antagonists; but the problem with those studies is that the NMDA antagonist is always administered within a short time after or before, or even simultaneously with, the NMDA agonist or other substance known to evoke neurotoxicity. The results of these studies, which show a near abolition of brain damage compared to controls, are not surprising in the least. What I would be more interested in seeing is a study that addresses itself to the elucidation of what happens when an NDMA antagonist is administered to humans in sane doses who were not in the process of, or on the cusp of, incurring brain damage due to some excitotoxic agent or event. That would be more telling. Though you may well be right, in the meantime I do believe I will avoid any and all potent NMDA antagonists just to be safe.

-----

It's not really an interesting or useful question to ask which recreational drugs do or do not cause one or more of a narrow range of permanent or long-lasting undesireable changes in brain structure or function, IMHO. In using drugs, people universally wish to avoid any and all unsavory effects, not just esoteric ones or those meeting a rather stringent and exclusive set of arbitrary criteria. If this discussion is to continue, I propose we adopt an interim definition of 'neurotoxic' that applied to any drug which were able to cause any sort of undesirable gross or minute, macroscopic or microscopic neuroarchitectural changes whether with long-term or short-term use or by rebound effect (one has to stop sometime; why not take into consideration what happens then?). Of course, the drawback of that is that, with the adoption of such a definition, the only thing that can really be said at that point is "No, OP, there's hardly such a thing as a non-neurotoxic recreational drug".
 
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Opiates

NMDA excitotoxicity has been studdied to some extent as it relates to opiate tolerance. Neuronal Apoptosis Associated with Morphine Tolerance: Evidence for an Opioid-Induced Neurotoxic Mechanism
Tolerance to the analgesic effect of an opioid is a pharmacological phenomenon that occurs after its prolonged administration. Activation of the NMDA receptor (NMDAR) has been implicated in the cellular mechanisms of opioid tolerance. However, activation of NMDARs can lead to neurotoxicity under many circumstances. Here we demonstrate that spinal neuronal apoptosis was induced in rats made tolerant to morphine administered through intrathecal boluses or continuous infusion. The apoptotic cells were predominantly located in the superficial spinal cord dorsal horn, and most apoptotic cells also expressed glutamic acid decarboxylase, a key enzyme for the synthesis of the inhibitory neurotransmitter GABA.
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It looks like NMDA agonism is involved in the neuronal pathway(s) opiates take to the VTA (I theorize). Considering above, if glutamate induced extitotoxicity does raise opiate tolerance, then it could be considered as your brain's plasticity in action, attemting to adjust, rather than neurotoxicity.

I'm looking for some research on NMDA antagonists used with opiates besides morphine. If they work at preventing tolerance to other opiates, I would think that the excitotoxicity induced by morphine, is not limited to said drug.
 
^ Let us, for the sake of argument, say that NMDA-antagonists cause Olney's Lesions IN HUMANS.

So what? In the 70+ years that Ketamine has been used in medicine and recreationally, have we seen OL's effects in humans?

Why does Ketamine continue to be used after so many years if it is so toxic?

If you do a search on pubmed, you'll see an abundance (particularly in 2009) of research suggesting Ketamine as a therapeutic agent for MANY diseases, yet almost no research that proves that Ketamine SPECIFICALLY causes any damage.

Research on "NMDA antagonists" says about as much about Ketamine as research on Reserpine says about MDMA.
 
^ I don't believe you were being sarcastic about Lilly, but I actually do not deny that abuse of Ketamine can produce health problems, just like every other substance, including vitamins. My argument is simply that Ketamine itself has not, so far, been proven to cause any serious health issues with moderate use, and on the contrary, seems to be a very versatile medicine for a wide range of agonizing diseases (even something as unexpected as rabies! - will look for link if requested!).

It seems that much of Ketamine's stigma stems from two basic mythological ideas: 1. That it is related to PCP and therefore MUST be bad; and 2. That it is a horse-tranquilizer that puts holes in a person's head.

As for my personal experience, I'd been using Ketamine on and off for the past 6 years or so, and every time I used it, I was healed of some ailment or another. I have not experienced any of the things I read about except for this one time when I seriously abused it and felt some pain in my stomach. But besides that? nothing else.

Another interesting anecdote to share: Although I can vouch for the fact that chronic abuse of K seems to produce short-term, reversible impairment of linguistic-recall ("tip-of-the-tongue" syndrome), using K sporadically in small amounts has proven a fantastic study tool that helped me ace all of my very difficult university exams in Ancient Hebrew Grammar.

If you REALLY want to look at it objectively, there is more evidence that common day-to-day FOOD items are more toxic than Ketamine!
 
rocknroll714 said:
This is actually only partially true.

Methylphenidate has been demonstrated to be non-neurotoxic in adult rodents:

However, interestingly, it is neurotoxic in adolescents:

Considering a lot of us here are still teenagers and our brains are still developing this could be a bit of a concern. Not to mention all the six-year-olds on Ritalin these days. On the other hand methylphenidate appears to actually be neuroprotective and not just non-toxic in adults:

So I suppose if you're 25 or older you may not have anything to worry about and you should perhaps even pat yourself on the back for taking Ritalin. Then again these are all just rodent studies, and humans are obviously quite a bit different.
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I find it very stupid to give any chemicals to kids anyway. Only adult A(D)HDs should be treated with chemicals.
 
hamhurricane said:
the recent article "Hyperphosphorylated tau in the brains of mice and monkeys with long-term administration of ketamine" certainly raised some concerns for me.
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Honestly, honestly, do YOU know what in the seventh heaven is tau and what does it mean if it gets "hyperophosphorylated"?

I actually looked into it. It seems to have something to do with micro tubules. I still have no idea what this is all about. Maybe someone can enlighten me as to how this connect-the-dots study says anything about Ketamine's safety?

Rock: Oh yes, I am definitely biased toward the fact that Ketamine has been found to do a lot more good than bad. I suppose I should be concerned about my tau and its hyperphosphorylation, but for now I'm happy to know that it is doesn't seem to interfere with K's therapeutic effect :).
 
Tau protein phosphorylation is modulated by the enzyme GSK-3b. Lithium when used as a drug reduces tau phosophorylation. This is suspected to be one way that lithium acts on the CNS, as a GSK-3b inhibitor and enhancer of tau protein microtubule binding.
 
OK, but in theory if ketamine caused TPP and to a significant extent, one might expect to find signs of damage in the areas lithium is said to protect, say the hippocampus.

http://cercor.oxfordjournals.org/content/15/6/749.abstract

Not saying that this is supporting evidence for this phenomenon, but it looks like it could be an explanation of ketamine's short term effects on search and recall of episodic memory. I'm not really sure what, "left frontal activation is augmented by ketamine when elaborative semantic processing is required at encoding," would translate to in terms of changes in typical mentation. It is a short term use study, but at least it's on humans.

Also there is some evidence that just as methylphenidate's effects are age related, ketamine's effect on the brain is age dependent. This study indicates a significant reduction in hippocamampal Acetylcholine, which could further suggest a link between TPP and ketamine's effects on declarative memory. http://www.ncbi.nlm.nih.gov/pubmed/10669282

In the end it really comes down to anecdote and risk versus reward. It seems clear to me that ketamine will impair memory of the kind necessary to teach or lecture. So if your in that kind of profession or aspire to be, you might consider keeping any use moderate. That said, I have friends who LOVE the stuff, don't keep it moderate, and in practically all their cases I can say they aren't the kind of zombies our DARE officers told us we would become if we used PCP.

I'm not a pharmacologist, nor even a neuro scientist. I am active in a profession that requires understanding of language, so I have peripheral knowledge of pharmacology, neurochem, psychology, etc... But just like my knowledge of everything else, with one or two exceptions, it's limited. So please don't flame me for anything I just said.

Personally, I'm more interested in opiates. I haven't found any strong evidence that WD would be toxic, but I can imagine it does stimulate glucocorticoids which would at the least temporarily damage the hippocampus. Would that be confined to acute withdrawal, or would a diminished version also likely occur in PAWS? What would the impact of chronic use of suboxone be? I've managed to take bits and pieces and create kind of a picture. That said I'm not really sure what the combination of a partial agonist with naloxone would be, and there isn't much information on it's active metabolite norbuprenorphine. I recall reading it caused apoptosis of NG108-15 cells, which would lead to non cerebrum related nervous damage if I'm not mistaken?

Risk versus reward I guess... )o8
 
"A postmortem examination of five brains of elderly people with better memory than average—called "super aged" -- found that these individuals had less fiber-like tangles of tau protein than found in typical elderly brains, but a similar amount of amyloid plaque."
 
So far have any studies demostrated long term toxicity cause by methoxetamine?

It was studies to be a berfect hybrid between 3-methoxyphenylcyclidine ethycyclidine and ketamine, the ethyl was added to increase potency and thus reduce stress on liver and kidneys, The 3-methoxy seems to give it a higher DRI and opioid activity from what i can remember and it was considered far far less toxic even if smaller dosages can be a risk for uncarefull people.

Already the difference between racemic and s-ketamine is quite drastic.
 
^i too wonder about Methoxetamine.


Can someone actually show/prove that nitrous use is nuerotoxic at all in any way?
I thought it was like the one drug with no harmfull health effects?
(aside from vit B depletion if your huffing tanks of it daily)
 
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