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  • BDD Moderators: Keif’ Richards | negrogesic

which substances are Neurotoxic?

Many people say DXM (and other dissociatives like Ketamine) are neurotoxic without citing any medical evidence, simply referring to Olney's Lesions. I have yet to see any evidence that Olney's Lesions (or NAN) applies to humans. There have been medical studies where NAN has been observed in rodents, but never have humans proven to be susceptible to NAN. Until then, it's just not right to say K and DXM are neurotoxic (at least, not because of Olney's Lesions).

More info on this here: http://www.erowid.org/chemicals/dxm/dxm_health2.shtml
 
^^
Can you think of any chemicals that are neurotoxic in animals but not humans?

The brains of both animals and humans work in pretty similar ways...to say that you don't believe a chemical is neurotoxic because damage hasn't been proven in *humans* is a little over optimistic.
 
Well I kinda agree with you satricion. I think that 99.99% of the time, a drug which is neurotoxic in animals at dose X, is going to be neurotoxic in humans, but at dose Y.

The important differences between animals is generally pharmacokinetic, that is to say, the absorbtion, distribution, metabolism and excretion of drugs can vary significantly.

I think that Olneys lesions aren't going to be a big problem, because the doses used in animals are nearly always massive (with the exception of nitrous, but I'd like to see that repeated with a better measurement).
 
* Amphetamines used in small (for ADHD) amounts are probably not neurotoxic. The doses used in studies showing neurotoxicity were at least 10x higher than those used in Adderall/Dexedrine and also were done on meth, not regular amphetamine.
* Benzodiazepines - the examples that someone provided (that benzos are neurotoxic) are more of a "single-case" , not "normal". I haven't seen ONE study showing diazepam/clonazepam/alprazolam to be even slightly damaging to neurons.
* DXM - Onley's lesions have been shown at doses so high that no-one would use recreationally. And the studies are old and done poorly IMHO.
* Ketamine - there's no evidence that single dose of ket (~100mg) is neurotoxic.
* MDMA - there is some evidence that MDMA increases free radicals during dopamine release stage, and in the end damages serotonin receptors. But the studies are not totally interchangeable. To be sure - whenever you use MDMA it is wise and beneficial to load up on anti-oxidants - especially ALA [Alpha-Lipoic Acid] which has been shown in one study to _completely_ prevent MDMA's free radical neurotoxicity. Also Vit.E, Vit.C, Grape Seed Extract, Green Tea Extract are good anti-oxidants.
* LSD, Psylocybin, Weed, Heroin (&opiates), Nicotine - no evidence of neurotoxicity
* RCs - uknown status, they might or might not be
* Alcohol - the MOST neurotoxic drug of all (yet legal)
* GHB - the only 'drug' which is not only non neurotoxic, but actually neuro-protective (few studies show it, I can post them here if anyone wants). Some people consider it even one of the best anti-aging medicines of all time (it has many health benefits, apart from neuro-protection)

Just my 2 cents.
 
just from personal experience... a 3 day DXM bender messed up my ability to form sentances properly for several months. not proof thats its neurotoxic, but keep in mind something doesnt need to be neurotoxic to mess up your heaad.
 
satricion said:
^^
Can you think of any chemicals that are neurotoxic in animals but not humans?

The brains of both animals and humans work in pretty similar ways...to say that you don't believe a chemical is neurotoxic because damage hasn't been proven in *humans* is a little over optimistic.
Click to expand...
Ketamine is toxic in rats, creating Olney's Lesions, but not in primates. In the source I provided in my last post on this topic:

"In 1989, psychiatry professor John Olney reported that ketamine caused reversible changes in two small areas of the rat brain. 40mg/kg resulted in fluid-filled bags ("vacuoles") [Olney's Lesions] appearing inside cells. The bags disappeared after several days, unless high doses of the far more toxic PCP or close relative MK801 were repeatedly given, in which case some cell death was seen. Roland Auer injected monkeys with MK801 and was unable to produce any vacuoles."

Also:
"[Auer] doubted that it was even a remote possibility [that humans undergoing anesthesia with ketamine were at risk of Olney's Lesions] because of fundamental differences in metabolism between the rat and human brain." Remember that an anesthetic dose of ketamine is higher than any recreational dose. This article to continues to explain why ketamine (and close relative DXM) would not cause Olney's Lesions.

Another scientist, Frank Sharp, did a similar experiment. In his experiment, "Extensive attempts to produce toxic changes in monkeys had been a total failure at doses up to 10mg/kg i.m."

These experiments are the most convincing proof I have seen that ketamine and DXM do not cause Olney's Lesions in humans.

For more info, the article is located here: http://www.erowid.org/chemicals/dxm/dxm_health2.shtml
 
It might be interesting to note that Auer's investigations were never published... Also that Auer has previously had difficulties in even finding the vacuoles.

Though I've got to say trypt, the logic here is a bit cirucular. You say "NAN happens in rats but not humans", the other guy says "that sounds odd, whats a neurotoxin in rats, but not in humans?" and you says "ket is!".
 
BilZ0r said:
Though I've got to say trypt, the logic here is a bit cirucular. You say "NAN happens in rats but not humans", the other guy says "that sounds odd, whats a neurotoxin in rats, but not in humans?" and you says "ket is!".
Click to expand...
Whether my logic is circular or not, the evidence shows that primates simply are not affected by NAN/Olney's Lesions from ketamine or DXM.
 
Probably not too toxic - levels of toxicity of amphetamines were, in my understanding, measured at doses about 10 times higher than the highest normal prescribed dose of such amphetamines - but I could be incorrect. However, I am nearly 100% sure that the fact that its not too neurotoxic at prescription levels is viable.
 
Amazingly, I can only find a couple of papers looking at whether long term ADHD medication is toxic. You'd think it would be something worth looking at. And you know, if they did look at it, they would try and measure reuptake sites, which is a complete waste of time.

I'm not sure if there is enough research to conclude that olneys lesions don't occure in primates. I mean, I can only find a couple of studies. If you know of mroe, pleasure fill me in.
 
fairnymph said:
substantially neurotoxic: meth, amphetamine, DXM (in high doses as stated), nitrous oxide (whippets) , alcohol

mildy neurotoxic or not confirmed to be neurotoxic: MDMA, ketamine

not neurotoxic: LSD, salvinorin A (the active ingredient in salvia), cocaine, cannabis, mushrooms, opiates/opioids
Click to expand...

nitrous oxide is not neurotoxic as far as i know... what are your sources?
 
others

i read a long time ago (and forget the source, hebce reliability) the PCP has the same affect on the brain as mad cow disease/kuru/Creutzfeldt-Jakob Disease.

MPTP (look it up if unknown) can cause a disorder that is extremely similar to parkinson's disease within days of usage. Possible mitigating factors, which from my preliminary research may include: taking melatonin (vitimin supplement) within 12 hs, and possible genetics and/or nicoteine; as well as means of injestion, duration, and dosage. All they know is that for some reason not every one who mistakenly used it were affected.
-this chemical occurs when someone makes MPPP (demerol) wrong (illicitly).
-in some of the cases where it has surfaced it has been sold as heroin.
-there are a few making the claim that MPPP can eventually have similar effects.
 
PCP has the same affect on the brain as mad cow disease/kuru/Creutzfeldt-Jakob Disease
Click to expand...
* BilZ0r smacks his head against the table

Um, even IF the NMDA-antagonist mediated neurotoxicity is real, and does exsist in humans, it certainly is nothing like CJD...

See this figure. Note how the "holes" in BSE are extra cellular, and fucking large, even in mild BSE, while the hole in Olneys lesions are tiny, intra cellular vacuoles.

..and MPTP is so fucking rare it's not even worth talking about.
 
AlphaNumeric said:
I thought cocaine was pretty neurotoxic?
Click to expand...

as has been said, even long-term sustained cocaine IV to rats shows no evidence of neurotoxicity. Personality changes certainly, but there's no evidence of neuronal cell damage.

It's certainly cardiotoxic though
 
Re: others

astarythe said:
MPTP (look it up if unknown) can cause a disorder that is extremely similar to parkinson's disease within days of usage. Possible mitigating factors, which from my preliminary research may include: taking melatonin (vitimin supplement) within 12 hs, and possible genetics and/or nicoteine; as well as means of injestion, duration, and dosage. All they know is that for some reason not every one who mistakenly used it were affected.
-this chemical occurs when someone makes MPPP (demerol) wrong (illicitly).
-in some of the cases where it has surfaced it has been sold as heroin.
-there are a few making the claim that MPPP can eventually have similar effects.
Click to expand...

Why would melatonin prevent MPTP induced parkinsonism? It's caused by an interaction with MAOB. AFAIK only MAOB inhibitors have been shown of any real promise in protecting against this, though I may be wrong. Melatonin is an antioxidant, sure, but you dont even have very much of it. 3mg distributed throughout your entire body is rather little, and probably of no antioxidant significance.
 
BilZ0r said:
I'm not sure if there is enough research to conclude that olneys lesions don't occure in primates. I mean, I can only find a couple of studies. If you know of mroe, pleasure fill me in.
Click to expand...

AFAIK animals have only ever been shown to have olney's lesions after the administration of sufficient quantities of NMDA antagonists to achieve anaesthesia... I cant remember the source, but I seem to recall it was referenced.

Incidentally coadministering benzodiazepines with NMDA antagonists eliminates all potential neurotoxicity.
 
re: Melatonin- If its true, its because of it being a non-specific anti-oxidant(1, 2), just like how it protects in animal stroke models (there's also interesting evidence about it being a GABA-A modulator(3, 4))

animals have only ever been shown to have olney's lesions after the administration of sufficient quantities of NMDA antagonists to achieve anaesthesia... cant remember the source
Click to expand...
Yeah, it was probably me, I'm a really big doubter of Olney's lesions at recreational doses
 
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