Ketamine and N2O

I came across this paper a while ago and was quite worried about the content. Read through and see what you think.

I have since seen arguments that Onley's lesions do not occur in humans and also aruments that they do, if anybody has any references to back up either I would be greatful for a link.
Should isoflurane be more available through a GP/harm reduction group?
Many people are not aware of the potential dangers of a commoonly used combination of drugs.
What are your thoughts as to how people can be educated about this, or if you have any evidence about the subject mentioned in the paper please post them here.


pdf

I've read through about half the paper so far and it is indeed slightly worrying considering my previous weekend was spent combining these exact two drugs... However whenever I read about neurotoxic damage involving ketamine I always notice that they talk about doses like 20-50 mg/kg. Now that's a hell of a lot of K for a human to take recreationally. Also the nitrous exposure they mention in this paper seems to be about 75% for 3 hours continuously. Which is also a lot more than the average recreational user would take.
Still something to be concerned about but perhaps not as bad as it would initially seem, thankfully.

In Ketamine: Dreams and Realities, Jansen states that 40mg/kg in rats is a pre-anestetic dose. So, the studies that mentioned damage at this dose wouldn't be irrelevant, if it weren't for the fact that rat brains' metabolisms are much faster than humans, which increases damage. Also, ketamine binds to many receptors supposedly, and some of these in humans will calm down the brain.

There are many drugs that are supposed to stop neurotoxicity from occuring, from benzodiazepines to LSD and 2c-b.

Interestingly, I've got images from that very paper uploaded... just ignore that BSE bit


Personally, my views on olneys lesions are thusly: The doses are so fucking high, they have little to do with humans, and b) Olney's lesions have never been shown to have a behavioural correlate, so until they do, I'm not concerned.

GFunk, I'm not sure you can say a sub-anaesthetic dose in a rat is equivalent in terms of damage to what a sub-anaesthetic dose in a human would cause.
Unless the damage is somehow being caused *by* the anaesthetic action itself (i.e it is the effect on brain function that causes the damage rather than some chemical reaction) I think the way to calibrate equivalent doses for a study such as this would be two doses that cause the same concentrations of ketamine to be found in the brain tissues.

Well its always mighty hard to scale between species... and drug effect is as much a logical way to scale as anything else, depending on what you're looking at.

Olneys theories are that the widescale inhibtion of excitation caused by NMDA receptor antagonism, leads to a an inverse lack of inhibition (because no one is exciting the inhibitory cells), hence, certain cells are able to fire like buggery and cause excitotoxic damage on cells which recieve input from them...

..This is of course crazy rubbish. A) If the damage was caused by excitotoxicity, then the cells would look like cells which have suffered from excitotoxicity, but they don't.
B) Excitotoxicity is blocked by NMDA antagonists, which there are extremely high concentrations of, when Olneys lesions are induced.