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(this is excerpted largely from the DXM FAQ's "Side Effects" section)
When NMDA antagonists were first studied they seemed like a dream come true: here were drugs which could block from part to all of the damage from strokes, head injury, hypoxia, polio, and a variety of other conditions. However, it seems that nature never gives something for nothing, and here too there was another side to the coin.
The dream ended when Olney et al. demonstrated that animals given high doses of dizocilpine (MK-801), a new dissociative used in research, showed curious vacuoles (essentially, tiny holes) in their brains. Specifically, the vacuoles showed up in the posterior cingulate cortex and retrosplenial cortex (see I.1 for an explanation of what these parts of the brain do). Further research showed that other indicators of damage were present, such as proliferation of microglia, secretion of a protein called HSP70 (Heat-Shock Protein 70), and expression of certain genes.
Since then, Onley's lesions, also known as NMDA Antagonist Neurotoxicity or NAN, have been discovered with ketamine, PCP, and dextrorphan (the metabolite of DXM), as well as a bunch of dissociative drugs you won't find outside of a research lab. PCP causes additional damage to the cerebellum and other areas, by the way.
For a long time, nobody knew whether Olney's lesions applied to human beings or not, or at what dosage they applied. The amount of ketamine used to knock out a rat, for example, is obviously different than the amount used for humans; it's also not the same dosage in mg/kg (milligrams per kilogram) either. And different effects of drugs "scale" differently too.
However, several things have happened recently which have led me to conclude that Olney's lesions apply to humans at recreational doses. First, I've received reports from many hundreds of users of DXM, some of whom have used it heavily and been clearly harmed. Second, more recent studies have shown that damage occurs to lab animals' brains even at lower doses (including ordinary anaesthetic doses of ketamine and dizocilpine!). Third, reports of ketamine-related brain damage have started to show up. Finally, the type of impairment people are reporting coincides exactly with the areas of the brain damaged in lab animals.
If you think you might be suffering from Olney's lesions, DON'T PANIC. You may just have depleted neurotransmitters, or induced long-term (but reversible) changes to neuroreceptor function. If you feel you are impaired, STOP USING NOW, and stay clean for several months before you get worried. Many people have told me that their "brain damage" cleared up after a few months.
IMPORTANT NOTE: Olney's lesions are WORSE in female animals than males, probably because females have different limbic connections. This may apply to humans.
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