This is a fairly detailed file which covers a type of brain damage known as NMDA Antagonist Neurotoxicity or Olney's Lesions (after the researcher who discovered it). It also covers other risks of using dissociatives, and how to minimize them. If you currently use, have used, or plan to use, any dissociative (drug which blocks NMDA receptors or which is a dissociative anaesthetic), then you should read this document. This includes ketamine, PCP, dextromethorphan, and nitrous oxide; see Section iv. below for more information.
In addition to brain damage, these drugs can also trigger psychosis, limbic seizures, temporal lability, depression, and other neurological and psychological diseases much more frequently than other types of drugs. The dissociatives can be highly addictive to a minority of users. In comparison, the marijuana and the serotonergic psychedelics (LSD, psilocybin mushrooms, peyote, DMT) are many times safer.
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.
An interesting aside here, many people who really like dissociatives have told me they find them so attractive because they help to take away a near-constant self-consciousness, an almost self-absorbing embarassment or "inner critic". While I don't think any one part of the brain can be the "home" of anything so complex, I am willing to accept that the posterior cingulate may be a major contributor to self-evaluation gone haywire. The good news is, there are healthier ways of getting beyond this problem; see III.4 below.
The overactive cells begin to heat up, use up their energy supply generate toxic waste products, and/or let in too many calcium ions.
Regardless of the mechanism, or whether the mechanism is none of the above, the overactivity seems to cause intracellular organelles (notably mitochondria and endoplasmic reticulum) to malfunction.
The mitochondria probably lose their proton gradient and allow their innards to spill into the surrounding cell material, where they cause all sorts of trouble, possibly including forming free radicals which cause further damage to the cell. Another possibility is that the free radicals come first, and they cause damage to the mitochondria and other organelles. Mitochondrial damage can occur within 15 minutes of the drug dose, the endoplasmic reticulum is damaged 30 minutes, and in both cases gets worse as time progresses. The free radicals, basically, destroy everything in the cell like a rampant two-year-old on a spending spree through Toys-R-Us.

To put it bluntly, taking excessive doses of dissociatives make certain parts of your brain fry like the proverbial egg-on-the-frying-pan in the "This is Your Brain on Drugs" commercial.