I have a pretty good handle on pharmacokinetics and pharmacodynamics. There are some drugs that shift from one compartment to the next. For instance, propofol, used of surgical anaesthesia, is given intravenous. It rapidly distributes to the brain, where it exerts it's anaesthetic effects. It then further distributes to the fatty tissue, where it really wants to be. As long as the infusions continues, everything is fine. As soon as the infusion is stopped, no more "fresh" propofol is being delivered to the brain, and it redistributes to the adipose tissue. Fentanyl will do this as well. An IV dose rapidly accumulates in the brain, it has lots of blood flowing through it, and fentanyl loves the highly lipid environment of the brain. With time, fentanyl begins to move into the more poorly perfused adipose tissue, where it is even happier. Eventually most of the fentanyl leaches out of the brain in this second phase of distribution to enter the fat. This is sort of like a three compartment model.
I don't know of a case where a drug cycles in and out and then back into any single tissue, that seems pretty far fetched. I can imagine cases where it could be possible, but don't know of any. However, when you are dealing with knocking back one of the main excitatory, mucking around with calcium channels, whose millions of roles have effects on almost every aspect of the global neuronal function, many of them that oppose each other. There are so many possible ways by acting on neuronal circuits and feedback loops that the actions of this drug can itself cause waves and cycles of brain effects without the need for the drug to move from compartment to compartment.
As for causing structural changes to the brain, that is something that would take a substantial amount of damage and destruction for it to become apparent. I really don't think these sorts of structural changes would occur without there being significant neurological and psychological symptoms that would alert persons that things are falling apart. Of course, if they never sober up to see that their brain function is deteriorating, and continue with using, the outcome could be disastrous.
As for these structural differences in the brains of long term schizophrenia patients, they are not as simple as you might think. Are these changes the cause of schizophrenia, or the result of schizophrenia. Are the produced by the long term antipsychotic drugs that these patients are on? Is atrophy a function of there impoverished educational, social, and emotional lives they often live, especially when they are hospitalized.
Who knows. Daily drug use is a poor way to live your life, at least, for me, it was a terrible choice. Very occasional, moderate, careful use for recreation are something totally different. Daily use of most any psychoactive drug is likely to be detrimental to your long term quality of life (here I should mention that this applies to me and the choices that I made, different people, with different sets of substances may have different result, some better, some much worse). It would be surprising if messing around THE major excitatory neurotransmitter (90% of all excitatory messages are relayed by it), especially at the receptor most intimately linked with the formation, maintenance, and retrieval of memory and the storage of the bits an bytes of our lives could not, possible, cause some extremely dramatic negative benefits. Play smart is all I say.
