In short it fucks with the pleasure receptors (dopamine, etc) to such a degree that they cannot regenerate to the way they were previous to meth use. With opioids for example even with the needle it is said by most doctors that the brain's opioid receptors return to normal about 1yr after the cessation of opiate use and abstinence from opioids. With methamphetamine this recovery is not possible even after long periods of time, since the mechanism of both releasing and of re-uptake of dopamine neurotransmitters are such disrupted during meth use, even if used in moderation like once every 5 days (smoking and injection in particular cause the most damage).
The pleasure and reward system are completely 're-written' and most meth users most often smoke, meaning in maximum 10 sec the drug reaches the brain and severely disrupting the reward system more so than crack cocaine because not only is there constant dopamine released but the re-uptake of dopamine is also blocked so that the dopamine is accumulated in the membrane until the drug wears off in which case both the free flow of dopamine stops being released and the re-uptake is no longer blocked, in essence removing the dopamine barricade that is the re-uptake.
The dopamine released 'on masse' during the long duration high but also the barricade causing the dopamine constantly released to be closed from the natural re-uptake results in a dopamine concentrated area in the brain, now depleted and having minimal dopamine to release nor having any dopamine stocked up in the re-uptake, the user is faced with a 'crash' accompanied by depression, absolute inability to sleep (no matter how strong the sedative) and the increasing feelings of depression ranging from light to extreme for the next 8-10hrs and is felt upward to the 2nd day, mostly from lack of sleep along with a very fast running mind thinking all kinds of depressing things.
When faced with this feeling, instead of taking a sedative like a benzodiazepine and attempting to sleep, the vast majority (over 80% users) choose to re-dose on meth again in order to bring their buzz back. The more this is done, the harder the crash and its not uncommon for people to stay awake for upwards to 4-5 days at a time and sleep for 2 days when they crash, mind you, by this time in full delirium that is not able to distinguish hallucination from reality. Also once every 5 days isn't really moderation because snorting can last an easy 12hr-16hr with a 10hr-12hr comedown along with 1-2 days residual effects and maybe 1 day to actually 'heal' in which the meth is probably going out your system which is why you use again.
Remember that meth is very addictive, even for people who not only hate but detest stimulants, like heroin users looking to stay wake for cheap instead of more costly bumps of coke or the traditional caffeine & cigarettes who do not intend for meth to be their main drug but something to keep them up ends up consuming them; they believe it helps them do more work but in reality they are completely spun in that I've seen someone inject H, then 4min later hit a meth pipe. When I asked why he's smoking meth when he had both crack and good soft on him he said 'I have to work, don't I?' to which it seemed that he made some sense but after spending the next 20min with him it was ridiculous. He received about 3 calls, after each call he'd weight x amount for all 3, then after placing the H in his pocket, he'd place his scale in the pocket, maybe do 1 more meth hit b/c shit hes got to work, and then repeat everything except weighting, checking his pockets over and over completely sketched out and what would have taken 3 minutes on H, took him 20min-25min on meth.
