Well, it's not that simple. It's reasonable to expect that you could see some increased level of oxidative and excitotoxicity. It's harder to draw a bright line around the dopaminergic system specifically because some level of neuronal death is expected over the course of a lifetime. We lose 5-10% starting with middle age yet don't tend to show parkinsonian symptoms until 60-80% are gone.
It's pretty reasonable to expect reversing DAT and inhibiting VMAT2 increases oxidative flux, the question is really how much not if. Methheads certainly get "brain damage", but is nudging the average loss from 5-10% to 7-12% "damage"? Is it meaningful? Over 30, 40 years that could very well add up.
Meth is also used as an ADHD treatment. I think the reason is just the dosages that are used by addicts compared to people who just need the ADHD treatment.
A typical legitimate therapeutic methamphetamine dose is around ~20mg (up to maybe 60mg a day). A typical dose used by addicts is around 1 gram. And it's usually smoked, resulting in immediate bioavailability.
It's pretty reasonable to expect reversing DAT and inhibiting VMAT2 increases oxidative flux, the question is really how much not if. Methheads certainly get "brain damage", but is nudging the average loss from 5-10% to 7-12% "damage"? Is it meaningful? Over 30, 40 years that could very well add up.