^^That isn't necessarily the case either. A pretty good review of this issue can be found here: Advokat C. Literature review: Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD.
Journal of Attention Disorders. 2007;11(1):8–16.
The old conventional wisdom was that in therapeutic doses typically prescribed, taken orally and never in extended 'binge' style durations, psychostimulants are not neurotoxic, while at the large doses taken for recreational purposes, they are. This was supported by years of clinical observations and a slew of animal studies indicating that extremely large doses of methylphenidate given to animals (mostly rodents) for quite some time produces very minimal brain damage. It was largely assumed that this was also true of the amphetamines when taken therapeutically. The studies that showed that amphetamine was seriously neurotoxic involved continuous IV administration of doses greater than 15 mg/kg/day for several days. Their results were not believed to be generalizable to typical clinical use in humans of doses in the .1-.5mg/kg range, once or twice a day, orally.
Recently, things have change. First, with the recognition of adult adhd, prescribed doses increased, sometimes up to almost 1mg/kg. Further, both to curb abuse and to extend treatment coverage, long-lasting formulations were designed. Several recent studies have attempted to simulate those conditions in animals (now including primates). As long as doses are under 15mg/kg per day, or the duration limited to three days or less, rats only suffer short-term dopamine depletion, avoiding actual damage to dopamine nerve terminals. Unfortunately, it turns out that primates in general are more susceptible to amphetamine neurotoxicity than rodents. In baboons and squirrel monkeys, doses as small as .67mg/kg, administered twice daily for 4 weeks significantly reduced striatal dopamine concentration, transport density, and vmat sites:
Here we demonstrate that amphetamine treatment, similar to that used clinically for adult ADHD, damages dopaminergic nerve endings in the striatum of adult nonhuman primates. Furthermore, plasma concentrations of amphetamine associated with dopaminergic neurotoxicity in nonhuman primates are on the order of those reported in young patients receiving amphetamine for the management of ADHD.
Source: Ricaurte GA, Mechan AO, Yuan J, et al. Amphetamine Treatment Similar to That Used in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder Damages Dopaminergic Nerve Endings in the Striatum of Adult Nonhuman Primates.
J Pharmacol Exp Ther. 2005;315(1):91–98. doi:10.1124/jpet.105.087916.
Does that mean therapeutic doses in adult humans are neurotoxic? Well, maybe. On the one hand, we are more similar to baboons than rats, so ceteris paribus what is true for baboons is more likely to be true for us than what is true for rats. On the other hand, there is no consistent evidence that people who have been treated with psychostimulants for the entire lives are more likely to develop parkinsonism or other related neurological impairments. It is plausible though that we might miss this, for a variety of reasons, the main being that there is no longitudinal study that tracks people who have been chronically treated with psychostimulants their entire lives. Of course, even if we did have evidence of that, it wouldn't necessarily mean that the amphetamine was neurotoxic; it could simply be the result of the same underlying dopaminergic dysfunction that was behind the ADHD.
In short, there is a lot we don't know, and it is an extremely complicated puzzle, but there is reason to be concerned:
At present, the reason for the apparent contradiction between results in primates, showing neurotoxic effects of low-dose AMPH, and those in rats, showing neurotrophic effects, is not apparent. However, recent neuroimaging studies in ADHD-diagnosed humans may be relevant. Several reviews have described an elevation of the striatal dopamine transporter (DAT) availability in children and adults with ADHD (Madras, Miller, & Fischman, 2005; Spencer et al., 2005; Volkow, Wang, Fowler, & Ding, 2005). Moreover, after methylphenidate treatment DAT availability is lowered in both children and adults (Krause, la Fougere, Krause, Ackenheil, & Dresel, 2005 and references therein; Madras et al., 2005; Spencer et al., 2005). Relationships between DAT density and treatment response to MPH have also been observed. Decreased DAT binding has been associated with a positive treatment response, whereas low DAT availability did not “seem to respond to therapy with MPH” (Krause et al., 2005). Unfortunately, such results may be confounded by the fact that, depending on the time between stimulant administration and the neuroimaging procedure, a portion of the decreased binding could be because of MPH occupation of DAT sites rather than DAT downregulation. It must also be kept in mind that primate and rodent models do not “have” ADHD. Nevertheless, comparisons of individuals treated with MPH or AMPH as children, with those who were not given stimulants, might be informative. Somewhat surprisingly, the “effects of repeated therapeutic doses of amphetamine on DAT density in living human brain are unknown” (Madras et al., 2005, p. 1403).
In summary, recent pharmacological developments, of long-acting AMPH formulations coupled with clinical developments in the diagnosis of ADHD, raise new questions about the neurobiological effects of stimulant therapy. Answers to these questions may not only be relevant for understanding the etiology, therapy, and treatment of ADHD but could also have broad implications for our concepts of the general processes that mediate behavioral and intellectual development.
Source -- the conclusion of the 2007 review article I mentioned initially (pp. 15-16).
Given all of the evidence, while it is premature to say anything too definitive about the existence/nature/extent of the neurotoxicity of therapeutic doses of amphetamine, from a harm reduction standpoint, it makes sense to presume that they are somewhat neurotoxic and make decisions accordingly.
