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Particularly, the amphetamine "vyvanse". If one was to take a 30mg dose once a day for 50+ years, would it damage brain function at all? Would the brain simply get used to the drug and become 100% tolerant to it? Would the brain damage be permanent? Would the brain's performance be improved for the whole time taking the medication? These are some of the questions I have regarding ADHD amphetamines.

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This section from the Wikipedia page on Neuroplasticity indicates (emphasis mine)

Reviews of MRI studies on individuals with ADHD suggest that the long-term treatment of attention deficit hyperactivity disorder (ADHD) with stimulants, such as amphetamine or methylphenidate, decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.

The following studies are cited as reference:

I had a quick read on these papers and they do not appear to isolate Vyvanse (lisdexamfetamine) specifically. The one from 2012 doesn't even mention it; the other two address both methylphenidate and lisdexamfetamine. Each paper has their own limitations, for instance, standardization concerning comorbid conditions, age, etc.

From what I can understand, long-term use of ADHD stimulants in individuals with ADHD (this is important) does not appear to be associated with brain damage, but rather the opposite, they appear to promote "normalization" of certain structural deficiences. Not all deficiences, though (i.e. effects visible on the right anterior cingulate cortex (ACC) but not on the left ACC).

The paper from Spencer et al cites another - Potential adverse effects of amphetamine treatment on brain and behavior: a review (Berman, Steven M. et al 2009). I didn't have a chance to look into that just yet.

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If one was to take a 30mg dose once a day for 50+ years, would it damage brain function at all?

You ask a very good question, but I'm going to rephrase it for you: Is the chronic administration of low doses of methylphenidate (Ritalin), amphetamine (Adderall) or methamphetamine (Desoxyn) neurotoxic in humans?

The answer:

  • High doses of methylphenidate are neurotoxic

  • High doses of amphetamine are neurotoxic

  • High doses of methamphetamine are neurotoxic

But despite being biologically plausible, very little research exists on whether long-term administration of these drugs in low doses is neurotoxic.

This topic is poorly understood for the number of people knowing the answer would be relevant.

Evidence of neurotoxicity in non-human primates

To date, I've only been able to find a couple papers examining this very topic.

In non-human primates, there's evidence to suggest that that chronic low doses of amphetamine could be:

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

Pharmacotherapy with amphetamine is effective in the management of attention-deficit/hyperactivity disorder (ADHD), now recognized in adults as well as in children and adolescents. 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. These findings may have implications for the pathophysiology and treatment of ADHD. Further preclinical and clinical studies are needed to evaluate the dopaminergic neurotoxic potential of therapeutic doses of amphetamine in children as well as adults.

The problem with the above study is that it was led by a researcher called Ricaurte, who screwed up when he reported in 2002 that a single recreational dose of MDMA is neurotoxic. He had to later retract his findings when he learned that that the drug bottles were mislabeled and they'd accidentally administered methamphetamine instead. See here.

Conversely, there's also evidence to suggest that that low doses of amphetamine aren't neurotoxic:

Literature Review: Update on Amphetamine Neurotoxicity and Its Relevance to the Treatment of ADHD

Objective: A review of amphetamine treatment for attention-deficit/hyperactivity disorder (ADHD) was conducted, to obtain information on the long-term neurological consequences of this therapy. Method: Several databases were accessed for research articles on the effects of amphetamine in the brain of laboratory animals and ADHD diagnosed individuals. Results: In early studies, high doses of amphetamine, comparable to amounts used by addicts, were shown to damage dopaminergic pathways. More recent studies, using therapeutic regimens, appear contradictory. One paradigm shows significant decreases in striatal dopamine and transporter density after oral administration of “therapeutic” doses in primates. Another shows morphological evidence of “trophic” dendritic growth in the brains of adult and juvenile rats given systemic injections mimicking “therapeutic” treatment. Imaging studies of ADHD-diagnosed individuals show an increase in striatal dopamine transporter availability that may be reduced by methylphenidate treatment. Conclusion: Clarification of the neurological consequences of chronic AMPH treatment for ADHD is needed. (J. of Att. Dis. 2007; 11(1) 8-16)

Summary

There's very little evidence either way. It's possible. Personally, I really think this needs to be examined in more detail.

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  • $\begingroup$ This was a great answer, thank you for this. $\endgroup$
    – Ted Taylor of Life
    Jul 23, 2020 at 16:35

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