<p><a href="https://en.wikipedia.org/wiki/Neuroplasticity#ADHD_stimulants" rel="nofollow noreferrer">This section from the Wikipedia page on Neuroplasticity</a> indicates (emphasis mine)</p>

<blockquote>
  <p>Reviews of <a href="https://en.wikipedia.org/wiki/Magnetic_resonance_imaging" rel="nofollow noreferrer">MRI</a> studies on individuals with <a href="https://en.wikipedia.org/wiki/ADHD" rel="nofollow noreferrer">ADHD</a> suggest that the
  <strong>long-term treatment</strong> of <a href="https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder" rel="nofollow noreferrer">attention deficit hyperactivity disorder</a> (ADHD)
  <strong>with stimulants</strong>, such as <a href="https://en.wikipedia.org/wiki/Amphetamine" rel="nofollow noreferrer">amphetamine</a> or <a href="https://en.wikipedia.org/wiki/Methylphenidate" rel="nofollow noreferrer">methylphenidate</a>, <strong>decreases
  abnormalities in brain structure and function</strong> found in subjects with
  ADHD, and improves function in several parts of the brain, such as the
  <a href="https://en.wikipedia.org/wiki/Caudate_nucleus" rel="nofollow noreferrer">right caudate nucleus</a> of the <a href="https://en.wikipedia.org/wiki/Basal_ganglia" rel="nofollow noreferrer">basal ganglia</a>.</p>
</blockquote>

<p>The following studies are cited as reference:</p>

<ul>
<li><p><a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0447.2011.01786.x" rel="nofollow noreferrer">Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects</a> (Frodl <em>et al</em> 2012)</p></li>
<li><p><a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/1485446" rel="nofollow noreferrer">Meta-analysis of Functional Magnetic Resonance Imaging Studies of Inhibition and Attention in Attention-deficit/Hyperactivity Disorder: Exploring Task-Specific, Stimulant Medication, and Age Effects</a> (Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K 2013)</p></li>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3801446" rel="nofollow noreferrer">Effect of Psychostimulants on Brain Structure and Function in ADHD: A Qualitative Literature Review of MRI-Based Neuroimaging Studies</a> (Spencer TJ, Brown A, Seidman LJ, <em>et al</em> 2013)</p></li>
</ul>

<p>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.</p>

<p>From what I can understand, long-term use of ADHD stimulants <em>in individuals with ADHD</em> (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 <em>all</em> deficiences, though (i.e. effects visible on the right anterior cingulate cortex (ACC) but not on the left ACC).</p>

<p>The paper from Spencer <em>et al</em> cites another - <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670101/" rel="nofollow noreferrer">Potential adverse effects of amphetamine treatment on brain and behavior: a review</a> (Berman, Steven M. <em>et al</em> 2009). I didn't have a chance to look into that just yet.</p>

CC BY-SA 4.0
2018-06-29T09:56:15.223Z
In related news, [Long-term ADHD Medications Decrease Drug Efficacy by Increasing Dopamine Transporters](https://www.healthline.com/health-news/mental-long-term-adhd-medications-increase-dopamine-transporters-051613#1).
Marc.2377
CC BY-SA 4.0
2018-06-04T00:54:43.280Z
2018-06-27T21:40:19.883Z
2018-06-27T21:40:19.883Z
Marc.2377
<blockquote>
<p>If one was to take a 30mg dose once a day for 50+ years, would it damage brain function at all?</p>
</blockquote>
<p>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?</p>
<p>The answer:</p>
<ul>
<li><p>High doses of methylphenidate are neurotoxic</p>
</li>
<li><p>High doses of amphetamine are neurotoxic</p>
</li>
<li><p>High doses of methamphetamine are neurotoxic</p>
</li>
</ul>
<p>But despite being biologically plausible, very little research exists on whether long-term administration of these drugs in low doses is neurotoxic.</p>
<p>This topic is poorly understood for the number of people knowing the answer would be relevant.</p>
<h3>Evidence of neurotoxicity in non-human primates</h3>
<p>To date, I've only been able to find a couple papers examining this very topic.</p>
<p>In non-human primates, there's evidence to suggest that that chronic low doses of amphetamine could be:</p>
<blockquote>
<p><a href="http://jpet.aspetjournals.org/content/315/1/91.short" rel="nofollow noreferrer"><strong>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</strong></a></p>
<p>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. <strong>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.</strong> 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.</p>
</blockquote>
<p>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 <a href="https://www.nytimes.com/2003/12/02/science/research-on-ecstasy-is-clouded-by-errors.html" rel="nofollow noreferrer">here</a>.</p>
<p>Conversely, there's also evidence to suggest that that low doses of amphetamine aren't neurotoxic:</p>
<blockquote>
<p><a href="http://journals.sagepub.com/doi/abs/10.1177/1087054706295605" rel="nofollow noreferrer"><strong>Literature Review: Update on Amphetamine Neurotoxicity and Its Relevance to the Treatment of ADHD</strong></a></p>
<p><em>Objective:</em> 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. <em>Method:</em> Several databases were accessed for research articles on the effects of amphetamine in the brain of laboratory animals and ADHD diagnosed individuals. <em>Results:</em> <strong>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.</strong> <em>Conclusion:</em> Clarification of the neurological consequences of chronic AMPH treatment for ADHD is needed. (J. of Att. Dis. 2007; 11(1) 8-16)</p>
</blockquote>
<h3>Summary</h3>
<p>There's very little evidence either way. It's possible. Personally, I <em>really</em> think this needs to be examined in more detail.</p>

CC BY-SA 4.0
2020-07-23T16:35:21.473Z
This was a great answer, thank you for this.
Ted Taylor of Life
CC BY-SA 4.0
2018-06-04T14:31:01.407Z
2018-06-28T17:24:00.683Z
2020-06-17T09:55:31.633Z
faustus
<p>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.</p>

<neuroscience><performance><brain-development>
Do ADHD drugs harm the brain?
Kelsey
# Do ADHD drugs harm the brain?

(Asked by: username_0 on 2015-02-25)

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.

**Tags:** neuroscience, performance, brain-development


---

## 2 answers

### Answer by username_1 on 2018-06-04. Score: 5

[This section from the Wikipedia page on Neuroplasticity](https://en.wikipedia.org/wiki/Neuroplasticity#ADHD_stimulants) indicates (emphasis mine)

> Reviews of [MRI](https://en.wikipedia.org/wiki/Magnetic_resonance_imaging) studies on individuals with [ADHD](https://en.wikipedia.org/wiki/ADHD) suggest that the
> **long-term treatment** of [attention deficit hyperactivity disorder](https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder) (ADHD)
> **with stimulants**, such as [amphetamine](https://en.wikipedia.org/wiki/Amphetamine) or [methylphenidate](https://en.wikipedia.org/wiki/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](https://en.wikipedia.org/wiki/Caudate_nucleus) of the [basal ganglia](https://en.wikipedia.org/wiki/Basal_ganglia).

The following studies are cited as reference:

* [Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects](https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0447.2011.01786.x) (Frodl *et al* 2012)
* [Meta-analysis of Functional Magnetic Resonance Imaging Studies of Inhibition and Attention in Attention-deficit/Hyperactivity Disorder: Exploring Task-Specific, Stimulant Medication, and Age Effects](https://jamanetwork.com/journals/jamapsychiatry/fullarticle/1485446) (Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K 2013)
* [Effect of Psychostimulants on Brain Structure and Function in ADHD: A Qualitative Literature Review of MRI-Based Neuroimaging Studies](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3801446) (Spencer TJ, Brown A, Seidman LJ, *et al* 2013)

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](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670101/) (Berman, Steven M. *et al* 2009). I didn't have a chance to look into that just yet.

> **Comments:**
> **username_1**: In related news, [Long-term ADHD Medications Decrease Drug Efficacy by Increasing Dopamine Transporters](https://www.healthline.com/health-news/mental-long-term-adhd-medications-increase-dopamine-transporters-051613#1).  

---

### Answer by username_2 on 2018-06-04. Score: 4

> 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**](http://jpet.aspetjournals.org/content/315/1/91.short)
>
> 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](https://www.nytimes.com/2003/12/02/science/research-on-ecstasy-is-clouded-by-errors.html).

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**](http://journals.sagepub.com/doi/abs/10.1177/1087054706295605)
>
> *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.

> **Comments:**
> **username_3**: This was a great answer, thank you for this.  

---

