<p><strong>Short answer</strong><br>
All neuropsychopharmaceuticals, including the tryptamines, are potentially neurotoxic depending on the dose at which they are ingested.   </p>

<p><strong>Background</strong>  </p>

<p>Neurotoxicity is, arguaby, a broad definition. According to the NIH, neurotoxicity can be caused by processes ranging from radiation to transplants, and from chemical toxins to cosmetics. <a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Neurotoxicity-Information-Page" rel="nofollow noreferrer">NIH defines neurotoxicity as</a>:</p>

<blockquote>
  <p>Neurotoxicity occurs when the exposure to natural or manmade toxic substances (neurotoxicants) alters the normal activity of the nervous system. This can eventually disrupt or even kill neurons, key cells that transmit and process signals in the brain and other parts of the nervous system. Neurotoxicity can result from exposure to substances used in chemotherapy, radiation treatment, drug therapies, and organ transplants, as well as exposure to heavy metals such as lead and mercury, certain foods and food additives, pesticides, industrial and/or cleaning solvents, cosmetics, and some naturally occurring substances.</p>
</blockquote>

<p>LSD is a tryptamine <a href="https://i.sstatic.net/BdPGX.png" rel="nofollow noreferrer">(Shulgin, &amp; Shulgin, 1997)</a>, see Fig. 1.</p>

<p><a href="https://i.sstatic.net/BdPGX.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/BdPGX.png" alt="LSD"></a><br>
<sup>Fig. 1. LSD contains the tryptamine structure (in red). source: <a href="https://www.shroomery.org/forums/showflat.php/Number/3039286/fpart/all/vc/1" rel="nofollow noreferrer">Shroomery</a></sup></p>

<p>Secondly, every compound is toxic when taken in large quantities. For instance, water can kill, referred to as <a href="https://en.wikipedia.org/wiki/Water_intoxication" rel="nofollow noreferrer">water intoxication</a>, for example as seen in people tripping on MDMA and taking in too much water <a href="https://www.scientificamerican.com/article/strange-but-true-drinking-too-much-water-can-kill/" rel="nofollow noreferrer">(Ballantyne, 2007)</a>. Oxygen, another key to life, is a deadly gas when taken in artificially high concentrations for too long. Likewise, neuropharmacologically active compounds will hence eventually become neurotoxins. This, because the definition of <em>neurotoxic</em> is indeed quite broad (source: <a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Neurotoxicity-Information-Page" rel="nofollow noreferrer">NIH</a>):</p>

<blockquote>
  <p>Neurotoxicity occurs when the exposure to natural or manmade toxic substances (neurotoxicants) alters the normal activity of the nervous system. This can eventually disrupt or even kill neurons, key cells that transmit and process signals in the brain and other parts of the nervous system. </p>
</blockquote>

<p>Thus when you ask</p>

<blockquote>
  <p>are tryptamines, including LSD [sic] generally neurotoxic?  </p>
</blockquote>

<p>Then the answer is yes, depending on the dose.</p>

<p>Reversely, then, every neurotoxin becomes non-toxic once taken below a certain threshold dose. If this is what you refer to by 'microdosages', then yes, even the most potent toxin becomes harmless.</p>

<p>To specifically answer your question with regard to LSD and psilocin: LSD is suspected to be neurotoxic at clinically applied dosages <a href="https://www.ncbi.nlm.nih.gov/pubmed/26966135" rel="nofollow noreferrer">(Larsen, 2014)</a>, and psilocin can result in convulsions and death follow massive overdose <a href="https://link.springer.com/chapter/10.1007/978-1-4757-4552-8_14" rel="nofollow noreferrer">(Gold <em>et al</em>., 2003)</a>.</p>

<p><sub><strong>References</strong><br>
<strong>-</strong> <a href="https://www.scientificamerican.com/article/strange-but-true-drinking-too-much-water-can-kill/" rel="nofollow noreferrer">Ballantyne, <em>Sci Am</em> 2007</a><br>
<strong>-</strong> <a href="https://link.springer.com/chapter/10.1007/978-1-4757-4552-8_14" rel="nofollow noreferrer">Gold <em>et al</em>., <em>Atlas of Clinical Neurology</em>, Springer. pp 503-24</a><br>
<strong>-</strong> <a href="https://www.ncbi.nlm.nih.gov/pubmed/26966135" rel="nofollow noreferrer">Larsen, <em>Hist Psychiatry</em> (2016); <strong>27</strong>(2):172-89</a><br>
<strong>-</strong> <a href="https://erowid.org/library/books_online/tihkal/tihkal.shtml" rel="nofollow noreferrer">Shulgin &amp; Shulgin, Tihkal - The Continuation, pp. 490-99</a></sub>  </p>

CC BY-SA 3.0
2017-11-27T07:34:49.013Z
@AliceD i have had a look at your references. you are confusing danger with neurotoxicity.
faustus
CC BY-SA 3.0
2017-09-02T19:42:34.273Z
Thanks fir the reply, I'm familiar with the Denmark study. I think I remeber reading somewhere that they did that study on people with mental illness, so it's not really a valid study, seeing as they probably would have already been at risk for those outcomes. I'm wondering if there have been other studies on this, if not I'm hoping someone with a good understanding of neurology could theorize on it based on current knowledge of head drugs interact with receptors or other biological mechanisms.
user8398574
CC BY-SA 3.0
2017-09-02T20:45:45.430Z
@user8398574 and the study cited done in rats is better extrapolatable to healthy humans you reckon? One way or another, sure my references are not exhaustive, yet it firmly stands it ground, yes, indole alkaloids are potentially neurotoxic.
AliceD
CC BY-SA 3.0
2017-09-05T07:52:16.623Z
Thanks again, I everything is lethal at a certain dose, I should have clearified, I'm more curious about normal dose levels.
user8398574
CC BY-SA 3.0
2017-09-05T08:04:37.240Z
Now *that* is the whole point I am making in my answer - what is 'normal'?
AliceD
CC BY-SA 4.0
2020-04-14T09:44:41.777Z
@AliceD You clearly don't understand what neurotoxicity is. See my comment to the question. Neurotoxicity doesn't merely describe potentially dangerous neuropharmacology, it describes _precisely_ direct damage to neuron cells, as exemplified by serotonin dopamine releasing agents (such as amphetamines and MDMA), which cause massive release of monoamines into synaptic clefts directly causing oxidative damage to the neuron. 5-HT2 agonists, including tryptamines, LSD, and many other compounds, mimic neurotransmitters, they do not release them. They are NOT neurotoxic under the real definition.
JoseOrtiz3
CC BY-SA 4.0
2020-04-14T09:55:02.457Z
@OrangeSherbet - thanks for your thoughts on this. Critical views are highly appreciated. I've added a source counter-arguing your standpoint.
AliceD
CC BY-SA 4.0
2020-04-14T10:23:42.020Z
@AliceD It is futile to counter-argue reality. You haven't encountered the term enough in literature to understand when it is used and what it means, you simply introduced yourself to a topic you aren't familiar with and redefined a word as you saw fit. In particular, the single-author paper you linked on LSD doesn't even use the word properly, and only remarks "we should consider the neurotoxic potential of LSD". To demonstrate neurotoxicity, you have to directly measure neurons, usually with flourescent imaging, to determine structural damage to nervous tissue. (1/2)
JoseOrtiz3
CC BY-SA 4.0
2020-04-14T10:25:37.777Z
Convulsions and death are not signs of neurotoxicity, they are signs of dangerous neuropharmacology. Neurotoxicity shows up as damage to axons, dendrites, or death of entire nerve cells.
JoseOrtiz3
CC BY-SA 4.0
2020-04-14T10:35:16.467Z
Here is an overview of neurotoxicity. https://link.springer.com/article/10.1007/BF03033362
"Evolution of the science of neurotoxins has broadened the term to also encompass endogenous substances and metabolites capable of initiating apoptotic,
necrotic or necroptotic events leading to neuronal cell
death. " In particular, increasing amounts of neurotoxins implies neuron cell death. Convulsing, getting sick, dying is completely tangential. Neurotoxicity regards toxicity specifically to neuron cells.
JoseOrtiz3
CC BY-SA 4.0
2020-04-14T10:51:46.450Z
I would post an answer if the question wasn't closed. For now, it is sufficient to inform readers that you have redefined a well-defined neuropharmacological term "neurotoxicity" such that every molecule in existence becomes a neurotoxin. Other errors include failing to understand that MDMA is a classic neurotoxin not because of "water intoxication" but because it is a serotonin dopamine norepinephrine releasing agent - if you didn't know that, you shouldn't have answered. Ketamine and other NMDA antagonists are neurotoxins. But 5-HT agonists, including 5-HT2 agonists, are not neurotoxic.
JoseOrtiz3
CC BY-SA 4.0
2020-04-14T12:19:48.363Z
@OrangeSherbet - I know what MDMA is.... Please stop lecturing me the obvious and don't tell me what I should answer or not. I did not re-define anything. Then NIH re-defined it too. And I don't particularly appreciate your patronizing tone either.
AliceD
CC BY-SA 4.0
2017-09-02T19:11:24.030Z
2020-04-14T09:53:13.580Z
2020-04-14T09:53:13.580Z
AliceD
<p>It's commonly stated by numerous people that LSD and trytamines like DMT and psilocin are physically harmless and not neurotoxic. Is there evidence for this? </p>

<p>I recently read <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047954/" rel="nofollow noreferrer">5-meo-Dipt which is a tryptamine might be neurotoxic</a>. Why would 5-meo-Dipt be neurotoxic but DMT and psilocin not be? From my understanding some people micro-dose with LSD and some tryptamines to feel sharper and increase felt intelligence. </p>

<p>Why would one tryptamine neurotoxic and others make someone feel more intelligent? Obviously "feel" is self reported and subjective, but I'm assuming there might be some truth to this if <a href="https://www.theverge.com/2017/4/24/15403644/microdosing-lsd-acid-productivity-benefits-brain-studies" rel="nofollow noreferrer">people aren't tripping when experiencing these micro dosing effects</a>. LSD isn't a tryptamine, but I think some people do similar things with tryptamines. I'm hoping someone with a better understand of neurology can answer this. </p>

<p>To restate my question are typtamines and LSD generally neurotoxic and if not, could you please link to a study on it and what mechanism makes 5-meo-dipt possibly different, could other factors might have lead to a wrong conclusion, like for example harmful environment stress on rats or do you think all tryptamines are neurotoxic?</p>

<p>I'm trying to understand the possible reasons or lack there of for neurotoxicity in LSD and tryptamines but there seems to be lack of reliable sources.</p>

CC BY-SA 3.0
2017-09-01T15:31:20.923Z
Are you specifically questioning the effects of microdoses?
mflo-ByeSE
CC BY-SA 3.0
2017-09-01T18:10:48.333Z
Thanks for the reply, no I'm curious if there has every been a study that verified whether most tryptamines and LSD are neurotoxic or not, if not can this be determined based on current understanding of these drugs without a formal study. Also I'm curious as if they aren't neurotoxic, how is 5-meo-Dipt different?
user8398574
CC BY-SA 4.0
2020-04-14T09:18:31.693Z
Neurotoxicity is a very specific term in neuropharmacology. The answer from @AliceD is factually incorrect. Neurotoxicity in recreational drugs is exemplified by dopamine serotonin releasers, which include amphetamines and substituted amphetamines, which cause permanent damage via oxidative stress to neurons stemming from massive release of neurotransmitters. 5-HT2 agonists, the group of drugs you attempted but failed to describe, are not neurotoxic. They do not damage neurons precisely because they are agonists; they mimic neurotransmitters, they do not release them like neurotoxic drugs do.
JoseOrtiz3
CC BY-SA 4.0
2020-04-14T09:55:39.943Z
@OrangeSherbet - I disagree and have updated my answer below. Cheers
AliceD
<neuroscience><psychopharmacology>
LSD and tryptamines harmless or neurotoxic?
user8398574
# LSD and tryptamines harmless or neurotoxic?

(Asked by: username_0 on 2017-09-01)

It's commonly stated by numerous people that LSD and trytamines like DMT and psilocin are physically harmless and not neurotoxic. Is there evidence for this?

I recently read [5-meo-Dipt which is a tryptamine might be neurotoxic](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047954/). Why would 5-meo-Dipt be neurotoxic but DMT and psilocin not be? From my understanding some people micro-dose with LSD and some tryptamines to feel sharper and increase felt intelligence.

Why would one tryptamine neurotoxic and others make someone feel more intelligent? Obviously "feel" is self reported and subjective, but I'm assuming there might be some truth to this if [people aren't tripping when experiencing these micro dosing effects](https://www.theverge.com/2017/4/24/15403644/microdosing-lsd-acid-productivity-benefits-brain-studies). LSD isn't a tryptamine, but I think some people do similar things with tryptamines. I'm hoping someone with a better understand of neurology can answer this.

To restate my question are typtamines and LSD generally neurotoxic and if not, could you please link to a study on it and what mechanism makes 5-meo-dipt possibly different, could other factors might have lead to a wrong conclusion, like for example harmful environment stress on rats or do you think all tryptamines are neurotoxic?

I'm trying to understand the possible reasons or lack there of for neurotoxicity in LSD and tryptamines but there seems to be lack of reliable sources.

**Tags:** neuroscience, psychopharmacology

> **Comments:**
> **username_1**: Are you specifically questioning the effects of microdoses?  
> **username_0**: Thanks for the reply, no I'm curious if there has every been a study that verified whether most tryptamines and LSD are neurotoxic or not, if not can this be determined based on current understanding of these drugs without a formal study. Also I'm curious as if they aren't neurotoxic, how is 5-meo-Dipt different?  
> **username_2**: Neurotoxicity is a very specific term in neuropharmacology. The answer from @username_3 is factually incorrect. Neurotoxicity in recreational drugs is exemplified by dopamine serotonin releasers, which include amphetamines and substituted amphetamines, which cause permanent damage via oxidative stress to neurons stemming from massive release of neurotransmitters. 5-HT2 agonists, the group of drugs you attempted but failed to describe, are not neurotoxic. They do not damage neurons precisely because they are agonists; they mimic neurotransmitters, they do not release them like neurotoxic drugs do.  
> **username_3**: @OrangeSherbet - I disagree and have updated my answer below. Cheers  

---

## 1 answers

### Answer by username_3 on 2017-09-02. Score: 3

**Short answer**  
All neuropsychopharmaceuticals, including the tryptamines, are potentially neurotoxic depending on the dose at which they are ingested.

**Background**

Neurotoxicity is, arguaby, a broad definition. According to the NIH, neurotoxicity can be caused by processes ranging from radiation to transplants, and from chemical toxins to cosmetics. [NIH defines neurotoxicity as](https://www.ninds.nih.gov/Disorders/All-Disorders/Neurotoxicity-Information-Page):

> Neurotoxicity occurs when the exposure to natural or manmade toxic substances (neurotoxicants) alters the normal activity of the nervous system. This can eventually disrupt or even kill neurons, key cells that transmit and process signals in the brain and other parts of the nervous system. Neurotoxicity can result from exposure to substances used in chemotherapy, radiation treatment, drug therapies, and organ transplants, as well as exposure to heavy metals such as lead and mercury, certain foods and food additives, pesticides, industrial and/or cleaning solvents, cosmetics, and some naturally occurring substances.

LSD is a tryptamine [(Shulgin, & Shulgin, 1997)](https://i.sstatic.net/BdPGX.png), see Fig. 1.

[![LSD](https://i.sstatic.net/BdPGX.png)](https://i.sstatic.net/BdPGX.png)  
Fig. 1. LSD contains the tryptamine structure (in red). source: [Shroomery](https://www.shroomery.org/forums/showflat.php/Number/3039286/fpart/all/vc/1)

Secondly, every compound is toxic when taken in large quantities. For instance, water can kill, referred to as [water intoxication](https://en.wikipedia.org/wiki/Water_intoxication), for example as seen in people tripping on MDMA and taking in too much water [(Ballantyne, 2007)](https://www.scientificamerican.com/article/strange-but-true-drinking-too-much-water-can-kill/). Oxygen, another key to life, is a deadly gas when taken in artificially high concentrations for too long. Likewise, neuropharmacologically active compounds will hence eventually become neurotoxins. This, because the definition of *neurotoxic* is indeed quite broad (source: [NIH](https://www.ninds.nih.gov/Disorders/All-Disorders/Neurotoxicity-Information-Page)):

> Neurotoxicity occurs when the exposure to natural or manmade toxic substances (neurotoxicants) alters the normal activity of the nervous system. This can eventually disrupt or even kill neurons, key cells that transmit and process signals in the brain and other parts of the nervous system.

Thus when you ask

> are tryptamines, including LSD [sic] generally neurotoxic?

Then the answer is yes, depending on the dose.

Reversely, then, every neurotoxin becomes non-toxic once taken below a certain threshold dose. If this is what you refer to by 'microdosages', then yes, even the most potent toxin becomes harmless.

To specifically answer your question with regard to LSD and psilocin: LSD is suspected to be neurotoxic at clinically applied dosages [(Larsen, 2014)](https://www.ncbi.nlm.nih.gov/pubmed/26966135), and psilocin can result in convulsions and death follow massive overdose [(Gold *et al*., 2003)](https://link.springer.com/chapter/10.1007/978-1-4757-4552-8_14).

**References**  
**-** [Ballantyne, *Sci Am* 2007](https://www.scientificamerican.com/article/strange-but-true-drinking-too-much-water-can-kill/)  
**-** [Gold *et al*., *Atlas of Clinical Neurology*, Springer. pp 503-24](https://link.springer.com/chapter/10.1007/978-1-4757-4552-8_14)  
**-** [Larsen, *Hist Psychiatry* (2016); **27**(2):172-89](https://www.ncbi.nlm.nih.gov/pubmed/26966135)  
**-** [Shulgin & Shulgin, Tihkal - The Continuation, pp. 490-99](https://erowid.org/library/books_online/tihkal/tihkal.shtml)

> **Comments:**
> **username_0**: Thanks fir the reply, I'm familiar with the Denmark study. I think I remeber reading somewhere that they did that study on people with mental illness, so it's not really a valid study, seeing as they probably would have already been at risk for those outcomes. I'm wondering if there have been other studies on this, if not I'm hoping someone with a good understanding of neurology could theorize on it based on current knowledge of head drugs interact with receptors or other biological mechanisms.  
> **username_3**: @username_0 and the study cited done in rats is better extrapolatable to healthy humans you reckon? One way or another, sure my references are not exhaustive, yet it firmly stands it ground, yes, indole alkaloids are potentially neurotoxic.  
> **username_0**: Thanks again, I everything is lethal at a certain dose, I should have clearified, I'm more curious about normal dose levels.  
> **username_3**: Now *that* is the whole point I am making in my answer - what is 'normal'?  
> **username_4**: @username_3 i have had a look at your references. you are confusing danger with neurotoxicity.  
> **username_2**: @username_3 You clearly don't understand what neurotoxicity is. See my comment to the question. Neurotoxicity doesn't merely describe potentially dangerous neuropharmacology, it describes _precisely_ direct damage to neuron cells, as exemplified by serotonin dopamine releasing agents (such as amphetamines and MDMA), which cause massive release of monoamines into synaptic clefts directly causing oxidative damage to the neuron. 5-HT2 agonists, including tryptamines, LSD, and many other compounds, mimic neurotransmitters, they do not release them. They are NOT neurotoxic under the real definition.  
> **username_3**: @OrangeSherbet - thanks for your thoughts on this. Critical views are highly appreciated. I've added a source counter-arguing your standpoint.  
> **username_2**: @username_3 It is futile to counter-argue reality. You haven't encountered the term enough in literature to understand when it is used and what it means, you simply introduced yourself to a topic you aren't familiar with and redefined a word as you saw fit. In particular, the single-author paper you linked on LSD doesn't even use the word properly, and only remarks "we should consider the neurotoxic potential of LSD". To demonstrate neurotoxicity, you have to directly measure neurons, usually with flourescent imaging, to determine structural damage to nervous tissue. (1/2)  
> **username_2**: Convulsions and death are not signs of neurotoxicity, they are signs of dangerous neuropharmacology. Neurotoxicity shows up as damage to axons, dendrites, or death of entire nerve cells.  
> **username_2**: Here is an overview of neurotoxicity. https://link.springer.com/article/10.1007/BF03033362 "Evolution of the science of neurotoxins has broadened the term to also encompass endogenous substances and metabolites capable of initiating apoptotic, necrotic or necroptotic events leading to neuronal cell death. " In particular, increasing amounts of neurotoxins implies neuron cell death. Convulsing, getting sick, dying is completely tangential. Neurotoxicity regards toxicity specifically to neuron cells.  
> **username_2**: I would post an answer if the question wasn't closed. For now, it is sufficient to inform readers that you have redefined a well-defined neuropharmacological term "neurotoxicity" such that every molecule in existence becomes a neurotoxin. Other errors include failing to understand that MDMA is a classic neurotoxin not because of "water intoxication" but because it is a serotonin dopamine norepinephrine releasing agent - if you didn't know that, you shouldn't have answered. Ketamine and other NMDA antagonists are neurotoxins. But 5-HT agonists, including 5-HT2 agonists, are not neurotoxic.  
> **username_3**: @OrangeSherbet - I know what MDMA is.... Please stop lecturing me the obvious and don't tell me what I should answer or not. I did not re-define anything. Then NIH re-defined it too. And I don't particularly appreciate your patronizing tone either.  

---

