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Amphetamine/meth/MDMA killing non-DA/5-HT neurons

R

rnd.id.

Bluelighter
Joined
Jan 1, 2006
Messages
179
We all know about possible DA/5-HT axon terminal damage with these drugs, but this review basically says they cause cell death all over the place?

http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2009.05141.x/full#ss3 (free full text)

Recent studies indicate that the damage produced by these drugs may be more widespread than originally believed.
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In addition, METH, MDMA and d-amphetamine damage a population of nonmonoaminergic neurons and their processes in rat parietal cortex (somatosensory cortex). In mice, high-dose METH leads to cell death in a variety of brain areas including the striatum, cortex (frontal, parietal, and piriform), indusium griseum, medial habenular nucleus, hippocampus, tenia tecta, and fasciola cinerea. More recently, a low dose of METH has been shown to damage cell bodies in rat prefrontal cortex of behaviorally sensitized rats, whereas an escalating binge dose of METH damages pyramidal neurons in the frontal cortex, CA3 and dentate gyrus regions of the hippocampus, and calbindin interneurons of the striatum. Finally, there are several more recent reports of amphetamine toxicity to DA-containing neurons and their terminals in mouse olfactory bulb and rat retina.
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Studies of mechanisms underlying METH toxicity to neuronal cell bodies are relatively recent and indicate that an early event in METH toxicity to nonmonoaminergic striatal and somatosensory cortical neurons might be a release of GLU that initiates a chain of events culminating in apoptosis.
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As a layman, I have no idea how relevant this is to human use. Haven't sifted through the references, but I hope this kind of gross damage happens only with ridiculous doses given to mice and rats...
 
Jesus. Really reinforcing to uncover newer ways in which we are destroying ourselves as a species - and on subtler levels, too. Really interesting article, though. Given their relatively long history of therapeutic, recreational and toxic use, I would have assumed science would have uncovered such widespread neurotoxicity sooner than this.

It makes me wonder about most pharmaceuticals since most in use today have a much shorter spectrum of study in human subjects than amphetamine and its derivatives.

That's interesting about the rat retina, I've always noticed on my amp script prescription information sheets how an adverse effect can be visual disturbances.

~ vaya
 
Well let's be realistic though, we can't just take isolated rat studies and conclude anything from them, of course studies such as this should be brought up and stimulant users should be aware of them. However, it becomes a problem if we make any strong conclusions pre-maturely. Stimulants have been around for a hell of a long time, and can be quite safe when it comes to actual practice and not just hypothetical "neurotoxicity" studies in rats. Of course a lot of bluelighters are familiar with recreational stimulant use, but there are people for which stimulants have been literal life savers, those who have actual cellular damage and benefit tremendously from increased activity in certain parts of their brain. Science is very new, and it'll take a long time before such studies actually have good predicting power, but as of now most studies in journals can be very disappointing if you take them seriously. Are stimulants neurotoxic? As a general answer, yes, from a little to a lot, depending on the situation. This doesn't mean you take every study seriously though, you have to look at the full broad picture, and even then things can be very vague and change drastically over time. I would pay far more attention to actual OBSERVED effects whether positive or negative on the specific patient themselves rather than such studies, we have a hard time using studies done on humans to guide treatment for a specific person, just imagine what would happen if we used studies not even done on the same species. Laymen can't just open up PubMed and draw conclusions from abstracts, even "scientists" get no where when they do this. My point is we can't discuss anything about this abstract that will be fruitful, except say "oh yes there is that possibility of that happening, great, and this means absolutely nothing in day to day practice because we have no clue how this fits in with everything else". Disappointing, but that is the way it is now, we're just barely seeing the start of a proper foundation to discover the nature of the human brain.
 
Just wait until you start looking into transgenerational epigenetic changes... *shudder*
We're going to be a race of sterile autistic fucktards in 3 or 4 generations if the studies I've been reading are correct.

Hell look at the whole SSRI/autism link.
 
Epsilon Alpha said:
Hell look at the whole SSRI/autism link.
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I had not heard of this. Do you have any pertinent articles you'd be willing to share with me on the subject?

Amu said:
Disappointing, but that is the way it is now, we're just barely seeing the start of a proper foundation to discover the nature of the human brain.
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Truth (now that you've made me think about it). The wisdom in your posts inspires me, Amu.

~ vaya
 
 
The SSRI-autism study is very recent and will require more investigation before evidence for this association is considered unequivocal... From the number of former METH users I know who are now occupying the higher echelon's of society, I'm not really sure how detrimental the neurotoxic effects are, but I suspect they can't be much worse than those of ethyl alcohol.
 
Thanks for posting those articles; it may take me a bit to sort through but this is an interesting area of study.

One issue I had with the second link is that in the Summary the researchers state, "...The prevalence of autism, a neurodevelopmental condition resulting from genetic and environmental causes, has increased dramatically during the last decade. Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise."

Properly, though, hyperserotonemia is "serotonin syndrome." It doesn't look like they were intending to implicate serotonin syndrome in so many cases that it could cause an appreciable rise in the prevalence of autism because A.) SSRI's don't typically, or even at all frequently, cause/result in serotonin syndrome and B.) hyperserotonemia is so serious a condition I'm sure many of the pregnant women would have died before brining the autistic child into the world. I'm feelin' like the researchers should choose their terminology *way* more carefully, especially in studies with implications that could completely change the prescribing guidelines for SSRI's!

Nevertheless thanks again Epsilon Alpha!

~ vaya
 
Thing is though, a lot of AD's may accumulate in the fetus and I really haven't seen anything either way suggesting that the fetal brain is more or less susceptible to the effects of 5HT.
Still, it is quite possible that lower levels of 5HT in the brain or perhaps another mechanism of AD's can exert significant effects on the fetal brain and genome. More research is definitely needed.
 
Amu: I generally agree, but still thought this might be relevant to HR, especially if there are ways of avoiding some of the damaging mechanisms discussed in the paper (focusing on protecting 5-HT/DA axons only may be a bit of a red herring depending on how applicable the paper is to typical doses in humans).
 
rnd.id. said:
Amu: I generally agree, but still thought this might be relevant to HR, especially if there are ways of avoiding some of the damaging mechanisms discussed in the paper (focusing on protecting 5-HT/DA axons only may be a bit of a red herring depending on how applicable the paper is to typical doses in humans).
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Yes, certainly. I assume agents administered for protecting 5-HT/DA axons would protect against all oxidant species. The problem is we don't have much evidence for what protects DA/5-HT axons in the first place, except for relatively weak studies done on rats, I think thorough experimentation needs to be done.
 
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