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Neurotoxicity of amp vs cocaine, risk of anhedonia

PlatoX

PlatoX

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Apr 12, 2015
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I have just been reading about the devastating condition of Anhedonia caused by MDMA/SSRIs which has forced me to revaluate the risk level of various drugs.


I was aware that MDMA is neurotoxic, and that if using it then a space of apx 3 months is required for the serotonin system to rebalance. I thought if used sparingly a few times a year, then adverse effects would be rare. However anhedonia is a living nightmare, just horrific, and it seems that it’s not uncommon.
My MD usage is about once every 3 months, but I do binge at festivals which I hit 3 times each summer (i.e. 9 days heavy usage within 3 months).


Coke by comparison is not neurotoxic. I am aware it is cardiotoxic however I think it is likely that the body can repair this type of damage, whereas anhedonia can last years or be permanent. So cocaine, with the correct usage protocol (admittedly requiring a willpower of steel) will not lead to long term brain or other damage?
So with my MD now in the trash, I am currently looking at nootropics for a relatively safe high, mostly pro social, that I can safely take at least once per week. Any suggestions?
 
MDMA is cardiotoxic as well, (valvular heart disease/cardiac fibrosis due to 5-HT2B stimulation), I believe this contributed to the original creator of MDMA's demise (at least he had to replace a faulty valve I believe). Cocaine does harm small arteries of the heart, I don't know whether this is relevant with recreational use at a rate like you're talking about (I suppose we should take into account that if you make it to 70 years old our medical technology will be better). But I think that cocaine and things like dextroamphetamine/Ritalin are indeed less harmful to the brain than MDMA, especially concerning serotonin.

I would honestly rather you find Ritalin than Cocaine though, this might stop the cardiotoxic effects while producing a similar high. I think there are some harmful adulterants going around in cocaine lately. And I have heard that Cocaine's neurotoxicity is very similar to Ritalin, it sounds like there is risk of oxidative stress especially concerning binge administration, but in my mind the main damage is going to occur during sleep deprivation, so get plenty of sleep and if you have the means try to find a drug to help you sleep (an anti-adrenergic drug like clonidine works very well for stimulant comedowns but a good GABA drug is better than nothing). You can take plenty of antioxidants (especially Vitamin E) to try to counteract the oxidative stress. Metabolization of dopamine produces harmful ROS.
 
Shulgin only used very sparsely though. Are you sure it is fair to blame MDMA on the heart valve problems? All the other drugs he tested were potentially 5HT2b agonists as well.
 
Coke will not cause neurotoxicity. It can lead to permanent changes in monoamine neurotransmitters if abused over long periods of time, though with sensible use you have nothng to worry about. I used to believe MDMA is potentially neurotoxic for humans but then read some studies by Franz Vollenweider and his team which pretty much proved that therapeutic doses (75-125mg) used alongside psychotherapy does not lead to neurotoxicity. Evidence shows that that plain amphetamine in the forms of adderall and dexedrine are more likely to result in neurotoxicity at therapeutuc doses. As Cotcha Yankinov wisely suggested I would use plenty of antioxidants and magneisum alongside both of them
 
aced126 said:
Shulgin only used very sparsely though. Are you sure it is fair to blame MDMA on the heart valve problems? All the other drugs he tested were potentially 5HT2b agonists as well.
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That is very true, it definitely could've been from the other drugs. If I remember right some of the other drugs have even higher affinity for 5HT2B. I wonder what the reality of the MDMA and valvular heart disease is, one study put the number as high as 30% of young MDMA abusers having regurgitation.. Very scary.. But hopefully those study participants were heavy abusers..
 
Cotcha Yankinov said:
That is very true, it definitely could've been from the other drugs. If I remember right some of the other drugs have even higher affinity for 5HT2B. I wonder what the reality of the MDMA and valvular heart disease is, one study put the number as high as 30% of young MDMA abusers having regurgitation.. Very scary.. But hopefully those study participants were heavy abusers..
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It seems to me like neurological problems would be your main concern if you were to take that much MDMA to induce heart valve problems. People took fenfluramine every single day and lots had no problems at all, and to my knowledge it is a much stronger 2b agonist. What is the source of the study you mentioned?
 
Found it! http://www.ncbi.nlm.nih.gov/pubmed/17950805 -Study of 29 users and 29 nonusers - Nonusers were clear on all accounts while 21% of users had mitral valve regurgitation, 45% had tricuspid regurgitation, 14% had mild aortic regurgitation and then "valvular strands" were present in 21% of users. "Eight subjects - 28 percent - who took MDMA had abnormal echocardiographic results using the United States Food and Drug Administration's criteria for appetite suppressant-induced valvular heart disease, compared with none in the control group". I would have to assume that the different valvulopathies were overlapping in some individuals, which is a whole lot scary to me than solely mild mitral valve dysfunction. If anyone has access to the full study and could tell us anything about the user population that would be lovely. Hopefully these are really heavy abusers.

That some people seem to get valvular heart disease while others don't suggest that there might be a genetic vulnerability component, or maybe there is a direct correlation between 5-HT2B and use, that is to say that if you use enough you're guaranteed to get it, but this could be figured by sifting through the study data. Maybe the users who did have VHD have a higher lifetime total for pills compared to users who did not get it.

Apparently MDA is a 5-HT2B agonist as well (makes sense with its 5-HT2A agonism), I wonder if the VHD comes mostly from MDA rather than MDMA. I've heard from one source that MDA has higher affinity for 5-HT2B than MDMA, though it did not give real affinities. I wonder if excessive plasma serotonin contributes greatly as well, as it does with carcinoid heart syndrome. In that case 5-HTP could be a contributing factor and should be ruled out in that study's patient populations.
 
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Oh, and I guess I should try to actually help the OP lol. Dopamine is a very robust system but dopamine receptor downregulation (resulting in anhedonia) is certain to happen with enough use, concerning cocaine I don't think we're talking about short periods like a couple times once a month but rather if you used every day for a couple weeks I would expect you to feel glum when not using. Serotonin with MDMA on the other hand can be very fragile and you can have adverse reactions even on your first pill, and it is indeed neurotoxic so if you abuse it enough you will be recovering for years.

Ultimately Ritalin is probably the safest bet.
 
There are only 58 subjects in total, way less than the recommended standard of 100. They didn't test the subjects before they ever took MDMA and we don't know their diet, drug & prescription intake and possible genetic factors/evironmental effects on the the genetic expression. It looks like a quasi experiment to me, so it isn't really saying much at all (I suppose).
 
Abuse of any stimulant can cause anhedonia in the long term, especially if you already had it to begin with and were taking them to self-medicate. MDMA is a stronger releasing agent (although I read that cocaine had recently been determined to be a releasing agent, rather than merely a reuptake blocker as previously believed, it's still considerably weaker than MDMA), and so will likely cause you more problems on a shorter timescale.

Neither of these drugs should ever even be considered as a nootropic. Not only do they not give a very productive effect (or "high" if you will, though a good nootropic shouldn't really give an effect describable as a high) at all, but their after-effects are generally crippling, and long-term they're extremely counter-productive. Limit them to use as occasional party drugs, not daily productivity enhancers.
 
RS127445 is a selective antagonist for 2B that I've seen used in studies, just curious what's your interest in 2B antagonists?
 
No real interest, although just thinking about it, maybe they can be used to prevent adverse effects of otherwise effective drugs (fenfluramine, for example).
 
I was thinking that was your curiousity, it sounds like fenfluramine works mostly via 5HT2C so this sort of research chemical that has 1000x times selectivity over 2C and 2A would be great, I think concerning MDMA there's no way to block 5-HT2B without diminishing the experience so I think a good way to prevent cardiac fibrosis in practice would be dosing something like Risperidone on the comedown to stave off some of the 2B activation from metabolites.
 
Seppi said:
See this post.
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I would honestly expect more in the way of reductions of hippocampal neurogenesis related to stress hormones with titrated therapeutic doses and fallout from chronic fragmented sleep rather than straight up neurotoxicity, but I suppose dopamine auto oxidation damage is a possibility but theoretically shouldn't be that important concerning titrated doses. Then again I don't think we're talking about titrated doses.
 
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thank you for the suggestions. I'll research ritalin.

luckily for me I do have pretty good control over my substances, I can take or leave cocaine. Playing with serotonin does sound like a crazy risk. Out of interest though, once down regulation of dopamine receptors occurs, how quickly do they recover. are we talking months or years or never? TBH I've been fascinated by how many people (e.g. rock stars) can binge for decades, then pull it together in their old age. As Lemmy said in an interview, the only drug he ever saw people die on was heroin.
 
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