Serotonergic lesions alter effects of drugs of abuse

[Deleted member 137730]

I have done some research into this topic. It seems that people that have done a decent amount of serotonergic neurotoxins like meth, mdma, ect ,have atypical reactions to a variety of drugs. I believe this atypical reaction is due to serotonergic lesions altering a whole host of neural systems.

I would like some personal accounts from people and comments. Im not going to list studies to back any of what i say, but will provide them through PM if someone is very interested, they are annoying to dig up.

some generalities i have concluded:

Serotonergic lesions induce anxiety if the lesion is partial, full lesions actually reduce anxiety along with most feeling in general.

atypical response or total lack of response to all serotonin based psychs

paradoxical loss of opiate reward and analgesia

Glutamate alterations seem to incur, anhedonia seems prominent which is strange given intact DA systems.

Strange personality changes, blurry vision.

Anyone have specific accounts of drugs that were altered and how they were altered after extensive use of mdma,meth,mda,meph, ect or other purported serotonergic neurotoxins.

 

[Deleted member 137730]

Also lets not get into a debate about whether certain MDxx substances cause serotonin lesions, humor me here.

 

[3rd_I_blind]

How do you expect to start up a decent discussion if you are not willing to provide the articles? A lot of good scientific literature is annoying to dig up, plus you have to sift through 10 irrelevant articles for every decent one. So why are you asking others to do that kind of work, if you can't even begin by doing some prior effort by yourself? Don't get me wrong...I think your hypothesis could be interesting. But your attitude comes off as a bit lazy, although you might not be aware.

Most of the symptoms you sum up sound like results reported in animal experiments and not in human subjects with serotonergic lesions. It would be very unlikely that someone would use the amounts of MDMA used in that kind of animal experiments and live to tell the tale (for starters, due to the size difference humans are more prone to overheating or to suffer cardiax arrest). As far as I know, MDMA neurotoxicity in humans is primarily dopaminergic by nature while in rats it is primarily serotonergic and in mice it is a bit of both. Then there is always the big difference between simple results in an animal experiment (mouse does not swim, mouse stays on open arm in elevated plus-maze) and what it actually would mean in a human situation.

 

[Deleted member 137730]

How do you expect to start up a decent discussion if you are not willing to provide the articles? A lot of good scientific literature is annoying to dig up, plus you have to sift through 10 irrelevant articles for every decent one. So why are you asking others to do that kind of work, if you can't even begin by doing some prior effort by yourself? Don't get me wrong...I think your hypothesis could be interesting. But your attitude comes off as a bit lazy, although you might not be aware.

Most of the symptoms you sum up sound like results reported in animal experiments and not in human subjects with serotonergic lesions. It would be very unlikely that someone would use the amounts of MDMA used in that kind of animal experiments and live to tell the tale (for starters, due to the size difference humans are more prone to overheating or to suffer cardiax arrest). As far as I know, MDMA neurotoxicity in humans is primarily dopaminergic by nature while in rats it is primarily serotonergic and in mice it is a bit of both. Then there is always the big difference between simple results in an animal experiment (mouse does not swim, mouse stays on open arm in elevated plus-maze) and what it actually would mean in a human situation.

Yes your right, thats obviously exactly why i am asking for anecdotal reports, as there is not much research on people.

I didn't provide articles because for one, most are based on animals so they arnt all that relevant (though not all), also alot of it is based through my own observations and hearing other peoples anecdotal reports which of course doesn't constitute an actual study. I mean sure i could post the animal studies, but i wasn't sure anyone would care which is why i offered to pm them.

I just wanted to hear if people had any anecdotal human reports i could add to my personal inventory. I certainly don't think giving your own unique report on this topic is asking others do research for me, as its not a researchable topic!

To answer your other points, plenty of people use high enough doses to be comparable to animal studies but again its really not relevant anyway.

In the absence of any real human research I was hoping to get personal accounts as thats all i can go by. It has nothing to do with lazyness at all and i might add that you came off pretty presumptuous as you seem to have misread the purpose of the thread- to collect unique human data on this topic that as is doesn't exist anywhere else in researched form.

I really didn't want this thread to start off by being accused of being lazy for not posting data that doesn't really exist.. unless you want to extrapolate animal data.

 

[3rd_I_blind]

Ahh, I guess I missed the point of your thread, searching for human case reports on the symptoms reported in animal experiments.

I must say I am afraid the (scientific) value of the reports you might be able to get is questionable though. Since there is a lack of proper control, it would be very hard to tie any report directly to (serotonergic) neurotoxicity caused by MDMA or a similar substance.

What are the typical dosage you have found in animal experiments? I wonder because you say consumption in the human situation will in some cases be comparable, but rats - for instance - are generally dosed at the 30-60 mg/kg level. This equals 2.5-5 grams in your average human being, and rats are usually dosed only once, not spread out over multiple hours.
I'm not trying to bust your balls or anything, I am just trying to point out that the extent to which you see brain lesions in animal research is hardly to be expected in any human. Therefore, the symptoms you came up with are not likely to be reported as well.

EDIT: I did not accuse you of being lazy, why do you put so much emphasis on that part? I only said your attitude came off as lazy, that's all there is to it really.

 

[MeDieViL]

30mg/kg in a rat is not 30mg/kg in a human, that said there is enough evidence that the neurotoxic damage in rats is not comparable to the damage humans may have at all, so using rodent models as something that can explain human long term effects doesnt make much sense.

When calculating the dose species differences, 40mg/kg is a dose humans can ingest.

 

[Deleted member 137730]

Ahh, I guess I missed the point of your thread, searching for human case reports on the symptoms reported in animal experiments.

I must say I am afraid the (scientific) value of the reports you might be able to get is questionable though. Since there is a lack of proper control, it would be very hard to tie any report directly to (serotonergic) neurotoxicity caused by MDMA or a similar substance.

What are the typical dosage you have found in animal experiments? I wonder because you say consumption in the human situation will in some cases be comparable, but rats - for instance - are generally dosed at the 30-60 mg/kg level. This equals 2.5-5 grams in your average human being, and rats are usually dosed only once, not spread out over multiple hours.
I'm not trying to bust your balls or anything, I am just trying to point out that the extent to which you see brain lesions in animal research is hardly to be expected in any human. Therefore, the symptoms you came up with are not likely to be reported as well.

EDIT: I did not accuse you of being lazy, why do you put so much emphasis on that part? I only said your attitude came off as lazy, that's all there is to it really.

Im not concerned about controls and whatnot, this isn't a professional study. I was just looking for patterns and trends that seem to come up alot with frequent use of serotonergic neurotoxins. I might look at the rat data to see if I see any similarities, but thats about it.

Not to bust your balls either haha, but i know mdma dealers that eat their own stash and its not unheard of for them to go up to 10 grams a day sometimes of pure. They also do it for months in a row and throw in large amounts of injected methamphetamine along with injecting the mdma. Id say there is a good chance they are seeing similar damage to the rats in MDMA studies over long periods of time. I've seen what it does to them and their behaviors and it fascinates me.

Again this isnt a case study, its just out of scientific curiosity.

 

[Deleted member 137730]

30mg/kg in a rat is not 30mg/kg in a human, that said there is enough evidence that the neurotoxic damage in rats is not comparable to the damage humans may have at all, so using rodent models as something that can explain human long term effects doesnt make much sense.

When calculating the dose species differences, 40mg/kg is a dose humans can ingest.

I agree that is why i didnt post rodent studies in the first place. Its also why we have to rely on anecdotal reports to see trends. Im well aware of the metabolism differences in rats as well as the difference in regenerative strength relating to neural damage.

 

[bignig5971]

I am not sure if dxm counts but i abused it heavily everyday for 3 years. The magic from most drugs is gone now where those same drugs used to give me pleasure. I still smoke but even that takes on a very different edge. I still have my intellect because I'm close to graduating from a good university. My mood has never been the same. I can go back to specific dates and say that days is when my brain chemistry changed for the worse.

 

[MeDieViL]

Not to bust your balls either haha, but i know mdma dealers that eat their own stash and its not unheard of for them to go up to 10 grams a day sometimes of pure. They also do it for months in a row and throw in large amounts of injected methamphetamine along with injecting the mdma. Id say there is a good chance they are seeing similar damage to the rats in MDMA studies over long periods of time. I've seen what it does to them and their behaviors and it fascinates me.

Its allways funny how when abusing several differend neurotoxic drugs, allways MDMA gets blamed (drugs dont even need to cause neurotoxiticy, who says epigenetic changes arent at play here, or the other drug isnt at fault) not referring to your example but to ppl in general abusing mdma, meth, ketamine, dxm, opiates, alcohol and whatever, however when they start showing long term problems, its allways that damn mdma that did it!

 

[3rd_I_blind]

Its allways funny how when abusing several differend neurotoxic drugs, allways MDMA gets blamed (drugs dont even need to cause neurotoxiticy, who says epigenetic changes arent at play here, or the other drug isnt at fault) not referring to your example but to ppl in general abusing mdma, meth, ketamine, dxm, opiates, alcohol and whatever, however when they start showing long term problems, its allways that damn mdma that did it!

Interesting take on the neurotoxicity. However, one could argue that drug-induced neurotoxicity (which is usually excitotoxicity, oxidative toxicity or a combination of both) is always epigenetic by nature. The result is namely cell death by apoptosis, which requires epigenetic changes to take place. One could also reason oppositely: If drugs would cause epigenetic changes that lead to the selective loss of neurons, those epigenetic changes can be defined as neurotoxic in nature.

Part of the reason MDMA gets most of the blame might be the history of certain other substances you mention. Ketamine and opiates/opioids have a long history of beneficial medical use, accompanied with vast amounts of literature on the potential neurotoxic/adverse effects. So they are both more or less accepted, and their dangers are documented. Alcohol is an accepted drug too, and though I am not really knowledgeable about alcohol neurotoxicity, I believe the hepatotoxicity would overshadow long-term brain effects. It would also seem reasonable to assume alcohol is not a selective neurotoxin, while MDMA is selectively targeting (for instance) the hippocampus and striatal region. Lastly - although I admit it is hard to find a decent review on the subject where MDMA is compared to other drugs of abuse, so I might be wrong here - MDMA is a potent neurotoxin. We can keep slapping each other silly with the 'once every 3 months no permanent damage' routine, but it's just a fact that MDMA has neurotoxic effects at the typical dose used at a party. Especially when also considering other factors at the party that contribute to neurotoxicity (loud noise, heat, type of beverages consumed, constant dancing).

 

[Cheshire Squirrel]

I'm quite curious actually on the topic of MDMA and neurotoxicity. This may seem like an arbitrary post to this thread, but 3rd_I_blind where did you find journal articles indicating selective neurotoxicity to the hippocampus and striatal region? I'm eager to read up on some of this.

 

[3rd_I_blind]

This may seem like an arbitrary post to this thread, but 3rd_I_blind where did you find journal articles indicating selective neurotoxicity to the hippocampus and striatal region?

Some articles, haven't read them all so no flaming if irrelevant plz.

Effect of tyrosine depletion on long-term hippocampal neurotoxicity of MDMA; the article also mentions specific striatal neurotoxicity. LINK

Article studying the effects of MDMA on neonatal BDNF levels; BDNF is reduced in hippocampus and striatal region, evidence for specific hippocampal neurotoxicity is named in particular. LINK

Study exploring the protective effects of memantine on MDMA neurotoxicity. Isolated striatal tissue produced ROS under influence of MDMA, while specific hippocampal neurotoxicity (as assessed by paroxetine binding density) was prevented by memantine supplementation. LINK

Another study using paroxetine binding to assess neurotoxicity, this time to investigate the fitness of 5-HT tissue levels to assess neurotoxicity. Specific hippocampal and cortical neurotoxicity is mentioned, striatal neurotoxicity is also mentioned briefly. LINK

Another nice study, comparing the effects on the SERT with 5-HT tissue levels; hippocampus and striatum are specifically mentioned. LINK

Last study for this post, emphasizing the fact I mentioned previously, that the conditions under which MDMA are usually used enforce the neurotoxicity. Again, hippocampus and striatum are specifically mentioned. LINK

So...now let's talk about my reward for all this time-consuming article-humping.

 

[literate]

In my experience, MDMA is just so incredibly physically benign I find the notion of its 'neurotoxicity' laughable at best and also government fueled propaganda in my opinion to boot. Yes, it quits working at some point; this fact limits its abuse potential. Enjoy it while you can, or abstain if you'd rather.

Now, let's discuss the following:
1. CH3CH2OH-->delirium tremens, dementia, liver failure
2. benzos-->horrible, protracted, physically dangerous withdrawal including but not limited to tremendous anxiety, panic attacks, and life threatening seizures following dependence
3. heroin, morphine, oxycodone, fentanyl, methadone, et al-->ever tried 40mg/kg or the equivalent of one of these little beauties-->you're and this too happens all the time

Clinically, ("in practice"), MDMA has been shown to reduce short term memory recall in a battery of psychological functions test among former heavy users, and that was IT.

 

[3rd_I_blind]

Now, let's discuss the following:
1. CH3CH2OH-->delirium tremens, dementia, liver failure
2. benzos-->horrible, protracted, physically dangerous withdrawal including but not limited to tremendous anxiety, panic attacks, and life threatening seizures following dependence
3. heroin, morphine, oxycodone, fentanyl, methadone, et al-->ever tried 40mg/kg or the equivalent of one of these little beauties-->you're and this too happens all the time

Pardon me, sir, but it seems you have forgotten to mention the:
- Anxiety and paranoia
- Fatigue and irritability
- Depression
- Dizziness and insomnia
- Diarrhea or constipation
- Trismus and bruxism
- Desorientation leading to severe anxiety or panic attacks
- Severe hyperthermia, possibly resulting in multiple organ failure
- Myocardial infarct or heart failure
- Excessive hemorrhage or stroke
- Vasculitis
- Cardiac arrhythmia and palpitations
- Myoclonal effects
- Pulmonary hypotension and circulatory shock
- Retrograde or anterograde amnesia
- (Severe) delirium
Which can result from using moderate to excessive doses of MDMA, either after the peak has passed or when the serotonin runs out.

Perhaps you ever heard that MDMA can impair your judgment? This would probably mean it also impairs your judgment on its own 'benign' physical effects.

 

[literate]

Perhaps you consider MDMA to be hard drug. I do not.

 

[3rd_I_blind]

Perhaps you consider MDMA to be hard drug. I do not.

Perhaps you consider calling it all a governmental funded propaganda-conspiracy and ignoring anything that points in the opposite direction intelligent behavior or harm reduction. I do not.

 

[literate]

Well, one time they enhanced the colors in some brain scan pictures, added the caption "Ecstasy puts holes in your brain," and then widely distributed the resulting propaganda.

I doubt your government would do that, but ours did.

 

[pLur4eVer<33]

Well, one time they enhanced the colors in some brain scan pictures, added the caption "Ecstasy puts holes in your brain," and then widely distributed the resulting propaganda.

I doubt your government would do that, but ours did.

HAH I LOVE THIS ^

and i have blurry vision sometimes too

 

[F1n1shed]

Literate get the fuck out of here, no one wants you here. This is advanced drug section where people care about their brains, hence they research. If you want to protect your drug and call mdma a soft drug, you belong in the ecstasy discussion with fellow etards. Over there people talk about how they can keep the 'magic' instead of try to learn about the toxic damage that is occurring. I use mdma once in a while and i notice changes every time, since the beginning.
Mdma is a heavy neuro toxin, thus i put it in the section of hard drugs. You may not get addicted to it, but even with moderate use it can put some noticeable changes in your life. There are more reports saying it is neuro toxic to some degree, than those saying it isn't proven to be.