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Serotonergic lesions alter effects of drugs of abuse

literate said:
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.
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That is really shitty politics, but some governments have a history of communicating this way, LOL. Anyway...propaganda does not automatically mean the opposite is true. It would be very ignorant to consider all scientists as government-funded brainwashers that only produce results that underscore some hidden agenda. Why would they, for instance, publish reports where compounds are searched to protect against MDMA-induced neurotoxicity? That would not make any sense if it was all propaganda.

By the way, the concept of 'soft' and 'hard' drugs has never received much support from the scientific community. So you are probably taking it way too semantic if you state that you regard MDMA as a soft drug, thus declaring its potential risks are non-existent. Alcohol is regarded as soft drugs too, for fuck sake...
 
Based on the drugs I've used and abused, I do NOT classify benzodiazepines or opiates as 'hard' drugs. Why? Because I've never been severely addicted to either and their immediate effects truly are rather 'weak' compared with the stimulants or psychedelics I've used/abused. Just because you haven't experienced the bad side-effects of particular drugs does not mean they can't cause them. I consider LSD one of the hardest drugs. Why? Because it left me with HPPD and severe anxiety for 1.5 years. A drug that last 1.5 years? No thanks...

Now, I admit, that I am wrong on both accounts. Opiates and benzodiazepines can be truly crippling, life altering (for the worse) drugs, and the majority of people will do LSD and not be changed for the worse (may even gain positive insights). But for me, this is the way she went. Hard vs Soft drugs is a ridiculous black vs white mentalitiy. The truth is that it is a sliding scale, which differs for every individual, which is obvious from my experiences as well as countless others. MDMA ranks somewhere in the middle, for me. Not life altering, but not benign.

In response to the OP:

I've abused Mephedrone and used MDMA probably 15 times in my life. I can say that stimulants EXCEPT MDMA were ruined for me from my abuse of Mephedrone. Opiates, I still enjoy, but I do feel that something is missing from them, I even become agitated/pissed off feeling on them sometimes. Alcohol is weird, though it's always been a strange one for me. Psychedelics still work just fine, my HPPD from LSD arose pre-Meph/MDMA, cleared up after 1.5 years and I've used Mushrooms and 4-aco-dmt 3x over the past 4-5 months with no negative side-effects to note and good trips each time. I feel the LSD can NEVER be used again, nor any really strong psychedelic such as DMT, but occasional Psilocin use should be OK. I don't even think I will use it again though...I'm kinda over drugs these days...I feel I've caused enough harm now, haha, time to re-build.
 
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3rd_I_blind said:
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. :p
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Ah hah, wow a lot of rat in vivo studies included in that. I appreciate the shag effort. Your reward is helping educate another comrade in the pursuit of a well-rounded psychopharmacology background of knowledge.

Thank you!
 
Cheshire Squirrel said:
Your reward is helping educate another comrade in the pursuit of a well-rounded psychopharmacology background of knowledge.
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Karma ftw, eh? ;)

Glad to be of assistance. If you have any other questions, please feel free to ask. Psychopharmacology was always one of my favourite subjects. My best mate is currently getting his MSc in psychopharmacology, so I could always relay the real tricky questions to him. =D
 
MeDieViL said:
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.
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I once read a paper that compared active dose of MDMA between rats and humans and they found the active dose to be that same based on mg/kg. The duration was shorter in rats however. Other drugs the dose may be largely different but I think for MDMA at least 40mg/kg for a rat is MASSIVE.
 
Not a single decent reply in here, i don't understand why this happens in every freaking post I make that even mentions MDMA. It just turns into a "ooh i love mdma omg it is so safe blah blah blah" thread.

For one I mentioned ALL of the substituted amphetamines, I didn't single out mdma as being any worse. I also said, lets assume that they are neurotoxic, while obviously it can't be proven.

Funny no one has even mentioned methamphetamines neurotoxicity, guess you can't argue about that one so why talk about it....

Anyway, i suppose no one is going to post an experience so just close the thread out.
 
MeDieViL said:
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!
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MDMA often gets blamed by people because MDMA is strongly correlated with inducing psychiatric problems anecdotally and in the literature. It's really no coincidence.

Smoking was known to cause cancer 50 years before it was proven to definitively. People saw it causing cancer, but because there was no hard proof they went into denial and kept smoking. Now many of those people are dead from cancer.

Keep on rollin- bben
 
bben said:
Not a single decent reply in here, i don't understand why this happens in every freaking post I make that even mentions MDMA. It just turns into a "ooh i love mdma omg it is so safe blah blah blah" thread.

For one I mentioned ALL of the substituted amphetamines, I didn't single out mdma as being any worse. I also said, lets assume that they are neurotoxic, while obviously it can't be proven.
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In our defence you planned the seed of the neurotoxic debate. If you didn't want discussion of whether or not mdma is neurotoxic you should have avoided using the word neurotoxic. Especially since it is very much debateable if its neurotoxic or neuroadaptive. Both of which could cause similar serotonin related symptoms. You shouldn't have mentioned lesions if you didn't want people to debate it. Just say your looking for people who have used/abused amps and wonder if they had certain symptoms. Its like going into a creationist forum and saying lets discuss the big bang and assume god dosen't exist. You gonna get debate regardless.
 
If we wish to examine the effects of 5ht-ergic lesions (which are? necrotized cells? pruned axons?...for neurons which have/had 5ht receptors?), we'd need to establish cases where the presence of such lesions is certain, in order to have a functioning independent variable for the study.

This requires either objective evidence of such lesions (and no wide-scope cranial biopsies for humans, sadly! :P) or certain knowledge of how to induce such lesions. Participants with a history of mdma or methamp overuse wouldn't be reliable enough in incurring these lesions and would present confounds.

You could try to find those unfortunate few who used 4-cl-amp or 4-iodo-amp at recreational levels, to use as case studies...

ebola
 
bben said:
MDMA often gets blamed by people because MDMA is strongly correlated with inducing psychiatric problems anecdotally and in the literature. It's really no coincidence.

Smoking was known to cause cancer 50 years before it was proven to definitively. People saw it causing cancer, but because there was no hard proof they went into denial and kept smoking. Now many of those people are dead from cancer.

Keep on rollin- bben
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Care to share that literature? AFAIK all those study's refer to polydrug use and those looking at mdma itself didndt find much evidence for long term problems, unless ive missed something, so if you have more data, please post it here.

Anecdotally? You mean those polydrugusers blaming mdma?
 
bben said:
Not a single decent reply in here, i don't understand why this happens in every freaking post I make that even mentions MDMA. It just turns into a "ooh i love mdma omg it is so safe blah blah blah" thread.

For one I mentioned ALL of the substituted amphetamines, I didn't single out mdma as being any worse. I also said, lets assume that they are neurotoxic, while obviously it can't be proven.

Funny no one has even mentioned methamphetamines neurotoxicity, guess you can't argue about that one so why talk about it....

Anyway, i suppose no one is going to post an experience so just close the thread out.
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Actually, i was referring to meth's neurotoxicity when you posted your example of dealers injecting meth while also taking mdma, with your post you gave the impression that you only referred to mdma as the big problem.
 
bben said:
It just turns into a "ooh i love mdma omg it is so safe blah blah blah" thread.
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You know, i often stated i'm a poly drug user, i also repeatedly stated that poly drug use HAS indeed been associated with long term problems (wheter its caused epigenitic changes or neurotoxiticy) however i do state that i didnt see any evidence that mdma causes long term emotional problems, yet i often get the argument that i dilude myself, my question then is, how can i dilude myself if i allready stated that my own drug use is capable of causing those issues?

I know you arent referring to me, but often when people are skeptical of this kind of issues, they get a simular reply.

I do like the idea of this thread, however if you make some statements you will likely turn it into a discussion like this.

Chaos destroy posted my exact toughts.
chaos_destroy said:
In our defence you planned the seed of the neurotoxic debate. If you didn't want discussion of whether or not mdma is neurotoxic you should have avoided using the word neurotoxic. Especially since it is very much debateable if its neurotoxic or neuroadaptive. Both of which could cause similar serotonin related symptoms. You shouldn't have mentioned lesions if you didn't want people to debate it. Just say your looking for people who have used/abused amps and wonder if they had certain symptoms. Its like going into a creationist forum and saying lets discuss the big bang and assume god dosen't exist. You gonna get debate regardless.
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I heavily abused MDMA

I have anxiety

I used to love amphetamine but now it makes me a paranoid wreck

I used to smoke alot of cannabis but it now makes me a paranoid wreck

I can no longer enjoy MDMA, it just doesn't really do much for me.. (I have had seriously long breaks)..

I do not get euphoria from codeine

The 1 time i tried smack (albeit low doses) i did not get euphoria..

Didn't get much from 50mg aMT

Didn't get much from 2 6-APB pellets (don't know dose) They were real..
 
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I note that at least one Russian (I think) user of p-TAP, an MDMA-like drug, noted that he found it had long-term seratonogenic after effects much worse than E itself. The problem is that it's really not going to be possible to look at users brains until they are dead.

Sometimes it's hard to separate the direct damage from the drug from associated damage (not eating or sleeping properly, not having a regulated lifestyle and so on).

I know that methamphetamine is supposed to be far more toxic than plain dextroamphetamine but I never bothered to study the details. It just seemed plain to me that such potent compounds were very likely to be seriously harmful.

Maybe you should look into the studies on p-Cl amphetamine? I think it's used to model the neurotoxic effects of other amphetamines by virtue (?) of it being pretty harmful even at moderate dose levels.
 
You may wanna post this in ED but take out the parts about serotonergic lesions and just ask: Have you abused MDMA? Have you found it affects other drugs in such and such a way, etc etc..
 
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