neurology question regarding seretonin loss and MDMA

[nuke]

^^ This is true, but the elevations of cognitive deficits in users seems to point towards some manner of damage... This is obfuscated by the co-administration of other neurotoxic drugs such as METH by MDMA users (since almost all MDMA users are polydrug users).

The average human dose of MDMA IV is .50-.80mg/kg. Rats prefer .25-1mg, usually around .5mg, for self-administration. Most of the studies done relating to neurotoxicity are done at 5mg/kg-20mg/kg IP/IV/SC, which is about 5-40 times the average human doses, plus you have much faster peak plasma levels as compared to oral... Not only that, but rats produce more MDA from MDMA than human users do, and MDA is more neurotoxic. This to some extent makes them useless; until they start doing 1.5mg/kg-2mg/kg oral in rats, I don't we'll be able to come to any conclusions, though my gut feeling is in the long run it won't look great.

 

[MeDieViL]

The damage you've done to your serotonergic system is probably permanent. Tryptophan hydroxylase tends to recover after a while (4-6 weeks), and SERT seems to come back after a while too, though serotonin levels in the brain never seem to return to quite the same (or so it seems from smaller order mammals). This is probably from damage to the axons and/or the destruction of the serotonin storage vesicles

Additionally, the serotonergic system handles the damage kind of strangely; the neurons can sort of regenerate, but not in a completely correct way.

MDMA neurotoxicity is a very complex thing, and the loss of magic sort of effect is probably an adaption of the mind to MDMA as well as damage to the serotonin system.

i wonder what piracetam's role is in this als it seems to bring the magic back for alot of ppl, reporting it to be even better then the first roll....

as for taking breaks, anecdotally it seems that taking a 3 month break doesnt do much but that taking longer breaks did seem to bring some of the magic back (only 2 anecdotal reports about the longer breaks)

edit: allmost forget, taking HUGE doses of 5htp a while beforehand seems to bring magic back too, but also there are only 2 anecdotal reports about this is i'm not too sure about this ones

 

[MeDieViL]

i also tend to agree that less seems more

for example, huge doses are terrible, they leave me scared, seeing everyone fighting at a rave, thinking everyone wants to attack me or something

even tough the magic is gone, lower doses seem better

The damage you've done to your serotonergic system is probably permanent. Tryptophan hydroxylase tends to recover after a while (4-6 weeks), and SERT seems to come back after a while too, though serotonin levels in the brain never seem to return to quite the same (or so it seems from smaller order mammals). This is probably from damage to the axons and/or the destruction of the serotonin storage vesicles

Additionally, the serotonergic system handles the damage kind of strangely; the neurons can sort of regenerate, but not in a completely correct way.

MDMA neurotoxicity is a very complex thing, and the loss of magic sort of effect is probably an adaption of the mind to MDMA as well as damage to the serotonin system.

i remember one post saying that an SSRI should reverse the neurotoxic damage from MDMA and bring the magic back, he didnt list any sources tough
but i tend to agree that loss of magic is caused by neurotoxiticy, as vitamine c in one studie slowed tolerance in one study, however this could also be because of the decreased peak

 

[fastandbulbous]

It's one of those subtle effects, which you don't notice unless you look at the long term changes in neuronal plasticitity. Your internal model of reality is continouosly in flux and if you start to integrate the insights gained from MDMA into your everyday life, the difference between the drug state and your normal perception of reality becomes less, so you perceive the effects as being less dramatic - the 'loss of magic/wonderment/awe' is an adaptive process. Of course the neurochemical changes produced from MDMA use have an input into the situation, but part of it is that it's no longer the novelty it originally was.

That applies to an awful lot of psychoactive drugs, entactogens & dissociatives being the most extreme cases

 

[djfriendly]

Sorry for the OT, but:

For example, let's assume you've never done ecstasy before. Your seretonin block is as big as it will ever be. At this point, it is recommended that you take 120 mg.s of MDMA to manipulate all of your seretonin and acheive the true MDMA high.

Who recommends 120mg for a first time user? 100mg or even less is usually sufficient in that case.

 

[Le Junk]

Sorry for the OT, but:



Who recommends 120mg for a first time user? 100mg or even less is usually sufficient in that case.

120 mg.s is the book recommended dosage. It's been in multiple publications on the subject and is also recommended by the drug guru himself, Shulgin. To quote Shulgin, "any initial dosage of less than 120 mg.s, should be considered a different drug entirely".

The fact of the matter is that most users nowdays do not know what the 'true" MDMA high is like, due to a lack of mg.s per pill. That's why I always suggest doing a thorough EZ Complete 5 step test beforehand. Once you know the pill is mostly pure, then drop two out of the shoot, followed by one and hour and a half later. That will most likely give you the MDMA high you've been seeking all along.

Le Junk

 

[DaCubanRaver]

It's one of those subtle effects, which you don't notice unless you look at the long term changes in neuronal plasticitity. Your internal model of reality is continouosly in flux and if you start to integrate the insights gained from MDMA into your everyday life, the difference between the drug state and your normal perception of reality becomes less, so you perceive the effects as being less dramatic - the 'loss of magic/wonderment/awe' is an adaptive process. Of course the neurochemical changes produced from MDMA use have an input into the situation, but part of it is that it's no longer the novelty it originally was.

That applies to an awful lot of psychoactive drugs, entactogens & dissociatives being the most extreme cases

im going to have to agree with you on here.
Here's a good read: http://mdma.net/#mdmatox
towards the bottom of the section they also bring this point up.

"Perhaps we shouldn't be so surprised at the "loss of magic". The liver (and the brain) is adapted to life on the African savannah. Our vital organs can't know the difference between the elixir of life and a poison. MDMA has the attributes of both, and in the African bush, the latter is a more realistic outcome. Yet we won't be trapped in brutish states of consciousness for ever. In the near future, functional analogues of MDMA promise to enhance mental health, add perpetual magic to our lives, and beautify our troubled minds. Empathetic bliss isn't inherently toxic; though its reactive metabolites may be. In principle, the psychopathologies of everyday life can all be cured. MDMA offers a foretaste of life in post-Darwinian paradise; but it delivers, at best, only a fleeting hint of the magic to come. "

 

[kidamnesiac]

fwiw:
on the less is more topic, i find <80mg to be a much better experience than >80mg. a lot of the subtleties can be lost at the higher doses from the peripheral stimulation, imho. I have no explanation for this.

I usually find shulgin low on other drugs.

 

[Le Junk]

fwiw:
on the less is more topic, i find <80mg to be a much better experience than >80mg. a lot of the subtleties can be lost at the higher doses from the peripheral stimulation, imho. I have no explanation for this.

I usually find shulgin low on other drugs.

It's actually listed as 120 mg.s to start followed exactly 1 and 1/2 hours later by 1/3 to 1/2 of your initial dose in more than just multiple publications on the subject. In fact, the book entitled "Ecstasy, The MDMA Experience" has the author experimenting with doses of 80 mg.s, then at a later date 100 mg.s, then at the last date 120 mg.s. He describes in full detail the experiences at each level of administration, citing that 120 mg.s was an entirely different experience alltogether, adding that he felt this was where the "true" MDMA effect actually took place.

Considering the legal tablets I started with in the 80's were 250 mg.s a piece, I would definately have to agree wholeheartedly with those previously mentioned figures. The author of the above mentioned book did describe feelings of peace and enlightenment at the lower doses, but didn't feel the awsome power of the drug that he said actually "consumed him" until he hit the 120 mg. mark. Just some food for thought.

Now, I do agree that less is sometimes more, and that taking 10 pills a night will actually be less enjoyable, and more than not, miserable. But taking at least 120 mg.s to start is simply the base for which all shoul start out with. This is why alot of newbies will often enter threads or posts that they believe this was actually the first time they've ever really rolled, when they finally come across a pill or powder with a higher content of MDMA.

Le Junk

 

[kidamnesiac]

160mg of 100% mdma, verified with GC/MS and zero tolerance to stimulants, offered next to nothing for me besides a lot of peripheral stimulation similar to racemic amphetamine.

The human beast is such a poor lab animal.

 

[Le Junk]

160mg of 100% mdma, verified with GC/MS and zero tolerance to stimulants, offered next to nothing for me besides a lot of peripheral stimulation similar to racemic amphetamine.

The human beast is such a poor lab animal.

Multiple or single dosing of the 160 mg.s on the same night I presume?

Le Junk