waiting period between mdma and meth doses

[whos there]

so i apologise if this has been discussed before, but ive been thinking about the way that most people will advise at least a few month break between mdma doses, but noone ever seems to caution on the period between doses of methamp. then i came across this,

[SIZE=-1] The Neurotoxic Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and Methamphetamine on Serotonin, Dopamine, and GABA-ergic Terminals: An In-Vitro Autoradiographic Study In Rats
by
Armstrong BD, Noguchi KK.
Department of Psychiatry and Biobehavioral Science,
University of California at Los Angeles,
NPI 760 Westwood Plaza Room 67-373,
Los Angeles, CA 90024, USA.
Neurotoxicology. 2004 Dec;25(6):905-14

ABSTRACT

Damage to serotonin (5-HT) terminals following doses of 3,4-methylenedioxymethamphetamine (MDMA) is well documented, and this toxicity is thought to be related to dopamine release that is potentiated by the 5-HT(2A/2C) agonist effects of the drug [Neurotoxicology 19 (3) (1998) 427]. Although MDMA and methamphetamine (METH) have some similar dopaminergic activities, they differ in their 5-HT agonistic properties. It is reasoned that the study of the resultant toxicity following equimolar doses of MDMA and METH on both dopamine and 5-HT terminals should offer a comparison of the ability of these drugs to induce neurotoxicity. In order to measure the toxic effects to the brain, rats were given equimolar doses of MDMA (40mg/kg/day) and METH (32mg/kg/day) in subcutaneously implanted osmotic minipumps for a period of 5 days, and in-vitro autoradiography using [ [Formula: see text] ]-paroxetine, [ [Formula: see text] ]-mazindol, [ [Formula: see text] ]-methylspiperone, and [ [Formula: see text] ]-flunitrazepam, was performed on brain sections. The results showed that METH was more toxic to 5-HT terminals than MDMA in forebrain regions, including the anterior cingulate, caudate nucleus, nucleus accumbens, and septum. METH was also more toxic than MDMA to dopamine terminals in the habenula, and posterior retrosplenial cortex. Therefore, we find that METH was more toxic to 5-HT and dopamine terminals in specific brain regions in both pre and post-synaptic sites following continuous equimolar dosing.

so following that logic, basically what im asking is, besides the obvious addiction potential for meth vs mdma, why dont users ever warn against taking, i dont know, a week off shit to sleep and come down? but most people tend to binge like crazy then crash for a day or two, sometimes they wont crash til their body finally gives out on them. molly i can wait 3 months (well no, prolly not 3..) and still not be near where i should be with ~200mg quality powder. with meth im always pretty twacked, but then again meth is very different from mdma...so maybe serotonin degrades/downregulates quicker than DA?

maybe il try rolling everyday for a week and see how that dumbed out feeling compares to the soul crushing despair that comes with a week long meth binge. bet id eat and sleep a whole lot better, if the serotonin syndrome didnt kill me first.
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[aced126]

I have actually always wondered about this. For one I know that MDMA will lose its efficacy very very quickly if dosed often (once a week as you said), but this is not the case with meth. About neurotoxicity, again I am not too sure. Most of the meth will enter the dopaminergic neuron and release dopamine like that. With MDMA on the other hand, some of it will operate via that mechanism, but a lot of it will enter the serotonergic neuron and release 5ht. This then causes loads of downstream effects including increased dopamine activity as mentioned due to 2a/2c agonism. Although note that meth does release 10% of 5ht which MDMA is capable of releasing. Maybe dopamine is produced at a faster rate than 5ht, so dopaminergic acting drugs can be readministered often with efficacy, whereas after initial MDMA release, something seems to be inhibiting further 5HT release/production (maybe TPH inhibition of something else in the pathway) which means that repeated MDMA dosing will yield effects more and more to do with direct dopamine release rather than 5ht mediated effects. Just my speculations...

 

[Cotcha Yankinov]

The main reason why you can repeatedly use meth and still get high is the dopamine system is much more.. "robust" is the term usually used. Dopamine your brain can stock up on again in a couple of hours and likely never really run dry (same with adrenaline), serotonin takes a lot longer though. Meth is definitely toxic to serotonin but I don't believe serotonin is necessary for the regular amphetamines as much, compared to MDxx without serotonin you wouldn't feel much at all, not even have as much dopamine release through 5-HT2A/C.

I think one of the reasons why there is a "only use MDMA once in a while" kinda thing is that one of the early theories in serotonin axon damage is that once you run out of serotonin the SERT starts taking dopamine into the serotonin terminal, and if it's metabolized there it makes ROS that harm the axon. So don't use MDMA to the point where you run out of serotonin was the kinda thinking behind preventing that form of toxicity.

If I had to guess I'd say you'd get less kick out of frequent dosing MDxx due to a mixture of vesicles not having serotonin, down regulation of receptors and tryptophan hydroxylase, but the one I'd really be concerned about is the serotonin toxicity. The SERT imaging studies show things returning to normal-ish levels in many weeks but this is thought to be not a sign that there wasn't any permenant damage done but that there was rewiring that happened. I suspect until this rewiring happens and serotonin can fire better I'd expect some loss of magic. I do wonder what MDMA will do to a person that's serotonin has rewired over and over... Maybe that is loss of magic? There is also the matter of 5-HT2B with MDMA. Could be the main victim regarding receptor down regulation. Loss of magic is an interesting subject though, seems to happen potently with some people and MDMA, you can always get a kick out of meth even though it won't be like the first time. I suspect it's just that dopamine/adrenaline dominates in mediating meth's effects.

Alexander Shulgin originally said 4 times a year max on the MDMA by the way and I'd have to agree with him, careful with those brain cells of yours! Also ANTIOXIDANTS

 

[mb-909]

Serotonin takes way longer to regenerate and it is produced in the raphe nuclei => it needs some time to reach the serotonin regulated neurons. As far as I remember MDMA isn't releasing as much Serotonin as other drugs, but is more of an inhibitor of said transmitter. The overall effect is probably more a product of releasing oxymoron and the combination of the neurotransmitters than serotonin alone. I am new to this field, but as far as I know there are many side effects, which can be either the result of receptor regulation /depression, changes in the endocrine regulated system or other unknown factors: big changes in blood flow in the frontal lobe for up to 3-6 weeks, inhibition of cyp2D6 for up to a week, changes in the endocrine and serotonin system. Besides showing problems with verbal memory, the other short term memory related tasks seem not to differ that much (or long term memory, depending on the definition). If MDMA toxicity is really such a big kind of deal, I don't know, but in the end it is mostly dose dependent. Some suggest that alcohol maybe more toxic than MDMA, with MDMA being specific and alcohol being a blast, explosion (firecracker style)...

As most of the time the doses used in this experiment are way over the typical used doses in human...

http://www.maps.org/research-archive/mdma/MDMA_FINAL _IB-edition-7_1Aug13.pdf

 

[whos there]

so maybe il skip that week long molly binge after all

 

[Dresden]

If MDMA and methamphetamine are so bad for you, then something bad should happen after you take them NOT including having to have your brain dissected to show it. I'm talking, clinically, something bad and major should happen. It simply isn't the case.

 

[clubcard]

I think 4 times a year is a GOOD IDEA. What was it PJ O'Rouke said about MDMA 'Turn on, Tune in, Turn up late for work on Teusday'.

Of course, who knows whats in the pills & powders being sold as MDMA.

I spotted a simple, legal (in UK) MDMA replacement which I posted - Seiko was the only one to draw it and check the law.

 

[dopamimetic]

The toxicity (depletion / tolerance / loss-of-magic) isn't that directly coupled with the effects, imho. 4,4'-DMAR has been very different in this regard and I really wanna do this one again (knowing the bad reputation.. I've been reckless and it went out good. Wouldn't do with a new compound.) ... don't know if it's due to some MAOI effect though.