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Low Dose MDMA and Upregulation

Zalo

Zalo

Bluelighter
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Oct 11, 2012
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Hey BlueLight,

According to this article http://www.drugs-forum.com/forum/showthread.php?t=25637 it states that, "Small doses of MDMA (equivalent to a human dose of <1mg/kg) cause up-regulation. This appears to stimulate the development of new serotonin neurons," and, "In contrast to the administration of high doses of MDMA that act as a selective serotonergic neurotoxin in animals, the administration of low concentrations of MDMA produce the opposite effect, stimulating neuronal growth. MDMA’s release of serotonin modulates receptor enzymes and stimulates astrocytes to release Neurotrophic Growth Factors (NGF). These actions, in turn, cause neurons to develop and innervate new target areas in the brain. (75-77) Stimulating neurons to morphologically reorganize, known as neuroplasticity, has the potential to correct underlying causes of neurochemical imbalances. It may be possible to re-engineer neuronal structures and activity to create a biochemical state of lasting well being and happiness. (78 )"

I'm curious to know the effects of low doses of MDMA. I'm aware that research in this area is minimal to non-existent, so I'm mostly looking for new ideas or continuing ideas on this topic.

Thank you.
 
Folley said:
I've had thoughts on using MDMA in a similar fashion.. but in reality, it's a neurotoxin. You should be limiting your exposure to it as much as possible.


It just doesn't seem safe to me
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Just like the article says, MDMA is neurotoxic at high doses, but not at low doses even suggesting the opposite. I wouldn't be surprised if the 'afterglow' that many users report is due a positive, yet temporary, change in serotonin functionality immediately post ingestion. I'd be intrigued to see what sort of doses would be used - going to read the article.

EDIT: Seems like they recommend .25-.45mg/kg. Very low doses indeed.
 
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Also, its under a 1mg dose..With this in mind, I rather take a nootropic such as noopept or piracitam rather than waste 1mg of precious MDMA everyday.
 
SilentRoller said:
Also, its under a 1mg dose..With this in mind, I rather take a nootropic such as noopept or piracitam rather than waste 1mg of precious MDMA everyday.
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1mg/kg. So that's 80mg for me weighing 80kg. Noopept or Piracetam aren't going to stimulate a positive re-organization of your serotonin system.
 
ive taken 80mg before and enjoyed it, however i found duration of happiness was only about an hour....

then out come the ket snuff bullet ....lol
 
Darksidesam said:
ive taken 80mg before and enjoyed it, however i found duration of happiness was only about an hour....

then out come the ket snuff bullet ....lol
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This is considering MDMA as a form of anti-depressant taken daily, not just using it for a buzz at a rave like we all do. I'm really tempted to try low doses, like 30-40mg daily for 2-3 weeks just to see if anything happens.
 
SilentRoller said:
Also, its under a 1mg dose..With this in mind, I rather take a nootropic such as noopept or piracitam rather than waste 1mg of precious MDMA everyday.
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I agree here, just seems like a waste of good mdma. I still wait a descent amount of time between rolls, but when I roll I like to roll hard. 77 mgs would be a huge tease for me then I'd have to redose and I wouldn't get to where I should have if I just took 180 off the bat.
 
My guess would be for this to work you shouldn't want to exceed 0.5mg/kg
Any more and you're getting a buzz and this could lead to redosing to get a full roll on
 
Sorry Jwillis, but you are wrong here. Noopept does simulate NGF.....



Sources:

We showed that the nootropic drug increases expression of neurotrophic factors in the hippocampus. Our results are consistent with the hypothesis that neurotrophin synthesis in the hippocampus determines cognitive function, particularly in consolidation and delayed memory retrieval. Published data show that neurotrophic factor deficiency in the hippocampus is observed not only in advanced Alzheimer's disease, but also at the stage of mild cognitive impairment (pre-disease state). In light of this our findings suggest that Noopept holds much promise to prevent the development of Alzheimer's disease in patients with mild cognitive impairment
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http://www.ncbi.nlm.nih.gov/pubmed/19240853

Mechanistically, single doses of noopept at 0.5mg/kg (as well as 28 days of chronic dosing at the same dose) noted increases in both NGF and BNDF mRNA concentrations in the rat hippocampus, with a greater relative increase in NGF and no apparent tolerance developing over 28 days. The authors hypothesized that the increase in these factors (neurotrophin factors) is associated with chronic improvement in memory associated with Noopept, as some trials noted greater improvements following chronic dosing (rats and humans) while neurotrophins are known to be associated with long-term memory enhancement
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http://examine.com/supplements/Noopept/#ref4 (a page which lots of information leading to scientific studies supporting the above)

Why bother taking 1mg/kg of MDMA when you can dose noopept on a daily basis for a week or two and acheive the same thing.
 
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I'm tempted to try this out on myself. I feel too curious about this to wait till I get into post-graduate research. I'm wondering if sub-threshold doses would yield any results.
 
^^I wouldn't do it if I were you. The best case scenario is that by using MDMA this way, you may get some SERT upregulation (something you wouldn't really notice immediately in day-to-day life), or the worst case scenarion (more likely): It doesn't work as expected, you screw your tolerance, you get brain-zaps...the list goes on. Using 1mg/kg of MDMA daily is not a good thing.....

EDIT - Just re-read your post, and noticed it doesn't say daily use. Still, it just seems like a pointless exercise when you can just have a few months break from all drugs and heal your brain that way.
 
I was thinking more along the lines of 20mg daily, like 0.25-0.3mg/kg. Also, if the neuronal growth was due to the serotonin being released by MDMA then one could assume that MDAI would be a safer option for testing. I'm sure it's not this cut and dry though.

Edit: Read your edit. It's less to do with healing my brain so that I can increase my frequency of MDMA use (it seems like that's what you were implying) and more to do with finding possible methods to cure depression/anxiety.
 
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I agree, I don't think its as clear cut as it first appears, and I wouldn't really want to be the one to test the theory either. On a related note (as I was just thinking about MDAI), whats ones thoughts on an MDMA & MDAI combo? Does it scream serotonin syndrome or what? I only got thinking about it as I thought MDMA + more serotonin would be interesting.....
 
JWills20 said:
1mg/kg. So that's 80mg for me weighing 80kg. Noopept or Piracetam aren't going to stimulate a positive re-organization of your serotonin system.
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The fuck..? 80mg? Everyday? and you expect that to help with... ANYTHING?


MDMA is metabolized DIRECTLY into a number of neurotoxins, even if the main chemical doesn't have a damaging effect alpha-methyldopamine and other metabolites WILL. Anyone attempting this before more research is conducted is putting their health in the hands of a single study.. I just can't see how this could have any benefit over other safer drugs that were designed to be used in this fashion.
 
I'd imagine something like this to take effect rather quickly compared to other safer drugs, like the immediate anti-depressant effects of post low dose ketamine. Perhaps it's not the best example since they are completely different drugs, but I hope you understand the point I'm trying to make.

Anyways, I've never looked into this, but is MDMA itself without metabolites neurotoxic? I'd imagine that taking low doses, like 20-30mg, would produce very little neurotoxicity, even if MDMA itself was neurotoxic, that taking anti-oxidants pre, during, and post ingestion would most likely eliminate any possible damage. I'd have to agree with you though that 80mg daily would be a ridiculous dosage.

At this point it is pretty much blind speculation however, but I was just interested in new ideas on this topic.
 
Folley said:
The fuck..? 80mg? Everyday? and you expect that to help with... ANYTHING?


MDMA is metabolized DIRECTLY into a number of neurotoxins, even if the main chemical doesn't have a damaging effect alpha-methyldopamine and other metabolites WILL. Anyone attempting this before more research is conducted is putting their health in the hands of a single study.. I just can't see how this could have any benefit over other safer drugs that were designed to be used in this fashion.
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Before I write this post, I'm not endorsing regular low dose MDMA, this is quite simply speculation founded from a few scientific studies. I also never said i'm taking 80mg of MDMA. It was an example of 1mg/kg to correct SR's post which appeared to misinterpret it as just 1mg of MDMA. For the purpose of improving psychological well-being, NOT HAVING A GOOD TIME, i'd guess the doses would be nearer 20-40mg.

MDMA is metabolized DIRECTLY into a number of neurotoxins, even if the main chemical doesn't have a damaging effect alpha-methyldopamine and other metabolites WILL
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It's pretty well recognised that MDMA is not particularly neurotoxic at usual recreational doses, hence why it is being administered to humans in clinicals settings. I'd imagine the neurotoxicity of MDMA, at doses ranging between 20-40mg, is pretty negligible - it's barely even psychoactive. To say that the metabolites will definitely cause damage doesn't appear to be true. What's not to get? High doses = neurotoxicity. Low-medium doses = insignificant neurotoxicity. You can further battle against oxidation if you supplement anti-oxidants or even use an SSRI to block the site from the dopamine radicals, but that's not useful for low doses and would further complicate I'd imagine.

Everyday? and you expect that to help with... ANYTHING?
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How is a low dose going to help with anything? Read the research and it suggests a reason why. I'm not saying this theory is true, but the scientific rationale is there and it does make sense. Other than neurotoxicity, which is an unrealistic danger of low dose MDMA, what would be stopping a study into this? It might work, it might not.

@SilentRoller. Thanks for linking some studies into the smart drugs, I really haven't read anything about them so I'm not going to comment on what they can and can't do. I'd imagine, and this is complete speculation, that the NGF induced by MDMA would be more selective to serotonin networks than noopept or piracetam. Hence the authors of the original article wrote 'It may be possible to re-engineer neuronal structures and activity to create a biochemical state of lasting well being and happiness.' Whereas the smart drugs probably modulate NGF more selective toward cognitive enhancing neural structures - hence there name. That'd be my guess at the difference - I could well be wrong though.

About SS: I've no idea if MDAI & MDMA would have a risk of SS. It is quite dependent on their actions of serotonin release. If MDAI caused serotonin release via a different mechanism to MDMA, then the risk would probably be very real. If they have similar mechanisms then they'd be fighting against each other for the binding sites etc, similar to MDMA & SSRI's, which wouldn't cause a realistic risk. Many pills in the 90s were a combination of MDxx and Serotonin Syndrome was still very rare. Similarly, many users mix MDA with MDMA and do not experience SS. For these reasons, I'd imagine that the MDxx family of compounds do not synergize well enough to cause such a severe amount of serotonin that induces the syndrome. For this reason, I would say that MDAI & MDMA would, most likely, not cause SS.
 
^ The majority of studies saying lower doses are not damaging are only talking about a SINGLE dose... not everyday use over an extended period of time.



if it's simple serotonergic action that is causing the upregulation than surely there are MUCH safer alternatives
 
Taking 80mg of MDMA everyday would be the death of me. Low dose MDMA feels like shit, I'd much rather be sober.
 
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