• MDMA &
    Empathogenic
    Drugs

    Welcome Guest!
  • MDMA Moderators: Esperighanto

I have a dubious theory

I

Illuminateur

Bluelighter
Joined
Nov 2, 2009
Messages
62
And I'm not recommending trying this out.

Hypothesis: Doing coke while on MDMA will result partial reduction of neurotoxic danger.

Facts:
1. MDMA causes release of large amounts of serotonin(5HT), resulting in running out after 4-6 hours.

2. One of the dangers of E is that when you run out of serotonin, dopamine binds to the serotonin receptors and that's bad.

3. Postloading with L-Dopa(5HTP for the Dopamine system) increases neurotoxicity due to the larger amounts of dopamine available.

4. Cocaine releases dopamine resulting in a similar drop in dopamine levels afterwards.

SO: Using cocaine to release dopamine during the MDMA induced high level of serotonin activity would:
1. Prevent that dopamine from doing neurotoxic stuff in 5HT receptors and stay where it belongs in D1 and D2.
2. Cause a drop of available Dopamine afterward to do bad things when the serotonin is low.
3. You'd also probably crash.
 
Also if:

1. Preloading with 5HTP makes your receptors less serotonin sensitive.
2. 5HTP, and high carb, low protein diets shifts the balance of Dopamine/Serotonin to serotonin, reducing dopamine.

Then would preloading the previous day->hour or so before with L-Dopa make less serotonin available, creating Higher sensitivity when you let it back with MDMA and 5HTP?
 
MDMA is dangerous when referring to neurotoxicity because agonism of 5-ht2a receptors releases large amounts of glutamate and this poses a potential threat because of excitotoxicity. Your brain has extraodinary capabilities of protecting itself from excitotoxicity, but it cant 100% prevent all of it. So your theory is, not so be rude, not correct...
 
The theory of dopamine replacement has been dis-proven and more people are leaning towards receptor down-regulation.
 
doing coke on pills completely dulls the roll.

doing coke previous to pills completely dulls the roll.

not sure if this helps prove or disprove your theory...

(experience)
 
haha, this might explain why I love blasting fat lines after coming down off pills. would be great if this were true.

I love how people are so cavalier about saying that coke kills a 'roll' too. I do coke when I am on E all the time and it works just fine for me.
 
bben said:
I dont think hes claiming it would eliminate neurotoxicity, but it could reduce it. Any time you take mdma pretty much, there will be some toxicity regardless of what you do, it just wont likely be noticable.

Glutamate plays a minor role in ecstasys neurotoxicity anyway, stop being pedantic.
Click to expand...

You're actually very wrong with that statement. Glutamate is the most abundant excitatory, and overall general neurotransmitter in the brain. Agonismof 5-ht2a serotonin receptors causes glutamate release. Your brain has the ability to upregulate silenced glutamatergic receptors (AMPA receptors) in the case of too much glutamate overwhelming a neuron. This essentially prevents massive damage to a neurons structure, mainly the post-synaptic membrane.

When you get punched in the head enough, glutamate is released. Why do you think some unfortunate boxers like Muhammod Ali has parkinsons? They've been punched all over their head and this had caused excessive glutamate release. Now, they have way too many excitatory synapses which cause abnormal uptake of glutamate and causes involuntary muscle movement.
 
can you back up that hypothesis with documentation? posting research to back up your statements is usually the best way to go about resolving disagreements like this.

its well known that receptors are rather fragile and can be destroyed via overstimulation, but i've never heard anything about excess glutamate causing parkinsons, etc.

besides, parkinsons results when 80-90%+ of your dopamine-producing neurons die off, and its the lack of dopamine that causes the involuntary muscle jerks, etc, because dopamine can act as either an excitatory or inhibitory neurotransmitter, depending where its binding.

as for mdma neurotoxicity, read this post, and this one. and there's other neurotoxicity information in that thread too, if you just wanna read the whole thing.
 
Last edited:
tathra said:
can you back up that hypothesis with documentation? posting research to back up your statements is usually the best way to go about resolving disagreements like this.

its well known that receptors are rather fragile and can be destroyed via overstimulation, but i've never heard anything about excess glutamate causing parkinsons, etc.

besides, parkinsons results when 80-90%+ of your dopamine-producing neurons die off, and its the lack of dopamine that causes the involuntary muscle jerks, etc, because dopamine can act as either an excitatory or inhibitory neurotransmitter, depending where its binding.

as for mdma neurotoxicity, read this post, and this one. and there's other neurotoxicity information in that thread too, if you just wanna read the whole thing.
Click to expand...

Dopamine receptors are very resilient when it comes to overstimulation. I think Dopamine receptors have one of the fastest rebound times from down-regulation. There are plenty of articles about Post-synaptic density (PSD-95 etc.) protein families and how they upregulate otherwise silenced neurotransmitter receptors to compensate for either internal or external stress. They are built into neuronal membranes for the exact reason of protecting a neuron from overstimulation.

They are now thoroughly researching this set of protein families and find ways to manipulate them for treatment of ALL kinds of mental disorders and neurodegenerative diseases. This is part of the genetic research that people in the field are looking into in order to actually change dysfunctional DNA coding.
 
Illuminateur said:
And I'm not recommending trying this out.


4. Cocaine releases dopamine resulting in a similar drop in dopamine levels afterwards.
Click to expand...

Cocaine is a DA reuptake inhibitor, it does not release DA.

There are some experiments (see the relevant ADD topics, too much clonazapam and ethanol tonight to go find them) that have shown that DARI's do have some neuroprotective effects with MDMA (while DA release agents in general are somewhat neurotoxic, ex: (meth)amphetamine).

Some descriptions of the toxicity is that DA gets into places where 5HT normally would be (except it's all been released by the MDMA) and gets metabolized to a species which causes oxidative stress and kills neurons.
On the other hand, there are studies that suggest that the neurotoxicity results from direct metabolites of MDMA itself....
 
bben said:
Show me some research that says glutamate is repsonsible for ecstasys toxicity, because if its true, i would love to know about it. Links?

Also im pretty sure theres alot of other drugs that increase glutamate huge amounts, and they arnt nearly as toxic as mdma has the potential to be.
Click to expand...

http://www.ncbi.nlm.nih.gov/pubmed/...med_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1

"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine, MDMA, XTC, X, E] is a psychoactive recreational hallucinogenic substance and a major worldwide drug of abuse. Several reports raised the concern that MDMA has the ability to induce neurotoxic effects both in laboratory animals and humans. Despite more than two decades of research, the mechanisms by which MDMA is neurotoxic are still to be fully elucidated. MDMA induces serotonergic terminal loss in rats and also in some mice strains, but also a broader neuronal degeneration throughout several brain areas such as the cortex, hippocampus, and striatum. Meanwhile, in human "ecstasy" abusers, there are evidences for deficits in seronergic biochemical markers, which correlate with long-term impairments in memory and learning. There are several factors that contribute to MDMA-induced neurotoxicity, namely, hyperthermia, monoamine oxidase metabolism of dopamine and serotonin, dopamine oxidation, the serotonin transporter action, nitric oxide, and the formation of peroxinitrite, glutamate excitotoxicity, serotonin 2A receptor agonism, and, importantly, the formation of MDMA neurotoxic metabolites. The present review covered the following topics: history and epidemiology, pharmacological mechanisms, metabolic pathways and the influence of isoenzyme genetic polymorphisms, as well as the acute effects of MDMA in laboratory animals and humans, with a special focus on MDMA-induced neurotoxic effects at the cellular and molecular level. The main aim of this review was to contribute to the understanding of the cellular and molecular mechanisms involved in MDMA neurotoxicity, which can help in the development of therapeutic approaches to prevent or treat the long-term neuropsychiatric complications of MDMA abuse in humans."
 
Mantis Style said:
There are several factors that contribute to MDMA-induced neurotoxicity, namely, hyperthermia, monoamine oxidase metabolism of dopamine and serotonin, dopamine oxidation, the serotonin transporter action, nitric oxide, and the formation of peroxinitrite, glutamate excitotoxicity, serotonin 2A receptor agonism, and, importantly, the formation of MDMA neurotoxic metabolites.
Click to expand...

all we've established now is that glutamate excitotoxicity is a contributing factor to mdma's neurotoxicity, one of 9 different things. this reads like the formation of mdma neurotoxic metabolites is the biggest cause, not glutamate excitotoxicity.
 
You must log in or register to reply here.
Top