Supplementing with Dopamine Precursors as a Route for Increasing MDMA Neurotoxicity?

[Jabberwocky]

A friend was telling me about some research he and his group had done in a lab, feeding (not injecting) mice with tryptophan and 5-HTP. It had previously been discovered that if you inject mice with 5-HTP they produce much more serotonin than normal. He established that this also happens if you feed them the 5-HTP.

OK, not so interesting at least for this topic. What is interesting is that they found elevated levels of serotnin stored in dopaminergic neurons. Wow, they thought! It makes sense, since the same enzyme that decarboxylates 5htp to 5HT decarboxylates L-dopa to Dopamine.

They then tried the opposite of this and fed mice L-Dopa and tyrosine (some they fed just L-Dopa, some they fed just tyrosine). In fact they observed that the mice they fed took up the L-Dopa, converted it to Dopamine, and stored it in serotonergic neurons! Holy cow!

A (possible) route for MDMA neurotoxicity is the reuptake of dopamine through serotonin transporters (and a subsequent degradation into some nasty byproducts).

My question: would the fact that having ambient dopamine stored in serotonergic neurons increase the likelihood of this reuptake and therefore increase the amount of damage through this route?

So, would supplementing with tyrosine or L-Dopa before an MDMA experience potentiate neurotoxicity?

If so, this might be a good empirical avenue toward testing the truth of this theory of MDMA neurotoxicity-

 

[Ham-milton]

I really don't recomend supplementing with L-Dopa unless psychosis is your goal.

 

[Jabberwocky]

Nobody is suggesting anybody supplement with L-Dopa and or tyrosine, both can cause issues with mental stability -

its just a theoretical Q for some of the more knowledgable folks - I don't want it to derail into a what supplement is best thread really -

 

[LuxEtVeritas]

perhaps all this shows is if you have any neurotransmitter in a higher normal ratio than the others than there is a (greater?) potential for storage in neurotransmitter neurons other than those specific for said neurotransmitter

this would happen with any drug that increases the release of neurotransmitters to any significant degree (assumably) and preferentially toward grerater enhancement of one

perhaps simply after there is an increase of neurotransmitters there can become a concommitant saturation of neuronal storage sites and hence if one type is full than the related sites may be potential storage sites

did he use very high amounts of the substrates in mice and do mice have higher amounts of decarboxylase substrates?..if so this may set th shift...there may be a threshold of course....

 

[5-HT2]

The rate-limiting step in the synthesis of both dopamine (DA) and serotonin (5-HT) is 5-hydroxylation of the amino acid precursor by tyrosine hydroxylase or tryptophan hydroxylase, respectively. Supplementing with L-DOPA or 5-HTP skips this step and therefore allows the production of more of neurotransmitter than the normal biochemical equilibrium would otherwise allow. The next step in the biosynthetic pathway is decarboxylation of the now hydroxylated amino acid by aromatic acid decarboxylase (AADC). AADC is relatively nonselective compared to the hydroxylases, so it can do the same job in all monoamine neurons. 5-HT neurons don't have tyrosine hydroxylase, and DA neurons don't express tryptophan hydroxylase, so under normal conditions one type can't synthesize the other type's transmitter. However, both types of neurons express aromatic amino acid transporters. Thus, if you skip the amino acid specific step by supplementing with L-DOPA or 5-HTP, they will be taken up by all monoamine neurons, subsequently decarboxylated to dopamine or serotonin, respectively, and then accumulated in vesicles by vesicular monoamine transporter subtype 2 (VMAT2).

A (possible) route for MDMA neurotoxicity is the reuptake of dopamine through serotonin transporters (and a subsequent degradation into some nasty byproducts).

My question: would the fact that having ambient dopamine stored in serotonergic neurons increase the likelihood of this reuptake and therefore increase the amount of damage through this route?

The serotonin transporter (SERT) located on the plasma membrane of the 5-HT neurons and mediates the reuptake of 5-HT from the extracellular space back into the 5-HT neurons. MDXX causes the massive release of 5-HT, and to a lesser extent, DA, through their respective plasma membrane transporters on the corresponding monoamine neurons. When the SERT does not have MDXX bound, it will run in the normal direction, taking up 5-HT with relatively high affinity and also other monoamines, such as DA, with lower affinity. In my understanding of the DA-oxidative radical model of MDXX neurotoxicity, the SERT's importance is primarily as a mechanism for the dopamine to get inside serotonin neurons. L-DOPA supplementation will lead to the synthesis, storage, and release of DA by 5-HT neurons, so therefore, there will be more extracellular DA floating around for reuptake by their axon terminals.

So, would supplementing with tyrosine or L-Dopa before an MDMA experience potentiate neurotoxicity?

If so, this might be a good empirical avenue toward testing the truth of this theory of MDMA neurotoxicity-

Yes and yes. To go a step further, I would predict that at high enough doses of L-DOPA, there would be neurotoxicity even in the presence of SSRIs, because the 5-HT neurons are actually synthesizing DA and therefore there will be some intracellular DA around no matter what.

 

[Jabberwocky]

thanks 5HT for the informative post-

why hasn't someone done this experiment yet then? There seems to be such meager evidence for MDxx neurotoxicity that you would think there would be some in depth studies on it - even the US could get behind some studies that would prove MDxx being neurotoxic -

 

[silek65]

Hi,

Is this confirmed? Let me say something and then ask what to do in this case.

My friends and me have some problems with a Loss of Magic that comes really fast when using bk-MDMA (Methylone).
All of us takes some break from bk-MDMA, but some are still Amphetamine users - from a time to time.

Anyway more then a week ago we have tried crystal MDMA (doeses ~120mg) and after 30-40min, each of us fell asleep and also no one felt the MDMA euphoria.

Last saturday (one week break from previous) I did administrated MDMA 100mg and ~80mg of Amphetamine from the street as a one orally shoot.

In 30-40min I didn't fell asleep and it was pretty ok, but still without any euphoria.

It was strange anyway and I was considering to take some recovery with 5-HTP and L-Dopa for short time 10 days with a break for full 3 days and take a try if MDMA is going to be working or not.

--
For 10 days:
in the morning:
breakfast with Magnesium, Vitamin B-6, B-12 and C

30 minutes after:
2x capsule (100mg?) of Keizen's 5-HTP - which contains 50mg of 5-HTP and other Ingredients: Cellulose, Magnesium Stearate, Silicon Dioxide, Gelatin (capsule).

During a day, at same time:
15-30 minutes of physical exercise program (increase effects of L-Dopa)

At night:
1x capsule (400mg) of "DOPA Mucuna" from Now Foods - it contains 120mg of L-Dopa
1x glass of quality Orange Juice - 200-300ml

Cons/Warnings (2):
- "elevated levels of serotnin stored in dopaminergic neurons"
- "converted it to Dopamine, and stored it in serotonergic neurons! Holy cow!"

Note from research (1):
- (L-Dopa) if user has have a low level of carbon in his body, then L-Dopa additionally should be administrated with glucose/sugars to prevent hypoglycemia (low blood sugar).
--

Now I'm wondering if I should do this or not - I'm still trying to find a way to increase MDMA quality (maybe I should stop to take amphetamine?).

Thank you
Best Regards

 

[clubberdude]

Hi,

Part of message cut...

Now I'm wondering if I should do this or not - I'm still trying to find a way to increase MDMA quality (maybe I should stop to take amphetamine?).

Thank you
Best Regards

Piracetam might help, I know it potentiates MDMA quite nicely for me (though not why I take Piracetam - I find it beneficial in many other ways), and many others have reported good things.

Abstinence and keeping total doses/frequency of dosing of MDMA lower helps tolerance to build as well.

 

[pofacedhoe]

Hi,

Is this confirmed? Let me say something and then ask what to do in this case.

My friends and me have some problems with a Loss of Magic that comes really fast when using bk-MDMA (Methylone).
All of us takes some break from bk-MDMA, but some are still Amphetamine users - from a time to time.

Anyway more then a week ago we have tried crystal MDMA (doeses ~120mg) and after 30-40min, each of us fell asleep and also no one felt the MDMA euphoria.

Last saturday (one week break from previous) I did administrated MDMA 100mg and ~80mg of Amphetamine from the street as a one orally shoot.

In 30-40min I didn't fell asleep and it was pretty ok, but still without any euphoria.

It was strange anyway and I was considering to take some recovery with 5-HTP and L-Dopa for short time 10 days with a break for full 3 days and take a try if MDMA is going to be working or not.

--
For 10 days:
in the morning:
breakfast with Magnesium, Vitamin B-6, B-12 and C

30 minutes after:
2x capsule (100mg?) of Keizen's 5-HTP - which contains 50mg of 5-HTP and other Ingredients: Cellulose, Magnesium Stearate, Silicon Dioxide, Gelatin (capsule).

During a day, at same time:
15-30 minutes of physical exercise program (increase effects of L-Dopa)

At night:
1x capsule (400mg) of "DOPA Mucuna" from Now Foods - it contains 120mg of L-Dopa
1x glass of quality Orange Juice - 200-300ml

Cons/Warnings (2):
- "elevated levels of serotnin stored in dopaminergic neurons"
- "converted it to Dopamine, and stored it in serotonergic neurons! Holy cow!"

Note from research (1):
- (L-Dopa) if user has have a low level of carbon in his body, then L-Dopa additionally should be administrated with glucose/sugars to prevent hypoglycemia (low blood sugar).
--

Now I'm wondering if I should do this or not - I'm still trying to find a way to increase MDMA quality (maybe I should stop to take amphetamine?).

Thank you
Best Regards

bunk mdma- or not enough