3 replies to this topic

[corpina]

Due to a long stint of drug abuse in my early twenties (some adderall and cocaine) and lifestyle (TV, video games, porn, internet), I'm setting out to "repair" the dopamine system in my brain with supplements.

 

Currently I'm working on a system to track markers of long-term, sustained dopamine upregulation: mood, productivity, and subjective well-being.

 

Here's what I'm stacking at the moment (rationale/literature for each is below):

• R-ALA
• Uridine
• Vitamin B12, Trimethylglycine, and 5-MTHF
• Vitamin B­6​, Vitamin C​, Selenium
• Wild green oat extract / avena sativa
• N-Acetyl L-tyrosine 
• Mucuna pruriens
• L-Phenylalanine
• Maca

I'm currently testing optimal dosing and frequency of each, and whether the effects of individual supplements have synergistic or inhibitory effects.

 

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R-ALA 

via DHA & EPA

 

ALA is the parent compound of Omega 3 and can be converted by enzymes into the longer chain Omega 3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosaheaxaenoic acid). [source]

 

I've chosen ALA over EPA and DHA because it can be purchased as a solid, and thus potentially mixed in with other ingredients in a stack.

 

The conversion of the plant-based omega-3 ALA to the long-chain EPA and DHA may be increased in vegans and vegetarians who do not eat fish, suggest results from the European Prospective Investigation into Cancer and Nutrition (EPIC). [source]

 

EPA and DHA shown to have benefits in regulating the dopamine pathway in rats. [sources: 1, 2, 3, 4]

 

Uridine + DHA shown to benefit Parkinson's patients: "oral administration of the phosphatide precursors uridine and DHA can ameliorate the impairment in dopaminergic terminals and transmission in 6-OHDA-lesioned rat striata, probably by increasing the amount of synaptic membrane generated by surviving striatal neurons." [source]

 

Uridine

 

Rats given uridine-5′-monophosphate had increased acetylcholine and dopamine. [sources: 1, 2]

 

The chemical uridine promotes the creation of new dopamine receptors in the brain, an effect which is more pronounced in brains with fewer dopamine receptors. This is done by activating the D1 and D2 receptor signaling cascade, which stabilizes spikes of dopamine activity that would normally “burn out” receptors and reduce their effective number. Modulation also increases the rate of new receptor formation in areas where they are less dense, effectively increasing the number and density of dopamine receptors. Choline – particularly CDP-choline – also has the potential to increase dopamine receptor density. [source]

 

Though, the reported effects on dopamine receptor up-regulation may be short lived.

 

Vitamins B12, 5-MTHF & Trimethylglycine 

 

Contribute to and regulate the SAM cycle. Rationale for choosing precursors over direct SAMe given here by Abelard Lindsay: 

 

 

Adding SAM-e directly would, in my opinion, be suboptimal as research shows it does not do anything to lower homocysteine levels]. Providing highly bioactive forms of b-vitamins involved in the conversion of homocysteine to SAM-e and L-Cysteine and adding betaine to help methylate homocysteine would seem to be the most optimal route to optimizing the SAM cycle and there is research to support this.

 

D4 receptor methylation activity is influenced by the availability of 5-MTHF, (5 methyl tetrahydrofolate), the active form of folate. If there is not enough 5-MTHF present, then dopamine receptors will not be activated... even if there are high levels of dopamine present. [ref]

 

Point of concern: it's possible to take too much folic acid, and it also interacts with certain drugs. 

 

Vitamins B6, C & Selenium

 

Essential vitamins contributing to dopamine production:

 

 Vitamin B6 helps convert L-Dopa into dopamine, Vitamin C helps convert dopamine into norepinephrine (increasing alertness and attention), and selenium protects brain cells while regulating the amount of dopamine-producing enzymes in the brain. Each of these also have important antioxidant properties that protect cells from damage during the production and metabolism of dopamine. [ref]

 

 

 

Wild green oat extract / avena sativa

 

Evidence here is inconclusive and insubstantial, especially for long-term studies:

 

It appears that the cognitive benefit of acute WGOE supplementation does not persist with chronic treatment in older adults with normal cognition. It remains to be seen whether sustained effects of WGOE supplementation may be more evident in those with mild cognitive impairment. [source]

 

LE sells this as "Dopa-Mind" but I haven't tried it myself. Like others, I'm dubious about WGOE. 

 

N-Acetyl L-Tyrosine (NALT)

 

N-Acetyl L-Tyrosine (NALT) is an acetylated form of L-Tyrosine. It breaks down to L-Tyrosine in the kidneys and is more soluble than Tyrosine supplements. It is an amino acid that produces noradrenaline and dopamine. [source]

 

Mucuna pruriens

 

A good source of L-DOPA, and contains some other molecules that may aid the benefits of L-DOPA.

 

Two benefits here worth noting, via Examine:

 

"The reduction in dopamine seen in infertility seems to be reversed with L-DOPA ingestion; theoretically L-DOPA ingestion should unilaterally increase dopamine."

 

"Possible symptoms reduction in Parkinson's Disease related to the L-DOPA content and theorized (but not proven) peripheral dopamine decarboxylase inhibitor; this is notable as a L-DOPA and carbidopa combination supplement is the reference for reducing parkinson's symptoms."

 

L-Phenylalanine

 

A precursor to L-Tyrosine, which is converted to dopamine in the brain. 

 

Maca

 

Activates the dopaminergic system, increases libido. 

 

"In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain. [source]"

 

I get a lot of mileage out of maca when used sparingly... once a week or every other week. Beyond that, it tends to slightly depress my mood. 

[LiveWell]

Watch out for the Mucuna Pruriens. It works great but can cause down-regulation of your dopamine receptors.

 

Following to see how this goes for you. 

[corpina]

Watch out for the Mucuna Pruriens. It works great but can cause down-regulation of your dopamine receptors.

 

Following to see how this goes for you. 

 

Noted, thanks for the heads up. 

 

I looked around a bit on the forums and found some interesting comments on receptor downregulation.

 

There's this thread:

 

 

No, [mucuna pruriens does not cause dopamine receptor downregulation/tolerance]. It contains precursors that convert directly into dopamine..doesn't bind directly however - if you take a TON OF IT - you are flooding the brain with dopamine in a like way to the parkinsons drug ; levodopa..it's basically the same thing - the herb contains the amino-chemical; L-DOPA but it would be in and out of your system quicker than say, carbidopa or LEVODOPA SRR. It does lower prolactin fairly effectively, and like 5-HTP - it doesn't depend on your brains hydroxylase enzymes thus your body/brain has no need to 'produce' dopamine in terms of synthesis because it is already in an active form

 

And this

 

Mucuna Pruriens, just like psychostimulants(amphetamine, Ritalin etc.) and dopamine agonists would increase dopaminergic signaling temporarily, probably resulting in euphoria, clarity of thought, increased motivation, increased sex drive, overall increases in focus/concentration and energy etc.

 

However, just like psychostimulants, the dopamine receptors will probably downregulate and the brain will slow down production of dopamine, resulting in withdrawal symptoms if you quit Mucuna Pruriens after long term use.

 

emphasis mine

 

From the above it sounds as if, when dopamine is abundant, receptors are downregulated. The cell's way of saying "we don't need more dopamine signaling". If that's the case, then does it even make sense to use supplements that stimulate dopamine production? 

But it's not that simple, as evidenced by comments and sources in this thread: 

 

 

Nicotine increases reward sensitivity:

http://www.ncbi.nlm....pubmed/16192981

 

Chronic Oral Nicotine Normalizes Dopaminergic Function:

http://www.jneurosci...7/4681.full.pdf

 

Perhaps, rather than going after dopamine directly, I should heavily stack precursors and cofactors and let the brain "rebalance" itself, in tandem with lifestyle changes like yoga, diet, meditation, outdoor exercise, etc. 

[pointlessrepetition]

Hey OP, just wanted to make sure you know that R-ala is the R- isomer of alpha lipoic acid, NOT the plant-based version of omega 3, alpha linolenic acid, that you're describing in your post. Hopefully you already figured that out or it was a mistake. I doubt it's killing you but if you're a vegetarian/vegan like your post suggests you should probably take care of that as soon as possible. You'd have to be pretty deficient at this point being a vegetarian and omega 3s are pretty important.