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L-Dopa: Implications, Interactions, Toxicity

selegiline depenyl toler

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#1 KoolK3n

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Posted 16 April 2013 - 02:54 AM


L-Dopa: Implications, Interactions, Toxicity

What exactly is L-Dopa?
As you can see with the image link below, Dopa is the end stage of DA (Dopamine) production right before AADC (Aromatic L-Amino Acid Decarboxylase) synthesizes it into DA. It is used to treat Parkinsons disease.
http://upload.wikime...iosynthesis.svg

Isn’t L-Dopa toxic?
Yes, primarily through oxidative stress.
SAM-e: http://www.ncbi.nlm....ubmed/11223018/
N Acetyl Cysteine: http://www.ncbi.nlm.nih.gov/pubmed/10864903
Vitamin C: http://www.ncbi.nlm.nih.gov/pubmed/7552304
Inositol?: http://www.ncbi.nlm.nih.gov/pubmed/10486178
Carnosine (Beta Alanine): http://cat.inist.fr/?aModele=afficheN&cpsidt=17093360
Baicalin: http://www.ingentaco...000010/art00009

Why L-Dopa?
Disregarding neurotoxicity, the problem with stimulants is tolerance or downregulation. Specifically for Deprenyl, unless there is an unknown mechanism, the only correlation explaining tolerance is the decreased activity in TH (Tyrosine Hydroxylase; refer to diagram at the beginning of the post), this limits the amount of Dopamine produced and as a result homeostasis takes place. Methods to try and upregulate or increase the activity of TH has proven elusive. This is why I brought up Dopa. To bypass that rate-limiting factor TH and directly be utilized. This in of itself provides a significant hurdle that needs to be overcome in order to successfully integrate L-Dopa with the CNS. Luckily, many of these obstacles have been removed already, which I’ll get too momentarily.

Since I’ve already proposed methods of significantly reducing neurotoxicity, the only thing now is to figure out how to use Dopa efficiently. If Dopa is taken orally/sublingually/transdermally/intravenously it still needs to deal with the PNS (Peripheral Nervous System) before crossing the BBB (Blood Brain Barrier). To my knowledge, there is no benefit to having increased DA throughout the body. And in doing so results in more harm than good (i.e. Nausea, vomiting). To prevent this, Carbidopa needs to taken with Dopa. Carbidopa inhibits AADC and does not cross the BBB (good thing). That means only the brain is primarily affected by Dopa. This also means two things, 1. Lowers dosage required and 2. Longer plasma concentration time. This also works for 5HTP.

Next point, Dopa negatively interacts with serotonergic processes as explained here:
http://www.ncbi.nlm.nih.gov/pubmed/22762478
http://www.hindawi.c...pd/2012/370190/
SSRIs potently inhibits and downregulates SERT (Serotonin Transporter).

To stay on the safe side, it is recommended to start at a very low dose and titrate up very slowly to something like:
L-Dopa Neurotoxicity Attenuation List – High Dose
SSRI – Average Therapeutic Dose
Selegiline – Moderate Dose (?)
L-Dopa/Carbidopa– Low Dose (Multiple Dosing)
5-HTP – Very Low Dose (Multiple Dosing)
Still this combo is highly experimental and warrants the utmost caution.

Edited by KoolK3n, 16 April 2013 - 03:11 AM.

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#2 Mr. Pink

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Posted 16 April 2013 - 02:57 AM

you should look into mucana pruriens (sp?). it is L-dopa without the excitotoxicity. but in general, there are neurological disorders caused by upregulating dopamine (psychosis, for example).
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#3 **DEACTIVATED**

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Posted 16 April 2013 - 02:45 PM

I see you've started your new thread.

What do you think of this: http://www.sciencedi...169328X96002707

Abstract

Chronic treatment of aged rats with deprenyl prevents age-induced protein oxidation in substantia nigra and protects tyrosine hydroxylase (TH) enzyme against inactivation [11]. With these precedents, we treated adult rats with deprenyl for 3 weeks in order to get further insight in the mechanism by which deprenyl exerts such actions. After completing the treatment, dopamine (DA) levels markedly increased in both striatum and substantia nigra while levels of the acid DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), decreased in the two brain areas, thus proving MAO-inhibiting properties of the treatment. We then studied the cellular expression of TH mRNA by in situ hybridization. Following treatment with deprenyl, levels of TH mRNA were significantly higher in individual dopaminergic nigral cell bodies than in those of control rats (+74%). Western blotting analysis of TH enzyme amount revealed a positive effect of the treatment in both the terminal field (+44%) and the cell body region (+31%). This correlation between TH mRNA and amount was also extended to TH enzyme activity in the two brain areas studied, which significantly increased in striatum (+57%) and substantia nigra (+35%) following deprenyl treatment. Taken together, our results clearly suggest a TH-inducing effect of deprenyl in the dopaminergic nigrostriatal system, which seems to be independent of its protective action against oxidative stress described previously. These results expand our knowledge about the beneficial effect of deprenyl in the therapy of Parkinson's disease.


Keywords

  • Striatum;
  • Substantia nigra;
  • Tyrosine hydroxylase;
  • mRNA expression;
  • Western blot analysis


Does this confirm or deny the decrease in tyrosine hydroxlase associated with Deprenyl?

edit: Also, what do you think of low dosages of Deprenyl? Perhaps all this homeostasis is a result of over dosing. In one study that shows chronic selegiline dosages of 10mg/day significantly reduced TH mRNA levels in substantia nigra and ventral tegmental area. That's way above the doses I'd ever consider.

http://link.springer...0210-001-0492-z


Edited by CrackaLackN, 16 April 2013 - 03:00 PM.


#4 **DEACTIVATED**

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Posted 16 April 2013 - 03:10 PM

Continuing.. http://www.sciencedi...014299996005304

Abstract

After acute administration of the monoamine oxidase inhibitor clorgyline there is a reduction of aromatic l-amino acid decarboxylase and tyrosine hydroxylase activity in the mouse striatum. Similar responses were seen after administering the non-selective monoamine oxidase inhibitor pargyline and high, but not low, doses of the selective monoamine oxidase-B inhibitor deprenyl. Changes of tyrosine hydroxylase activity were observed only when substaturated concentrations of the pteridine cofactor were used for the assay. The monoamine oxidase inhibitors altered the abundance of aromatic l-amino acid decarboxylase and tyrosine hydroxylase mRNA in the midbrain. Pargyline and high doses of deprenyl increased aromatic l-amino acid decarboxylase mRNA, while clorgyline initially decreased and then increased it. All three compounds caused an early decrease of tyrosine hydroxylase mRNA. The acidic metabolites of dopamine appeared most affected by pargyline and clorgyline, supporting the notion that deamination of striatal dopamine in rodents is primarily by monoamine oxidase-A. Our results suggest that striatal tyrosine hydroxylase and aromatic l-amino acid decarboxylase are apparently modulated via different mechanisms in response to perturbation of dopamine metabolism.


Keywords

  • Dopamine;
  • Aromatic l-amino acid decarboxylase;
  • Tyrosine hydroxylase;
  • Monoamine oxidase;
  • Striatum;
  • (Modulation)


Perhaps further confirming the less likely chance of decrease tyrosine hydroxlyase activity with low doses. If so, the decrease could be due to the inhibition of MAO-A, not B.

By the way, does Deprenyl inhibit MAO-A after 5mg/day or 10mg/day?


Edited by CrackaLackN, 16 April 2013 - 03:16 PM.


#5 KoolK3n

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Posted 16 April 2013 - 04:23 PM

Thanks for the input Crackalackn.
Won't be able to reply til late afternoon again. Expect many updates.

#6 KoolK3n

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Posted 17 April 2013 - 03:09 AM

Perhaps further confirming the less likely chance of decrease tyrosine hydroxlyase activity with low doses. If so, the decrease could be due to the inhibition of MAO-A, not B.

By the way, does Deprenyl inhibit MAO-A after 5mg/day or 10mg/day?


My guess is a weak yes due to chronic exposure but its miniscule inhibition shouldn't be an issue.
That second link you provided does match this one: http://link.springer...1007/BF02815121 So MAO-B does not influence TH...how weird. Here is another link that's compatible with what you think: http://www.ncbi.nlm..../pubmed/9423934. The dose used extended far into MAO-A territory. So I guess MAO-A inhibition needs to be reconsidered. Memantine also stimulates AADC http://www.ncbi.nlm....pubmed/9871440. Okay, what explains tolerance then from low-doses of Deprenyl? I have another guess as to why.

It maybe from up regulation of COMT and MAT. Those enzymes are involved in the metabolism of DA, another reference pic: http://upload.wikime...e_breakdown.svg. It can be reasonably assumed that Deprenyl naturally raises Dopa levels since all the other pathways are as well. Here is a study using exogenous L-Dopa: http://www.ncbi.nlm....pubmed/11520127. This up regulation would make sense as homeostasis occurs.

Again, to the best of my knowledge, inhibiting these metabolic enzymes means one step closer to near total inhibition of DA/NE degradation. Keep in mind, total inhibition of these enzymes is not safe, some levels are required for normal processes. Preventing the extra up regulation is what should stay inhibited. As of now, I'm not aware of a MAT inhibitor. Most people online recommend a COMT inhibitor such as EGCG or another relatively harmless substance. An issue arises, these don't cross the BBB thus not exerting any therapeutic potential of inhibiting COMT in the brain, which is what we want for tolerance reduction.

More studies: http://www.ncbi.nlm..../pubmed/8479601 and http://www.ncbi.nlm....pubmed/10855949 (more useful link). I need more time to analyze what this means though unless others can chime in. Anyways, the only potent COMT inhibitor that passed the BBB was Tolcapone. Tolcapone has a serious side-effect profile that shouldn't be taken lightly plus a prescription is needed to obtain it.

Note to self: Get a computer. Tablets/iPhones don't cut it.

Edited by KoolK3n, 17 April 2013 - 03:15 AM.


#7 KoolK3n

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Posted 17 April 2013 - 05:30 PM

Interesting read in the meantime:
http://www.socialanx...-enzyme-182919/
And
http://library.iyte....muh/T000081.pdf
Yayyyy

Edited by KoolK3n, 17 April 2013 - 05:46 PM.


#8 KoolK3n

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Posted 18 April 2013 - 05:45 PM

Omg...huge ass update tonight or tomorrow!!

Edited by KoolK3n, 18 April 2013 - 05:45 PM.


#9 KoolK3n

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Posted 18 April 2013 - 09:41 PM

Selegiline vs Rasagiline:
http://www.sciencedi...210533612000731
If money isn't an issue, Rasagiline may be a better option

Carbidopa:
Niacin synthesis is disrupted by Carbidopa: http://www.truestarh...es/1339004.html
Supplementation might be necessary.

Regarding COMT:
http://library.iyte....muh/T000081.pdf
http://www.if-pan.kr.../2012/4_808.pdf
So if this translates correctly, in-vivo inhibition should be achieved. I'm surprised out of all the possible candidates, Olive Leaf (Rutin), was a viable option. Though, I think adding more selective substances is necessary for stronger COMT inhibition.

With inhibition of MAO-B and COMT, it looks like DA has almost "no where" to go. Some of the other metabolic routes include DBH (Dopamine Beta Hydroxylase), which should stay uninhibited. Doing so aggrevates possible orthostatic hypotension, nasal stiffness, etc. http://en.wikipedia....lase_deficiency. Inhibiting DBH inhibits NE synthesis (not good).

--

Anyways, I completely forgot to talk about VMAT changes from increased dopamine. So from the increased DA from AADC & TH up regulation, COMT inhibition, and L-Dopa exogenous addition, VMAT has some extra work to do:
http://www.biomedsea...002444.g002.jpg

According to Wiki: "VMAT is the main target of methamphetamine. By acting as a competitive antagonist, methamphetamine blocks the presynaptic cell's ability to use VMAT to package the above mentioned neurotransmitters into vesicles. The result is increased neurotransmitter release that is not dependent on the phasic activity of the presynaptic cell." Ahhh so this is what contributes to Meth induced neurotoxicity. Meth and other illicit stimulants downregulate VMAT over the long term. This reduction in VMAT is correlated with depression. Tetrabenazine is an inhibitor of VMAT and it's most common side-effect is depression. http://en.wikipedia....i/Tetrabenazine
VMAT works by essentially packaging NTs (neurotransmitters) into little boxes, preparing those boxes for delivery into the synaptic cleft. Packaging them prevents early metabolism and subsequently oxidation. There are no studies to answer my question which is can VMAT keep up with all that extra DA created? What if it can't and is forced to have it metabolized early? This is the difference between safely increasing neurotransmission and oxidative stress.
I've been looking for means to upregulate VMAT and found the protein DJ-1:
http://www.ncbi.nlm....pubmed/22887838
http://eprints.lib.h...1-4_813-818.pdf

[Sodium] Phenylbutyrate upregulates DJ-1 (without neuronal stress) therefore upregulating VMAT2!!
http://en.wikipedia...._phenylbutyrate
http://www.ncbi.nlm....pubmed/21372141
Next group buy?!

Edited by KoolK3n, 18 April 2013 - 09:55 PM.

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#10 owtsgmi

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Posted 19 April 2013 - 12:50 AM

Memantine is an NMDA receptor antagonists which many (me included) have used to eliminate the tolerance of dopamine enhancers, such as selegiline and rasagiline. I take a small dose of memantine every third or fourth day to keep the rasagiline working. I space out the memantine and keep the dose to a minimum, otherwise it's not good.

Edited by owtsgmi, 19 April 2013 - 12:51 AM.


#11 KoolK3n

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Posted 19 April 2013 - 01:13 AM

Memantine is an NMDA receptor antagonists which many (me included) have used to eliminate the tolerance of dopamine enhancers, such as selegiline and rasagiline. I take a small dose of memantine every third or fourth day to keep the rasagiline working. I space out the memantine and keep the dose to a minimum, otherwise it's not good.


Yes, memantine has already been recommended. From reading others experiences, 10mg/d is the optimal dose for cognitive enhancing purposes (Ach A7 up regulation) and tolerance prevention. Anything higher results in adverse effects. Wait, third to fourth day?! owtsgmi say whattttttttt

Edited by KoolK3n, 19 April 2013 - 01:20 AM.


#12 KoolK3n

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Posted 19 April 2013 - 02:36 AM

Another update tomorrow. The end is nigh!

#13 BioFreak

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Posted 19 April 2013 - 11:55 AM

Or one could simply use mucuna seed powder(NO EXTRACT). In comparison to pure l-dopa it does:
increase the other catecholamines
acts as a neuroprotectant
shows longer and stronger effects then l-dopa
increases serotonin, too.

Besides studies showing this, its my personal experience too.

#14 KoolK3n

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Posted 19 April 2013 - 11:59 AM

Or one could simply use mucuna seed powder(NO EXTRACT). In comparison to pure l-dopa it does:
increase the other catecholamines
acts as a neuroprotectant
shows longer and stronger effects then l-dopa
increases serotonin, too.

Besides studies showing this, its my personal experience too.

Please provide studies.

#15 BioFreak

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Posted 19 April 2013 - 12:06 PM

http://examine.com/s...ucuna Pruriens/

I think they reference only human studies. Knock yourself out and tell me what you think.

#16 KoolK3n

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Posted 19 April 2013 - 12:15 PM

http://examine.com/s...ucuna Pruriens/

I think they reference only human studies. Knock yourself out and tell me what you think.

Ok thanks. I'll analyze it in my next update.

#17 owtsgmi

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Posted 19 April 2013 - 11:12 PM

Memantine is an NMDA receptor antagonists which many (me included) have used to eliminate the tolerance of dopamine enhancers, such as selegiline and rasagiline. I take a small dose of memantine every third or fourth day to keep the rasagiline working. I space out the memantine and keep the dose to a minimum, otherwise it's not good.


Yes, memantine has already been recommended. From reading others experiences, 10mg/d is the optimal dose for cognitive enhancing purposes (Ach A7 up regulation) and tolerance prevention. Anything higher results in adverse effects. Wait, third to fourth day?! owtsgmi say whattttttttt


I've had more than one person question whether spacing memantine out that much could have any real effect, but it works for me. I am not taking it for D2 Agonism, but as an NMDA Antagonist. If I don't take it at all I start getting mild OCD and the rasagiline starts making me edgy (i.e., all the classic stim tolerance issues). And, if I take it too often I get serious cognition problems. If I even took 10mg a day I would be a total doofus.

It's possible it may be interacting with my other noots. I do take piracetam and a bunch of magnesium each day. Oh, and I do take the 2mg or so sublingually. I am not sure how much it gets potentiated that way.

EDIT: I just checked out the half-life of memantine and it is 60-100 hours (i.e., 2.5- 4.1 days)!

Edited by owtsgmi, 19 April 2013 - 11:17 PM.


#18 KoolK3n

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Posted 20 April 2013 - 12:51 AM

I've had more than one person question whether spacing memantine out that much could have any real effect, but it works for me. I am not taking it for D2 Agonism, but as an NMDA Antagonist. If I don't take it at all I start getting mild OCD and the rasagiline starts making me edgy (i.e., all the classic stim tolerance issues). And, if I take it too often I get serious cognition problems. If I even took 10mg a day I would be a total doofus.

It's possible it may be interacting with my other noots. I do take piracetam and a bunch of magnesium each day. Oh, and I do take the 2mg or so sublingually. I am not sure how much it gets potentiated that way.

EDIT: I just checked out the half-life of memantine and it is 60-100 hours (i.e., 2.5- 4.1 days)!


Ok thanks for sharing this. It looks like even 10mg/d is a bit excessive. No wonder no one saw any nootropic effect at the recommended 20-30mg/d dose! So do you think that 5mg/d or every other day be fine? This saves a lot of money.

Also, what is your Rasagiline dose? I was thinking of supplementing 2mg/d.

Btw I won't be able to update til either Sunday night or Monday afternoon. I'm in the midst of traveling right now and checked into a hotel.

Edited by KoolK3n, 20 April 2013 - 12:52 AM.


#19 owtsgmi

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Posted 22 April 2013 - 05:41 AM

Ok thanks for sharing this. It looks like even 10mg/d is a bit excessive. No wonder no one saw any nootropic effect at the recommended 20-30mg/d dose! So do you think that 5mg/d or every other day be fine? This saves a lot of money.

Also, what is your Rasagiline dose? I was thinking of supplementing 2mg/d.

Btw I won't be able to update til either Sunday night or Monday afternoon. I'm in the midst of traveling right now and checked into a hotel.


I take 1/8th of a 10mg (200mg pill weight) memantine pill every 3 to 4 days (sublingually). In addition, I take 1/4 of a 1mg (80mg pill weight) rasagiline pill every other day (sublingually).

I'm sure the sublingual dose potentiates the dose. I think I originally did it that way to save money.

The only real problem is cutting the pills and then keeping track of the days so I take the pills on the right day. I decided I to come up with a daily dose that works. I am going to try 10mg of both pills per day (equates to .125mg ras and .333mg mem per day sublingual). Don't know when I'll find time to crush the pills, measure the doses out, etc.)

I don't know how much dopamine you need, but this is more than sufficient for me. I also use caffieine and uridine, so I am getting dopamine in multiple ways.

#20 chris106

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Posted 02 June 2013 - 05:50 PM

Any updates? I plan on trying rasagaline in the near future, too. That being said - is there any chance to get selegeline or rasagaline without a prescription via internet-order?
If anyone knows about this, I'd really appreciate if you'd PM me ;)

#21 chris106

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Posted 02 June 2013 - 07:00 PM

Never mind, searched some more and found a few sources after all. Maybe interesting for others here as well? -

http://www.sunshinep...10-Tablets.html

http://www.antiaging...ry=selegiline (just scroll down, they offer both for reasonable prices - can't vouch for them myself, though)

http://www.qhi.co.uk (for some reason I can't post the full link - just search for "deprenyl" on their main page. It should show two
results - one brand and one generic!)

http://www.docsimon....pe=&fsub=SEARCH (as you see, not yet in stock. But should they get it soon, I bet it will be dirt cheap :) )


Now, if anyone can vouch for any of these vendors from experience - feel free to comment :)

Edited by chris106, 02 June 2013 - 07:01 PM.


#22 KoolK3n

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Posted 07 June 2013 - 02:58 AM

Any updates? I plan on trying rasagaline in the near future, too.

Besides the use of tyrosinase inhibitors, there isn't much. Again, this isn't recommended for beginners and is merited only as a last resort for tolerance reduction. I have yet to try Rasagiline/Selegiline, but for me when I do, I plan to combine with various other drugs at once like Zoloft, Buspar, N Acetyl cysteine, Inositol, Memantine, and a couple others. To some, starting all these drugs at once may look stupid and it probably is but I don't care. I wanna go about this with overwhelming synergistic force :)

#23 brainslugged

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Posted 07 June 2013 - 08:45 AM

This is great. It is neat to see L-Dopa having a good use, and it being used safely.

For tolerance, Methylene Blue may help.

Selegiline seems to greatly raise Nitric Oxide levels (http://www.ncbi.nlm....pubmed/10867219) (http://www.ncbi.nlm..../pubmed/9721939)

Does rasagaline do the same thing? I couldn't find anything on it, and it would be a very useful thing to know.

Medievil was hypothesizing that Methylene blue could be used to lower amphetamine tolerance by reducing NO activity. I didn't see any further explanation or sources from him, but I did find a few studies on pubmed about the topic (http://www.ncbi.nlm....pubmed/22034069) (http://www.ncbi.nlm....pubmed/19816675). Aparently, NO has a negative effect on D2, and a positive effect on D1. I don't know enough about the process to really say, but from what I make out, it looks like the NO may actually be a more direct mechanism then memantine, as it seems to be mediated by NMDA receptors. Obviously, not blocking NMDA receptors would be best (per Medievil, memantine reduces fear elimination, and I would suppose it probably has farther implication as well) if we could target the more specific mechanism, but I can't tell if the NO actually downregulates the receptors or if it is just decreasing transmission by some other means. Either way, inhibiting that NO activity is going to probably make Selegiline's effects more favorable, as D2 is normally better than D1, and you would be tilting the scales to D2.

Methylene blue looks like a good candidate for reducing the NO activity (http://www.ncbi.nlm..../pubmed/7679577) (http://www.ncbi.nlm..../pubmed/7505944). The only problem is that there is one report of nausea when MB is taken with Selegiline. Combining the two will also result in complete MAO inhibition, so you may want to at least be a bit tentative about what you eat. I assume that Selegiline sublingual would not cause much MAO-B inhibition in the liver, and MB is (I am pretty sure) a reversible inhibitor of MAO-A, so technically there shouldn't be any problems, but I wouldn't get too cocky and eat a pound of brie or something.

One thing, though, I don't understand the reference for inositol in the main thread. It links to a study about a D2 agonist? But, hey, if you can use inositol and not get negative effects, go for it. It has been a miracle supplement for many (non-genetically related) people in my family.

Also, memantine sublingual, although it seems like a good idea may not be all that helpful. Wikipedia says that its bioavailability is ~100%.

Good luck. I am interested to know the effects you get and if it is effective. If you care to share, I would also be interested in knowing your specific goal of this stack.

EDIT: Just thought, if nausea is a problem with selegiline and MB combined, domperidone may be able to help. It is a D2/D3 antagonist that doesn't cross the BBB. There may be... other side effects, though. It is used clinically to help with lactation.

Edited by brainslugged, 07 June 2013 - 08:50 AM.


#24 owtsgmi

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Posted 07 June 2013 - 08:55 AM

Also, memantine sublingual, although it seems like a good idea may not be all that helpful. Wikipedia says that its bioavailability is ~100%.


Good to know this. This should allow sprinkling some memantine in some sort of daily pill. I might try to dose the memantine orally to see if the effects are the same.

#25 KoolK3n

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Posted 15 June 2013 - 04:19 AM

For tolerance, Methylene Blue may help.

Methylene blue looks like a good candidate for reducing the NO activity (http://www.ncbi.nlm..../pubmed/7679577) (http://www.ncbi.nlm..../pubmed/7505944). The only problem is that there is one report of nausea when MB is taken with Selegiline. Combining the two will also result in complete MAO inhibition, so you may want to at least be a bit tentative about what you eat. I assume that Selegiline sublingual would not cause much MAO-B inhibition in the liver, and MB is (I am pretty sure) a reversible inhibitor of MAO-A, so technically there shouldn't be any problems, but I wouldn't get too cocky and eat a pound of brie or something.


This was actually suggested to me on another forum site. The process wasn't elaborated at all so I kinda ignored his advice. I guess this wouldn't hurt to try in combination with other drugs as long as the doses are kept low. This stuff is dirt cheap too which is my deciding factor!

Sorry I'm not familar with NO but doesn't it have some benefits like vasodilation?


One thing, though, I don't understand the reference for inositol in the main thread. It links to a study about a D2 agonist? But, hey, if you can use inositol and not get negative effects, go for it. It has been a miracle supplement for many (non-genetically related) people in my family.


Inositol may significantly upregulate D2 receptor density.
http://www.ncbi.nlm....pubmed/11267629

Eventually adding all these drugs creates too many variables for me to keep track of. I wanted to throw Inositol into the stack because of it's consistency and effectiveness for most people.

Also, memantine sublingual, although it seems like a good idea may not be all that helpful. Wikipedia says that its bioavailability is ~100%.


I'm gonna keep the dosage low for financial sakes. 5mg/d. The sheer amount of papers on the benefits of Memantine across the spectrum of mental disorders is to tempting to ignore.

Good luck. I am interested to know the effects you get and if it is effective. If you care to share, I would also be interested in knowing your specific goal of this stack.


Thanks for asking. My stack is designed to combat the depression and ADHD like symptoms I have. More specifically, I would like to overcome the lack of motivation/energy I have including introversion. I'm not the kind of introverted that doesn't enjoy social interactions. I love talking to people and going out but it's the expenditure of energy it takes to keep the conversation enjoyable. It's exhausting and makes life pretty difficult. I used to have horrible anxiety during my teen years ("chest exploding") but that has since morphed into the symptoms I have now. I also have a couple annoying physical complaints that moderately fuel my symptoms like wearing glasses, height/frame, acne, etc (too embarassing). At least LASIK and the evil Accutane will relieve the big physical issues I have. I've been able to pull through only because of my workaholic tendency. This has only masked the symptoms and has only dug the hole deeper for me later.

After a couple years of failed attempts with supplements, exercise, meditation, and diet. I realized this doom wouldn't go away so I gave up hope and started playing around with drugs (weed, LSD, alcohol, benzos). Shortly after came along Adderall and thats when everything changed. After many many months of research and experimentation, I successfully created the "best" recreational drug stack nearly side-effect free and no tolerance buildup as long as I followed my prewritten protocols. The days I was on it was amazing but unfortunately, after a year, I realized this wasn't cutting it. I needed to find a more permanent solution. I need something for daily use. It was psychologically painful to witness having only 1-2 days a month of content (NZT like effects) and 95% of the time being plain ole "me". Hence came along this stack I'm about to undergo.

My stack as planned:
-Zoloft w/Buspar & Melatonin SR (Neurogenesis):
http://www.ncbi.nlm....pubmed/22998742
http://www.xconomy.c...ingle_page=true
-Rasagiline
-Memantine
-N AcetylCystine (Augments SSRI):
http://www.ncbi.nlm....pubmed/23419244
http://www.ncbi.nlm....pubmed/22327021
http://www.ncbi.nlm....pubmed/22820675
-Inositol
-Olive Leaf w/Rutin (COMT Inhibition) (Links in previous posts)
-Methylene Blue (Maybe)
-Accutane (Maybe, if Doxycycline doesn't work which it isn't)

Already taking and might continue with future stack:
-Magnesium Chelated
-Taurine
-Fish Oil
-Creatine
-Niacinamide
-Turmeric w/Bioperine
-Ginger
-Doxycycline

Edited by KoolK3n, 15 June 2013 - 05:11 AM.


#26 brainslugged

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Posted 15 June 2013 - 08:19 AM

For tolerance, Methylene Blue may help.

Methylene blue looks like a good candidate for reducing the NO activity (http://www.ncbi.nlm..../pubmed/7679577) (http://www.ncbi.nlm..../pubmed/7505944). The only problem is that there is one report of nausea when MB is taken with Selegiline. Combining the two will also result in complete MAO inhibition, so you may want to at least be a bit tentative about what you eat. I assume that Selegiline sublingual would not cause much MAO-B inhibition in the liver, and MB is (I am pretty sure) a reversible inhibitor of MAO-A, so technically there shouldn't be any problems, but I wouldn't get too cocky and eat a pound of brie or something.


This was actually suggested to me on another forum site. The process wasn't elaborated at all so I kinda ignored his advice. I guess this wouldn't hurt to try in combination with other drugs as long as the doses are kept low. This stuff is dirt cheap too which is my deciding factor!

Sorry I'm not familar with NO but doesn't it have some benefits like vasodilation?

Yes, NO causes vasodilation. There are also two other routes of vasodilation, though, cAMP increase and through Ca+ channel blockage. Since both of these methods would actually be benefitial to stim tolerance/usage, I think it would be best to try to maximize these two while decreasing NO. I don't know how far we can do with that, though. There must be some sort of other implications for almost completely abolishing NO in favor of the other two. Still, I don't think that even just MB + stims will cause anything harmful as long as you aren't doing anything stupid and you take your blood pressure often, etc. MeDieVil took it for a few days, and I would think that he would comment on any negatives he felt, and it didn't kill him, so... I assume it seems safe. Plus, there are tests of methamphetamine + NOS inhibitors on animals, so I would assume that amphetamine would be fine. Just go with caution. In a few months, I may get to try it out, and I will probably make a thread if Medievil isn't back yet and hasn't tried it.

This was actually suggested to me on another forum site

That actually may have been me if it was on an imageboard, lol, so don't take that as 2 people giving you the same advice if so. Otherwise, I would like to know who suggested/what forum so that I can talk to them about it. The only other person I know of that has looked into it is Medievil, and he has been gone for quite some time, getting a bit worried about him actually.


One thing, though, I don't understand the reference for inositol in the main thread. It links to a study about a D2 agonist? But, hey, if you can use inositol and not get negative effects, go for it. It has been a miracle supplement for many (non-genetically related) people in my family.


Inositol may significantly upregulate D2 receptor density.
http://www.ncbi.nlm....pubmed/11267629

Eventually adding all these drugs creates too many variables for me to keep track of. I wanted to throw Inositol into the stack because of it's consistency and effectiveness for most people.

If I were you, I would add inositol after you get the other stuff worked out because it could be a huge confounding variable in the whole thing, and it isn't even really indicated for ADHD. In fact, it may make ADHD worse (http://www.ncbi.nlm..../pubmed/9169302).
I would guess that the upregulation of D2 was due to reduced activity. However, it is still interesting.

Inositol + stimulants is an interesting concept, though, and I would like to know how it pans out. The general idea I have is that increase in choline/serotonin could be helpful for reducing negative effects of increased dopa without significantly reducing beneficial effects. I don't know, though. It isn't a solid hypothesis, just based on conjecture, and I am pretty sure that it has been thought of and rejected before. I wouldn't take inositol with the initial stack. Really, I would add each thing individually if I were you with the exception of adding l-dopa and something to reduce horribly negative side effects/neurotoxicity at the same time.

Also, memantine sublingual, although it seems like a good idea may not be all that helpful. Wikipedia says that its bioavailability is ~100%.


I'm gonna keep the dosage low for financial sakes. 5mg/d. The sheer amount of papers on the benefits of Memantine across the spectrum of mental disorders is to tempting to ignore.

True, I am not trying to discourage you from taking Memantine. However, if it turns out that the MB hypothesis is right, then the same effects could be acheived by simply taking MB. NO inhibition is one of the actions from NMDA antagonism (http://www.ncbi.nlm....pubmed/19816675). Calcium channel inhibition is the next hope. The problem with Memantine is that inhibiting NMDA causes a lot more than just stim tolerance reduction. Theoretically, it changes memory consolidation (although maybe not for the worse or better, but it should be changed to be more even since the way Memantine works, it prevents 'excessive' NMDA activation while upregulating NMDA receptors, so I would reason that would mean same or slightly increased average activation with lower standard deviation, correct me if I am wrong, not too sure about tonic activation's effects on this) and may change fear extinction (NMDA agonists increase it http://www.ncbi.nlm....les/PMC3229759/).

The way it looks to me, memantine's effects may be able to be simulated in a more direct way by inhibition of either NOS or Calcium channel activity, or both.

Good luck. I am interested to know the effects you get and if it is effective. If you care to share, I would also be interested in knowing your specific goal of this stack.


Thanks for asking. My stack is designed to combat the depression and ADHD like symptoms I have. More specifically, I would like to overcome the lack of motivation/energy I have including introversion. I'm not the kind of introverted that doesn't enjoy social interactions. I love talking to people and going out but it's the expenditure of energy it takes to keep the conversation enjoyable. It's exhausting and makes life pretty difficult. I used to have horrible anxiety during my teen years ("chest exploding") but that has since morphed into the symptoms I have now. I also have a couple annoying physical complaints that moderately fuel my symptoms like wearing glasses, height/frame, acne, etc (too embarassing). At least LASIK and the evil Accutane will relieve the big physical issues I have. I've been able to pull through only because of my workaholic tendency. This has only masked the symptoms and has only dug the hole deeper for me later.

After a couple years of failed attempts with supplements, exercise, meditation, and diet. I realized this doom wouldn't go away so I gave up hope and started playing around with drugs (weed, LSD, alcohol, benzos). Shortly after came along Adderall and thats when everything changed. After many many months of research and experimentation, I successfully created the "best" recreational drug stack nearly side-effect free and no tolerance buildup as long as I followed my prewritten protocols. The days I was on it was amazing but unfortunately, after a year, I realized this wasn't cutting it. I needed to find a more permanent solution. I need something for daily use. It was psychologically painful to witness having only 1-2 days a month of content (NZT like effects) and 95% of the time being plain ole "me". Hence came along this stack I'm about to undergo.

Have you considered ritalin for the every-day stimulant? It is not as euphoric as amphetamine, but it may be just as good for getting work done, or at least be good enough.

I would strongly suggest against looking for NZT like effects in stimulants. That is a very, very dangerous path. Don't let it lead to abuse. Stimulants/increased dopamine is great, but it shouldn't be THAT great. Nothing against your judgement personally, but stimulants can have the effect of making it feel like NZT when it is mostly just the drug imairing judgement, they do that to everyone. I love stimulants because they can help with a lot of things, but they should be treated with respect, and probably not be used every day unless you absolutely cannot function without them. I understand that you are trying to find a better solution, but this is just a dangerous thing to chase. You can't chase that feeling of stimulants or you will either be let down or travel to self-destruction. Even if amphetamine can be used daily without tolerance, it may not be good to do.

My stack as planned:
-Zoloft w/Buspar & Melatonin SR (Neurogenesis):
http://www.ncbi.nlm....pubmed/22998742
http://www.xconomy.c...ingle_page=true
-Rasagiline
-Memantine
-N AcetylCystine (Augments SSRI):
http://www.ncbi.nlm....pubmed/23419244
http://www.ncbi.nlm....pubmed/22327021
http://www.ncbi.nlm....pubmed/22820675
-Inositol
-Olive Leaf w/Rutin (COMT Inhibition) (Links in previous posts)
-Methylene Blue (Maybe)
-Accutane (Maybe, if Doxycycline doesn't work which it isn't)

Already taking and might continue with future stack:
-Magnesium Chelated
-Taurine
-Fish Oil
-Creatine
-Niacinamide
-Turmeric w/Bioperine
-Ginger
-Doxycycline

No L-Dopa? I am confused.

Unless the situation is dire, DO NOT take accutane. That stuff is poison. Seriously, unless you are facing the possiblity of being seriously disfigured by your acne, don't take it. Have you tried Minocycline? Accutane destroys you. Several family members have had life altering bowl disease from taking it.

Another thing, I think it may be either redundant or dangerous to inhibit both COMT and MAO. I don't know, I know almost nothing about COMT.

Also, something very important, don't take Methylene blue with methamphetamine (or MDMA). I don't know if you would ever substitute meth for amphetamine, but don't do it while on MB because it may kill you, I am not sure. The MAOI activity and SRI activity could be enough to cause severe serotonin syndrome with meth's moderate serotonin releasing properties. I am not sure, but best not to risk it because the risk seems pretty high. (also just a good idea not to take meth in general)
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#27 KoolK3n

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Posted 16 June 2013 - 02:14 AM

Plus, there are tests of methamphetamine + NOS inhibitors on animals, so I would assume that amphetamine would be fine. Just go with caution. In a few months, I may get to try it out, and I will probably make a thread if Medievil isn't back yet and hasn't tried it.


Okay. I was just a bit concerned because AMPHs are vasoconstrictors and thought adding a NOS inhibitor would overdue it.

That actually may have been me if it was on an imageboard, lol, so don't take that as 2 people giving you the same advice if so. Otherwise, I would like to know who suggested/what forum so that I can talk to them about it. The only other person I know of that has looked into it is Medievil, and he has been gone for quite some time, getting a bit worried about him actually.


I just went back to check it. Apparently I mistakened Methylene Blue with Blue Lotus. My bad. It was on NaturesHerbForum. It's littered with spam now which is part of the reason why I left.

If I were you, I would add inositol after you get the other stuff worked out because it could be a huge confounding variable in the whole thing, and it isn't even really indicated for ADHD. In fact, it may make ADHD worse (http://www.ncbi.nlm..../pubmed/9169302).
I would guess that the upregulation of D2 was due to reduced activity. However, it is still interesting.

Inositol + stimulants is an interesting concept, though, and I would like to know how it pans out. The general idea I have is that increase in choline/serotonin could be helpful for reducing negative effects of increased dopa without significantly reducing beneficial effects. I don't know, though. It isn't a solid hypothesis, just based on conjecture, and I am pretty sure that it has been thought of and rejected before. I wouldn't take inositol with the initial stack. Really, I would add each thing individually if I were you with the exception of adding l-dopa and something to reduce horribly negative side effects/neurotoxicity at the same time.


Oh wow. I didn't think it would've aggrevated ADHD symptoms. My goal with Inositol was to synergize with an SSRI in reducing depression/anxiety through independent pathways. So I'd be fighting it on two fronts essentially. So to exagerate it, the comparison would be a benzo in which reducing anxiety will also mean inducing cognitive "dysfunction". How bad can Inositol make ADHD? If it really does have the comparable efficiency rate as SSRIs as claimed, I'd still go for it. But I'll take your advice. I'll slowly titrate my dose up starting at 3-4g.

True, I am not trying to discourage you from taking Memantine. However, if it turns out that the MB hypothesis is right, then the same effects could be acheived by simply taking MB. NO inhibition is one of the actions from NMDA antagonism (http://www.ncbi.nlm....pubmed/19816675). Calcium channel inhibition is the next hope. The problem with Memantine is that inhibiting NMDA causes a lot more than just stim tolerance reduction. Theoretically, it changes memory consolidation (although maybe not for the worse or better, but it should be changed to be more even since the way Memantine works, it prevents 'excessive' NMDA activation while upregulating NMDA receptors, so I would reason that would mean same or slightly increased average activation with lower standard deviation, correct me if I am wrong, not too sure about tonic activation's effects on this) and may change fear extinction (NMDA agonists increase it http://www.ncbi.nlm....les/PMC3229759/).

The way it looks to me, memantine's effects may be able to be simulated in a more direct way by inhibition of either NOS or Calcium channel activity, or both.


That second link you provided is tempting me to try MB even more even if anxiety isn't really my primary problem. Keep in mind, I also wanted to take Memantine for it's Alpha7 antagonism. The guy that suggested Blue Lotus to me experimented with Memantine and generally had good results all around (stim tolerance, cognitive boost). The antagonism is followed by an upregulation which is the desired goal. Though I haven't looked at the studies referenced on Wiki yet.

Side note about fear extinction. I heard the Kappa receptor is involved with fear but I haven't bothered researching it.

Have you considered ritalin for the every-day stimulant? It is not as euphoric as amphetamine, but it may be just as good for getting work done, or at least be good enough.

I would strongly suggest against looking for NZT like effects in stimulants. That is a very, very dangerous path. Don't let it lead to abuse. Stimulants/increased dopamine is great, but it shouldn't be THAT great. Nothing against your judgement personally, but stimulants can have the effect of making it feel like NZT when it is mostly just the drug imairing judgement, they do that to everyone. I love stimulants because they can help with a lot of things, but they should be treated with respect, and probably not be used every day unless you absolutely cannot function without them. I understand that you are trying to find a better solution, but this is just a dangerous thing to chase. You can't chase that feeling of stimulants or you will either be let down or travel to self-destruction. Even if amphetamine can be used daily without tolerance, it may not be good to do.


If I was to ever consider a reuptake inhibitor. It would be Focalin XR as the half-life of Ritalin/Concerta being too short and also effecting the PNS (unnecessary).

I'm not one to abuse drugs. Disregarding money, I have a fairly good understanding of drugs enough to understand how destructive it can get. Even more common ones like weed and tobacco. It's usually subtle with a poor excuse to continue. I've kept my usage to a minimum and a year later with some self-control. My tolerance and abuse hasn't built at all.
My stack doesn't consist of stimulants. I was just gonna say it when you said it with stims impairing judgement. Yes, I agree, in certain situations, stims are fantastic but it's still flawed even in it's prime. For example, during my earlier months with my recreational stack, when I was "high" (was using below therapeutic doses), I would make plans ahead of time so if I was busy in the zone, I would make plans that required my current high 12 hours later. Even though I knew my current awesome feelings would be nonexistent later, I thought I would push through. When the 12 hours came, I just wasn't in the mood to commit as strongly as before. This is an example of impaired judgement. You think the hypomanias gonna last when it just isn't. I still kinda have this problem to this day but it's better now.

Not only that but figuratively it forces the brain to operate at a level I'm not particularly comfortable with at times. Basically, I'm not me. My crazier side takes over and does whatever it feels. With my stack, I wanna sustain a natural feeling to it but also have enough strong benefits.

No L-Dopa? I am confused.


If I add L-Dopa, I'll have to commit to a lot of more supplements to reduce neurotoxicity and that would be one huge stack! L-Dopa would be my last addition if I'm not seeing good results.

Unless the situation is dire, DO NOT take accutane. That stuff is poison. Seriously, unless you are facing the possiblity of being seriously disfigured by your acne, don't take it. Have you tried Minocycline? Accutane destroys you. Several family members have had life altering bowl disease from taking it.


I have pondered over and avoided Accutane for way too long and for good reasons but I really think it's time to make a pact with the devil. Minocycline is identical to Doxycycline and my other two relatives who've tried Minocycline failed and resorted to Accutane. The success rate is so high and eliminating my acne would be a +1000 to my ego. If Doxy doesn't work and I go on Accutane, I plan on continuing my gallon of water daily method and Green Vibrance shake (73 different ingredients with 25 billion probiotics per serving!!). Green Vibrance didn't do shit for me for anything when on it for 13+ months but I hope it'll reduce some of the GI side effects of Accutane.

Another thing, I think it may be either redundant or dangerous to inhibit both COMT and MAO. I don't know, I know almost nothing about COMT.

Also, something very important, don't take Methylene blue with methamphetamine (or MDMA). I don't know if you would ever substitute meth for amphetamine, but don't do it while on MB because it may kill you, I am not sure. The MAOI activity and SRI activity could be enough to cause severe serotonin syndrome with meth's moderate serotonin releasing properties. I am not sure, but best not to risk it because the risk seems pretty high. (also just a good idea not to take meth in general)


A lot of people have taken both Selegiline and COMT inhibitor like EGCG or Olive Leaf and report success. Yadayada tried it and liked the combo. COMT's function is similar to MAO in which is degrades certain neurotransmitters like dopamine. Certain COMT inhibitors are used as treatment for Parkinsons.

Once I begin my stack, my recreational stack will have to be put on hold for a while. I'm not that unthrilled to do so. Would have liked to at least try MDMA once for the hell of it (seperate topic with seperate list of supplements to prevent neurotoxicity). But again, it's not a big deal. I'd also have to abstain from recreational weed for good. I'll stick to light beer whenever possible hehe. But overall, I think my days of not only illegal drug usage is over but also studying neuroscience like a madman is slowly coming to a close and will if this stack is successful. It's been fun learning the brain but I think I still need to explore other avenues as well aka living life before returning to this field with maybe a career involved.

Edited by KoolK3n, 16 June 2013 - 02:18 AM.

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#28 brainslugged

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Posted 21 June 2013 - 07:24 AM

Okay. I was just a bit concerned because AMPHs are vasoconstrictors and thought adding a NOS inhibitor would overdue it.


Yeah, I am still a bit worried about it. Just be careful, not that I think you won't.

Oh wow. I didn't think it would've aggrevated ADHD symptoms. My goal with Inositol was to synergize with an SSRI in reducing depression/anxiety through independent pathways. So I'd be fighting it on two fronts essentially. So to exagerate it, the comparison would be a benzo in which reducing anxiety will also mean inducing cognitive "dysfunction". How bad can Inositol make ADHD? If it really does have the comparable efficiency rate as SSRIs as claimed, I'd still go for it. But I'll take your advice. I'll slowly titrate my dose up starting at 3-4g.

The side effects were pretty bad in me, worst side effects that I have ever had, but I haven't taken many meds with well-known side-effects.

I read somewhere that ADHD-PI, when it is close to combined type but not quite there, could be due to a problem covering the hyperactivity/impulsivity side. Kinda a double dysfunction where there is ADHD-C underneath, but then there is something else causing fatigue and suppression of impulse, so the H and I parts aren't really absent, just counteracted, hence PI subjects do not react as well to medicine because you are only solving one of the diseases. I can't even remember where I read it, though. It wasn't in a scientific journal.

Inositol solved a lot of problems but also caused otherwise absent (or highly subdued) H/I symptoms. I can't help but think that there COULD be some truth to the dual-disease speculation.

That second link you provided is tempting me to try MB even more even if anxiety isn't really my primary problem. Keep in mind, I also wanted to take Memantine for it's Alpha7 antagonism. The guy that suggested Blue Lotus to me experimented with Memantine and generally had good results all around (stim tolerance, cognitive boost). The antagonism is followed by an upregulation which is the desired goal. Though I haven't looked at the studies referenced on Wiki yet.

Interesting. Let us know how it goes. I am wanting to look into antagonism for upregulation, but right now I don't have much faith in the whole concept of it. I guess by decreasing tonic activity (constant, background activation) through antagonism, you could sensitize the receptors and they would be more responsive to purposeful activation. I am not sure if that is how it works though, it could very well be the oposite or it could just be complete nonsense. Otherwise, upregulation via antagonism doesn't seem like a very good goal. The receptors will, at maximum, return to homeostasis activation levels, right? More receptors, but they are also being antagonized, so what does it matter? I need to look up more about it, but I have been busy recently.

I wonder if nicotine upregulates alpha-7 as well.

Side note about fear extinction. I heard the Kappa receptor is involved with fear but I haven't bothered researching it.

Interesting. From a quick search, I didn't see much solid evidence about kappa receptors helping with fear extinction, but mu receptors look pretty promising. Interestingly, MB reduces mu opioid receptor tolerance... (even though that study indicates that MB does not have direct activity on NOS, it probably does)

If I was to ever consider a reuptake inhibitor. It would be Focalin XR as the half-life of Ritalin/Concerta being too short and also effecting the PNS (unnecessary).

I'm not one to abuse drugs. Disregarding money, I have a fairly good understanding of drugs enough to understand how destructive it can get. Even more common ones like weed and tobacco. It's usually subtle with a poor excuse to continue. I've kept my usage to a minimum and a year later with some self-control. My tolerance and abuse hasn't built at all.
My stack doesn't consist of stimulants. I was just gonna say it when you said it with stims impairing judgement. Yes, I agree, in certain situations, stims are fantastic but it's still flawed even in it's prime. For example, during my earlier months with my recreational stack, when I was "high" (was using below therapeutic doses), I would make plans ahead of time so if I was busy in the zone, I would make plans that required my current high 12 hours later. Even though I knew my current awesome feelings would be nonexistent later, I thought I would push through. When the 12 hours came, I just wasn't in the mood to commit as strongly as before. This is an example of impaired judgement. You think the hypomanias gonna last when it just isn't. I still kinda have this problem to this day but it's better now.

Not only that but figuratively it forces the brain to operate at a level I'm not particularly comfortable with at times. Basically, I'm not me. My crazier side takes over and does whatever it feels. With my stack, I wanna sustain a natural feeling to it but also have enough strong benefits.

I understand. Well, if this stack is successful, I will be happy to take it.

I didn't experience much of the planning problems you described while on ritalin. The only problem I had of that sort was making my schedule over-ambitious for the summer/fall, but I thought that I would surely be able to get stimulants perscribed (that was my main distortion, feeling like everything would work out), it wasn't of the same nature. If the stack fails, I would suggest focalin over dextroamphetamine, but lets hope it doesn't fail. Ritalin provides a very calm and complacent feel IME, contrary to amphetamine which I hear is more speedy.

I have pondered over and avoided Accutane for way too long and for good reasons but I really think it's time to make a pact with the devil. Minocycline is identical to Doxycycline and my other two relatives who've tried Minocycline failed and resorted to Accutane. The success rate is so high and eliminating my acne would be a +1000 to my ego. If Doxy doesn't work and I go on Accutane, I plan on continuing my gallon of water daily method and Green Vibrance shake (73 different ingredients with 25 billion probiotics per serving!!). Green Vibrance didn't do shit for me for anything when on it for 13+ months but I hope it'll reduce some of the GI side effects of Accutane.

Well, I am not going to argue. Good luck. It IS cyst-like acne, right? Otherwise you really need to think it over. If it isn't cystic, be sure you have tried retin-a, exfoliates, and benzoyl peroxide.

I had moderate, non-cystic acne, and I used benzoyl peroxide in the morning, salicylic acid wash at night after a shower, rewashed face, retin-a, and it helped control it for most of my Highschool years. I don't need it anymore, but it was a big help when I would use it. I assume you have tried these, but it couldn't hurt to mention them before you take accutane.

A lot of people have taken both Selegiline and COMT inhibitor like EGCG or Olive Leaf and report success. Yadayada tried it and liked the combo. COMT's function is similar to MAO in which is degrades certain neurotransmitters like dopamine. Certain COMT inhibitors are used as treatment for Parkinsons.

interesting. I will have to check that out. I was unaware that they could be combined together with good results.

Once I begin my stack, my recreational stack will have to be put on hold for a while. I'm not that unthrilled to do so. Would have liked to at least try MDMA once for the hell of it (seperate topic with seperate list of supplements to prevent neurotoxicity). But again, it's not a big deal. I'd also have to abstain from recreational weed for good. I'll stick to light beer whenever possible hehe. But overall, I think my days of not only illegal drug usage is over but also studying neuroscience like a madman is slowly coming to a close and will if this stack is successful. It's been fun learning the brain but I think I still need to explore other avenues as well aka living life before returning to this field with maybe a career involved.

Man, I feel you on that last point. My major is computer science, and that is where I plan to hold a job, but psychology and pharmacology have all but taken over my free time, especially in the last year. I know more about medicine than I know about programming, lol. There is just so much to learn. You read a study, and then you look up "oh I wonder what that is", "hmm... what other medicines do this" and before you know it, you have spent the entire day. Pubmed abstracts and wikipedia pages are just perfectly formed into bite-sized pieces, ha ha.

Too many interests, not enough time, money, or concentration.

#29 KoolK3n

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Posted 06 July 2013 - 05:53 AM

Hey brain_slugged, I apologize for not replying to ur latest post. I didn't know what else to add lol. Now I am in the process of setting up my stack. (To everybody) If it isn't obvious enough, the discussion has moved away from L-Dopa, disregard everything after post #24. With that I have some news regarding my upcoming stack. I was finally able to have Sertraline prescribed today but more importantly, I changed up my stack quite considerably given my budget and new "research".
Here it is now:
-Inositol
-Selegiline 2.5-5mg/d
-Olive Leaf
-B Complex
-Turmeric/Magnesium/Omega 3
-Zoloft 100mg/d
-Acetyl Cysteine 1200mg/d
-Amisulpride 12.5-25mg/d
-Zinc/Ginger
-Lugols Iodine
-Acetyl L-Carnitine 500mg-1000mg/d
-Phosphatidylserine 400mg/d
-Metadoxine 1000mg/d

When I started adding all these new drugs, Rasagiline looked like it would cost too much to maintain. I also dropped Memantine for N-AcetylCysteine. Meh no real reason besides cost. And I added Metadoxine for its purported effect on ADD. Not ADDH. But this drug is expensive. The last addition is Amisulpride, an antipsychotic. I don't wanna get into the mechanics but look up low-dose CFS on google. I actually just bought all three drugs off of UnitedPharmacies.com at $240 total. I looked up reviews for it and it seemed legit but I'm still anxious as hell. Fingers crossed.

Edited by KoolK3n, 06 July 2013 - 06:07 AM.


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#30 KoolK3n

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Posted 06 July 2013 - 05:12 PM

Wow upon further investigation, UnitedPharmacies was a very poor and stupid choice. I asked them not to charge my card, in the meantime I transferred all my money to my savings account. I'm switching to US bank soon anyway. In comclusion, I'm going to order Metadoxine from AllDayChemist, Selegiline from Antiagingsystems, and Amisulpride from Nobledrugstore.com (previously ordered Clomid and quality was good).

Edited by KoolK3n, 06 July 2013 - 05:14 PM.





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