114 replies to this topic

[MrHappy]

I'd taper down - again, this is coming from my personal experiences only.

[MrHappy]

Reposting from Wolfeye in the 'experiences' thread:

Quote

METHYLENE BLUE INHIBITS SEROTONIN TRANSPORTER FUNCTION.


Background and purpose. Methylene Blue (MB) is commonly employed as a therapeutic tool for methemoglobinemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause serotonin (5-HT) toxicity, when administered with a serotonin reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targets that may contribute to MB toxicity have not been identified. Given the role of the 5-HT transporter (SERT) in the regulation of extracellular 5-HT concentrations, the present study aimed to characterize the effect of MB upon SERT. Experimental approach. Live cell imaging, in conjunction with the fluorescent SERT substrate 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP(+) ), [(3) H]5-HT uptake and whole-cell patch-clamp techniques were employed to examine the effects of MB on SERT function. Key results. In EM4 cells expressing GFP-tagged human SERT (hSERT) MB produced a concentration-dependent inhibition of ASP(+) accumulation (IC(50) : 1.4 ± 0.3 µM). A similar effect was observed in N2A cells. Uptake of [(3) H]5-HT was decreased by MB pretreatment. Furthermore, patch-clamp studies in hSERT expressing cells indicated that MB significantly inhibited 5-HT evoked ion currents. 8-Br-cGMP pretreatment did not alter the inhibitory effect of MB on hSERT activity, and intracellular Ca(2+) levels remained unchanged during MB applications. Further experiments revealed that ASP(+) binding to cell surface hSERT was reduced after MB treatments. In whole-cell radioligand experiments, MB treatment (10 µM; 10 min) did not alter surface binding of the SERT ligand, [(125) I]RTI-55. Conclusions and implications: These results demonstrate that MB modulates SERT function and suggest that SERT may be an additional target upon which MB acts to produce 5-HT toxicity.

PMID: 21542830

[Logan]

I'm not so sure about the use of MB for me. I have a sensitive brain chemistry and I'm on SSRIs. I'm thinking about going as low as 10 mcg per dose. Being bipolar and on antidepressants and mood stabilizers, maybe it's just a good idea to leave this one alone for now.

This study MB's effects on the 5HT transporter have me a bit worried.

[manic_racetam]

I'm not so sure about the use of MB for me. I have a sensitive brain chemistry and I'm on SSRIs. I'm thinking about going as low as 10 mcg per dose. Being bipolar and on antidepressants and mood stabilizers, maybe it's just a good idea to leave this one alone for now.

This study MB's effects on the 5HT transporter have me a bit worried.

Honestly I've found MB to be a bit unpredictable... of course I've been taking unpredictable dosages as well.

I think if I was to stop cold turkey tomorrow I'd likely have a very depressive come down from this stuff. I can feel depression coming on about 4 hours after dosing and if I don't redose ASAP at that point I keep getting worse. I'm starting tapering down tomorrow and I should be off completely by the time my tianeptine arrives in the mail.

If I were you I wouldn't mess with it over 60mcgs while taking the other meds. But 10mcg would probably be a good starting point if you did want to experiment.

[chrono]

METHYLENE BLUE INHIBITS SEROTONIN TRANSPORTER FUNCTION.

...In EM4 cells expressing GFP-tagged human SERT (hSERT) MB produced a concentration-dependent inhibition of ASP(+) accumulation (IC(50) : 1.4 ± 0.3 µM).

Interesting study, thanks for reposting it. My first thought is that the IC50 of this effect is about 10x higher than that of MAO-A inhibition. Not sure if the full study says any of the other effects might be relevant at lower concentrations.

[MrHappy]

Anyone with PubMed fulltext access - any chance of a repost? PMID: 21542830

[niner]

METHYLENE BLUE INHIBITS SEROTONIN TRANSPORTER FUNCTION.

...In EM4 cells expressing GFP-tagged human SERT (hSERT) MB produced a concentration-dependent inhibition of ASP(+) accumulation (IC(50) : 1.4 ± 0.3 µM).

Interesting study, thanks for reposting it. My first thought is that the IC50 of this effect is about 10x higher than that of MAO-A inhibition. Not sure if the full study says any of the other effects might be relevant at lower concentrations.

Yeah, that's the first thing that jumped out at me too. This is an interesting effect, but unless people are venturing into some fairly high MB doses, I don't think this is going to be an issue. Further, inhibiting serotonin transporters isn't something that you tend to see an immediate effect from; the typical SSRI takes days or weeks to show antidepressant effects, don't they? And they have decently long half lives. I think that unless we were taking tens to hundreds of mgs of MB multiple times a day, this wouldn't be a big issue. However, at doses like those, the MAOI effect would have significantly kicked in already.

[chrono]

I just finished re-rendering the big MB threads; I'm bumping them all so everyone will know where they are.

Methylene Blue Experiences
Methylene Blue Dosing and Products
Methylene Blue Research
Methylene Blue and MAO Inhibition

These topics are interrelated, but we should try our best to keep discussions as topically segregated as realistically possible, to make the information easier to find in the future.

[SuperjackDid_]

Is safe to take with Cucurmin ?

I have stop Cucurmin today ,but cucurmin effect should still active .

20mcg feel slightly chest pain ,but i feel good effect, will reduce dose to 10mcg tomorrow.

My heart rate also drop to 45bpm.

Edited by Nootropix, 20 January 2012 - 03:22 PM.

[hooter]

Curcumin is also a maoi, don't mix.

[Krell]

Cell. 2012 Feb 3;148(3):421-33.
Resveratrol ameliorates aging-related metabolic phenotypes by
inhibiting cAMP phosphodiesterases.
Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H,
Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V,
Chung JH.
Source
Laboratory of Obesity and Aging Research, Genetics and Developmental
Biology Center, National Heart Lung and Blood Institute, National
Institutes of Health, Bethesda, MD 20892, USA.
Abstract
Resveratrol, a polyphenol in red wine, has been reported as a calorie
restriction mimetic with potential antiaging and antidiabetogenic
properties. It is widely consumed as a nutritional supplement, but its
mechanism of action remains a mystery. Here, we report that the
metabolic effects of resveratrol result from competitive inhibition of
cAMP-degrading phosphodiesterases, leading to elevated cAMP levels.
The resulting activation of Epac1, a cAMP effector protein, increases
intracellular Ca(2+) levels and activates the CamKKβ-AMPK pathway via
phospholipase C and the ryanodine receptor Ca(2+)-release channel. As
a consequence, resveratrol increases NAD(+) and the activity of Sirt1.
Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits
of resveratrol, including prevention of diet-induced obesity and an
increase in mitochondrial function, physical stamina, and glucose
tolerance in mice. Therefore, administration of PDE4 inhibitors may
also protect against and ameliorate the symptoms of metabolic diseases
associated with aging.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22304913

According to this article "rolipram reproduces all of the metabolic benefits
of resveratrol". But rolipram works by MAOI like MB, so does that make MB
the poor man's resveratrol?

[manic_racetam]

Is safe to take with Cucurmin ?

I have stop Cucurmin today ,but cucurmin effect should still active .

20mcg feel slightly chest pain ,but i feel good effect, will reduce dose to 10mcg tomorrow.

My heart rate also drop to 45bpm.

Nootropix,

Your heart rate dropped to 45bpm? That seems really low! Do you do a lot of rigorous exercise? If you aren't an intense athlete then that sounds like bradycardia... could it be a choline induced reduction in heart-rate?

[SuperjackDid_]

I not have do much exercise ,heart-rate drop with irregular heartbeat ,that seem pretty dangrous to me ,
Any Choline source not good to me ,most dangerous is Hyperzine i have almost dead of that . :( look like i'm not fit for
Acetylcholinesterase inhibitor


Right now i take Lecithin it not do anything on my heart-rate .

[mag1]

After reading many of these posts from the last few years, I am surprised by the absence of comments related to the genetics of serotonin processing. Some of the posters have noticed serotonin symptoms at low doses of MB. Doesn't this suggest that some people have a genetic
sensitivity to serotonin?

My genome scan revealed that I am heterozygous at rs6323 which is in the MAO A gene. This mutation would reduce clearance of serotonin.
I receive a free dose of Prozac!

Those with the risk allele at rs6323, and/or other mutations in MAO A (etc.) might be sensitive to MB, especially in combination with other inhibitors of MAO A.
MAO A.

[Lolofatty]

Please forgive my ignorance,

I'm just a layperson who is trying to wade through all of your references to dense medical and scientific articles.

Would 5-HTP be considered unsafe to take with MB? I take 50-100mg 5HTP and 3 doses of <1mg (around 70mcg) MB daily. I've only just started this regime and have noticed excess fatigue- though I also have recently weened off of Zoloft. Any advice would be much appreciated.

[mbdrinker]

I take Mb because there is no access to anything better. Health institutions no longer heal in my country and chemists shop sell some non working stuff like fake melatonin and phenibut. Mb is last psychedelic substance available. Bless pet shops. Pets are treated better nowadays than people.

[mbdrinker]

I have read somewhere that mb causes formation of stones in rhinos? Is it true? I want to increase the dose to get more mao inhibition  but that info is frightening.

[Lolofatty]

Hey guys, I started following this thread years ago and was taking MB. Now that I'm getting the new replies to this topic, I wanted to caution everyone against taking it. It depletes all of your guy bacteria, good and bad. I've had to keep rebuilding it ever since and regret supplementing with MB.

Edited by Lolofatty, 20 October 2021 - 06:58 PM.

[mbdrinker]

How do I you raise seratonin then? Without it I have insomnia. In Russia we have so called rotovirus or stomach flue. That disease is caught easily and attacks digestive system unrevertedly. I got 2 years ago and still have consequences: highly acid environment, desire to eat at night and wreckage of muscles of stomach so food tries to go back into neck. So I have too sleep on high pillows. Also I can no longer abuse alcohol on parties. Do you have this crap in USA or Western Europe? It seems to inflict permanent damage to digestive system. I bet it was artificially created somewhere in a lab. How is it connected with seratonin? I have read that desire to eat at night is indication of low melatonin and melatonin is produced from seratonin. Mb helps to raise seratonin and sleep well without much eating.

[mbdrinker]

Does leicomb kill bacteria? I take it as leico form. I have not noticed anything like increase in degree of farting which would be a sign of disbacteriosys. I think disbacteriosys is hype invented to sell kefir. Immune system kills pathogenic flora. Does alcohol kill bacteria? I guess so. But do alcoholics suffer disbacteriosys? I have not heard about it. But there is tolerance to mb. After couple of weeks euphoria passes and life returns to its grey state.

[kurdishfella]

Things like MAO inhibitor or things like LSD or adderall just increase the release of your existent neurontransmitters (or use your current baseline little longer). what you want is something that produces MORE of it which you can make happen by increasing the amount of enzymes of a particular thing and its activity so you end up with more and therefore it increases that neurontransmitters on all fronts everywhere to a higher base line.

[mbdrinker]

I don’t know such drugs to produce more enzymes. I was off from mb couple of months due to experiments with alcohol. Indeed it helped me more than phenibut or anything else. The idea is to take it in small doses 10 times a day to affect only gaba system. If taken more you may become sleepy, ie take doses allowing to drive a car. Phenibut in Russia is all fake now and 90% of alcohol. I have to seek hard to find quality alcohol. I hope freedom convoy will win hello from Russia to canada

[mbdrinker]

Alas, i have to disappoint you about mb and other serotogenic ads. They supress dht and increase estradiol. Mb have initiated gynecomastia. Refusal from mb will mean insomnia again

[qemist]

> They supress dht

 

That's great because I'm going bald (see pic).

[mbdrinker]

It's not your pic. You must look like a lier