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Methylene Blue boosts short term memory and attention (Human Study)

short term memorymethylene blue attention

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#1 BioFreak

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Posted 08 July 2016 - 07:04 PM


I don't know if this has been posted yet - the Study is from June 28th, so fairly new.   Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain

 

Purpose

To investigate the sustained-attention and memory-enhancing neural correlates of the oral administration of methylene blue in the healthy human brain.


Materials and Methods

The institutional review board approved this prospective, HIPAA-compliant, randomized, double-blinded, placebo-controlled clinical trial, and all patients provided informed consent. Twenty-six subjects (age range, 22–62 years) were enrolled. Functional magnetic resonance (MR) imaging was performed with a psychomotor vigilance task (sustained attention) and delayed match-to-sample tasks (short-term memory) before and 1 hour after administration of low-dose methylene blue or a placebo. Cerebrovascular reactivity effects were also measured with the carbon dioxide challenge, in which a 2 × 2 repeated-measures analysis of variance was performed with a drug (methylene blue vs placebo) and time (before vs after administration of the drug) as factors to assess drug × time between group interactions. Multiple comparison correction was applied, with cluster-corrected P < .05 indicating a significant difference.


Results

Administration of methylene blue increased response in the bilateral insular cortex during a psychomotor vigilance task (Z = 2.9–3.4, P = .01–.008) and functional MR imaging response during a short-term memory task involving the prefrontal, parietal, and occipital cortex (Z = 2.9–4.2, P = .03–.0003). Methylene blue was also associated with a 7% increase in correct responses during memory retrieval (P = .01).

 

Conclusion

Low-dose methylene blue can increase functional MR imaging activity during sustained attention and short-term memory tasks and enhance memory retrieval.

 

Full study:

http://pubs.rsna.org...diol.2016152893

 

Interview on Medscape with the Scientist:

http://www.medscape....warticle/865748

 

Well then... looks like I'll be trying this after all. :-D

 

 

 



#2 nightlight

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Posted 08 July 2016 - 07:40 PM

The 280mg is a lot higher dose (by 2-3 orders of magnitude) than microdosing suggested in earlier MB threads.

 


Edited by nightlight, 08 July 2016 - 07:40 PM.


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#3 gamesguru

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Posted 08 July 2016 - 08:12 PM

I mean they said 0.5-2.0 mg/kg, so it could be closer to 70mg.  And in theory something as little as 1mg, sustained daily over years, could produce a modest effect. Not all chemicals have a linear dose-response curve.



#4 thedevinroy

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Posted 10 July 2016 - 02:27 AM

I feel like this is in light of the Reddit thread, right?

So I dosed out 15mg and noticed increased feeling of uneasiness, like you're in a room full of awkward people who are drinking and talking to strangers but you are the sober one with the loud friends trying to score. It's a familiar feeling for me...

It's that dumbass bravery, too. Like you know it might look dumb to dance, but you are going to smile through it anyway and see the good in everything. As far as motivation to not be a dumbass... Not seeing it. I feel like if I took this at a party, my heart would explode or my brain would fizzle out from adrenaline fatigue. So I just want to lay down and think about life, get warm and drink mint tea.

MAOI effect is strong you could say...

Edited by devinthayer, 10 July 2016 - 02:35 AM.


#5 normalizing

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Posted 10 July 2016 - 03:11 AM

devinthayer, definitely dopaminergic?



#6 thedevinroy

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Posted 10 July 2016 - 05:09 AM

devinthayer, definitely dopaminergic?

 

Of several things, but yeah, clearly dopaminergic in this aspect:

 

https://en.wikipedia...triatal_pathway

 

Not so much, but still noticeable here:

 

https://en.wikipedia...olimbic_pathway

 

And the least of which was this one:

 

https://en.wikipedia...ortical_pathway



#7 thedevinroy

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Posted 10 July 2016 - 06:26 AM

Hey all, so I ran some numbers and have determined that there is in fact a HUGE error in my math, based on an old post I made years ago.

 

I was off by a factor of 17.7775308322809.  There is 408.883209142461 mg per mL and about 408.883209142461*0.05 = 20.4441604571231 mg per drop.

 

I ran the numbers based on 10 gallons and 3 ppm from one teaspoon as per their instructions, and I have determined that Kordon's methylene blue of 2.303% concentration is actually a molarity... or rather, a molar %.  To double check this, someone with some crude tools can weight out a mL, and if it is slightly higher than 1.3g, then this theory is verified.

 

That means my 15mg was actually 408.883209142461/23*15 ~= 267 mg.

 

Sorry to everyone I have misled.  Good news is that the dose you were taking before on Kordon MB is still the same price... in fact, it had greater bang for your buck per mg than you thought!  Not that I am any less sorry... still sorry...



#8 normalizing

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Posted 10 July 2016 - 02:45 PM

thats quite the dose you took. i was confused as to whats not to like about this being dopaminergic, but now that i see the mega dose you actually took, im surprised you didnt go full on blown schizo



#9 thedevinroy

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Posted 10 July 2016 - 03:25 PM

thats quite the dose you took. i was confused as to whats not to like about this being dopaminergic, but now that i see the mega dose you actually took, im surprised you didnt go full on blown schizo

Twitches and restlessness, fair too much adrenaline, insomnia, just relentlessness to the point of having no point to keep going. Sounds manic to me. I can keep going on the (side) effects... Tendency towards high energy conversation almost inappropriately so, irritability, stomach upset like butterflies when meeting a hottie, strange control over sensations (choosing to feel relaxed, focused, etc.) like NZT on limitless, passionate thinking, green urine, reduced body odor, obsessive behaviors like playing with hair to get it just right, enhanced upper level emotions like guilt/shame and empathy and happiness, and of course losing yourself posting on longecity.

Dosing down to 75mg using this new method. The half life is 5.25 hours, so that's about what I still have in my system, which is still noticeable. Peak cognition was probably 5 hours after taking it the first time, so that's a 130mg effective dose on a normal day and 75mg re-up in the afternoon. That's my new happy place.

Edited by devinthayer, 10 July 2016 - 03:34 PM.


#10 normalizing

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Posted 10 July 2016 - 03:31 PM

so twitches, restlessness and all that crap, none of the good stuff, not a single excited sensation, euphoria or enhanced libido? what kind of dopaminergic nightmare is this



#11 thedevinroy

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Posted 10 July 2016 - 03:35 PM

so twitches, restlessness and all that crap, none of the good stuff, not a single excited sensation, euphoria or enhanced libido? what kind of dopaminergic nightmare is this


I edited it :)

#12 normalizing

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Posted 10 July 2016 - 03:39 PM

what the hell... sounds like something ive experienced megadosing on ephedrine, yohimbine and phenethylamine with caffeine



#13 thedevinroy

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Posted 10 July 2016 - 03:42 PM

so twitches, restlessness and all that crap, none of the good stuff, not a single excited sensation, euphoria or enhanced libido? what kind of dopaminergic nightmare is this

I edited it :)

So peak cognition to me means that I had a better awareness of self/world and also control of myself. The best way I can describe it is a lack of self doubt combined with an ease in thinking ahead. That was going on when I went to bed. Still feeling some of the effects in that respect right now. To confirm, I'll take 75mg right now and report back later.

what the hell... sounds like something ive experienced megadosing on ephedrine, yohimbine and phenethylamine with caffeine


Yep. Pretty manic! And all at once? Man, you must have some tolerance...

#14 normalizing

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Posted 10 July 2016 - 03:46 PM

ive tolerated it for a while until i ended in emergency with thoughts of speed of light that i couldnt control i thought i was gone insane until they shot me with benzos



#15 thedevinroy

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Posted 10 July 2016 - 03:48 PM

ive tolerated it for a while until i ended in emergency with thoughts of speed of light that i couldnt control i thought i was gone insane until they shot me with benzos


Haha normalizing was normalized!
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#16 thedevinroy

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Posted 10 July 2016 - 04:44 PM

Found this:
https://www.drugs.co...ylene-blue.html

An absolute must read. Methylene Blue is contraindicated in those with G6PD deficiency, so know the statistics (high in eastern and African decent), signs (low folate, low iron, infantile jaundice), and symptoms (like hemolysis). Just to be on the safe side, if you are a high responder to Vitamin C, give MB a second cautious look.

Edited by devinthayer, 10 July 2016 - 04:49 PM.


#17 thedevinroy

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Posted 10 July 2016 - 04:47 PM

Anyway, that article also has the pharmacokinetics. Peak plasma concentration from oral dose occur 1 to 2 hours later. That's about now. Not noticing much in the way of cognition enhancement as described. I still haven't had my tea yet, so I'll report back after two black and one blueberry tea bags in a glass (same as last night).


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#18 JayZin

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Posted 10 July 2016 - 07:21 PM

methylene blue is a great way to induce hypertension folks; what the hell are ya'll doing dosing a nitric-oxide inhibitor?

Heart disease in the future.

http://www.ncbi.nlm....v/pubmed/788550

http://ispub.com/IJA/28/2/8425

https://www.aana.com...08_p271-274.pdf



#19 thedevinroy

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Posted 10 July 2016 - 07:55 PM

Anyway, that article also has the pharmacokinetics. Peak plasma concentration from oral dose occur 1 to 2 hours later. That's about now. Not noticing much in the way of cognition enhancement as described. I still haven't had my tea yet, so I'll report back after two black and one blueberry tea bags in a glass (same as last night).


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And slight changes but not much. Not watching TV. That's a plus. I'll keep this up for a few days, see where it takes me. Not as wired, but still feel a little of something.

#20 thedevinroy

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Posted 10 July 2016 - 08:16 PM

methylene blue is a great way to induce hypertension folks; what the hell are ya'll doing dosing a nitric-oxide inhibitor?
Heart disease in the future.
http://www.ncbi.nlm....v/pubmed/788550
http://ispub.com/IJA/28/2/8425
https://www.aana.com...08_p271-274.pdf

Your conclusion is puzzling, but yeah there is some NO synthase activity at a Ki of 2.7 micro moles.

http://www.ncbi.nlm....pubmed/7589219/

This is compared to a Ki of 27 nM for MAO-A.  It has some affinity for MAO-B, more in the range with NO Synthase:

 

http://www.ncbi.nlm....les/PMC2078225/

 

I guess what I'm saying is that it likely is serotonin syndrome and adrenaline are more responsible for the spike in blood pressure, not to say that the NO doesn't play a role...

But yeah, high blood pressure in the form of chronic hypertension is bad and should be monitored on any nootropic or drug of any sort.  You're not wrong to think that chronic use of something causing hypertension is going to be damaging to your heart over time.  It's not a folktale that stimulating drugs put stress on the heart (among other tissues) and cause premature failure, though research into heart disease itself is hard to quantify to my understanding regarding drugs that increase blood pressure.

 

In my opinion, this is the real reason we should be concerned:

 

http://www.ncbi.nlm....pubmed/20142303

 

It's MAOi effects kick in at any therapeutic dose.  1.6 micro moles is the concentration the the blood sees after a 0.75mg/kg IV transfusion.  That's why there are so many warnings about this stuff, and rightly so.  Serotonin toxicity/syndrome is a real problem that won't go away without time, charcoal, or 5-HT blocking antipsychotics.  That's why people can't be on anything serotonergic like SSRI's.


Edited by devinthayer, 10 July 2016 - 09:05 PM.


#21 normalizing

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Posted 11 July 2016 - 01:11 AM

so... for dopamine boost i was planning on 9-me-BC but methylene blue seems to be dopa-friendly too from what i gather and its much much cheaper. what do you guys think, go for the methy? 

btw i dunno if i have G6PD deficiency but i have reduced MTHFR enzyme activity which is related to folate malfunction or whatever, i wonder if that is to be taken in consideration...



#22 thedevinroy

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Posted 11 July 2016 - 02:31 AM

so... for dopamine boost i was planning on 9-me-BC but methylene blue seems to be dopa-friendly too from what i gather and its much much cheaper. what do you guys think, go for the methy?
btw i dunno if i have G6PD deficiency but i have reduced MTHFR enzyme activity which is related to folate malfunction or whatever, i wonder if that is to be taken in consideration...

MAOi effects are kind of their own animal. It isn't a release agent or reuptake inhibitor by itself, but they prevent the breakdown of natural release agents and monoamines which in turn have competitive inhibition.

So when you are happy, you feel happy for longer. When you are anxious, you feel anxious for longer. When you are excited, you stay excited for longer. Think of those feelings like drugs with typically very short half lives. If you extend the life of those drugs, they build up in your system more. So, by the end of an exciting conversation, your heart is ready to explode with adrenaline.

There is some baseline increase, but most of it is sensitivity to normal day to day rises in dopamine. Food tastes different, makes you feel elated for longer as another example. Baseline, you are pretty much the same.

I guess you could say that you get more bang for your buck in terms of distractions and micro progress but only if you keep at it long enough. The pomodoro technique was almost effective, for instance. That trick never worked for me, not once, but today I tried it again, and it worked the first time, not the second. Controlled distractions/breaks are easy for me to ignore and want to disrupt them.

Update. Definitely less side effects at the 75mg redose. I am considerably less restless and insomniac. Also, I am a little more focused today. Double win. Did run out of juice (metaphorical steam, not MB) about 30 minutes ago.

Edited by devinthayer, 11 July 2016 - 02:37 AM.


#23 thedevinroy

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Posted 11 July 2016 - 02:35 AM

I'm not sure the coincidence of MTFR and G6PD. If your iron and liver are happy, give it a shot. Worst that will happen is you'll have to eat kale and oranges. You're not injecting the stuff either, so only 75% is absorbed and at an arguably more S shaped curve to peak plasma levels (less linear). I had a tough time finding a molarity of peak plasma levels for oral dosing. Don't think I was successful.

Edited by devinthayer, 11 July 2016 - 02:45 AM.


#24 BioFreak

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Posted 11 July 2016 - 08:59 AM

I mean they said 0.5-2.0 mg/kg, so it could be closer to 70mg.  And in theory something as little as 1mg, sustained daily over years, could produce a modest effect. Not all chemicals have a linear dose-response curve.

 

From the study:

 

After the first set of MR imaging data was acquired, participants exited the imager. Then, 13 participants (the methylene blue group) were randomized to receive 280 mg (approximately 4 mg/kg) of oral U.S. Pharmacopeia-grade methylene blue (methylthioninium chloride USP; PCCA, Houston, Tex), and 13 participants (the placebo group) were randomized to receive food colorant (FD&C blue no. 2)

 

So the dosage was basically not focused on weight, but absolute dosage.



#25 gamesguru

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Posted 11 July 2016 - 12:37 PM

I feel bad for the people who got the food dye.

 

Yes but this is only one study, and similar ones [see below] have reported a benefit at one quarter the dose. My point about not all compounds exhibiting a linear dose-response curve still holds, and the burden remains on you to establish methylene blue as linear when all experience dictates contrary. People are reporting benefits BELOW 1mg. You have to ask yourself all the hype can be explained by the placebo effect...

Specifically, repeated low-dose (0.5-2.0 mg/kg) MB has long-lasting upregulation of brain cytochrome c oxidase activity [20, 24-26]. MB readily crosses the blood-brain barrier because of its high lipophilicity [15].

Low-dose MB has recently been shown to reduce neurobehavioral impairment in optic neuropathy [19, 27], traumatic brain injury [28], Parkinson's disease [23, 29], Alzheimer disease [30-32], and ischemic stroke [4, 5, 33]. The goal of this article is to review relevant MB literatures in relation to neuroprotection in experimental stroke models.



#26 normalizing

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Posted 11 July 2016 - 01:59 PM

well, i went back to an expired selegiline for now. see how it goes, so far nothing and im not sure if the expired date is the problem or what but even before when it was new it didnt do much for me. too weak of MAOI? i might switch to MB eventually if reputable source is spotted but i wonder whats the comparison in MAOI effect between selegiline and MB?



#27 normalizing

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Posted 11 July 2016 - 02:07 PM

ok i solved this problem "L-Deprenyl, also an MAO-B inhibitor, metabolizes to L-amphetamine and L-methamphetamine, which are both norepinephrine releasing agents. In contrast, D-deprenyl additionally has dopaminergic effects and has been found to be reinforcing in scientific research, whereas L-deprenyl is not known to have any appreciable psychological reinforcement"

 

so selegiline is basically useless. not sure why i didnt pay attention the first time i used it. time to DUMP!



#28 BioFreak

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Posted 11 July 2016 - 05:46 PM

 

I feel bad for the people who got the food dye.

 

Yes but this is only one study, and similar ones [see below] have reported a benefit at one quarter the dose. My point about not all compounds exhibiting a linear dose-response curve still holds, and the burden remains on you to establish methylene blue as linear when all experience dictates contrary. People are reporting benefits BELOW 1mg. You have to ask yourself all the hype can be explained by the placebo effect...

Specifically, repeated low-dose (0.5-2.0 mg/kg) MB has long-lasting upregulation of brain cytochrome c oxidase activity [20, 24-26]. MB readily crosses the blood-brain barrier because of its high lipophilicity [15].

Low-dose MB has recently been shown to reduce neurobehavioral impairment in optic neuropathy [19, 27], traumatic brain injury [28], Parkinson's disease [23, 29], Alzheimer disease [30-32], and ischemic stroke [4, 5, 33]. The goal of this article is to review relevant MB literatures in relation to neuroprotection in experimental stroke models.

 

 

No offense, but there is no burden on me. I was just referring to the dosage levels of the study I posted, as nothing in your post indicated you referred to anything else... But this discussion between us is probably just a communication problem, as I do not state that other studies use similar dosages or that the dosage response curve is linear, but please quote me if I did. Don't know where you got that. :-D

 

Anyways, I don't advocate the use of high methylene blue, if anyone was misunderstanding me. Please, if you quote from studies, also link to them.

 

How good is the bio availability per oral anyways? How clear is it that (only) cytochrome c oxidase activity upregulation is behind the positive effects? The dosage in the quote is pretty specific about cytochrome c oxidase.

 

 


Edited by BioFreak, 11 July 2016 - 05:53 PM.


#29 gamesguru

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Posted 11 July 2016 - 05:51 PM

If the study did not evaluate 0.5mg/kg, why are you so quick to dismiss it as still therapeutic. That's why the burden rests on you. Others are claiming effects below 1mg (~0.02mg/kg !!)

 

The cytOx effects are strongly related to the cognitive restoring effects, 50-90%. But it's not related to the discussion of dose vs. effect.


Edited by gamesguru, 11 July 2016 - 06:13 PM.


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#30 BioFreak

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Posted 11 July 2016 - 06:06 PM

Wow. You don't seem to read my posts and instead read something into it that I did not say. This is getting pointless, and unproductive.

 

I never dismissed 0.5mg/kg as being therapeutic. I never claimed what you read into my posts, therefore there is no burden of proof on me. Why is there no burden of proof? Because I did not make any statements that I would have to proof. You would be completely right, if I said those things, but I did not. You read between the lines where there is nothing to read.

 

Instead I would suggest you to get familiar with the concept of "mind reading" from CBT:

 

 

Cognitive distortions are errors or biases in thinking that can lead to faulty assumptions, and can worsen mood. Cognitive Therapy teaches that much of what fuels depression and anxiety are patterns of distorted thinking. Thus to reduce depression and anxiety, it can be very helpful to learn to recognize and respond to common cognitive distortions.

One common cognitive distortion is mind reading, which is assuming you know what other people think.

 

http://cogbtherapy.c...ns-mind-reading

 

Again, no offense, but you read things into my posts that I did simply not state.







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