Posted by morgan miller on September 19, 2011, at 19:15:33
In reply to Re: 40% down to 25% » morgan miller, posted by SLS on September 19, 2011, at 15:40:08
Hey Scott, Methylene Blue basically enhances mitochondrial function, and is a fairly potent MAOI at higher doses.
Here are some quotes/abstracts from studies on MB:
"Neuroprotective strategies, including free radical scavengers, ion channel modulators, and anti-inflammatory agents, have been extensively explored in the last 2 decades for the treatment of neurological diseases. Unfortunately, none of the neuroprotectants has been proved effective in clinical trails. In the current study, we demonstrated that methylene blue (MB) functions as an alternative electron carrier, which accepts electrons from NADH and transfers them to cytochrome c and bypasses complex I/III blockage. A de novo synthesized MB derivative, with the redox center disabled by N-acetylation, had no effect on mitochondrial complex activities. MB increases cellular oxygen consumption rates and reduces anaerobic glycolysis in cultured neuronal cells. MB is protective against various insults in vitro at low nanomolar concentrations. Our data indicate that MB has a unique mechanism and is fundamentally different from traditional antioxidants. We examined the effects of MB in two animal models of neurological diseases. MB dramatically attenuates behavioral, neurochemical, and neuropathological impairment in a Parkinson disease model. Rotenone caused severe do... [...]"
"Posterior cingulate/retrosplenial cortex (PCC) hypometabolism is a common feature in amnestic mild cognitive impairment and Alzheimer's disease. In rats, PCC hypometabolism induced by mitochondrial dysfunction induces oxidative damage, neurodegeneration and memory deficits. USP methylene blue (MB) is a diaminophenothiazine drug with antioxidant and metabolic-enhancing properties. In rats, MB facilitates memory and prevents neurodegeneration induced by mitochondrial dysfunction. This study tested the memory-enhancing properties of systemic MB in rats that received an infusion of sodium azide, a cytochrome oxidase inhibitor, directly into the PCC. Lesion volumes were estimated with unbiased stereology. MB's network-level mechanism of action was analyzed using graph theory and structural equation modeling based on cytochrome oxidase histochemistry-derived metabolic mapping data. Sodium azide infusions induced PCC hypometabolism and impaired visuospatial memory in a holeboard food-search task. Isolated PCC cytochrome oxidase inhibition disrupted the cingulothalamohippocampal effective connectivity, decreased the PCC functional networks and created functional redundancy within the thalamus. An intraperitoneal dose of 4 mg/kg MB prevented the memory impairment, reduced the PCC metabolic lesion volume and partially restored the cingulothalamohippocampal network effects. The effects of MB were dependent upon the local sub-network necessary for memory retrieval. The data support that MB's metabolic-enhancing effects are contingent upon the neural context, and that MB is able to boost coherent and orchestrated adaptations in response to physical alterations to the network involved in visuospatial memory. These results implicate MB as a candidate intervention to improve memory. Because of its neuroprotective properties, MB may have disease-modifying effects in amnestic conditions associated with hypometabolism."
http://www.alzforum.org/new/detail.asp?id=2203
"Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.
Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN.
SourceNutrition & Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA. hatamna@chori.orgAbstract
Methylene blue (MB) has been used clinically for about a century to treat numerous ailments. We show that MB and other diaminophenothiazines extend the life span of human IMR90 fibroblasts in tissue culture by >20 population doubling (PDLs). MB delays senescence at nM levels in IMR90 by enhancing mitochondrial function. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37-70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium. MB also induces phase-2 antioxidant enzymes in hepG2 cells. Flavin-dependent enzymes are known to use NAD(P)H to reduce MB to leucomethylene blue (MBH2), whereas cytochrome c reoxidizes MBH2 to MB. Experiments on lysates from rat liver mitochondria suggest the ratio MB/cytochrome c is important for the protective actions of MB. We propose that the cellular senescence delay caused by MB is due to cycling between MB and MBH2 in mitochondria, which may partly explain the increase in specific mitochondrial activities. Cycling of MB between oxidized and reduced forms may block oxidant production by mitochondria. Mitochondrial dysfunction and oxidative stress are thought to be key aberrations that lead to cellular senescence and aging. MB may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer disease.""Inhibition of hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation.
Wang AM, Morishima Y, Clapp KM, Peng HM, Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP.
SourceDepartment of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.Abstract
The Hsp90/Hsp70-based chaperone machinery regulates the activity and degradation of many signaling proteins. Cycling with Hsp90 stabilizes client proteins, whereas Hsp70 interacts with chaperone-dependent E3 ubiquitin ligases to promote protein degradation. To probe these actions, small molecule inhibitors of Hsp70 would be extremely useful; however, few have been identified. Here we test the effects of methylene blue, a recently described inhibitor of Hsp70 ATPase activity, in three well established systems of increasing complexity. First, we demonstrate that methylene blue inhibits the ability of the purified Hsp90/Hsp70-based chaperone machinery to enable ligand binding by the glucocorticoid receptor and show that this effect is due to specific inhibition of Hsp70. Next, we establish that ubiquitination of neuronal nitric-oxide synthase by the native ubiquitinating system of reticulocyte lysate is dependent upon both Hsp70 and the E3 ubiquitin ligase CHIP and is blocked by methylene blue. Finally, we demonstrate that methylene blue impairs degradation of the polyglutamine expanded androgen receptor, an Hsp90 client mutated in spinal and bulbar muscular atrophy. In contrast, degradation of an amino-terminal fragment of the receptor, which lacks the ligand binding domain and, therefore, is not a client of the Hsp90/Hsp70-based chaperone machinery, is enhanced through homeostatic induction of autophagy that occurs when Hsp70-dependent proteasomal degradation is inhibited by methylene blue. Our data demonstrate the utility of methylene blue in defining Hsp70-dependent functions and reveal divergent effects on polyglutamine protein degradation depending on whether the substrate is an Hsp90 client."http://www.sciencedaily.com/releases/2009/09/090929181808.htm
"Methylene blue administered post-training improves memory retention in avoidance and appetitive tasks, and restores spatial memory impaired by an inhibitor of cytochrome oxidase. Methylene blue may improve memory retention by increasing brain oxygen utilization. We investigated which doses improve memory without nonspecific behavioral effects, and whether methylene blue enhances brain oxygen consumption. Different doses were evaluated 24 h after administration in wheel running, feeding, open field habituation and object recognition tests. The 110 mg/kg methylene blue-treated rats were not different from saline-treated rats in locomotion or feeding behavior. The 50100 mg/kg doses decreased running wheel behavior. The 4 mg/kg dose improved behavioral habituation and object memory recognition. Dose-dependent effects of methylene blue on brain oxygen consumption revealed that low concentrations increased brain oxygen consumption in vitro and 24 h after in vivo administration. Therefore, methylene blue doses that increase brain oxygen consumption also facilitate memory retention."
One of many reports on MB experiences:
"Brainfogged, on 21 June 2011 - 03:57 PM, said:
Does the drug alter DNA?
Im sorry, I responded to the wrong quote on my response to brainfogged. The answer is no, this is from pg 2 of the link I provided. It can alter DNA given circumstances, but these are usually extreme cirumstances and unlikely.
"This photosensitization thing seems quite absurd, to me anyways. MB isn't something brand new. It's been around for ages, used at concentrations way beyond 100nM (~1mg!) in humans and no ill "photosensitization" effects have been reported to my knowledge. Considering ~200mg of MB is used routinely for methylhemoglobinemia, and anywhere from ~733mg (12mg/kg/day) to ~1,500mg (24mg/kg/day) in humans is used to treat malaria with few ill effects (the minimal dosage needed to see any toxic effect what so ever from MB is estimated around 600mg from the rat toxicological studies)... Yeah, I'm sorry, but these studies with crayfish neurons (sunlight is actually 137 mW/cm2 at nigh noon, staring directly into the sun; so the crayfish study used three times the amount of energy that sunlight has, and you already can't stare directly into the sun, MB notwithstanding) and fungi (which used mM amounts of MB in their study) just don't cut it for me. Also, do we even know what doses were used in PMID: 6603875? They did say that vitamin E completely stopped any photosensitization by MB, and considering the issue is singlet oxygen production, which is made constantly all the time in our bodies, including our eyes, I really don't worry - the human body is quite apt at not only dealing with but actually using super oxide for a variety of signals.
I have no doubt, and this is only my opinion, that you have nothing to worry about with your retina and MB at these doses, what so ever. Not to mention humans have a better antioxidant system than most creatures on this planet, and even many mammals, our retinas are not prone to failure by any direct "sensitization" effect, and retinas can heal quite well. It's only if you lose the optic nerve or degenerate the retina faster than it can heal (usually this is genetic) that you run into trouble; and I'm afraid MB at these dosages just isn't going to be able to do that. You'll lose your lens long before retina trouble, more likely than not, since the lens is one of the very rare things that aren't turned over."
My Experience with Methylene BlueMy first day: I bought Methylene blue from the aquarium last night. Prepared it, a 60 microgram solution, its very easy thing to do , you just need a eye dropper, a few cups and a measuring glass.
When I took it I felt great energy. My thoughts were easily facilitated, it was as if I got the stereotypical "this is how I am usually supposed to feel" feeling. Which this could actually be the case because its increasing metabolism in the places of your brain that need it.
This nootropic has a different feel to it. I can say it definitely takes away social anxiety no problem, because it feels like your young again, where your whole world is focused on what's in front of you. That was the biggest effect I noticed. The second biggest thing I noticed, is the learning after the fact process. I could say that MB does help with thinking while doing a task due to the relaxed nature of how you feel which I just described as reduced social anxiety, but I would say that the biggest nootropic effect is after the fact learning. I felt when I would read or do something, after I am done, I feel like I fully understand the subject thoroughly and can implement it from there on out, whether it is a life lesson or an academic lesson or even a logical lesson. I would say that methylene blue facilitates the idea "fool me once shame on you, fool me twice shame on me" but without the fool me twice, because the MB facilitated the full understanding of the subject after the first try. Sort of..kind of..like selectively putting what is in your long term memory. Ask me more questions, if you ask me a question Ill be able to answer it instead of me just rambling. MB also definetly increases the energy department, I have in the past always felt tired when I knew I shouldn't or I would get tired much faster than other people, and I feel like MB kicks that completely out the door. Not only do you get the energy from optimal mitochondrial processing, but I feel like most people get tired quickly due to stress, and it seems as if it eliminates stress (or makes stress not seem as monumental as people can make it) thus facilitating more energy with a relaxed state of mind.
There are more effects I will continue to right about when I come across them again. Im taking 60 micrograms right now each dosing, and I dose periodically, mostly 4 hours apart, we'll see what happens.
Smoking marijuana and Methylene Blue - Very Nice, I guess you can describe it as how people would idealize the typical marijuana experience: (no nervousness, boosted creativity, mood increase, and talkative)
I would also be interested if I could see the difference in ratio of compound to side effects of methylene blue compared to an adderall or even an SSRI that people are likely to be prescribed"
Here's an explanation of how to get and use a low dose of MB from a product like Kordon's. For you and I, I think staying at between 60 and 100 mcg is a safe dose, considering we are going to be on drugs that inhibit serotonin reuptake. Viibryd inhibits serotonin reuptake right? Anyway, higher doses of MB would likely inhibibit MAO A too much for it to be safe for those of use taking certain antidepressants.
" Dosing Explained:
Quotefish methylene blue
is 2.303% w/v so that is 2.303 grams in 100cc of distilled purified
water. Take a ml or 1/100th = 23 mg / ml (1ml = 1 dropperful) .. Take
2 ml or 2 dropperfuls = 46mg , place it in 30ml water and you get a
dilution of 1.53 mg /ml. There 20 drops to a ml in a medicine
dropper, so 1.53 mg divided by 20 = .075 mg which is 75 microgram- we
only want 60mcg, so let's go back to the 2 dropperfuls X 60mcg/75mcg =
1.6 dropperful in 30 ml medicinal dropper bottle and qs to 30ml which
now gives the 60mcg per DROP!
In short, 1.6 ml of fish-store MB in 28.4 ml of distilled water, at 20 drops to the ml, one drop gives a 60 mcg dose. Or use Perrier. Whatever floats your boat.
To be precise one can buy measuring equipment, including tenths-of-a-milliliter accurate pipettes in a drug store, the section with medicine dispensers.
Explained More: Get a eye dropper from CVS like they are like 2 dollars. Fill up 30 ml of water which is about 1/8 of a cup and keep it to the side. With a ~2% concentration MB, (1 eye dropper full is about 20 drops...there is 20 drops to a mL in standard eye droppers). Put 2 dropperfuls (which is 2 mL...which is 40 drops) of 2% MB into the 30mL of water already prepared in a cup. Create another 1/8 cup (30mL) of water without MB and put it to the side. Take ~36 drops from the previous mixture of MB and water, and then transfer that to the new 30mL of water. Then you have about 60 micrograms per drop when taken from the new mixture."The appeal of MB for me is that it appears to be very safe at very low doses, it's effective for many that have given anecdotal reports, it has some good research coming out, it may increase physical energy along with mental energy(for me they always go hand in hand), and I desperately need a boost in cognitive function.
Morgan
poster:morgan miller
thread:994620
URL: http://www.dr-bob.org/babble/20110914/msgs/997219.html