Methylene Blue as a Nootropic at nanogram doses
  • I recently became intrigued by reports of methylene blue being used as a nootropic and possible life extension drug. I will summarize these reports soon; for now here are links to extremely lengthy threads on experiences, dosing, research, and MAO inhibition.

    The short version is that methylene blue appears to be extremely safe at doses up to 600mg, has been used to treat malaria at ~200mgs for a century, and seems to have nootropic effects at the microgram to low milligram dose range, at which is acts as a powerful enhancer of mitochrondrial metabolism and is also a potent antioxidant. Methylene blue is a reversible MAOI at mg-level doses, but the consensus is that there should be minimal MAOI activity at microgram doses, and some users have tried it in conjunction with SSRIs without ill effect.

    I bought a bottle of MB in 1% solution, which is 1 gram per 100mL. A couple of users had reported strong effects at doses as low as 1mcg, so I decided that was where I would start. However, I got my math wrong, and ended up dosing just 50-100 nanograms! Regardless, I experienced strong effects!

    First, my method of dilution: At 1 gram per 100mL, my solution was 10mg/mL to start with, or 500mcg per drop. I diluted a single drop of this into 50mL of water, yielding a 10mcg/mL solution. I then diluted 1mL of this intermediary solution with 9mL of water, yielding a 1mcg/mL solution, which I erroneously labeled 1mcg/drop and treated as such. I administered 1 drop of this solution sublingually every 3-4 hours for 3 days. I noted the following effects:
    • increased heart rate
    • an energized feeling
    • an unusual 'fuzzy' sensation in the head and extremities
    • clearheadedness
    • increased feelings of interest
    • increased productivity
    • improved mood
    • increased enthusiasm
    • decrease in stress response
    • improved ease of getting out of bed upon waking
    • increased vividness of internal imagery and auditory representations
    • slightly decreased social inhibition
    • increased social comfort and confidence
    • increased verbal fluidity
    • slightly improved ability to attend to multiple stimuli
    • marked improvement in ability to perceive and respond to social cues in real time (decrease in after-the-fact rumination about what I 'should have said')
    • substantially increased appetite/frequent hunger and thirst
    • mild GI upset
    • substantially greater sensitivity to alcohol hangovers

    My perceived increase in metabolism (hunger, energy) was accompanied by spontaneous weight loss, approx. 1.5 pounds over 3 days, from 161lbs to 159.5.

    One of the most unusual qualities of MB at this dosage that I noticed was a 'buzzy' feeling which was similar in nature to the feeling induced by very low doses of serotonergic hallucinogens.

    I also experienced a rebound effect after discontinuing MB. I actually felt kind of sick, lightheaded and with poor appetite, for the whole next day after concluding the experiment. There have been some viruses going around, and I could have picked one up (I typically don't get all the way sick, because I take 100mg of lactoferrin 2x daily as soon as I feel anything coming on.) The second day after discontinuation, today, I feel back to normal. Only one other user of methylene blue has reported hangover effects as far as I'm aware, and he was taking 1-4mg daily for several weeks at a time. This could be a fluke; I'm not sure.

    Upon discovering that I'd been dosing much lower than I believed, I did some searching to see if any drugs were known to be active at such tiny doses. I came  across this curious paper on the effects of ultra low (ng) doses of morphine, naloxone, and ethanol on state-dependent memory:

    The researchers found that both naloxone and ethanol produced opposite effects at nanogram doses compared to milligram doses. They conclude:
    A review of the literature indicates that, for several drugs and chemicals, the effects of nanogram doses are the opposite of the effects of milligrams, because different doses have different sites as well as mechanisms of actions. In conclusion, from the above results one may suggest that, in determination of the dose-response of at least some drugs, the study of the effects of doses much lower than two orders of magnitude of the minimum effective dose are warranted.

    In reading over the experiences posted here by users of MB at 50-120mcg, I noticed that relaxation and even somnolence was a common, whereas I experienced activation at 50-100mcg.

    I'm going to try MB at 50mcg next. I'd love to see some other people try it at 50 nanograms, to see if their experiences are similar to mine.
  • After writing this I decided to try another brand of MB, in case the one I had contained some kind of impurity that might be causing me problems like the hangover effect. Most of the folks on Longecity are using this one, which is made for treating tropical fish, so that's what I went with.

    I mixed some up at the originally intended dose of 50mcg/drop, and tested it a number of times at 50-150mcg/day. At this dose, and with this product, I found the effects to be less powerful but more pleasant. I didn't take as detailed notes as before, but I did notice increased general energy and mental activity, without as much of a hangover effect and with no apparent interaction with alcohol. It's been a little while, but I may get back to testing this at some point in the future.

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  • dbot February 2013