The beauty of a placebo is that it doesn't matter how much you take. A microgram, a nanogram a picogram- all have fantastic results.
What makes you so sure it's a placebo effect in the microgram dosages?
There are a lot of things that point toward it. The 60 ug dose, the so-called "nootropic dose", was based on an erroneous estimate in an old post here. Someone was trying to hit a 100 nM systemic level, but that would take tens of milligrams (about a thousand times as much) from an oral dose. As it happens, MB is on the way to being approved for a couple different types of dementia, but the trial doses were 60mg three times a day. MB has some moderate MAO activity, but my recollection is that it would take 100+ mg to reach the IC50 for the most sensitive MAO subtype, orally. MB is an old drug- it's been used for over a century, with doses that have run to as much as half a gram.
MB is a very facile redox agent, and can rapidly accept or donate an electron, depending on its current oxidation state. Because of this, it exhibits nonlinear "hormetic" dose response relationships in a variety of physiological situations, as described in
this review. At first glance, this seems like an argument for activity at low concentrations, at least potentially. However, in every case studied, the concentrations with optimal effect are
wildly higher than 60mcg in a human. For example, in the review, optimal concentrations in animals, dosing either IP or IV were:
memory enhancement: 1 mg/kg
wheel running: 4 mg/kg
anxiolysis: 7.5 mg/kg
Ischemia/Reperfusion Injury: 3-20 mg/kg
in vitro experiments: 0.5 uM, which probably corresponds to multiple hundreds of mg when dosed orally in a human.
Drugs that are active at the microgram level are few and far between. In literally every biological response report that I've seen, the doses were orders of magnitude higher than 60 ug per human. On this basis, the odds of a potent nootropic effect at that dose are very low.
There are a couple other categories of observations that also play into my belief that the reported effects are placebo. First, the type of effects are mostly psychotropic, which is probably the easiest kind of effect to elicit by placebo. Second, the drug has a lot of hype behind it. Expectations are high. Third, the use of it involved brewing up an intensely colored solution and drinking it. This is a very placebogenic activity. Fourth, a lot of people from our forum have tried it, many (including myself) experimenting with a wide range of dosages. A lot of people have had experiences that they describe as incredible, and a lot of people have felt nothing. I've gotten to know a lot of these people through their posts and sometimes through PMs or personal meetings. I've noticed that the "responders" and "non-responders" are not randomly distributed. The responders TEND to be (i.e. these are NOT exclusive characterizations!) younger people with less scientific knowledge, more interest in nootropics. The non-responders TEND to be older people with more scientific knowledge who have a greater interest in health than in nootropics.
All this makes me lean strongly toward a placebo effect, though I can't rule out a drug response. If it exists, it would probably involve a terrifically subtle redox phenomenon that tends to go away with age, and perhaps experience.
