So its generally accepted around the forum that the advisable dose to take Methylene Blue for cognitive enhancement is 60 micrograms. Is there any logic behind this?
The suggested dose from the data I'm aware of is 0.16-0.64 mg/kg, mainly because;
- That is the human equivalent dose (H.E.D.) for 1-4 mg/kg that has been repeatedly tested in healthy rats for cognitive enhancement. [1][2][3][4][5] (divide by 6.2 to get the H.E.D. from rat data - see attachments)
- The proposed mechanisms behind cognitive enhancement (improved mitochondrial function through increased cytochrome C, redox activity) are again active around 1-5 mg in rats [4]
- And the human Alzheimer's trials also use a similar dose, although they would take it three times daily instead of once daily, and admittedly at the higher end of the range. They're trying to treat a very aggressive disease, not trying to optimize a healthy brain. [see attachments]
So whats up with the practically homeopathic dosing going on around here? People have literally been taking less that 1% of what seems to be needed to have positive effects.
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 1-10 mg/kg methylene blue-treated rats were not different from saline-treated rats in locomotion or feeding behavior. The 50-100 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.
Methylene blue (MB) is a metabolic enhancer that has been demonstrated to improve memory retention when given post-training in low doses in a variety of tasks in rats, including inhibitory avoidance, spatial memory (in both normal and metabolically-impaired subjects), object recognition, and habituation to a familiar environment. MB has been also shown to improve memory retention of extinction of fear conditioning in the rat. No experiments have been conducted to determine the effects of MB on more complex learning such as in discrimination tasks that require repeated days of training. This study examined the effects of daily MB on spatial discrimination memory in a baited holeboard maze. Following three days of discrimination training, subjects treated daily with post-training MB (1 mg/kg) reliably discriminated between rewarded (baited) and non-rewarded (unbaited) trials as indicated by a greater number of correct responses on rewarded trials than non-rewarded trials during the last three days of discrimination training. No such discrimination effects were observed in the saline-treated control group during the same training period. To determine whether the memory-enhancing effects of MB are associated with an increase in metabolic energy capacity in the brain, cytochrome c oxidation was measured in brains from rats treated with 1 mg/kg MB or saline for three days. The number of daily injections was chosen based on the behavioral data which revealed group differences three days after the beginning of MB treatment. Brain cytochrome oxidase activity in the MB-treated group was approximately 70% higher than in saline-treated rats. The findings suggest that repeated post-training MB may improve memory consolidation between days of learning by an induction in the enzyme cytochrome oxidase, leading to increased metabolic capacity in brain regions requiring more energy during discrimination learning.
Attached Files
Edited by Bateau, 18 August 2014 - 08:17 PM.