Methylene Blue (MB) is a brain-penetrating drug with putative neuroprotective, antioxidant and metabolic enhancing effects. In vitro studies suggest that MB enhances mitochondrial complexes activity. However, no study has directly assessed the metabolic effects of MB in the human brain. We used in vivo neuroimaging to measure the effect of MB on cerebral blood flow (CBF) and brain metabolism in humans and in rats. Two doses of MB (0.5 and 1 mg/kg in humans; 2 and 4 mg/kg in rats; iv) induced reductions in global cerebral blood flow (CBF) in humans (F (1.74, 12.17)5.82, p = 0.02) and rats (F (1,5)26.04, p = 0.0038). Human cerebral metabolic rate of oxygen (CMRO 2) was also significantly reduced (F (1.26, 8.84)8.01, p = 0.016), as was the rat cerebral metabolic rate of glucose (CMRglu) (t = 2.6 (16) p = 0.018). This was contrary to our hypothesis that MB will increase CBF and energy metrics. Nevertheless, our results were reproducible across species and dose dependent. One possible explanation is that the concentrations used, although clinically relevant, reflect MB's hormetic effects, i.e., higher concentrations produce inhibitory rather than augmentation effects on metabolism. Additionally, here we used healthy volunteers and healthy rats with normal cerebral metabolism where MB's ability to enhance cerebral metabolism might be limited.

Original languageEnglish
Pages (from-to)95-105
Number of pages11
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Issue number2_suppl
Early online date21 Feb 2023
Publication statusPublished - Nov 2023


Dive into the research topics of 'The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats'. Together they form a unique fingerprint.

Cite this