Acute

Human Data

Gosselin et al. have given methylene blue a toxicity rating of 4 [Gosselin, et al., 1984]. Acute exposure to methylene blue by intravenous injection has been found to cause hypertension, sweating, chest pain, confusion, nausea, vomiting, dizziness, and cyanosis, as well as urine and stool discoloration [Arena, 1986; Gennaro, 1985].

Large, oral doses of methylene blue may cause fever [McEvoy, 1989]. Methylene blue has also been reported to cause quadriplegia after intrathecal injection [Driesbach, 1980]. Subcutaneous injection of methylene blue may cause necrotic abscesses [Reynolds and Prasad, 1989].

Methylene blue induces hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) enzyme deficiency. Dark-skinned races have a higher incidence of methylene blue-induced hemolytic anemia than lighter skinned races, but the disease has not been noted in North American Indians or Eskimos [Thienes and Haley, 1972].

Methylene blue is a severe eye irritant [Lenga, 1988]. High concentrations of methylene blue have been found to induce corneal and conjunctival injury [Grant, 1986].

People just need to be aware that one has been tested by thousands if not millions of people while the other has not.

Can you post a link to the reference?

Methylene blue might be available in pure form, but that doesn't make it safer than syrian rue or caapi. From the sounds of it, probably it is more dangerous. You can easily extract high purity harmala alkaloids, so why would you bother using a chemical that's untested for this purpose and probably more dangerous?

Methylene blue was identified by Paul Ehrlich about 1891 as a successful treatment for malaria. It disappeared as an anti-malarial during the Pacific War in the tropics, since American and Allied soldiers disliked its two prominent, but reversible side effects: turning the urine green, and the sclera (the whites of the eyes) blue.

Clinical Toxicology Sep 2010

Methylene Blue: A Strong, but Poorly-Appreciated,
MAOI
Collins C,1 Hurley W.2
1University of Washington School of Pharmacy, Seattle,
WA, USA; 2Harborview Medical Center, Seattle, WA, USA

...Conclusions: This patient demonstrated
severe Serotonin Syndrome likely due to the concomitant
use of Escitalopram and Methylene Blue. Methylene
Blue is gaining increased use in cardiac and
parathyroid surgery, but the risk of concomitant use of
serotonergic agents and Methylene Blue is not well
appreciated. Methylene Blue should be considered a
strong MAO inhibitor and patients should be screened
for the use of serotonergic agents prior to undergoing
administration of Methylene Blue.
295.

Clinical Toxicology Sep 2010

Serotonin Syndrome Precipitated by Methylene
Blue
Smith C, Marshall SW, Crouch B, Caravati EM.
Utah Poison Control Center, College of Pharmacy,
University of Utah, Salt Lake City, UT, USA

...Conclusion: Administration of high dose
methylene blue for parathyroidectomy was associated
with serotonin syndrome in patients taking serotonergic
drugs before surgery. Whether this interaction can
be expected to occur at methylene blue doses which
are used to treat methemoglobinemia (1 mg/kg)
remains to be seen but should be considered.

https://onlinelibrary.wi....1365-2044.2009.06029.x

Small doses of methylene blue, previously considered safe, can precipitate serotonin toxicity

C. Schwiebert, C. Irving, P. K. Gillman

... We would like to add to the record a case from our practice, where definite serotonin toxicity was precipitated by only 1 mg.kg−1 of methylene blue. This case involved a young female with malignant disease of the pelvis, whose regular medication included the selective serotonin re‐uptake inhibitor paroxetine. She received 1 mg.kg−1 of methylene blue intraoperatively to aid cystoscopic identification of the ureteric ostia. Following emergence from anaesthesia she exhibited confusion, agitation, aphasia, ocular clonus, mydriasis, hyperreflexia and arterial hypertension. In the presence of an selective serotonin re‐uptake inhibitor, these signs allow the clear and unambiguous diagnosis of serotonin toxicity.

This case is the first to demonstrate a clear link between definitive serotonin toxicity and an methylene blue dose of < 5 mg.kg−1. It also provides evidence that the small dose of 1 mg.kg−1 provides MAO inhibition in vivo, and risks serotonin toxicity. We suggest that drug safety advice as well as clinical use of methylene blue should be modified accordingly.