25C-NBOMe Induces Neurotoxicity 50 Times More Potent Than Methamphetamine

[Pfafffed]

Not able to evaluate the quality of the study

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[tryp2fun]

I can evaluate this study. The IC50 values for 25C-NBOMe with various neuronal cells lines is 62-89 uM. A simple back of the envelope calculation, assuming an 80 kg male with 6 liters of blood volume gives the amount needed to reach 62 uM in the blood. This ignores metabolism, which is actually pretty fast for this compound. 372.3 g/mol (HCl salt of 25C) x 6.2x10^-5 mol/liter x 6 liters = 0.138 g or 138 mg! This is about 500 times higher than an effective dose of 25C. If you took that much, I don't think that you would have to worry about neural toxicity! This is not to say that 25C is safe, just that this is not the reason that it is dangerous. The problem with the NBOMe compounds seems to be that they are too selective for 5HT-2a receptors. Safer psychedelic compounds are active on both 5HT-2a and 5HT-2c receptors, which oppose one another (https://www.ncbi.nlm.nih.gov/pubmed/19322172).

 

[heatlessbbq]

DANGEROUS

 

[Pfafffed]

I can evaluate this study.

Thank you for that!

 

[Hodor]

The problem with the NBOMe compounds seems to be that they are too selective for 5HT-2a receptors. Safer psychedelic compounds are active on both 5HT-2a and 5HT-2c receptors, which oppose one another (https://www.ncbi.nlm.nih.gov/pubmed/19322172).

From what I understand, the issue is that NBOMe's somehow activate 5HT2a in such a way ("functional selectivity") as to cause different downstream effects when compared to other psychedelics.

Apparently, one of 5HT2a's effector pathways results in the release of Thromboxane A2, which is responsible for the aggregration of blood platelets. Forming miniature blood clots is already problematic, but when you combine it with the massive vasoconstriction caused by a psychedelic, you've got a recipe for life-threatening ischemia.

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