Comment · Wed, August 6, 2025 · ND Owner
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NDSocialMedia · 74 points
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ArcticPlatypus · 4 points
Oh that is amazing to hear that it is the highest macamide contained in the extract! The paper didn’t seem to clarify if it was a trace macamide or one of the dominant macamides in the root. I personally love this maca extract, been taking 1 capsule daily since it was released and I believe it’s genuinely provided a nice basal level of endo-cannabinoid action (improved libido especially at first, overall better mood in general). I’m curious to try mega-dosing at some point to see if I can achieve some noticeable CB1 activity.. if you know what I mean.
Does your team use any calculations to estimate serum concentrations of molecules in the extracts? I honestly need to take more time to learn how to make these estimations but it’ll be a lot of learning. I was recently estimating for the molecule Harmine, not for its MAO-A effects but more for its DYRK1-A inhibition effects which occur at higher concentrations. And ended up coming across a study where they used a dose of a brew containing 250 mg Harmine, and measured a serum concentration of 500 nM (0.5 micro molar) at its peak level. I know all molecules have different bioavailability and even reach different tissues in different quantities, so incredibly complicated to predict. But for the sake of simple comparison, what if we needed over 200 mg of “macamide C” to reach the IC50 for some of these effects we are seeking? With…
u/MisterYouAreSoDumb · ND Owner
Does your team use any calculations to estimate serum concentrations of molecules in the extracts?
We do use ADME to estimate pharmacokinetics and inform our formulations. It can help get a picture of things, but it is only an estimate based on the available data.
I know all molecules have different bioavailability and even reach different tissues in different quantities, so incredibly complicated to predict. But for the sake of simple comparison, what if we needed over 200 mg of “macamide C” to reach the IC50 for some of these effects we are seeking? With about 6.7 mg of this macamide C per 200 mg capsule, some rough math shows about 30 capsules would yield 200 mg of the compound. I know your team probably cannot condone taking such a megadose, but do you think these numbers are even in a reasonable ballpark? Or maybe much less is required.
Here is the target prediction for macamide C
It's interesting to see what the software predicts for receptor binding.
Here is the ADME for macamide C
You can see it is GI permeable, but it is low. That's because its LogP is a bit too high, and the length of the molecule itself. However, it is a fatty acid. Fatty acids have active transport. This cannot be accurately predicted by ADME. This is just looking at what the passive transport would look like based on the molecule. So we know it can passively, albeit in a low fashion, absorb in the GI tract. We also know it is a fatty acid that most likely will be picked up by the active transporters in the GI tract. This leads me to assume it has reasonably good bioavailability. However, I can't give you a real estimate of dosage to reach specific plasma levels without an actual pharmacokinetic study. There are just too many variables.