Imagine living in a world where edibles can’t get you high! Well, that’s an unfortunate reality for more people than you’d think. Between feedback from our students and plenty of comments on social media, I’ve learned that a solid amount of the population is confused about why they can get high smoking a joint but don’t feel a damn thing from a pot brownie. So what’s happening here?
It all has to do with genetics! Your genetic code controls everything about you, from what you look like, how you age, and what predispositions you may have to certain diseases, to how your liver metabolizes drug compounds. Although it is possible to alter your gene expression through lifestyle changes like exercising or being in ketosis, some elements of your physiology “are what they are.“
Your liver consists of enzymes that metabolize certain drugs. The result of drug metabolism creates metabolites from the original drug that can either become inactive, therapeutically active, or toxic. The liver’s primary mechanism for metabolizing drugs is from a group of cytochrome P-450 enzymes, and the level of these enzymes determines the rate of drug metabolism.
Certain drugs and foods can affect how P-450 enzymes metabolize drugs by slowing them down or speeding them up. Grapefruit is a significant culprit for inhibiting drug-metabolizing enzymes, which can cause severe adverse reactions and even overdose.
P-450 enzymes metabolize THC, CDB, and other cannabinoids. Depending on the expression of specific CYP2C9 gene variants, the metabolism of these cannabinoids may be why some people can or can’t get high from an edible.
Is there anything you can do to change your gene expression to get super baked on a couple of milligrams of THC? At this point, I haven’t found any cannabis-related studies on biohacking your drug-metabolizing genes, but I imagine someone will figure it out in the future!
Most of the folks I’ve chatted with who can’t get high from edibles have said they can feel a little high if they take 500+ milligrams of THC. However, the high only lasts a short time and isn’t even as intense as smoking. I have an idea why they may be feeling a little high with such a hefty dose.
When you smoke marijuana, the heat instantly decarboxylates the THCA into THC. Then your lungs, which have similar enzymes as your liver, metabolize a small amount of that THC into 11-hydroxy-THC.
When you ingest decarbed THC, your liver metabolizes more THC into 11-hydroxy-THC. The high takes a little longer to kick in, but it’s more intense because 11-hydroxy-THC is more potent at receptors than THC. What’s important to note here is that there is still THC in your system when you eat an edible, contributing to the high.
If someone can’t get high off an edible because their drug-metabolizing enzymes can’t convert THC into 11-hydroxy-THC, there is still good old THC floating through their veins. So if they took a high enough dose, they could get enough THC in their system to feel high. However, it will not feel as intense or last as long as even an inhalation high due to the low bioavailability of ingested THC.
The good thing is there is a super simple solution for those of you who can’t get high off edibles! JUST SMOKE THE WEEDS!