Countless people spend money on products to pass a urine drug test for cannabis. They don’t know that whether they will pass is already written in their DNA.
I recently covered a scientific study on how your genes affect your sensitivity to cannabis. It explained how a variant at a specific place in your DNA can increase how easily you get high. But it gets even better for these lucky bastards…they are also much less likely to fail a drug test for cannabis!
THC metabolism by CYP2C9
Here is a quick primer in case you didn’t read the previous article on your genes and cannabis.
Below is the main metabolic pathway of THC. THC is metabolized to the psychoactive metabolite 11-OH-THC. 11-OH-THC is further metabolized to the inactive metabolite THC-COOH, which is the most important metabolite for urine drug tests.
This metabolism is performed by an enzyme called CYP2C9. The gene for CYP2C9 has more than 50 genetic polymorphisms. The wild-type version (i.e. the most common version) of the gene is called CYP2C9*1. There is a specific polymorphism that has significance for drug metabolism called CYP2C9*3. The CYP2C9*3 variant has significantly decreased enzyme activity.
A clinical study determined that after administering a single oral dose of THC, people with the *3/*3 genotype had 3-fold higher THC levels in their blood than subjects with the *1/*1 genotype.
Effect of CYP2C9*3 on THC-COOH
The CYP2C9*3 polymorphism does not only affect levels of THC in your body. If you look at the above metabolic pathway, you can see that it should also have a strong impact on levels of THC-COOH. In fact, study subjects with the *3/*3 genotype had 3-fold lower THC-COOH levels.
Where does all the THC go in people with a CYP2C9*3 genotype if not down the pathway to THC-COOH? There are other metabolic pathways (that I didn’t show) that produce other metabolites. These metabolites mostly do not get excreted into the urine and even if they do, they are not detected by confirmatory drug tests (see here for the difference between a screening and confirmatory drug test).
Having a CYP2C9*3 genotype may be even better than you realize if you are a regular cannabis user. Because levels of THC are higher with the CYP2C9*3 genotype (if you are taking edibles) and the high lasts longer (if you are smoking), that means that you can eat lower doses and smoke cannabis less often than people with the regular wild-type CYP2C9 gene and still be just as high.
This plot above shows the relative levels of THC-COOH if people of different genotypes adjust their doses to get the same amount of combined THC and 11-OH-THC as wild-type users. This analysis shows that if you have the CYP2C9 *3/*3 genotype, your THC-COOH levels will be only 15% of a wild-type person! This is because you only need to take half the dose and your body will only produce one third as much THC-COOH from that dose.
Urine drug testing for cannabis and CYP2C9 pharmacogenetics
Let’s take a look at how this might play out if you have a drug test coming up. I pulled data from a study of cannabis users who start abstaining and have their urine tested on a daily basis. The group I looked at smoked one joint per day on average.
It took 7 days for the urine THC-COOH levels of the average subject to fall below 15 ng/mL, which is the typical cutoff for the GC-MS confirmatory test.
I then plotted the expected urine THC-COOH levels of people with the CYP2C9 *3/*3 genotype based on the fact that urine levels should be directly proportional to blood levels (and thus, urine levels should also be 2/3 lower). The results show that it would only take 2 days for the average person with a CYP2C9 *3/*3 genotype to fall below the cutoff, assuming they consume an equal amount of cannabis.
Since we know that people with the CYP2C9 *3/*3 genotype have higher levels of THC, it is likely that they reduce their cannabis consumption to compensate. If these people also reduced their cannabis dose by half, their urine THC-COOH levels would fall below the cutoff in less than a single day after their last dose!If you have a CYP2C9*3 gene, you are at reduced risk of failing a drug test. You are probably ingesting less cannabis (but still getting just as high) and on top of that, less of the THC is converted to the THC-COOH metabolite that will cause a positive on a urine drug test. You, my friend, have won the genetic lottery!
I will soon cover how you can test your own genes to determine what version of the CYP2C9 enzyme you have. Sign up for the mailing list to stay up to date![Featured image: Flickr/ MIKI Yoshihito]
Last modified: June 16, 2017