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Cannabis and Genes

How Your Genes Affect Your Response To Cannabis Part II

There was such much to explain about your DNA and cannabis that I divided it into 2 posts. Here is the link to the first one. I am going to dive right into the cannabis research.

Cannabis Studies 

Cannabis researchers decided to test if and how any SNPs in the CYP2C9 gene affect the way humans metabolize THC. Here’s what the studies showed:

A 2005 study which appeared in Biochem Pharmacol found that CYP2C9*3 version, produced by C allele carriers, metabolized 30% less THC than the CYP2C9*1 version, produced by A allele carriers. The study used enzymes in a petri dish rather than human subjects. The next step would be to use human subjects to try and replicate the results of the laboratory study. The $64,000 question is will it have a similar effect on human subjects?

A 2009 clinical study published in Clin Pharmacol Ther addressed that question by using 43 human volunteers. They were given 15 mg of oral THC and their levels of THC, 11-OH-THC and THC-COOH were measured. Their verbal response to how THC affected them was also recorded.

The results indicate that for each C allele variation, there is a reduction in the effectiveness of the CYP2C9 gene in breaking down THC. CC carriers had 3 times more active THC in their system than AA carriers. AC carriers had 2 times the THC of AA carriers.

Summary of the different variants and their effects:

  • AA is the most efficient variant in its ability to break down THC most completely and quickly. It causes the least amount of drowsiness. You get less high from edibles and from smoking. The effects of edibles last a shorter amount of time.
  • AC is the moderate variant where you get somewhat drowsy, moderately high from edibles and from smoking. The effects of edibles last for a longer time than AA but shorter than CC.
  • CC is the least efficient variant. It does not break down THC as efficiently as AA or AC. You experience the most amount of drowsiness. You get very high from edibles and from smoking. The effects of edibles last much longer.

In regards to drug testing, it is important to know that THC-COOH is stored in your fat which will determine how long it takes to detoxify from your system:

  • For AA carriers, the active metabolite THC-COOH remains in the urine for about 30 days.
  • For AC carriers, THC-COOH remains in the urine for somewhere between a few days and 30 days.
  • For CC carriers, because so little THC gets converted into THC-COOH at all, it only remains in the urine for a few days.

The Subjective Effects of the Study

Participants were asked to report their subjective experience over a period of 3 days.

CC carriers were drowsier and experienced a longer effect from ingesting THC. Surprisingly, these same participants still experienced more drowsiness 72 hours later than the AC and AA carriers.

Please note that in this study, cannabis edibles were used as the delivery method. There is a difference in how the CYP2C9 functions regarding smoking vs edibles.

  • With edibles, they start breaking down in the stomach, so CYP2CP is active before you feel the psychotropic effects of THC. It affects the intensity and the duration.
  • With smoking, CYP2CP does not initially affect the intensity of the psychotropic effects, but it affects the duration.

Why it is important to know which variant of CYP2CP you have:

As I mentioned in Part I, THC is just one of many substances that CYP2CP metabolizes which include substances like blood thinners and NSAIDs. If you are an AA carrier, you have a higher incidence of intestinal bleeding from ibuprofen due to poor metabolism by your CYP2CP gene.

Furthermore, this study is just the tip of the iceberg in understanding the complexities of how your unique SNPs affect the efficiency of your CYP2CP gene. It is important to understand that there are some differences among the carriers of the same variant.

More importantly, the metabolism of THC by your SNPs is only a small component of how your body reacts to cannabis. There are several other genes which affect your response to cannabis:

  • FAAH gene controls your neurological reward response to cannabis.
  • COMT gene controls impairment of short-term memory after consuming THC.
  • SLC66A gene acts with COMT in controlling executive functioning. It also affects decision making after consuming THC.
  • PENK gene affects cannabis dependence.
  • ATK1, CNR1 and ABCB1 genes impact the likelihood of negative or psychosis-like symptoms after consuming THC.

I hope you found this subject as fascinating as I did!

Source:, How Your DNA Affects Your Response To Cannabis – The CYP2C9 Gene, Dec 4, 2017.

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