CYP3A4 Induction
CYP3A4 is an enzyme found mainly in your liver. It can metabolize THC and 11-OH-THC, but a key point is that it only forms certain metabolites (2005 study, 2007 study). Specifically, it forms metabolites that are not excreted into your urine and are not detected by tests (what I call the alternate metabolic pathways). So having greater CYP3A4 activity is beneficial for THC detox.
CYP3A4 is an “inducible” enzyme. This means that it is possible to stimulate your body to make more of it. A 2013 study revealed what happens to THC metabolism when CYP3A4 was induced for 9 days with a drug called rifampicin.
CYP3A4 induction only slightly reduced average THC levels and did not change the half-life of THC, probably because of “flow-limited clearance”. This means that your liver actually metabolizes THC as fast as it can be delivered, so it is limited by liver blood flow. Making more enzyme cannot make it be cleared any faster.
However, a very large reduction was seen in 11-OH-THC levels after CYP3A4 induction. The ratio of 11-OH-THC to THC was reduced by 5.9-fold and the 11-OH-THC elimination rate was increased by 228%. This reduction can be explained by two factors:
- Reduced formation of 11-OH-THC. Even without increasing total THC clearance, a greater fraction of THC is metabolized to alternate pathways instead of 11-OH-THC.
- Increased clearance of 11-OH-THC. The total clearance of 11-OH-THC is increased, and probably a greater fraction is also metabolized to alternate pathways.
FAQ
Inducing CYP3A4 can cause interactions with other drugs or herbal supplements that are metabolized by this enzyme. It may increase the clearance of these drugs and reduce their effectiveness.
Therefore, anyone taking other drugs should consult with their physician and/or pharmacist before taking CYP3A4 inducers.
Let’s conservatively assume that there is no change in THC and the decrease in 11-OH-THC levels is proportional to the increase in the elimination rate.
When CYP3A is fully induced, urine THC metabolite levels can be reduced by 56%.
It will help the majority of people, but everyone responds differently depending on their genetics.
Some people have CYP3A4 variants with little activity, so inducing it will not help. Other people may have a weaker induction response and their enzyme levels will not increase as much.
Treatment with a CYP3A4-inducing drug will start to have an effect immediately, but it takes time for your body to produce more enzyme.
A detectable increase in CYP3A4 activity can occur within 2 days, but the maximum effect is not reached until 1 to 2 weeks of treatment.
CYP3A4 levels remain induced even after you stop taking the inducer.
After maximum induction, it can take up to 2 weeks for CYP3A4 activity to return to their baseline levels.
The time to return to baseline may be less if CYP3A4 was only partially induced.