I am often asked about the combination of drugs with cannabis. It is important to understand that there is a difference between the methods of consumption. Once we swallow the oil it comes through the digestive tract to the liver, where it is broken down by enzymes. People react differently to cannabis. A small dose in one person will have a different effect than that of another.
A fundamental and important thing is the genetic difference between people in terms of enzymes.
For example, there is a difference between 6 people taking a single dose of THC orally. Some had no change, and some had a high jump on the THC level.
A family of enzymes that decompose cannabinoids is called cytochrome P450 (CYP).
When cannabis is consumed in ingestion or ingestion, so-called edibles, this enzyme system will also have an effect on both the duration of the effect of cannabis and the intensity of the effect.
The duration of the effect is determined by the time the materials are removed from the system.
The intensity of the effect depends on the metabolism before the substance reaches the bloodstream.
Both CBD and THC depend on the enzyme CYP3A4 for their breakdown.
This information is also supported by laboratory research ,  and clinical research .
To understand how important the activity of the CYP3A4 enzyme is, look at the graph below:
The ketoconazole (a CYP3A4 inhibitor) was given to the participants prior to the consumption of stevex (a product given in spray for multiple sclerosis patients based on cannabis based on an equal ratio of THC: CBD)
What happened was that the level of THC and plasma plasma increased by 80%!
On the other hand, note that the level of THC metabolite, 11-OH-THC, increased 350% !!!
This is very significant since the psychoactive activity of the metabolite, 11-OH-THC, is much stronger than the THC itself, when the cannabis containing THC is ingested.
What is really important to understand is that enzyme activity CYP3A4 is highly dependent on your genetics.
There is a very big difference between people. Between 10 and 100 times between one and the other, under the influence of cannabis.
In 2011 found a genetic mutation * 22 (rs35599367> C> T). The allele is * 22, with significantly lower activity. Statistically one out of every 17 white people has the gene, and drug clearance by CYP3A4 is slower in 30-40%
Now do you understand why they say to start with a little and go up slowly?
Most people should be careful about the amount of cannabinoids they consume because studies show that the genetic mutation can be found in them.
for further reading: