CBD and Medication: What are Cytochrome P450 Enzymes?

CBD Drug Interactions: The Role of Cytochrome P450 Enzymes

Ever wondered why different people react to certain drugs differently?

Some people will experience extreme side effects with a very common over the counter painkiller while others will experience virtually nothing thus requiring something more potent.

This is caused by genetic variability in the P450 enzymatic structure.

The cytochrome P450 enzyme class is named from the mechanism of binding, heme pigment, and light absorbance.

With more than 50 enzymes in the class, at least six metabolize about 85% of the common prescription meds on the market.

These enzymes are most prominent in your liver where most of the metabolization of medication happens. However, they are also present in your small intestine, placenta, and kidney.


P450 enzymes are not only paramount to the metabolism of medications but also for other important functions. For example, P450 enzymes are essential to the production of cholesterol and steroids.

They also help rid your body of toxins, which is done by one of two processes.

The first being the contribution of an element to the toxin to make it more potent thus fade out quickly. The other is to break down the toxin into sub-elements that are easier for your body to take in.

The first process is true for alcohol and THC from cannabis.

Factors Determining Extent of Inhibition

The P450 enzymes contribute to metabolism of drugs by oxidation. This works to make the drug more water-soluble, as this form is the easiest for your kidney to filter.

Your cytochrome system can be enhanced or inhibited by certain chemicals, CBD is one of those chemicals.

Cannabidiol (CBD) works to displace other competitors on the field thus preventing metabolism of other compounds.

The extent of this depends on several factors, the first being the dosage of CBD administered. A low dosage has been found to have no effect on cytochrome P450 action.

In 2013, a report on Sativex clinical trial indicated that there was no interaction with CYP450 at 40 mg of sublingual spray.

However, 25 mg of orally administered CBD was found to block the metabolism of a drug. This report also demonstrates the second factor, which is method of CBD consumption.

A study in 1993 demonstrated effects on the other side of the spectrum at 120 mg of CBD.

It was found to inhibit a significant amount of action for two specific enzymes: 2C and 3A. 2C was especially sensitive to CBD inhibitory effects even at lower doses.   

It also matters if CBD isolate was used or if whole plant (full-spectrum) CBD therapy was applied.

These factors affect how CBD binds to the cytochrome before and after oxidation. The ability of CBD to combat the psychoactive effects of THC is attributed to this process.

Animal studies have shown that pretreatment of the brain with CBD slows down conversion of THC into the potent version of the element.

The same process is responsible for the efficacy of CBD to treat hangovers.

Application of The CBD – P450 Relationship

Cancer Treatment

How P450 enzymes effect the treatment of cancer with CBD

One of the biggest issues in cancer treatment, especially in the later stages, is being able to achieve the highest possible dose of chemotherapy without inducing toxicity.

By reducing enzymatic degradation of the chemo, duration of action is increased and so is positive effect.

With this in mind, if the current dosage of chemo is not working for a patient and there is need to adjust it up. 

Instead of inching closer to the chemotherapeutic toxicity threshold, how about using CBD instead? The same dosage will be far more effective when combined with cannabidiol.

There is a chance for some traces of toxicity from prolonged treatment. CBD has been found to have cyto-protective properties that would combat this problem.

Epilepsy Treatment

How treating epilepsy with CBD is effected by P450 enzymes

A study at Massachusetts General Hospital was published in 2015. Where a number of epileptic children were involved to look in to the effects of CBD in treatment of epilepsy.

It was found that CBD elevated the plasma levels in the children. Thus, the long-term blood concentration of the anticonvulsant and its respective metabolite were increased.

The children suffered side effects similar to those of overdosing on the drug so the doctors adjusted the dosages down.

The drug was still effective at the lower dosage and the side effects stopped. This is to say that through the same process as above, the drug was able to stay in the blood for a lot longer than it had before the use of CBD.

This allows your body to benefit from the prolonged exposure.

There have been reports of CBD causing an increase in seizures, which is contrary to the above info.

There are explanations for this of course. A low dosage of CBD will surely inhibit enzymatic degradation. However, the dosage would be too small for the anti-convulsant properties to be enjoyed.

To combat this problem, it is recommended that the dosage of CBD be increased by a little bit and/or a change of consumption method.

It is also advisable to include a little bit of the non-psychoactive form of THC, THCA.

CBD Induces P450 Enzymes (Contrary Action)

CBD has also been found to have the capability to induce P450 enzymes. This means that instead of slowing down metabolism of drugs, it would enhance the process.

The effects could be adverse.

There is also a possibility that the drug prescribed is not among the 85% outlined for P450 enzymatic action.

In this case, you might experience some side effects of contraindication. Most of the common signs of this would be excessive sedation, slowed speech, lower motor function, and adverse effect on cognition.

Just like the inhibitory properties, the increase in enzyme synthesis would be brought about by different factors with genetic variability right at the top.

This paired with dosage and the type of drug involved make for a good explanation for this turn around.

All in all, before using CBD with prescribed medication, you must do your due diligence which includes talking to your physician.

By understanding the mechanism of action, potential harm is avoided!

Understand Mechanism of Action

Does the P450 Enzyme Metabolize the Drug?

Remember, P450 enzymes metabolize less than 90% of the marketed drugs. This means that there is still a good number that are not subjected to the oxidation process.

It would therefore not be relevant if one’s genetic makeup leads to P450 induction or inhibition. However, if it does there is a need to wonder.

How Does CBD Interact with Said Drug?

If the CYP class does not metabolize the drug, then how else could CBD affect the efficacy of the drug?

If it is, will the CBD inhibit or induce the enzyme action? What effect will this action have on the efficacy and function of the drug?

It’s important that you talk with your doctor to get the answers to these questions before you begin the use of CBD!

Signs of Pharmaceutical Toxicity

You should know what signs to look for to indicate toxicity.

Toxicity is usually brought about by excess consumption of the drug and its corresponding metabolite in your blood.

The drug will usually have some side effects printed on the package literature. Read through this and find out what to expect if things go the negative way and bring about such a problem.

Your physician should also educate you on the signs of toxicity and what to do to mitigate them.

Regular Monitoring

In the epilepsy trial involving children, doctors would not have known that there was a need to adjust the dosage if they had not been monitoring the children closely.

It is possible to test for proper function of the cytochrome system.

This should be done as often as the physician advises. Tests should also be done to check for levels of toxins from the drug in the blood.

CBD is Friendly Either Way

In some cases, you might be faced with a choice between CBD and the prescribed therapy.

In this case, the decision lies with you and your physician. You should rest easy in the assurance that even if the dosage prescribed is way too low, CBD will fill out the rest of the need. CBD is indicated for most of the illnesses anyway.


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