Cannabidiol, also commonly known as CBD, is one of the primary active compounds found in cannabis and hemp. In recent years, countless research studies have been carried out into the potential benefits of CBD. It is thought to be antioxidant, anti-inflammatory, and have neuroprotective effects, and may be useful in the treatment of a variety of conditions.
Although we are continually expanding our awareness regarding how CBD and other cannabinoids may benefit our bodies and minds, far less is understood about how these chemicals are processed when they are ingested.
This is a problem, since if CBD is ever to be taken seriously as a drug, it is vital that we know exactly how it works. This includes understanding how the body metabolizes CBD, and how it could interact with other medications.
In this article, we examine the current knowledge of CBD metabolism and look at why this information is essential to anyone wishing to use this popular product.
What is Metabolism?
Before we can understand how CBD is metabolized, we first need to know how metabolism works in general. Metabolism is a word which gets thrown around a lot. It is often referred to in relation to weight loss or gain, with some people claiming to have a ‘fast’ or ‘slow’ metabolism. What people are talking about here is their basal metabolic rate, or the number of calories a particular person needs to keep their body functioning while at rest.
Although it is sometimes referred to as metabolism, basal metabolic rate is quite different from the metabolism of CBD and other drugs. Here we are talking about the rate at which CBD is broken down by the body into different compounds known as metabolites.
This process happens to anything that you put into your body. For example, when you eat a meal, carbohydrates are broken down into sugars, fats into triglycerides, and proteins into amino acids. Metabolism transforms your food into substances which can actually be used by your cells, and is under the control of chemicals called enzymes.
Drugs are metabolized in a similar way, and much of this happens in the liver. The metabolism of drugs by the liver is known as the ‘first pass effect’ or ‘first pass metabolism.’
First Pass Metabolism and CBD
When you take CBD orally, either as an oil, tincture, capsules, or edibles, it has to pass through your digestive system. In the intestines, it is absorbed into your bloodstream and transported to the liver through the hepatic portal system. In your liver, CBD is broken down into its metabolites by enzymes. These metabolites are then transported to the heart, and circulated around your body in the bloodstream.
Unfortunately, first pass metabolism of CBD is quite inefficient. A large proportion of CBD and its metabolites are excreted in the urine and feces, meaning that many of their benefits are literally flushed away.
Various studies have found that a high percentage of CBD is excreted in its original form, along with many different metabolites. There are estimated to be around 100 different metabolites of CBD, but the one found in the highest concentrations is known as 7-COOH-CBD.
When CBD passes through the digestive system in this way, the amount that your body is actually able to use is reduced. This is why, although taking CBD orally is convenient, it significantly reduces what is known as the ‘bioavailability’ of the compound.
Increasing the Bioavailability of CBD
CBD products can be expensive, so to get the most for your money you will want to choose the option that provides the best bioavailability. This will ensure that your body can absorb the maximum amount of CBD and reduce the amount that is wasted.
As we know, consuming CBD orally leads to reduced bioavailability and increased wastage thanks to the first pass effect. The World Health Organization (WHO) has published figures estimating that as little as 6% of your CBD may be absorbed following oral consumption. However, capsules and edibles are the most convenient way to take your CBD, especially if you are constantly on the go.
If you prefer to take CBD this way, it is thought that you can increase its bioavailability by taking it after some food. Food containing fatty acids is thought to be particularly useful as it may help to reduce the first pass effect. Some CBD oils come premixed with olive oil or MCT oil, which should work similarly.
Another way to increase the bioavailability of CBD oil is by taking it sublingually, under the tongue. There is a high concentration of blood vessels in this area, enabling CBD to be absorbed directly into your bloodstream and bypass the digestive system. You can take advantage of this by holding your CBD oil under your tongue for 60–90 seconds before swallowing.
Smoking is another effective way to increase CBD bioavailability. When you smoke CBD, either as an e-liquid or high-CBD cannabis strain, it enters your bloodstream directly via your lungs.
Finally, you could try applying CBD topically as a cream or ointment. Although CBD cannot enter the bloodstream through the skin, it can be absorbed through the pores and act directly on cannabinoid receptors in the area. This means that topical CBD creams may be especially beneficial for localized conditions such as inflammation of a particular joint or muscle.
It is also thought that the bioavailability of CBD can be increased by combining it with another cannabinoid known as CBDA. CBDA is present in raw cannabis and changes into CBD when it is heated, a process called decarboxylation. One study tested this theory by treating nine healthy volunteers with both heated and unheated CBD extracts. The results showed that 24 hours later, CBD concentrations in the blood were twice as high after taking unheated CBD compared with the heated extract.
Could CBD Affect Other Medication?
Understanding how CBD is metabolized is important not only in terms of bioavailability, but also because it could affect the way other drugs work. Many drugs, including CBD, are broken down in the liver by an enzyme called cytochrome P450.
Because of this, if you take certain drugs together they may act as competitors for this enzyme. This means that one drug will not be metabolized as quickly as the other, and it will remain in the bloodstream for longer.
This effect was one of the first pharmacological observations of CBD, way back in 1942. Researchers noticed that when 600 mg of CBD was taken for 5 –12 days, it increased the activity of hexobarbital, a barbiturate drug which was used as an anesthetic during the 1940s and 50s. CBD was found to decrease the clearance rate of hexobarbital by 36%, and increase its bioavailability by as much as 10%.
A later study from 2015 found that similar effects were seen when combining CBD with clobazam, a common anti-epileptic drug. Ten of 13 epileptic children being treated with this drug had a significant reduction in seizures while using CBD, despite reducing their clobazam dosage throughout the study period. Interestingly, one of the metabolites of CBD has a similar structure to one of the metabolites of valproic acid, another common anti-seizure drug. However, whether this metabolite is responsible for CBD’s antiepileptic effects or not remains to be confirmed.
In some cases, increasing the bioavailability of drugs may be beneficial, but it may also increase the risk of side effects and toxicity. One example of this is the blood thinning medication warfarin which is also metabolized by cytochrome P450. Taking CBD alongside this medication has the potential to increase the risk of serious bleeds unless the dosage is strictly monitored.
Another example is certain chemotherapy drugs which could remain in the body in toxic levels if taken with high enough doses of CBD. This is why it is essential that you consult a physician before starting CBD treatment, especially if you take any other over-the-counter or prescribed medications.
How is CBD Metabolized? Final Thoughts
When taken orally, CBD passes through the digestive tract to the liver where it is metabolized by enzymes including cytochrome P450. This is known as the ‘first pass effect’ and can significantly reduce the bioavailability of CBD. It may also cause CBD to interact with any drugs taken at the same time as they compete for the attention of this enzyme.
CBD bioavailability can be increased by bypassing the digestive system using methods such as sublingual dosing, smoking, and topical application. However, there is still some risk of drug interactions, so it is always advisable to exercise caution.
If you take any other medication alongside your CBD, be sure to let your physician know so that they can monitor your dosage and reduce it if necessary. Increasing the bioavailability of your drugs could be a good thing, but if not done correctly, it could be extremely dangerous too.