How is CBD Metabolized? A Fact-Checked Guide [2023 Update]

Hemp extract contains over 421 substances spread across 18 different classes of chemicals. Nearly all of these chemicals have to be metabolized to be utilized and excreted by the body.  In this article, we’re going to explain how CBD is metabolized by the human body and what kind of interactions it has with other metabolites.

 

What is Metabolism?

Metabolism is the process by which your body breaks down various compounds that it is exposed to or that you ingest. It’s how you convert food into nutrients or take complex chemicals and break them down into smaller pieces that your body can use to synthesize what it needs.

For example, your digestive tract breaks down food into energy and nutrients, so your metabolism is a crucial part of your physiology that takes place across your entire body. However, a huge portion of the metabolization process is conducted in the liver.

When any supplement reaches the liver, it comes into contact with liver enzymes. These enzymes are the keys to unlocking specific chemical reactions. We’ll explain later how and what enzymes are involved with CBD metabolism.

 Metabolism provides the body with all the energy it needs to perform various voluntary and involuntary actions. Your body needs this energy to breathe, circulate blood, adjust your hormone levels, for growth, and to repair any damaged cells.

 

Factors that influence your metabolism

Like most physiological systems, how your metabolism functions varies considerably from individual to individual. Factors that affect metabolism include:

●     Age

• Your age affects the overall speed of your metabolism. Generally speaking, the older you are, the slower your metabolism will function.
• Muscle loss and the aging of internal organs are the primary factors contributing to the slowdown in metabolism.

●     Body Size

• Body size also affects metabolic rate. In most animals that regulate temperature with body heat, the smaller the body, the faster the base metabolic rate.
• Some of this is due to smaller bodies losing heat faster than larger ones.

●     Genetic Differences

• Like most physiological processes - an individual's metabolism is greatly affected by their genetics. Someone might be able to easily metabolize certain compounds because their genes make them produce certain enzymes more efficiently.
• A similar individual without these genes might metabolize certain compounds much more slowly.

●     Medications

• Various medications and supplements can speed up or slow down metabolism. For example, one of the most well-known ones -caffeine can speed up your metabolism.
• Some supplements slow down your metabolism - Beta blockers, corticosteroids, and various others can all have this effect.

●     Sex

• If you’re male or female, then this also affects your overall metabolic rate. Differences in testosterone and estrogen and differences in muscle mass mean that males usually have faster metabolisms than females.

●     Underlying health conditions

• Various health conditions can impact metabolism. Some of these include type I and type II diabetes, gout, and hypoglycemia.

When metabolizing any supplement, the body goes through two distinct processes or phases - which are outlined below.

Phase I Metabolism (CYP450)

The first step in metabolizing any foreign substance can involve several steps - oxidation, reduction, hydrolysis, and cyclization:

• Oxidation - adding oxygen to a compound and/or loss of electrons.
• Reduction - removal of oxygen and/or gaining electrons.
• Hydrolysis - breaking molecules apart by reactions with water.
• Cyclization - reactions that convert open chain compounds to close chained compounds.

All of these reactions rely upon a specific group of enzymes primarily located in the liver, which are collectively known as the cytochrome P450 monooxidase system or CYP450.

Phase II Metabolism (Conjugation)

The second phase of metabolism involves a process known as conjugation. This process adds another functional group to the metabolites formed during phase I. When referring specifically to cannabinoids, glucuronic acid is the primary conjugation species used.

Conjugation is important because it allows the body to neutralize or deactivate certain compounds, and it also increases both water solubility and renal clearance. This helps the body to eliminate substances through the kidneys, the feces, or both.

How is CBD Metabolized by My Body?

After being administered orally in the form of gummies, capsules, or mints, cannabidiol (CBD) is primarily metabolized by the cytochrome P450 enzymes, specifically CYP2C19 and CYP3A4. The vast majority of this process happens in the liver, but a small amount also occurs in the gut.

After CBD enters the body, it’s converted into many metabolites as the body breaks down the compound. Some of the major metabolites include 7-OH-CBD and 7-COOH-CBD.

Phase I metabolism of CBD primarily involves the CYP3A4, CYP2C19, and CYP2D6 enzymes, and the vast majority of phase II metabolism is carried out by the UDP-glucuronosyltransferases UGT1A9 and UGT2B7.

Your body excretes most CBD and metabolites through the kidneys. However, further metabolism occurs from subsequent fecal and urinary excretion of additional metabolites.

There have been some scientific studies into the impact of CBD and inhibition of THC metabolism. However, it’s currently believed that the pharmacokinetics of THC are not meaningfully affected by CBD. THC is a psychoactive compound.

There is also strong evidence that CBD doesn’t convert to THC in the GI tract. However, CBD metabolism is similar to that of THC, with primary hydroxylation to 7-hydroxy cannabidiol (7-OH-CBD), the major pharmacologically active metabolite which is further converted to the inactive metabolite 7-COOH-CBD.

What is the First-Pass Effect?

The first pass effect is a phenomenon that occurs when CBD is administered orally - whether that’s via capsules, edibles, or gummies. Once ingested, the CBD will move to the GI tract and then to the liver, where it will be metabolized. Once the CBD leaves the liver it will enter the bloodstream, which then distributes the CBD’s metabolites and various parent compounds throughout the body.

The first-pass effect influences the overall concentration of CBD and its metabolites in the bloodstream, especially when compared to other methods of administration. There is evidence showing that lymphatic absorption of lipophilic compounds like CBD (substances that combine or dissolve in fats), increases overall absorption and bypasses the liver.

Inhaling CBD causes it to enter the bloodstream immediately through the lungs. This means that the same dose of CBD taken in different ways can produce diverse effects. The composition of the oral CBD also alters how absorbable/bioavailable it is for the body. For example, oil-based is much harder for the body to absorb than water-soluble CBD.

Effects of Eating vs. Fasting on Oral Intake of CBD

Taking any substance with food vs on an empty stomach can drastically affect its overall absorption in the human body. When CBD is ingested on an empty stomach, overall absorption into the blood is markedly reduced.

CBD has up to four times greater absorption after ingestion of a fatty meal, so eating before administering CBD will improve the absorption across your whole body.

What is CBD Pharmacokinetics?

Pharmacokinetics is how your body processes a supplement - how a substance moves into, through, and out of the human body, and the entire time course of its absorption, its bioavailability, distribution, metabolism, and excretion.

Learning about Pharmacokinetics is essential for understanding the onset, magnitude, and duration of CBD’s pharmacologic effects - which allows you to maximize the benefits and minimize potential side effects.

Pharmacokinetics also includes how CBD is absorbed by the body and metabolized by the liver and other tissues. Another term for absorption is bioavailability - which simply means how much of a given substance can be processed and used by the body. The greater the bioavailability of a compound, the more efficiently your body can process and use it.

The overall absorption factor for CBD is greatly affected by the delivery mechanism of the substance - CBD is naturally oil-based, which makes it more difficult for your body to absorb and benefit from. NextEvo’s Smartsorb technology counteracts this by converting CBD into a water-soluble format.

• Smartsorb has some key benefits over other CBD products - it gets into your system in as little as 10 minutes.
• Allows a greater amount of CBD to be delivered to your body, vs. other brands where 90% is destroyed by the digestive process.
• One capsule of Smartsorb is equivalent to 4x the amount of CBD in oil-based formulations.

Can CBD Interact With Other Medications?

Cannabinoids such as CBD can interact with other medications because they can compete for the same metabolic pathways that those medications use. When two or more compounds require the same enzymes to be metabolized, they’re both forced to wait in the same slot - when the enzymes are available the compounds will then be processed.

Your metabolism and liver can only process so much at a given time - this means that if a metabolic pathway is having to process multiple competing compounds, it will slow down the metabolic processes involved.

What are Some Moderate Risk Interactions with CBD?

The below list of medications are less likely to interact with cannabinoids, even with daily use. However, caution is advised when taking any prescription medicine alongside cannabinoids.

Always talk to your doctor when using CBD in combination with prescription medication.

• Amlodipine besylate
• Bulsafin
• Carbamazepine
• Citalopram (Celexa)
• Desipramine
• Valsartan (Diovan)
• Lisinopril
• Metoprolol
• Hydrochlorothiazide
• Atorvastatin
• Melitracen
• Adderall
• Prilosec
• Propofol

In many cases, CBD in light doses has minimal interactions with drugs, but if you do take other medications, it’s important to double-check for any risk interactions.

What is the Half-Life of CBD?

The half-life of a substance is the time that it takes for the body to reduce its concentration by half. Many factors can affect this, how frequently someone uses a substance and the quantity of the substance can both increase or decrease the half-life respectively.

• The half-life of CBD is around 1 - 2 days for infrequent users and up to 5 days for heavy users.
• A heavy user is classified as someone who takes 10 mg of CBD per day for at least 2 weeks straight.
• CBD remains longer in people who take it daily compared to those who use it occasionally.

 Summary

Substances that can be classified as cannabinoids all follow the same metabolic pathway - once administered, they are mostly metabolized in the liver. The enzymes that are collectively referred to as CYP450 complex breaks down each cannabinoid into further metabolites.

The CBD is converted into 7-OH-CBD, then 7-COOH-CBD, and then into even smaller conjugates that can be much more easily filtered and eliminated by the kidneys and bile.

Understanding how CBD is metabolized is key to determining the most effective doses for you, and it’s also helpful in spotting any negative interactions with other medications.

CBD metabolism is a quickly growing area of study - but there are still many unknowns to discover. One thing for sure is that CBD is increasingly growing in popularity, and more scientific research is needed before all the intricacies are known.