How Does Cannabidiol (CBD) Work?

Shanti Ryle
Shanti Ryle - Content Writer

Aug 27 2021 - 6 min read

In this article, we deep dive into how CBD, one of the best known cannabinoids (chemicals) in cannabis works. The science is a little complicated, but we hope you gain a better understanding of CBD and its uses as medicine.

Table of contents
  1. Introduction to CBD
  2. What is Cannabidiol (CBD)?
  3. How Does CBD Affect the ECS and Other Receptors
  4. Does CBD Block THC?
  5. The Entourage Effect

Introduction to CBD

“How does CBD work?” Honestly, nobody knows the precise, definitive answer yet. Should someone say to you, “I know exactly how CBD works, and it’s all you need”, ask to see the science, research and numbers, and be very suspicious.

CBD is a complex compound, as it interacts with a wide range of receptors in the human body in a variety of ways. This has made CBD particularly difficult to understand, especially when it comes to how it interacts with other cannabinoids and medications.

Download Free Guide to CBD

However, if someone says, “I might know how CBD works, here’s some research supporting what I say, and we must also take into account other cannabinoids and terpenes and how they interact with CBD,” then sit down, buy that person a coffee and talk to them.  To look at how various cannabinoids and terpenes work, check out our handy cannabinoid-terpenoid table here. If you need a definition of a scientific term, see our glossary.

Free Cannabinoid and Terpene Guide

Now, here’s where we explain the mechanics of how CBD works.

Molecular Structure - CBD
CBD molecular structure.

What is Cannabidiol (CBD)?

CBD constitutes one of at least 150 cannabinoids found in the cannabis plant. As one of cannabis’ major phytocannabinoids, CBD accounts for up to 40% of the plant’s extract. CBD has few if any intoxicating effects for most people (though some have reported mild psychoactivity) and may even dampen the effects of tetrahydrocannabinol (THC) – more on this below.

In its raw form in the plant, CBD exists as its precursor: cannabidiolic acid (CBDA). CBDA becomes CBD after aging or decarboxylation (heating).

How Does CBD Affect the ECS and Other Receptors

Knowing which receptors CBD affects (and remember, science doesn’t know precisely how, where and why CBD works yet) is key to understanding its medical uses.

5-HT1A Serotonin Receptors

CBD is a partial agonist of the 5-HT1A receptor, a serotonin receptor. Serotonin is a chemical messenger which is linked to our mood. CBD being a partial agonist means that it binds to a receptor, but only at partial efficacy compared to a full agonist. CBD’s interaction with serotonin receptors may explain its effectiveness as an antidepressant, anxiolytic and even a neuroprotective chemical.

See our pages on anxiety, depression, and PTSD to learn more about how cannabis and CBD can help with mental health and mood disorders.

TRPV1 vanilloid receptor

Research indicates that CBD has the potential to “desensitize” the TRPV1 receptor. The TRPV1 receptor helps to regulate our body temperature and is also a heat and pain sensing receptor. This interaction gives CBD its analgesic (pain-killing), antiemetic (nausea-beating), and seizure-beating properties.

μ- and σ-opioid receptor allosteric modulators

Another reason why CBD may have analgesic properties is that it is an allosteric modulator of μ- and σ-opioid receptors, meaning CBD changes how pain signals are processed. Allosteric modulators are like a volume control, helping turn up or down how much the body listens to a particular signal. Allosteric modulators attach themselves to sites other than the main receptor site (which are called “orthosteric modulators”). This interaction may also help explain CBD’s potential use in treating opioid addiction.

What is the Best CBD Oil?

CB1 and CB2 receptors and the immune system

Both CB1 and CB2 receptors play an important role in immune system function. CBD can suppress cytokine production, thereby reducing inflammation associated with immune response. However, CBD has a low affinity for CB1 and CB2 receptors but can affect the way other cannabinoids interact with these receptors.

The immunomodulatory effects of cannabinoids can be both a pro and a con, depending on a patient’s goals and current medication. For example, if you are using immunotherapy for cancer cannabinoids are contraindicated (i.e. they clash).

CBD may help control glutamate N-methyl-D-aspartate (NMDA) receptors in the brain

The NMDA receptor is a type of glutamate receptor and it is important for neuroplasticity and memory retention. This gives CBD neuroprotective properties and potentially helps regulate brain functions like learning, memory formation, and mood. This interaction may also explain CBD’s anticonvulsive effects, as well as its use as an antipsychotic.

There is a lot of complicated scientific theory and supposition behind these hypotheses. Still, it’s a very interesting area of research, and targeting the endocannabinoid system (ECS) could be the future of drugs and medications, especially considering cannabis’s safety and therapeutic profile.

CBD inhibits the liver enzyme cytochrome P450 (CYP 450)

The liver is where most drugs are metabolized, meaning that CBD can inhibit the processing of many other drugs. This is why it is important to speak with a doctor before taking cannabis products if you are already using medications. For example, those using anti-epileptic drugs (AEDs) and benzodiazepine-based medications will need to taper their use to prevent the buildup of dangerous levels of benzodiazepines in the blood. The CYP 450 enzyme also processes some types of antibiotics, so CBD can interfere with their metabolization.

CYP450-51A1; ribbon model of human CYP51A1 with heme (green) and ketoconazole, both as balls, after PDB 3LD6.
Author: Ayacop; Source. CC0.

Does CBD Block THC?

Many people believe that CBD reduces the psychoactivity THC gives by blocking it in the body. In fact, it seems that THC and CBD work differently in the human body, making the “CBD blocks THC” theory too simplistic.

CBD both competes and works in tandem with THC, rather than blocking it across the board. THC is a CB1 receptor agonist, whereas CBD works indirectly on the CB1 and CB2 receptors (and has a low affinity for them). This means CBD does not block THC but rather modulates the effect THC has on cannabinoid receptors.

However, there are some animal studies showing that CBD inhibits the conversion of THC to 11-OH-THC, meaning that CBD may have some inhibitory effect on THC after all. CBD may also prevent dopamine system disturbance, while THC overstimulates the ERK pathway which leads to dopamine system disturbance. How this mechanism works and at what dosage is yet to be determined.

This interaction between THC and CBD also helps explain the different effects between cannabis strains. Cannabis varieties high in THC but with little-to-no CBD tend to be very psychoactive but with a shorter duration. THCV, which in low doses inhibits THC and increases its psychoactive effects in higher doses, is another example of the interplay between cannabinoids.

High-CBD/low-THC varieties may have little psychoactive (or, more accurately, less intoxicating) effect, but can still produce a sense of relaxation or balance, as CBD enhances anandamide signaling. High-THC/high-CBD strains may have some of their intoxicating effects lessened, but the duration may last longer. 1:1 THC:CBD ratios can be intoxicating in high doses, but many find that 1:1 ratios aren’t overwhelmingly psychoactive in low or medium doses.

The Biphasic Effects of CBD

As CBD is an indirect antagonist of the CB1 receptors, it can actually have more stimulating than sedative effects in small doses. However, in higher doses, CBD often produces more relaxing effects. This biphasic interaction suggests that although CBD doesn’t bind or interact with cannabinoid receptors directly, it certainly plays a role in determining how they behave. High doses of CBD may help inhibit the enzyme FAAH (which breaks down THC/anandamide), increasing the amount of anandamide available in the body. This will not intoxicate the way THC does but can certainly help induce relaxation. It creates a physiological difference and affects the mind and body in its own way.

In this sense, CBD is technically psychoactive. Biphasic effects can be confusing, as many people would expect a higher dose to produce more of whatever a low dose causes. But while cannabis’ complexity makes it difficult to understand, it’s also highly variable and useful for a multitude of health problems.

The Entourage Effect

Remember, CBD works better when other phytocannabinoids and terpenoids are present. CBD on its own may not be as effective, requiring higher doses or even being ineffective for specific conditions. Combine it with a bit of THC (even in non- or low-psychoactive amounts) and the plant’s terpenes, however, and it features a variety of helpful uses.

Download Free Guide to CBD

While this guide covers the basics, you can read more details on CBD and other cannabinoids for different conditions here.

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Written by
Shanti Ryle
Shanti Ryle

Shanti Ryle is a content marketer with more than half a decades’ experience writing about cannabis science and culture. Her work has been featured in Forbes, Weedmaps News/Marijuana.com, Wall Street Journal, and other publications.

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