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How Does Cannabidiol (CBD) Work?

The fact is, the only definitive answer available at the moment is “nobody knows precisely, as of yet”. Should someone say to you presently, “I know exactly how CBD works, and it’s all you need”, ask to see the science, research and numbers, and be very suspicious. However, if they say, “I might know how it 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 as well,” then sit down, buy that person a coffee and talk to them. They sound like someone worth listening to!


So here’s where we explain why CBD might work …

The Basics – What is Cannabidiol (CBD)?

CBD’s chemical formula is C21H30O2. CBD is one of at least 144 cannabinoids found in the cannabis plant. CBD is one of cannabis’s major phytocannabinoids, and accounts for up to 40% of the plant’s extract. CBD does not seem to have intoxicating effects for most people (though some have reported a mild psychoactive effect), and may, in fact, dampen the effects of tetrahydrocannabinol (THC).

In its raw form, CBD is known as cannabidiolic acid (CBDA). CBDA becomes CBD after aging and/or decarboxylation (heating). CBDA also has a precursor – cannabigerolic acid (CBGA), which is the precursor to both tetrahydrocannabinolic acid (THCA) and CBDA. CBGA is turned into CBDA with the help of the plant enzyme CBDA Synthase. Catalysis from CBGA to CBDA follows the same pathway that CBGA to THCA does, with the only difference being that a different enzyme catalyzes them – THCA Synthase catalyzes CBGA to THCA.

What Receptors Does CBD Affect?

As far as we know, CBD is an indirect antagonist of the body’s cannabinoid receptors CB1 and CB2, a 5-HT1A (a serotonin receptor) partial agonist, TRPV1 (vanilloid receptor) agonist, and allosteric modulator – a substance that indirectly influences an agonist or inverse agonist – of the μ- and σ-opioid receptors. CBD is said to be analogous to the endocannabinoid 2-Arachidonoylglycerol (2-AG), an endogenous agonist of the CB1 receptor. 2-AG’s chemical formula is C23H38O4.

So How Does CBD Affect the ECS and Other Receptors?

Knowing what receptors CBD effects (and remember, we don’t know precisely how, where and why CBD works as of yet) is key to understanding its medical uses.

  • 5-HT1A Serotonin Receptors – CBD is a partial agonist of the 5-HT1A receptor. CBD being a “partial agonist” means that it binds to a receptor, but only at partial efficacy in comparison to a full agonist. That CBD works on serotonin receptors may explain why it can be so effective as an antidepressant, anxiolytic and even neuroprotective!
  • TRPV1 vanilloid receptor – CBD has the potential to “desensitize” the TRPV1 receptor. This gives CBD its analgesic (pain-killing), antiemetic and seizure-beating properties.
  • μ- and σ-opioid receptor allosteric modulators – Another reason why CBD may have analgesic properties. This may also help explain why CBD may be useful in treating opioid addiction.
  • CB1 and CB2 receptors both play an important role in the functioning of the immune system. CBD can suppress cytokine production, thereby reducing inflammation. However, CBD has a low affinity for CB1 and CB2 receptors, but can affect the way other cannabinoids interact with these receptors
  • May help control glutamate NMDA receptors in the brain, giving CBD not only neuroprotective properties, but also potentially helping regulate brain functions like learning, memory formation and mood. Targeting these receptors may also give CBD some of its anticonvulsive effects, as well as having use as an antipsychotic.

There is a lot of complicated scientific theory and supposition behind this, but it’s obviously a very interesting area of research, and targeting the endocannabinoid system (ECS) could be where drugs and medications are going in the future, especially considering cannabis’s safety and therapeutic profile.

Does CBD “Block” THC?

Many people claim that CBD “reduces” the psychoactivity THC gives by “blocking” it. Now, this may be true in rodents like rats and mice, but it seems that THC and CBD work differently when it comes to humans. This means that the “CBD blocks THC” theory is not quite right.

The reason why people thought CBD “blocks” THC is because it inhibits the production of fatty acid amide hydrolase (FAAH), which causes an increase in the amount anandamide found in the body. However, this might well be wrong. CBD may increase the amount of anandamide found in the body by essentially letting anandamide stay present in the body for longer, as opposed to inhibiting FAAH. CBD may be competing or working in tandem with the body’s own cannabinoids, rather than “blocking” or “inhibiting” them per se. THC is a CB1 receptor agonist, whereas CBD works indirectly on the CB1 and CB2 receptors, meaning it probably does not “block” THC.

This also helps explain some things about the effects certain strains might have. Strains high in THC but with little-to-no CBD tend to be very psychoactive, but don’t last very long (made doubly so with the presence of THCV, which in low doses inhibits THC). High-CBD-low-THC strains may have little psychoactive effect, but can still produce a “relaxed body” or even  feeling due to the body’s increased levels of anandamide. High-THC-high-CBD strains may have some of their psychoactivity “smoothed out”, but the duration of the effects may last longer. However, there are some studies showing that CBD inhibits the conversion of THC to 11-OH-THC, meaning that CBD may have some inhibitory effect on THC. How this mechanism works and at what dosage still needs to be found out.

The Entourage Effect

Remember, CBD works better when other phytocannabinoids and terpenoids are present. CBD on its own may not be effective. Combine it with a bit of THC and the plant’s terpenes, however, and you have some medication to be proud of!

Anything Else?

Lots, but we’re going to keep it as simple as possible. We might also be able to research all of this better if CBD and cannabis weren’t federally illegal! It is politics rather than science that prevents us from seeing cannabis as medicine.

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