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Home » Blog » Hemp Education » CBD Oil Effects: Cannabidiol’s Influence on the Endocannabinoid System

CBD Oil Effects: Cannabidiol’s Influence on the Endocannabinoid System

CBD oil effects feature image: four bottles of cannabidol oil on a white background

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The benefits of cannabidiol oil are well documented. Medicinal uses are far-reaching, and scientific studies have proven cannabidiol to be effective for pain relief, insomnia, anxiety, seizures and much more. How does CBD achieve these effects at the anatomical level? Let’s examine CBD oil effects and the mechanisms that result in the sought-after reliefs.

A Lesson in the Endocannabinoid System

To understand CBD oil effects on the body, you need to understand how the human anatomy works. It all comes down to the endocannabinoid system (ECS). The ECS is not unique to humans; it’s found in virtually all vertebrate species.

The ECS is located throughout the body and not concentrated in a single area. It consists of these three major components:

  • Cannabinoid receptors
  • Endocannabinoids
  • Metabolic enzymes

Cannabinoid Receptors

Cannabinoid receptors are located on cell surfaces and detect changing conditions taking place outside of the cell. It transmits information to the cell, and the cell responds and adapts accordingly. The two primary receptors include CB1 and CB2.

CB1 resides mostly in the brain and nervous system. When you ingest or vape THC, the psychoactive cannabinoid binds with CB1 receptors, leading to the high and stoned sensation.

CB2 resides mostly in the immune system, including immune cells and macrophages. This receptor mainly regulates pain and inflammation.


Endocannabinoids, also known as endogenous cannabinoids, are molecules that bind to CB1 and CB2. The body produces endocannabinoids naturally and on demand as needed.

Various types of endocannabinoids exist. One of the more researched forms is a molecule called anandamide, which facilitates pain reduction, healthy sleep cycles, anxiety relief and more. Some people have referred to anandamide as the “bliss molecule” due to its antidepressant-like effects.

Endocannabinoids are retrograde signalers.  Most neurotransmitters only travel in one direction, from a presynaptic cell to a postsynaptic cell. Endocannabinoids direct information from the post- to the presynaptic cell. The signaling informs the latter to produce more or less of certain chemicals and hormones.

Metabolic Enzymes

These enzymes metabolize endocannabinoids right after they’re used and no longer needed. Unlike hormones and neurotransmitters, endocannabinoids are never stored and reserved for later use.

These three ECS components regulate everyday bodily functions, such as our circadian rhythm, appetite, mood, memory, pain, and pleasure/reward system.

How Do Cannabinoids Fit In?

Researchers are just beginning to understand the complex role of cannabinoids on the endocannabinoid system1. To keep the explanation simple, cannabinoids mimic the behavior of endocannabinoids and bind to cannabinoid receptors in a similar fashion. Cannabinoids derived from cannabis are known as phytocannabinoids, though they’re typically referred to as cannabinoids.

As it turns out, thendocannabinoid system recognizes and responds to phytocannabinoids the same way as internally-produced endocannabinoids.

Phytocannabinoids Versus Endocannabinoids

Despite having near-identical influences on the ECS, phyto- and endocannabinoids2 do have some differences. One may wonder, for example, why it is that humans don’t get high naturally from endocannabinoids. It comes down to the metabolic enzymes, which do not break down THC the way it does with endocannabinoids. This allows THC to remain in the body for prolonged periods and exert psychoactive influences.

Unlike endocannabinoids, which only interact with CB receptors, phytocannabinoids may also interact with other receptor types, neurons and neurotransmitters.

Effects of CBD on the Endocannabinoid System

CBD interacts with the endocannabinoid system in a different way than THC and other cannabinoids. For starters, it does not bind to CB1 and CB2 receptors. The effects on the cannabinoid receptors are more indirect. One way it does this is by stopping the metabolic enzymes from breaking down the body’s natural supply of endocannabinoids.

Studies3 show that CBD inhibits the fatty acid amide hydrolase, a type of metabolic enzyme that causes anandamide inactivation.  In other words, CBD increases availability of endogenous cannabinoids. This is why CBD does not produce the high you get from THC; there is no direct interaction between cannabidiol and cannabinoid receptors. The benefits of pain relief and relaxation is from the greater bioavailability of anandamide and other endocannabinoids.

CBD Oil Effects on Non-Cannabinoid Receptors

As mentioned, one way phytocannabinoids differ from endocannabinoids is the ability to interact with other receptors. Cannabis is a pleiotropic substance, meaning it affects the ECS via multiple molecular pathways.

CBD, in particular, has been shown in studies to interact with opioid receptors in the brain. This explains the medical research4 supporting CBD use for managing opiate withdrawal.

Another study5 reveals an interaction between CBD and vanilloid (TRPV1) receptors. This receptor acts as an ion channel and mediates pain, inflammation, and body temperatures. TRPV1 also mediates the effects of various medicinal herbs.

Some people also take CBD for cancer management. This is because CBD also binds with peroxisome proliferator activated receptors (PPARs). Studies6 show that CBD activates these receptors and induces tumor regression in the lungs.

These are just some of the non-cannabinoid receptors CBD has some level of influence on. Some estimates indicate that CBD interacts with as much as 65 types of receptors. You can see now why the effects of CBD are far-reaching and why hemp as medicine is gaining traction.

Does Taking Phytocannabinoids Inhibit Endocannabinoid Production?

Some folks have expressed concerns that taking too much CBD from an external source may suppress the body’s natural ability to produce endocannabinoids. Taking anabolic steroids or TRT, for example, certainly hurts the body’s ability to produce testosterone naturally. Is it the same when taking CBD oil?

There are no studies that suggest this may be a possibility. CBD doesn’t even bind directly to CB receptors. Remember, as we mentioned, CBD actually elevates certain endocannabinoids by inhibiting metabolic enzymes.

What Causes the Calm-Inducing Effects of CBD?

Most people who take CBD oil report a feeling of ease and the ability to forget about their problems for the moment. What attributes to this feeling of immense relaxation?

One other non-cannabinoid receptor is the 5-HT1A receptor, which according to studies7, regulates serotonin, or the “feel-good” hormone.

Aside from regulating serotonin, the 5-HT1A receptor has also been linked to other biological and neurological responses, such as anxiety, sleep, appetite and pain perception. This explains why CBD use also helps improve deficiencies in these areas. The 5-HT1A can actually produce both an excitatory and inhibitory response, depending on the triggering chemical or molecule.

CBD has an inhibitory response on 5-HT1A. This inhibits the receptor’s ability to signal the slow-down of serotonin production, thus leading to more output of the calming hormone.

What About THC and Anxiety?

CBD, for the most part, does not induce anxiety. Unfortunately, the same cannot be said of CBD products with THC. Some people have reported feelings of extreme paranoia, disorientation and inability to complete even the simplest of tasks, such as walking straight or sending a text. These sensations are not uncommon among first-time users who try a friend’s THC-laced Rice Krispies Treat or other edibles.

Why does this happen with THC, but not CBD? What is taking place at the ECS level? Remember that unlike CBD, THC actually binds to the CB1 and CB2 receptors. This causes a surge of neurotransmitter releases, including serotonin, dopamine and GABA. GABA is especially relevant in this instance; this neurotransmitter inhibits the firing of certain neurons, including the neurotransmitter norepinephrine. Norepinephrine induces alertness; in excess, it can also cause anxiety. GABA, therefore, induces relaxation by suppressing norepinephrine.

In some people, suppressed norepinephrine can cause a rebound effect. This leads to an overstimulation of the brainstem’s limbic forebrain, which regulates arousal and overexcitement. In turn, this leads to excess cortisol release, causing stress and anxiety. While not everyone who ingests THC experiences this phenomenon, those who do say they don’t ever want to go through that again. The lesson here is to stick with CBD-only products from reputable suppliers.

To avoid a bad experience, only buy from licensed suppliers. Our Where to Buy section contains a listing of reliable CBD manufacturers.

CBD Effects on Epilepsy

One other notable use of CBD is reducing the frequency and severity of epileptic seizures. Researchers are exploring CBD as a viable alternative; roughly one-third of epilepsy patients do not respond to traditional anticonvulsants. This is where CBD for seizures comes in as a viable alternative.

CBD also interacts with glutamate receptor agonists, sodium ion channels and GATA-binding factors (GATA2) in the brain. These are the same systems that traditional anticonvulsants target by binding themselves to these neurons and altering the ion flow. Epileptic seizures are triggered by abnormal electrical activity, which is believed — at least to some degree — to originate from the ion flow between ion channels, glutamate receptors and GATA2.

CBD Effects Are Complex and Warrant Further Studies

The studies of CBD oil on the human anatomy are still limited. There are still interactions with the ECS system that we haven’t even yet begin to understand. What we do know so far, though, is that CBD appears to have a positive effect based on scientific studies and anecdotal experiences from thousands of sworn users.


Medical References

PACHER P, BÁTKAI S, KUNOS G. The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacol Rev. 2006;58(3):389-462. [PMC]
Fisar Z. Phytocannabinoids and endocannabinoids. Curr Drug Abuse Rev. 2009;2(1):51-75. [PubMed]
Bisogno T, Hanuš L, De P, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001;134(4):845-852. [PMC]
Ren Y, Whittard J, Higuera-Matas A, Morris C, Hurd Y. Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin-seeking and normalizes discrete mesolimbic neuronal disturbances. J Neurosci. 2009;29(47):14764-14769. [PMC]
Costa B, Giagnoni G, Franke C, Trovato A, Colleoni M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharmacol. 2001;143(2):247-250. [PMC]
Ramer R, Heinemann K, Merkord J, et al. COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013;12(1):69-82. [PubMed]
Resstel L, Tavares R, Lisboa S, Joca S, Corrêa F, Guimarães F. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009;156(1):181-188. [PMC]
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Christopher Walker

Christopher Walker has a degree in Neuroscience from Duke University, and is the research writer for The Universal Plant. He has dedicated his life to helping men and women around the world educate themselves and take action to improve their health with natural plant-based and nutrient therapies. Follow him on Instagram @_christopherwalker