The Science of CBD: Is Cannabidiol a TRPV1 Activator?

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What are the TRPV1 receptors, and what do they have to do with CBD? It turns out that CBD’s potential interaction with the TRPV1 receptors is one of the hottest topics in the CBD industry right now, and many leading scientists are convinced that increased TRPV1 activation helps explain CBD’s reported antiepileptic, analgesic, and anti-inflammatory effects. Learn more about the science of CBD by delving into this beneficial cannabinoid’s relationship with your body’s TRPV1 receptors.

What Are TRPV1 Receptors?

TRPV is an acronym for “transient receptor potential cation channel subfamily V.” The TRPV1 receptor is just one of dozens of receptors in the TRP family, and it functions as both a receptor and an ion channel.

Receptors in the TRPV family are known as “vanilloid receptors” due to their affinity with certain beneficial compounds in vanilla beans. Therefore, the TRPV1 receptor is also known as the “vanilloid receptor 1.” What’s more, the TRPV1 receptor is sometimes called the “capsaicin receptor” since it’s the main receptor that capsaicin, an anti-inflammatory compound found in chili peppers, binds to when it enters the body.

How Do Your TRPV1 Receptors Impact Your Health?

The TRPV1 receptors in your body play a big role in determining how your body experiences pain1. Technically, the main function of TRPV1 is to cause searing pain, but prolonged TRPV1 activation actually reduces pain. Confused? The key factor here is “desensitization.”

As some of the most sensitive neuroreceptors in your body, your TRPV1 receptors can be triggered by practically any pain stimulus. With prolonged exposure to activating agents, however, TRPV1 receptors desensitize and require a greater threshold for activation. Substances that directly deactivate the TRPV1 receptors may be dangerous, but through increased activation and subsequent desensitization, a number of compounds reduce your pain threshold by interacting with your TRPV1 receptors.

Where Are TRPV1 Receptors Found in Your Body?

Most of your body’s TRPV1 receptors are concentrated in your peripheral nervous system, which consists of all the nerves in your body aside from your brain, brainstem, and spinal column. Since this neuroreceptor plays such a critical role in how you experience pain, it’s necessary for TRPV1 receptors to be distributed evenly throughout the various limbs and tissues in your body.

Smaller concentrations of TRPV1 receptors are present in the brain. These receptors play different roles than TRPV1 receptors found in the peripheral nervous system. Scientists are keenly interested in the role that brain-based TRPV1 receptors may have in the development of various neurological diseases.

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Can CBD stop seizures and reduce inflammation via TRPV1 activation?

More Benefits of Increased TRPV1 Receptor Activation

In addition to mediating the experience of pain, increased activation of your TRPV1 receptors may offer a variety of other benefits:

1. Epilepsy

Recent research indicates that the TRPV1 receptors may play a role in the genesis and symptoms of epilepsy2. People with epilepsy have more TRPV1 receptors in their temporal lobes than people who don’t have this condition, and it appears that desensitizing the TRPV1 receptors in the brain may prevent seizures.

2. Inflammation

Inflammation is a normal, healthy immune response. Your body uses inflammation as a first-line mechanism of healing when you’ve been physically injured, and this beneficial type of inflammation is called acute inflammation.

When inflammation becomes persistent, however, it transforms into an autoimmune disorder called chronic inflammation, and the main symptom of chronic inflammation is tissue degradation and pain. According to one study3, “TRPV1 agonists may act as anti-inflammatories in certain inflammatory and autoimmune conditions in vivo.” Essentially, this means that TRPV1 activation appears to treat inflammation by reducing the overall activity of the body’s inflammatory mechanisms.

The authors of this study go on to explain why TRPV1 activation may not be the be-all, end-all when it comes to inflammation and pain reduction:

“Given the potential deleterious effects of inhibiting the population of channels with a protective function, caution should be taken in the use of potent TRPV1 antagonists as a general strategy to treat inflammation.”

In this statement, the authors express that the overall inflammation-reducing effects of TRPV1 activation may be dangerous because they also suppress acute inflammation. TRPV1 activation may be such a potent anti-inflammatory treatment that it also reduces your sensitivity to acute injuries that require immediate medical attention.

3. Other Functions

For years, scientists were only aware of TRPV1’s relationship with the sensation of burning pain and its interaction with capsaicin. According to one study4, however, recent years have brought with them a “virtual avalanche” of new potential functions of the TRPV1 molecule, and the authors of this study list some of these functions for our benefit (emphasis added):

“TRPV1 may also be involved in an array of vitally important functions, such as those of the urinary tract, the respiratory and auditory systems. Moreover, TRPV1 could also be involved in the maintenance of body and cell homeostasis, metabolism, regulation of hair growth, and development of cancer.”

It’s clear that we’ve only just started learning about all the ways that TRPV1 activation and subsequent desensitization may be beneficial. It’s equally clear, however, that the potential benefits of TRPV1 activation are numerous, and this neuroreceptor most likely plays a much larger role in our health and well-being than we realize.

Potential Side Effects of TRPV1 Receptor Activation

We don’t know enough about TRPV1 activation yet to be sure that increasing the activation of this neuroreceptor doesn’t cause side effects. At present, however, there’s only one potentially deleterious effect of TRPV1 activation that’s worth being aware of.

Out-of-control inflammation is one of the leading causes of pain. It’s important to remember, however, that inflammation is designed to be a beneficial function. The inflammation and pain you experience when you break your leg, cut yourself, or sustain another type of injury is what alerts you that you’re in danger and need to go to the hospital. Without inflammation, it’s hard to know when you’ve been badly hurt.

While some types of anti-inflammatory mechanisms only reduce chronic inflammation, TRPV1 appears to also reduce acute inflammation, which could reduce the intensity of the pain response to serious injuries. Many people with chronic inflammation would be more than happy to take this risk, but it still bears consideration that TRPV1 activation seems to cause an overall “numbing” effect that could harm your ability to respond appropriately to life-threatening stimuli.

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What’s the science behind CBD and TRPV1?

Does CBD Activate the TRPV1 Receptors?

A growing body of research indicates that CBD is a direct agonist of the TRPV1 receptors in your body. As the opposite of an antagonist, an agonist activates neuroreceptors, which means that CBD appears to increase the activation of your TRPV1 receptors. As we’ve covered, consistent TRPV1 activation leads to the desensitization of these neuroreceptors, which, in turn, reduces your sensation of pain. Here are some of the most notable pieces of scientific evidence that support CBD’s agonist activity at the TRPV1 receptors and explain what this potential activation means for your health:

1. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability.

This study begins by acknowledging5 that “transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy.” Therefore, controlling the expression and activation of TRPV1 may reduce the progression of epileptic symptoms and potentially prevent epilepsy altogether.

The authors of the study go on to say it’s been observed that “the two nonpsychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity.” Nonpsychotropic compounds are substances that don’t cause psychological effects, and CBD’s lack of psychoactive activity is one of the reasons why it’s shaping up to be such a promising treatment for epilepsy.

As a result of their research, the facilitators of this study found that “CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1.” These results indicate that the observed beneficial effects of desensitization of TRPV1 receptors can be achieved with the administration of cannabidiol.

NOTE: According to the U.S. Food and Drug Administration (FDA), CBD’s potential antiepileptic benefits aren’t theory anymore, they’re fact; with the approval of the CBD-based drug Epidiolex as a treatment for certain types of epilepsy, the FDA admits that CBD shows strong enough antiepileptic benefit to merit its acceptance as a mainstream pharmaceutical drug.

2. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation

In this study6, researchers found that CBD exerts antihyperalgesic effects, which means that this cannabinoid appears to reduce increased sensitivity to pain. The facilitators of this study sought to determine whether the CB1, CB2, or TRPV1 receptors were responsible for CBD’s observed pain-fighting effects. In the end, the study determined that the “TRPV1 receptor could be a molecular target of the CBD antihyperalgesic action,” which means that the reported analgesic effects of CBD may be caused by this cannabinoid’s activation and desensitization of the TRPV1 receptors.

Along the way, the facilitators of the study found that “[c]annabinoid CB1 receptor selective antagonist SR141716 did not reverse the CBD antihyperalgesic effect,” which ruled out CB1 activity as being responsible for CBD’s pain-fighting effects. Furthermore, the study found that “[c]annabinoid CB2 receptor specific antagonist SR144528 did not reverse the CBD antihyperalgesic effect,” which helps explain the importance of this study’s final results: “TRPV1 receptor selective antagonist CPZ reversed the CBD antihyperalgesic effect.”

Since blocking the action of the TRPV1 receptor stopped CBD from reducing pain, this study indicates that CBD’s activation of the TRPV1 receptors is most likely the mechanism behind CBD’s observed pain-fighting benefits. The authors of the study promote this hypothesis by stating that “the antihyperalgesic effect of CBD is mediated by TRPV1 receptors and does not involve the cannabinoid receptor subtypes CB1 and CB2.”

How does this study conclude CBD might be most useful for treating pain? It’s simple:

“In pathological conditions, such as neuropathy and rheumatoid arthritis, in which TRPV1 receptor sensitivity and expression are increased (Amaya et al., 2003Rashid et al., 2003), the nontoxic and nonpsychoactive compound CBD, may represent an useful pharmacological alternative in the treatment of the disease-associated chronic pain.”

3. Antiseizure properties of cannabidiol (CBD) are attenuated in the absence of transient receptor potential vanilloid 1 (TRPV1) receptors (S53.004)

The title of this study7 is a mouthful. Essentially, the scientists who conducted this research found that rats with blocked TRPV1 receptors didn’t experience reduced seizures when they were fed CBD. On the other hand, the study found that the control group of rats, which didn’t receive TRPV1 antagonists, experienced potent antiepileptic effects when CBD was administered.

These results provide scientific data supporting the hypothesis that TRPV1 activation caused by CBD may be able to prevent seizures. If true, administering CBD to the central nervous system may be just as beneficial as administering it to the peripheral nervous system. While applying CBD to the peripheral nervous system appears to reduce localized pain, CBD applied to the central nervous system appears capable of preventing seizures.

4. Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis

This study8 postulates that, out of all the neurological mechanisms affected by cannabinoids, TRPV1 activation might be the most promising in the treatment of rheumatoid arthritis (RA). The authors of the study observed the effects of endocannabinoids, which are cannabinoids naturally found in the body, on the CB1, CB2, and TRPV1 receptors.

While CBD doesn’t interact with the CB1 or CB2 receptors very strongly, research has confirmed that this cannabinoid interacts strongly with the TRPV1 receptors. This study found that TRPV1 has the potential to modulate the pain associated with rheumatoid arthritis, and it also identified a variety of other mechanisms of action that increased activation of TRPV1 receptors throughout the body.

To come to these conclusions, researchers inhibited the production of fatty acid amide hydrolase (FAAH), which exhibits a suppressing effect on the endocannabinoid system. The results? The researchers found that “FAAH inhibition leads to analgesic and anti-inflammatory effects via desensitization of TRPV1,” which means that the desensitization of TRPV1 caused by CBD may lead to reduced pain and inflammation throughout the body.

What’s the Best Way to Activate Your TRPV1 Receptors with CBD?

Unlike some of the mechanisms of action of CBD, different CBD application methods cause completely different effects when it comes to your TRPV1 receptors. Here are some of the best ways to use CBD to treat various TRPV1-related conditions:

1. Oral Administration

Oral administration may be the best way to prolong the purported TRPV1-activating effects of CBD. While oral administration is not the most bioavailable way to administer CBD, it offers the longest-lasting effects of any CBD administration method.

Any CBD that you administer orally is gradually released as it makes its way along your digestive tract. It generally takes 45-60 minutes or orally-administered CBD to take effect, but the effects of oral CBD products can last as long as six hours or more.

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2. Sublingual Administration

Sublingual administration (administration under the tongue) of CBD may be the best way to experience the reported antiepileptic effects of CBD. The area underneath your tongue borders a huge artery, and this section of permeable tissue is covered with mucus, which allows easy transfer of the CBD molecule from a sublingually-applied tincture into your bloodstream.

Any CBD applied sublingually be absorbed into the lingual artery and transferred rapidly to the brain. In the event of seizure onset, for instance, sublingual administration of CBD may reduce the symptoms of the seizure by rapidly sending CBD molecules to desensitize the TRPV1 receptors in the brain. If the TRPV1 receptors play any role in other brain-originated conditions, like depression, psychosis, or anxiety, sublingual administration would also, in theory, be the best administration route.

Most sublingually-administered treatments are swallowed shortly after they are applied. Therefore, sublingual administration of CBD also offers the benefits of oral administration. After the immediate effects provided by holding CBD under your tongue, swallow your CBD to experience long-term, reduced-potency benefits.

To experience the benefits of sublingual CBD administration for yourself, use CBGenius tinctures. The new Full-Spectrum CBD-Plus Oil Elixir – 1500mg is the strongest CBGenius CBD oil tincture available, and it offers the additional dietary benefits of hemp seed oil.

3. Pulmonary Administration

Pulmonary administration of CBD rapidly delivers cannabidiol molecules into your bloodstream. However, your lungs filter out a significant portion of the CBD vapor you inhale, which reduces the effectiveness of this administration method.

While the effects of inhaled CBD vapor set in nearly instantly, they usually dissipate within half an hour. Therefore, it’s best to pair the use of a CBD vape product, like our Flavored Prefilled 200mg CBD Vape Cartridge, with the application of a CBD product that has a longer-lasting effective window. Even so, vaping CBD is a potent way to fight back against the sudden onset of anxiety or pain.

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4. Transdermal Administration

Transdermal, or topical, administration of CBD may be the best way to treat localized pain and inflammatory disorders. For instance, this method of administration may be ideal for treating rheumatoid arthritis and neuropathy.

Some forms of transdermal administration may be more effective than others for delivering CBD into your bloodstream. While oil-based CBD topicals, for instance, are generally only effective at the site of administration, water-based topicals like our CBGenius CBD creams and lotions are designed to provide efficient update of CBD into the bloodstream.

Before wider effects occur, however, it appears that topical administration of CBD affects the TRPV1 receptors in the area administration directly. The main purpose of the TRPV1 receptors in the peripheral nervous system is the mediation of the pain sensation, so topical administration of CBD may rapidly desensitize the TRPV1 receptors in the area of administration. This local desensitizing effect appears to reduce both chronic and acute inflammation and suppress the sensation of pain.

Summing It Up: CBD and the TRPV1 Receptors

There’s still so much we don’t know about CBD. The more we learn about this cannabinoid, however, the more fascinating cannabidiol becomes; as we progress in our series, we’ll provide details on even more of CBD’s apparent mechanisms of action. TRPV1 activity is one big piece of the puzzle when it comes to explaining CBD’s effects scientifically, and as research into both the TRPV1 receptors and the CBD molecule advances, we’re sure to find out a lot more about the observed interaction between these two biological agents.

Here’s a brief summary of the important points we’ve covered regarding CBD and TRPV1:

  1. In addition to mediating the perception of pain, the TRPV1 receptor also appears to be involved in a variety of neurological and metabolism-related processes;
  2. As an agonist or activator, CBD appears to desensitize TRPV1 receptors;
  3. As a result, CBD has been reported to reduce the intensity of pain stimuli and reduce the epilepsy-triggering effect of increased TRPV1 expression;
  4. Therefore, CBD may be an effective treatment for pain, epilepsy, and a variety of neurological, metabolism-related, and other disorders.

When it comes to CBD, knowledge is half the battle. We’ll only be truly comfortable with cannabidiol once we understand exactly how it works, and at CBGenius, we understand how important it is for consumers to be able to trust CBD. As our series continues, we’ll uncover even more secrets of CBD and continue explaining how the seemingly magical effects that this cannabinoid offers do, indeed, have rational, scientific explanations.

Sources

  1. TRPV1: A Target for Next Generation Analgesics
  2. TRPV1 Channel: A Potential Drug Target for Treating Epilepsy
  3. Role of Transient Receptor Potential Vanilloid 1 in Inflammation and Autoimmune Diseases
  4. TRPV1 function in health and disease.
  5. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability.
  6. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation
  7. Antiseizure properties of cannabidiol (CBD) are attenuated in the absence of transient receptor potential vanilloid 1 (TRPV1) receptors (S53.004)
  8. Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis

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