Why Does CBD Work So Well?

If you’ve been following the news, you may have noticed that cannabidiol (CBD) is becoming a modern-day panacea. Hundreds of thousands of people are using CBD to regulate their stress and moods, to treat insomnia, to fight runaway inflammation and more — all without the “high” that can make regular treatment with cannabis impractical.

Definitive Medical Studies


These therapeutic properties are not just hearsay from the bud-tender at your local dispensary. CBD’s effectiveness has been confirmed — or is currently being confirmed — by dozens of clinical trials in the United States for FDA-approved medications.

Some of the conditions currently being treated with CBD in clinical trials include:

  • Anxiety
  • Post-traumatic stress disorder (PTSD)
  • Chronic pain
  • Parkinson’s disease
  • Drug and alcohol addiction
  • Epilepsy
  • Schizophrenia
  • Cancer
  • … and more

Supplementing with CBD

Most people who supplement with CBD find this plant-derived molecule to be very effective, and many find so much relief that they stop using pharmaceutical treatments (which often come with nasty side effects).

But you may be wondering — given that CBD relieves so many people of so many seemingly unrelated conditions “How can one little molecule accomplish so many different things across the human body?”

Researchers have been puzzling over this exact same question. Scientists already know CBD is beneficial for a wide variety of medical conditions, so most of the research they're conducting focuses on deciphering how CBD exerts its therapeutic effects. New research articles featuring cannabidiol are published almost every other day, and more than 65 different targets of this molecule have already been identified!

If you’re considering incorporating CBD into your self-care routine (or if you’re already supplementing with it), you may want to know more about the different ways CBD affects your body.

Scientists believe that the most important targets for CBD’s therapeutic potential are:

  • The Endocannabinoid System
  • Serotonin Receptors
  • Pain Receptors
  • Gene Activation Receptors
  • Other Receptors
  • Enzymes

Your brain uses chemical messengers known as neurotransmitters — and their corresponding receptors — to pass signals between different cells. Neurotransmitter receptors sit on the surface of neurons and other cells, waiting for the messengers to fire them into action.

Neurotransmitters are essential to your health, and imbalances are linked to many diseases and mental disorders. For this reason, a wide variety of prescription drugs (like antidepressants and painkillers) target your different neurotransmitter systems.

CBD impacts many different neurotransmitter systems, and its strongest effects are on the endocannabinoid and serotonin systems.

Endocannabinoids + Phytocannabinoids

Your endocannabinoid system influences memory, mood, immunity, appetite, and cardiovascular health — to name just a few. Elevated or depressed production of endocannabinoids can have repercussions throughout your body.

Much research has been done on THC (the sister-molecule of CBD) exploring how THC resembles your body’s natural endocannabinoids and can directly stimulate your endocannabinoid receptors. This effect is the main source of THC’s therapeutic (and psychoactive) properties, and it can provide relief to those of us with endocannabinoid deficiencies.

Unfortunately, THC can also overstimulate your receptors. If this happens, your cells will compensate by decreasing the number of receptors, further imbalancing your endocannabinoid system. But when consumed along with THC, CBD buffers its negative impacts on your endocannabinoid system.

And when consumed by itself, Cannabidiol naturally increases your endocannabinoid levels, but also  protects your endocannabinoid receptors from being over-activated. That’s an impressively versatile little molecule!

How does CBD modify endocannabinoid receptors?

Studies indicate that CBD binds to CB1 (one of your brain’s endocannabinoid receptors) at a different spot from where other cannabinoids normally bind to the receptor. This process, called allosteric modulation, leaves the binding site free, but changes the shape of the receptor so that it has a weaker binding affinity — rendering it less responsive.

Although decreasing your body’s endocannabinoid response might seem counterintuitive, many disruptions to the endocannabinoid system actually stem from an overactive system. If your body struggles with the burden of constant anxiety or excess weight, then your receptors are probably being overstimulated, and CBD could give your endocannabinoid system the break it needs.

Scientists also believe that this dampening effect is the reason why CBD can buffer the psychoactive properties of THC.

How does CBD boost your body’s endocannabinoids?

Countless studies also indicate that CBD actually increases your natural endocannabinoid levels. There are a number of reasons why CBD can elicit this effect, but the strongest evidence suggests that CBD competes for binding proteins with endocannabinoids — binding proteins that are responsible for transporting these neurotransmitters for breakdown.

This process, where natural levels of a neurotransmitter are elevated because your body is less efficient at recycling them, is called reuptake inhibition. This term might ring a bell for those familiar with SSRIs (selective serotonin reuptake inhibitor), pharmaceutical drugs commonly prescribed for depression and anxiety.

Serotonin (5-HT)

Speaking of serotonin, there’s a good chance you already know that this neurotransmitter has a large impact on mood and emotions in the brain, but you might not know that serotonin is used throughout your body for many other purposes, including digestion, bone synthesis and cardiovascular function. Though we’re accustomed to thinking of serotonin being in the brain, 95% of your body’s serotonin is located in the gut.

So where does CBD fit in?

Within the brain, CBD can mimic serotonin by binding and activating your body’s 5-HT1A serotonin receptors — likely a major contributor to CBD’s anti-anxiety properties. These effects have contributed to the view that CBD holds potential as a tool for addiction recovery.

Pain Perception (ion channel receptors)

CBD also interacts with plenty of other receptors — completely outside of our neurotransmitter systems — but rather than responding to molecules or neurotransmitters, some of these receptors are designed to respond to sensations — like temperature.

TRPV1 (short for transient receptor potential cation channel subfamily V member 1) is one such receptor, located throughout your body where it detects temperature and delivers the sensation of scalding heat and pain. TRPV1 is essential for helping you quickly respond to situations that could damage your body — like if you accidentally place your hand on a burning hot pan.

Unfortunately, when faced with inflammation or injury, chemicals released by your body can increase the sensitivity of these pain receptors.

Fortunately, some molecules — such as the active compound in chili peppers, Capsaicin — can activate and then desensitize TRPV1 receptors. Similarly, CBD also desensitizes these pain receptors, and this effect on TRPV1 is considered pivotal to CBD’s usefulness in treating epilepsy and arthritic pain.

Turning Genes On & Off (nuclear receptors)

Though most receptors exist on the outside of our cells, some are actually located within the cell.

One class of receptors that CBD activates is actually positioned on the nucleus of your cells. The peroxisome proliferator-activated receptor γ (PPARγ), when activated, changes which genes in your DNA actually get to be expressed.

PPARγ is mostly located in fat tissue cells and the immune system, and its main function is to help regulate metabolism. When activated, PPARγ triggers fat cells to capture circulating lipids and store them, helping to lower blood glucose levels and improve insulin sensitivity. This activity makes PPARγ an important target for diabetes treatment.

Stimulation of PPARγ also reduces production of inflammatory molecules by the body while increasing its production of antioxidants. This dual activity provides neuroprotection when inflammation could be detrimental, particularly after stroke or other traumatic brain injuries.

Research finds that CBD activates this receptor, perhaps a key reason for CBD’s anti-inflammatory and neuroprotective functions. This effect on PPARγ has also been linked to CBD's therapeutic potential for ulcerative colitis, multiple sclerosis and Alzheimer’s disease.

Added bonus: Not only does it increase your body’s production antioxidants, CBD is also a potent antioxidant itself — which is why many skincare products now include CBD for directly-applied skin protection.

Orphan Receptors

Cannabidiol also interacts with other receptors that have less-defined roles in the body. One such receptor is GPR55 (short for G-protein-coupled receptor 55, which pretty much translates to “receptor we know nothing about #55.”) Some scientists have suggested re-naming GPR55 as an endocannabinoid receptor — since it binds with cannabinoids and shares some functional and stimulatory overlap with other endocannabinoid receptors.

Though it’s still being investigated, in only the last few years GPR55 has been connected to appetite, insulin secretion, bone density, and (most significantly) cancer proliferation

Instead of activating the GPR55 receptor, CBD appears to block the function of this receptor and is therefore called an antagonist or inverse agonist of GPR55. Because GPR55 helps cancer cells proliferate, it’s hypothesized that CBD’s action against GPR55 is why it appears to protect against cancer proliferation.

In a recent study of mice with pancreatic cancer who were taking a chemotherapy drug, mice given CBD survived three times as long as mice who only got the cancer drug.

Enzymes

So far we’ve focused on how CBD interacts with receptors — which then results in a downstream effect (like a change in your perception of pain). But in addition to receptors, CBD has been shown to interact directly with a variety of enzymes and other proteins in your body.

Some of these enzymes are important to the systems we’ve already covered. For instance, some studies have shown that CBD inhibits the enzyme that normally degrades the “bliss” endocannabinoid, anandamide.

Other enzymes targeted by CBD are involved with cholesterol metabolism, mitochondria function, and melatonin synthesis — to name a few.

However, a class of enzymes which deserves special mention is cytochrome p450. Cytochrome p450 enzymes are involved with metabolism — the breakdown of molecules by your body. These enzymes are especially important for your body’s ability to metabolize drugs into inactive or more-active compounds.

How does CBD interact with prescription drugs?

It turns out that CBD is a potent inhibitor of some cytochrome p450 enzymes. CBD’s interaction with cytochrome p450 probably contributes to its above-mentioned therapeutic effects — but could also pose a health risk when combined with certain prescription drugs.

If you currently take a pharmaceutical drug that is processed by cytochrome P450 (they often come with a warning not to consume with grapefruits) – CBD may interfere with your body’s ability to process these pharmaceuticals.

However, this does not rule out CBD as a treatment option. In fact, CBD might help increase the effectiveness of your medication — thus lowering your required dose.

Depending on how the drug is processed by cytochrome p450, CBD could elevate or decrease the concentration of the active compound in your bloodstream. Correspondingly, you might have to decrease or increase the amount of medication you are taking.

If you are taking drugs that are processed by cytochrome p450 (ie warfarin, anti-epileptics, HIV antivirals, and chemotherapy), you absolutely should consult with your physician before taking CBD. (Some doctors are already gaining experience at accommodate their patients who take CBD.) Your doctor might suggest extra blood monitoring in order to keep these drugs at a healthy level in your bloodstream.   

In Summary

Cannabidiol is becoming a popular supplement for a broad spectrum of uses. At the base of CBD’s health benefits is a wealth of solid scientific research that shows how CBD interacts with numerous neurotransmitter systems, enzymes, and receptors that control pain perception and gene expression.

Although CBD is not a panacea for all modern ills, it does have scientifically-proven anti-anxiety, anti-inflammatory, anti-seizure, antioxidant, and anti-tumor activities.

With dozens of clinical trials currently in the works, you can expect to see CBD gaining popularity as a prescription for a wide variety of diseases and disorders in the near future.

Fortunately, while the US federal government considers “CBD” to be a medical drug (and a drug that can costs tens of thousands of dollars per year), CBD-rich hemp extract is the perfect alternative — as both a daily supplement and as an occasional holistic remedy.


Written by: Genevieve R. Moore PhD

Tagged with: CBD Foria Basics
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