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CB1 Receptors: What Do They Do?

Published by Dr. Venn-Watson
Dr. Eric Venn-Watson’s Highlights
  • The endocannabinoid system controls many processes that help keep our bodies regulated.

    CB1 receptors are a part of the endocannabinoid system that interacts with endocannabinoids and cannabinoids, special chemical compounds responsible for stimulating the endocannabinoid system. 

    The body needs fatty acids to synthesize endocannabinoids, and fatty15 has recently been recognized as a precursor to the second-ever discovered fully-acting endocannabinoid, known as PDC.

As we learn more about the endocannabinoid system and how it regulates bodily functions, we also learn about which parts of the system are responsible for what processes and how stimulating these parts can help us maintain a healthier life. 

An integral part of the endocannabinoid system is the receptors. Receptor activation happens when a receptor agonist or receptor antagonist binds to the receptor and either produces or prevents a particular outcome. 

There are two receptors in the endocannabinoid system: cannabinoid CB1 receptors and cannabinoid CB2 receptors. Together, we’ll discuss endocannabinoid signaling and the particular importance of the CB1 receptors. 

First, it’s helpful to have a basic understanding of the endocannabinoid system itself. 

What is the Endocannabinoid System?

Newly discovered, the endocannabinoid system and its endogenous ligands have only been researched heavily since the late 1990s. This system of chemical signals and receptors is located throughout our bodies and brains. 

As such, the study of the endocannabinoid system and the effects of cannabinoids includes both neuroscience and medical science. The endocannabinoid system controls numerous functions in the body. 

Because of its proximity to gamma-aminobutyric acid (GABA) and other neurotransmitters, it plays a role in functions like sleep, mood, appetite, blood sugar, hormones, learning and memory, emotional processing, parts of the immune response, and even pain regulation.

How the Endocannabinoid System Works

The endocannabinoid system relies on interaction with its cannabinoid receptors to trigger neuron synapses and appropriate responses. There are two types of receptors: CB1 and CB2. 

CB2 Receptors

These receptors are found primarily in the peripheral nervous system. These receptors are closely involved with the immune system and therefore play a role in helping keep us well, and regulating our immune responses, like inflammation triggered by cannabinoid agonists. 

CB2 receptors also interact with calcium channels to regulate muscle movements and influence parts of vision, hearing, and touch. 

CB1 Receptors

Cannabinoid receptor type 1 is found primarily in axons within the cerebellum and spinal cord in the central nervous system (CNS). CB1 receptors are G protein-coupled receptors, or (GPCR). 

The CB1 receptors are dictated by the CNR1 gene, which has two transcript variants. This essentially means that there are two ways that mRNA can read this gene, which may slightly influence the presentation of your CB1 receptors.

These receptors are more numerous than any other type of receptor in the brain. They express themselves primarily in parts of the brain like the pyriform cortex, the hippocampus, and the basal ganglia. 

CB1 receptors are responsible for most of our body’s homeostatic functions, like basal body temperature regulation, hunger, thirst, respiration, and pulse. 

Their functions include, but are not limited to: 

  • Interacting with potassium ion channels to help maintain electric voltage in the cells.
  • Influencing glutamate and GABA to suppress excitation and inhibitory responses.
  • Interacting with mitogen-activated protein kinase (MAPK) intracellular signaling pathways.
  • Modulating adenylate cyclase to influence levels of cAMP, a cellular messenger that interacts with neurotransmitters and hormones.
  • Interacting with allosteric modulators to promote homeostasis.

These receptors work on a feedback system that allows for both the inhibition of responses and neurotransmitters (known as negative feedback) and the increase of these responses and neurotransmitters (known as positive feedback). 

Why Are CB1 Receptors Important?

Because CB1 receptors play a vital role in our homeostasis, understanding them better can lead to advances in our ability to stay healthy and in our ability to restore our bodies to wellness when we are sick. 

Some of the most common illnesses that affect the American population make up a condition known as metabolic syndrome. These illnesses include:

  • Obesity. This is defined as having a BMI over 30. Because CB1 receptors play an active role in hunger, stimulating these receptors may help decrease hunger, and studies of mouse brains and rat brains have consistently supported this theory. 
  • Unhealthy cholesterol and blood pressure. These negative health markers can increase the risk of heart disease, heart attack, and stroke.
  • Insulin resistance. A precursor to diabetes, this condition happens when cells become resistant to insulin and can no longer use it properly. 

Higher levels of the body's endogenous cannabinoids (which we’ll discuss below) have been associated with lower rates of metabolic syndrome. 

There’s also promise that being able to stimulate synaptic responses among CB1 receptors could help provide new therapies for mental health. 

What Are Endocannabinoids? 

The body produces endocannabinoid receptor ligands, which are molecules that interact with these receptors. Two have been discovered, both of which are derivatives of arachidonic acid. 

  1. Anandamide. This endocannabinoid is also known as AEA. It’s known as the bliss molecule because it actively engages with hippocampal CB1 receptors responsible for regulating pain and sleep. 

Although it can bind to CB2 receptors, it doesn’t do it very well, so it’s not considered a fully-acting endocannabinoid. 

  1. 2-Arachidonoylglycerol (2-AG). Prevalent in the central nervous system, this endocannabinoid helps release neurotransmitters. It actively engages in processes that control memory, energy, emotional regulation, and pain.

Unlike anandamide, this endocannabinoid can bind with CB1 and CB2 receptors, making it a fully-acting endocannabinoid. 

These are the two endogenous cannabinoids your body produces. Still, other compounds in nature and synthetically created interact with the endocannabinoid system and your CB1 and CB2 receptors. 

What Are Cannabinoids?

Cannabinoids are plant-based or synthetic compounds that interact with CB1 and CB2 receptors. THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol) are two of the most potent. Both come from the cannabis sativa plant. 

THC is fully acting, binding with both receptors and triggering the dopamine release in the hippocampus. CBD can’t bind very well with either receptor, but it’s a good modulator of the psychoactive effects that THC can cause. Synthetic cannabinoids currently have no therapeutic purpose and are used only recreationally.

Why Are Fully-Acting Endocannabinoids Important?

For the highest level of receptor interaction, endocannabinoids that can stimulate both CB1 and CB2 receptors are necessary. Your body’s endocannabinoids are made by synthesizing certain lipids (fatty acids) using enzymes. Your body makes one readily (2-AG), but the field of pharmacology has long awaited the discovery of another, and now, we have it. 

What Is Pentadecanolycarnitine (PDC)?

Researchers have discovered the second-ever, fully-acting endocannabinoid known as pentadecanolycarnitine (PDC). The body uses a fatty acid called pentadecanoic acid (C15:0) and carnitine, a chemical produced by the brain, to synthesize PDC, which can fully interact with both CB1 and CB2 receptors. 

This is big news because it means that supplementing our bodies with this particular fatty acid could help produce more of this fully-acting endocannabinoid we can use to help achieve homeostasis and protect us against illness. 

How Was It Discovered?

While helping dolphins live healthier lives, Dr. Stephanie Venn-Watson, a veterinary epidemiologist, discovered that some geriatric dolphins had fewer age-related illnesses than others.

Dr. Venn-Watson found that higher circulating levels of a particular fatty acid were responsible for many of the health benefits seen in the healthiest dolphins. She went further, looking into the health benefits of this molecule in human populations and, three years later, published her findings in Nature's Scientific Reports in 2020.

What fatty acid was responsible for the health benefits, you ask?

The fatty acid was C15:0, aka pentadecanoic acid. This odd-chain, essential, saturated fatty acid can reverse cellular aging, giving our cells a fighting chance to remain healthy as they age.

Where C15:0 Is Found

C15:0 is primarily found in trace levels in whole-fat dairy products and some types of fish and plants. However, increasing your intake of whole-fat dairy products comes with extra calories, sugars, and high levels of the "bad" even-chain saturated fats.

A solution? Fatty15

Fatty15 is a breakthrough supplement borne from scientific discovery, containing one pure ingredient, FA15™, the pure-powder, vegan-friendly, sustainably-produced, award-winning version of C15:0. What’s more, science supports that fatty15 has more clinically relevant benefits than the purest form of omega-3 (EPA).

In fact, in these studies, the pure C15:0 ingredient in fatty15 had 26+ more cellular benefits than omega-3, repaired 83% of cell types (versus 33% with EPA), and was safe for all 12 cell types at all doses. In comparison, at the highest dose, EPA was toxic to 33% of cell systems.

Better and safer for our cells, and necessary for creating more PDC, this little fatty acid has a big job, and just one pure, vegan-friendly capsule per day is enough to restore your circulating levels of C15:0 and bring your body back into balance. 

Fatty15: The Gateway to PDC

The endocannabinoid system controls many processes in your body that keep you healthy. CB1 receptors inside the system regulate many of our bodies’ homeostatic functions. We can interact with these responses by stimulating these receptors to help increase our overall wellness. 

PDC is the second-ever fully-acting endocannabinoid that can bind to CB1 and CB2 receptors. Your body needs C15:0 to make it; the easiest way to get it is by daily supplementation with fatty15. 

Fatty15 is the solution for helping increase your body’s ability to produce more endocannabinoids and helping you feel more balanced. By taking fatty15 you get the benefits of an essential fatty acid and a fully acting endocannabinoid. 




Sources:

The endocannabinoid system: Essential and mysterious | Harvard Health

Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic Potential | PMC

Cannabinoid receptors: where they are and what they do | PubMed.gov

Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health | Scientific Reports

Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? | Scientific Reports

Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems | PLOS ONE

Article Structure of a Signaling Cannabinoid Receptor 1-G Protein Complex|Science Direct

Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review | PMC

CB1 cannabinoid receptor-mediated modulation of food intake in mice | PMC

Profile photo for Eric Venn-Watson

Eric Venn-Watson M.D.

Eric is a physician, U.S. Navy veteran, and Co-founder and COO of Seraphina Therapeutics. Eric served over 25 years as a Navy and Marine Corps physician, working with the special forces community to improve their health and fitness. Seraphina Therapeutics is a health and wellness company dedicated to advancing global health through the discovery of essential fatty acids and micronutrient therapeutics.

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