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The Role of the Endocannabinoid System in Fertility

Published by Dr. Venn-Watson
Dr. Eric Venn-Watson’s Highlights
  • The endocannabinoid system supports numerous systems in your body that help your body self-regulate. 

    Many aspects of fertility require self-regulation of ovarian hormones, uterine tissues, and muscles. 

    Stimulation of the ECS can support the regulation and balance of reproductive functions. 

The endocannabinoid system (ECS) has been studied for decades, but in recent years we’ve learned much about what this intricate signaling system does to help sustain balance in our bodies. 

The ECS helps keep your body in a state of homeostasis by helping to regulate systems like thermoregulation, mood, appetite, sleep, metabolism, and even fertility. Together, we’ll look at how it affects fertility and what you can do to support the ECS and achieve better overall equilibrium in your health. 

A Brief Overview of the Endocannabinoid System

The endocannabinoid system can seem very complex if you aren’t familiar with it. In many ways, it is, but we’ll break it down into three easy-to-understand parts: receptors, enzymes, and endocannabinoids. 


Two types of receptors make up the endocannabinoid system. These receptors are found all over the body and work by collecting data and sending it back to your brain to let your control center know a change is needed to help maintain balance. 

  • CB1 Receptors. These receptors are primarily found on the neurons in your brain and spinal cord. They are the most numerous type of receptor and outnumber CB2 receptors. They are directly involved with the regulation of mood, sleep cycle, respiration, body temperature, cognition, and even pain.
  • CB2 Receptors. These receptors are located in your immune tissue and digestive tract. They help aid in digestive processes, help keep your immune function balanced and self-regulated, and also play a role in sensory processing (your ability to see, hear, and touch).

These receptors need stimulation by compounds that bind to them and help trigger signaling pathways that effectuate regulatory changes in the body that help bring you back to homeostasis. Those compounds are called cannabinoids. 


Your body makes compounds that bind with the receptors of the ECS and stimulate them, helping start the signaling process that helps keep your body balanced. For years, it was believed there were only two cannabinoids made the body (i.e. endocannabinoids): anandamide, or “AEA,” and 2-Arachidonoylglycerol, or “2-AG.”

  • AEA is only able to bind with CB1 receptors. It’s been referred to as the “bliss” molecule because it stimulates the same receptors and areas of your brain that plant-based cannabinoids (like THC) do. 

AEA is rapidly broken down by the body, lasting only about 30 minutes once it is produced. 

  • 2-AG is more abundant than AEA and can bind to both CB1 and CB2 receptors, which means it is considered “fully acting.” However, like AEA, 2-AG is rapidly metabolized and has a very short half-life. 

In a groundbreaking new study, researchers discovered that our bodies make a third endocannabinoid, the second-ever discovered, fully-acting endocannabinoid we know of. Pentadecanoylcarnitine, or “PDC,” can bind two both receptors and has a longer lifespan inside our cells than AEA or 2-AG. Later, we’ll discuss how PDC is made. 


Once endocannabinoids have been used to stimulate the receptors in the ECS, your body needs to get rid of them, and they do this by using enzymes to break them down. 

  • AEA is broken down by fatty acid hydrolase.
  • 2-AG is broken down by monoacylglycerol lipase.

These enzymes metabolize the endocannabinoids and ensure they are safely removed from our systems. 

Now, let’s look at how the ECS’s system of signaling and balancing plays a role in fertility. 

Understanding Fertility 

It might seem like pregnancy happens easily for people who have never had issues trying to become pregnant, and for many people, that is true. However, fertility is complex, and for those who struggle with fertility, it can seem like a challenge. 

For pregnancy to occur, a healthy sperm must successfully implant a mature, healthy egg. This egg must then implant into the uterus lining and be supported successfully until the baby has grown to term. 

The ECS plays a role in fertility at several different phases. 

Egg Maturation

During each menstrual cycle, follicles form on the ovaries. These follicles house oocytes, which are immature eggs. Until ovulation, the eggs remain in the follicles, and one egg will grow to maturity. 

The ECS is active during egg maturation. AEA levels rise and are present in special hormone-producing cells (called granulosa) within the ovaries, helping ensure hormonal balance and ensuring the mature egg reaches maturity. 

Transportation of An Embryo to the Uterus

Once an egg has been fertilized, it needs to travel to the uterus, and it does this by way of the fallopian tube, or oviduct. The muscles in the oviduct contract to move the embryo to the uterus. 

Ovarian hormones control the regulation of these contractions, and receptors of the ECS located in the fallopian tube tissue indicate that this regulation is also governed by the modulation of these receptors. 

Implantation of the Fertilized Egg

When a mature, fertilized egg reaches the uterus, it needs to implant into the tissue lining the uterus, called the endometrium. The endometrium tissue changes throughout the menstrual cycle. The changes in these tissues allow for egg implantation after ovulation and allow for the shedding of the tissue if an egg is not implanted. 

Again, hormones are at work. Hormones regulate the changes in endometrial tissue and, along with them, the ECS. Recently, researchers discovered that the ECS specifically regulates endometrium tissue by controlling how the cells of the endometrium move and contract. 

Why This Is Important

Considering the influence of the ECS at several different phases of conception could mean huge leaps in how we understand, diagnose and treat fertility issues. 

Stimulation of the ECS by the body’s own endocannabinoids can help restore regulation and balance to the hormones it interacts with and can directly impact fertility. But first, we must produce endocannabinoids, preferably fully-acting ones like 2-AG and PDC. Because PDC is longer-lasting in our bodies, supporting ways of producing this important compound makes sense. 

How Is PDC Made?

The body makes endocannabinoids by synthesizing certain fatty acids. To make PDC, the body needs a fatty acid called pentadecanoic acid, or C15:0. 

What Is C15:0?

C15:0 is an odd-chain, saturated fatty acid that science supports as the first essential fatty acid to have been discovered since the omegas more than 90 years ago. Essential means our bodies need it to maintain our health and wellness but cannot readily make it on their own. 

Although we’ve heard that all saturated fats are bad, science supports that this is not the case. 

This class of odd-chain, saturated fatty acids, specifically C15:0, is beneficial to our health. In addition to helping us create PDC, C15:0 has also been associated with better metabolic, immune, liver and heart health.* 

How Do We Get C15:0?

Unlike other fatty acids, you may not be getting enough C15:0 through your diet. It’s found primarily in full fat dairy products. However, simply increasing your whole fat dairy intake may not be an ideal solution because that would also mean ingesting additional calories and bad, pro-inflammatory, even-chain, saturated fatty acids. Thankfully, there’s a solution. 

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Researchers studying the health and longevity of dolphins discovered a relationship between a particular fatty acid in the diets of some of these animals that aged more healthily than others. You guessed it; that fatty acid was C15:0. They dug deeper and studied the effects of this fatty acid in humans, publishing their results in Nature Scientific Reports in 2020. Since 2020, there have been more than 70 scientific publications highlighting the essentiality and benefits of C15:0.

As a result, they developed fatty15, the first and only supplement to contain FA15™. This pure, vegan-friendly, sustainably-produced, award-winning, version of C15:0 is the smart way to restore your circulating levels of C15:0, make more PDC, and support your overall health and wellness.*

Get Fatty, Get Balanced

Your body is designed to operate in a state of perfect balance. Support its ability to balance by fueling it with C15:0, the fatty acid that helps it make more of the endocannabinoid it needs. 

Ready to get started? Order your trial kit of fatty15 here, or learn more about what C15:0 can do here



The Biodisposition and Metabolism of Anandamide in Mice | Journal of Pharmacology and Experimental Therapeutics

Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health|PubMed.gov

The endocannabinoid pathway and the female reproductive organs in|JME.bioscientifica.com

Endocannabinoid system regulates migration of endometrial stromal cells via cannabinoid receptor 1 through the activation of PI3K and ERK1/2 pathways - Fertility and Sterility

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

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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