A New Endocannabinoid? | A Look Into PDC

WRITTEN BY MELANIE FLORES AND DR. SWATHI

Many of us have heard of the two major cannabinoids that come from the cannabis plant, tetrahydrocannabinol (THC) and cannabidiol (CBD). There are also endocannabinoids that are created on demand by and in our bodies called endocannabinoids. It turns out there are actually several other  endocannabinoids that are synthesized to help regulate physiological processes internally. Each of these endocannabinoids possess different proposed effects. Several of these chemicals have been studied in various clinical trials, but many more continue to be discovered every year.

What are Endocannabinoids?

Before we go into the discovery of endocannabinoids, it is important that you understand the endocannabinoid system (ECS) in the human body. The ECS was discovered in the 1990s and found not only in mammals, but also in different species such as fish, reptiles, and birds.  The ECS controls many of the important cognitive and regulatory functions of the body and helps us maintain a sense of homeostasis. The ECS helps balance emotions, pain, temperature, sleep, memory, digestion, stress, appetite,  inflammation, and immune responses.

Cannabinoids are a group of chemicals that relate to each other based on their physical structure and shape. While cannabinoids are acquired exogenously from the cannabis plant, like THC and CBD, endocannabinoids are actually made independently by the human body. Once your body produces an endocannabinoid, the molecule binds to a specific cannabinoid receptor. The main cannabinoid receptors in the body are CB1 and CB2. Once bound to a receptor, endocannabinoids proceed to produce a wide range of regulatory effects on the body. The two most common endocannabinoids are named anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

Discovery of Pentadecanoylcarnitine (PDC)

The discovery of this “new” endocannabinoid was completed by a husband-wife duo, Stephanie and Eric Venn-Watson, in San Diego, California. The Venn-Watsons research bottlenose dolphins through the US Navy Marine Mammal Program.  Pentadecanoic acid is found in full-fat dairy, along with other fatty foods such as fish. Pentadecanoic acid is known to play a role in regulating physiological processes such as pain control, mood, sleep, and inflammation.It was discovered that PDC is synthesized in the mammalian body from a dietary saturated fatty acid called pentadecanoic acid (C15:0).

A 2015 study completed by Stephanie Venn-Watson revealed a link between higher circulating levels of the saturated fatty acid C17:0 and a reduced risk of chronic metabolic disease and low iron levels in bottlenose dolphin models. A second study showed that when these dolphins were fed a consistent high C15:0 specific fish diet, they had lowered levels of insulin and cholesterol, and were also at a decreased risk for developing anemia. A 2020 study tested the effects of C15:0 on human cells and similar benefits in lowering anemia and cholesterol levels were found.

A third study completed by Stephanie Venn-Watson in 2022 showed that the endocannabinoid PDC had dose-dependent anti-inflammatory activities across five cell systems that mimicked cardiovascular, immune, pulmonary, skin, and abnormal disease states. The study also revealed that PDC targeted and activated both CB1 and CB2. Additionally, PDC was also seen to mimic the neurotransmitters serotonin and inhibit histamine. Serotonin regulates happiness, focus, body temperature, sleep, libido, and appetite. Histamine inhibitors are known as antihistamines and are often used to alleviate allergies.

Looking Ahead

The detection of PDC, brings the total count of endocannabinoids discovered to 8. The other 7 endocannabinoids found include Anandamide (AEA), 2-AG, Palmitoylethanolamide (PEA), Docosahexaenoyl ethanolamide (DHA-EA), Docosahexaenoyl-glycerol (DHG), Eicosapentaenoyl ethanolamide (EPA-EA), and Eicosapentanoylglycerol (EPG). The anti-inflammatory benefits of PDC indicate that the chemical could be studied in future clinical trials for the attenuation of immune, cardiovascular, skin, and pulmonary ailments.

In January 2021, the Venn-Watsons that discovered PDC launched a product that contains pure Pentadecanoic acid called “Fatty15 '' through their company Seraphina Therapeutics. They hold licensing rights from the US Navy to commercialize C15:0. The product is being promoted for overall health and wellness, and the fact that it increases PDC in the body is being highlighted as one of its essential benefits. As more research comes out exploring the possible benefits of C15:0 and PDC in the body, more supplements and clinical trials are bound to appear.

Although these results all seem very promising, additional human trials and further research is needed before any clear conclusions can be made about PDC and the possible effects of deficiency and supplement addition.

References

1. Tran T, Varanasi S. The endocannabinoid system: How does it work? Element Apothec.https://elementapothec.com/blogs/news/how-does-the-endocannabinoid-system-work?_pos=2&_sid=30a6b91dd&_ss=r. Accessed March 6, 2023. 
2. Seltenrich N. Dolphin study identifies hitherto unknown endocannabinoid. Project CBD.https://www.projectcbd.org/dolphin-study-identifies-hitherto-unknown-endocannabinoid.Published September 10, 2022. Accessed January 31, 2023.
3. Venn-Watson S, Reiner J, Jensen ED. Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health. Sci Rep. 2022;12(1):13717. doi: 10.1038/s41598-022-18266-w. PMID: 35999445; PMCID: PMC9399118.
4. Venn-Watson, Stephanie K et al. Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins. PloS. 2015;10(3). doi:10.1371/journal.pone.0132117
5. Venn-Watson, Stephanie et al. Modified fish diet shifted serum metabolome and alleviated chronic anemia in bottlenose dolphins (Tursiops truncatus): Potential role of odd-chain saturated fatty acids. PloS. 2020;15(4).doi:10.1371/journal.pone.0230769
6. Venn-Watson, S., Lumpkin, R. & Dennis, E.A. Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential?. Sci Rep. 2020; 10(8161). https://doi.org/10.1038/s41598-020-64960-y
7. Tsuboi, Kazuhito et al. Endocannabinoids and related N-acylethanolamines: biological activities and metabolism. Inflammation and regeneration.2018; 38 (28). doi:10.1186/s41232-018-0086-5

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This article was edited by Dr. Swathi and was written by Element Apothec Scientific Communications Intern, Melanie Flores. She is a Doctor of Pharmacy (PharmD) student at Oregon State University and Oregon Health & Science University College of Pharmacy in Portland, Oregon.