Learning the Endocannabinoid System: Sunil Pai, MD Interview

By Curt Robbins

This article is the second in a series of interviews with a licensed clinical practitioner regarding the central role of the endocannabinoid system (ECS) in human health. This installment covers the wellness benefits of less common varin phytomolecules, such as CBDV and THCV, introduces the theory of endocannabinoid deficiency, and explores the efficacy of cannabinoids like CBD for dogs and cats.  

Sunil Pai, MD is an internationally recognized expert in integrative medicine based in Albuquerque, New Mexico and author of the critically acclaimed 2016 book An Inflammation Nation. He is a lecturer and a contributing author to medical textbooks and scientific journals. Pai is a practicing doctor who combines an evidence-based approach with 20 years of clinical experience. Each year, he educates thousands of physicians and medical professionals about the nuanced biochemistry involved in the administration of hemp-derived cannabinoids and terpenes for the treatment of a variety of disease states and conditions.

Curt Robbins: Thanks for taking time from your clinical schedule, Dr. Pai. In this installment, let’s cover the relationship between the ECS and the immune system, with a focus on how a healthy ECS affects immune function and disease states. 

Sunil Pai, MD:  The ECS is one of the self regulatory systems of the immune system. The goal is to demonstrate a healthy ECS response. However, with the rise of chronic diseases due to a variety of dietary, lifestyle, and environmental factors, many have a dysfunctional ECS. This leads to a decreased ability to self-regulate certain aspects of their immune system that are involved in bodily systems such as the regulation of inflammation and digestion, mood and memory, and direct physiological responses such as repairing tissue mechanisms and defense against infections.  

The goal of establishing and maintaining a healthy ECS, via a healthy lifestyle, is key. Those who enjoy a relatively balanced ECS experience something called homeostasis. The majority, who lack homeostasis, often benefit significantly from the use of cannabis or hemp. 

I want to emphasize that, although use of plant medicines such as hemp is important, it is only a part of the overall actions that one can take to balance their immune system. In fact, when one leads a healthier lifestyle, the need for cannabis and hemp medicine is actually decreased. Also, homeostasis involves maximum benefit from relatively small maintenance doses (which also involve the least expense, an important issue for many patients, especially those on a fixed income).  

CR: Several phytomolecules other than cannabidiol (CBD) and tetrahydrocannabinol (THC) have been revealed, via a wealth of peer-reviewed research studies, to provide wellness benefits. Among these are varin cannabinoids like CBDV, CBGV, and THCV. Why are the varin analogs of cannabinoids appealing to clinical practitioners like yourself?

SP: The volume of new research regarding the other cannabinoids in cannabis and hemp provides information about use of different cannabinoid analogs for targeting specific physiological responses or particular  mechanisms of relief.  This allows clinical practitioners, over time, to utilize these plant medicines to treat specific health conditions—as opposed to an inferior broad-based support approach. Most research today remains limited to petri dishes or animals, unfortunately, but it provides us with solid guidance and direction for future research efforts.

CBDV, or cannabidivarin, is non-psychoactive. Early data suggests that CBDV may be useful in the treatment of epilepsy, nausea, Rett Syndrome, Fragile X, and Autism Spectrum Disorder. Unfortunately, a recent placebo-controlled human trial conducted by a pharmaceutical company failed to demonstrate benefits. However, this might be due to the use of high-dose CBDV and the lack of other balancing cannabinoids that some believe are involved in an ‘entourage effect’ involving enhanced efficacy. 

CBGV, or cannabigerovarin, is also non-psychoactive and has demonstrated promise for use with inflammation-based conditions such as arthritis and fibromyalgia, including skin conditions. Research suggests that CBGV might enhance the effects of THC because it may help the infamous cannabinoid to bind more effectively to cellular ECS receptors found throughout the body, including in the brain and bones. Additionally, CBGV may help improve the bioavailability of CBD and, thus, provide a physiological boost for this cannabinoid (and perhaps others). Products that feature more CBGV may help improve the THC response from cannabis and the CBD response from hemp.

Unlike most varin cannabinoids, THCV, or tetrahydrocannabivarin, is mildly psychoactive at low doses and sometimes more psychoactive than its cousin THC at potent doses. It has demonstrated benefits for improving alertness and alleviating depression. This special cannabinoid may also reduce pain through analgesia, regulate blood glucose, suppress appetite—of value with eating disorders and diabetes—reduce panic attacks from social anxiety and PTSD, and contribute to bone health…both slowing degeneration and stimulating regeneration. THCV has also been shown to help in treatment of the neurological, cognitive, and motor control symptoms associated with Alzheimer’s and Parkinson’s.

After clinicians and patients better understand the roles of these analogs, they can choose cannabis strains, blends, and products that achieve better targeted results for particular health conditions and needs. I recommend that clinicians and patients carefully review the cannabinoid profile from cannabis or hemp products for which they are considering consumption by checking the Certificate of Analysis, or COA. A COA should be provided by either the legal retail dispensary or the licensed manufacturer, depending on the jurisdiction. 

If a dispensary or manufacturer cannot provide a COA, I recommend avoiding their products. In cases lacking a COA, consumers and patients must rely on marketing and sales tactics versus actual ingredient lists and relative ratios. Because there is no overarching federal regulation governing how these products are formulated and manufactured, a great deal of variance exists in the market with respect to their potency, purity, and safety.

CR: The theory of endocannabinoid deficiency suggests that an ECS that is deficient in cannabinoids loses balance, a state called homeostasis, and that a lack of homeostasis often results in a variety of disease states or other health vulnerabilities. What is your opinion of the relationship between ECS health and potential disease states resulting from a lack of homeostasis?

SP: Probably most people have an endocannabinoid deficiency at some level. Disease is the loss of homeostasis within the overall body, on different levels, due to physiological, anatomical, immunological, biochemical, and even spiritual causes. Most modern humans are not as healthy as in times past, in my opinion. I cover this topic in detail in my book An Inflammation Nation. 

Avenues of improvement for the average North American include the Standard American Diet (SAD) and lifestyle, avoidance or removal of environmental toxins, avoidance or removal of infections resulting from bacteria, virus, or parasites, and decreased stress—to name only a few. When humans develop deficiency-related conditions, this state often leads to additional inflammation-based conditions or symptoms. This, in turn, creates a downward spiral. Put simply, immune dysfunction leads to the body’s inability to fight, fix, and repair. 

The ECS plays a major role in the healing process. When the body is healthy, ECS receptors do not need to be as active and exist in more of a resting state. When the body is diseased and seeking homeostasis, CB1 and CB2 receptors in the ECS are in an active state. However, the overall health of the body is what most influences the effectiveness of any ECS response.

CR: Dozens of companies offer hemp-based products for pets such as dogs and cats. How do these mammals benefit from cannabinoids like CBD and THC?

SP: All mammals have an ECS. This means that cannabinoids such as CBD may play an important role in the treatment of certain ailments in dogs and cats. For example, benefits may be pronounced in breeds of dogs that are prone to diseases such as hip arthritis. The available research on CBD for pets has demonstrated benefits for asthma, arthritis, anxiety, seizures, and cancer. In my practice, I have many patients who have used CBD from hemp, a broad spectrum featuring zero THC, for their pets who have reported great results. 

One must remember that animals are more sensitive to CBD due to differences in number of receptors and lower weight and size compared to humans. I tend to recommend starting with the lowest possible amount based on a particular pet’s weight. As in pediatrics, pet owners should employ very low doses of cannabinoids such as CBD based on the pet’s weight. Products that allow pet owners to calculate and dose according to body weight, such as tinctures, are of obvious value.

I don’t recommend the use of THC products for animals unless given under direction of a veterinarian. Dogs and cats feature different metabolic processes and are, in some cases, extremely sensitive, both via the consumption avenues of inhalation and ingestion. THC can actually be dangerous for many pet breeds. Sadly, pet deaths have resulted from ingestion of medical-grade, high-potency THC products. Again, THC may be helpful in certain use case scenarios, but proper veterinarian guidance should always be obtained.

There’s just as much interest in the marketplace for cannabis and hemp products for pets as there is for humans. Many pet products, like human nutritional supplements, are relatively unregulated. Often, brands employ lower quality cannabis or hemp and other herbal ingredients, including fillers, flavors, and animal by-products, especially in snack treats. I recommend extreme caution and thorough investigation when it comes to pet products. Again, I tell my patients and colleagues to always seek a COA from a certified laboratory prior to using a product for pets or humans.