The Endocannabinoid System 101

The endocannabinoid system (ECS) is an extensive biological system comprised of specialized cannabinoid receptors, endogenous lipid-based endocannabinoids, and enzymes responsible for synthesizing and metabolizing the endocannabinoids to maintain a regular supply. All combined, research has now demonstrated that this highly sophisticated, self-regulatory system affects a wide variety of tissues and functions in the human body.

Phytocannabinoids, derived from plants like Cannabis sativa, stimulate the same cannabinoid receptors, eliciting therapeutic effects like pain modulation and relaxation. How the ECS functions is still not completely understood, but as research races to keep up with a burgeoning cannabis industry, scientists are rapidly unraveling the mysteries of this powerful system.

What is the Endocannabinoid System (ECS)?

Discovered in the 1990s, the ECS is thought to be one of the most vital and vast receptor systems for sustaining good health. It affects many of our biological processes. Not just for humans, but also for all vertebrate animals, and some invertebrate too.

The system contains cannabinoid receptors, the “locks” and a group of diverse chemical compounds called cannabinoids, the “keys.” The body produces its endogenous cannabinoids, most notably anandamide and 2-arachidonoylglycerol (2-AG).

Endocannabinoids are found in the immune system, the central nervous system, the brain, organs, connective tissue, and glands.

So, where does hemp fit into the picture?

There’s a reason why hemp works so well with the ECS. It has a set of keys to the kingdom! Hemp contains elevated levels of Cannabidiol (CBD), an active phytocannabinoid that works synergistically with other secondary phytocannabinoids and compounds like terpenes and flavonoids.

What does the ECS do?

The primary objective of the ECS is to maintain homeostasis. The word homeostasis comes from the Greek words for the “steady.”  For our purposes, it means providing a state of internal stability necessary for survival, despite fluctuations in our external environment. The ECS is also involved in many physiological processes like appetite, sleep, digestion, mood, memory, metabolism, neuroprotection, hormones, and heart function.

What Are The Locks And Keys?

The ECS has a series of receptors on cells throughout the body designed to accept cannabinoids. There are two main types of receptors, cannabinoid 1 (CB1) and cannabinoid 2 (CB2) that receive three types of cannabinoids:

  • Endocannabinoids – The cannabinoids our body makes
  • Phytocannabinoids – Natural plant cannabinoids
  • Synthetic Cannabinoids – Synthetically created in a lab

CB1 is mostly found in the brain, and also the lungs, kidney, liver, bones, heart, male and female reproductive organs. This receptor is more keyed into tetrahydrocannabinol, the main cannabinoid found in marijuana.

CB2 lives in the immune system, with a significant presence in the spleen as well as the lungs, liver, bone, and muscle.

The Last Piece Of The ECS Puzzle

Metabolic enzymes, FAAH and MAGL, are used by the ECS to accelerate chemical reactions and efficiently break down cannabinoids once they’ve served their purpose.

In Conclusion

Maintaining homeostasis is critical to human health and longevity. The discovery of the Endocannabinoid System has revealed a novel way for practitioners to help their patients maintain homeostasis. By working with patients on an individual basis, it’s now possible to use products containing hemp-derived cannabidiol to elicit specific therapeutic effects. As research on the ECS continues to expand, the future of ECS-targeted therapy is one of the most exciting developments in modern medicine.

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CBD Dosing


Hemp-derived cannabidiol (CBD) is still relatively new, so standards for dosing and prescribing have not been universally established. In fact, the FDA has yet to establish an RDI for CBD, meaning it does not have an official serving size.

Considering CBD acts as an antagonist of CB1 receptors and at higher doses can saturate these receptors and act on numerous other receptors on the body, the general consensus with CBD dosing is to “Start Low and Go Slow”. By following this, the ideal dosing level can be established for each individual patient.

Dosing Considerations

To date, no fatalities with phytocannabinoid use, CBD have been reported. The general consensus is that chronic use of CBD specifically is well-tolerated in humans, with doses up to 1,500 mg/day considered safe. (REF)

When prescribing oral hemp-derived CBD, some basic guidelines can be taken into consideration. Typical standard dosing of CBD extracts starts at 10mg or 1ml per day, depending on extraction and equivalency. Some products will allow for micro-dosing at 2.5 to 5 mg, which may be advised based on what other medications and supplements a patient is taking.

Standard dosing has not been established for cannabidiol, regardless of condition. However, early research and reviews are revealing suggested dosing for a select number of conditions.

Insomnia – 160mg per day (REF)

Social Anxiety Disorder – 400-600mg per day (REFREF)

Arthritic Pain – no dosing guidelines exist, but animal trials are pointing to 25mg/kg as an effective starting dose (REFREFREFREF)

Treatment-Resistant Epilepsy in Pediatric Population – 10 to 20 mg/kg/day (REF)

  • Note: current clinical trials demonstrating the effectiveness of CBD in treating children with Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS) only applies to Epidiolex, an FDA-approved pharmaceutical extract of CBD. There is no current research using non-standardized CBD extracts in TRE.


Clinicians: if you are using these guidelines, you are reminded that you do so at your own risk/discretion. These guidelines are intended to act as a review of existing clinical research on cannabidiol dosing recommendations. As clinical trials are released and dosing guidelines are updated, we will periodically update this section.

Additionally, if you would like to submit an article that provides context for dosing recommendations, please send it to our Integrative Medical Advisory team for review via

Last Updated: January 25, 2019

CBD Safety

Numerous small studies of CBD safety have been conducted and the current conclusion is that an upper tolerable limit has not been established. To date, no significant central nervous system, vital sign or mood side effects have been observed at doses of up to 1500 mg/day (oral) or 30 mg (intravenous) in both acute and chronic administration. (REF)

Based on in vitro observation of Interleukin 8 and 10 inhibition and lymphocyte apoptosis, there may be some theoretical risk of immunosuppression. (REF)

Long-term trials have not been established, so practitioners are cautioned to restrict long-term of use of cannabidiol-containing products to a limited period.

General Patient Recommendations

  • Start Low. Go Slow.
  • CBD oils are slow-acting and long-lasting. Consume slowly and deliberately.
  • There are no reported cases of lethality and CBD has minimal reported side effects, but beware of potential side effects at doses higher than 500mg per day.
  • Always note the equivalency factor in dosing to calculate the quantity of mg being consumed per dose.
  • Sublingual consumption is faster-acting that oral consumption.
  • Drowsiness from CBD use is unlikely, but due to the varied effect per person, patients are encouraged to consume CBD-containing products in a safe and comfortable environment, at least for the first few weeks of use.

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The 2018 Farm Bill Passes

On December 20, 2018, the 2018 Farm Bill was signed into law by President Donald Trump. Included in the law is a provision that legalizes the domestic cultivation, production, and commercial development of hemp and hemp products at the federal level.  Under these new regulations, hemp is defined as “the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol [THC] concentration of not more than 0.3 percent on a dry weight basis.”

The 2018 Farm Bill removed hemp and, therefore, hemp-derived cannabidiol (CBD), from Schedule 1 of the Controlled Substances Act, effectively paving the way for legal hemp cultivation, production, and distribution. CBD is a phytocannabinoid derived from Cannabis sativa that is becoming increasingly well-known for its purported health benefits.

The Hemp Business Journal estimates that the U.S. hemp industry will be worth approximately $1.9 billion by 2022, much of which can be attributed to CBD. Considering the recent FDA-approval of Epidiolex, the first cannabis-derived CBD-based pharmaceutical approved by the FDA, it’s also likely that there will be an increase in phytocannabinoid-containing pharmaceuticals.

Following the signing of the 2018 Farm Bill, the FDA release two key statements. The first classified three hemp-derived ingredients as GRAS (generally recognized as safe). The second specified that the phytocannabinoids THC and CBD are considered drug ingredients, and as such, are not currently permitted for use in food and supplements. Hemp industry lobbying associations, including U.S. Hemp Roundtable, are working with the FDA to issue a new regulation allowing for hemp-derived CBD to be included in food and supplements.

As a result of these announcements, what’s likely to happen is an increase in hemp-derived products industry-wide, including fabrics, food products, and cosmetics. Once the reclassification of THC and CBD, there will also likely be an explosion in phytocannabinoid-containing over-the-counter products. Until then, access to high-quality CBD-containing supplements will remain somewhat limited.

Research in this field is growing at an exponential rate, so practitioners can expect to witness significant developments this year when it comes to dosing recommendations and standard of care. For instance, a basic Pubmed search using the term “cannabidiol” reveals that nearly 200 studies were published in Q4 2018 on this topic alone, not to mention THC or the wide variety of therapeutic terpenes found in Cannabis sativa.

The future of hemp-derived CBD and its associated products is bright. At NPFS, we look forward to working with our practitioners in using the highest-quality CBD-containing products to develop optimal treatment plans for their patients.

A new era of medicine has arrived and we’re in this journey together!

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The Current Legal Status of Hemp-Derived Cannabidiol

Agricultural hemp products are now federally legal in the United States, having been removed from the Controlled Substances Act with the signing of the 2018 Farm Bill on December 20, 2018. This means that hemp-derived ingredients, including cannabidiol (CBD), are no longer classified as controlled substances or illegal. However, what remains in limbo is the FDA’s stance on CBD, currently (as of the writing of this article) not allowing CBD to be listed as a food or supplement ingredient.

In a statement issued by FDA commissioner Scott Gottlieb, MD following the signing of the 2018 Farm Bill, it’s stated that: Congress explicitly preserved the agency’s current authority to regulate products containing cannabis or cannabis-derived compounds under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and section 351 of the Public Health Service Act. In doing so, Congress recognized the agency’s important public health role with respect to all the products it regulates. This allows the FDA to continue enforcing the law to protect patients and the public while also providing potential regulatory pathways for products containing cannabis and cannabis-derived compounds.

At the same time that this statement was issued, the FDA released another statement confirming that hulled hemp seed, hemp seed oil, and hemp seed protein powder are generally recognized as safe (GRAS) based on their intended conditions of use. In other words, hemp-seed derived ingredients, in general, are considered safe for human consumption.

The FDA still maintains that CBD and Tetrahydrocannabinol (THC), the two most active phytocannabinoids found in Cannabis sativa, are to be classified as FDA-approved drugs since they were subjected to clinical trials prior to being marketed in the food and supplement market. To date, only one CBD-containing drug, Epidiolex, has been approved for consumption by the FDA.

Furthermore, what is yet to be confirmed are standardized clinical dosing recommendations with ingredients like CBD and THC. There are no current industry-accepted guidelines for dosing based on conditions, and these ingredients are, therefore, not included in medical standards of care.

As a result, the current legality of hemp-derived CBD remains somewhat in limbo, but all signs point to the FDA approving hemp-derived CBD for use in foods and supplements within the coming months. Federally, CBD is now legal for general consumption, but due to its previous classification as a drug ingredient, the FDA still needs to issue a formal change in regulation to allow CBD to be used in foods and supplements.

It is suggested that all clinicians prescribing hemp-derived CBD products to their patients do so with caution. Dosing should be conservative until further research establishes dosing standards.

For more information about dosing recommendations and a review of the current literature, click here. 2018 Year in Review

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