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Cannabis and the Endocannabinoid System

The Wonders of CBDs

CBD Molecule

Cannabinoids are the chemical compounds made by the cannabis plant that unlock its many healing secrets.

There are over 100 known cannabinoids and these chemicals imitate the endocannabinoids naturally produced in the human body.

The shiny little crystals you see on cannabis buds are called trichomes where cannabinoids are stored.

Human bodies (and many animals) have endocannabinoid systems (ECS), meaning that cannabinoids are naturally made so they can bind to endocannabinoid receptors creating changes in our physiology.

To understand the master gland and immune system of the human body it is crucial to have a basic understanding of the endogenous cannabinoid system, otherwise known as the endocannabinoid system (ECS).

The endocannabinoid system is essential to human health because it maintains homeostasis in the body.

Research into the endocannabinoid system has increased in recent years as scientists begin to reveal how complex and important this system is to our bodies.

The legal cannabis movement started in San Francisco in the early 1990’s when it was discovered that cannabis treated many symptoms that AIDS patients suffered from, including pain.

It was medical marijuana laws that changed the legal status of cannabis nationwide, opening the doors for research and an adult-use market and creating a path towards full legalization.

Cannabis patients across the country have used the plant to treat a growing number of medical conditions.

In Colorado alone, there are nine different qualifying conditions for a medical card: cancer, glaucoma, HIV or AIDS, cachexia (wasting syndrome), persistent muscle spasms, seizures, severe nausea, severe pain, and Post Traumatic Stress Disorder (PTSD).

What Do CBD’s Do?

The endocannabinoid system (ECS) is responsible for maintaining homeostasis in the body. Homeostasis is defined as: “any self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival.”

If homeostasis is successful, life continues; if unsuccessful, disaster and ill health ensues.

The endocannabinoid system is made up of three parts:

cannabinoid receptors, endocannabinoids, and metabolic enzymes.

• Endocannabinoid receptors are found throughout the body on the surface of cells in the brain, organs, tissues, and glands. These receptors are embedded in cell membranes and produce varying reactions when stimulated by cannabinoids.

• Cannabinoids come from two distinct places — the body, which produces naturally occurring endocannabinoids, and foods like the cannabis plant, which produces phytocannabinoids.

• Metabolic enzymes act like a natural referee in that they destroy endocannabinoids once they are used up by the body. The two main metabolic enzymes are fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

This self-regulating system ensures the interaction of CBDs with the ECS only happens when needed and therefore keeps the workings of the endocannabinoid system relatively quiet to the conscious brain.

Because homeostasis is so important to health, all vertebrates and invertebrates are known to have an endocannabinoid system.

Cannabinoids can also be produced synthetically. Marinol (dronabinol) and Cesamet (nabilone) are synthetic versions of THC that have FDA approval to be marketed and sold as a prescription drug.

Synthetic cannabinoids do unlock the endocannabinoid system to produce effects, but they often fail to incorporate the entourage effect which states that the sum of the different cannabinoids works better as a whole unit than any cannabinoid individually.

With an understanding of the endocannabinoid system and its role in ensuring homeostasis in the body, it may be easier to see how this could be true.

The Endocannabinoid System

Despite its critical importance, the endocannabinoid system (ECS) was only discovered in the early 1990s when Lisa Matsuda, a researcher at the National Institute of Mental Health, and her colleagues discovered a DNA sequence that defines a THC-sensitive receptor in a rat’s brain.

This discovery was quickly followed up with further evidence by Dr. Raphael Mechoulam, the famous chemist who discovered THC.

With less than 30 years of research, the endocannabinoid system is one of the least studied systems in the body.

Currently, restrictions on cannabis research limit what scientists can examine in terms of furthering the understanding of how cannabis and hemp interact with the endocannabinoid system.

Two cannabinoid receptors have been discovered by researchers: CB1 and CB2.

CB1 is found in the central and peripheral nervous system. It’s also found in the brain and is the receptor that THC interacts with, giving the user a “high.”

CB2 receptors are predominantly found in the immune system and the gastrointestinal system where they regulate inflammatory responses in the bowels.

CB2 receptors are also found in the brain, although not as densely as CB1 receptors.

These receptors, a large part of the endocannabinoid system, play roles in regulating cardiovascular activity, appetite, mood, memory, and pain in the body.

CBD does not fit exactly into either CB1 or CB2 receptors.

CBD stimulates both receptors and causes a reaction without binding directly, creating changes in cells that contain them.

CBD also binds to a protein-receptor couple, TRPV-1, responsible for regulating body temperature, pain, and inflammation.

CBD is also known for counteracting the effects of THC, activating serotonin receptors, and inhibiting a gene attributed to several cancers.

CBD has grown in popularity recently as research and anecdotal evidence increasingly demonstrates the impact it can have on the body.

The body’s endocannabinoid system reacts to CB1 and CB2 based upon the organ or bodily system that is sensitive to one or both.

The brain is especially sensitive to CB1, the lungs to CB1, the spleen to CB2, the vascular system CB1, the pancreas to CB1 & CB2, the liver to CB1 & CB2, reproductive organs to CB1, the colon to CB2, the muscles to CB1, the immune system to CB2, and the bones to CB2.

The endocannabinoid system (ECS) is also involved in regulating a variety of physiological and cognitive processes including fertility, pregnancy (during pre- and postnatal development) appetite, pain-sensation, mood, and memory, and in mediating the pharmacological effects of cannabis.

The ECS is also involved in mediating some of the physiological and cognitive effects of voluntary physical exercise in humans and other animals, such as contributing to exercise-induced euphoria as well as modulating locomotor activity and motivational salience for rewards.

In humans, the plasma concentration of certain endocannabinoids (i.e., anandamide) have been found to rise during physical activity;

since endocannabinoids can effectively penetrate the blood–brain barrier, it has been suggested that anandamide,

along with other euphoriant neurochemicals,

contributes to the development of exercise-induced euphoria in humans, a state colloquially referred to as a runner’s high.

Cannabinoids

Cannabinoids are broadly known for their anti-seizure, anti-inflammatory, anti-nausea, anti-fungal, and anti-cancer effects — and science has just scratched the surface.

How much these effects are expressed is a result of the entourage effect is not fully known.

The entourage effect states that the cannabinoids work better in tandem than they do alone.

THC and CBD produce stronger healing properties together that are shown differently based on their concentrations and the presence of other cannabinoids. In addition, terpenes, the oils that give cannabis its fragrance, contribute to the therapeutic effects of the plant on the body when paired with cannabinoids.

The powerful combination of these naturally occurring chemicals produces the medical effects that have given cannabis its reputation as a wondrous medical agent.

In California, there are twelve qualifying conditions for a medical cannabis card, including one described as, “any other chronic or persistent medical symptom that substantially limits the ability of the person to conduct one or more major life activities (as defined by the Americans with Disabilities Act of 1990) or, if not alleviated, may cause serious harm to the patient’s safety or physical or mental health.”

There are over 100 known cannabinoids and we’ve only briefly described a few.

There is a lot more research to be done to understand the intricacies of each cannabinoid and how they interact with each other.

Cannabinoids can bind to receptor sites in either the brain (CB-1) or the body (CB-2).

Cannabinoids will produce different effects on the body depending on which type of receptor site they bind to.

Cannabis strains are filled with multiple cannabinoids that when consumed, bind to these sites, creating a symphony of effects on the body and thus corresponding to the wide variety of healing properties.

This is why one plant can treat many different conditions.

Cannabinoids begin as cannabinoid acids that are activated when heated.

This heat-based activation, also known as decarboxylation, removes the acid from the molecule, turning it into a bioavailable compound that the body can register.

The decarboxylated molecule is often more powerful and produces a different effect on the body than the acidic version. This is why you see both “THCA” and “THC” when looking at the contents of a cannabis strain.

Here is a list of a few of the well-known types of cannabinoids and their effects:

THCA

Delta 9 THC is arguably the most widely known cannabinoid. When people refer to “getting high” they are referring to the experience of the psychoactive effects of THC.

THC begins as THCA, tetrahydrocannabinolic acid, which is one of the most abundant cannabinoids found in cannabis.

When THCA is heated and turned into THC, it binds to CB1 receptors in the brain producing psychoactive effects.

THC is the only known cannabinoid to produce a psychoactive response, a high, and strong therapeutic benefits.

CBDA
Cannabidolic acid is very abundant in the cannabis plant and turns into CBD when heated.

Preclinical studies demonstrate that CBDA is a strong antiemetic used to treat vomiting and nausea and is often given to mitigate the side effects of opioid use or chemotherapy.

CBD
Cannabidiol has exploded in popularity in recent years.

CBD has been the subject of much scientific interest after it hit the mainstream in 2014, following a CNN documentary in which a non-psychoactive, CBD rich cannabis strain, helped a five-year-old girl with severe epilepsy drastically reduce her daily seizure count.

The FDA has approved the first ever CBD-based drug for seizures. CBD is making waves in its ability to treat pain, nausea, anxiety, sleep disorders, and more.

CBGA
Cannabigerolic acid is a precursor to one of the three main cannabinoid lines: THCA, CBDA, and CBCA.

CBGA is the chemical parent to THC and CBD. Enzymes direct it down one of these lines before heat can change it into different forms. CBGA can help reduce inflammation and relieves pain.

CBG
Cannabigerolic is considered a minor cannabinoid because it is present in very low levels. It’s also powerful in treating glaucoma because it is a strong vasodilator meaning that it widens blood vessels. This helps increase blood flow and provide oxygen to the tissues that need it.

CBG is showing promise as an effective antibacterial, anticancer, and neuroprotectant.

CBCA
Cannabichromenic acid is one of the three main cannabinoid lines. It is used to treat fungal infections like athlete’s foot and ringworm.

CBC
Cannabichromenic, binds poorly to CB1 receptors in the brain, but it binds well with other pain-related receptors, helping to increase the body’s levels of natural endocannabinoids. CBC may be impactful against cancer because of this. CBC has also been shown to be an inhibitor of acne.

In conjunction with the THC and CBD, CBD also appears to have antidepressant effects.

CBN
Cannabinol is the result of THCA over time breaking down and turning into CBN. CBN has been shown to delay symptom onset of Lou Gehrig’s disease in mice indicating that it may help with motor neural diseases. CBN is also known for its anti-asthmatic, anti-inflammatory, and sedative properties.

THCV
Tetrahydrocannabivarin is similar to THC, but with a few less carbon atoms. THCV has been shown to be an anticonvulsant, has neuroprotective properties and may be an appetite suppressant.

CBDV
Cannabidivarin is a less potent version of CBD. The CBDV molecule is similar to CBD but has been changed in some ways. CBDV is an anti-nausea and anti-epileptic. CBDV is a powerful anticonvulsant. A 2012 study shows that CBDV stopped seizures in mice and rats.

In general, CBDs, cannabidiols, can be taken into the body in different ways – from smoking cannabis to eating CBD-rich food substances, as a drink, as an aerosol spray into the cheek, or transdermally.

CBD oil, containing only CBD derived from hemp as the active ingredient, is legal in all 50 States and has no tetrahydrocannabinol (THC) in the oil. Some types of CBD oil may contain THC or one of many other CBD-like compounds that can be refined into a distillate and then made into oils, pills, foods, candies, drinks, many forms of hash, salves, creams, and many other substances used as medicine.

Other Foods that Contain CBDs

You may be surprised to know that cannabinoids aren’t limited to their presence within cannabis and hemp plants and feature in many household foodstuffs that you probably already have in your kitchen.

The cannabinoids that are produced in plants are called phytocannabinoids.

So, if you want to enhance your body’s own endocannabinoid system, look at the following list of foods and consider adding them to your diet.

Black Pepper contains the terpene beta-caryophyllene (BCP) that will bind to the same cannabinoid receptors that THC does and produces a calming, relaxing effect and is also known for its anti-inflammatory action. Current research is going on into BCP’s effects within cancer treatment and for conditions such as arthritis and osteoporosis. To achieve instant and natural calming effects, it is recommended to eat 3 or 4 cloves (high in BCPs) or use them in cooking or teas.

Dark Chocolate that contains cacao as its main ingredient is high in anandamide. Cacao or its full name Theobroma Cacao (translates as “food of the gods”) has been known to be a superfood for millennia. It contains a high concentration of a cannabinoid called anandamide, which is also naturally produced in the body. Anandamide is known as the body’s own natural antidepressant and is often referred to as the human body’s natural version of THC.

Rosemary, Cloves, Basil, Oregano, Lavender & Cinnamon all contain cannabinoids, most commonly beta-caryophyllene (BCP). The terpene’s present in these herbs help contribute to the specific aroma that each one has. These terpenes are also present in marijuana plants and contribute to their aromas.

Hops – humulus lupulus – share a common ancestor with the cannabis family of plants if you follow the history back to the Order Urticales and the Family Cannabinaceae — they share similar properties genetically.

Flax Seed has many compounds within it that are very similar to the cannabinoid cannabidiol (CBD) as well as containing CBD itself. The CBD within flax has anti-inflammatory properties and develops autoimmune response.

CBD Legal Status

In the United States, CBD’s legal status depends on the source from which it is derived. When derived from marijuana it is a Schedule I controlled substance under the federal Controlled Substances Act (CSA). When CBD is derived from hemp or some other lawful source it is not a controlled substance. Hemp is excluded from the definition of marijuana under the Controlled Substances Act (CSA). CBD is not specifically scheduled in the CSA and is therefore lawful when derived from hemp, which is not a controlled substance and the definition of which includes cannabinoids.

In 2013, a CNN program brought increased attention to the use of CBDs in the treatment of seizure disorders. Since then, 16 states have passed laws to allow the use of CBD products with a doctor’s recommendation (instead of a prescription) for treatment of certain medical conditions. This is in addition to the 30 states that have passed comprehensive medical cannabis laws, which allow for the use of cannabis products with no restrictions on THC content. Of these 30 states, eight have legalized the use and sale of cannabis products without requirement of a doctor’s recommendation.

The 2014 Farm Bill legalized the sale of “non-viable hemp material” grown within states participating in the Hemp Pilot Program. This legislation defined hemp as cannabis containing less than 0.3% of THC delta-9, grown within the regulatory framework of the Hemp Pilot Program.

The 2018 Farm Bill allowed for interstate commerce of hemp derived products (CBD oil), though these products still fall under the purview of the FDA.

Legal CBD Oil and Your Health

The body’s endocannabinoid system is vital for the overall balance of the immune system, sleep, the digestive tract, cognitive functioning, and the health of the nervous system.

Hemp extract, which is legal in all 50 States (CBD oil) has been shown to provide incredible support to the human endocannabinoid system.

Numerous studies have proven CBD oil to relieve chronic pain, reduce anxiety and depression, as well as benefit heart health and many other ailments.

Also, hemp extracted CBD oil has been used to treat patients diagnosed with Parkinson’s, Alzheimer’s, diabetes, and even cancer with positive effects.

According to an article published in Forbes in 2018, the CBD market was looking to grow by 700% by the year 2020 because of positive health benefits experienced by a growing number of individuals.

According to a new estimate from cannabis industry analysts The Brightfield Group, the hemp CBD market alone could hit $22 billion by 2022.

Skeptics who assume CBD is just 21st-century snake oil, may be surprised to learn that the substance is being studied as a potential treatment for maladies as diverse as schizophrenia, insomnia and cancer.

“CBD is the most promising drug that has come out for neuropsychiatric diseases in the last 50 years,” said Dr. Esther Blessing, an assistant professor at New York University School of Medicine, who is coordinating a study of CBD as a treatment for post-traumatic stress disorder and alcohol use disorder.

“The reason it is so promising is that it has a unique combination of safety and effectiveness across of very broad range of conditions.”

The National Institutes of Health database lists about 150 studies involving CBD as a treatment for conditions as varied as infantile spasms and Parkinson’s disease. And the research has led to medical treatments.

The Food and Drug Administration approved a cannabidiol-based drug called Epidiolex as a treatment for severe forms of epilepsy, representing the first government-sanctioned medical use for CBD.

Preliminary research also indicates that CBD may be effective as an antipsychotic in reducing the symptoms of schizophrenia, with fewer side effects compared with current antipsychotic drugs.

CBD has also shown promise to reduce cravings among people addicted to opioids, according to a study published in Neurotherapeutics in 2015.

It may fight cancer, too. The authors of a review published in the British Journal of Clinical Pharmacology in 2012 wrote: “evidence is emerging to suggest that CBD is a potent inhibitor of both cancer growth and spread.”

CBDs and Evolution

What is the evolutionary impetus for the creation of cannabinoids? Even single-cellular organisms like cyanobacteria – the descendant of the original photosynthetic bacteria – produce chemicals that act on cannabinoid receptors. But the cannabinoid receptors evolved much later, first appearing in the ancient Hydra (not the god) around 500 million years ago.

It is still unclear why plants produce cannabinoids without corresponding receptors to bind with. Some insects do the same. There may be an undiscovered mechanism by which plants regulate themselves with phytocannabinoids that has yet to be found – like so many other aspects of the ECS.

In humans, the ECS has developed into a homeostatic system – a fundamental adaptive mechanism that enables our bodies to maintain health through the stresses of life.

CBDs are all the rage these days and has become a wellness craze.

Unfortunately, it is fashionable to fixate on a single cannabis component. But we should not lose sight of the fact that well-known herbal medicine provides countless remedies relevant to modern disease.

Ultimately, purified pharmaceuticals are not inherently superior to multicomponent, whole plant formulations.

These whole plant remedies have been used for millennia and we would be well-advised to not forget the wisdom of the ancients.

At this point in time, single-molecule CBD and single-molecule THC are both FDA-approved medications.

The medical development of cannabinoids should build upon traditional knowledge and herbal folk-wisdom, which often involved a mixture of various CBD herbs and foods, including CBD-rich cannabis, which has been part of the human pharmacopeia for thousands of years.

At least with herbs we have a long, successful history, while novel pharmaceutical development is experimental without many longitudinal studies.

History, on the other hand, has proven that hemp and other CBD rich foods, herbs, drinks and spices have been at the heart of the human diet since our first ancestors discovered CBD-rich nourishment which is crucial for human health.

As we welcome hemp and cannabis back into the pantheon of medicinal herbs, let’s honor the “crude” plants that have sustained humankind since time immemorial.

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Continue reading CBD May Be the “Missing Link”! – Understanding Cannabis and the “Endogenous Cannabinoid” or Endocannabinoid System.