An Overview of Cannabinoids, Endocannabinoids, and the Endocannabinoid System

April 25, 2021

Our understanding of cannabis and the interaction within our bodies is rapidly evolving. A few years ago, most people had never heard of cannabinoids outside of CBD and THC. Even those unfamiliar with the culture discover there is far more to the plant than the abundantly available compounds. Lesser abundant or ‘rare’ cannabinoids are gaining momentum thanks to recent research and the increased demand among CBD users.

All cannabis compounds evolve from the cannabinoid precursor, CBGa, during the plant’s lifecycle. Understanding this development and how these compounds interact with our bodies is essential in finding the best product for the individual. This article lays out the complexities of cannabinoids, endocannabinoids, and the endocannabinoid system to put consumers in a better purchasing position.

Cannabinoids – Our Current Understanding of the Prominent and Rare Cannabis Compounds

While cannabinoids differ slightly in molecular formula, weight, and structure, each is produced naturally at different rates. There are currently two categories of cannabis, marijuana and hemp. Cannabis plants with abundant THC levels are considered marijuana, and plants with high yields of CBD are considered hemp (1). Each type of cannabis also produces the ‘rare’ cannabinoids, CBG, THCv, and CBC. Cannabis plants only naturally have a limited amount of the rare cannabinoids, generally between 0.1% and 10%. (2)

CBG and CBGa

All cannabinoids naturally convert from a form of CBGa, also known as the ‘mother cannabinoid.’ During the plant’s lifecycle, CBGa, the acidic pre-decarboxylated form of CBG, cyclizes primarily into CBDa and Delta-9 THCa. (3) The remaining amounts of CBGa can then be decarboxylated or activated by heat and used in CBG products.

Delta-9 THC and Delta-9 THCa

The cannabinoid that is still federally illegal in the majority of countries around the world is Delta-9 THC. Its ability to activate receptors in the brain produces the notorious ‘high’ and is the reason it has been demonized the past century.

THCa is the form of THC that exists in flower. Cannabis consumers activate the cannabinoid by lighting dry flower on fire. The industry used to view the acidic forms of cannabinoids like THCa as useless, but experts are discovering potential medical uses for these compounds in their natural states.

CBD and CBDa

The non-intoxicating cannabinoid abundantly found in hemp flowers has attracted people outside the cannabis community for medical benefits. CBD use is a worldwide phenomenon that isn’t slowing down. Experts believe CBD delivers relief to a number of conditions by inhibiting certain enzymes in our endocannabinoid system. (4)

CBDa, the acidic form of CBD, has gained attention because of its ability to inhibit the COX-2 enzyme, the same mechanism as NSAIDs (anti-inflammatory drugs). (5)

CBC and CBCa

CBC or cannabichromene is another rare cannabinoid naturally converted from CBGa. CBC’s benefits are currently far from fully understood. Still, cannabis researchers have found that CBC combined with other cannabinoids like THC could increase the anti-inflammatory effects of the extract. (6)

THCv

Tetrahydrocannabivarin is a cannabinoid with a similar structure as THC created through the biosynthesis of CBGva (7). THCv is usually only found in trace amounts, but cannabis connoisseurs have found certain strains with up to 1% THCv potency, such as Durban Poison. Unlike THC, THCv suppresses the appetite. (8)

Delta-8 THC

Delta-8 THC is the latest cannabinoid to gain mainstream attention because it can be created from hemp and deliver a high. Users describe the effects of D8 as a milder version of Delta-9 THC. Delta-8 activates the same receptors as marijuana products but at a lower efficacy. (9)

Did You Know Cannabinoids Are Not Exclusive to Cannabis?

THC brought attention to cannabis because of the psychoactive effects. Our knowledge of cannabinoids is rooted in understanding the effects of cannabis, but there are other plants with similar compounds. Plants such as coneflower, liverwort, electric daisy, chocolate, and black pepper all contain compounds that deliver health benefits and are similarly structured molecularly to cannabinoids. (10)

Synthetic Cannabinoids

Nearly a decade ago, ‘spice’ or ‘k2’ could be purchased at a head shop or online with the promise of delivering the same effects as THC. These products are synthetic cannabinoids, sprayed on plant matter. The synthetics are created in a lab without the need for actual cannabis flowers.

Today, we are seeing another rise in artificial cannabis compounds because of the CBD boom. Manufacturers are creating synthetics in a lab to avoid their country’s ban on hemp production to produce CBD products. Synthetic cannabinoids are illegal in the United States but are mistakenly purchased online by unethical retailers.

Synthetic cannabinoids also have a history of being developed for medicinal purposes. Professor Raphael Mechoulam, known as the ‘father of cannabis research’ believes synthetics are the key to bridging the gap between cannabis and pharmaceutical industries. He recently unveiled his latest discovery, cannabidiolic acid methyl ester (EPM301). Stabilizing acidic forms of cannabinoids is possible by a simple chemical procedure allowing the cannabinoid to be more adapt for pharmaceutical production. (11)

Using synthetics in drug therapy is not a new practice. The FDA approved a synthetic form of THC and a synthetic analog of THC in the 1980s to treat HIV/Aids induced anorexia and chemotherapy-induced nausea. (12)

What is the Endocannabinoid System?

The endocannabinoid system or ECS is the complex network of endocannabinoids, endocannabinoid receptors, and enzymes believed to regulate bodily functions like mood, memory, inflammation, anxiety, memory, appetite, and the sleep-wake cycle. The ECS reason human (and all other mammals) react when they introduce cannabinoids into the body.

Endocannabinoids

Naturally produced neurotransmitters called endocannabinoids are responsible for activating the receptors that deliver the effects of cannabis. We are currently aware of two endocannabinoids, anandamide and 2-AG.

THC is structured similarly to the endocannabinoid anandamide. They both are capable of binding with receptors altering normal brain function. (13)

2-AG also can bind with receptors in the brain, creating psychoactive effects. A prominent study argues that 2-AG, not anandamide is the ‘true natural ligand for cannabinoid receptors.’ The researchers allowed primates to self-dose anandamide, 2-AG, and nicotine and evaluated drug-taking behaviors. (14)

While the study results supported their argument, we are far from fully understanding how we can utilize endocannabinoids to deliver benefits.

Endocannabinoid (CB) Receptors

There are two types of endocannabinoid receptors. CB1 receptors are primarily located in the brain and central nervous system, while CB2 can be found throughout the body, mainly in the digestive system.

After cannabinoid consumption, they either directly bind with CB1 and CB2 or promote the production of endocannabinoids with the affinity to activate the receptors. (15)

What are Terpenes?

Terpenes are aromatic plant oils used to attract and deter predators. The essential oils produced from plants also contain medicinal properties, similar to the significant and rare cannabinoids.

All plants possess terpenes, but cannabis contains an abundant and diverse array of plant compounds allowing specific strains to have different effects.

Pinene

Sativa dominant strains feature high amounts of terpenes like pinene that deliver uplifting effects. Pinene is a natural bronchodilator meaning it can widen the bronchi or major air passages of the lungs. (16)

Myrcene

The sedating effects of myrcene are believed to be responsible for the relaxing effects of indica dominant strains. Myrcene alone is believed to sedate users. Besides cannabis, myrcene is commonly found in hops and pepper.

What are Flavonoids?

Flavonoids are another aspect of the cannabis plant. These compounds are found naturally in many fruits, vegetables, wine, tea, and chocolate. They are rich in antioxidants that keep the body healthy and lower the risk of major chronic health conditions.

The Entourage Effect

The belief that the entirety of the cannabis plant, including all the cannabinoids and terpenes naturally produced, delivers a more beneficial experience than isolated compounds is known as the ‘entourage effect.’ Famous cannabis researchers Professor Raphael Mechoulam and Shimon Ben-Shabat first described the phenomenon in 1998. (17)

While the consensus of the industry is that whole plant extracts are more beneficial, scientists have yet to understand the ‘entourage effect fully.’

Choosing the Right Cannabinoid Product

CBD and THC products come in three available options. Full spectrum, broad spectrum, and isolates. In the past, these terms were exclusive to the two most abundant cannabinoids. As the rare cannabinoids gain popularity, more companies are offering products featuring CBG or CBC as the central cannabis compound.

Full Spectrum – A cannabis product with a full array of cannabinoids and terpenes.
Broad Spectrum – Also a full-plant extract, excluding THC in the extraction process.
Isolate – When a cannabinoid is isolated from all other plant matter.

Once a cannabis consumer understands the different chemical compounds available and how they interact with our bodies, they are in a much better position to make a purchasing decision. We recommend taking full-plant products, whether they are CBD or THC dominant. Cannabis synergy may not be proven, but there are different benefits associated with other cannabinoids and terpenes that could create a better consumer experience.

List of Current Notable Cannabinoids

THC (tetrahydrocannabinol)
THCA (tetrahydrocannabinolic acid)
Delta 8 THC (delta-8-Tetrahydrocannabinol)
CBD (cannabidiol)
CBDA (cannabidiolic acid)
CBN (cannabinol)
CBG (cannabigerol)
CBC (cannabichromene)
CBL (cannabicyclol)
CBV (cannabivarin)
THCC (tetrahydrocannabiorcol)
THCV (tetrahydrocannabivarin)
THCP (tetrahydrocannabiphorol)
CBDV (cannabidivarin)
CBCV (cannabichromevarin)
CBGV (cannabigerovarin)
CBGM (cannabigerol monomethyl ether)
CBE (cannabielsoin)
CBT (cannabicitran)

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Please note that this article was written by a 3^rd-party author who is a specialist on the topic of CBD, hemp and cannabis. Any information or recommendations contained within this article, are independent to the opinion of RUDERALEX CBD and our employees. We make no claims for any of our products, please read our disclaimer for additional information.