What are cannabinoids?

17. 07. 2024

• Phytocannabinoids
• Endocannabinoids
• Synthetic cannabinoids
• Pharmaceutical cannabinoids
• Cannabinoids in other plant species
• Conclusion: what are cannabinoids?

A cannabinoid is any compound, natural or synthetic, that interacts with the endocannabinoid system (ECS). The ECS is a system found in all mammals, reptiles and fish.

This system is very complex and scientists are still trying to better understand how it works. So far, the ECS has been found to play a role in regulating hormone levels, mood, appetite, sleep, memory, reproductive function and much more.

There are three main types of cannabinoids:

Phytocannabinoids - cannabinoids produced by plants

Endocannabinoids - cannabinoids naturally produced by the body

Synthetic cannabinoids - artificially created cannabinoids

When talking about cannabinoids, most people specifically refer to the compounds produced in cannabis. So far, a total of 144 individual cannabinoids have been discovered in the cannabis plant, with more being discovered every few years.

The most prominent cannabinoid in cannabis is THC, which is the active substance that makes users feel psychoactive effects.

However, the cannabis plant is much more dominated by CBD, which is considered the primary active ingredient when it comes to the plant's health benefits. This cannabinoid is completely non-psychoactive and offers an impressive range of health benefits. CBD does not work on its own. There are dozens of other cannabinoids in the plant that also offer their own medicinal benefits.

Table of cannabinoid benefits

Health benefit	CBD	THC	CBN	CBG	CBC	THCV
Pain relief	✓		✓	✓	✓
Alleviation of inflammation	✓	✓	✓	✓
Acne prevention	✓				✓	✓
Brain protection	✓		✓	✓	✓	✓
Mood regulation	✓	✓			✓
Alleviation of epilepsy	✓
Alleviating anxiety	✓			✓
Appetite stimulation			✓	✓
Decreased appetite	✓	✓				✓
The fight against cancer	✓	✓		✓	✓
Relief from glaucoma symptoms		✓	✓	✓
Sleep support	✓	✓	✓		✓

I. Phytocannabinoids

Phytocannabinoids are compounds that mimic the effects or structure of cannabinoids naturally produced by the body (endocannabinoids). They activate or block receptors in the endocannabinoid system. The cannabis plant is the largest natural source of phytocannabinoids. It contains approximately 144 individual compounds, each with unique effects on the body.

Some phytocannabinoids stimulate ECS receptors, while others inhibit them. CBD is unique because it acts as a regulator - it acts to both increase and decrease ECS activity to bring the system into overall balance. In this section, we will discuss the most common phytocannabinoids produced by the cannabis plant, including how they work and what benefits they provide.

1. CBD (cannabidiol)

CBD (cannabidiol) is the primary cannabinoid in the cannabis plant. It is completely non-psychoactive and provides a long list of health benefits thanks to its ability to regulate the ECS.

There is a lot of research on the effects of CBD and there are even a few pharmaceutical products that use CBD as an active ingredient to treat various health conditions. While the use of CBD has many benefits, its ability to block pain, suppress inflammation, and promote a relaxed mental state prevails.

 

The benefits of CBD include:

- Relieves pain and inflammation

- Promotes mental health and well-being

- Promote healthy skin

- Protects the brain

- Support digestive function

- May protect the cardiovascular system

- Supports reproductive health

- Regulate hormones and metabolism

How CBD works:

CBD works by regulating the endocannabinoid system. The interaction is very complex - scientists are still trying to understand exactly how this unique cannabinoid actually works. Biochemically, CBD binds to ECS receptors (both CB1 and CB2), inhibits GPR55 receptors, and stimulates serotonin 5-HT1A receptors. CBD has also been shown to interact with a number of other receptors - including adenosine, PPARs (stimulates), TRPV1 (stimulates), Mg2+?ATPase (inhibits), 15?lipoxygenase (inhibits), and many others.

CBD vs. CBDa

The natural form of CBD is CBDa - cannabidiolic acid. The acid group breaks off when exposed to heat or oxygen. Raw CBD products often contain high concentrations of CBDa, while products containing processed CBD have a higher CBD content.

Both versions have very similar effects on the body. There is evidence to suggest that CBDa has a stronger effect on the body, but research is still very limited. The vast majority of CBD research uses the decarboxylated form - CBD.

2. CBDV (cannabidivarin)

CBDV is structurally very similar to CBD and shares many of the same benefits with it. The concentration of CBDV in cannabis plants is very low - we categorise it as a minor cannabinoid.

Not much research has been done on CBDV, but things are about to change. GW Pharmaceuticals, the company that makes the FDA-approved CBD drug called Epidiolex, is developing a new drug based on the CBDV molecule called GPW42006. The company is conducting several large-scale clinical trials looking at the effects of CBDV on the treatment of epilepsy.

Animal testing has shown that CBDV can inhibit acne formation by controlling the amount of sebum produced by the skin.

 

In vitro studies show that CBDV can activate vanilloid (TRPV1) receptors, which are involved in pain transmission and temperature regulation. It is believed that CBDV may offer benefits in the fight against pain due to this effect.

The benefits of CBDV include:

- May offer neuroprotective effects

- Relieves pain

- May reduce the severity of epileptic seizures

- Blocks acne formation

3. CBC (Cannabichromene)

CBC (Cannabichromene) is the third most abundant cannabinoid after THC and CBD. It is completely non-psychoactive like CBD, but has a slightly different set of benefits.

This cannabinoid is much less studied than CBD, but there is some evidence to suggest that it is a promising candidate for inhibiting cancer cell growth, relieving pain and protecting neurons in the brain. Other studies have shown that CBD can reduce sebum production and thus suppress acne formation. CBC has also been shown to have significant antidepressant effects in mice at a dose of 20 mg/kg.

 

The benefits of CBC include:

- Relieves pain

- Protects brain and nerve cells

- May regulate mood and alleviate symptoms of depression

- Promotes relaxation and sleep

- May slow the growth of cancer cells

- Prevents the formation of acne

4. CBCV (cannabichromevarine)

CBCV has a similar structure and effect profile to CBC. Unfortunately, there is very little information on the effects of this cannabinoid and most research on the effects of CBCV is theoretical in nature.

There has been research that has suggested that CBCV has anticonvulsant and anticancer effects, but further research is needed to confirm this effect.

 

The benefits of CBCV include:

- It may slow the growth of cancer cells

- May relieve epileptic seizures

5. CBG (cannabigerol)

CBG (cannabigerol) is the precursor to CBD, THC and CBC. It is often referred to as the parent cannabinoid. Most cannabis varieties produce low concentrations of CBG (less than 1 %). However, cannabis plants harvested before full maturity contain much more CBG than usual.

This cannabinoid has become popular among health scientists for its unique health benefits. CBG oils, CBG concentrates and CBG flowers are becoming increasingly common on the market.

One of the most important benefits of using CBG is its effects on a health problem affecting the eye called glaucoma. This disease involves an increase in intraocular pressure causing pain. CBG has been shown to reduce intraocular pressure, leading to pain relief. Animal studies have shown that CBG can protect the integrity of skin suffering from various dry skin syndromes.

Animal studies have shown that CBG inhibits the development of colon cancer in mice, stimulates appetite, offers neuroprotective effects against Huntington's disease, and protects against inflammatory bowel disease.

 

The benefits of CBG include:

- Stimulates appetite

- Relieves anxiety

- Protects nerve and brain cells

- May protect against cancer

- Inhibits the psychoactive effects of THC

- Relieves symptoms of glaucoma

- Inhibits bacterial growth

- Reduces inflammation

- May alleviate dry skin syndrome

6. CBGM (cannabigerol monomethyl ether)

Very little is known about CBGM, which shares the basic structure of the more important cannabinoid, CBG. Although the basic structure is similar to CBG, this compound is classified as an ether, which could give it a very different set of effects compared to the better known CBG molecule.

CBGM was discovered in 1968 while a group of Japanese scientists were studying the chemical composition of a variety of cannabis called Minamiashigara No 1.

 

The benefits of CBGM include:

- May offer neuroprotective benefits

- May stimulate appetite

- May offer supportive effects against epileptic seizures

7. CBGV (cannabigerovarine)

Not much is known about the therapeutic effects of CBGV, but new research is beginning to emerge. What we know so far about CBGV is that it may offer analgesic effects due to its ability to stimulate vanilloid (TRPV1) receptors, which are closely involved in pain transmission.

Animal studies have shown that CBGV increases sebum production in the skin and may offer supportive effects for complaints involving dry skin. Other studies have shown that CBGV may protect the gastrointestinal tract from inflammatory disorders such as Crohn's disease or ulcerative colitis.

 

The benefits of CBGV include:

- It can relieve the problems associated with dry skin

- May protect the digestive tract from inflammatory disorders

8. CBL (cannabicyclic acid) can help protect the health of the body.

Very little is known about the effects of CBL. To date, the only studies that have been conducted on this compound have focused on mapping its chemical structure.

Interestingly, a sample of cannabis found in a tomb in Central Asia contained CBL as the predominant cannabinoid in the sample, along with CBN.

 

9. CBN (cannabinol)

CBN (cannabinol) is a metabolite of THC that ages and decays. Plants that are overripe or have been stored for long periods of time have the highest CBN content.

This cannabinoid is not psychoactive but has strong sedative effects. This cannabinoid is believed to be the primary compound that contributes to the sedative effect of some cannabis varieties.

Dr. Ethan Russo, a leading cannabis scientist, claims otherwise. He says earlier research conducted in the 1970s came to the wrong conclusion. CBN is not as sedating as previously thought - the sedative effects were more likely the result of other derivatives in the cannabis plant in varieties high in CBN (such as terpenes).

Animal studies have shown that CBN can offer neuroprotective effects in ALS, inhibit bacterial growth, stimulate appetite, reduce inflammation associated with arthritis and reduce intraocular pressure in glaucoma.

 

The benefits of CBN include:

- May slow the progression of ALS

- Protects brain and nerve cells

- Relieves glaucoma pain

- Inhibits bacterial growth and infection

- Stimulates appetite

- Reduce inflammation

- Relieves pain and inflammation in arthritis

- May promote sleep

10. CBV (cannabivarin)

CBV is an analogue of CBN, which means it shares the same structure, but in a mirrored way.

The effects of CBV have not been well studied, but many experts assume that they are similar to those of CBN because of the similarity in the shape of these molecules. CBV is a by-product of THCV that is broken down when exposed to heat or oxygen.

 

11. Delta-9-THC (Δ9-tetrahydrocannabinol)

Delta-9 THC is the primary psychoactive cannabinoid in the cannabis plant. It works by stimulating endocannabinoid receptors, some of which trigger the release of serotonin in the brain. It is these effects on serotonin that cause the psychoactive effects on the user.

Any cannabis plant that produces more than 0.3% THC is considered psychoactive, while anything with 0.3% or less is not. Laws around THC vary from country to country. In small doses (less than 15 mg), delta 9 THC is a mild sedative, while higher doses have a stimulant effect.

 

The benefits of delta 9 THC include:

- Appetite stimulant

- Sedative (low doses)

- Stimulant (high doses)

- Creates a euphoric feeling

- Inhibits inflammation

- May relax muscles

- Relieves glaucoma pain

- Reduces feelings of nausea

12. Delta-8-THC (Δ8-tetrahydrocannabinol)

Delta 8 THC is an analogue of delta 9 THC. In chemistry, an analogue is a slightly different version of the same molecule. In the case of delta 8 THC and delta 9 THC, the difference is in the location of the double bond - apart from that, the two compounds are identical.

Despite how similar the two chemicals are in terms of structure, there are key differences in how they interact with the body.

Delta 8 THC has roughly half the psychoactive effects as delta 9 THC. It is a popular alternative to delta 9 THC because it is secular in many parts and provides similar effects without causing negative side effects such as anxiety or paranoia.

The cannabis plant does not actually produce delta 8 THC. There are no enzymes in the plant that produce this cannabinoid. Instead, the plant produces delta 9 THC, which can degrade over time to produce delta 8 instead. For this reason, there are no plants that produce high concentrations of delta 8 THC. Producers make delta 8 THC extracts by chemically degrading delta 9.

The benefits of delta 8 THC include:

- Stimulates appetite

- Mild euphoria

- Clear sensation when psychoactive

- Inhibits inflammation

- Relieves chronic pain

13. THCV (tetrahydrocannabivarin)

THCV (tetrahydrocannabivarin) is considered a minor cannabinoid because most cannabis varieties contain only trace amounts of it.

However, recent interest in this almost non-psychoactive cannabinoid has led breeders and cannabis extraction companies to develop varieties and concentrates with high THCV content. What is the difference between THC and THCV?

Structurally, the only thing that distinguishes THC from THCV is two carbon atoms. Beyond that, however, THC and THCV differ in very fundamental ways. THCV is not only non-psychoactive, it has also been shown to reduce the psychoactive effects of THC. This cannabinoid inhibits some of the effects of THC (such as increased heart rate) and enhances others (anticonvulsant activity).

 

Animal studies have shown that THCV can modify insulin sensitivity in diabetes, offer protective effects against neurological disorders such as Parkinson's disease, and prevent acne formation. Early in vitro studies show that THCV stimulates bone and collagen formation, making it particularly useful in bone and joint diseases such as osteoporosis or arthritis.

The benefits of THCV include:

- Reduces the psychoactive effects of THC

- May reduce insulin resistance

- May protect against Parkinson's disease

- Prevents acne formation

- Reduces appetite

- Protects brain and nerve cells

II. Endocannabinoids

Endo- refers to compounds "inside" the body. These compounds are produced by the body's own cells to interact with the endocannabinoid system.

The two main endocannabinoids (anandamide and 2-AG) are responsible for the major activity in the ECS. Others, such as OAE, NADA, and LPI, account for a smaller percentage of activity in specific tissues.

Endocannabinoids are classified as eicosanoids, a class of compounds produced from arachidonic acid. The body produces many different eicosanoids that it uses as chemical messengers to treat inflammation, allergies, immune activity, pain transmission, cell growth, reproductive cycles, and the like.

 

Anandamide

Anandamide, also known as arachidonoylethanolamine, is considered a primary regulator of the endocannabinoid system (ECS). It is found in every tissue type in the body, but has the highest concentration in organs outside the brain.

The name, anandamide, comes from the Sanskrit word for bliss - amide. It is often referred to as the "bliss" molecule and is thought to play a role in creating feelings of competitiveness and satisfaction.

2-AG

2-AG stands for 2-arachidonoylglycerol. It is the second primary endocannabinoid in the body and accounts for the majority of endocannabinoid activity in the brain. This endocannabinoid is an agonist for both CB1 and CB2 receptors.

Virodhamine (OAE)

OAE stands for O-arachidonoyl-ethanolamine (OAE). This minor cannabinoid is much less studied than anandamide or 2-AG. So far it has been found to act as a full agonist for CB2 receptors and a partial agonist for CB1 receptors.

N-arachidonoyl dopamine (NADA)

NADA is a minor endocannabinoid with similar activity to anandamide. It binds to both CB1 receptors and vanilloid (TRPV1 receptors).

Lysophosphatidylinositol (LPI)

This compound has not been officially confirmed as an endocannabinoid. However, initial research suggests that it binds to the endocannabinoid receptor GPR55. Further research is needed to understand the effects of this compound and its role in the endocannabinoid system.

III. Synthetic cannabinoids

Synthetic cannabinoids have a similar structure to naturally occurring cannabinoids but are produced in the laboratory.

Most synthetic cannabinoids are structurally similar to THC. After 2010, there was a boom in synthetic cannabinoids as manufacturers looked for products they could sell as 'legal psychoactive substances'. At the time, similar cannabis products were illegal, but synthetic derivatives were not. Products containing these synthetic THC compounds were sold in stores and online as 'legal'.

Synthetic cannabinoids were sold under the common names 'spice' or 'K2'. They were produced by spraying dried leaves with a mixture of synthetic cannabinoids. These products were then smoked in the same way as cannabis. These compounds were notorious for their side effects, which ranged from severe headaches to lung damage to seizures.

 

Today, marijuana is legal in many parts of the world and all psychoactive substances are illegal only until proven safe under the New Psychoactive Substances Act of 2013 (USA). 'Spice' is now only available on the black market but remains unpopular due to its negative side effects, high risk and easy availability of natural cannabis.

Synthetic cannabinoids may not always have the same structure as natural cannabinoids. True cannabinoids are classified as eicosanoids - which use arachidonic acid as a base. You can find synthetic cannabinoids in the form of aminoalkylindoles, 1,5-diarylpyrazoles, quinolines and arylsulfonamides, which are very different from naturally occurring cannabinoids but interact with the same receptors.

List of synthetic cannabinoids:

- JWH-018

- JWH-073

- JWH-200

- AM-2201

- UR-144

- XLR-11

- AKB4

- Cannabicyclohexanol

- AB-CHMINACA

- AB-PINACA

- AB-FUBINACA

IV. Pharmaceutical cannabinoids

In the last few years, there has been a major push in the pharmaceutical space to develop new cannabinoid-based drugs.

Several large pharmaceutical companies such as GW Pharmaceuticals, Solvay Pharmaceuticals, Pharmos and Valeant Pharmaceuticals are investing heavily in the "cannabinoids as drugs" space.

Sativex®

Sativex is one of the best known and most researched pharmaceutical cannabis products. It is manufactured by the British pharmaceutical giant, GW Pharmaceuticals. It is used in the treatment of pain caused by multiple sclerosis and cancer.

This medicine is in the form of an oral spray containing THC and CBD in a 1:1 ratio. Sativex uses natural sources of CBD and THC.

Epidiolex®

Epidiolex is the only CBD product approved by the FDA for the treatment of epileptic disorders (Dravet Syndrome and Lennox-Gastaut Syndrome). It is also used to treat a condition called Tuberous Sclerosis Complex.

This product is manufactured by pharmaceutical giant Greenwich Biosciences, a subsidiary of GW Pharmaceuticals, which specialises in the development of cannabinoid-based medicines in the United States.

Dexanabinol®

Dexanabinol is a synthetic cannabinoid but does not interact with the endocannabinoid system. Instead, this compound binds to NMDA glutamate receptors, where it acts to reduce convulsions and offers broad neuroprotective effects. This product is manufactured by the American pharmaceutical company Pharmos.

Marinol®

Marinol is a synthetic version of delta-9-THC manufactured by Unimed Pharmaceuticals (a subsidiary of Solvay Pharmaceuticals). This FDA-approved drug is used to treat vomiting in cancer patients, as a pain reliever in multiple sclerosis, and to stimulate appetite in AIDS patients.

 

Cesamet®

Cesamet is a synthetic derivative of THC. It has a similar shape and effects, but the structure is slightly different from THC. This drug is manufactured by Valeant Pharmaceuticals International to treat side effects of cancer treatment, such as vomiting and neuropathic pain. This drug was one of the first on the market, gaining FDA approval back in 1985.

Cannabinor

This drug was developed by Pharmos, which is also the manufacturer of dexanabinol. Cannabinor is a synthetic cannabinoid that binds exclusively to CB2 endocannabinoid receptors. It is used to reduce inflammation, improve bladder control and relieve chronic pain.

CT-3

CT-3 is a synthetic cannabinoid modelled on the THC metabolite THC-11-oic acid. It is used to treat neuropathic pain and muscle spasticity in patients with multiple sclerosis. This product is manufactured by Indevus Pharmaceuticals.

Taranabant

This synthetic molecule binds to CB1 endocannabinoid receptors but causes their opposite effect (inverse agonist). It is used to reduce appetite as a potential weight loss tool. This drug never made it into phase III clinical trials. The creator, Merck, stopped development after finding that too many patients suffered side effects, including anxiety and depression.

V. Cannabinoids in other plant species

While cannabis is the king of cannabinoids, there are several other species that produce compounds that can also interact with the endocannabinoid system. Below are a few other plant species that contain cannabinoids:

Echinacea purpurea (purple coneflower) - produces compounds called N-alkylamides, which have been shown to interact with CB2 endocannabinoid receptors.

Acmella oleracea - produces a group of compounds called N-isobutylamides that stimulate CB2 receptors

Piper methysticum (Kava kava) - one of the active ingredients, yangonin, interacts with CB1 endocannabinoid receptors

Camellia sinensis (Chinese tea tree) - the catechins in the tea tree have an affinity for endocannabinoid receptors

Tuber melanosporum (black truffle) - contains the endocannabinoid anandamide

Radula marginata (liverwort) - contains a cannabinoid called perrottetinene, which is very similar in structure to THC

Conclusion: what are cannabinoids?

Cannabinoids are a large and diverse group of chemicals that interact with the endocannabinoid system. These are found in all our organs, including the skin, blood vessels and immune system. The cannabinoids produced by our own bodies are called endocannabinoids and the cannabinoids produced by plants such as cannabis are called phytocannabinoids.

These compounds offer an impressive array of benefits that range from regulating our sleep, hormone levels, pain transmission, inflammation, appetite and many more. The most common cannabinoids are THC, CBD and CBG. They are popular health supplements to support everything from fighting chronic pain and inflammation to mood disorders such as anxiety or depression.

 

Author: Canatura

 

   

Photo: Shutterstock

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