Types of Cannabinoids | Endocannabinoid Deficiency

Cannabinoids are a large and diverse group of substances that can be classified in several ways. Still, it is most beneficial to understand the diversity of cannabinoids as follows: endocannabinoids, phytocannabinoids, and synthetic cannabinoids. Clinical endocannabinoid deficiency (CECD) is a medical theory that proposes that a deficiency of endocannabinoids is the underlying pathophysiology of migraines, fibromyalgia, and irritable bowel syndrome. The deficiency may sometimes start in the womb due to maternal obesity. In our latest article we talked about CBD, now find out more about Types of Cannabinoids and Endocannabinoid Deficiency below.

endocannabinoid deficiency

FAQ about Cannabinoids

What is CECD (Endocannabinoid deficiency)?

Clinical endocannabinoid deficiency (CECD) is a medical theory that proposes that a deficiency of endocannabinoids is the underlying pathophysiology of migraines, fibromyalgia, and irritable bowel syndrome.

What is ECS (Endocannabinoid system)?

The endocannabinoid system (ECS) is a complex cell-signaling system identified in the early 1990s by researchers exploring THC, a well-known cannabinoid. Cannabinoids are compounds found in cannabis.

What are the 3 types of cannabinoids?

Endocannabinoids, Phytocannabinoids and Synthetic cannabinoids.

What is the difference between Endocannabinoids, Phytocannabinoids and Synthetic cannabinoids?

The main difference between phytocannabinoids, endocannabinoids, and synthetic cannabinoids is that synthetic cannabinoids are entirely artificial and developed in the laboratory.

What is the endocannabinoid system (ECS)?

So what is ECS – endocannabinoid system? The prefix “endo-” means the inside or inner part of something. Internal cannabinoids were discovered by studying the properties of tetrahydrocannabinol (THC – the most well-known abbreviation for the English word “tetrahydrocannabinol”). Compounds have been observed in humans and mammals chemically similar to THC, a phyto-(plant) cannabinoid. THC is the principal psychoactive constituent of the Cannabis sativa plant, more commonly known as marijuana.
Professor Di Marzo, in 1998 summarised the main functions of the ECS as “to relax, eat, sleep, forget and store.”

So, what does the ECS consist of?

ECS consists of endocannabinoids (compounds that bind to cannabinoid receptors), receptors (proteins that receive chemical signals from outside the cell), and enzymes (proteins that speed up biochemical reactions). The two main endocannabinoids are arachidonoylethanolamide, nicknamed anandamide from the Sanskrit word for ‘bliss,’ and 2-arachidonoylglycerol (2-AG).

Endocannabinoids

  • Anandamide is essential for memory, appetite, sleep, and pain relief. Imbalances in anandamide levels can lead to a decreased sense of happiness, increased fear and anxiety, and difficulties in coping with stress.
  • 2-AG is involved in many (patho)physiological functions such as emotions, cognition, energy balance, pain sensation, and inflammation of the nervous system (N. Murataeva, A. Straiker, K. Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS”).
  • In 2019, researchers at the University of Illinois published a paper on discovering four more endocannabinoids and their derivatives. They are synthesized in the body from two essential omega-3 fatty acids, mainly found in fish and dietary supplements.
  • The latest discovery is a molecule called pentadecanoylcarnitine (PDC). According to a paper published in Scientific Reports in August 2022 describing the discovery of PDC and preliminary tests, it is synthesized in the body from another dietary fatty acid known as pentadecanoic acid or C15:0. This acid is found mainly in full-fat dairy products. Still, it is also some fish, plants, and other foods. PDC binds to CB1 and CB2 receptors, amongst others, and may be necessary for various physiological processes related to regulating inflammation, pain, mood, and sleep.

Receptors

  • Receptors can be considered locks, and the corresponding chemical (natural or synthetic) can be used as a key if it has the proper structure.
  • CB1 is the name of the cannabinoid receptor, which is best known for its effects on neural function in the brain. Through the CB1 receptor, THC affects short-term memory, pain, emotions, hunger, and more.
Receptors CB1 CB2
  • The less studied CB2 receptor, located mainly in the periphery (outside the brain), is also critical. CB2 is a crucial immune system receptor and influences pain and inflammation.
  • The third receptor, TRPV1 (transient receptor potential vanilloid-one), mediates pain signals through a mechanism different from endogenous cannabinoids and opioids but is sensitive to desensitization: that is, when continuously stimulated, it eventually becomes unresponsive or slows down its response to stimulation. This opens up therapeutic possibilities for finding agents that effectively reduce certain types of neuropathic pain.

Enzymes

  • The third component of the ECS is biosynthetic and degradative enzymes that produce or degrade anandamide and 2-AG, respectively. Cannabidiol has also been found to inhibit the enzyme fatty acid amidohydrolase (FAAH), which degrades the endocannabinoid anandamide. In this way, cannabidiol potentiates and prolongs the effects of anandamide, similar to how SSRIs (Selective Serotonin Reuptake Inhibitors) increase the activity of serotonin in treating depression.
  • The three components of the ECS – endocannabinoids, their regulatory enzymes, and receptors – can be considered crucial mediators of physiological homeostasis (balance), ensuring that the various body systems function within strict parameters and are neither under nor over-active.
Enzymes 2-ag
  • The endocannabinoid system plays a vital role in our health and well-being. Indeed, this system is a crucial regulator of the human body, from regulating mood and appetite to replacing pain and inflammation. Further research into the endocannabinoid system will undoubtedly reveal even more amazing insights into how the human body works.

Different Types of Cannabinoids

Cannabinoids, naturally occurring chemical compounds in cannabis, can be found in the plant. To help maintain stability and health, these compounds can act directly on or indirectly on cannabinoid receptors. Cannabinoids are absorbed into the body through cannabinoid receptors. These receptors are most often found in the brain and immune system. These are the most prevalent cannabinoids found within cannabis.

Endocannabinoids and Endocannabinoid Deficiency

Endocannabinoids are a type of natural ligands that bind to cannabinoid receptors. Ligands are molecules that bind to other molecules. In the body, ligands bind to cell receptors and cause changes in the cell. This can be a change in the cell’s behavior or a chemical reaction within the cell.

Endocannabinoids are produced by most organisms in the animal kingdom, as noted in Robert J. Silver’s article “The animal endocannabinoid system”. Both endocannabinoids and cannabinoid receptors form the endocannabinoid system, which regulates various physiological processes such as neurotransmitter release, pain perception, and digestive, cardiovascular, and hepatic functions. That is called Endocannabinoid Deficiency.

difference-between-endocannabinoids-and-phytocannabinoids

CB1 and CB2 receptors

The two most common endocannabinoids are anandamide and 2-arachidonoylglycerol. Endocannabinoids act as a key that acts on the primary cannabinoid receptors CB1 and CB2 (which should be thought of as a lock). Causing their activation and subsequent action. CB1 receptors are mainly found in the central nervous system and are responsible for the effects produced by neurological processes and psychoactive ‘secondary’ effects.

CB2 receptors are found primarily in the immune system and regulate immunomodulatory effects (ensuring that cells can fight infectious agents). In addition, CB2 receptors have recently been detected in the central nervous system and microglia cells and are also present in specific neurons. There are also other receptors with which internal cannabinoids interact to regulate the body system.

Phytocannabinoids

Phytocannabinoids, the plant (phyto)cannabinoids, are a class of compounds characterized by 21 carbon atoms. Found in nature only in the plant Cannabis Sativa L. More than 113 phytocannabinoids have been discovered, including their acid and neutral forms and transformation products. So only non-psychoactive phytocannabinoids can be synthesized directly by the plant. Therefore, the main phytocannabinoids present in fresh plant material are Δ9-THCA, CBDA, CBGA, and CBCA.

However, the carboxyl group is unstable and easily lost (CO2 evolution) when exposed to heat or light, leading to the conversion into active neutral forms. The acidic phytocannabinoids undergo partial decarboxylation during the biomass drying process. Subsequently, the acidic phytocannabinoids and some of their dynamic neutral conditions (Δ9-THC, CBD, CBG, and CBC) are mainly found in the dry plant material. Once in the animal or human body, they interact similarly to endocannabinoids.

Synthetic cannabinoids

Synthetic cannabinoids

The main difference between phytocannabinoids, endocannabinoids, and synthetic cannabinoids is that synthetic cannabinoids are entirely artificial and developed in the laboratory. An example of a synthetic cannabinoid is dronabinol, the active ingredient in MARINOL®. A medicine supplied in capsules and used in the USA since 1985 to prevent nausea, vomiting, loss of appetite, and weight loss. Another example of a synthetic cannabinoid is nabilone, the active ingredient in CESAMET®. So a drug approved to control nausea and vomiting caused by cancer chemotherapy. Both drugs are approved for these purposes in the USA, UK, Switzerland, Canada, and Spain.

JWH 018 and JWH 073

Some CB1 receptor-selective cannabinoids, such as JWH-018 and JWH-073, have been used as psychoactive ingredients in so-called smart drugs that mimic the effects of cannabis. So these drugs are called Spice. There is not much information on the results of synthetic cannabinoids on humans. Although some have already been shown to cause more anxiety and panic attacks than phytocannabinoids. Synthetic cannabinoids have been developed as research tools for cannabinoid research, but they have never been shown to be reliable for human use in clinical trials. In theory, they should never have left the laboratories where they were developed and synthesized.

JWH 018 and JWH 073

In the 2018 article “Synthetic cannabinoids dramatically increase aminotransferase levels. Natural cannabinoids do not” (Synthetic cannabinoids severely elevate aminotransferase levels. Natural cannabidiol does not” by Donish Cushing et al. states that synthetic compounds are dangerous. Dangerous because “the human body does not have the tools needed to catabolize synthetic cannabinoids”. Finnaly, this is because the new cannabinoid molecules synthesized are chemically very different from their naturally occurring counterparts. So this means the human body does not have the proper enzymes to break them down, which can be very dangerous.