cannabinoids & The Endocannabinoid System

Consumer awareness of the effects of THC and the potential uses of other cannabinoids such as CBD is increasing. But what exactly are these family of compounds, and how did we discover the mechanisms which allow them to function with our body?

What exactly are cannabinoids?

Cannabinoids are compounds which originate from cannabis (hemp or marijuana) or are produced naturally in humans and animals. They can be split into two depending on the source:

(1) Phyto-cannabinoids (pCBs), where “phyto” means plant. Chemicals produced by cannabis and to a certain extent, other plants. Examples include CBD and THC, although over 100+ exist. 

(2) Endo-cannabinoids (eCBs), where “endo” is short for endogenous, meaning internal. eCBs are naturally occurring compounds found in nearly any (with a vertebrate) living animal via a network of neurons and receptors called the endocannabinoid system. Two of the most researched eCBs are called Anandamide and 2-AG.

table of cannabinoids
Quote about the Endocannabinoid System

Interestingly, regardless of source, cannabinoids have a similar method of action when utilised by the body. Meaning both types of cannabinoids act on the same receptors in our body. Suggesting the human body is predisposed to absorb cannabinoids!

All of this is made possible through the complex and still relatively unknown neurotransmitter network science is still evaluating, the endocannabinoid system (ECS).

The endocannabinoid system

Researchers in the 1960s were able to isolate numerous pCBs from the cannabis plant for the first time, kickstarting a wave of increased research into cannabis. By analysing the effects of these isolated compounds, scientists were able to unearth a complex web of receptors, enzymes and neural pathways which directly target the absorption of cannabinoids, known today as the endocannabinoid system (ECS). The ECS is a sizeable endogenous signalling network, regulated by our diet, sleep, exercise, stress, and a variety of other factors, including exposure to pCBs such as CBD.

It was originally thought that the ECS existed only in mammals, today is widely accepted this complex system is found across in nearly all animals; evolving within our anatomy over 600 million years ago. As a consequence, this network is deeply connected to a variety of physiological and neurological functions within the body.

The ECS consists three different parts:

– Endocannabinoids.

– Enzymes to break down cannabinoids (applies to both pCBs and eCBs).

– Receptors which bind to cannabinoids.


The ECS is known for influencing homeostasis, the body’s way of maintaining an equilibrium of physiological and neurological functions such as temperature, blood sugar levels, stress and anxiety. Studies indicate the ECS regulates major levers in wellbeing, including sleepstresspain, and appetite.

You can think of it as an internal autopilot, overseeing interconnected functions and using negative feedback loops to adjust course were necessary to stay within defined parameters. A good example is body temperature when you feel hot, you sweat, and when you feel cold, we shiver. Crossing a pre-set threshold triggers a corrective action in terms of cooling you down or warming you up, controlled by the ECS.

ECS receptors

The ECS carries out its role as a regulator of bodily functions by numerous cannabinoid receptors. The receptors CB1 and CB2 are found plentifully across the body and are thus the most well documented and discussed.

  • CB1: Concentrated in the central nervous system, encompassing the brain and nerves in the spinal cord. Also found around peripheral organs and tissues such as the spleen, white blood cells, and parts of the gastrointestinal and urinary tracts. THC binds with the CB1 receptor like a lock and key, which is what causes its psychoactive effects. CBD doesn’t fit; instead, it alters the shape of the receptor. The lack of direct receptor connectivity is the core premise behind why CBD is thought to modulate the effects of THC, acting as a go-between CBD blocks THC from binding

  • CB2: Mainly found in nerves within the peripheral nervous system, including the gut and immune system and concentrated in white blood cells, the tonsils and the spleen.


Similar to how serotonin and dopamine are the routes for neurochemical release across your body, eCBs are couriers of the ECS. To date, research has predominately explored two major eCBs: Anandamide and 2-arachidonoylglycerol (aka 2-AG).

Anandamide, discovered in the 1990s, is a neurotransmitter derived from arachidonic acid (an omega 6 fatty acid). Its name originates from ananda, translating to bliss in Sanskrit. Research indicates that it is active in regulating vital physiological functions, such as memory and appetite. More recently, the compound has been suggested as the reason why sprinters feel ‘runners high’!

2-AG is the most abundant eCB found in the body. Similar to anandamide, 2-AG is thought to play an essential role in the regulation of appetite, immune system functions and pain management.

Phytocannabinoid Acids

To date, we are aware of over 100 different plant cannabinoids. Most of which are found in minute quantities and near undetectable levels in commercial cannabis. Primarily, due to the traditional breeding of cannabis plants naturally high in THC to cater to consumer demand for recreational weed.

Cannabis doesn’t directly produce the pCBs we are accustomed to, such as THC or CBD. Instead, it synthesises a variety of acids which later turn into cannabinoids via heat (decarboxylation). There are eight primary acids produced by cannabis.

  • CBGA (Cannabigerolic acid)
  • THCA (Δ9-Tetrahydrocannabinolic acid)
  • CBDA (Cannabidiolic acid)
  • CBCA (Cannabichromenenic acid)
  • CBGVA (Cannabigerovarinic acid)
  • THCVA (Tetrahydrocanabivarinic acid)
  • CBDVA (Cannabidivarinic acid)
  • CBCVA (Cannabichromevarinic acid)

The CGBA enzyme is known as the mother cannabinoid, since it produces THCA and CBDA, which (always) turn into THC and CBD when heated. 

table of phytocannabinoids

Major Phytocannabinoids

THC (Δ9–tetrahydrocannabinol): The well-established status quo compound for cannabis. THC is highly psychoactive and the reason why cannabis users feel ‘high’.

As THC passes through the CB1 receptors located primarily in the hippocampus section of the brain, a common side effect of high recreational doses is short term memory impairment. However, medicinally, THC (where legal) is used increasingly to treat a variety of conditions, especially those considered chronic. THC is commonly used as a treatment for chronic neuropathic pain, stimulating appetite in cancer patients and as a wildcard in treatment-resistant insomnia in conjunction with CBD.

CBD (Cannabidiol):A non-psychotropic cannabinoid, picking up speed recently in the wellbeing space. Its consumption is thought to increase endocannabinoid production, anandamide in particular, improving mood. Research is still on-going, but CBD has gained significant traction throughout the world as a compound with medicinal potential. In particular, studies indicate cannabidiol has the potential to be used to improve anxiety, inflammation, epilepsy and chronic pain.

Minor Phytocannabinoids

CBG (Cannabigerol): A non-intoxicating compound. CBGA is known as the mother cannabinoid, as it is usually converted to either CBDA or THCA (which lead to CBD and THC). Given how these compounds are synthesised, more THC means less CBG and CBD (and vice versa).

CBN (Cannabinol): A mildly psychoactive cannabinoid, and the result of the degradation of THC when exposed to oxygen. As a result, it is primarily found in older cannabis plants and flowers. Recent research indicates it is a powerful sedative and acts on pain with similar efficacy as THC.

CBC (Cannabichromene): Another non-intoxicating cannabinoid, researchers believe it works with other cannabinoids to produce ‘the entourage effect, where cannabinoids are work more effectively together than in silo.

CBGV (Cannabigerivarin): It is a homolog of CBD (has a similar chemical structure to CBD) and is non-psychotropic. Research into this compound has only recently become popular, and scientists believe it could be useful as a potential anticonvulsant.

THCV (Tetrahydrocannabivarin): Similar in structure to THC but not much else is known about this compound. Cannabis usually only contains trace amounts of THCV.

CBDV (Cannabidivarin): Another homolog of CBD and non-psychotropic. Its use is currently being explored for managing epilepsy by GW pharmaceuticals.

CBCV (Cannabichromevarin): Non-psychoactive and found more so in Indica strains. Research is still ongoing to discover its usage potential.

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Disclaimer: Views expressed here do not necessarily reflect those of Nature Leaf and its staff. This article is not intended to provide medical advice, diagnosis, treatment, cure or prevention for any disease. Nature Leaf products have not been evaluated by the MHRA.