Introduction to Cannabinoids

Cannabinoids and the Endocannabinoid System

In 1964 Raphael Mechoulam and Yechiel Gaoni opened a new perspective to marijuana, publishing the structure of Tetrahydrocannabiol (THC). After this, researchers as well as consumers of marijuana start to be more interested in microstructure of cannabis and its influence on our body. In the mid-1980s chemist found way to synthesize pure THC (Marinol). According to experienced cannabis users, Marinol had different effect than the normal plant. Now it was clear that all effects of Marijuana is not caused just by THC but also by another bioactive compounds inside plant.

First sign of positive feedback with no undesirable effect came with first test of clinical trials with almost equal amounts of  Cannabidiol (CBD) and THC in England 1999. This CBD/THC, 1:1 ratio showed better results on multiple sclerosis patients instead of application of THC without CBD. Cannabidiol  has been demonstrated to have no psychotropic effect. However, there are other non-psychotropic cannabinoids with great therapeutical influence on health like: Tetrahydrocannabivarin (THCV), Cannabigerol (CBG) and Cannabichromene (CBC).

In the last few years, research on cannabinoids has grown exponentially. At the end of 2015 there was around 23 000 articles containing the word “cannabinoid”. So its an average of two scientific publications per day in last 20 years. This prove a continuous greater interest in research to learn more about Cannabis and its cannabinoids effects.

Cannabinoids as well as endocannabinoids play an important role in our body system, supporting and ruling coordination and communication between cells.

Inside the endocannabinoid system there are two main receptors known as CB1 and CB2. The structure of this two receptors is slightly different. As it picture shows CB1 and CB2 follows pattern of G-protein with seven passes through cell membrane.

CB1 receptors are located primarily in the nervous system, but also found in reproductive tissues, connective tissues, adipose tissues, and other glands and organs. The CB2 receptors are found primarily in cells of the immune system, but during situations of injury or inflammation, the CB2 receptors can also be created and up-regulated in other tissues where they’re not normally found.

Endocannabinoids are molecules made in our body to interact with cannabinoid receptors. Anandamide (Ānanda (Sanskrit: आनन्द) menas bliss or happiness¹) and 2-arachidonoyl glycerol (2-AG). Theses 2 endocannabinoids are arachidonic acid derivatives and synthesized on cell membrane form precursors.  Autocrine signalling is the main purpose of endocannabinoids. They travel from cell to cell transporting important messages for activation or deactivation of some process in our body. Once information is delivered to the proper cell, endocannabinoids will be hydrolysed by enzyme Fatty Acid Amide Hydrolase (FAAH) witch hydrolase Anandamide and Monoaglycerol lipase (MAGL)  degrades 2-AG. However, this is not the only function of endocannabinoids they also can control voltage gated ion channels and ligand-gated ion channels.

Balance in endocannabinoid system is related to occupation of CB1 and CB2 receptors. Some biochemical test shows that optimal activation of CB1 receptors will cause antidepressant and anti-stress activity in rodents. Endocannabinoid system is not responsible just for immunity but it regulates proliferation, integumentary system which creates skin and hair cells. If scientist in near future find way out how to keep the endocannabinoid system in balance, then it will be much easier to control some of skin conditions like psoriasis, eczema, acne, dermatitis, systemic sclerosis, etc).

Stefan Živanović

References:

1. Dustin Sulak, An Introduction to the Endocannabinoid System, O’Shaughnessy’s, 2015, 16-3.
2. Bisogno T., Ligresti A., Marzo Di Vincenzo, The endocannabinoid signalling system: Biochemical aspects, Pharmacology, Biochemistry and Behavior, 2005, 81, 224-238.
3. Infographic : Cannabis Synthetic Cannabinoids.png
4. Hindu Philosophy on Wikipedia
5. Leafly: Is your endocannabinoid system in balance?
6. Nature Going Smart: Understanding the endocannabinoids system might change your life
7. Sclabs: Learn Cannabinoids