by Tom Russell November 15, 2020
Hemp has a long history of commercial use and has been consumed as both an herb and a food in cultures around the world.
Despite hemps many applications, including paper, oil, biofuel, rope and clothing, it has had a poor reputation for the last 100 years or so. During this time cannabis has been banned in almost every country.
While hemp doesn’t have the same intoxicating qualities as cannabis, authorities often fail to see the difference, resulting in its farming being restricted, prohibited or controlled.
Research into the components of cannabis has been conducted intermittently for over a century. Towards the end of the 19th century, cannabinol (CBN) was the first of the phytocannabinoids to be isolated.
Much later in the 1930s, its structure was discovered by Robert Sidney Cahn. This helped to build a picture of how cannabinoids work. However, there was still very little understanding of which molecules could be found in cannabis and what they did.
CBD was isolated from cannabis in 1940 by Roger Adams and his colleagues in the U.S. However, the attention it received was short-lived. THC was extracted in 1942 and became famous as the most potent, abundant and active of the cannabinoids.
In 1963, Israeli chemist Dr Raphael Mechoulam was successful in his efforts to describe the structure and chemistry of cannabidiol. Because of the attention on THC as the most ‘psychoactive’, CBD was cast aside as a ‘non-active precursor to THC’.
Detailed research into cannabis and its components was tricky when it was actively prohibited in most countries. Not only were opportunities restricted but the overwhelming opinion of the pharmaceutical community was that the future of cannabis lay in ‘its isolated components, the cannabinoids and their synthetic derivatives’.
This meant that research often focused on the chemical building blocks of the plant and how they could be used elsewhere, rather than how they interacted naturally with each other and the mammalian brain.
While research into cannabis and its components continued through the following decades it wasn’t until the late eighties that the next clue to CBD’s importance was uncovered. In 1988, during a government-funded study, Allyn Howlett and William Devane discovered receptor sites located in the mammalian brain that interact with substances found in cannabis.
This receptor became known as CB1. Later, CB2 receptors were discovered in the peripheral nervous system. In 1992, Lumír Ondřej Hanuš and William Anthony Devane discovered anandamide, the first "human cannabinoid", an endogenous cannabinoid neurotransmitter. It acts as a chemical signal and interacts with CB1 receptors.
This combination of receptors and human cannabinoids (endocannabinoids) became known as the endocannabinoid system (ECS). Once it was discovered, its function was explored in depth. The ECS is used as a signalling system for the processes involved in homeostasis. This is the mechanism which maintains healthy balances in your body.
Anandamide is also known as the ‘bliss molecule’ and is responsible for the ‘runner’s high’ that follows vigorous exercise. While it is found in the human body is also present in chocolate. Later another signalling molecule was discovered and was named 2-Arachidonoylglycerol (2-AG). Both endocannabinoids interact in different ways and provide different functions.
As the understanding of the ECS grew, governments supported more research and more cannabinoids were discovered. The next challenge was to see how these all fit together.
Raphael Mechoulam led the next phase of discoveries by uncovering more about the structure of individual cannabinoids. He was instrumental in bringing CBD to the public’s attention.
At the start of the 21st century, cannabidiol grew in popularity. Larger numbers of people began to recognise its effect on general health and well-being. In 2009, labs finally began testing strains of cannabis to see how much CBD was contained in each one.
Varieties that contained more than 4% CBD, by dry weight, became known as ‘CBD rich’. This made it easier for people to find and use strains they knew were high in CBD. Now that people could identify when they had consumed CBD, stories of its effects began to circulate.
CBD finally ascended to its current rock star status when pharmacologists begun to understand how it interacts with the endocannabinoid system. CBD’s molecular structure gives it many positive attributes but its role in boosting the ECS is by far the most fascinating.
Many cannabinoids, THC included, bind directly with either the CB1 or CB2 receptors. CBD is different because it doesn’t. Instead, CBD works to promote your body’s own endogenous cannabinoid neurotransmitter, anandamide.
Anandamide interacts with your cannabinoid receptors and allows your body to respond quickly and efficiently to imbalances. Because anandamide is usually produced to be used immediately, it has a short life. Once it has completed its task it’s broken down into its component parts. This breakdown is started by enzymes.
CBD prevents these enzymes from starting the breakdown of anandamide allowing the levels to build up in your body. Higher levels of anandamide have been found to allow your body to improve its own wellbeing.
The real beauty of this story is that it is cyclical. It starts with the separation of the cannabinoids as they are isolated. Plans were made to synthesise them into substances with new properties.
However, CBD could not be truly separated from its plant origins. Despite its use in pure form when it began to be used as a food supplement, studies soon showed that it was much more effective when used alongside other cannabinoids and plant substances. When taken with small amounts of the other natural chemicals found in cannabis, they influence how it interacts with the ECS. This gives a better and wider-ranging effect.
These are the key global figures who have shaped the short history CBD.
R. S. Cahn was a British chemist for many years until his retirement in 1965. He specialised in stereochemistry and introduced the Cahn-Ingold Priority Rules which allow systematic naming of stereoisomers of molecules. He was a fellow of the Royal Institute of Chemistry and editor of the Journal of the Chemical Society from 1949 until 1963.
R. Adams was an American organic chemist. He became a hugely influential scientist thanks to his work on finding the compositions of many natural substances such as complex vegetable oils and plant alkaloids. Not only did he isolate cannabidiol from Cannabis Sativa he also showed its relationship to cannabinol (CBN) and tetrahydrocannabinol (THC).
Dr Mechoulam conducted extensive research into cannabis pharmacology over many years (Bialer, 2018). Much of the understanding we have today of how cannabinoids are structured and their effects stem from his work. He is a natural products chemist and focuses mostly on the chemistry of substances from plants.
In the sixties, he was surprised to find out that while morphine had been isolated from opium 150 years ago, and cocaine had been isolated 100 years ago, the chemistry of cannabis was not well known. To build a chemical basis for their research his team started looking at the chemistry of cannabinoids.
Professor Howlett and her then research student William Devane were based at St. Louis University Medical School, Missouri. Their research into cannabinoids allowed them to understand how they interact with the body. Professor Howlett’s current work continues to focus on how some drugs can target specific neurons.
In 1992, Dr Hanuš and William Devane (now a molecular pharmacologist) successfully isolated and described the structure of the first endogenous cannabinoid neurotransmitter ever discovered: anandamide. Dr Hanuš continues being an active researcher of medicinal cannabis and an advocate of its use as "one of the safest known medications" (iDNES.cz, 2010).
The history of CBD is filled with misunderstanding and prohibition. However, thanks to those who kept researching and providing the public with facts, we can now make up our own mind.
As hundreds of new studies have been commissioned, we are set to know more about CBD than ever before. As we gain a better understanding of CBD it is bound to affect how it is viewed and how it can be used.
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Tom Russell
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Tom Russell writes extensively about CBD oil and other groundbreaking food supplements. He and his wife share their home with two daughters and a lifetime’s collection of books.