Underwater shot of a diver after the jump in the sea and breaking water surface. This photo contains noise as a result of very low light conditions

Deciphering Cannabis: a Deep-dive into its Cannabinoid Constituents

Underwater shot of a diver after the jump in the sea and breaking water surface. This photo contains noise as a result of very low light conditions

Cannabis is a complex plant. Its chemical profile includes over 500 compounds and over 100 cannabinoids, with more being discovered each year. While research on cannabis has been rising steadily, there is still much that we do not understand about cannabinoids and the way they work with the human body.

At Goodbody, we believe in sticking to evidence. This is why all of our products undergo Phytovista Labs testing and certification, and why we are so proud of our research partnership with King’s College London. However, we understand that navigating the world of CBD and cannabinoids can get very confusing. Not only is the history and science behind cannabis intricate, but popular media sources will often inflate or overly simplify available evidence.

If you have been looking for a reliable companion to decipher cannabis, look no further!

This article will help you get a clear sense of what is known, and what can still only be guessed, about cannabinoids. A good way to start is by taking a step back–and by this we mean way back – to where the history of cannabis is woven with that of humanity, and where both lose themselves in myth.

The Lost Origins of Medicinal Cannabis

When reading up about the history of cannabis, you are likely to come across references to a Chinese text, called the Shen Nong Ben Cao Jing, the Shen-nung Pen-tsao Ching, or simply the Ben Jing. This is thought to be the world’s oldest so-called ‘pharmacopoeia’ in which the uses and effects of drugs and medicines are documented. According to scholars, the text laid the foundations for traditional Chinese herbal medicine, by introducing the first classification of medicinal plants in the region. It’s a great example of how ancient civilisations were already using cannabis for medicinal purposes, and even documenting its effects.

In the Ben Jing, cannabis (the old Chinese name is “Ma Fen”), alongside other herbs like Chinese cinnamon and ginseng, are classified as what roughly translates to as ‘superior’ or ‘noble’ herbs. These herbs were grouped as they were thought not to have any harmful or toxic effects, and were instead thought to have ‘stimulating properties’. The plant’s positive medicinal effects include remedying energetic imbalances, called ‘the seven damages,’ as well as having the ability to heal vital organs known as ‘the five viscera’. On the other hand, hemp seed was thought mainly to ‘supplement the centre’ of the body and ‘boost the qi’’ (the energy flow of life). As in any good pharmacopoeia, the Ben Jin includes a list of side-effects. The book states that when consumed in large amounts, cannabis may make one ‘behold ghosts’. Little else is said in the text about cannabis. You can consult the book yourself for other amusing anecdotes, including one about herbs that supposedly make you fly.

If you have chanced on the Ben Jin before, you’ll have realised that there was already a great deal of confusion surrounding cannabis – even back then. Despite an absence of formal scientific research in these ancient times, the documentation of cannabis’ effects demonstrates a first attempt to understand how this plant affects the human body. Its description of cannabis’ effects might be confused at times, but is indicative of a true belief that cannabis was a sort of multi-tasking do-all, heal-all cure. The Ben Jin’s date of publication is also up for debate – some sources trace it back to 2737 BC, others to around 2500 BC, and others to 50 AD. As it turns out, it’s not even certain there ever was a Ben Jin to begin with. The first full passages of the text come from the writings of an academic called Tao Hong-Jing (456-536 AD), which were supposedly copied from Shen Nong’s original Ben Jin text. All that remains today are rough copies of sections of Hong-Jing’s text, so a copy of a copy of the original document. Whether or not Shen Nong and his Ben Jing really existed will remain a mystery, and likely lie more in the realm of myth rather than fact. Today, Shen Nong takes on the form of a legendary figure, described as a sage ruler whose name translates to ‘Divine Farmer,’ he was first credited with teaching humans how to farm and classify herbs. Although Shen Nong’s historical existence is disputed, he remains an important hero of Chinese culture, as one of the three sacred originators of Chinese life-arts.

Discovering Cannabinoids: from plant to body

How do we travel from ancient Chinese manuscripts to present-day reality? The long answer would take us on a world tour, tracking cannabis usage down the ages. In short, cannabis was used in traditional and ancient medicine for centuries, particularly for treating pain but also other ailments. In addition to this, hemp was cultivated throughout the world for textile production, and was a hugely important crop. The mid-19th century would bring with it the dawn of modern cannabis science, when European doctors exploring the world were exposed to and became interested in, the plant that we know today as cannabis.

One pioneer worth remembering is Sir William Brooke O’Shaughnessy. While working as an assistant surgeon with the East India Company, O’Shaughnessy conducted experiments on animals and patients, noting the pain relief, calming, and anticonvulsive effects of cannabis. The fame of cannabis grew to the point that Queen Victoria’s personal physician is said to have prescribed it to her to help ease menstrual pains. By 1937, at least two thousand cannabis medicines–so-called ‘patent medicines’–existed in the West, with over 280 manufacturers producing cannabis tinctures and the like.

The first phytocannabinoid (found the Greek ‘phuton’, plant) to be isolated was cannabinol (CBN), a mildly psychoactive component that forms in aged cannabis and was discovered around the end of the 19th century. It would take several more decades before the structure of CBN would be deciphered. Its chemical synthesis took place in 1940, followed shortly by the discovery of a second phytocannabinoid: cannabidiol, or CBD. A few years later, THC (delta-8 and delta-9) were first extracted. However, the chemical profiles of delta-9 THC and of CBD, were only unveiled later on, in the early 1960s.

We owe these advances in our understanding of delta-9 THC and CBD to the Israeli Raphael Mechoulam and his laboratory, which also synthesised the first ‘enantiomers’ of CBD and delta-9 THC. Quick chemistry lesson: a molecule’s enantiomer is basically its mirror image, with one of the two often responsible for particular physiological effects, and the other potentially countering them or playing no active role. A drug with two enantiomers can be considered as two different drugs: an activator, or ‘agonist,’ and an ‘antagonist’ version. This research, therefore, allows us to further understand the interactions of delta-9 THC and CBD with our bodies, as well as what chemical properties were driving their effects. This leads us nicely onto the endocannabinoid system.

The cannabinoids within: the endocannabinoid system (ECS)

Most of us know that cannabis and the cannabinoid constituents that are found in cannabis interact with our bodily systems and cells to have different effects on our wellbeing and our mental state. However, what some of you might not know is that the body naturally produces its own type of cannabinoids! These have come to be known as ‘endocannabinoids,’ from the Greek word ‘endo,’ meaning ‘within.’ The term ‘endocannabinoid system’ refers to a complex network of molecules, receptors, enzymes, and pathways which control the production of, and response to, cannabinoids.
 This is a fascinating system to say the very least, as mysterious as it is promising. In the words of DiPatrizio, an assistant professor at the University of California, Riverside, School of Medicine: ‘There is so much that’s still unknown about (the endocannabinoid) system. It looks to be regulating every physiological system in the body.
 Essentially, endocannabinoids share the basic lipid-based structure as phytocannabinoids (the cannabinoids in cannabis), and both bind to the same receptors populating our bodies, or (as in the case of CBD) modify these receptors’ abilities to bind with cannabinoids.

The evolutionary origin of endocannabinoids is still rather obscure, though studies suggest that CB receptors also occur in all mammals and birds, amphibians, fish, sea urchins, molluscs (among other genera), with the primordial CB receptor having evolved at least 600 million years ago. The history of endocannabinoids, on the other hand, is fairly recent, and rather clear. The first discoveries took place in the early 1990s when researchers stumbled upon a nervous receptor (CB1) that appeared to react specifically with psychoactive cannabinoid substances, such as THC. The reasoning went something like this: if the brain contains cannabinoid receptors, then surely it must also contain cannabinoids. A rush to locate the first endogenous cannabinoid ensued, which soon culminated in the breakthrough discovery of the molecule ‘anandamide.’ Raphael Mechoulam and his team chose the name from the Sanskrit word for bliss or happiness, ‘ananda.

This meant another piece of the cannabinoid puzzle was filled in. The identification of CB1, alongside that of another main receptor (CB2), has subsequently broadened our sense of how, and where, the endocannabinoid system operates.

The answer: the system is pretty much ubiquitous, with receptors turning up everywhere from reproductive to adipose tissues, and from the anterior eye to the pituitary gland. In general, we might say that while CB1 receptors abound in the central nervous system and parts of the enteric nervous system (which controls the digestive tract), the expression of CB2 receptors mainly concerns the immune system. As such, CB2 receptors are found in the spleen, white blood cells, and the thymus–an organ that plays a vital role in the early formation of adaptive immunity.

As research progresses, it is becoming increasingly difficult to tell precisely where CB1 occur as opposed to CB2 receptors, with some scientists terming CB2 the ‘cannabinoid receptor with an identity crisis.’ Once again, we would encourage you to avoid oversimplifications: CB2 expression does also concern the brain (this was seen by tracking neuroinflammation)–though the extent of this remains controversial. A simple way of putting it would be to say that the endocannabinoid system works as a network, bridging mind and body in ways that we are only beginning to understand.

Recent decades have continued to chart the territories of this network, to the point where we can now be confident in the fact that the endocannabinoid system plays a number of important physiological and regulatory functions, such as the regulation of mood, metabolism, the storage of energy, pain sensation, and the immune system. These exciting new discoveries have led to popular claims that the ECS ‘maintains homeostasis’ in the body. It is a pretty definitive statement and does seem to put to rest much of the doubts surrounding the potential role of cannabinoids.

We should nonetheless keep in mind that the ‘homeostasis’ associated with the ECS in the scientific literature often concerns the regulation of energy balance and metabolism, rather than a universal ‘harmony’ of all bodily and neurological processes. We’ve now learnt that there are cannabinoids that are produced by our bodies, just as they are produced by the cannabis plant. Deepening our understanding of the relations between the two–cannabinoids and the body–is bound to yield groundbreaking discoveries concerning the way our bodies function.

Cannabis: the plant

Let’s continue our deep dive with a quick whistle-stop tour of the cannabis plant. There are three species that make up the Cannabis genus: Cannabis sativa, Cannabis indica and Cannabis ruderalis. A genus is simply the taxonomic level above a species, which describes groups of species that share similar physical characteristics. The Cannabis genus, in turn, is part of the Cannabaceae family. Over the years, varieties of each of the three species have been bred, often with the aim of enriching the concentration of certain cannabinoids or other constituents, making plants more suitable for a variety of different uses. For example, low-THC varieties, which are more commonly known as ‘hemp’, have historically been used for making textiles. On the flip-side, high-THC varieties have also been sought after and bred, forming the so-called  ‘marijuana’ strains that are commonly associated with intoxicating and mind-altering effects.  
There are over 100 known cannabinoids that are present in cannabis plants. Still, the two usually present in the highest levels are THC and CBD, which explains why much of our knowledge and research today is centred around these two cannabinoids. However, the way in which CBD and THC interact with our bodies is very different. Without getting into too much biochemistry, THC has intoxicating effects because it partially activates both the CB1 and CB2 endocannabinoid receptors that we touched on earlier. This then has downstream effects on other signalling molecules involved with other processes in our body and brain, creating the ‘high’ that THC is associated with. CBD, on the other hand, affects our body differently. The interactions that CBD has in our body are also not as well understood as those of THC, as research into these pathways is still developing. It is currently thought that CBD also has a slight affinity for the CB1 and CB2 receptors, but is thought not to have the same activating effect, and has been suggested even to inhibit the activating effect of other cannabinoids. Multiple studies have pointed to different interactions of CBD with other receptors and signalling pathways. Further research will allow these mechanisms to be fully elucidated. Interestingly, it has also been proposed that CBD may alter the effects of THC on the body when the two are consumed together.  

The Future of Cannabinoids

As we’ve mentioned, cannabinoid research is still only in its infancy. Cannabis is a well-researched plant, but with so many cannabinoid constituents with such varied functions and effects, there is still a great way to go in order for these interactions to be thoroughly characterised and understood. If you glance at any recently peer-reviewed study on cannabis, you will notice that calls for future high-quality studies are pervasive, the evidence is often modest, and definite answers are few. The issue has in part to do with practical constraints of conducting long-term clinical trials on humans, so that the bulk of research comes from experimental animal models, with limited applicability to humans. With over a hundred cannabinoids in cannabis, and with each cannabinoid likely interacting with multiple systems in our body, there’s a lot of work to be done. In addition to this, each individual has a different metabolism and biological makeup, and so even detailed research won’t be able to provide us with a one size fits all solution.
However, the issue is also a societal and political one. It is hardly a secret that cannabis science and therapeutics suffers from the notorious reputation of THC. The public health hazards associated with THC and the fact that cannabinoid consumption was illegal for years impaired research in this area. When it comes to CBD, important questions such as its interactions with other cannabinoids, or the preferable dosage and mode of assuming CBD, beg for further examination.
As a company, we take the stance that we welcome regulations in order to bring CBD to people in a regulatory fashion so that it’s trusted – therefore our message to the world is that we always want to take the high road and welcome regulations.
That being said, it does feel like cannabis is slowly moving beyond its negative connotations, and that knowledge of all the cannabinoids’ intricate workings has been gradually unveiled for the benefit of all. Cannabis research might have been more accessible back in the nineteenth century, given a lack of regulation, but at the same time, the uncontrolled and unregulated nature of research meant that findings were not nearly as robust and reliable as they are today. Nowadays, researchers studying cannabis, as well as other controlled substances, have to comply with strict regulations which vary from country to country. In general, in order for research to make it into a respected peer-reviewed journal, any findings have to be backed by robust and repeatable evidence. The growth in governmental control as well as the development of our research industry as a whole have been instrumental in driving positive developments in the industry. We hope that the future holds more positive change and that brands focus on producing the highest quality products that will build consumer trust, creating greater stability in the market which will also support further research in the field.

 Goodbody is here for you

At Goodbody, we’re committed to providing you with the best possible CBD experience. That’s why we’ve got plenty of guidance and educational content on our website so that you can stay informed! Check out our CBD Guide page for everything you need to know about CBD and wellness.
 If you’ve already had a read, and you’re ready to try it out, why not check out some of our top-quality CBD products? If you’re looking for something to help you get a good night’s rest, our Calm collection is the place to go if you’ve been feeling hectic or overwhelmed, and finally, last but not least, have a look at our Relief collection if you’ve got any aches or pains that you want to relieve.

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