Why Cannabis Gets Us High

Dr. Raphael Mechoulam identified two cannabinoid receptors in the human body back in the 1980s. The CB-1 receptor, found predominantly in the brain, is also located in other parts of the body such as various fat and muscle cells, the liver, lungs, digestive tract and kidneys. It has various functions, including the conversion of fats in the liver. The CB-2 receptor is primarily located in the immune system, and is widely distributed in the brain and the digestive system, where it is thought to moderate inflammation.

While it has been suggested that the presence of these receptors is a clear sign that humans are meant to use Cannabis, these same receptors are also found in most animal life forms, including the sea cucumber – demonstrating that they play a wider role in our organism than just allowing us to get high. What is clear is that the human body produces chemicals that connect to these receptors: these are endocannabinoids. Five have so far been identified – arachidonylethanolamide (AEA; anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine, and N-arachidonoyl-dopamine (NADA). 

Anandamide affects both cannabinoid receptors in the human body, and is quite similar to THC. This endocannabinoid has been shown to impair working memory in rats, and to be a key element in stimulating appetite and regulating our moods. We now also know that it has the potential to inhibit the proliferation of human breast cancer. 2-AG is a CB-1 receptor 'agonist' (meaning that it provokes a biological reaction upon binding to the receptor) and is present in high levels in the central nervous system. The compound has been shown to be an analgesic produced in relationship to stress-related pain (such as a sport injury) in order to protect the body temporarily. Noladin ether’s function in humans is not yet known. Similarly, virodhamine is found within the brain but is relatively under-researched thus far. NADA is an agonist of the CB-1 receptor.

Today, an increasing amount of interest is paid to the study of the ECS, not only to understand the role it plays in the regulation of the metabolism but also to understand the psychoactive effects of individual cannabinoids and how they work in combination. Despite strong restrictions limiting the amount of research into Cannabis, we have gained a fair understanding of the way the elements contained in the plant can affect the human body. Thus far, 421 chemical elements have been identified – including 85 different cannabinoids whose exact effects on the body are still being investigated.

Through focusing on the most prevalent natural cannabinoids – THC, CBD and CBN – we have a good understanding of the interaction between them and our own ECS. THC (tetrahydrocannabinol) is the primary psychoactive element in Cannabis, responsible for the high you can experience from ingesting it. It has been shown to be efficient in moderating pain and connects equally to the CB-1 and CB-2 receptors in the body.

420+ chemical compounds... just a coincidence, right? (Photo: Deedee)

CBD (cannabidiol) is a non-psychoactive compound that does not connect to the cannabinoid receptors but rather influences the ability of other compounds to connect to the receptors. This compound is rich in medical properties: an anti-psychotic, an anxiolitic (tranquilizer) and anti-depressant; it also helps to relieve convulsions, inflammation and nausea and is structurally very similar to THC. CBN (cannabinol), on the other hand, is the main product of THC degradation: there is little in a fresh plant but levels increase when stored. One can observe this reaction occurring on Cannabis flowers subjected to lengthy exposure to light and air, as the resin glands turn from milky white to amber. Interestingly, CBD and CBN were discovered in the 1940s, decades before THC was first isolated.

The advances we have seen in the medical applications of C. sativa have been spreading in waves in recent years. Worldwide debates about the necessary end to the plant's prohibition has reached the level of groups such as the World Health Organization (WHO) and groundbreaking work, including this first publication of an entire Cannabis genome, continues to fuel hope. From chronic pain to muscle spasticity, lack of appetite to sleeping disorders, psychosis and schizophrenia: the medical value of Cannabis has been shown to be vast and controversial, and still far from entirely understood.

Even this cuddly koala can get high (Photo:Yenhoon)

Understanding the reasons behind this could lead to developments not only for the medical field but also in enhancing strains for other sectors such as textiles and nutrition. Industrially, we could develop more efficient industrial hemp strains, concerning both fiber production for the textile industry; and to enhance hurd/shive production (woody, fibrous core of hemp stalks) in order to provide even more efficient alternatives to petroleum products such as plastics. The possibilities are endless.

We are now beginning to understand how different chemicals combine in Cannabis to produce its various compounds. More specifically, we understand the pathways undergone to produce some of the cannabinoids upon which scientists are focusing today – not just THC, CBD and CBN but also the less famous cannabinoids, including CBC (cannabichromene). THC, CBD and CBC are the result of bio-synthesis from the same substrate: cannabigerolic acid (CBGA). This substrate synthesizes into three enzymes: tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA), which in turn synthesize into THC, CBD and CBC, respectively.

Identifying these pathways and the permutations undergone to produce the resulting cannabinoid compounds gives us the first insight into how genetic manipulation could enable the development of ailment-specific strains, through directing these permutations.

Tailor made strains for tailored needs... fiction seems one step closer to becoming reality.