© Helius Therapeutics 2018

HOW MEDICINAL
CANNABIS WORKS

Attitudes towards cannabis are shifting as credible medical research continues to reveal the plant’s profound therapeutic effects. Many people have experienced the benefits of medicinal cannabis on the human body, so let’s explore its method of action. 

 

The chemical compounds in cannabis affect the endocannabinoid system (ECS), a central component of the health and healing of every human and almost every animal. Scientists estimate that the endocannabinoid system evolved in primitive animals over 600 million years ago.

 

The endocannabinoids and their receptors are found in the brain, organs, connective tissue, glands and immune cells, all throughout the body. The ECS is responsible for managing a vast range of physiological processes including mood, memory, pain-sensation, appetite, and regulating the psychoactive effects of cannabis.​

A brief history of the ECS 

 

The endocannabinoid system (ECS) was defined in the early 1990’s when Lisa Matsuda announced that her team at the National Institute of Mental Health had first identified a THC-sensitive receptor in lab rat brains.The path to the discovery of the endocannabinoid system, however, started more than a century earlier. In 1895, researchers T. Barlow Wood, W.T. Newton Spivey, and Thomas Hill Easterfield became the first to isolate and identify a cannabis-derived cannabinoid, cannabinol (CBN).

 

Over the next 70 years, researchers identified more cannabinoids, including R. Adams and others who identified and isolated CBD in 1940, and in 1964, Ralph Mechoulam and colleagues isolated and identified tetrahydrocannabinol (THC). Following those monumental breakthroughs, researchers spent decades exploring those cannabinoids and their properties. 

 

It was in the early and mid-1990s Mechoulam and colleagues officially discovered the endocannabinoid system. It happened after he and his team were able to locate and identify two of the body’s naturally produced major endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG).

 

Since then, scientists around the world have worked to learn more about the endocannabinoid system, our naturally occurring cannabinoids, and the ways cannabis alters this balance. In just the last two decades, over 23,000 scientific studies have been published, referencing the therapeutic effects of cannabis.  

An integrated system

 

Three key integrated mechanisms make up the ECS:

 

  • Enzymes responsible for creating and destroying cannabinoids 

  • Receptor sites on cells to receive cannabinoids 

  • Endocannabinoids themselves (cannabinoid-like compounds that are naturally produced by the human body)

 

These mechanisms are predominantly responsible for communication within the body to best regulate various biological responses. 

 

We now know the body produces its own natural equivalents to phytocannabinoids, like THC and CBD, found in the cannabis plant. These are known as endocannabinoids (anandamide and 2-AG). Knowledge that our bodies create their own cannabinoids has opened the door to understanding their purpose.

A physiological response

 

Endocannabinoids are created in response to needs within the larger physiological system and are largely understood to be used for the body’s regulatory functions. Working backwards on presynaptic cells, they control the volume at which communicating signals are sent. It is in this way that endocannabinoids affect duration and intensity of the wide range of physiological processes under their control.

 

The endocannabinoid system is linked to a number of important processes, concentrated in the brain, nervous system, and reproductive organs. However, it does not affect regions of the brain controlling heart and lung function, making cannabis neuroprotective. This is one of the main reasons that fatal overdoses of cannabinoids do not occur. 

Cannabinoids balance homeostasis  

 

Whenever there are deviations from homeostasis in the body’s functions, the endocannabinoid system is activated and begins to respond accordingly by synthesising endocannabinoids, which act as neurotransmitters.

 

When the body creates neurotransmitters for the endocannabinoid system, they are picked up by specialised cannabinoid receptors, which sit on the surface of cells. These receptors are found in a wide range of physiological regions, such as in: 

 

  • The immune system 

  • Organs and glands 

  • Connective tissue 

  • The brain (most significantly)

 

Like a key fits into a lock, endocannabinoids interact with these receptors and transmit information about changing conditions to kick-start a response, with the goal of helping the body achieve homeostasis, or equilibrium, within the body to counteract outside influences.

Receptor sites and cannabinoids

The endocannabinoid system’s receptor sites include CB1 and CB2 receptor variants, which respond differently to certain cannabinoids, such as THC, CBD and CBN. CB1 receptors are most prevalent in the central nervous system and are linked to the following benefits: 

 

  • Modulation of stress and anxiety 

  • Increased appetite 

  • Decreased nausea 

  • Balance of immune system 

  • Inhibition of tumours

CB2 receptors are found mostly on cells in the immune system and tend to dominate in fighting inflammation and damage to tissue. Some cells can even contain both types of receptors, each responsible for a different function.

There are two major endocannabinoids; 2-arachidonoylglycerol (2-AG) and Anandamide (AEA). 2-AG is considered a full agonist of both CB1 and CB2 receptors. This means that it binds with, and fits well inside, both receptors to activate them to stimulate a physiological response. 

Anandamide is considered a partial agonist of both receptors because, while it binds with and activates the receptors, it doesn’t fit as well inside them and subsequently doesn’t trigger such a powerful physiological response.

 

Once the function that had deviated from homeostasis returns to equilibrium, and the endocannabinoids are no longer needed – the third piece of the system, metabolic enzymes, breaks down and degrades them.

How the system affects our health

Since discovering the endocannabinoid system and its mechanisms, researchers have worked to further understand how the endocannabinoid system may be used therapeutically to treat a wide range of clinical conditions and symptoms, such as to: 

  • Decrease pain 

  • Fight cancer

  • Prevent neurodegenerative diseases

  • Promote general health

 

Overall, research indicates that the endocannabinoid system helps ensure that the body’s immune and central nervous systems are running correctly. Finding ways to modulate the endocannabinoid system’s activity opens pathways to a vastly disparate set of chronic diseases and disorders.

How cannabinoids work with the ECS

As scientists learn more about the endocannabinoid system, they also explore the role that cannabis-derived cannabinoids like THC, cannabidiol (CBD), cannabinol (CBN), and others could play in supporting health. Cannabinoids mimic the behaviour of endocannabinoids and interact with the cannabinoid receptors to augment the endocannabinoid system. As the cannabinoids interact with the cannabinoid receptors, they stimulate various physiological responses.

Cannabinoids have the potential to treat many diseases and conditions

A popular theory about how the ECS affects our overall health, is the proposed endocannabinoid deficiency syndrome, or CECD. This suggests that, for some people, the body does not generate enough endocannabinoids (Smith and Wagner, 2014). This concept, originally proposed by researcher E.B. Russo in 2004, further suggests that the deficiency could be the root cause of many autoimmune disorders, including migraines, fibromyalgia, and IBS (Russo, 2004)

By modulating the ECS, several diseases and conditions can potentially be treated, including: 

  • Pain 

  • Inflammation 

  • Arthritis 

  • Multiple sclerosis 

  • Anorexia 

  • Crohn's disease and IBS

  • Epilepsy 

  • Cancer 

  • Glaucoma 

  • Obesity 

  • Schizophrenia 

  • Cardiovascular disorders 

  • Parkinson’s disease 

  • Huntington’s disease 

  • Alzheimer’s disease 

  • Tourette’s syndrome 

 

One of the main obstacles to the acceptance and use of cannabis and its active cannabinoids in medicine is the problem of abuse for its psychoactivity. However, this issue does not arise in a number of possible approaches to the regulation of the endocannabinoid system: 

  • When an antagonist to the CB1 receptor is applied 

  • When the production or transportation of endocannabinoids is altered 

  • When a non-psychoactive agonist to the CB2 receptor, like CBD, is used for therapeutic results (Pacher and Kunos, 2013).

 

Phytocannabinoids, like the CBD and THC from cannabis, directly affect the endocannabinoid system. However, it has also been shown that non-psychoactive phytocannabinoids from other plants, and even other compounds like terpenes and flavonoids, are picked up by receptors in our endocannabinoid systems (Gertsch et al, 2010)

Because small doses of phytocannabinoids can encourage the body to create more naturally occurring endocannabinoids and their receptors, it may be possible to bolster the sensitivity of our native systems with regular cannabinoid supplements (Pacher et al, 2006).

Extensive studies show great potential for using this vital system to the benefit of patient health. Helius and scientists around the world are engaged on ongoing research to better understand the impact of the endocannabinoid system on our overall health and how supplementing our natural endocannabinoid production with plant-based cannabinoids may play a significant therapeutic role in our wellbeing.