How Cannabis Works When Treating Disease

Scientific studies have revealed that cannabis has a very clear effect on the human body, but until -just over two decades ago, it wasn’t understood why. Since the discovery of endocannabinoid receptors and the endocannabinoid system, the use of cannabis in the treatment and/or management of a variety of medical conditions, diseases and their associated symptoms has been of great interest to medical researchers.

To understand exactly how cannabis/medical marijuana works when treating illness, it is important to have a background on what the endocannabinoid system is and how it works.

The Endocannabinoid system (ECS)

Since its discovery in 1992, scientists have found that the endocannabinoid system (ECS) is responsible for regulating (i.e. balancing or keeping in homeostasis) a host of bodily functions and cognitive processes. Some of these include:

• Fertility, pregnancy, pre- and postnatal development
• Appetite
• Energy balance and metabolism
• Stress response
• Inflammation
• Immune system function
• Pain sensation
• Memory
• Mood
• Sleep 
• Physical exercise
• Temperature regulation
• Pleasure / reward

It is basically involved in nearly every bodily function and process.

This system is comprised of three parts¹:

• Endocannabinoids – The body naturally produces chemical compounds which are ‘cannabis-like’ in nature. These are referred to as cannabinoids or endocannabinoids. The word ‘endo’ means ‘internal’ – endocannabinoids are cannabinoids produced within the body. Endocannabinoids identified to date include:
• Anandamide (AEA)
• 2-arachidonoylglycerol (2-AG)
• N-arachidonoyl dopamine (NADA)
• Noladin ether (2-arachidonyl glyceryl ether)
• Virodhamine
• Cannabinoid receptors – These are receptors within the body that endocannabinoids bond with. To date, two types of cannabinoid receptors have been identified (and some researchers believe there is a third type that is yet to be discovered):
• CB1 receptors – These are located in the central nervous system (i.e. the nerves of the brain and spinal cord)
• CB2 receptors – These are found in the peripheral nervous system (i.e. all nerves outside of the central nervous system), digestive system and within certain cells of the immune system. 
• Metabolic enzymes – These are responsible for the production and breakdown of cannabinoids.

The endocannabinoid system maintains balance in the body and homeostasis in each of its functions via endocannabinoids (think of these as chemical keys) which then bind with cannabinoid receptors (think of these as locks) which tell the body when to start (unlock) or stop (lock) a specific function. Its functioning is precise and meticulous – for example, if one system has an issue, say for example hormones become imbalanced for some reason, the endocannabinoid system will work to restore balance without affecting the other systems through the release of targeted endocannabinoids. Once balance is restored, in order to ensure that it is not tipped in the opposite direction, metabolic enzymes then break down any endocannabinoids that have not found a receptor to bind with.

Clinical endocannabinoid deficiency

When there is a disruption to the natural function of the endocannabinoid system for some reason, dysfunction in one or more of the bodily process this system governs may be experienced, resulting in illness and disease.

Researchers like the renowned cannabinoid researcher Dr Ethan Russo have found evidence that those with certain medical conditions (migraine, fibromyalgia, irritable bowel syndrome and related treatment-resistant conditions) exhibit lower levels of endocannabinoids, and may benefit from supplementation with cannabinoids such as those found in cannabis, in order to help restore balance (homeostasis) within the body².

While research into correcting endocannabinoid deficiency is still in the early stages, the results are promising and with the increasing availability of medical marijuana as well as THC and CBD based supplements, there is sure to be more evidence available in the near future.

Cannabis and its effects on the endocannabinoid system

The cannabis plant contains phytocannabinoids³ with chemically similar structure to the natural cannabinoids that occur in the human body. As they are not produced within the human body, these are referred to as exogenous cannabinoids (i.e. those that are produced externally by another source). In cannabis plants, these compounds are found in the form of cannabinoid acids which have insecticidal and antibiotic properties and are primarily produced by the plant as a defence mechanism against predators.

These acids are:

• CBCA (Cannabichromenenic acid)
• CBCVA (Cannabichromevarinic acid)
• CBDA (Cannabidiolic acid)
• CBDVA (Cannabidivarinic acid)
• CBGA (Cannabigerolic acid)
• CBGVA (Cannabigerovarinic acid)
• THCA (Δ⁹-tetrahydrocannabinolic acid)
• THCVA (Tetrahydrocanabivarinic acid)

When these acids are exposed to heat energy, they undergo a chemical reaction known as decarboxylation, and the acid makeup is removed, converting these into neutral plant cannabinoids that yield the compounds that most are familiar with:

• CBC (Cannabichromene)
• CBCV (Cannabichromevarin)
• CBD (Cannabidiol)
• CBDV (Cannabidivarin)
• CBG (Cannabigerol)
• CBGV (Cannabigerivarin)
• THC (Delta-9–tetrahydrocannabinol)
• THCV (Tetrahydrocannabivarin)

Of these, the most commonly recognised when it comes to medicinal use are CBD and THC. THC is the only plant cannabinoid that has proven intoxicating effects that result in a state of euphoria or ‘high’, hence it’s popularity in recreational use. THCV may also have intoxicating properties but these are dose dependant.

THC’s effect on the endocannabinoid system

Endocannabinoids work as neurotransmitters (chemical messengers that transmit information from one cell to another) within the brain and nervous system. Neurotransmitters interact with a variety of receptors in order to regulate a number of bodily functions and therefore have numerous effects. The phytocannabinoid THC bind to both CB1 and CB2 receptors and activates these in the same way that endocannabinoids do.

When a person smokes marijuana or ingests cannabis-based medications that contain THC the phytocannabinoids present attach to the CB1 receptor in the brain and creates a feeling of euphoria or a ‘high’. The endocannabinoid (i.e. a naturally occurring cannabinoid in the body) that usually attaches to this receptor and whose chemical structure is very similar to that of THC, is called anandamide. Anandamide plays a role in the regulation of pleasure, pain, appetite, cognition, mood, memory and emotion, movement, co-ordination, sensory function and time perception.

Although the two are similar in chemical structure, the reason that anandamide doesn’t cause a high and THC does is due to an enzyme called Fatty Acid Amid Hydrolase (FAAH) which rapidly breaks down naturally occurring anandamide but does not break down THC. This means that THC remains active with a much greater effect for longer periods. 

When this occurs, THC essentially binds to the receptors that anandamide usually would, disrupts the normal function and indirectly boosts the feel-good hormone dopamine in the brain’s reward system at levels higher than are usually experienced in response to anandamide signalling. THC also blocks the transmission of pain signals to the brain, which means they are then not felt.

The effects of CBD on the endocannabinoid system

Cannabidiol or CBD is another phytocannabinoid produced by the cannabis plant. Unlike THC, it does not have any psychoactive properties and does not induce feelings of euphoria or a high when consumed.

This is because unlike THC, CBD does not bind to the receptors directly, but instead inhibits the FAAH enzyme which slows the breakdown of anandamide, this leads to a greater build-up of the endocannabinoid in the brain and increases its impact on various systems throughout the body. It is also one of the reasons why CBD is beneficial to those suffering from anxiety.

Cannabis treatment potential

The true potential of medical cannabis to treat various health conditions and diseases is only just beginning to be realised. 

Due to the fact that the phytocannabinoids contained in cannabis can stimulate the activity of the endocannabinoid system, they are an obvious focus for medical research. 

The cannabinoids contained in cannabis are beneficial for medical purposes and act as⁴:

• Bronchodilators (i.e. they open up the airways which may be useful for those suffering from asthma)
• Pain relievers (especially for those with neuropathic pain conditions)
• Anti-inflammatories
• Muscle relaxants and antispasmodics (i.e. drugs that reduce or prevent muscle spasms, especially those experienced with multiple sclerosis (MS))
• Antiemetics (these help to prevent nausea and vomiting, specifically in those undergoing chemotherapy or cancer-related treatments)
• Appetite stimulants (THC helps those with diseases that cause decreased appetite and wasting such as Cancer and AIDS, as well as those suffering from anorexia) 
• Neuroprotective antioxidants – THC slows the production of plaque-forming proteins in brain cells which are characteristic of Alzheimer’s disease and dementia⁵ 
• Anti-epileptics (especially in the treatment of seizures in those with Dravet syndrome and Lennox-Gastaut syndrome)
• Sedatives
• Anti-anxiety agents and mood enhancers⁶
• Opioid addiction treatments (Opioids are a type of painkiller, cannabis reduces pain and boost the opioid’s effectiveness which means that fewer opioids in lower doses are required. This enables professionals to wean addicts off opioids)⁷

It is important to note that while Cannabis has a number of beneficial properties, it is not without side effects. As such, appropriate dosage is necessary, and it is advisable to always consult your medical practitioner before using any cannabis products to treat the symptoms your particular health condition.

References

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2. Russo E. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016;1(1):154-165. doi:10.1089/can.2016.0009 
3. Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2(6):241-254. doi:10.1177/2045125312457586
4. Grotenhermen F. Clinical Pharmacodynamics of Cannabinoids. Journal of Cannabis Therapeutics. 2004;4(1):29-78. doi:10.1300/j175v04n01_03
5. Cao C, Li Y, Liu H et al. The Potential Therapeutic Effects of THC on Alzheimer's Disease. Journal of Alzheimer's Disease. 2014;42(3):973-984. doi:10.3233/jad-140093
6. Tambaro S, Bortolato M. Cannabinoid-related Agents in the Treatment of Anxiety Disorders: Current Knowledge and Future Perspectives. Recent Pat CNS Drug Discov. 2012;7(1):25-40. doi:10.2174/157488912798842269
7. Wiese B, Wilson-Poe A. Emerging Evidence for Cannabis' Role in Opioid Use Disorder. Cannabis Cannabinoid Res. 2018;3(1):179-189. doi:10.1089/can.2018.0022