What are cannabinoids?

Cannabinoids could be a cornerstone of pain relief and healing with cannabis. They are a class of chemical compounds derived from hemp and cannabis that interact directly with the cannabinoid receptors found throughout the endocannabinoid system (“ECS”). The potential benefits of medical marijuana can be attributed to the phenomenon of cannabinoids activating the CB1 and CB2 receptors in the brain and body. When CB1 and CB2 receptors are activated, we have the ability to improve how our body’s different systems and organs function.

Cannabinoids and terpenes develop in the resin glands, or trichomes, on the flower and leaves of cannabis plant. Other plants produce cannabinoids, but they are found in the highest concentration in cannabis. Terpenes and cannabinoids typically work together to develop a strain’s particular flavor and potential resulting high, a phenomenon known as the entourage effect (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/). The different cannabinoids and terpenes interact synergistically to potentially amplify the benefits of the plant’s individual components. Essentially, the whole plant is greater than the sum of its parts. Today, growers aspire to breed strains with high concentrations of both compounds due to their potential therapeutic effects.

The majority of medical marijuana research focuses on the study of cannabinoids. They are similar in structure to the neurotransmitters, which we call “endocannabinoids”, located in our peripheral and central nervous system. The network of these endocannabinoids in our bodies is called the endocannabinoid system.

There are two types of receptors, CB1 and CB2 receptors, that these neurotransmitters communicate with. When receptors are activated, they have the potential to influence how our body systems and organs function. Proper communication between the two may affect how we feel emotionally and physically. For instance, THC binds with CB1 receptors which are found in abundance in certain regions in the brain. It is believed that this is why individuals may have experienced an intoxicating high when they consumed THC.

The ECS controls the human body’s core physiological processes like pain, mood, appetite, memory and more. When this nervous system falters, the compounds derived from cannabis may help our bodies regain their natural balance and stability (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/). When we consume cannabis, these compounds may communicate on a cellular level with certain neurotransmitters.

According to our historical understanding of cannabis, humans have been interested in the potential medical benefits of the plant for around 3,000 years. However, our understanding of the ECS didn’t develop in order to solely help humans function better. Yes, we have a dynamic, biological connection with the plant. One that allows us to reap its potential therapeutic benefits. But, humans aren’t the only species to have an ECS. In fact, it is present in all vertebrate species – any animal that has a backbone has an ECS. Scientists have discovered that this system actually existed long before humans.

Researchers have developed theories about the initial development of the ECS. Many think that the abundance of CB1 receptors in the brain suggests that it took hundreds of millions of years for this level of endocannabinoid signaling to evolve.

According to Dr. John McPartland, a renowned cannabis expert and botanist, the ECS first started developing 600 million years ago (https://www.cannabis-med.org/membersonly/mo.php?aid=2002-01&fid=2002-01-3&mode=a&sid=). To put that in perspective, sponges were considered a complex life form at that time. When deciphering the evolution of cannabis, researchers estimate that the plant evolved approximately 34 million to 6 million years ago which places it millions of years after the ECS began developing in animals (https://www.leafly.com/news/cannabis-101/cannabis-evolution-what-do-we-know-about-the-plants-earliest-orig).

So, why did the endocannabinoid system evolve in the first place? We’re honestly not all that sure. We know that endocannabinoids and their receptors are located all throughout our internal systems. We also know that they play a crucial role in how the brain signals the rest of the body, but beyond that, it remains somewhat of a mystery.

WHY DOES THE CANNABIS PLANT PRODUCE CANNABINOIDS?
Based on the evolutionary timeline of the endocannabinoid system and the cannabis plant, it seems that cannabinoids didn’t develop for the potential benefit of humans. However, there are a few existing theories. Many scholars believe that cannabinoids contribute to the overall health of the cannabis plant. The chemical compounds have antioxidant properties which may serve as a protective mechanism. In plants, antioxidants can neutralize harmful free radicals that UV rays produce. These compounds may help protect the plant’s cellular structure.

Another theory is that cannabinoids, especially THC, may have developed to prevent animals and possibly pests from eating the plant. Most animals are susceptible to the psychoactive effect of THC, so perhaps these compounds developed as a Mechanism to protect the plant.

CANNABINOIDS AS A POTENTIAL FORM OF MEDICINE
In history, Cannabinoids may have been used as a form of medicine for thousands of years. Many different cultures and religions have historically recorded the plant as a form of potential treatment. Despite the potential wellness benefits (as noted in the latest edition of the National Academies of Science Technology, and Medicine, (The Health Effects of Cannabis and Cannabinoids:  The Current State of Evidence and Recommendations for Research) cannabis remains illegal at the federal level. Interestingly, the U.S. government owns a patent for the potential medical properties of cannabinoids. Patent No. 6,630,507 titled “Cannabinoids as antioxidants and neuroprotectants” was issued in 2003 to the United States of America by the Department of Health and Human Services. The patent states,

“The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia.”

Even though multiple government agencies have publicly acknowledged the potential benefits of cannabis, the plant remains a Schedule I substance. Luckily, the tides are changing and cannabis reform laws are progressing every day, opening up the field to scientific research.

In general, using medical cannabis as a potential treatment aims to connect certain cannabinoids with the right receptors. When this occurs, we are potentially equipped to offset the damages from external factors, like disease and stress. Studies have illustrated that when we get sick from certain conditions, our bodies lack the correct amount of endocannabinoids. This is the basis of a new theory called a Clinical Endocannabinoid Deficiency. (Cannabis and Cannabinoid Research Volume 1.1, 2016)   Cannabinoids derived from cannabis may be able to mimic our naturally produced endocannabinoids to help get our bodies back on track.

The goal with cannabis as a potential therapeutic treatment is to achieve homeostasis which means to cultivate a healthy internal environment. Cannabis may have preventative qualities. Some researchers believe that if we can maintain a homeostatic (or balanced) environment, we won’t develop certain conditions or symptoms. Though more research is needed, mounting evidence suggests that cannabinoids, along with proper nutrition, exercise and overall self-care, may be key to keeping our bodies balanced and functioning at their best.

LIST OF MAJOR CANNABINOIDS IN CANNABIS
Different types of cannabinoids have different potential effects. Certain ones may be able to provide pain relief while others may have anticonvulsant properties. The potential benefits of these chemical compounds are diverse, but more scientific studies are needed to truly understand their versatility and potential therapeutic effects.

TETRAHYDROCANNABINOLIC ACID
Tetrahydrocannabinolic Acid (THC-A) is a non-psychoactive cannabinoid. THC-A is typically the most abundant cannabinoid in raw cannabis. When THC-A is heated to a high enough temperature, it immediately converts to THC. This process, called decarboxylation, also occurs naturally as fresh cannabis dries and cures. Decarboxylation is simply what happens when carbon dioxide is released from the plant. Some patients juice raw cannabis to access the potential benefits of medical marijuana without consuming THC. Additionally, exposure to air for extended periods of time can cause THC-A to lose hydrogen atoms. When this occurs, THC-A can convert to cannabinol acid (CBN-A). Like THC-A is the precursor to THC, CBN-A is the precursor to the cannabinoid CBN.

A 2011 study (https://www.jstage.jst.go.jp/article/bpb/34/5/34_5_774/_pdf) found that THC-A was able to inhibit two enzymes, COX-1 and COX-2, that contribute to symptoms like fever, pain, and swelling. Anti-inflammatory medications, like aspirin, are taken to target these enzymes. The study showed that THC-A was able to inhibit these enzymes by up to 30%, illustrating significant anti-inflammatory properties. The compound has also illustrated antiemetic (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792001/) and neuroprotectant (https://pubmed.ncbi.nlm.nih.gov/28853159/) activity in certain studies. A 2018 study (https://www.liebertpub.com/doi/pdf/10.1089/can.2018.0010) discovered that THC-A was able to induce apoptotic cell death in colon cancer and polyp cells, suggesting possible future therapeutic value as an anti-tumor agent.

TETRAHYDROCANNABIVARIN
Tetrahydrocannabivarin (THC-V) is a potentially potent psychoactive cannabinoid. Research studies are examining its potential effects on certain psychological conditions such as PTSD. It may have anxiolytic (https://journals.sagepub.com/doi/abs/10.1177/0269881115615104) properties and has also shown promise as a potentially effective treatment for certain types of psychosis (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337703/). Limited rodent studies have indicated that THC-V can decrease appetite (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671751/).

DELTA-9-TETRAHYDROCANNABINOL
Delta-9-tetrahydrocannabinol (THC) is the most well-known cannabinoid and the main psychoactive compound in cannabis. THC is a fairly versatile cannabinoid. Notably, THC may have a significant antiemetic effect (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165951/). Many cancer patients use it to potentially reduce nausea and vomiting associated with chemotherapy treatments. It may also be used to stimulate appetite, making it a potentially useful medical agent for wasting syndrome and anorexia.

THC may be beneficial for pain management (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/). The analgesic properties may be useful for potentially easing chronic pain stemming from multiple conditions. Patients struggling with sleep-related issues may also benefit from THC. Studies have found that the compound can reduce rapid eye movement (https://www.ncbi.nlm.nih.gov/pubmed/178475) during sleep which could help limit PTSD-related nightmares, providing more restful sleep. Many patients also state that it may help them fall asleep easily. Other common uses may include protecting the nervous system, reducing muscle spasms and providing a sense of relaxation and stress relief.

CANNABIDIOL
Cannabidiol (CBD) is another versatile cannabinoid with potential therapeutic effects. The non-intoxicating properties make it more applicable to those who need and want to stay clear-minded. One of the most appealing potential aspects is how CBD may actually mitigate the unwanted side effects of THC (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/), like intoxication and increased heartbeat. CBD may have powerful anti-inflammatory properties (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/). The compound may also be useful for treating certain mental health conditions and CBD may be an anxiolytic and antipsychotic agent (https://www.nature.com/articles/tp201215).

Some of CBD’s most studied attributes are its antiseizure properties (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819831/). You might have heard of the high CBD strain, Charlotte’s Web. It was developed for a young girl named Charlotte who suffered from Dravet’s syndrome, a rare form of epilepsy. A tincture derived from this strain helped reduce the hundreds of weekly seizures Charlotte endured to only a few. This was an unbelievable feat that catalyzed the medical marijuana movement. It is also a prime example of how impactful cannabinoid therapy may be.

CANNABINOL
Cannabinol (CBN) naturally occurs when cannabis is exposed to heat and light. It’s typically found in amounts of less than 1%. It may have very minimal psychoactive properties. There is very limited research on CBN to date.

CANNABIGEROL
Cannabigerol (CBG)  is a non-intoxicating cannabinoid that is found in minimal amounts (less than 1%) in medical marijuana. CBG is the chemical precursor to THC and CBD. CBG has the potential for chronic pain management (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/#b42). One study found that CBG may have potential as an anti-cancer agent (https://www.ncbi.nlm.nih.gov/pubmed/25269802). Along with THC-A, the compound was able to inhibit the growth (https://www.ncbi.nlm.nih.gov/pubmed/25269802) of colorectal cancer cells in mice which slowed the colon cancer growth. It may also be able to block receptors that cause cancer cell growth. This is very preliminary research that warrants further research, but medical studies are still a long way from proving CBG’s efficacy as an anticancer agent in humans.

CANNABIDIVARIN
Cannabidivarin (CBD-V) is a non-intoxicating cannabinoid that may have anticonvulsant effects in certain rodent studies. It is being researched for its potential in treating epilepsy.

IN SUMMARY
Understanding the different types of cannabinoids is essential to using medical marijuana as a therapeutic treatment. Preliminary scientific research shows that the potential benefits of medical marijuana are vast, but further clinical studies are required to understand how these various properties can be harnessed for effective medical use in humans. However, through initial research and extensive anecdotal evidence, it’s clear that the cannabis plant has certain properties that can potentially help patients alleviate a range of symptoms.