Approximately 545 chemical compounds have been identified in marijuana to date. Of these, 113 are classified as ‘phytocannabinoids.’ They are better known as cannabinoids and are naturally occurring compounds in cannabis plants. For the record, ‘phyto’ means to be ‘derived from plants.’ The phytocannabinoids interact and bind together with other compounds such as flavonoids and terpenes.
The best-known cannabinoids are THC and CBD; although others such as CBN and CBC are gaining a greater level of prominence. You will find the greatest concentration of cannabinoids in the marijuana plant’s resin, which is found in its trichomes. Contrary to what opponents of the cannabis industry claim, different strains contain differing levels of phytocannabinoids, with THC and CBD usually the most abundant.
In contrast to phytocannabinoids, endocannabinoids are produced in the body. They interact with cannabinoid receptors (CB1 and CB2) of humans and animals. There are also synthetic cannabinoids manufactured artificially, which are more likely to gain FDA approval to treat specific medical conditions!
The unique phytocannabinoids found in marijuana have resulted in the plant being championed as a means of treating certain medical conditions. Cannabinoids are also generally insoluble in water but are soluble in non-polar organic solvents.
Why Do Marijuana Plants Produce Phytocannabinoids?
The human body produces cannabinoids for survival as it tries to achieve a state of balance (homeostasis). It is the same story for cannabis plants. They also produce phytocannabinoids to survive as a more direct response to any external issues faced by the plants. As they are primarily produced by the trichomes, cannabinoids cover the plant’s surface as a means of protection against inclement weather and predators.
When you think about it, marijuana grows in a variety of climates; including on mountains, in cold weather, and tropical conditions. THCA is a cannabinoid that converts to the THC that gets us high with the aid of time and heat. Cannabinoids are produced in tiny glands that coat the surface of the plant. These trichomes help the plant in the following ways:
- Protection against frost when growing in a cold climate.
- Protection against predators such as insects.
- Reducing loss of moisture in windier locations.
- Preventing overheating when growing in dry and arid conditions.
- Attracting pollinators.
Marijuana isn’t the only plant to produce trichomes, but its psychoactive properties are almost unique. What isn’t known is why specific phytocannabinoids such as THC are produced. It is theorized that THC is an antimicrobial. Plants are susceptible to germs but don’t have an immune system like animals. As a result, they need to produce a range of chemicals to keep them safe against infection.
However, it seems as if strains with high levels of THC are no more resistant to pest infestations and pathogens than low THC strains. THC itself could help protect marijuana plants from UV light. Ultimately, while scientists have yet to find a definitive reason for the development of phytocannabinoids, it seems likely that they serve a protective function at the very least.
Phytocannabinoids are produced through the process of biosynthesis; this involves enzymes triggering chemical reactions to create complex molecules from simple ones. The enzymes that help produce cannabinoids include THCA, CBCA, and CBDA. The enzymes take CBGA and CBGVA, known as ‘central cannabinoid precursors,’ and convert them into cannabinoids like CBDA and THCA.
At this point, you need to activate cannabinoids such as THC and CBD through the process of decarboxylation. It is a fancy term for exposing the cannabinoids to enough heat for a specific period. During decarboxylation, chemical compounds lose carbon atoms and release CO2 (this process can also occur due to environmental stresses).
THCA gets converted into THC, CBDA gets converted into CBD, and so on. At this point, cannabinoids can be broken down into other cannabinoids through exposure to oxygen, a process known as oxidation. CBD can be oxidized into CBND or CBE, for instance.
How Do Phytocannabinoids Interact with Our Endocannabinoid System (ECS)?
As we already mentioned, the ECS is contained within the human body. While marijuana has been around for thousands of years, we weren’t really aware of how weed interacts with the body until recently. Remember, the substance has been prohibited in the United States since 1937, and the nation used its vast international influence to ‘encourage’ other countries to follow suit.
As a result, while scientific advancement was occurring in other fields, we continued to be left in the dark about cannabis. Although the brain’s opiate receptor was discovered in 1973, we didn’t know that the brains of mammals have receptor sites that respond to the chemicals found in weed until 1988, when it was discovered by William Devane and Allyn Howlett. These sites became known as cannabinoid receptors, and two have been identified to date (CB1 and CB2) although scientists now believe there is a third which is called GPR55.
The CB receptors are the most abundant type of neurotransmitter receptor in the mammalian brain! The CB1 receptor was the first to be identified, followed by CB2 in the early 1990s. CB1 receptors are primarily found in the central and peripheral nervous system, and CB2 receptors are mainly found in the immune cells. CB1 receptors control the release of neurotransmitters such as dopamine and serotonin, while CB2 receptors are involved in anti-inflammation and pain relief.
In 1992, the endocannabinoid anandamide (AEA),was discovered at Jerusalem’s Hebrew University. The same research team later discovered endocannabinoids such as 2-AG, DEA, and 2-AGE.
Anandamide is often known as the ‘bliss molecule’ and is a cannabinoid the body produces naturally that happens to mimic THC closely. When you use marijuana, THC enters the body and binds with the CB1 and CB2 receptors, just like anandamide. This process activates neurons in the body.
Anandamide regulates activities such as appetite, mood, pleasure, and memory. There is also research which suggests that the cannabinoid causes ‘runner’s high’, a feeling of euphoria associated with exercise.
2-AG is known for affecting the central nervous system. It is formed via a complex process that involves arachidonic acid which contains DAG, a substance that reacts with glycerol. 2-AG is believed to be crucial in regulating our immune system, and it could also help with pain management.
The ECS performs a variety of tasks, but its main goal is to ensure the body is in a state of homeostasis. Whenever an imbalance is detected, the body synthesizes cannabinoids that interact with the CB receptors. The result is the stimulation of a chemical response that helps bring the body back to its state of balance. However, everyone’s ECS is unique, and some people have a Clinical Endocannabinoid Deficiency.
There are numerous reasons why this happens; including the body not producing enough CB receptors, failing to synthesize enough endocannabinoids, producing too many enzymes which break down the cannabinoids, or external factors such as medication or food which decrease ECS signaling. In theory, the phytocannabinoids contained in marijuana can help individuals with a Clinical Endocannabinoid Deficiency.
As the rate of endocannabinoid production can vary significantly from one person to the next, and the level of CB receptors in our bodies is also different, the potential impact of phytocannabinoids on your ECS is hard to predict.
Therefore, if your body doesn’t produce enough cannabinoids, it could have an impact on anandamide or 2-AG. If you are in this situation, consuming marijuana, and its cannabinoids could compensate for the lack of natural cannabinoid production. It is a process comparable to that of women using synthetic hormone replacement therapy to counteract the effects of the menopause.
Interestingly, a study by D’Souza et al., published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging in 2016, found that prolonged use of weed reduces the number of CB1 receptors available for activation.
In other words, if you smoke your brains out, you could reduce the potential medicinal effect of weed. Incidentally, human brain imaging shows that abstaining from marijuana for just 48 hours allows the system to become ‘sensitive’ to the effects of cannabinoids once again. Therefore, if you find that weed isn’t treating your symptoms as well as before, it is best to stay off it for a couple of days rather than trying to increase the dosage.
What Are the Names of Some Phytocannabinoids?
With hundreds of molecules capable of interacting directly with our body and mind, it is fair to say that future marijuana research should be filled with exciting discoveries. However, mass prohibition has ensured that the science behind how cannabis works is not fully understood.
Remember, there are over 500 chemical compounds in the marijuana plant. Much has been written about THC and CBD because they are the most abundant compounds, but the role of ‘minor’ cannabinoids, terpenes, and flavonoids, could be greater than we think. For example, terpenes are believed to enhance the therapeutic efficacy of cannabinoids like CBD and THC.
Dr. Raphael Mechoulam came up with the term ‘entourage effect’ to describe how a combination of marijuana compounds is likely to be more effective than any isolated compound. Other researchers suggest that the term ‘ensemble effect’ is more accurate as it describes the process of marijuana compounds cooperating. The term ‘entourage effect’ seems to suggest that one cannabinoid dominates while the rest follow.
In case you were wondering, here are the names of a few phytocannabinoids; some are better known than others.
THC – Delta-9-tetrahydrocannabinol
THC activates the CB1 receptor and is famed for being the main intoxicating compound of marijuana. Those who use the herb to get high do so because of THC. While the precise nature of the compound’s effects on the brain varies, it binds to the CB1 receptors in your brain’s reward center.
You will typically experience a feeling of euphoria. THC is championed as an analgesic due to its interaction with CB1 receptors in the midbrain region.
CBD – Cannabidiol
CBD is the second most abundant phytocannabinoid in weed and is known for NOT providing an intoxicating feeling. Indeed, CBD is often marketed as providing ‘healing without the high.’ It is linked with a variety of medical benefits including as a painkiller, anti-inflammatory, and anti-anxiety. As well as being derived from marijuana, CBD comes from the industrial hemp plant, which is now federally legal to grow in the United States.
THCA – Tetrahydrocannabinolic Acid
Believe it or not, THCA is the most abundant phytocannabinoid found in raw marijuana. It doesn’t get you high, but once you decarboxylate it (usually via heat), it converts into THC. THCA is said to be anti-emetic and neuroprotective. Few people try it because of a desire to get high!
THCV & THCVa – Tetrahydrocannabivarin & Tetrahydrocannabivaric Acid
You will only find tiny amounts of THCV in weed although it is said to be useful in the treatment of obesity, while also having antiepileptic effects.
THCVa is THCV’s acidic form.
CBDA – Cannabidiolic Acid
Like THCA, CBDA gets converted into a different cannabinoid (CBD) through decarboxylation. Scientists are still trying to find out what properties CBDA has, although it is believed to be an anti-nausea and anti-tumor agent.
CBN – Cannabinol
There has been a greater degree of interest in CBN as a medicinal agent in recent times. It is believed to play a significant role in weed’s sedative effects. CBN is often the third most abundant cannabinoid in weed but is seldom available in a concentration of more than a fraction of one percent.
It is actually a degraded form of THC, so if you want more CBN in your marijuana, you can take the risk of harvesting your crop later than normal. To date, CBN is used as a sleep aid due to its sedative effects, but it may also help treat osteoporosis.
CBDV & CBDVa – Cannabidivarin & Cannabidivarinic Acid
CBDV is a ‘relative phytocannabinoid’ of CBD as both come from CBGVA, a cannabinoid precursor. It is said to have anticonvulsant properties.
CBDVa is the acidic form of CBDV and is found in raw weed.
CBC – Cannabichromene
CBC is created when CBCA (cannabichromene carboxylic acid) is decarboxylated. It is said to improve the rate of neural cell production that aids brain function.
CBG – Cannabigerol
The compound CBG is created when CBGA is decarboxylated. It has a weak bond with the CB1 and CB2 receptors but can potentially be used to treat conditions such as IBS and Huntington’s.
Final Thoughts on Phytocannabinoids
While it may seem like a long article, the truth is, we have barely scratched the surface of what phytocannabinoids are, and how they affect the body and mind. The main reason for this is due to a relative lack of research. Prohibition has hurt scientific research into this fascinating plant, and we are now playing catch up in a major way. With perhaps 100 million or more people using weed, it is well past time that unencumbered research is allowed across the globe.
So far, we know that the body has an endocannabinoid system, and the phytocannabinoids in cannabis interact with CB receptors in the brain and central nervous system, as well as throughout the body. The fact that our brain naturally produces cannabinoids helps explain why weed has potential therapeutic effects. As research intensifies, we’ll hopefully prove that weed is an effective medicine, and also know why this is the case.