One of the main reasons cannabis has so many diverse uses is the plant’s ability to produce a wide variety of different chemicals. In fact, there are over 500 different chemicals identified in cannabis. Some, like terpenes and flavonoids (the compounds responsible for much of the color, taste, and smell of cannabis), are common in many different types of plants. But more than 100 of these chemicals are cannabinoids — molecules which share chemical similarities with THC and can have effects in the body. These cannabinoids from cannabis are more specifically called phytocannabinoids, referring to their original plant source. 1 2
You’ve likely heard of the cannabinoid tetrahydrocannabinol (THC), which provides cannabis with much of its medicinal value and also produces the mind-altering effects. Another commonly known cannabinoid is cannabidiol (CBD), which is praised for its medicinal benefits without the intoxicating effects. While these are the most well known and abundant cannabinoids, there are a plethora of other cannabinoids produced by the plant.
In fact, the cannabis plant doesn’t actually produce THC and CBD at all. Instead, the plants produce all cannabinoids in their acid forms: THCA and CBDA. We usually convert these cannabinoids to their neutral forms, THC and CBD, by applying heat.
To truly understand how any type of medical marijuana might affect you, it’s important to have a basic understanding of how these active chemicals interact with your body and each other.
How cannabinoids interact with the body
In the 1990’s scientists researching cannabinoids discovered the endocannabinoid system (ECS), which is comprised of three parts:
- cannabinoid receptors
- enzymes involved in producing and recycling endocannabinoids
One of the most important pieces of the ECS are the receptors. The CB1 and CB2 receptors are the primary receptors in this system and can be found throughout the human body. THC, a plant cannabinoid, is known to interact with both of these receptors.
Humans don’t produce THC, so researchers set out on a quest to discover why these receptors exist within the body. What they found was that all vertebrates on Planet Earth have these receptors, which interact with chemicals that the body produces naturally — called endocannabinoids. These endocannabinoids are produced by cells within the body in response to external factors, like pain or temperature. Endocannabinoids include the more well known molecules 2-AG and anandamide, as well as many less known endocannabinoids like virodhamine, and 2-arachidonoyl glycerol ether. 3
This interaction between the endocannabinoids and their corresponding receptors plays a crucial role in maintaining your body’s internal balance or homeostasis. The endocannabinoid system regulates some very important aspects of your health, including:
- Blood pressure
- Body temperature
- Heart rate
- Immune response
- Muscle control
- Pain response
So, as you can imagine, it’s pretty important to keep this system in good working condition.
Researchers suggest that endocannabinoid deficiencies could underlie many health conditions that respond well to cannabis. From depression and arthritis, to fibromyalgia and Crohn’s disease, there are lots of conditions that we currently have no explanation for that may arise from a poorly functioning endocannabinoid system. This deficiency remains contentious among medical experts, but more science continues to build to support the idea and explain why cannabis seems to be so effective for certain refractory disorders.
The cannabinoids found in the cannabis plant, which are often called phytocannabinoids to distinguish them from endocannabinoids, are very similar to the endocannabinoids that our bodies produce naturally. When consumed, these phytocannabinoids mimic endocannabinoids and interact with our CB1 and CB2 receptors or other parts of the ECS.
Cannabinoid effects and interactions
There are over 144 known cannabinoids, and they are all different. Some are found naturally in the plant, while others have been found in various other plants or in burned cannabis resin. Still, the way that these chemicals are produced often entails a chain of chemical transitions from one cannabinoid to another.
In other words, some cannabinoids start out as one cannabinoid and then are converted by the plant or by a person into another. For example, THC begins in the cannabis plant as CBGA—the plant converts into THCA and then when you heat it by sparking up, it turns into THC. If you notice similar names for two different cannabinoids, they are likely part of the same chain of transformations.
These changes might be slight when it comes to the chemical structure, but these small shifts can cause big differences when it comes to the medicinal effects. As cannabinoids transform from one form to another, their level or type of psychoactivity and their specific therapeutic effects may change.
These cannabinoids won’t all work the same, and different cannabinoids activate the ECS in a variety of ways.
The entourage effect
To make things more complicated, cannabinoids’ effects may be influenced by other cannabinoids, terpenes or flavonoids present in the cannabis being consumed. This therapeutic synergy is known as the ‘entourage effect,’ and is an acknowledgment that cannabis’ active chemicals seem to work together to create effects that wouldn’t come from any of their parts individually. This is why the cannabis industry is hyperfocused on terms like “full spectrum.”
When it comes to the entourage effect, the most supported examples relate to THC and CBD. Cannabis growers have long known about CBD’s ability to influence the high that cannabis produces, but scientists have only recently been able to measure specific effects. Most studies now suggest consuming THC and CBD simultaneously may actually reduce the severity of commonly known THC side effects like memory impairment or feelings of anxiety. If this is true, and it generally is accepted as true, then THC + CBD is the simplest example we can find. The science gets trickier when you consider the multitude of cannabinoids and terpenes made by the plant.
With so many different chemicals, the potential combinations are almost infinite when considering how many different strains of cannabis there are. Each strain has a unique blend of these active chemicals, and can sometimes give surprising effects. The entourage effect has proven to be difficult to study and evidence to support our understanding is still being amassed.
Still, having a general idea of the effects of the primary cannabinoids can be a big help in determining which products are best suited to you.
What are the most common cannabinoids?
Perhaps the most common misconception about cannabis relates to the plant’s production of THC. When the cannabis plant produces cannabinoids, it actually produces their “acidic form.” For example, tetrahydrocannabinol (THC) is produced by cannabis as THCA–tetrahydrocannabinolic acid. It’s only once the flower is heated that the THCA converts to THC.
Another name for these cannabinoid acids is “raw” cannabis. What’s interesting is that these cannabinoid acids, despite being most dismissed as inactive, may actually offer a lot of therapeutic potential. Cannabinoid acids may still be absorbed into the body, but don’t seem to make it into the brain, which is probably why they were originally written off as therapeutic cannabinoids.
All cannabinoids are produced within the cannabis plant as cannabinoid acids. Generally all cannabinoid acids are derived from just one “mother” cannabinoid–CBGA (cannabigerolic acid). The plant must first produce CBGA before converting to the better known cannabinoids like THCA or CBDA (cannabidiolic acid). Very little “activated” cannabinoids are found in fresh cannabis flower – most will be in the acidic form and get decarboxylated into THC, CBD, or CBG upon smoking.
Delta-9 THC, usually referred to as just THC, tends to get the most attention as the most plentiful cannabinoid in the modern cannabis plant, and the one that causes the well-known psychoactivity or “high” associated with cannabis. It’s also praised for its strong medicinal effects, which continues to be utilized by patients all over the world.
How is THC used and what does it help with?
- One common use of THC is for pain relief. In fact, pain is the most common reason patients use cannabis, and THC plays a huge role in this. While many cannabinoids offer pain relief, some studies show that THC can bring the highest level of pain relief—beating out alternatives like CBD. This makes it a very popular option for those seeking pain relief.
- Others find THC helpful for its mood-boosting abilities. Some animal studies show that THC can act similarly to an antidepressant, uplifting a depressed mood and calming anxiety. Regular, long-term use though may actually increase the risk of anxiety or depression, according to some studies.
- In addition, THC has been shown to help with issues like nausea, muscle spasms, and sleep disorders, along with other conditions. It is also a powerful anti-inflammatory agent, neuroprotective agent, and antioxidant. THC can even shift your metabolism to help avoid weight gain, as studies suggest cannabis users tend to eat more but weigh less than non-users.
- Of course, for some, THC’s psychotropic properties can be a big deterrent to use–some people just don’t enjoy getting high. Side effects like mental confusion, short term memory loss, shifts in time perception, rapid heart-rate, lowered coordination and anxiety can make it an uncomfortable experience for some, especially at higher doses. Still, these effects only happen for some and typically lessen or go away all together as tolerance to THC builds. For many, these side effects can also be reduced by combining THC with other cannabinoids or terpenes. 4
CBD is another common cannabinoid, which has gained a lot of notoriety in recent years as the “non-psychoactive cannabinoid.” Despite the hype, it turns out that CBD is psychoactive, because it can alter mood by easing anxiety and depression. But it doesn’t have the same kind of disorienting effects as THC like mental confusion, shifts in time perception, short-term memory loss or lack of coordination. That is, it won’t get you high.
Most CBD users report that their mind feels and functions normally, though some do report feeling different. The reason for the lack of high is that CBD does not strongly interact with the CB1 receptors of the ECS, which are responsible for mediating the intoxicating effects of THC. Instead, CBD interacts with a handful of other important receptor sites in the brain, including certain serotonin and dopamine receptors. 5 6
This powerful cannabinoid is able to help with many conditions. It is used to relieve pain, reduce inflammation, and as mentioned above, fight anxiety.
In addition, the World Health Organization recently reported that CBD can help treat epilepsy, Alzheimer’s disease, cancer, psychosis, Parkinson’s disease, and other serious conditions. The organization also concluded that CBD is exceptionally safe to use, having no known negative side effects or potential for addiction. This cannabinoid is under broad investigation for the treatment of many diseases, but so far sufficient evidence only exists for a few conditions, including pediatric seizure disorders.
THCV and other ‘varins’
From a chemistry perspective, these cannabinoids have two fewer carbon atoms, or a shorter tail, than better-known cannabinoids like THC and CBD. This shorter carbon tail may seem like a minor change, but it contributes heavily to the unique pharmacologic activity of these cannabinoids. There is much more to learn about the “varins” which may hold promise in managing weight loss, diabetes, cholesterol problems, autism, seizures, and more. 7
Probably the best-known of this group is tetrahydrocannabivarin (THCV), though it is much less common and less abundant than THC or CBD. This cannabinoid has a lot in common with its chemical cousin THC, but has a slightly different chemical structure and effect profile. This alteration in chemical structure means that, unlike THC, it may function as more of a blocker than an activator of CB1, but the data around this is conflicting.
Reported to produce a relaxing, euphoric, and energizing high, THCV may help block the anxiety-inducing effects of THC when the two are used together. It also holds promise as a weight-loss aid—by reducing appetite and boosting metabolism, and as diabetes treatment by helping with blood sugar control and insulin production. To add to this, THCV may help promote new bone cell growth and prevent weakening bones, and can even act as a neuroprotectant in conditions like Parkinson’s disease. 8
There are numerous other cannabinoids that end in “V” too. This group includes CBGV, CBCV, and CBDV, which are increasingly becoming the focus of medical research.
Cannabigerol (CBG) is a common cannabinoid found in essentially all cannabis plants. Like all of the cannabinoids mentioned so far, CBG is produced as CBGA in the trichome of the cannabis flower. All the primary cannabinoids are created from CBGA. This is how CBGA got its nickname of “mother of all cannabinoids.” CBG has also been dubbed a non-psychoactive cannabinoid, but similar to CBD this probably isn’t accurate. The limited science we do have suggests CBG is active at a number of non-cannabinoid receptors. 9
Early research shows CBG can have potential for a wide range of issues. CBG is an effective pain reliever and an anti-inflammatory agent. It can act as a neuroprotectant against degeneration in conditions like Huntington’s disease and has been shown to promote neurogenesis, the regrowing of new brain cells. Studies show CBG may help fight against colorectal, prostate and oral cancer. 10
CBG can act as an antibacterial against resistant bacterial strains like MRSA, help with psoriasis and other skin conditions, and may even aid in regulating emotions like an antidepressant.
Cannabinol (CBN) is known best for being the cannabinoid that is created when THC ages – it is a natural byproduct of THC degradation. In fact, as THC ages a significant amount it can naturally convert to CBN – up to 20%% per year. Some CBN can also be formed when THC is heated to high temperatures, like when smoking. While this might not sound appealing, it has so many medicinal benefits that some prefer older cannabis because it often has high CBN levels. 11
CBN is regularly cited in marketing materials as having sedative effects, however there is little research to support this claim. The limited research suggests CBN alone doesn’t seem to have a sedative effect (at least no more than THC), but had a more sedating effect when combined with THC. 12 13
This suggests cannabis high in CBN and THC a useful option for insomnia, and other research shows CBN can stimulate appetite, ease glaucoma, combat inflammation and autoimmune conditions, and work as a powerful antibiotic, which all makes sense given its close relation to THC.
Perhaps the least common of the “standard” cannabinoids made in the plant, CBC (cannabichromene) is another cannabinoid made from CBG with some important effects. Like CBN, CBC is a powerful antibiotic, shown to help with infections that are resistant to other treatments.
Just like all of the other cannabinoids mentioned, scientists have identified CBC starts in the cannabis plant as CBCA (cannabichromenic acid) and is produced by enzymes from CBGA. But little is known about its pharmacology. 14
CBC might also help protect the brain from neurodegenerative conditions like Alzheimer’s. Studies show that CBC not only protects the brain, it could encourage your brain to grow new brain cells, at least if you’re a rat taking CBC.
Find the cannabinoid that’s right for you
This list of cannabinoids is just the beginning. There are many more cannabinoids out there to learn about, and the research is only just getting started in this field.s. Still, this should give you enough information to get started finding the cannabinoids that are right for you. With so many different cannabinoid options, you can learn to find the ones that fit your needs — and avoid the ones that don’t.
- Lafaye G, Karila L, Blecha L, Benyamina A. Cannabis, cannabinoids, and health. Dialogues Clin Neurosci. 2017;19(3):309-316. doi:10.31887/DCNS.2017.19.3/glafaye
- Berman P, Futoran K, Lewitus GM, et al. A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis. Sci Rep. 2018;8(1):14280. Published 2018 Sep 24. doi:10.1038/s41598-018-32651-4
- Fezza F, Bari M, Florio R, Talamonti E, Feole M, Maccarrone M. Endocannabinoids, related compounds and their metabolic routes. Molecules. 2014;19(11):17078-17106. Published 2014 Oct 24. doi:10.3390/molecules191117078
- Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982;76(3):245-250. doi:10.1007/BF00432554
- Seeman P. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose. Transl Psychiatry. 2016;6(10):e920. Published 2016 Oct 18. doi:10.1038/tp.2016.195
- Melas PA, Scherma M, Fratta W, Cifani C, Fadda P. Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research. Int J Mol Sci. 2021;22(4):1863. Published 2021 Feb 13. doi:10.3390/ijms22041863
- Stone NL, Murphy AJ, England TJ, O’Sullivan SE. A systematic review of minor phytocannabinoids with promising neuroprotective potential. Br J Pharmacol. 2020;177(19):4330-4352. doi:10.1111/bph.15185
- Walsh KB, McKinney AE, Holmes AE. Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses. Front Pharmacol. 2021;12:777804. Published 2021 Nov 29. doi:10.3389/fphar.2021.777804
- Tahir MN, Shahbazi F, Rondeau-Gagné S, Trant JF. The biosynthesis of the cannabinoids. J Cannabis Res. 2021;3(1):7. Published 2021 Mar 15. doi:10.1186/s42238-021-00062-4
- Nachnani R, Raup-Konsavage WM, Vrana KE. The Pharmacological Case for Cannabigerol. J Pharmacol Exp Ther. 2021;376(2):204-212. doi:10.1124/jpet.120.000340
- Ross, S.A. and Elsohly, M.A. CBN and Δ9-THC concentration ratio as an indicator of the age of stored marijuana samples. UNPDC Data and Analysis Bulletin (1999).
- Fernandes, Mario, et al. “Modification of Delta-9-THC-Actions by Cannabinol and Cannabidiol in the Rat.” Psychopharmacologia, vol. 38, no. 4, 6 June 1974, pp. 329–338., https://doi.org/10.1007/bf00429130.
- Takahashi, R. N., and I. G. Karniol. “Pharmacological Interaction between Cannabinol and d9-Tetrahydrocannabinol.” Psychopharmacologia, vol. 41, no. 3, 17 Sept. 1975, pp. 277–284., https://doi.org/10.1007/bf00428937.
- Tahir MN, Shahbazi F, Rondeau-Gagné S, Trant JF. The biosynthesis of the cannabinoids. J Cannabis Res. 2021;3(1):7. Published 2021 Mar 15. doi:10.1186/s42238-021-00062-4
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