What are Cannabinoids? | Guide | CBDNerds 2021
Inside the Chemistry of Hemp: A Comprehensive Guide to Cannabinoids
Cannabinoids are a group of natural compounds that can interact with our body’s cannabinoid receptors.
These cannabinoid receptors are a part of a complex signaling network that controls our immune system, metabolism, feelings of pain, anxiety, and much more.
Most cannabinoids come from cannabis (phytocannabinoids) but some are also produced by the human body (endocannabinoids) and can be made synthetically in a lab.
Many people are familiar with THC and CBD. These two cannabinoids have received a lot of attention due to being the most abundant active compounds in cannabis and are widely utilized for their health effects.
In reality, however, cannabis contains over 120 different cannabinoids, including the likes of cannabinol (CBN), cannabidivarin (CBDV), and many others.
These are considered “minor” cannabinoids because of their relatively small concentrations in most cannabis plants. But similar to CBD and THC, these substances also have many potential health benefits and uses. Here is your comprehensive guide to cannabinoids.
How Cannabinoids Work
Cannabinoids produce their health effects primarily through interacting with the body’s endocannabinoid system (ECS). There’s also evidence that many cannabinoids, such as CBD, interact with other, non-cannabinoid receptors in the body as well.
Cannabinoids and the Endocannabinoid System
The ECS is dedicated entirely to interacting with cannabinoids, which is why most of the effects of phytocannabinoids are mediated by this essential system.
Consisting of cannabinoid receptors, endocannabinoids, and metabolic enzymes, the ECS works to maintain homeostasis: a state of balance within the body.
Receptors are protein molecules present on cells that interact with specific substances and produce various effects.
Many cannabinoids can interact directly with the two cannabinoid receptors in the body, CB1 and CB2. They do so by binding to them in a similar manner as our body’s naturally produced endocannabinoids such as anandamide and 2-AG.
These receptors are found in all parts of the body, with CB1 being especially abundant in the brain and CB2 in immune system tissues.
Furthermore, research has shown that cannabinoids can interact with several other receptors that may eventually be considered as part of the ECS, such as GPR119 and GPR55.
On top of that, cannabinoids can also have less direct effects on the ECS. One of the best examples of this is CBD. While it doesn’t bind to cannabinoid receptors directly, it can modulate the function of the CB1 receptor and suppresses enzymes that break down endocannabinoids.
Other Cannabinoid Mechanisms
Aside from the ECS, cannabinoids have also been shown to interact with many other receptors present throughout the body.
Other targets noted by research studies include the central nervous system receptors for neurotransmitters such as serotonin, glycine, and GABA. These receptors control functions including memory, learning, and mood modulation. 
Finally, cannabinoids can have other non-receptor effects, such as blocking transporter proteins.
How Do Cannabinoids Differ from Each Other?
Although cannabinoids are quite similar in structure, they have some slight differences that account for their varying effects. As a result, distinct cannabinoids can affect your body quite differently. The best example of this is CBD and THC.
THC is widely recognized for its mind-altering psychotropic effects which can include euphoria, impaired memory, and decreased motor skills. It's most commonly found in the flower of medical marijuana.
Meanwhile, CBD and many other cannabinoids, such as CBN and CBG, are non-psychoactive, which means they don’t alter your mental state.
THC and CBD also have various beneficial health effects some of which are similar, while others are unique to each cannabinoid.
For example, both cannabinoids may treat pain and inflammation, but only THC has shown a positive effect on Tourette’s syndrome, whereas CBD is recognized for its potent anxiety-relieving properties.
Furthermore, cannabinoids can enhance and modify each other’s effects, a phenomenon known as the entourage effect. For example, both CBD and the minor cannabinoid THCV seem to reduce the psychotropic effects of THC.
This may explain why whole-plant cannabis products are more effective and produce fewer side effects than pure THC or CBD on their own.
Cannabinoids vs Cannabinoid Acids
Another important distinction to be aware of is between cannabinoids and cannabinoid acids.
Cannabis plants don’t directly make THC, CBD, or other cannabinoids. Instead, they produce their acidic forms, such as THCA and CBDA, which are precursors to these cannabinoids.
When heat is applied to these cannabinoid acids, they undergo a process called decarboxylation and lose their acid group, becoming THC, CBD, and so forth. That’s why these resulting cannabinoids are sometimes referred to as “activated.”
Although we’re more familiar with the non-acidic form of cannabinoids, their acidic counterparts can also have beneficial health effects. Besides, all acidic cannabinoids are non-psychotropic, so they won’t get you high.
Unsurprisingly, their levels are highest in raw cannabis and decrease when the plant material is dried or exposed to heat.
There’s no official definition for which cannabinoids count as “major.” However, most references to major cannabinoids typically include CBGA, THCA, CBDA, CBCA, and their non-acidic forms. In turn, these cannabinoids can convert into many more “minor” cannabinoids.
CBGA & CBG
Cannabigerolic acid (CBGA) is widely regarded as the “mother of all cannabinoids.” This means that cannabis plants produce CBGA first before it’s converted into other cannabinoids.
CBG is considered the next big thing in the cannabis industry because much like CBD, it’s a non-intoxicating cannabinoid with many potential health benefits. These include:
- Antibacterial properties
- Anti-inflammatory effects in studies of mice with multiple sclerosis and inflammatory bowel disease 
- Neuroprotection against Parkinson’s disease in mice
- Inhibition of colon cancer cell growth
- Appetite stimulation, offering a non-intoxicating alternative to THC for wasting caused by diseases such as cancer and HIV
THC & THCA
Tetrahydrocannabinol (THC) is the best-known cannabinoid because it’s largely responsible for the psychoactive effects of cannabis. These include impaired short-term memory and motor skills, euphoria, and, in some susceptible individuals, anxiety, and paranoia.
However, research has shown that THC also has many beneficial effects and is used to help with many symptoms and disorders, including:
- Pain and inflammation
- Nausea and vomiting
- Wasting and loss of appetite
- Tourette’s syndrome
- Multiple sclerosis
- Opioid withdrawal
Like most cannabinoids, THC starts out in its acidic form — tetrahydrocannabinolic acid (THCA). THCA is a non-intoxicating cannabinoid that’s been shown to have some beneficial effects, including anti-inflammatory, neuroprotective, anti-obesity, and anti-cancer qualities.
Raw cannabis plants are high in THCA. This gets converted into THC when exposed to heat.
CBD & CBDA
Cannabidiolic acid (CBDA) is the acid version of cannabidiol (CBD). These non-psychotropic cannabinoids come with a wide variety of health benefits.
CBD is best known as the main active ingredient in CBD oil, which is used by an increasing number of people worldwide to support their overall health and address specific symptoms and conditions.
CBD is one of the most well-studied cannabinoids. Although it’s most recognized for its effectiveness in treatment-resistant epilepsy, research suggests that it may also help with a long list of health issues, including:
- Anxiety disorders and depression
- Drug addiction
- Inflammation and pain
- Sleep issues
- Neurodegenerative conditions
It also seems to have much stronger effects on the serotonin receptor than CBD, which means CBDA may be particularly helpful for neurologic issues linked to serotonin dysfunction, such as seizures.
Most CBD products lack CBDA because they’re decarboxylated (heated) during production, which converts it all into CBD. However, in raw cannabis plants, 95% of the CBD is present in the CBDA form.
CBCA & CBC
Cannabichomenic acid (CBCA) and cannabichromene (CBC) are another pair of non-intoxicating cannabinoids produced from CBGA.
They haven’t seen too much research, but CBC has been reported to relieve pain, inflammation, act as an antidepressant, and even support the functions of neural stem progenitor cells, which are crucial to healthy brain function and have real potential in the treatment of neurodegenerative diseases.
It may also have positive effects on seizures, Huntington’s, and Parkinson’s disease.
Minor cannabinoids get their name from their relatively small concentrations in cannabis plants and the fact that most of them are derived from major cannabinoids.
There are well over 100 minor cannabinoids in cannabis but we will look at the ones that have received the most attention.
Cannabinol (CBN) is a minor, non-intoxicating cannabinoid produced when THC is exposed to oxygen. That’s why CBN concentrations are low in raw cannabis but can reach significant levels in older plants.
Many people believe that CBN is helpful for sleep issues because aged cannabis has stronger sleep-inducing effects.
However, this belief is somewhat misguided. Rather than promoting sleep on its own, research indicates that CBN might enhance the sedating effects of THC.
Much like CBG, CBN is predicted to grow in popularity in the near future thanks to the overwhelming interest in CBD.
Tetrahydrocannabivarin (THCV) is an analog of THC, which means it’s structure is very similar. Despite this, THCV does not appear to share its cousin’s intoxicating effects.
This minor cannabinoid has been shown to have several beneficial properties. Most notably, it can reduce appetite and help regulate blood sugar and insulin sensitivity, making it a serious candidate for the treatment of obesity and diabetes.
Another study also found that THCV displayed the strongest anti-acne effects out of five studied minor cannabinoids.
Cannabicyclol (CBL) is a non-psychotropic cannabinoid produced when CBC degrades from sunlight exposure. Given that it's only been recently discovered, we don’t know too much about CBL’s effects.
Cannabidavarin (CBDV) is a non-intoxicating minor cannabinoid similar in structure to CBD. Much of the interest in this cannabinoid has revolved around its anti-epileptic effects.
The company GW Pharmaceuticals — which recently released the first CBD-only pharmaceutical drug, Epidiolex — is currently testing CBDV in clinical trials of epilepsy.
Cannabichromevarin (CBCV) is a minor, non-intoxicating cannabinoid first identified in 1975.
Like other cannabinoids ending in “V,” it’s an analog of its close cousin CBC, which means it has a similar structure but with a slight difference.
CBCV hasn’t seen much research so we don’t know too much about its effects.
Cannabigerol monomethyl ether (CBGM) is a minor cannabinoid related to CBG. Like other rare cannabinoids, we don’t know too much about its effects due to a lack of research.
Cannabielsoin (CBE) is a minor cannabinoid metabolite of CBD. So far, studies of mice, guinea pigs, and some other animals have shown that CBD can be metabolized (breaks down) into CBE. Presumably, a similar process occurs in humans when we ingest CBD.
Aside from hypothesizing that CBE plays a role in the effects of CBD, there is not much additional research into CBE yet.
Cannabicitran (CBT) is a relatively rare minor cannabinoid. There haven’t been many studies looking at this cannabinoid, so we don’t know much about its health effects.
The cannabis plant contains dozens of phytocannabinoids. Not to mention, it contains an array of terpenes, flavonoids, and phytonutrients. These natural compounds have serious potential in helping with a wide variety of health conditions.
We already know a good deal about the benefits of CBD and THC, which are increasingly utilized by individuals and their doctors to relieve a wide range of conditions from chronic pain to treatment-resistant epilepsy.
But much remains to be discovered about the less-known minor cannabinoids, which represent the next great frontier in cannabis research. We hope our guide to cannabinoids helped shine a light on these minor cannabinoids. And we hope we'll have the ability to share more about them in the near future.
Frequently Asked Questions
Is CBD a cannabinoid?
Yes, cannabidiol (CBD) is one of the two most abundant cannabinoids in cannabis plants.
What do cannabinoids do to the body?
Cannabinoids produce a wide range of health effects by interacting with cannabinoid receptors and other bodily systems.
What are examples of cannabinoids?
THC and CBD are the two best examples of cannabinoids. However, the complete list includes hundreds of chemical compounds, including not only those from cannabis but also endocannabinoids made by the human body and even synthetic cannabinoids.
What type of drug is cannabinoids?
Cannabinoids get their name from their ability to interact with our body’s cannabinoid receptors. Some cannabinoids are psychoactive (any substance that affects the brain) or psychotropic (any substance that changes your mental state, which means affecting how you perceive the world) drugs.
 Morales, Paula, Dow P. Hurst, and Patricia H. Reggio. "Molecular targets of the phytocannabinoids: a complex picture." Phytocannabinoids. Springer, Cham, 2017. 103-131.
 Brown, A. J. "Novel cannabinoid receptors." British journal of pharmacology 152.5 (2007): 567-575.
 Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94.
 Starkus, J., et al. "Diverse TRPV1 responses to cannabinoids." Channels 13.1 (2019): 172-191.
 Xiong, Wei, et al. "Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors." Journal of Experimental Medicine 209.6 (2012): 1121-1134.
 Bakas, T., et al. "The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABAA receptors." Pharmacological research 119 (2017): 358-370.
 Booz, George W. "Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress." Free Radical Biology and Medicine 51.5 (2011): 1054-1061.
 Müller-Vahl, Kirsten R., et al. "δ9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial." The Journal of clinical psychiatry (2003).
 Blessing, Esther M., et al. "Cannabidiol as a potential treatment for anxiety disorders." Neurotherapeutics 12.4 (2015): 825-836.
 Russo, Ethan B. "The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain." Frontiers in plant science 9 (2019): 1969.
 Englund, Amir, et al. "The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: a placebo-controlled, double-blind, crossover pilot trial." Journal of Psychopharmacology 30.2 (2016): 140-151.
 Pamplona, Fabricio A., Lorenzo Rolim da Silva, and Ana Carolina Coan. "Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis." Frontiers in neurology 9 (2018): 759.
 Citti, Cinzia, et al. "A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ 9-tetrahydrocannabinol: Δ 9-Tetrahydrocannabiphorol." Scientific reports 9.1 (2019): 1-13.
 Appendino, Giovanni, et al. "Antibacterial cannabinoids from Cannabis sativa: a structure− activity study." Journal of natural products 71.8 (2008): 1427-1430.
 Granja, Aitor G., et al. "A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis." Journal of Neuroimmune Pharmacology 7.4 (2012): 1002-1016.
 Borrelli, Francesca, et al. "Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease." Biochemical pharmacology 85.9 (2013): 1306-1316.
 Valdeolivas, Sara, et al. "Neuroprotective properties of cannabigerol in Huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice." Neurotherapeutics 12.1 (2015): 185-199.
 Borrelli, Francesca, et al. "Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid." Carcinogenesis 35.12 (2014): 2787-2797.
 Brierley, Daniel I., et al. "A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT] 9-tetrahydrocannabinol, elicits hyperphagia in rats." Behavioural pharmacology 28.4 (2017): 280-284.
 Ruhaak, Lucia Renee, et al. "Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa." Biological and Pharmaceutical Bulletin 34.5 (2011): 774-778.
 Moldzio, Rudolf, et al. "Effects of cannabinoids Δ (9)-tetrahydrocannabinol, Δ (9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures." Phytomedicine 19.8-9 (2012): 819-824.
 Palomares, Belén, et al. "Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity." Biochemical Pharmacology 171 (2020): 113693.
 De Petrocellis, Luciano, et al. "Non?THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro?apoptotic effects and underlying mechanisms." British journal of pharmacology 168.1 (2013): 79-102.
 Mechoulam, Raphael, et al. "Cannabidiol–recent advances." Chemistry & biodiversity 4.8 (2007): 1678-1692.
 Hen-Shoval, D., et al. "Acute oral cannabidiolic acid methyl ester reduces depression-like behavior in two genetic animal models of depression." Behavioural brain research 351 (2018): 1-3.
 Takeda, Shuso, et al. "Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis." Drug metabolism and disposition 36.9 (2008): 1917-1921.
 Bolognini, D., et al. "Cannabidiolic acid prevents vomiting in S uncus murinus and nausea?induced behaviour in rats by enhancing 5?HT1A receptor activation." British journal of pharmacology 168.6 (2013): 1456-1470.
 Russo, Ethan B. "Cannabis therapeutics and the future of neurology." Frontiers in integrative neuroscience 12 (2018): 51.
 Maione, Sabatino, et al. "Non?psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action." British journal of pharmacology 162.3 (2011): 584-596.
 Izzo, Angelo A., et al. "Inhibitory effect of cannabichromene, a major non?psychotropic cannabinoid extracted from Cannabis sativa, on inflammation?induced hypermotility in mice." British journal of pharmacology 166.4 (2012): 1444-1460.
 El-Alfy, Abir T., et al. "Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L." Pharmacology Biochemistry and Behavior 95.4 (2010): 434-442.
 Shinjyo, Noriko, and Vincenzo Di Marzo. "The effect of cannabichromene on adult neural stem/progenitor cells." Neurochemistry international 63.5 (2013): 432-437.
 Stone, Nicole L., et al. "A Systematic Review of Minor Phytocannabinoids with Promising Neuroprotective Potential." British Journal of Pharmacology (2020).
 Izzo, Angelo A., et al. "Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb." Trends in pharmacological sciences 30.10 (2009): 515-527.
 Karniol, Isac G., et al. "Effects of Δ9-tetrahydrocannabinol and cannabinol in man." Pharmacology 13.6 (1975): 502-512.
 Zurier, Robert B., and Sumner H. Burstein. "Cannabinoids, inflammation, and fibrosis." The FASEB Journal 30.11 (2016): 3682-3689.
 Weydt, Patrick, et al. "Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival." Amyotrophic Lateral Sclerosis 6.3 (2005): 182-184.
 Farrimond, Jonathan A., Benjamin J. Whalley, and Claire M. Williams. "Cannabinol and cannabidiol exert opposing effects on rat feeding patterns." Psychopharmacology 223.1 (2012): 117-129.
 Wong, Hayes, and Brian E. Cairns. "Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain." Archives of oral biology 104 (2019): 33-39.
 Abioye, Amos, et al. "Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes." Journal of Cannabis Research 2.1 (2020): 1-6.
 Garcia, C., et al. "Symptom?relieving and neuroprotective effects of the phytocannabinoid Δ9?THCV in animal models of Parkinson's disease." British journal of pharmacology 163.7 (2011): 1495-1506.
 Scutt, A., and E. M. Williamson. "Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB 2 receptors." Calcified Tissue International 80.1 (2007): 50-59.
 Oláh, Attila, et al. "Differential effectiveness of selected non?psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment." Experimental dermatology 25.9 (2016): 701-707.
 Vigli, Daniele, et al. "Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome." Neuropharmacology 140 (2018): 121-129.
 Iannotti, Fabio Arturo, et al. "Effects of non?euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice." British Journal of Pharmacology 176.10 (2019): 1568-1584.
 Rock, Erin M., et al. "Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ9?tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats." British journal of pharmacology 170.3 (2013): 671-678.
 Hollander, Eric. Cannabidivarin (CBDV) Versus Placebo in Children with Autism Spectrum Disorder (ASD). Albert Eintsein College of Medicine, Inc. Bronx United States, 2018.
 YAMAMOTO, Ikuo, et al. "Identification of cannabielsoin, a new metabolite of cannabidiol formed by guinea-pig hepatic microsomal enzymes, and its pharmacological activity in mice." Journal of pharmacobio-dynamics 11.12 (1988): 833-838.