You’ve heard of THC and CBD, but they’re far from the only cannabinoids. Here’s a look at what these natural compounds are, how they work, and their health effects.
Published February 5, 2021
What are cannabinoids?
Cannabinoids are naturally occurring compounds found in cannabis. More specifically, there are phytocannabinoids (plant-derived ones) and endocannabinoids (those made by your body).
Research has shown that phytocannabinoids have a wide range of potential health benefits. So far, over 100 of these compounds have been identified. However, tetrahydrocannabinol (THC) and cannabidiol (CBD) have received the most attention.
The cannabis plant doesn’t make cannabinoids directly. Instead, it produces cannabinoid acids such as cannabigerolic acid (CBGA), cannabidiolic acid (CBDA), and tetrahydrocannabinolic acid (THCA). When these acidic cannabinoids are exposed to heat and light, they undergo decarboxylation and turn into the “activated” forms we’re accustomed to, like CBD and THC.
How do cannabinoids work?
Cannabinoids have slightly different structures, which account for their varying effects. Having said that, all of them interact with your body’s endocannabinoid system (ECS). Discovered in the 1990s, this key system consists of endocannabinoids, the cannabinoid receptors they activate (CB1 & CB2), and special enzymes 1 Skaper, S. D., & Di Marzo, V. (2012). Endocannabinoids in nervous system health and disease: the big picture in a nutshell. .
THC can activate these receptors directly. CBD, on the other hand, doesn’t have a direct effect on cannabinoid receptors. Instead, it appears to reduce the breakdown of anandamide, one of the two main endocannabinoids made by your body. Some phytocannabinoids can also interact with other parts of the body. For example, CBD has been shown to activate serotonin receptors 2 De Gregorio, D., McLaughlin, R. J., Posa, L., Ochoa-Sanchez, R., Enns, J., Lopez-Canul, M., … & Gobbi, G. (2019). Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain, 160(1), 136. .
Understanding the major cannabinoids
A complete list of cannabinoids includes over 140 compounds 3 Citti, C., Palazzoli, F., Licata, M., Vilella, A., Leo, G., Zoli, M., … & Cannazza, G. (2018). Untargeted rat brain metabolomics after oral administration of a single high dose of cannabidiol. Journal of pharmaceutical and biomedical analysis, 161, 1-11. . However, most of them are present in very small quantities. The most prominent cannabinoids in cannabis are THC, CBD, CBG, CBC, and CBN.
THC is usually the most abundant cannabinoid and is largely responsible for the intoxicating cannabis high. Depending on the person, dosage, and the precise chemical composition of cannabis, THC’s psychoactive effects can range from pleasant euphoria and relaxation to anxiety, psychosis, and panic 4 Lowe, D. J., Sasiadek, J. D., Coles, A. S., & George, T. P. (2019). Cannabis and mental illness: a review. European archives of psychiatry and clinical neuroscience, 269(1), 107-120. .
These effects result from THC activating your CB1 receptors, although it can also bind to CB2 5 Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin. British journal of pharmacology, 153(2), 199-215. . This makes it similar to anandamide, the “bliss molecule” endocannabinoid that’s believed to play a role in the euphoric 6 Fuss, J., Steinle, J., Bindila, L., Auer, M. K., Kirchherr, H., Lutz, B., & Gass, P. (2015). A runner’s high depends on cannabinoid receptors in mice. Proceedings of the National Academy of Sciences, 112(42), 13105-13108. “runner’s high.” However, whereas endocannabinoids are broken down quite quickly, the effects of the phytocannabinoid THC can last longer.
Research has shown that cannabis, which is high in THC, may help with chronic pain, inflammation, nausea, wasting and loss of appetite associated with HIV, Tourette’s syndrome, cancer, multiple sclerosis, neurodegenerative disorders, glaucoma, addiction, depression, sleep disorders, and other conditions 7 Abrams, D. I. (2018). The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report. European journal of internal medicine, 49, 7-11. .
CBD is the second-most abundant cannabinoid in most strains of cannabis. The major exception to this is hemp, a cannabis variety with high CBD and low THC levels.
Unlike its psychotropic cousin, CBD is completely non-intoxicating. That’s because instead of binding to cannabinoid receptors directly, “CBD 8 Tham, M., Yilmaz, O., Alaverdashvili, M., Kelly, M. E., Denovan‐Wright, E. M., & Laprairie, R. B. (2019). Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol‐dimethylheptyl at the type 1 and type 2 cannabinoid receptors. British journal of pharmacology, 176(10), 1455-1469. . This may explain why CBD seems to counteract the psychoactive side effects of THC, such as anxiety and psychosis 9 Niesink, Raymond JM, and Margriet W. van Laar. “Does cannabidiol protect against adverse psychological effects of THC?.” Frontiers in psychiatry 4 (2013): 130. .
Additionally, CBD has been shown to reduce the effects of an enzyme that breaks down anandamide, one of the two main endocannabinoids made by your body 10 Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., … & Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational psychiatry, 2(3), e94-e94. . This results in higher anandamide levels, supporting its beneficial effects.
CBD can also interact with many other molecules in the body, including TRP channels that help sense pain, temperature, and other senses, and serotonin, glycine, and opioid receptors, and various inflammation-regulating pathways 11 Mlost, J., Bryk, M., & Starowicz, K. (2020). Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action. International journal of molecular sciences, 21(22), 8870. .
Research suggests that CBD has a wide range of potential health benefits, including beneficial effects on epilepsy, anxiety, pain, inflammation, nausea, depression, arthritis, neurodegenerative conditions, drug addiction, and more 3 Citti, C., Palazzoli, F., Licata, M., Vilella, A., Leo, G., Zoli, M., … & Cannazza, G. (2018). Untargeted rat brain metabolomics after oral administration of a single high dose of cannabidiol. Journal of pharmaceutical and biomedical analysis, 161, 1-11. .
Cannabigerol (CBG) is considered one of the “minor” cannabinoids because it’s not usually present in high quantities in cannabis. CBG hasn’t seen much research, but the available evidence suggests that it acts more like CBD than THC.
It doesn’t interact strongly with CB1 and CB2 receptors and affects many non-endocannabinoid systems, including serotonin (5HT1A) and alpha-2 adrenergic receptors, and TRP channels 13 Nachnani, R., Raup-Konsavage, W. M., & Vrana, K. E. (2021). The Pharmacological Case for Cannabigerol. Journal of Pharmacology and Experimental Therapeutics, 376(2), 204-212. .
There’s growing interest in CBG because it’s another non-psychotropic cannabinoid with many potential benefits, including anti-inflammatory, antibacterial, neuroprotective, anticancer, and appetite-stimulating effects 14 Deiana, S. (2017). Potential medical uses of cannabigerol: a brief overview. Handbook of Cannabis and Related Pathologies, 958-967. .
Another non-intoxicating minor cannabinoid, cannabichromene (CBC) appears to activate CB2 but not CB1 receptors 15 Udoh, M., Santiago, M., Devenish, S., McGregor, I. S., & Connor, M. (2019). Cannabichromene is a cannabinoid CB2 receptor agonist. British journal of pharmacology, 176(23), 4537-4547. . It also seems to interact with many of the same molecules as CBD, such as TRP channels, and works in synergy with THC 16 Marcu, J. P. (2016). An overview of major and minor phytocannabinoids. Neuropathology of drug addictions and substance misuse, 672-678. .
Research suggests that CBC may have anti-inflammatory 18 Maione, S., Piscitelli, F., Gatta, L., Vita, D., De Petrocellis, L., Palazzo, E., … & Di Marzo, V. (2011). Non‐psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. British journal of pharmacology, 162(3), 584-596. , neuroprotective 19 Shinjyo, N., & Di Marzo, V. (2013). The effect of cannabichromene on adult neural stem/progenitor cells. Neurochemistry international, 63(5), 432-437. , and antidepressant effects 20 El-Alfy, A. T., Ivey, K., Robinson, K., Ahmed, S., Radwan, M., Slade, D., … & Ross, S. (2010). Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology Biochemistry and Behavior, 95(4), 434-442. .
CBN is somewhat unique because it’s produced when THC is exposed to oxygen 21 Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V., & Mechoulam, R. (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends in pharmacological sciences, 30(10), 515-527. . That’s why there’s little CBN in raw cannabis, but concentrations can reach a notable level in older plants.
CBN is widely considered to be an effective sleep aid because many cannabis users find that aged cannabis makes them more sleepy. In reality, rather than promoting sleep on its own, CBN may enhance the sedative effects of THC.
Aside from that, studies have shown that CBN may have neuroprotective 22 Weydt, P., Hong, S., Witting, A., Möller, T., Stella, N., & Kliot, M. (2005). Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotrophic Lateral Sclerosis, 6(3), 182-184. , anti-inflammatory 23 Zurier, R. B., & Burstein, S. H. (2016). Cannabinoids, inflammation, and fibrosis. The FASEB Journal, 30(11), 3682-3689. , pain-relieving 24 Wong, H., & Cairns, B. E. (2019). Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Archives of oral biology, 104, 33-39. , and appetite-stimulating qualities 25 Farrimond, J. A., Whalley, B. J., & Williams, C. M. (2012). Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology, 223(1), 117-129. . It seems to bind more strongly to CB2 receptors than CB1.
As we mentioned earlier, all phytocannabinoids start out as cannabinoid acids. First, the plant produces cannabigerolic acid (CBGA) 26 Aizpurua-Olaizola, O., Soydaner, U., Öztürk, E., Schibano, D., Simsir, Y., Navarro, P., … & Usobiaga, A. (2016). Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes. Journal of natural products, 79(2), 324-331. , which is considered the “mother cannabinoid.” Various enzymes then convert this CBGA into THCA, CBDA, CBCA, and its non-acidic form CBG.
Raw cannabis contains relatively high amounts of cannabinoid acids, and their levels decrease as the plants are dried and exposed to heat, undergoing decarboxylation.
Cannabinoid acids are non-intoxicating and can have just as many beneficial effects as their regular, “activated” forms. For example, research has demonstrated that:
THCA may have anti-inflammatory 27 Ruhaak, L. R., Felth, J., Karlsson, P. C., Rafter, J. J., Verpoorte, R., & Bohlin, L. (2011). Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biological and Pharmaceutical Bulletin, 34(5), 774-778. , neuroprotective 2 De Gregorio, D., McLaughlin, R. J., Posa, L., Ochoa-Sanchez, R., Enns, J., Lopez-Canul, M., … & Gobbi, G. (2019). Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain, 160(1), 136. , anticancer 29 De Petrocellis, L., Ligresti, A., Schiano Moriello, A., Iappelli, M., Verde, R., Stott, C. G., … & Di Marzo, V. (2013). Non‐THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro‐apoptotic effects and underlying mechanisms. British journal of pharmacology, 168(1), 79-102. , and anti-obesity effects 30 Palomares, B., Ruiz-Pino, F., Garrido-Rodriguez, M., Prados, M. E., Sánchez-Garrido, M. A., Velasco, I., … & Muñoz, E. (2020). Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity. Biochemical pharmacology, 171, 113693.
CBDA has shown anti-inflammatory properties 31 Takeda, S., Misawa, K., Yamamoto, I., & Watanabe, K. (2008). Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug metabolism and disposition, 36(9), 1917-1921. and has particularly strong effects on the serotonin receptor 32 Russo, E. B. (2018). Cannabis therapeutics and the future of neurology. Frontiers in integrative neuroscience, 12, 51.
There are many other minor cannabinoids, including CBL, CBGM, CBE, CBT, and the “varin” cannabinoids CBGV, THCV, CBDV, and CBCV, which have a slightly different structure from their regular counterparts.
We don’t know too much about how they work or their potential benefits since research is scarce. However, CBDV is being explored as a potent anti-epileptic compound 33 ill, T. D. M., Cascio, M. G., Romano, B., Duncan, M., Pertwee, R. G., Williams, C. M., … & Hill, A. J. (2013). Cannabidivarin‐rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor‐independent mechanism. British journal of pharmacology, 170(3), 679-692. , whereas THCV has been shown to reduce appetite, help regulate blood sugar 34 Abioye, A., Ayodele, O., Marinkovic, A., Patidar, R., Akinwekomi, A., & Sanyaolu, A. (2020). Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes. Journal of Cannabis Research, 2(1), 1-6. , and protect against neurodegenerative conditions 35 García, C., Palomo‐Garo, C., García‐Arencibia, M., Ramos, J. A., Pertwee, R. G., & Fernández‐Ruiz, J. (2011). Symptom‐relieving and neuroprotective effects of the phytocannabinoid Δ9‐THCV in animal models of Parkinson’s disease. British journal of pharmacology, 163(7), 1495-1506. .
Will cannabinoids get you high?
THC is the only cannabinoid that scientists know for sure can get you high.
There’s also a widespread belief that its derivative CBN has weaker psychotropic effects, but research hasn’t confirmed this. Instead, one early study suggested that CBN may enhance THC’s psychotropic effects while being non-intoxicating on its own 36 Karniol, I. G., Shirakawa, I., Takahashi, R. N., Knobel, E., & Musty, R. E. (1975). Effects of Δ9-tetrahydrocannabinol and cannabinol in man. Pharmacology, 13(6), 502-512. .
Meanwhile, older THCV studies, another minor cannabinoid, found that it may have intoxicating effects that are about 25% as strong as THC 37 Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British journal of pharmacology, 163(7), 1344-1364. . However, it only seems to produce these effects when taken in higher doses.
Some other minor cannabinoids may have psychotropic effects as well, but more research is needed.
There are many cannabinoids, but THC and CBD have received the most attention because they’re the two most abundant.
THC is the main intoxicating cannabinoid, although its close cousin THCV may have weaker psychotropic effects when taken in larger doses. Additionally, some cannabinoids, such as CBN, may enhance the intoxicating effects of THC.
Cannabinoids have shown an impressive range of beneficial effects, highlighting their immense potential in treating various symptoms and conditions.
Is CBD a cannabinoid?
Yes, cannabidiol (CBD) is a phytocannabinoid (plant-derived cannabinoid) found in cannabis. It’s most abundant in hemp, a low-THC variety of the plant.
What do cannabinoids do to the body?
Cannabinoids can interact with your endocannabinoid system, which is tasked with keeping your body in a healthy state of balance. They can also influence many other molecules, such as serotonin and opioid receptors.
What are examples of cannabinoids?
A complete list of cannabinoids includes over 140 compounds. However, most of them are present in very small quantities. THC and CBD are the best-known examples of cannabinoids. Other prominent cannabinoids include CBG, CBC, CBN, THCV, CBDV, and cannabinoid acids such as CBDA and THCA.
What is cannabinoids on a drug test?
A cannabis drug test looks for the presence of THC or its metabolites. That’s why THC-free cannabis products will not result in a positive drug test.
Gleb Oleinik is a freelance writer from Vancouver, Canada with a passion for educating people about the benefits of CBD, hemp, and cannabis. He knows the CBD industry inside and out and has read hundreds of research studies about cannabinoids, helping him translate complex scientific ideas into plain language. When he’s not writing, Gleb likes to spend his time in the gym, out in nature, and working on his website projects.