What are cannabinoids?
Cannabinoids [1, 2] are a group of complex chemical compounds, formed due to biosynthesis [3] in certain plants, and are capable of binding with the cannabinoid receptors of our brain and the rest of the body. The cannabinoid receptors are protein-based cell membrane receptors that interact with the endocannabinoid [7] system of our body.
The endocannabinoid system is a biological system that covers the entire expanse of our body, including our brain. It controls various physical and mental processes, like the immune system, appetite, mood, and is responsible for maintaining homeostasis.
It was accidentally discovered by scientists while studying the effects of cannabis on our body and mind. So, where all are they found?
Where are Cannabinoids found?
Cannabinoids are found both in nature and within our body. Intrigued?
Well, a wide range of cannabinoids is found in nature. But they are mostly concentrated in cannabis family of plants, like marijuana and hemp. Depending on where in the world they grow, their chemical composition and properties differ.
For instance, Cannabis Sativa [4], which grows in the US, has a different composition from Cannabis Indica, which grows in India. While extracts from the first strain have many therapeutic effects, the latter is usually used to make recreational drugs.
However, these cannabinoids are found in cannabis in an acidic form, which renders them a bit less effective on the human body. Their effects are enhanced once they are activated. For that, all that is needed is to expose the plant extract to heat, light or prolonged storage time.
Natural Sources of Cannabinoids, Instead of Cannabis:
- Black Pepper
- Cacao
- Kava
- Echinacea
- Flaxseed
- Liverwort
- Electric Daisy
- Black Truffles
- Labrador (Rhododendron)
- Hops
- Mangoes
- Keeribos
Cannabinoids can also be found in human bodies.
They are known as endocannabinoids [6, 8]. In fact, their presence has been detected in all animals with a spinal cord. Anandamide or Arachidonoylethanolamine [9, 10], often dubbed as the “bliss molecule”, is one such cannabinoid. It is responsible for a person feeling happy, excited or euphoric. Its absence or dearth can cause depression, anxiety, and other mood-related conditions and disorders.
Types of Cannabinoids
#1 Cannabis-derived
Cannabinoids are found in abundance in nature. But, they are mostly concentrated in plants, which is why they are called phytocannabinoids. Among them, cannabis has the highest concentration of cannabinoids [11]. Cannabis has over 120 cannabinoids, but the most predominant ones are:
- CBD (cannabidiol): Key non-psychoactive cannabinoid; believed to have quite a few health benefits owing to the way it interacts with the endocannabinoid system, which mostly seems to be opposed to the way THC does; potentially counters THC’s effects.
- THC (tetrahydrocannabinol): Main psychoactive/intoxicating cannabinoid; mostly responsible for the much-famed marijuana “high”.
- THCA (tetrahydrocannabinolic acid): Inactive and a lesser effective form of THC.
- CBDA (cannabidiolic acid): The inactive and lesser effective form of CBD, quite like THCA. Decarboxylation, which requires heat, light or prolonged storage time, usually does the trick!
- CBN (cannabinol): Formed due to degradation of THC, it is not usually found in a fresh plant; slightly psychoactive, it generally enhances the effects of CBD oil (which is becoming a popular therapeutic agent for managing a lot of health issues).
- CBG (cannabigerol): A minor component of cannabis plants, it has no psychoactive effects. Instead, it is believed to have some health benefits; it acts quite like CBD; its presence in any drug composition enhances CBD’s effects and counters THC’s effects.
- CBC (cannabichromene): This is a non-psychoactive cannabinoid. Unlike other such cannabinoids, it does not counter the effects of THC; mainly has a direct effect on endocannabinoids; usually found in tropical strains of cannabis.
- CBL (cannabicyclol): Non-psychoactive; not found in fresh plants like CBN; created by the degradation of CBC.
- CBV (cannabivarin)/cannabivarol: Non-psychoactive; found in very small amounts in cannabis plants; created by the degradation of THCV, THV.
- THCV (tetrahydrocannabivarin): Present in cannabis strains found in central, south and southeast Asia as well as southern Africa (Cannabis Indica); mainly counters THC’s effects.
- CBDV (cannabidivarin): Found mostly in the northwest Himalayan strains; non-psychoactive; has many medical uses, and is currently under active experimentation.
- CBCV (cannabichromevarin): Found in very small amounts; acts more like CBC and THCV. More studies need to be done to know its exact properties.
- CBGV (cannabigerovarin): Non-psychoactive; believed to have similar health benefits as CBD and CBG; believed to enhance the effects of other cannabinoids. More studies need to be done to know its exact properties.
- CBGM (cannabigerol monomethyl ether): Much like CBG, found mostly in cannabis strains from northeast Asia (mostly Japan); an ether compound usually created when acidic solvents are used to separate cannabis compounds.
- CBE (cannabielsoin): Created when CBD breaks down, hence a metabolite of CBD; no psychoactive effects.
- CBT (cannabicitran): Except for its chemical composition and properties, not much is known about its interaction with other living beings. More studies are required on this cannabinoid.
#2 Other Plants:
Cannabinoids found in other plants are:
- Yangonin: Found in the Kava plant
- Beta-caryophyllene: Some medicinal plants
- Anandamide: Found in black truffles, chocolates
- Perrottetinene: Found in liverwort
Information on such phytocannabinoids is scarce for now. Hopefully, studies will reveal more ways in which we can have access to cannabinoids that aren’t derived from cannabis.
- Endocannabinoids: Humans, like many other animals, also produce certain cannabinoids from within their body. They are:
- Arachidonoylethanolamine (Anandamide or AEA): Remember the bliss molecule we discussed earlier? This behaves quite like THC. It was the first endocannabinoid to be discovered. It has anti-inflammatory and appetite-curbing effects.
- 2-Arachidonoylglycerol (2-AG): Found in higher levels in the central nervous system than anandamide. Its presence seems to spike among females of all species of animals with a spinal cord, during pregnancy.
- 2-Arachidonyl glyceryl ether: It triggers sedation, hypothermia, intestinal immobility, and mild anti-nociception in mice.
- N-Arachidonoyl dopamine (NADA): Behaves quite like anandamide.
- Virodhamine/O-arachidonoyl-ethanolamine (OAE)
- Lysophosphatidylinositol (LPI)
#3 Synthetic Cannabinoids:
Yes, humans have found ways to imitate cannabinoids too! While some of them have been developed for medical purposes, most of them were for research alone [12].
Some cannabinoids of the latter type have, however, been released into the general population, causing much damage to human health.
For instance, K2 or Spice [14], which many people, who are in the know of the CBD industry and illicit drugs, have heard of.
Some medications with synthetic cannabinoids or cannabinoid analogs:
- Nabilone (Medications: Cesamet, Canemes): Synthetic cannabinoid, having effects similar to THC. It is a Schedule II drug.
- Rimonabant (SR141716): Synthetic cannabinoid with anti-obesity and smoking cessation properties.
Other synthetic cannabinoids developed for research purposes include:
- JWH-018: This is the scientific name for “spice”.
- JWH-073: Similar to the one above
- CP-55940: Much more powerful than THC.
- HU-210: 100 times more potent than THC
- HU-331: A cannabinoid with anti-cancer properties; derived from CBD.
- WIN 55,212-2
- SR144528
- JWH-133
- AM-2201
- Dimethylheptylpyran
Are they beneficial or detrimental to human health?
Used in the right proportion, cannabinoids can be a boon. But in the wrong amount, it can be a bane. [13] The degree of good or bad effects depends on both the quantity and quality of cannabinoids.
While CBD is known to have many healing effects on the body and no intoxicating properties, THC is notorious for being a hallucinogen, with very few benefits. The latter has quite a few undesirable effects that may seem pleasurable at first, but in high amounts can be detrimental to human health.
Cannabis has quite a few non-psychoactive cannabinoid components, like CBD, which can help manage the symptoms of some autoimmune diseases that are otherwise incurable conditions. The reason for that is that cannabinoids bind with some specific cannabinoid receptors that influence the immune system’s responses.
Whereas, psychoactive cannabinoids, like THC, gives people a mind-altering effect – the famous marijuana “high”, which makes normal life activities almost impossible, among other things.
Then again, CBD too can have some adverse effects, if taken in too high amounts. Although rare and very mild, these adverse effects are counterproductive to the benefits that cannabidiol can offer if taken with discretion or in the right dose.
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Research citations:
- Cannabinoid Toxicity; Brian F. Kelly; Thomas M. Nappe; Last Updated on March 14, 2019; https://www.ncbi.nlm.nih.gov/books/NBK482175/
- Cannabis, cannabinoids, and health; Dialogues in Clinical Neuroscience; September 2017; Genevieve Lafaye, MD, Laurent Karila, MD, PhD, Lisa Blecha, MD, Amine Benyamina, MD, PhD; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741114/
- Complete biosynthesis of cannabinoids and their unnatural analogues in yeast; Nature; Feb 27, 2019; Luo X, Reiter MA, d’Espaux L, Wong J, Denby CM, Lechner A, Zhang Y, Grzybowski AT, Harth S, Lin W, Lee H, Yu C, Shin J, Deng K, Benites VT, Wang G, Baidoo EEK, Chen Y, Dev I, Petzold CJ, Keasling JD; https://www.ncbi.nlm.nih.gov/pubmed/30814733
- The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research; National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda; Washington (DC): National Academies Press (US); Jan 12, 2017; Chapter 2: Cannabis – https://www.ncbi.nlm.nih.gov/books/NBK425762/ Chapter 4: Therapeutic Effects of Cannabis and Cannabinoids – https://www.ncbi.nlm.nih.gov/books/NBK425767/
- Phytocannabinoids beyond the Cannabis plant – do they exist? British Journal of Pharmacology; June 2010; Jürg Gertsch, Roger G Pertwee, and Vincenzo Di Marzo; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931553/
- Endocannabinoid system: An overview of its potential in current medical practice; Neuro Endocrinology Letters; 2009; Mouslech Z, Valla V; https://www.ncbi.nlm.nih.gov/pubmed/19675519
- Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System; International Journal of Molecular Sciences; March 13, 2018; Shenglong Zou and Ujendra Kumar; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/
- An introduction to the endogenous cannabinoid system; Biological Psychiatry; Oct 30, 2015; Hui-Chen Lu1,2 and Ken Mackie; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/
- Discovery and isolation of anandamide and other endocannabinoids; Chemistry & Biodiversity; August 2007; Hanus LO; https://www.ncbi.nlm.nih.gov/pubmed/17712821
- Anandamide and endocannabinoid system: an attractive therapeutic approach for cardiovascular disease; Therapeutic Advances in Cardiovascular Disease; July 16, 2018; Virna Margarita Martín Giménez, Sandra Edith Noriega, Diego Enrique Kassuha, Lucía Beatriz Fuentes, and Walter Manucha; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009078/
- Molecular Targets of the Phytocannabinoids-A Complex Picture; Prog Chem Org Nat Prod; March 10, 2017; Paula Morales, Dow P. Hurst, and Patricia H. Reggio; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/
- Synthetic Cannabinoids; American Journal of Medical Sciences; July 2015; Mills B, Yepes A, Nugent K; https://www.ncbi.nlm.nih.gov/pubmed/26132518
- The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research; National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda; Washington (DC): National Academies Press (US); The National Academies Collection: Reports funded by National Institutes of Health; January 2017; https://www.ncbi.nlm.nih.gov/pubmed/28182367
- The K2/Spice Phenomenon: emergence, identification, legislation and metabolic characterization of synthetic cannabinoids in herbal incense products; Drug Metabolism Reviews; Sep 24, 2013; Lisa K Brents and Paul L. Prathe; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100246/
