In learning your way around the burgeoning CBD space, you hear a lot about “full-spectrum” or “whole-plant” preparations, and other compounds like terpenes, terpenoids, and flavonoids. The cannabis plant isn’t just a repository for CBD or THC, even if they are the most talked-about cannabinoids today. Some of the current literature tells us that the cannabis plant has around 500 individual compounds in it. This is important to consider, as evidence suggests that part of why a phytocannabinoid like CBD is therapeutically effective lies in the way it works in synergy with other compounds present in the cannabis plant.
Raphael Mechoulam, the storied “father” of cannabis science, dubbed this synergy the “entourage effect” back in 1998. A study done by Mechoulam and a team of Israeli and Italian researchers discovered that the healing benefit of the endocannabinoid 2-AG was enhanced when it was used in combination with other cannabinoid and noncannabinoid compounds, but that many of these compounds showed no special benefit or significance when tested on their own. This led to an understanding that compounds derived from cannabis are often more effective when used synergistically and that they in fact can amplify one another’s effects. The “entourage effect” is a simple concept, but a powerful one when it comes to CBD.
Particularly potent are many of the 100+ terpenes that are part of the cannabis plant. Terpenes are naturally occurring hydrocarbons (hydrogen/carbon compounds) that are commonly found in the essential oils of plants. They are potent, aromatic substances that give plants their scent, and are especially important in the wild. Cannabis and other plant terpenes can deter herbivorous animals from trying to eat them, repel insects, attract herbivore predators and parasites, and serve as shields against some bacteria and fungi. “Terpenes” and “terpenoids” are often used interchangeably, but by definition “terpenoid” refers to a terpene that has been denatured via drying or curing (oxidization) or by chemical modification. Terpenes and terpenoids are already used in alternative healing—they are the constituents of aromatherapy.
Chemically speaking, there are different categories of terpenes based on how many units of isoprene (a 5-carbon molecule) they contain—monoterpenes, diterpenes, triterpenes, and so on. Although there are many occurring terpenes in the cannabis plant, some are only present in trace amounts. The more prominent terpenes have been the subject of various studies, and are shown to confer therapeutic benefits, especially as a complement to CBD. An extensive 2011 British Journal of Pharmacology review by Dr. Ethan Russo states: “Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.” Here are some of the more prevalent terpenes in cannabis, along with some ideas about how they contribute therapeutically to the entourage effect:
Limonene is a monocyclic monoterpenoid compound that is actually formed from pinene (see below). It’s a component of citrus rinds as well as herbs like rosemary, juniper, and peppermint. Plants have evolved to make limonene as a kind of natural insecticide, but it is well tolerated and has many benefits on humans. It is a proven antifungal and antibacterial agent, and may have anticancer benefits as well—there are current clinical trials on oral limonene in the treatment of breast cancer. Limonene has even been shown to aid in weight loss.
Myrcene is a monoterpene that’s quite prevalent in cannabis. It also can be found in citrus fruits, bay leaves, eucalyptus, wild thyme, lemongrass, and other plants. It is known to have the ability to affect the blood-brain barrier, increasing its permeability so that chemicals can pass through more quickly. (This is why some people say that eating a ripe mango before smoking marijuana enhances the high.) Myrcene has effects as an anti-carcinogen, and has also been shown to be an analgesic and anti-inflammatory. One study published in 2014 also proved myrcene to be effective in the treatment of peptic ulcers.
Alpha- and beta-pinene are two structural isomers of pinene, a bicyclic (meaning its molecule has two rings) monoterpenoid and the most widely occurring terpenoid in nature. It is found in abundance in pine resin, in many conifers and nonconiferous plants, and in some citrus fruits. Pinene has been used in traditional Chinese medicine for many years. It has anti-inflammatory effects, expectorant and bronchodilation effects, and can be used as an antiseptic. A-pinene has been shown to have potential as an anti-cancer agent as well.
Linalool is a noncyclic monoterpenoid that is a critical precursor in the formation of vitamin E. It has been identified in several different plant families and even in some fungi. The Environmental Protection Agency (EPA) has approved linalool for use in pesticides, and it is also used as a flavoring agent. It is found in many bath and body products and tends to have a floral scent. Therapeutically speaking, linalool is shown to have relaxing effects and has been used as a sleep aid for centuries. A study done in 2015 showed that linalool can reduce lung inflammation caused by cigarette smoking, which suggests that it can also reduce damage to the lungs caused by cannabis smoking and inhaling carcinogenic pollutants. Linalool is also shown to have indirect cognitive and emotional benefits due to its anti-inflammatory properties, and has the potential to aid in the treatment of Alzheimer’s disease.
Beta-caryophyllene is a sesquiterpene that is commonly found in leafy greens, black pepper, oregano, and other herbs. Because it binds directly to the endocannabinoid system’s (ECS’s) CB2 receptors, it holds great potential as a treatment for inflammation and autoimmune disorders. It also has gastroprotective qualities and is helpful in treating peptic ulcers. Beta-caryophyllene is the only terpene known to directly interact with the ECS. Other terpenes exert their effects via other channels.
Nerolidol is a sesquiterpene that is known to make the skin more absorbent, making it a useful additive in topical preparations. It tends to have a floral and “woody” scent. It has been studied as an antimalarial agent and also has antifungal properties, and sedative properties. It can be found in abundance in orange peels.
Phytol is a diterpine and a byproduct of chlorophyll degradation. It is a GABA neurotransmitter inhibitor, and therefore has a calming effect.
The terpenes discussed above, again, are generally part of the whole cannabis plant and are seen as having benefits independent of and in complement to cannabinoids like CBD. They are all GRAS (generally recognized as safe) according to the standards of the U.S. Food and Drug Administration (FDA) and other organizations as additives in food and personal-care products. In addition to the specific properties enumerated above, many terpenes (with the exception of myrcene), like CBD, are shown to counteract the effects of THC, suggesting that terpene-cannabinoid combinations can help to mitigate the psychoactive effects of THC in tandem where THC is a necessary part of therapy. But it’s also important to recognize the importance of terpenes as part of the cumulative therapeutic effect of whole-plant cannabis, even with low or no THC content. Terpenes have far-reaching and powerful medicinal effects. Back to Russo, he tells us that cannabinoid-terpenoid interactions “could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections.”