In many cases, inflammation is the body’s natural defense against further damage. However, over-active inflammation is the cause of many diseases, ranging from arthritis to irritable bowel syndrome. These conditions can be severely debilitating and tend to gradually worsen. Many degenerative inflammatory diseases are associated with older age, meaning that as humans continue to extend the average life span through medical advancements, inflammatory diseases will affect a larger and ever-growing population. In this article, we’ll take a look at the anti-inflammatory effects of terpenes and terpenoids, non-psychoactive chemical components of cannabis.
Inflammation and the biochemical processes that surround it are controlled by complex signaling and gene expression. Nuclear factor-kB (NF-kb) is considered the major regulator in the pathogenesis of inflammatory diseases. It is a protein complex that controls transcription of DNA, specifically parts of DNA that relate to the body’s manner of dealing with septic shock, cancer, inflammation, and immune response. In most diseases where unwanted inflammation is occurring, this protein group is over-active itself, continually producing inflammation response where none is needed. The ideal anti-inflammatory medicine therefore would reduce NF-kb levels, telling the body to shut off inflammation. Although many inflammation agents exist now (such as common aspirin), the challenge is finding a medicine that does not affect other responses of the body or have any unwanted side-effects.
In the area of inflammation, terpenoids found in cannabis show promise. Although many cannabis users are familiar with the primary psychoactive ingredient, THC, few are aware of the multitude of other non-psychoactive chemicals found in cannabis. One group of these, terpenoids, unlike cannabidiol or THC is common with many other plants. In fact, terpenoids are found in almost every fruit, plant, and some insects. They’re commonly consumed by humans and recognized as generally safe to digest by the US Food and Drug Administration. Since these chemicals are highly volatile and evaporate easily, they are responsible for many of the flavors and smells that we experience. Although scientists have identified over 20,000 such chemicals in nature, about 200 exist in cannabis in both trace amounts and more significant portions. Since THC and CBD have no smell independently, it is the terpenoids in cannabis that lend each strain its unique bouquet of smells, ranging from citrus-like fruity perfumes to deep chocolate-like pungency. Although the terpenoids produced in each plant depend on soil conditions, sunlight, and environmental stress, the primary profile of terpenoids in a plant is largely genetic, which means that any given plant from a strain will have a similar chemical profile of terpenoids as that of another. This quality allows breeders and seed banks to quickly verify or rule out claims of a particular genetic heritage.
Beyond giving cannabis strains flavor though, terpenoids have long been known to have medicinal properties of their own. The following cannabis terpenoids have been found to have medicinal value:
Alpha-Pinene
This terpene is often found in conifers (hence the name originating from pine sap), and is a “powerful inhibitor of the NF-kB system” (Zhou et al.) Research indicates that the presence of this terpenoid inhibits the movement of NF-kB into some cells, thus preventing inflammation.
Beta-Caryophyllene
Beta-caryophyllene is “gastro-protective” (Lee) and ideal for reducing inflammation in the intestines (such as that causing Irritable Bowel Syndrome). It is also one of the only known terpenes that is also capable of binding to the traditional cannabinoid receptors that THC and CBD bind to. This interaction underscores that the interaction between THC and non-individually-psychoactive components of cannabis likely have much more interaction and interdependence than originally thought.
Limonene
As it’s name suggest, limonene yields a citrus flavor. Researchers (Berchtold et al.) have observed that limonene derivatives can play a role in inhibiting the proliferation of some cancers, at least in preliminary research. However, the real star of the limonene family is linalool, which applied topically, can help ease skin irritation such as acne and skin burns (Lee).
Myrcene
Present in most varieties, Myrcene is a sedative, muscle relaxant, and anti-inflammatory compound. Myrcene not only shows promise in attenuating NF-kB over-expression, but also generally stimulates the body to relax thus “quieting” irritation.
A key point to note is that many terpenoids are destroyed during the process of creating extracts. Due to the very reason that they are so pungent (easy evaporation), these molecules quickly escape into the air at temperatures much lower than required to extract THC. A similar process occurs with edibles. For this reason, every step away from natural plant material results in fewer terpenoids. Despite this, edibles and topical applications are still likely the best routes of administration for patients hoping to benefit from cannabis terpenoids, with topical applications well suited for joint inflammation and edibles being well suited for intestinal problems (ie. releasing terpenoids the entire route of the intestine).
Of course, several large mysteries remain. Why do cannabis plants produce these terpenoids? The general consensus is that the terpenoids play a role in defense of their host plant, with many being toxic to insects or disabling their immune systems. Other suspected roles include protecting plants from disease, dryness, or fungus growth, which is why some strains are more resistant to mold than others. However, many terpenoids’ functions remain entirely unknown, and it’s possible that the plants simply out-evolved their utility but continued to produce them.
The second, more vital mystery in terms of medicinal value is what exact pathways are leading to NF-kB suppression. To date, most studies have centered around changes in chemicals that flag inflammation, such as IKK complex proteins, IkB proteins, the DNA-binding activity of NF-kB. While these are great indicators for monitoring inflammation, none of these locate the target molecule upstream that is leading to those changes. According to Kawai et. Al, a number of terpenoids are known to affect targets upstream, and it is likely one of these will shed light on the specific mechanism behind NF-kB suppression.
As always, any change in the body can lead to unwanted and dangerous side-effects. One known natural Nf-kB inhibitor, thalidomide, was prescribed as a sedative and anti-nausea drug, but was later pulled when it turned out to cause birth defects (Salminen et. al). “Natural” does not always equate with “healthy” (consider the deadly but natural poison hemlock for example). However, the more options available for treating inflammation, the more likely a key will be found that does not have toxicity or other unwanted side-effects. At this moment, cannabis is in a very good position to fill that role, with no chemical within it being found as toxic in the amounts present.
Berchtold, C.M., Chen, K.S., Miyamoto S. and Gould M.N. (2005) Perillyl alcohol inhibits a calcium-dependent constituitive nuclear factor –kB pathway. Cancer Research 65, 8558-8566.
Lee, Martin A. “Talking Terpenes”. 2013 April 8. <http://www.hightimes.com/read/talking-terpenes>.
Lorenzetti, B. B.; Souza, G. R. E. P.; Sarti, S. L. J.; Santos Filho, D.; Ferreira, S. R. H. (1991). “Myrcene mimics the peripheral analgesic activity of lemongrass tea”. Journal of Ethnopharmacology 34 (1): 43–48. doi:10.1016/0378-8741(91)90187-I. PMID 1753786
Salminen, M. Lehtonen, T. Suuronen, K. Kaarniranta, and J. Huuskonen (2008) Terpenoids: natural inhibitors of NF-kB signaling with anti-inflammatory and anticancer potential. Cellular and Molecular Life Sciences 65 2979-2999.
Zhou, J.Y., Tang, F.D., Mao, G.G. and Bian, R.L. (2004) Effect of alpha-pinene on nuclear translocation of Nf-kB in THP-1 cells. Acta Pharmacol. Sin. 25, 480-484.