Anti-inflammatory proprieties of caryophyllene: a dietary cannabinoid

Anti-inflammatory proprieties of caryophyllene

Terpenes: a “smelly” super-family

Terpenes are produced as secondary metabolites by many plants as a form of defence.

They are a diverse class of organic compounds with well over 30,000 members and attribute the aroma of each plant, reason for which they are commonly used for cooking, as well as in beauty-care products.

We looked onto the anxiolytic properties of some terpenes found in forests in this article “What if your psychiatrist prescribed a trip in the forest vs anti-depressants?”

Recent data suggest that some of the terpenes found within the cannabis plant possess anti-inflammatory and analgesic activity which is additional to the effects of classical phytocannabinoids and may generate synergistic interactions.

It has also been hypothesised that each terpene ratio inherently change the properties of the cannabis strains.(1)


What do cloves, hops, rosemary, cinnamon, cannabis & black pepper have in common?

β-Caryophyllene: a dietary cannabinoid

These are some of the most common plants which produce essential oils containing Caryophyllene.

(E)- β-Caryophyllene (BCP) is a widespread sesquiterpene (made of three isoprene units) and is commonly found in nature together with its isomers, Z-BCP and α-humulene or with BCP oxide.

The chemistry-geeks are probably familiar with the fact that terpenes & cannabinoids are indeed sister compounds, produced by the common relative Geranyl Pyrophosphate (GPP). Despite GPP might sounds like an absurd unknown molecule, cholesterol, which you may be more familiar with, also derives from GPP.

This is to say, from the same mother molecule many lipid molecules are born, so it should not come as a surprise that these natural compounds can affect our systems in a powerful way.

The anti-inflammatory activity of this terpene was established by folk medicine well before its mocaryophyllenelecular characterisation.  However, we are only starting to grasp the extensive therapeutic potential of this harmless & fragrant scent in the past 10 years.

In 2008 a mixed group of scientists working in Switzerland (the “German-speaking” side, Zürich), found β-Caryophyllene (BCP) to be the first “food-stuff” to activate directly Cannabinoid Receptor 2 (CB2), and exerts its anti-inflammatory property by binding selectively to them.(2) (Why is the endocannabinoid system so important for regulating inflammation? Find out here)

The group identified very specific effects following BCP binding: Ca2+ (used intra-cellularly as a signalling molecule) is released, initiating fast responses, whilst through a different pathway (MAPK), BCP signals all the way to the DNA in the nucleus, which, in turns, expresses or inhibits protein production, giving rise to effects later in time.

Ca2+ imaging: this machine is used in order to test the ability of compounds to initiate Ca2+ signalling. (This is a picture from my workset at UCD Conway lab)

Ca2+ imaging: this machine is used in order to test the ability of compounds to initiate Ca2+ signalling. (This is a picture from my workset at UCD Conway lab)

Scientific evidences of BCP anti-inflammatory properties


Cytokines are signalling molecules generally secreted by immune cells. Pro-inflammatory cytokines are released following an insult and contribute to further inflammation and sensitisation within the body. Compounds able to activate CB2 receptors (like BCP) inhibit cytokine expression following an insult, as it has been shown in a number of studies on human whole blood and rat macrophages (immune cells). (2, 3, 4)

Most of the knowledge that we have about BCP is however not in its pure form, but within a phytocomplex, such as a mixture of different terpenes in essential oils as normally found in nature.

For example, scientists studied the potent inhibition on pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6) with the Korean essential oil Artemisia fukudo, in which the main constituent is caryophyllene. (3)

Others focused on Greek essential oil Teucrium montbretii Benth. Ssp. heliotropiifolium, which also shows a predominance of caryophyllene (BCP & caryophyllene oxide), and found that in addition to effects on cytokines, Caryophyllene inhibits production of Nitric Oxide (NO), which further deteriorates inflammatory events. (4)

The group of Kim et al. observed similar inhibitory effects on NO, testing the Japanese Farfugium japonicum (L.) Kitamura essential oil, constituted mostly by β-caryophyllene. They also verified that the oil prevented prostglandins (PG) production, by blocking mRNA expression (protein expression) of the enzyme which makes them, namely, COX-2. (5)

To put it simply, prostaglandins amplify the pain mechanism and enhance vascular permeability (acute inflammation). Caryophyllene blocks their manufacture upstream.


Following in-vitro studies, further characterisation of the anti-inflammatory properties of BCP were examined on animals (rodents), using pure BCP orally in mice injected with an irritant (carrageenan). The paw of the poor lab animals showed oedema, an inflammatory response resulting from the initial release of histamine, serotonin and bradykinin, and the successive discharge of prostaglandins.

The recovery of the paw oedema was impressive (70%) in the animals treated with 5 mg/kg of BCP. 

The authors established that in order for the effects of BCP to take place, Cannabinoid Receptors (CB2) must be functional, since they examined the effects of this sesquiterpene both on “wild-type” animals (normal genetics) and on CB2 Knock-Outs (genetically engineered animals lacking CB2 receptors), finding no recovery in the second group. (2)

These results were confirmed by another study which examined the effects of a Brazilian essential oil (Eremanthus erythropappus), commonly known as candeia, which is composed mainly by sesquiterpenes (60.20%), with a significant predominance of b-caryophyllen (22.92%). Again, the above mentioned system with carrageenan was used to provoke oedema in the paw, as well as an inflammation in the linen of the lungs (pleurisy).

200 and 400 mg/kg −1 of the essential oil Eremanthus erythropappus were shown to protect the animals by reducing the volume of the oedema, inhibiting intracellular pathways involved in modulating the movement of inflammatory cells & mediators. (6)

Trans-Caryophyllene is the major component of the Brazilian Pterodon emarginatus Vogel. Oil, which has also induced a marked reduction in cytokines in mice treated with carrageenan intrapleurally. (7)

How can you benefit from this terpene?

In Cannabis this sesquiterpene is prevalent (12 to 35%) in dry flowers or extracts, wherein following decarboxylation most of the smaller & more volatile monoterpenes are lost. Thanks to the work of Gertsch and collegues, we now know that BCP can activate CB2 receptors very selectively (Ki =155 +-4 nM), therefore the concentrations found in the Cannabis plant are sufficient for intracellular signalling to be initiated. (1,2)

Although still speculative, it is very probable that Cannabis plants rich in Cannabidiol (CBD) as well as β-caryophyllene, would further boost the anti-inflammatory effects of the terpene “alone”.

CBD cannabis seeds are now increasingly common to find and many people use them for their anti-inflammatory effects.

The boiling point for BCP is lower than that of other cannabinoids (e.g. THC) so it is highly recommended to avoid combustion (smoking). If you like to vaporise your medicine, remember to use a vaporiser which allows you to set the temperature and check our “VAPORIZING- a guide to inhale cannabis without smoking” for further information.

As we have mentioned above, Caryophyllene is widespread amongst different plants, growing at any corner of the world. We only brushed through the surface of the number of studies carried out on this topic, which also showed evidences for analgesic, anxyolitic and anti-cancer effects of this terpene.

Essential oils can be used with several different methods, including:

  1. Indirect inhalation via a room diffuser or drops of oil placed near the patient (e.g., on a tissue)
  2. Direct inhalation used in an individual inhaler (e.g., a few drops of essential oil floated on top of hot water to aid a sinus headache),
  3. Aromatherapy massage which is the application to the body of essential oils diluted in a carrier oil.
  4. Other direct and indirect applications include mixing essential oils in bath salts and lotions or applying them to dressings.
  5. Oral administration, for which is important to consult with a therapist, as it may contain toxic solvents. (8)


Next time you are offered black pepper, don’t discount its high levels of β-caryophyllene!

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  1. Russo, E. (2011) Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology 163: 1344–1364
  2. Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J.Z., Xie, X.Q., Altmann, K.H., Karsak, M. and Zimmer, A. (2008) Beta-caryophyllene is a dietary cannabinoid
  3. Yoon, W.J.; Moon, J.Y.; Song, G.; Lee, Y.K.; Han, M.S.; Lee, J.S.; Ihm, B.S.; Lee, W.J.; Lee,N.H.; Hyun, C.G. Artemisia fukudo essential oil attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW264.7 macrophages. Food Chem. Toxicol.2010, 48, 1222-1229.
  4. Menichini, F.; Conforti, F.; Rigano, D.; Formisano, C.; Piozzi, F.; Senatore, F. Phytochemical composition, anti-inflammatory and antitumour activities of four Teucrium essential oils from Greece. Food Chem. 2009, 11, 670-686.
  5. Kim, J.-Y.; Oh, T.-H.; Kim, B.J.; Kim, S.-S.; Lee, N.H.; Hyun, C.-G. Chemical composition and anti-inflammatory effects of essential oil from Farfagium japonicum flower. J. Oleo Sci. 2008,57, 623-628.
  6. Sousa, O.V., Silvério, M.S., Del‐Vechio‐Vieira, G., Matheus, F.C., Yamamoto, C.H. and Alves, M.S. (2008) Antinociceptive and anti-inflammatory effects of the essential oil from Eremanthus erythropappus leaves
  7. Dutra, R.C.; Fava, M.B.; Alves, C.S.C.; Ferreira, A.P.; Barbosa, N.R. Antiulcerogenic and anti-inflammatory activities of the essential oil from Pterodon emarginatus seeds. J. Pharm.Pharmacol. 2009, 61, 243-250.
  8. Wildwood C: The Encyclopedia of Aromatherapy. Rochester, Vt: Healing Arts Press, 1996.

Viola Brugnatelli

Viola Brugnatelli is a Neuroscientist specialised in Cannabinoid circuitry & GPCRs signalling. Her academy and research training let her gain extensive experience on medical cannabis and terpenes both from preclinical as well as clinical perspective. In her vision, collective human knowledge behold the power for overall improvement of life, thus, it should be accessible and shareable. Viola is Founder of the science online magazine Nature Going Smart, and works as a consultant for companies & individual patients, as a speaker at seminars and workshops and as a lecturer in a CME course on Medical Cannabis in Italy, at the University of Padua.

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1 Response

  1. Can you know what sort of cannabis strain the most THC?

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