Beta Caryophyllene
The sesquiterpene β-caryophyllene is a major plant volatile found in large amounts in the essential oils of many different spice and food plants such as cloves (Syzygium aromaticum), oregano (Origanum vulgare L.), cinnamon (Cinnamomum spp.) and black pepper (Piper nigrum I.) (1,2,3).
β-Caryophyllene selectively binds to the CB2 receptor, resulting in anti-inflammatory effects in peripheral tissues (4,5). In vivo, CB receptors are activated by arachidonic acid-derived endocannabinoids, such as 2-arachidonoyl ethanolamine (anandamide or AEA) and 2-arachidonoylglycerol (2-AG) (6,7). CB2 receptor ligands have been shown to inhibit inflammation and fluid buildup (8), exhibit pain-killing effects (9), and play a protective role in the liver (10).
CB2 receptor agonists such as caryophyllene have been shown to reduce inflammation (11), cholesterol buildup (12) and bone weakening (13).
β-caryophyllene and medicinal plants containing β-caryophyllene have demonstrated a range of other useful properties (14), including anti-inflammatory (15), numbing (16), anti-proliferative (17), liver protective (18) and anti-stress (19) activities.
Pain-killing effects of β-caryophyllene have also been observed after local application (20,21,22).
β-Caryophyllene is a known agonist for the PPARγ protein which is protective of several biological systems including gastrointestinal, inflammatory and metabolic systems (23).
Beyond generalised gastrointestinal and related organ health, β-Caryophyllene has been found to be cytoprotective and to inhibit gastro-mucosal injuries and inflammation (36,37,38).
β-Caryophyllene has also been demonstrated to encourage bone mineralisation and suppress osteoclastogenesis, making bones more resistant to breakage (39).
β-Caryophyllene also enhances wound-healing by encouraging cell-migration to the damaged site (40,41).
Key references:
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CB2 Activity (4,5)
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Anti-stress (19)
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Anti-proliferative (17)
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Anti-inflammatory (15)
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Anti-bacterial
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Numbing (16)
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Gastroprotective (30,31,32)
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Pain-reducing (9)
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Liver protective (18,27,28,29)
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Reduces gut inflammation (11,24,25,26)
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Kidney protective (33,34,35)
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Assists with wound repair (40,41)

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21 - Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J.Z., Xie, X.Q., Altmann, K.H., Karsak, M., Zimmer, A., 2008. Beta caryophyllene is a dietary cannabinoid. Proc. Natl. Acad. Sci. USA 105, 9099-9104.
Bento, A., Marcon, R., Dutra, R., Claudino, R., Cola, M., Leite, D., Calixto, J., 2011. Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARy pathway. Am. J. Pathol. 178, 1153-1166.
Horvath, B., Mukhopadhyay, P., Kechrid, M., Patel, V., Tanchian, G., Wink, D.A., Gertsch, J., Pacher, P., 2012. B-caryophylllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependant manner. Free Radic. Biol. Med. 52, 1325-1333.
22 - Katsuyama, S., Mizoguchi, H., Kuwahata, H., Komatsu, T., Nagaoka, K., Nakamura, H., & Sakurada, S. (2013). Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. European journal of pain, 17 (5), 664-675.
23 - Bento, A. F., Marcon, R., Dutra, R. C., Claudino, R. F., Cola, M., Leite, D. F. P., & Calixto, J. B. (2011). β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. The American journal of pathology, 178 (3), 1153-1166.
24 - Cho, J. Y., Chang, H. J., Lee, S. K., Kim, H. J., Hwang, J. K., & Chun, H. S. (2007). Amelioration of dextran sulfate sodium-induced colitis in mice by oral administration of β-caryophyllene, a sesquiterpene. Life sciences, 80 (10), 932-939.
25 - Bento, A. F., Marcon, R., Dutra, R. C., Claudino, R. F., Cola, M., Leite, D. F. P., & Calixto, J. B. (2011). β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. The American journal of pathology, 178 (3), 1153-1166.
26 - Cho, J. Y., Choi, E. H., Kang, J. I., Choi, C., & Chun, H. S. (2013). Supercritical fluid extract from maca alleviates colitis induced by dextran sulfate sodium in mice. Food Science and Biotechnology, 22 (3), 859-864.
27 - Chaieb, K., Hajlaoui, H., Zmantar, T., Kahla-Nakbi, A. B., Rouabhia, M., Mahdouani, K., & Bakhrouf, A. (2007). The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 21 (6), 501-506.
28 - Varga, Z. V., Matyas, C., Erdelyi, K., Cinar, R., Nieri, D., Chicca, A., ... & Hasko, G. (2018). β-Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. British journal of pharmacology, 175 (2), 320-334.
29 - Varga, Z. V., Matyas, C., Erdelyi, K., Cinar, R., Nieri, D., Chicca, A., ... & Hasko, G. (2018). β-Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. British journal of pharmacology, 175 (2), 320-334.
30 - Paiva, L. A. F., Rao, V. S. N., Gramosa, N. V., & Silveira, E. R. (1998). Gastroprotective effect of Copaifera langsdorffii oleoresin on experimental gastric ulcer models in rats. Journal of ethnopharmacology, 62 (1), 73-78.
31 - Sharma, C., M Al Kaabi, J., M Nurulain, S., N Goyal, S., Amjad Kamal, M., & Ojha, S. (2016). Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Current pharmaceutical design, 22 (21), 3237-3264.
32 - Lemos, M., Santin, J. R., Mizuno, C. S., Boeing, T., Sousa, J. P. B. D., Nanayakkara, D., ... & Andrade, S. F. D. (2015). Copaifera langsdorffii: evaluation of potential gastroprotective of extract and isolated compounds obtained from leaves. Revista Brasileira de Farmacognosia, 25 (3), 238-245.
33 - Horváth, B., Mukhopadhyay, P., Kechrid, M., Patel, V., Tanchian, G., Wink, D. A., ... & Pacher, P. (2012). β-Caryophyllene ameliorates cisplatin-inducednephrotoxicity in a cannabinoid 2 receptor-dependent manner. Free Radical Biology and Medicine, 52 (8), 1325-1333.
34 - Sharma, C., M Al Kaabi, J., M Nurulain, S., N Goyal, S., Amjad Kamal, M., & Ojha, S. (2016). Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Current pharmaceutical design, 22 (21), 3237-3264.
35 - Loizzo, M. R., Tundis, R., Menichini, F., Saab, A. M., Statti, G. A., & Menichini, F. (2008). Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Proliferation, 41 (6), 1002-1012.
36 - Tambe, Y., Tsujiuchi, H., Honda, G., Ikeshiro, Y., & Tanaka, S. (1996). Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, β-caryophyllene. Planta medica, 62 (05), 469-470.
37 - Wright, K. L., Duncan, M., & Sharkey, K. A. (2008). Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. British journal of pharmacology, 153 (2), 263-270.
38 - Boyar, K. Leaky Gut Syndrome: Cannabinoids and the Endocannabinoid System (ECS) as a therapeutic target.
39 - Yamaguchi, M., & Levy, R. M. (2016). β-Caryophyllene promotes osteoblastic mineralization, and suppresses osteoclastogenesis and adipogenesis in mouse bone marrow cultures in vitro. Experimental and therapeutic medicine, 12(6), 3602-3606.
40 - Koyama, S., Purk, A., Kaur, M., Soini, H. A., Novotny, M. V., Davis, K., & Mescher, A. (2019). Beta-caryophyllene enhances wound healing through multiple routes. PloS one, 14(12), e0216104.
41 - Koyama, S., Purk, A., Kaur, M., Soini, H. A., Novotny, M. V., Davis, K., & Mescher, A. (2019). Synergetic influence of beta-caryophyllene on wound healing. BioRxiv, 611046.