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Caryophyllene is the terpene that gives spices like cloves and black pepper their characteristic taste/smell but it can also be found in many cannabis strains. Preclinical research indicates that caryophyllene can be therapeutic in many diseases. However, it must be noted that caryophyllene is only present in trace amounts (0.01-1%) in cannabis flowers which may not be enough to exert therapeutic effects on its own. Still caryophyllene may prove to be of therapeutic value at higher concentrations (extracts) or in combination with other cannabinoids and terpenes found in cannabis.

Chemical Name


Wikipedia Entry


Literature Discussion

Caryophyllene was found to be therapeutic in the following diseases:

  • Alcoholism (Al Mansouri et al., 2014)
  • Analgesic (Fiorenzani et al., 2014)(Klauke et al., 2014)
  • Anti-bacterial, anti-fungal (Selestino Neta et al., 2017)
  • Anti-convulsant (de Oliveira et al., 2016)
  • Anti-genotoxic/anti-oxidant (Alvarez-González et al., 2014)
  • Anti-inflammatory in alcoholic steatohepatitis (Varga et al., 2017)
  • Anti-inflammatory in Diabetes model (Basha and Sankaranarayanan, 2014, 2016)
  • Anti-inflammatory, anti-catabolic, pro-anabolic in osteoarthritis model (Rufino et al., 2015)
  • Anti-lymphoma, anti-neuroblastoma (Sain et al., 2014)
  • Anti-mutagenic (Di Giacomo et al., 2016)
  • Anti-neuroinflammatory in Alzheimer’s model (Hu et al., 2017)(Cheng et al., 2014)
  • Anti-neuroinflammatory in hypoxia Stroke model (Guo et al., 2014)
  • Anti-neuroinflammatory in Parkinson’s model (Ojha et al., 2016)
  • Anti-neutrophil chemotaxis (Andrade-Silva et al., 2016)
  • Anti-nociceptive (de Oliveira Júnior et al., 2017)(Katsuyama et al., 2013)
  • Anxiolytic (Galdino et al., 2012)(Bahi et al., 2014)
  • Atherosclerosis  (Zhang et al., 2017b)(Baldissera et al., 2017c)
  • cancer and analgesic (Fidyt et al., 2016)
  • Cerebral ischemia (Choi et al., 2013)(Chang et al., 2013)(Lou et al., 2016)(Zhang et al., 2017a)(Tian et al., 2016)
  • Chemosensitization to doxorubicin in cancer cell lines (DI Giacomo et al., 2017)(Ambrož et al., 2017)(Hanušová et al., 2017)(Ambrož et al., 2015)
  • Colorectal cancer and anti-bacterial (Dahham et al., 2015)
  • Endometriosis (Abbas et al., 2013)
  • Immunosuppressive in hypercholesterolemia (Baldissera et al., 2017a, 2017a, 2017b)
  • Increased liver fatty acid uptake and oxidation (Wu et al., 2014)
  • Insulin regulation (Suijun et al., 2014)
  • Liver fibrosis (Calleja et al., 2013)
  • Longevity in C. elegans (Pant et al., 2014)
  • Melanoma (Jung et al., 2015)
  • Mosquito larvicidal (Govindarajan et al., 2016)
  • Motor paralysis and neuroinflammation in MS model (Alberti et al., 2017)(Fontes et al., 2017)
  • Neuritogenesis in PC12 cells (Santos et al., 2017)
  • Neuroinflammation in Parkinson’s model (Javed et al., 2016)
  • Neuroprotective in seizures (Liu et al., 2015)
  • Non Alcoholic Fatty Liver Disease (Kamikubo et al., 2016)
  • Osteoporosis (Shan et al., 2017)(Yamaguchi and Levy, 2016)
  • Oviposition deterrent for Aedes aegypti (da Silva et al., 2015)
  • Vascular dementia (Lou et al., 2017)


Abbas, M.A., Taha, M.O., Zihlif, M.A., and Disi, A.M. (2013). β-Caryophyllene causes regression of endometrial implants in a rat model of endometriosis without affecting fertility. Eur. J. Pharmacol. 702, 12–19.

Al Mansouri, S., Ojha, S., Al Maamari, E., Al Ameri, M., Nurulain, S.M., and Bahi, A. (2014). The Cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice. Pharmacol. Biochem. Behav. 124, 260–268.

Alberti, T.B., Barbosa, W.L.R., Vieira, J.L.F., Raposo, N.R.B., and Dutra, R.C. (2017). (-)-β-Caryophyllene, a CB2 Receptor-Selective PhytoCannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of multiple sclerosis. Int. J. Mol. Sci. 18.

Alvarez-González, I., Madrigal-Bujaidar, E., and Castro-García, S. (2014). Antigenotoxic capacity of beta-caryophyllene in mouse, and evaluation of its antioxidant and GST induction activities. J. Toxicol. Sci. 39, 849–859.

Ambrož, M., Boušová, I., Skarka, A., Hanušová, V., Králová, V., Matoušková, P., Szotáková, B., and Skálová, L. (2015). The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in cancer Cells. Mol. Basel Switz. 20, 15343–15358.

Ambrož, M., Matoušková, P., Skarka, A., Zajdlová, M., Žáková, K., and Skálová, L. (2017). The Effects of Selected Sesquiterpenes from Myrica rubra Essential Oil on the Efficacy of Doxorubicin in Sensitive and Resistant cancer Cell Lines. Mol. Basel Switz. 22.

Andrade-Silva, M., Correa, L.B., Candéa, A.L.P., Cavalher-Machado, S.C., Barbosa, H.S., Rosas, E.C., and Henriques, M.G. (2016). The Cannabinoid 2 receptor agonist β-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration. Inflamm. Res. Off. J. Eur. Histamine Res. Soc. Al.

Bahi, A., Al Mansouri, S., Al Memari, E., Al Ameri, M., Nurulain, S.M., and Ojha, S. (2014). β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol. Behav. 135, 119–124.

Baldissera, M.D., Souza, C.F., Doleski, P.H., Leal, D.B.R., Stefani, L.M., Boligon, A.A., and Monteiro, S.G. (2017a). Enzymes that hydrolyze adenine nucleotides in a model of hypercholesterolemia induced by Triton WR-1339: protective effects of β-caryophyllene. Mol. Cell. Biochem.

Baldissera, M.D., Souza, C.F., Grando, T.H., Doleski, P.H., Boligon, A.A., Stefani, L.M., and Monteiro, S.G. (2017b). Hypolipidemic effect of β-caryophyllene to treat hyperlipidemic rats. Naunyn. Schmiedebergs Arch. Pharmacol. 390, 215–223.

Baldissera, M.D., Souza, C.F., Grando, T.H., Stefani, L.M., and Monteiro, S.G. (2017c). β-caryophyllene reduces atherogenic index and coronary risk index in hypercholesterolemic rats: The involvement of cardiac oxidative damage. Chem. Biol. Interact. 270, 9–14.

Basha, R.H., and Sankaranarayanan, C. (2014). β-Caryophyllene, a natural sesquiterpene, modulates carbohydrate metabolism in streptozotocin-induced diabetic rats. Acta Histochem. 116, 1469–1479.

Basha, R.H., and Sankaranarayanan, C. (2016). β-Caryophyllene, a natural sesquiterpene lactone attenuates hyperglycemia mediated oxidative and inflammatory stress in experimental diabetic rats. Chem. Biol. Interact. 245, 50–58.

Calleja, M.A., Vieites, J.M., Montero-Meléndez, T., Montero-Meterdez, T., Torres, M.I., Faus, M.J., Gil, A., and Suárez, A. (2013). The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br. J. Nutr. 109, 394–401.

Chang, H.-J., Kim, J.-M., Lee, J.-C., Kim, W.-K., and Chun, H.S. (2013). Protective effect of β-caryophyllene, a natural bicyclic sesquiterpene, against cerebral ischemic injury. J. Med. Food 16, 471–480.

Cheng, Y., Dong, Z., and Liu, S. (2014). β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 Mice through CB2 receptor activation and the PPARγ pathway. Pharmacology 94, 1–12.

Choi, I.-Y., Ju, C., Anthony Jalin, A.M.A., Lee, D.I., Prather, P.L., and Kim, W.-K. (2013). Activation of Cannabinoid CB2 receptor-mediated AMPK/CREB pathway reduces cerebral ischemic injury. Am. J. Pathol. 182, 928–939.

Dahham, S.S., Tabana, Y.M., Iqbal, M.A., Ahamed, M.B.K., Ezzat, M.O., Majid, A.S.A., and Majid, A.M.S.A. (2015). The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene β-Caryophyllene from the Essential Oil of Aquilaria crassna. Mol. Basel Switz. 20, 11808–11829.

Di Giacomo, S., Mazzanti, G., and Di Sotto, A. (2016). Mutagenicity of cigarette butt waste in the bacterial reverse mutation assay: The protective effects of β-caryophyllene and β-caryophyllene oxide. Environ. Toxicol. 31, 1319–1328.

DI Giacomo, S., DI Sotto, A., Mazzanti, G., and Wink, M. (2017). Chemosensitizing Properties of β-Caryophyllene and β-Caryophyllene Oxide in Combination with Doxorubicin in Human cancer Cells. Anticancer Res. 37, 1191–1196.

Fidyt, K., Fiedorowicz, A., Strządała, L., and Szumny, A. (2016). β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. cancer Med. 5, 3007–3017.

Fiorenzani, P., Lamponi, S., Magnani, A., Ceccarelli, I., and Aloisi, A.M. (2014). In vitro and in vivo characterization of the new analgesic combination Beta-caryophyllene and docosahexaenoic Acid. Evid.-Based Complement. Altern. Med. ECAM 2014, 596312.

Fontes, L.B.A., Dias, D.D.S., Aarestrup, B.J.V., Aarestrup, F.M., Da Silva Filho, A.A., and Corrêa, J.O. do A. (2017). β-Caryophyllene ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice. Biomed. Pharmacother. Biomedecine Pharmacother. 91, 257–264.

Galdino, P.M., Nascimento, M.V.M., Florentino, I.F., Lino, R.C., Fajemiroye, J.O., Chaibub, B.A., de Paula, J.R., de Lima, T.C.M., and Costa, E.A. (2012). The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, β-caryophyllene, in male mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 38, 276–284.

Govindarajan, M., Rajeswary, M., Hoti, S.L., Bhattacharyya, A., and Benelli, G. (2016). Eugenol, α-pinene and β-caryophyllene from Plectranthus barbatus essential oil as eco-friendly larvicides against Malaria, dengue and Japanese encephalitis mosquito vectors. Parasitol. Res. 115, 807–815.

Guo, K., Mou, X., Huang, J., Xiong, N., and Li, H. (2014). Trans-caryophyllene suppresses hypoxia-induced neuroinflammatory responses by inhibiting NF-κB activation in microglia. J. Mol. Neurosci. MN 54, 41–48.

Hanušová, V., Caltová, K., Svobodová, H., Ambrož, M., Skarka, A., Murínová, N., Králová, V., Tomšík, P., and Skálová, L. (2017). The effects of β-caryophyllene oxide and trans-nerolidol on the efficacy of doxorubicin in Breast Cancer cells and breast tumor-bearing mice. Biomed. Pharmacother. Biomedecine Pharmacother. 95, 828–836.

Hu, Y., Zeng, Z., Wang, B., and Guo, S. (2017). Trans-caryophyllene inhibits amyloid β (Aβ) oligomer-induced neuroinflammation in BV-2 microglial cells. Int. Immunopharmacol. 51, 91–98.

Javed, H., Azimullah, S., Haque, M.E., and Ojha, S.K. (2016). Cannabinoid Type 2 (CB2) Receptors Activation Protects against Oxidative Stress and Neuroinflammation Associated Dopaminergic Neurodegeneration in Rotenone Model of Parkinson’s Disease. Front. Neurosci. 10, 321.

Jung, J.I., Kim, E.J., Kwon, G.T., Jung, Y.J., Park, T., Kim, Y., Yu, R., Choi, M.-S., Chun, H.S., Kwon, S.-H., et al. (2015). β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice. Carcinogenesis 36, 1028–1039.

Kamikubo, R., Kai, K., Tsuji-Naito, K., and Akagawa, M. (2016). β-Caryophyllene attenuates palmitate-induced lipid accumulation through AMPK signaling by activating CB2 receptor in human HepG2 hepatocytes. Mol. Nutr. Food Res.

Katsuyama, S., Mizoguchi, H., Kuwahata, H., Komatsu, T., Nagaoka, K., Nakamura, H., Bagetta, G., Sakurada, T., and Sakurada, S. (2013). Involvement of peripheral Cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. Eur. J. pain Lond. Engl. 17, 664–675.

Klauke, A.-L., Racz, I., Pradier, B., Markert, A., Zimmer, A.M., Gertsch, J., and Zimmer, A. (2014). The Cannabinoid CB₂ receptor-selective phytoCannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol. 24, 608–620.

Liu, H., Song, Z., Liao, D., Zhang, T., Liu, F., Zhuang, K., Luo, K., and Yang, L. (2015). Neuroprotective effects of trans-caryophyllene against kainic acid induced seizure activity and oxidative stress in mice. Neurochem. Res. 40, 118–123.

Lou, J., Cao, G., Li, R., Liu, J., Dong, Z., and Xu, L. (2016). β-Caryophyllene Attenuates Focal Cerebral Ischemia-Reperfusion Injury by Nrf2/HO-1 Pathway in Rats. Neurochem. Res. 41, 1291–1304.

Lou, J., Teng, Z., Zhang, L., Yang, J., Ma, L., Wang, F., Tian, X., An, R., Yang, M., Zhang, Q., et al. (2017). β-Caryophyllene/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Improves Cognitive Deficits in Rats with Vascular Dementia through the Cannabinoid Receptor Type 2 -Mediated Pathway. Front. Pharmacol. 8, 2.

Ojha, S., Javed, H., Azimullah, S., and Haque, M.E. (2016). β-Caryophyllene, a phytoCannabinoid attenuates oxidative stress, neuroinflammation, glial activation, and salvages dopaminergic neurons in a rat model of Parkinson disease. Mol. Cell. Biochem. 418, 59–70.

de Oliveira, C.C., de Oliveira, C.V., Grigoletto, J., Ribeiro, L.R., Funck, V.R., Grauncke, A.C.B., de Souza, T.L., Souto, N.S., Furian, A.F., Menezes, I.R.A., et al. (2016). Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures. epilepsy Behav. EB 56, 26–31.

de Oliveira Júnior, R.G., Ferraz, C.A.A., Silva, J.C., de Oliveira, A.P., Diniz, T.C., E Silva, M.G., Quintans Júnior, L.J., de Souza, A.V.V., Dos Santos, U.S., Turatti, I.C.C., et al. (2017). Antinociceptive Effect of the Essential Oil from Croton conduplicatus Kunth (Euphorbiaceae). Mol. Basel Switz. 22.

Pant, A., Saikia, S.K., Shukla, V., Asthana, J., Akhoon, B.A., and Pandey, R. (2014). Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans. Exp. Gerontol. 57, 81–95.

Rufino, A.T., Ribeiro, M., Sousa, C., Judas, F., Salgueiro, L., Cavaleiro, C., and Mendes, A.F. (2015). Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. Eur. J. Pharmacol. 750, 141–150.

Sain, S., Naoghare, P.K., Devi, S.S., Daiwile, A., Krishnamurthi, K., Arrigo, P., and Chakrabarti, T. (2014). Beta caryophyllene and caryophyllene oxide, isolated from Aegle marmelos, as the potent anti-inflammatory agents against lymphoma and neuroblastoma cells. Anti-Inflamm. Anti-Allergy Agents Med. Chem. 13, 45–55.

Santos, N.A.G., Martins, N.M., Sisti, F.M., Fernandes, L.S., Ferreira, R.S., de Freitas, O., and Santos, A.C. (2017). The Cannabinoid beta-caryophyllene (BCP) induces neuritogenesis in PC12 cells by a Cannabinoid-receptor-independent mechanism. Chem. Biol. Interact. 261, 86–95.

Selestino Neta, M.C., Vittorazzi, C., Guimarães, A.C., Martins, J.D.L., Fronza, M., Endringer, D.C., and Scherer, R. (2017). Effects of β-caryophyllene and Murraya paniculata essential oil in the murine hepatoma cells and in the bacteria and fungi 24-h time-kill curve studies. Pharm. Biol. 55, 190–197.

Shan, J., Chen, L., and Lu, K. (2017). Protective effects of trans-caryophyllene on maintaining osteoblast function. IUBMB Life 69, 22–29.

da Silva, R.C.S., Milet-Pinheiro, P., Bezerra da Silva, P.C., da Silva, A.G., da Silva, M.V., Navarro, D.M. do A.F., and da Silva, N.H. (2015). (E)-Caryophyllene and α-Humulene: Aedes aegypti Oviposition Deterrents Elucidated by Gas Chromatography-Electrophysiological Assay of Commiphora leptophloeos Leaf Oil. PloS One 10, e0144586.

Suijun, W., Zhen, Y., Ying, G., and Yanfang, W. (2014). A role for trans-caryophyllene in the moderation of insulin secretion. Biochem. Biophys. Res. Commun. 444, 451–454.

Tian, X., Peng, J., Zhong, J., Yang, M., Pang, J., Lou, J., Li, M., An, R., Zhang, Q., Xu, L., et al. (2016). β-Caryophyllene protects in vitro neurovascular unit against oxygen-glucose deprivation and re-oxygenation-induced injury. J. Neurochem. 139, 757–768.

Varga, Z.V., Matyas, C., Erdelyi, K., Cinar, R., Nieri, D., Chicca, A., Nemeth, B.T., Paloczi, J., Lajtos, T., Corey, L., et al. (2017). Beta-caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. Br. J. Pharmacol.

Wu, C., Jia, Y., Lee, J.H., Jun, H., Lee, H.-S., Hwang, K.-Y., and Lee, S.-J. (2014). trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α. Bioorg. Med. Chem. Lett. 24, 3168–3174.

Yamaguchi, M., and Levy, R.M. (2016). β-Caryophyllene promotes osteoblastic mineralization, and suppresses osteoclastogenesis and adipogenesis in mouse bone marrow cultures in vitro. Exp. Ther. Med. 12, 3602–3606.

Zhang, Q., An, R., Tian, X., Yang, M., Li, M., Lou, J., Xu, L., and Dong, Z. (2017a). β-Caryophyllene Pretreatment Alleviates Focal Cerebral Ischemia-Reperfusion Injury by Activating PI3K/Akt Signaling Pathway. Neurochem. Res. 42, 1459–1469.

Zhang, Z., Yang, C., Dai, X., Ao, Y., and Li, Y. (2017b). Inhibitory effect of trans-caryophyllene (TC) on leukocyte-endothelial attachment. Toxicol. Appl. Pharmacol.