Limonene is a terpene commonly found in the peels of citrus fruits like lemons, limes, and oranges, as well as in cannabis flowers, spruce trees, and other plants. It is commonly used in foods, beverages, fragrances, cleaners, and cosmetics due to its pungent sweet citrusy aroma. It has been identified in peer-reviewed research as inducing anti-stress[1], anti-anxiety,[2] anti-depressant,[3] and anti-inflammatory (in the airways)[4]^,[5] effects in mouse models. It has also been identified as having antioxidant[6] and anti-cancer[7] properties in human trials and has been identified as a potential muscle relaxant[8] and relaxation aid[9]. When combined, these properties may implicate limonene as being helpful in the treatment of those suffering from related symptoms due to Qualifying Conditions.

[1] Komiya, M., Takeuchi, T. & Harada, E. “Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice.” Behavioural Brain Research 172, 240–249, DOI:10.1016/j.bbr.2006.05.006 (2006)

[2] Song Y, Seo S, Lamichhane S, Seo J, Hong JT, Cha HJ, Yun J. Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum. Phytomedicine. 2021 Mar;83:153474. doi: 10.1016/j.phymed.2021.153474. Epub 2021 Jan 21. PMID: 33548867.

[3] Lorigooini Z, Boroujeni SN, Sayyadi-Shahraki M, Rahimi-Madiseh M, Bijad E, Amini-Khoei H. Limonene through Attenuation of Neuroinflammation and Nitrite Level Exerts Antidepressant-Like Effect on Mouse Model of Maternal Separation Stress. Behav Neurol. 2021 Jan 29;2021:8817309. doi: 10.1155/2021/8817309. PMID: 33564342; PMCID: PMC7864762.

[4] Ryoji Hirota, Hiroyuki Nakamura, Sabah Asif Bhatti, Nlandu Roger Ngatu, Basilua Andre Muzembo, Narongpon Dumavibhat, Masamitsu Eitoku, Masayoshi Sawamura & Narufumi Suganuma (2012)“Limonene inhalation reduces allergic airway inflammation in Dermatophagoides farinaetreated mice.”Inhalation Toxicology 24:6, 373-381, DOI:10.3109/08958378.2012.675528 (2012)

[5] Patel, M., Narke, D., Kurade, M. et al. Limonene-induced activation of A2A adenosine receptors reduces airway inflammation and reactivity in a mouse model of asthma. Purinergic Signalling 16, 415–426 (2020). https://doi.org/10.1007/s11302-020-09697-z

[6] Crowell, P. L. & Gould, M. N. “Chemoprevention and Therapy of Cancer by d-Limonene.” Critical Reviews™ in Oncogenesis 5,1–22, DOI:10.1615/CritRevOncog.v5.i1.10 (1994).

[7] Chebet JJ, Ehiri JE, McClelland DJ, Taren D, Hakim IA. Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis. BMC Cancer. 2021 Aug 6;21(1):902. doi: 10.1186/s12885-021-08639-1. PMID: 34362338; PMCID: PMC8349000.

[8] do Vale TG, Furtado EC, Santos JG Jr, Viana GS. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown. Phytomedicine. 2002 Dec;9(8):709-14. doi: 10.1078/094471102321621304. PMID: 12587690.

[9] Joung, D., et al. “Physiological and Psychological Effects of Olfactory Stimulation with D-Limonene.” Advances in Horticultural Science, vol. 28, no. 2, 2014, pp. 90–94. JSTOR, http://www.jstor.org/stable/24586803. Accessed 1 Nov. 2022. 

Linalool is a naturally occurring terpene found most commonly in lavender and basil. Due to its sweet, floral aroma, it is often used as an additive in several household products like soap and perfume. Several animal studies have implicated this terpene in the potential treatment of various conditions, including depression[1], anxiety[2], stress[3], inflammation[4]^,[5], and pain[6]. In addition, animal models have demonstrated that linalool may possess anti-convulsant[7], anti-asthma[8], and sedative[9] properties. Human trials have even linked the usage of linalool-rich essential oils to menstrual pain relief[10]. Further research is warranted to fully investigate the health benefits of this terpene.

[1] Guzmán-Gutiérrez SL, Bonilla-Jaime H, Gómez-Cansino R, Reyes-Chilpa R. Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sci. 2015 May 1;128:24-9. doi: 10.1016/j.lfs.2015.02.021. Epub 2015 Mar 11. PMID: 25771248.

[2] Linck VM, da Silva AL, Figueiró M, Caramão EB, Moreno PR, Elisabetsky E. Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice. Phytomedicine. 2010 Jul;17(8-9):679-83. doi: 10.1016/j.phymed.2009.10.002. Epub 2009 Dec 3. PMID: 19962290.

[3] Nakamura A, Fujiwara S, Matsumoto I, Abe K. Stress repression in restrained rats by (R)-(-)-linalool inhalation and gene expression profiling of their whole blood cells. Journal of Agricultural and Food Chemistry. 2009 Jun;57(12):5480-5485. DOI: 10.1021/jf900420g. PMID: 19456160.

[4] Huo M, Cui X, Xue J, Chi G, Gao R, Deng X, Guan S, Wei J, Soromou LW, Feng H, Wang D. Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model. J Surg Res. 2013 Mar;180(1):e47-54. doi: 10.1016/j.jss.2012.10.050. Epub 2012 Dec 4. PMID: 23228323.

[5] Ma J, Xu H, Wu J, Qu C, Sun F, Xu S. Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation. Int Immunopharmacol. 2015 Dec;29(2):708-713. doi: 10.1016/j.intimp.2015.09.005. Epub 2015 Oct 1. PMID: 26432179.

[6] Peana AT, D’Aquila PS, Chessa ML, Moretti MD, Serra G, Pippia P. (-)-Linalool produces antinociception in two experimental models of pain. Eur J Pharmacol. 2003 Jan 26;460(1):37-41. doi: 10.1016/s0014-2999(02)02856-x. PMID: 12535857.

[7] Elisabetsky E, Brum LF, Souza DO. Anticonvulsant properties of linalool in glutamate-related seizure models. Phytomedicine. 1999 May;6(2):107-13. doi: 10.1016/s0944-7113(99)80044-0. PMID: 10374249.

[8] Kim MG, Kim SM, Min JH, Kwon OK, Park MH, Park JW, Ahn HI, Hwang JY, Oh SR, Lee JW, Ahn KS. Anti-inflammatory effects of linalool on ovalbumin-induced pulmonary inflammation. Int Immunopharmacol. 2019 Sep;74:105706. doi: 10.1016/j.intimp.2019.105706. Epub 2019 Jun 26. PMID: 31254955.

[9] Linck VM, da Silva AL, Figueiró M, Piato AL, Herrmann AP, Dupont Birck F, Caramão EB, Nunes DS, Moreno PR, Elisabetsky E. Inhaled linalool-induced sedation in mice. Phytomedicine. 2009 Apr;16(4):303-7. doi: 10.1016/j.phymed.2008.08.001. Epub 2008 Sep 27. PMID: 18824339.

[10] Ou MC, Hsu TF, Lai AC, Lin YT, Lin CC. Pain relief assessment by aromatic essential oil massage on outpatients with primary dysmenorrhea: a randomized, double-blind clinical trial. J Obstet Gynaecol Res. 2012 May;38(5):817-22. doi: 10.1111/j.1447-0756.2011.01802.x. Epub 2012 Mar 22. PMID: 22435409.

Caryophyllene (also known as β-Caryophyllene or BCP) is a terpene found in several common herbs and spices like cloves, black pepper, cinnamon, basil, and oregano. In cannabis, caryophyllene often contributes to a peppery, earthy flavor profile. Animal models have demonstrated a possible interaction of caryophyllene with the endocannabinoid system[1] as well as pain relief via CB2 activation[2]. Other animal studies have identified this terpene as a potential treatment for several conditions, including anxiety[3], depression[4], inflammation[5], and overall pain relief[6]. In addition, in vitro studies have evaluated the antioxidant[7] and sedative[8] effects of this terpene. Finally—and perhaps most noteworthy—both in vitro[9] and animal[10] studies have implicated caryophyllene as a potential treatment for cancer, with human trials demonstrating its potential to treat nausea[11].

[1] Poddighe L, Carta G, Serra MP, Melis T, Boi M, Lisai S, Murru E, Muredda L, Collu M, Banni S, Quartu M. Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion. Lipids Health Dis. 2018 Feb 5;17(1):23. doi: 10.1186/s12944-018-0661-4. PMID: 29402275; PMCID: PMC5799897.

[2] Klauke AL, Racz I, Pradier B, Markert A, Zimmer AM, Gertsch J, Zimmer A. The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol. 2014 Apr;24(4):608-20. doi: 10.1016/j.euroneuro.2013.10.008. Epub 2013 Oct 22. PMID: 24210682.

[3] Bahi A, Al Mansouri S, Al Memari E, Al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol Behav. 2014 Aug;135:119-24. doi: 10.1016/j.physbeh.2014.06.003. Epub 2014 Jun 13. PMID: 24930711.

[4] Hwang ES, Kim HB, Lee S, Kim MJ, Kim KJ, Han G, Han SY, Lee EA, Yoon JH, Kim DO, Maeng S, Park JH. Antidepressant-like effects of β-caryophyllene on restraint plus stress-induced depression. Behav Brain Res. 2020 Feb 17;380:112439. doi: 10.1016/j.bbr.2019.112439. Epub 2019 Dec 17. PMID: 31862467.

[5] Gushiken LFS, Beserra FP, Hussni MF, Gonzaga MT, Ribeiro VP, de Souza PF, Campos JCL, Massaro TNC, Hussni CA, Takahira RK, Marcato PD, Bastos JK, Pellizzon CH. Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model. Oxid Med Cell Longev. 2022 Feb 3;2022:9004014. doi: 10.1155/2022/9004014. PMID: 35154574; PMCID: PMC8831077.

[6] Paula-Freire LI, Andersen ML, Gama VS, Molska GR, Carlini EL. The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice. Phytomedicine. 2014 Feb 15;21(3):356-62. doi: 10.1016/j.phymed.2013.08.006. Epub 2013 Sep 20. PMID: 24055516.

[7] Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK. Volatile constituents from Cinnamomum zeylanicum fruit stalks and their antioxidant activities. J Agric Food Chem. 2003 Jul 16;51(15):4344-8. doi: 10.1021/jf034169i. PMID: 12848508.

[8] Rabbani M, Sajjadi SE, Vaezi A. Evaluation of anxiolytic and sedative effect of essential oil and hydroalcoholic extract of Ocimum basilicum L. and chemical composition of its essential oil. Res Pharm Sci. 2015 Nov-Dec;10(6):535-43. PMID: 26779273; PMCID: PMC4698864.

[9] Mannino F, Pallio G, Corsaro R, Minutoli L, Altavilla D, Vermiglio G, Allegra A, Eid AH, Bitto A, Squadrito F, Irrera N. Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells. Cancers (Basel). 2021 Nov 16;13(22):5741. doi: 10.3390/cancers13225741. PMID: 34830893; PMCID: PMC8616110.

[10] Dahham SS, Tabana Y, Asif M, Ahmed M, Babu D, Hassan LE, Ahamed MBK, Sandai D, Barakat K, Siraki A, Majid AMSA. β-Caryophyllene Induces Apoptosis and Inhibits Angiogenesis in Colorectal Cancer Models. Int J Mol Sci. 2021 Sep 29;22(19):10550. doi: 10.3390/ijms221910550. PMID: 34638895; PMCID: PMC8508804.

[11] Shim, Hyun & Song, Dong & Shin, Cheol & Yoon, Hyuk & Park, Young & Kim, Nayoung & Lee, Dong. (2019). Inhibitory Effects of β-caryophyllene on Helicobacter pylori Infection: A Randomized Double-blind, Placebo-controlled Study. The Korean Journal of Gastroenterology. 74. 199. 10.4166/kjg.2019.74.4.199.

Proven to be useful in defense against pests, ocimene can be found in several plants like basil, parsley, tarragon, and orchids. Like many other terpenes, ocimene is often used commercially for its sweet, floral, and herbaceous aroma. Although research is relatively limited, studies utilizing essential oils rich in ocimene isomers have shown promising results for various conditions. For example, one study[1] demonstrated the potential anti-inflammatory and antioxidant properties of this terpene. Another study[2] showed promising results for the use of ocimene to treat hypertension and diabetes. Several other studies have exhibited other useful properties of this terpene, including possible anti-bacterial[3], anti-fungal[4], anticonvulsant[5], and anti-tumor[6] applications.

[1] Karimian P, Kavoosi G, Amirghofran Z. Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages. Asian Pac J Trop Biomed. 2014 Mar;4(3):219-27. doi: 10.1016/S2221-1691(14)60235-5. PMID: 25182441; PMCID: PMC3868793.

[2] Oboh G, Ademosun AO, Odubanjo OV, Akinbola IA. Antioxidative properties and inhibition of key enzymes relevant to type-2 diabetes and hypertension by essential oils from black pepper. Adv Pharmacol Sci. 2013;2013:926047. doi: 10.1155/2013/926047. Epub 2013 Nov 21. PMID: 24348547; PMCID: PMC3856121.

[3] Mohadjerani M, Hosseinzadeh R, Hosseini M. Chemical composition and antibacterial properties of essential oil and fatty acids of different parts of Ligularia persica Boiss. Avicenna J Phytomed. 2016 May-Jun;6(3):357-65. PMID: 27462560; PMCID: PMC4930544.

[4] Ali NA, Sharopov FS, Al-Kaf AG, Hill GM, Arnold N, Al-Sokari SS, Setzer WN, Wessjohann L. Composition of essential oil from Tagetes minuta and its cytotoxic, antioxidant and antimicrobial activities. Nat Prod Commun. 2014 Feb;9(2):265-8. PMID: 24689306.

[5] Sayyah M, Nadjafnia L, Kamalinejad M. Anticonvulsant activity and chemical composition of Artemisia dracunculus L. essential oil. J Ethnopharmacol. 2004 Oct;94(2-3):283-7. doi: 10.1016/j.jep.2004.05.021. PMID: 15325732.

[6] Bomfim LM, Menezes LR, Rodrigues AC, Dias RB, Rocha CA, Soares MB, Neto AF, Nascimento MP, Campos AF, Silva LC, Costa EV, Bezerra DP. Antitumour Activity of the Microencapsulation of Annona vepretorum Essential Oil. Basic Clin Pharmacol Toxicol. 2016 Mar;118(3):208-13. doi: 10.1111/bcpt.12488. Epub 2015 Oct 6. PMID: 26348780.

With several common isomers, terpineol can be found naturally in many plants, including marjoram, lilacs, tea tree, and eucalyptus. This terpene usually conveys a sweet, herbal, and floral scent, which can explain why it is so commonly used in the cosmetic industry. Because terpineol is so abundant in nature, there has already been a decent number of studies conducted exploring the terpene’s various properties. Animal models have demonstrated the possible anticonvulsant[1], antinociceptive[2], anti-inflammatory[3], and gastroprotective[4] properties of terpineol. In addition, various in vitro studies have shown the antibacterial[5], antifungal[6], antioxidant[7], anti-cancer[8] and antiviral[9] potential of this terpene.

[1] Damião Pergentino de Sousa, Lucindo Quintans Jr. & Reinaldo Nóbrega de Almeida (2007) Evolution of the Anticonvulsant Activity of α-Terpineol, Pharmaceutical Biology, 45:1, 69-70, DOI: 10.1080/13880200601028388

[2] Quintans-Júnior LJ, Oliveira MG, Santana MF, Santana MT, Guimarães AG, Siqueira JS, De Sousa DP, Almeida RN. α-Terpineol reduces nociceptive behavior in mice. Pharm Biol. 2011 Jun;49(6):583-6. doi: 10.3109/13880209.2010.529616. Epub 2011 Mar 8. PMID: 21385090.

[3] de Oliveira MG, Marques RB, de Santana MF, Santos AB, Brito FA, Barreto EO, De Sousa DP, Almeida FR, Badauê-Passos D Jr, Antoniolli AR, Quintans-Júnior LJ. α-terpineol reduces mechanical hypernociception and inflammatory response. Basic Clin Pharmacol Toxicol. 2012 Aug;111(2):120-5. doi: 10.1111/j.1742-7843.2012.00875.x. Epub 2012 Apr 11. PMID: 22380944.

[4] Souza R, Cardoso M, Menezes C, Silva J, De Sousa D, Batista J. Gastroprotective activity of α-terpineol in two experimental models of gastric ulcer in rats. Daru. 2011;19(4):277-81. PMID: 22615669; PMCID: PMC3304384.

[5] Li L, Shi C, Yin Z, Jia R, Peng L, Kang S, Li Z. Antibacterial activity of α-terpineol may induce morphostructural alterations in Escherichia coli. Braz J Microbiol. 2015 Mar 4;45(4):1409-13. doi: 10.1590/s1517-83822014000400035. PMID: 25763048; PMCID: PMC4323317.

[6] An, Peipei & Yang, Xingbin & Yu, Jia & Qi, Jianrui & Ren, Xueyan & Kong, Qingjun. (2018). α-terpineol and terpene-4-ol, the critical components of tea tree oil, exert antifungal activities in vitro and in vivo against Aspergillus niger in grapes by inducing morphous damage and metabolic changes of fungus. Food Control. 98. 10.1016/j.foodcont.2018.11.013.

[7] Bicas JL, Neri-Numa IA, Ruiz AL, De Carvalho JE, Pastore GM. Evaluation of the antioxidant and antiproliferative potential of bioflavors. Food Chem Toxicol. 2011 Jul;49(7):1610-5. doi: 10.1016/j.fct.2011.04.012. Epub 2011 Apr 19. PMID: 21540069.

[8] Hassan SB, Gali-Muhtasib H, Göransson H, Larsson R. Alpha terpineol: a potential anticancer agent which acts through suppressing NF-kappaB signalling. Anticancer Res. 2010 Jun;30(6):1911-9. PMID: 20651334.

[9] An, Peipei & Yang, Xingbin & Yu, Jia & Qi, Jianrui & Ren, Xueyan & Kong, Qingjun. (2018). α-terpineol and terpene-4-ol, the critical components of tea tree oil, exert antifungal activities in vitro and in vivo against Aspergillus niger in grapes by inducing morphous damage and metabolic changes of fungus. Food Control. 98. 10.1016/j.foodcont.2018.11.013.