Terpinolene is found in a wide variety of plants and spices, including nutmeg, parsnips, cardamom, apples, cumin, and lilacs. The aroma profile of this terpene reflects this variety and can be described as a mix of floral, woodsy, sweet, and herbaceous. Due to its ‘fresh’ aroma, terpinolene is often used as an additive in cosmetic and household cleaning products. Several studies have investigated the effects of this terpene using essential oils (most notably tea tree oil) that are rich in terpinolene. Results suggest that this terpene may provide antioxidant[1]^,[2] and anti-bacterial[3] properties. In addition, animal models have demonstrated the sedative[4] effects of this terpene, as well as its potential to treat pain, inflammation[5], and even cancer[6].

[1] J Grassmann, S Hippeli, R Spitzenberger, E F Esltner. The monoterpene terpinolene from the oil of Pinus mugo L. in concert with alpha-tocopherol and beta-carotene effectively prevents oxidation of LDL. Phytomedicine 2005 Jun;12(6-7):416-23. doi: 10.1016/j.phymed.2003.10.005

[2] Kim HJ, Chen F, Wu C, Wang X, Chung HY, Jin Z. Evaluation of antioxidant activity of Australian tea tree (Melaleuca alternifolia) oil and its components. J Agric Food Chem. 2004 May 19;52(10):2849-54. doi: 10.1021/jf035377d. PMID: 15137824.

[3] Mazandarani, M. & Mirdeilami, Z. & Pessarakli, Mohammad. (2013). Essential oil composition and antibacterial activity of Achillea millefolium L. from different regions in North east of Iran. J. Med. Plants Res.. 7. 1063-1069.

[4] Ken Ito, Michiho Ito. The sedative effect of inhaled terpinolene in mice and its structure-activity relationships. Journal of Natural Medicines 2013 Oct;67(4):833-7. DOI: 10.1007/s11418-012-0732-1. Epub 2013 Jan 22.

[5] Macedo, E. et al. “Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation.” Brazilian Journal of Medical and Biological Research 49.7, DOI:10.1590/1414-431×20165103 (2016)

[6] Leanur Aydin, Hasan Turkez, Sener Tasdemir. Anticancer and antioxidant properties of terpinolene in rat brain cells. Arh Hig Rada Toksikol. 2013 Sep;64(3):415-24. DOI: 10.2478/10004-1254-64-2013-2365.

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. 

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.

As one of the most common terpenes present in the cannabis plant, myrcene can be found in cultivars worldwide. Often used as an additive in food manufacturing, myrcene can also be found naturally in mangos, lemongrass, and bay leaves. Various studies on animal models have shown some promising applications for this terpene, including sedation[1], muscle relaxation[2], anti-inflammation[3], and overall pain relief[4]. Analyses of essential oils high in myrcene content have also indicated the possible antioxidant[5] and anti-ulcer[6] properties of this terpene. Furthermore, research on mouse models has demonstrated the potential of this terpene to treat ischemic stroke, due to its neuro[7] and cardiac[8] protective effects.

[1] 78. Freitas JC, Presgrave OA, Fingola FF, Menezes MA, Paumgartten FJ. Effect of beta-myrcene on pentobarbital sleeping time. Braz J Med Biol Res. (1993) 26:519–23. [PubMed] [Google Scholar] [Ref list]

[2] 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.

[3] McDougall, J.J.; McKenna, M.K. Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis. Int. J. Mol. Sci. 2022, 23, 7891. https://doi.org/10.3390/ijms23147891

[4] Paula-Freire LI, Molska GR, Andersen ML, Carlini EL. Ocimum gratissimum Essential Oil and Its Isolated Compounds (Eugenol and Myrcene) Reduce Neuropathic Pain in Mice. Planta Med. 2016 Feb;82(3):211-6. doi: 10.1055/s-0035-1558165. Epub 2015 Nov 19. PMID: 26584457.

[5] Ojeda, Adriana & Van Baren, Catalina & Elechosa, Miguel & Juárez, Miguel & Moreno, Silvia. (2013). New insights into antibacterial and antioxidant activities of rosemary essential oils and their main components. Food Control. 31. 189–195. 10.1016/j.foodcont.2012.09.022.

[6] Bonamin F, Moraes TM, Dos Santos RC, Kushima H, Faria FM, Silva MA, Junior IV, Nogueira L, Bauab TM, Souza Brito AR, da Rocha LR, Hiruma-Lima CA. The effect of a minor constituent of essential oil from Citrus aurantium: the role of β-myrcene in preventing peptic ulcer disease. Chem Biol Interact. 2014 Apr 5;212:11-9. doi: 10.1016/j.cbi.2014.01.009. Epub 2014 Jan 27. PMID: 24480520.

[7] Ciftci O, Oztanir MN, Cetin A. Neuroprotective effects of β-myrcene following global cerebral ischemia/reperfusion-mediated oxidative and neuronal damage in a C57BL/J6 mouse. Neurochem Res. 2014 Sep;39(9):1717-23. doi: 10.1007/s11064-014-1365-4. Epub 2014 Jun 28. PMID: 24972849.

[8] Burcu GB, Osman C, Aslı C, Namik OM, Neşe BT. The protective cardiac effects of Β-myrcene after global cerebral ıschemia/reperfusion in C57BL/J6 mouse. Acta Cir Bras. 2016 Jul;31(7):456-62. doi: 10.1590/S0102-865020160070000005. PMID: 27487280.

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.