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.

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. 

As one of the rarer terpenes in cannabis, there are not many cultivars that test high in guaiol. It can be found most abundantly in Guaiacum plants, a genus of flowers typically found in tropical locations. Guaiol is thought to have a woody, floral scent, although it is often found in conjunction with pinene, which may result in a pine aroma. Because this terpene is relatively uncommon, there hasn’t been a great deal of research into it, although the few studies conducted show promising results. One animal study utilizing a guaiol-heavy essential oil demonstrated a reduction of fever and inflammation in vivo.[1] Another in vitro study explored the potential antibacterial and antioxidant properties of this terpene.[2] Furthermore, some in vitro studies have identified guaiol as a prospective cancer treatment[3]. Finally, and although further research is clearly warranted, a recent study implicated this terpene in the potential treatment of COVID-19.[4]

[1] Wêndeo Kennedy Costa, et al. “Essential Oil From Eugenia Stipitata Mcvaugh Leaves Has Antinociceptive, Anti-inflammatory and Antipyretic Activities Without Showing Toxicity In Mice.” Industrial crops and products, v. 144 ,. pp. 112059. doi: 10.1016/j.indcrop.2019.112059

[2] Mendes RF, Pinto NC, da Silva JM, da Silva JB, Hermisdorf RC, Fabri RL, Chedier LM, Scio E. The essential oil from the fruits of the Brazilian spice Xylopia sericea A. St.-Hil. presents expressive in-vitro antibacterial and antioxidant activity. J Pharm Pharmacol. 2017 Mar;69(3):341-348. doi: 10.1111/jphp.12698. Epub 2017 Jan 30. PMID: 28134988.

[3] Yang Q, Wu J, Luo Y, Huang N, Zhen N, Zhou Y, Sun F, Li Z, Pan Q, Li Y. (-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer. Oncotarget. 2016 Sep 20;7(38):62585-62597. doi: 10.18632/oncotarget.11540. PMID: 27566579; PMCID: PMC5308748.

[4] My TTA, Loan HTP, Hai NTT, Hieu LT, Hoa TT, Thuy BTP, Quang DT, Triet NT, Anh TTV, Dieu NTX, Trung NT, Hue NV, Tat PV, Tung VT, Nhung NTA. Evaluation of the Inhibitory Activities of COVID-19 of Melaleuca cajuputi Oil Using Docking Simulation. ChemistrySelect. 2020 Jun 8;5(21):6312-6320. doi: 10.1002/slct.202000822. Epub 2020 Jun 2. PMID: 32572383; PMCID: PMC7300966.

Previously known as α-caryophyllene, humulene is an isomer of the more commonly known terpene, β-caryophyllene. Not only do these terpenes share a molecular composition, but they also create similar earthy, peppery aromas and are often found together in nature. Some in vitro studies have shown that humulene may act as an anti-cancer agent[1], perhaps potentiated with the presence of β-caryophyllene[2]. Using essential oils rich in humulene, researchers have been able to demonstrate the potential anti-inflammatory[3] and antibacterial[4] effects of this terpene. Another study, using mouse models, concluded that humulene may also be able to treat allergic asthmatic airway inflammation[5]. Humulene is also often invoked as an appetite suppressant, although research supporting this claim is limited and warrants further investigation.

[1] Chen H, Yuan J, Hao J, Wen Y, Lv Y, Chen L, Yang X. α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling. Food Chem Toxicol. 2019 Dec;134:110830. doi: 10.1016/j.fct.2019.110830. Epub 2019 Sep 25. PMID: 31562948.

[2] Legault J, Pichette A. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol. 2007 Dec;59(12):1643-7. doi: 10.1211/jpp.59.12.0005. PMID: 18053325.

[3] Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM, Pianowski LF, Calixto JB. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007 Aug 27;569(3):228-36. doi: 10.1016/j.ejphar.2007.04.059. Epub 2007 May 22. PMID: 17559833.

[4] Pichette A, Larouche PL, Lebrun M, Legault J. Composition and antibacterial activity of Abies balsamea essential oil. Phytother Res. 2006 May;20(5):371-3. doi: 10.1002/ptr.1863. PMID: 16619365.

[5] Rogerio AP, Andrade EL, Leite DF, Figueiredo CP, Calixto JB. Preventive and therapeutic anti-inflammatory properties of the sesquiterpene alpha-humulene in experimental airways allergic inflammation. Br J Pharmacol. 2009 Oct;158(4):1074-87. doi: 10.1111/j.1476-5381.2009.00177.x. Epub 2009 May 8. PMID: 19438512; PMCID: PMC2785529.