How Terpenes Support Wellbeing

by Justyn Bostic
07.08.2020

Terpenes are a large class of organic compounds that naturally occur in hemp and other plants. Terpenes are extremely fragrant and have long been used for aromatherapy and other wellness treatments. In recent years, research has begun to reveal and support the specific ways that terpenes can support good health. In this post, we’ll review the research to explain what terpenes are, where they can be found, and how they can be used to support a healthy lifestyle.

Terpenes in the Wild

Terpenes are ubiquitous in the world of plants. There are more than 80,000 known terpenes and terpenoids (terpene-like substances) in the wild.(1) Different levels and combinations of these compounds give plants unique characteristics. For example, when you observe that plants smell pleasant, taste spicy, or cause certain biological effects, you are likely noticing terpenes at work. Some plants with a particularly pronounced terpene presence include pine trees, lavender, lemon, and peppermint.(2)

Terpenes have a range of functions that make them very important for plants. Some terpenes can attract pollinating insects to help plants reproduce. Other terpenes can ward off predatory animals with bitter tastes or smells. Finally, other terpenes may have anti-bacterial and anti-fungal properties that can protect plants from disease.(3)

Different plants have different terpene profiles, and there are some forms of terpenes that can only be found in individual species. There are also a few hundred key terpenes that are found in nearly all plants.(4) So while many plants share similar characteristics, individual species of plants like hemp can have particularly beneficial properties.(5)

A History of Wellness

Terpenes have been used directly and indirectly to support wellness for hundreds of years. Terpenes were used in many ancient medicinal blends, including mouthwashes, cough medicines, disinfectants, and insect repellents.(6) Further, many of the herbs and spices that are used to naturally preserve food owe their antimicrobial and insecticidal properties to terpenes.(7)

Today, many people try to harness the benefit of terpenes by simply immersing themselves in terpene-heavy atmospheres. The popular German practice of “Kneipp Therapy” holds up exercise in a forest (an environment full of tree terpenes) as one of its 5 key tenets.(8) 

Japan also has a long tradition of using forest terpenes to promote human health. In 2005, the country even instituted a national “forest bathing” initiative, called the “therapeutic effects of forests plan.”(9)

Amazingly, simply being in the presence of terpenes seems to be beneficial. For example, one recent study found that children gained serious immunological benefits after visiting forests, and received sustained relief from asthma and dermatitis.(10)

The fact that these ubiquitous tree terpenes can induce anti-inflammatory, neuroprotective, and anti-cancer effects has scientists excited.(11) However, because there are so many of these compounds, the vast majority of terpenes have not been studied yet.(12)

Hemp: The Terpene Trailblazer

Fortunately, the terpenes of one plant in particular have received some serious attention. There are many studies that focus on the medicinal properties of hemp terpenes.(13) This may come as a surprise to hemp industry insiders who frequently struggle to get medical attention due to hemp’s complicated legal status. However, it actually makes tons of sense given that hemp is one of the most common sources of medicinal terpenes.(14) 

Hemp plants naturally produce and accumulate terpenes in their glandular trichomes (the small buds on the surface of the plant).These terpene stores give each plant a unique odor and medical potential.(15) 

There are countless terpenes that may appear in hemp plants. However, some terpenes tend to appear in high levels across multiple plant species. These include(16):

Pinene

Myrcene

Limonene

Ocimene

Terpinolene

Beta Caryophyllene

Linalool

Humulene

All of these terpenes are found in varying degrees in hemp. The following sections will explore the different properties and wellness benefits of these terpenes.

Pinene

Pinene gets its name from pine trees. It is associated with a fresh, woody aroma reminiscent of a coniferous forest. Aside from occurring in pine needles and hemp plants, pinene can also be found in rosemary and sage(17)(18). There are two kinds of pinene, α-pinene, which is more associated with pine and woody aromas, and β-pinene, which is associated with rosemary and sage. Together, they have a wide range of medical benefits, including gastroprotective, anti-anxiety, anticonvulsant, and neuroprotective effects.(19)

Pinene has powerful antimicrobial properties. The terpene exhibits some anti-fungal effects(20) and potent antibacterial activity.  For example, one study found that pinene was able to increase the potency of commonly used antibiotics up to 512 times.(21) Pinene has also demonstrated some antimalarial activity, with α-pinene producing a particularly powerful effect.(22) 

Pinene may also plan an important role in protecting us from internal dysfunction. The terpene can reduce inflammation in humans by suppressing inflammatory or catabolic (destructive) pathways.(23) It can also defend the nervous system from cell death, making it a possible treatment for degenerative diseases like Alzeheimer’s and Parkinson’s.(24) Finally, pinene may have some anti-cancer effects(25): One study even found that rats exhibited significantly decreased cancer growth rates when immersed in fragrant, pinene heavy environments.

Alpha Pinene, in particular, has been shown to aid in inhibiting acetylcholinesterase, which in turn helps to counteract any memory loss associated with cannabis consumption.(27)

In addition to these effects, pinene also shows some promise as a treatment for mood and sleep disorders. Pinene has been shown to enhance sleep(28)and produce anti-anxiety-like effects in animal studies.(29)

Myrcene

Myrcene’s aroma is sometimes described as earthy, fruity, or clove-like. The terpene gets its name from Myrcia Sphaerocarpa, a Brazilian medicinal shrub, but it is also commonly found in hops, lemongrass, and mangos. It is frequently used for culinary purposes and in perfume.(30) However, myrcene may also have powerful analgesic, anti-inflammatory, and antioxidant effects. 

Some of the most exciting qualities of myrcene are its protective effects. Studies have found that myrcene has a protective effect on damaged heart tissue after strokes.(31) The terpene also demonstrates significant anti-inflammatory and anti-catabolic effects in humans. This may mean that it can slow, or entirely stop, cartilage destruction caused by aging or osteoarthritis.(31) Finally, myrcene may be able to reduce DNA damage, from harmful oxidants.(33)

Myrcene also has analgesic properties, making it a possible treatment for pain. Myrcene has been shown to reduce nerve pain in animals,(34)(35) and more recent studies have shown that myrcene has great potential in treating both long term and short term pain in humans.(36) While myrcene may be a mild sedative and muscle relaxant, animal studies have also suggested that it can increase anxiety in very high doses.(37)  This is your “couch lock” terpene.

Limonene 

Limonene is commonly found in citrus fruits, like lemons, oranges, and grapefruits. It has a bright citrusy aroma, and is frequently used for cleaning agents and aromatic cosmetic products. Limonene also has some exciting wellness benefits, as it can be used to support heart health, anticancer effects, and more. 

This terpene may be able to boost heart health in a few ways. One study found that when animals were given limonene, they ended up with lower LDL (bad) cholesterol, decreased blood sugar levels, and less liver fat when compared to a control group.(38) Another study found that limonene could reduce blood pressure in stroke-prone rats.(39) 

Limonene also has powerful anticancer benefits that have been confirmed by human studies alike. For example, humans who eat citrus fruits with the peel (peels are high in limonene) have a much lower chance of developing skin cancer than those who eat peeled fruits.(40) Women with breast cancer also exhibited significant reductions in tumor cell expression after just a few weeks of limonene supplementation.(41) 

Limonene also demonstrates solid anti-inflammatory and antioxidant effects. Limonene may inhibit free radicals to decrease inflammation and prevent cellular damage.(42) It may also relieve asthma, allergies, and ulcerative colitis.(43) Finally, limonene is actually incredible for anxiety as well; a lot of patients would gravitate toward it for that reason.(44)

Ocimene

Ocimene has a sweeter, floral aroma, and is found in things like mint, parsley, and orchids. 

Although it can be found all throughout nature, it is not as well-studied as some of the other terpenes. Still, essential oils with high concentrations of ocimene have induced anticonvulsant, antifungal, and anti-diabetic effects.(45) 

Wild tarragon has been used in folklore treatments of epilepsy for a very long time. Studies have recently revealed that the essential oils from this tarragon are packed with ocimene, and that they can produce anticonvulsant and sedative effects.(46)

Essential oils from water dropwort, a flowering plant, are also extremely high in ocimene. These oils exhibit antifungal and anti-inflammatory properties, and can be used for therapeutic purposes.(47) 

Finally, ocimene is also one of the key ingredients in black pepper oils, which show promise in treating type-2 diabetes and hypertension.(48) While this is exciting, more research certainly needs to be done on isolated ocimene.

Terpinolene

It is hard to describe the aroma of terpinolene. The terpene is commonly found in hemp, but it can also be found in nutmeg, cumin, and apples, none of which smell very much like each other. At best, terpinolene can be described as having an earthy but fresh aroma. To match its diffuse flavor profile, terpinolene also has a wide ranging set of wellness benefits. 

One exciting property of terpinolene is that it may be able to improve heart health. The terpene inhibits LDL (bad) cholesterol oxidation. It may also prevent the buildup of harmful arterial plaque and protect against coronary heart disease.(49)

Terpinolene may also have sedative effects. In one animal study, terpinolene from patchouli leaves exerted measurable sedation in mice.(50) 

Some other wellness benefits of terpinolene may include anti-cancer effects,(51)  antifungal effects,(52) as well as anti-inflammatory and analgesic effects.(53)

Beta Caryophyllene

Beta Caryophyllene is an exciting terpene with some very special properties. The compound can be found in black pepper, cloves, and cinnamon, and exudes a spicy, funky aroma. Caryophyllene interacts with our bodies endocannabinoid systems, making it a rather unique terpene with immense therapeutic potential.(54)  

Beta Caryophyllene is the only terpene in nature that can selectively bind with CB2 receptors throughout the body.(55) Because of the direct receptor site action, inflammatory responses in the body are more readily elicited.(56) This gives it the ability to treat a huge range of conditions. Beta Caryophyllene has already been shown to help treat colitis, osteoarthritis,(57) diabetes,(58) cerebral ischemia,(59) anxiety and depression,(60) liver fibrosis,(61) and cancer.(62) 

Beta Caryophyllene may even be a hidden source of longevity. In one study, scientists observed that caryophyllene modulated the genetic stress response of Caenorhabditis elegans, a small kind of worm. In doing so, it increased the life expectancy of these creatures by a stunning 22%.(63) Obviously there’s no guarantee that these results will translate to humans, but they are still a pretty exciting start.

Linalool

Linalool may be one of the most relaxing terpenes. The terpene is commonly found in lavender and rosewood, and has a signature herbal aroma. And while it has many biological effects, it is mostly known for its sedative properties. 

Human and animal studies have repeatedly demonstrated that breathing in linalool or lavender extract quiets and helps to inhibit excitatory responses in the nervous system. In mice, linalool has been found to decrease anxiety and aggressive behavior, while increasing positive social interactions.(64) These “anticonflict” effects have been further backed up by other studies.(65) 

Linalool has also demonstrated anticonvulsant effects(66) and antidepressant properties in similar animal studies.(67) Linalool can also act as a powerful analgesic when paired with CBD.(68)

Aside from promoting relaxation and relief, linalool can function as a great defense mechanism. The powerful terpene has been shown to reduce DNA damage,(69) exert antioxidant and antibacterial effects,(70) and fight cancer in humans.(71)

Humulene

Humulene is the characteristic terpene in hops, the bitter flowers that are frequently used to flavor beer. It can also be found in sage, and ginseng. As such, humulene often produces an earthy, bitter, and hoppy aroma. Humulene has very pronounced anti-inflammatory properties, making it a good potential treatment for local or systemic inflammation.(72)

Humulene has powerful anti-inflammatory effects.(73) In animal studies, the terpene has been used to decrease allergic inflammation of airways,(74) and promote healing in skin wounds.(75) 

Humulene has also demonstrated antitumor activity,(76) and antibacterial effects.(77)

It is occasionally reported that humulene works as an appetite suppressant. However, there is little scientific evidence to back up that claim. Regardless of if it keeps you sated or not though, there is still plenty to love about humulene.

Entourage Effects

Each strain of hemp contains a unique terpene profile. These varying terpene levels give different strains unique smells, tastes, and medicinal properties. While each terpene has a unique set of effects, they may also combine to produce even more significant entourage effects.(78) 

The idea behind entourage effects is that different hemp compounds can work synergistically together. So, while either of two terpenes might not produce an effect in isolation, the combination of the two could actually produce a big effect. It’s also important to note that terpenes can vary in effect when combined with different cannabinoids. For example, we tend to see CBD and linalool provide analgesic properties, while THC and linalool tend to create an overall stronger sedative effect.(79)

Terpenes can also interact with cannabinoids or flavonoids to produce further entourage effects. More research is still needed, putative benefits of hemp entourage effects include enhanced treatment of depression, anxiety, addiction, epilepsy, cancer, and infections.(80)

The Future of Terpenes

It may be tempting to start chasing specific terpenes, but a more organic approach will probably yield better results. Nature produces thousands of terpenes across hundreds of thousands of plant varieties. And all of these terpenes have unique flavors, wellness benefits, and potentials for interactions or entourage effects. 

In the future, we may know enough about terpenes and cannabinoids to formulate ultra-targeted blends for specific conditions. As of now, however, we are likely unable to match the diversity or creativity of the natural terpene blends that exist in hemp plants. 

Terpenes are at the nexus of science and holistic wellness. People all around the world have been using these compounds to support wellness for thousands of years, and that isn’t changing any time soon. As we use modern scientific methods to validate, understand, and explore terpenes, we may learn how to use a wider variety of plants to treat an even greater range of ailments.

Contributions By: 

Ashton Hayes, Sales Operations Manager, Open Book Extracts 

References

 

1) Zhou, F., Pichersky, E. More is better: the diversity of terpene metabolism in plants. Current Opinion in Plant Biology. 2020;55: 1-10.

2) Breitmaier, E. Terpenes: Flavors, Fragrances, Pharmaca, Pheromones. Wiley-VCH. 2016.

3) Ibid

4) Raguso, R.A., Pichersky, E. Why do plants produce so many terpenoid compounds? New Phytologist Trust. 2016;220:655-658

5) Booth J.K., Bohlmann J. Terpenes in Cannabis sativa – From plant genome to humans. Plant Science. 2019; 284: 67-72.

6) Raguso, R.A., Pichersky, E. Why do plants produce so many terpenoid compounds?

7) Ibid

8) Tsunetsugu Y, Park BJ, Miyazaki Y. Trends in research related to “Shinrin-yoku” (taking in the forest atmosphere or forest bathing) in Japan. Environ Health Prev Med. 2010; 15(1):27-37.

9)  Ibid

10) Seo, S.C., Park, S.J. et al. Clinical and immunological effects of a forest trip in children with asthma and atopic dermatitis. Iran J Allergy Asthma Immunol. 2015; 14(1): 28-36.

11) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402865/

12) Franklin, L et al. Terpene based pesticide treatments for killing terrestrial arthropods including, amongst others, lice, lice eggs, mites and ants. 2001.

13) Booth J.K., Bohlmann J. Terpenes in Cannabis sativa – From plant genome to humans.

14) Cox-Georgian D, Ramadoss N, Dona C, Basu C. Therapeutic and Medicinal Uses of Terpenes. Medicinal Plants. 2019 Nov 12:333–59.

15) Booth JK, Page JE, Bohlmann J. Terpene synthases from Cannabis sativa. PLoS One. 2017 Mar 29;12(3):e0173911.

16) Ibid

17) Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. Eur. J. Med. Chem. 2018;157:198–228.

18) Borges R.S., Ortiz B.L.S., Pereira A.C.M., Keita H., Carvalho J.C.T. Rosmarinus officinalis essential oil: A review of its phytochemistry, anti-inflammatory activity, and mechanisms of action involved. J. Ethnopharmacol. 2019;229:29–45.

19) Salehi B, Upadhyay S, Erdogan Orhan I, Kumar Jugran A, L D Jayaweera S, A Dias D, Sharopov F, Taheri Y, Martins N, Baghalpour N, Cho WC, Sharifi-Rad J. Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature. Biomolecules. 2019 Nov 14;9(11):738.

20) Rivera-Yanez C.R., Terrazas L.I., Jimenez-Estrada M., Campos J.E., Flores-Ortiz C.M., Hernandez L.B., Cruz-Sanchez T., Garrido-Farina G.I., Rodriguez-Monroy M.A., Canales-Martinez M.M. Anti-Candida Activity of Bursera morelensis Ramirez Essential Oil and Two Compounds, alpha-Pinene and gamma-Terpinene-An In Vitro Study. Molecules. 2017;22:2095.

21) Kovac J., Simunovic K., Wu Z., Klancnik A., Bucar F., Zhang Q., Mozina S.S. Antibiotic resistance modulation and modes of action of (-)-alpha-pinene in Campylobacter jejuni. PLoS ONE. 2015;10:e0122871.

22) van Zyl R.L., Seatlholo S.T., van Vuuren S.F. The biological activities of 20 nature identical essential oil constituents. J. Essent Oil Res. 2006;18:129–133.

23) Rufino A.T., Ribeiro M., Judas F., Salgueiro L., Lopes M.C., Cavaleiro C., Mendes A.F. Anti-inflammatory and chondroprotective activity of (+)-alpha-pinene: Structural and enantiomeric selectivity. J. Nat. Prod. 2014;77:264–269.

24) Porres-Martinez M., Gonzalez-Burgos E., Carretero M.E., Gomez-Serranillos M.P. In vitro neuroprotective potential of the monoterpenes alpha-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z. Nat. C. 2016;71:191–199.

25) Zhang Z., Guo S., Liu X., Gao X. Synergistic antitumor effect of alpha-pinene and beta-pinene with paclitaxel against non-small-cell lung carcinoma (NSCLC) Drug Res. 2015;65:214–218.

26) Kusuhara M., Urakami K., Masuda Y., Zangiacomi V., Ishii H., Tai S., Maruyama K., Yamaguchi K. Fragrant environment with alpha-pinene decreases tumor growth in mice.

27) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

28) Woo J., Yang H., Yoon M., Gadhe C.G., Pae A.N., Cho S., Lee C.J. 3-Carene, a phytoncide from pine tree has a sleep-enhancing effect by targeting the GABA(A)-benzodiazepine receptors. Exp. Neurobiol. 2019;28:593–601.

29) Kasuya H., Okada N., Kubohara M., Satou T., Masuo Y., Koike K. Expression of BDNF and TH mRNA in the brain following inhaled administration of alpha-pinene. Phytother. Res. 2015;29:43–47.

30) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

31) Burcu GB, Osman C, Asli C, et al. The protective cardiac effects of Beta-myrcene after global cerebral ischemia/reperfusion in C57BL/J6 mouse. Acta Cir Bras. 2016;31:456–462.

32) Rufino AT, Ribeiro M, Sousa C, et al. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. European Journal of Pharmacology. 2015; 750.

33) Mitic-Culafic, M. Zegura, B. et al. Protective effect of linalool, myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cells. Food and Chemical Toxicology. 2009; 47(1):260-266.

34) Paula-Freire LI, Molska GR, Andersen ML, et al. Ocimum gratissimum essential oil and its isolated compounds (Eugenol and Myrcene) reduce neuropathic pain in mice. Planta Med. 2016;82:211–216.

35) Rao VS, Menezes AM, Viana GS. Effect of myrcene on nociception in mice. J Pharm Pharmacol. 1990;42:877–878.

36) Jansen, C., Shimoda, L., Kawakami, J. K., Ang, L., Bacani, A. J., Baker, J. D., Badowski, C., Speck, M., Stokes, A. J., Small-Howard, A. L., & Turner, H. Myrcene and terpene regulation of TRPV1. 2019. Channels (Austin, Tex.), 13(1), 344–366.

37)  do Vale, T.G., Furtado, E.C. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba. Phytomedicine. 2019; 9(8): 709-714.

38) Jing L, Zhang Y, Fan S, et al. Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity. Eur J Pharmacol. 2013;715(1-3):46-55.

39) Wang, X., Li, G., & Shen, W. (2018). Protective effects of D-Limonene against transient cerebral ischemia in stroke-prone spontaneously hypertensive rats. Experimental and therapeutic medicine, 15(1), 699–706.

40) Hakim IA, Harris RB, Ritenbaugh C. Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin. Nutr Cancer. 2000; 37(2):161-168.

41) Miller JA, Lang JE, Ley M, et al. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. Cancer Prev Res (Phila). 2013;6(6):577-584.

42) Hirota R, Roger NN, Nakamura H, Song HS, Sawamura M, Suganuma N. Anti-inflammatory effects of limonene from yuzu (Citrus junos Tanaka) essential oil on eosinophils. J Food Sci. 2010;75(3):H87-H92.

43) Yu L, Yan J, Sun Z. D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways. Mol Med Rep. 2017;15(4):2339-2346.

44) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

45) Russo, E.B., Marcu J. Chapter Three – Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Advances in Pharmacology. 2017;80:67-137.

46) Sayyah M, Nadjafnia L, Kamalinejad M. Anticonvulsant activity and chemical composition of Artemisia dracunculus L. essential oil. J Ethnopharmacol. 2004;94(2-3):283-287.

47) Valente J, Zuzarte M, Gonçalves MJ, et al. Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L. essential oil. Food Chem Toxicol. 2013;62:349-354.

48) 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.

49) Grassmann J, Hippeli S, Spitzenberger R, Elstner EF. 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;12(6-7):416-423.

50) Ito K, Ito M. The sedative effect of inhaled terpinolene in mice and its structure-activity relationships. J Nat Med. 2013;67(4):833-837.

51) Okumura N, Yoshida H, Nishimura Y, Kitagishi Y, Matsuda S. Terpinolene, a component of herbal sage, downregulates AKT1 expression in K562 cells. Oncol Lett. 2012;3(2):321-324. doi:10.3892/ol.2011.491

52) Tosun I, Akyuz Z, Guler NC, et al. Distribution, virulence attributes and antifungal susceptibility patterns of Candida parapsilosis complex strains isolated from clinical samples. Med Mycol. 2013;51(5):483-492.

53) Macedo EM, Santos WC, Sousa BP Neto, et al. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation. Braz J Med Biol Res. 2016;49(7):e5103.

54) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

55) Finlay DB, Sircombe, KJ, et al. Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors. Front. Pharmacol. 2020.

56) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

57) Rufino AT, Ribeiro M, Sousa C, et al. 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. 2015;750:141-150.

58) Basha RH, Sankaranarayanan C. β-Caryophyllene, a natural sesquiterpene, modulates carbohydrate metabolism in streptozotocin-induced diabetic rats. Acta Histochem. 2014;116(8):1469-1479.

59) Chang HJ, Kim JM, Lee JC, Kim WK, Chun HS. Protective effect of β-caryophyllene, a natural bicyclic sesquiterpene, against cerebral ischemic injury. J Med Food. 2013;16(6):471-480.

60) 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;135:119-124.

61) Calleja MA, Vieites JM, Montero-Meléndez T, et al. The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation [published correction appears in Br J Nutr. 2013 Feb 14;109(3):583.

62) Legault J, Pichette A. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol. 2007;59(12):1643-1647.

63) Pant A, Mishra V, Saikia SK, et al. Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans [published correction appears in Exp Gerontol. 2016 Dec 1;85:128]. Exp Gerontol. 2014;57:81-95.

64) Linck VM, da Silva AL, Figueiró M, Caramão EB, Moreno PRH, Elisabetsky E. Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice. Phytomedicine. 2010;17(8-9):679–683.

65) Umezu T, Nagano K, Ito H, Kosakai K, Sakaniwa M, Morita M. Anticonflict effects of lavender oil and identification of its active constituents. Pharmacology Biochemistry and Behavior. 2006;85(4):713–721.

66) de Sousa DP, Nóbrega FFF, Santos CCMP, de Almeida RN. Anticonvulsant activity of the linalool enantiomers and racemate: investigation of chiral influence. Natural Product Communications. 2010;5(12):1847–1851.

67) Guzman-Gutierrez, S.L., Gomez-Cansino, R., et al. Antidepressant activity of Litsea glaucescens essential oil: Identification of β-pinene and linalool as active principles. Journal of Ethnopharmacology. 2012; 143(2): 673-679.

68) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

69) Mitic-Culafic, M. Zegura, B. et al. Protective effect of linalool, myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cells.

70) Jaradat, N., Adwan, L., et al. Variability of Chemical Compositions and Antimicrobial and Antioxidant Activities of Ruta chalepensis Leaf Essential Oils from Three Palestinian Regions. Biomed Res Int. 2017.

71) Iwasaki K, Zheng YW, Murata S, et al. Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer. World J Gastroenterol. 2016;22(44):9765-9774.

72) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

73) Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM, et al. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007;569:228–236.

74) 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;158(4):1074-1087.

75) 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;158(4):1074-1087.

76) Legault, Jean, et al. “Antitumor activity of balsam fir oil: production of reactive oxygen species induced by α-humulene as possible mechanism of action.” Planta medica 69.05 (2003): 402-407.

77) zizan N, Mohd Said S, Zainal Abidin Z, Jantan I. 2017. Composition and antibacterial activity of the essential oils of Orthosiphon stamineus Benth and Ficus deltoidea Jack against pathogenic oral bacteria. Molecules 22(12): 2135

78) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

79) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

80) Ibid

Terpenes are a large class of organic compounds that naturally occur in hemp and other plants. Terpenes are extremely fragrant and have long been used for aromatherapy and other wellness treatments. In recent years, research has begun to reveal and support the specific ways that terpenes can support good health. In this post, we’ll review the research to explain what terpenes are, where they can be found, and how they can be used to support a healthy lifestyle.

Terpenes in the Wild

Terpenes are ubiquitous in the world of plants. There are more than 80,000 known terpenes and terpenoids (terpene-like substances) in the wild.(1) Different levels and combinations of these compounds give plants unique characteristics. For example, when you observe that plants smell pleasant, taste spicy, or cause certain biological effects, you are likely noticing terpenes at work. Some plants with a particularly pronounced terpene presence include pine trees, lavender, lemon, and peppermint.(2)

Terpenes have a range of functions that make them very important for plants. Some terpenes can attract pollinating insects to help plants reproduce. Other terpenes can ward off predatory animals with bitter tastes or smells. Finally, other terpenes may have anti-bacterial and anti-fungal properties that can protect plants from disease.(3)

Different plants have different terpene profiles, and there are some forms of terpenes that can only be found in individual species. There are also a few hundred key terpenes that are found in nearly all plants.(4) So while many plants share similar characteristics, individual species of plants like hemp can have particularly beneficial properties.(5)

A History of Wellness

Terpenes have been used directly and indirectly to support wellness for hundreds of years. Terpenes were used in many ancient medicinal blends, including mouthwashes, cough medicines, disinfectants, and insect repellents.(6) Further, many of the herbs and spices that are used to naturally preserve food owe their antimicrobial and insecticidal properties to terpenes.(7)

Today, many people try to harness the benefit of terpenes by simply immersing themselves in terpene-heavy atmospheres. The popular German practice of “Kneipp Therapy” holds up exercise in a forest (an environment full of tree terpenes) as one of its 5 key tenets.(8) 

Japan also has a long tradition of using forest terpenes to promote human health. In 2005, the country even instituted a national “forest bathing” initiative, called the “therapeutic effects of forests plan.”(9)

Amazingly, simply being in the presence of terpenes seems to be beneficial. For example, one recent study found that children gained serious immunological benefits after visiting forests, and received sustained relief from asthma and dermatitis.(10)

The fact that these ubiquitous tree terpenes can induce anti-inflammatory, neuroprotective, and anti-cancer effects has scientists excited.(11) However, because there are so many of these compounds, the vast majority of terpenes have not been studied yet.(12)

Hemp: The Terpene Trailblazer

Fortunately, the terpenes of one plant in particular have received some serious attention. There are many studies that focus on the medicinal properties of hemp terpenes.(13) This may come as a surprise to hemp industry insiders who frequently struggle to get medical attention due to hemp’s complicated legal status. However, it actually makes tons of sense given that hemp is one of the most common sources of medicinal terpenes.(14) 

Hemp plants naturally produce and accumulate terpenes in their glandular trichomes (the small buds on the surface of the plant).These terpene stores give each plant a unique odor and medical potential.(15) 

There are countless terpenes that may appear in hemp plants. However, some terpenes tend to appear in high levels across multiple plant species. These include(16):

Pinene

Myrcene

Limonene

Ocimene

Terpinolene

Beta Caryophyllene

Linalool

Humulene

All of these terpenes are found in varying degrees in hemp. The following sections will explore the different properties and wellness benefits of these terpenes.

Pinene

Pinene gets its name from pine trees. It is associated with a fresh, woody aroma reminiscent of a coniferous forest. Aside from occurring in pine needles and hemp plants, pinene can also be found in rosemary and sage(17)(18). There are two kinds of pinene, α-pinene, which is more associated with pine and woody aromas, and β-pinene, which is associated with rosemary and sage. Together, they have a wide range of medical benefits, including gastroprotective, anti-anxiety, anticonvulsant, and neuroprotective effects.(19)

Pinene has powerful antimicrobial properties. The terpene exhibits some anti-fungal effects(20) and potent antibacterial activity.  For example, one study found that pinene was able to increase the potency of commonly used antibiotics up to 512 times.(21) Pinene has also demonstrated some antimalarial activity, with α-pinene producing a particularly powerful effect.(22) 

Pinene may also plan an important role in protecting us from internal dysfunction. The terpene can reduce inflammation in humans by suppressing inflammatory or catabolic (destructive) pathways.(23) It can also defend the nervous system from cell death, making it a possible treatment for degenerative diseases like Alzeheimer’s and Parkinson’s.(24) Finally, pinene may have some anti-cancer effects(25): One study even found that rats exhibited significantly decreased cancer growth rates when immersed in fragrant, pinene heavy environments.

Alpha Pinene, in particular, has been shown to aid in inhibiting acetylcholinesterase, which in turn helps to counteract any memory loss associated with cannabis consumption.(27)

In addition to these effects, pinene also shows some promise as a treatment for mood and sleep disorders. Pinene has been shown to enhance sleep(28)and produce anti-anxiety-like effects in animal studies.(29)

Myrcene

Myrcene’s aroma is sometimes described as earthy, fruity, or clove-like. The terpene gets its name from Myrcia Sphaerocarpa, a Brazilian medicinal shrub, but it is also commonly found in hops, lemongrass, and mangos. It is frequently used for culinary purposes and in perfume.(30) However, myrcene may also have powerful analgesic, anti-inflammatory, and antioxidant effects. 

Some of the most exciting qualities of myrcene are its protective effects. Studies have found that myrcene has a protective effect on damaged heart tissue after strokes.(31) The terpene also demonstrates significant anti-inflammatory and anti-catabolic effects in humans. This may mean that it can slow, or entirely stop, cartilage destruction caused by aging or osteoarthritis.(31) Finally, myrcene may be able to reduce DNA damage, from harmful oxidants.(33)

Myrcene also has analgesic properties, making it a possible treatment for pain. Myrcene has been shown to reduce nerve pain in animals,(34)(35) and more recent studies have shown that myrcene has great potential in treating both long term and short term pain in humans.(36) While myrcene may be a mild sedative and muscle relaxant, animal studies have also suggested that it can increase anxiety in very high doses.(37)  This is your “couch lock” terpene.

Limonene 

Limonene is commonly found in citrus fruits, like lemons, oranges, and grapefruits. It has a bright citrusy aroma, and is frequently used for cleaning agents and aromatic cosmetic products. Limonene also has some exciting wellness benefits, as it can be used to support heart health, anticancer effects, and more. 

This terpene may be able to boost heart health in a few ways. One study found that when animals were given limonene, they ended up with lower LDL (bad) cholesterol, decreased blood sugar levels, and less liver fat when compared to a control group.(38) Another study found that limonene could reduce blood pressure in stroke-prone rats.(39) 

Limonene also has powerful anticancer benefits that have been confirmed by human studies alike. For example, humans who eat citrus fruits with the peel (peels are high in limonene) have a much lower chance of developing skin cancer than those who eat peeled fruits.(40) Women with breast cancer also exhibited significant reductions in tumor cell expression after just a few weeks of limonene supplementation.(41) 

Limonene also demonstrates solid anti-inflammatory and antioxidant effects. Limonene may inhibit free radicals to decrease inflammation and prevent cellular damage.(42) It may also relieve asthma, allergies, and ulcerative colitis.(43) Finally, limonene is actually incredible for anxiety as well; a lot of patients would gravitate toward it for that reason.(44)

Ocimene

Ocimene has a sweeter, floral aroma, and is found in things like mint, parsley, and orchids. 

Although it can be found all throughout nature, it is not as well-studied as some of the other terpenes. Still, essential oils with high concentrations of ocimene have induced anticonvulsant, antifungal, and anti-diabetic effects.(45) 

Wild tarragon has been used in folklore treatments of epilepsy for a very long time. Studies have recently revealed that the essential oils from this tarragon are packed with ocimene, and that they can produce anticonvulsant and sedative effects.(46)

Essential oils from water dropwort, a flowering plant, are also extremely high in ocimene. These oils exhibit antifungal and anti-inflammatory properties, and can be used for therapeutic purposes.(47) 

Finally, ocimene is also one of the key ingredients in black pepper oils, which show promise in treating type-2 diabetes and hypertension.(48) While this is exciting, more research certainly needs to be done on isolated ocimene.

Terpinolene

It is hard to describe the aroma of terpinolene. The terpene is commonly found in hemp, but it can also be found in nutmeg, cumin, and apples, none of which smell very much like each other. At best, terpinolene can be described as having an earthy but fresh aroma. To match its diffuse flavor profile, terpinolene also has a wide ranging set of wellness benefits. 

One exciting property of terpinolene is that it may be able to improve heart health. The terpene inhibits LDL (bad) cholesterol oxidation. It may also prevent the buildup of harmful arterial plaque and protect against coronary heart disease.(49)

Terpinolene may also have sedative effects. In one animal study, terpinolene from patchouli leaves exerted measurable sedation in mice.(50) 

Some other wellness benefits of terpinolene may include anti-cancer effects,(51)  antifungal effects,(52) as well as anti-inflammatory and analgesic effects.(53)

Beta Caryophyllene

Beta Caryophyllene is an exciting terpene with some very special properties. The compound can be found in black pepper, cloves, and cinnamon, and exudes a spicy, funky aroma. Caryophyllene interacts with our bodies endocannabinoid systems, making it a rather unique terpene with immense therapeutic potential.(54)  

Beta Caryophyllene is the only terpene in nature that can selectively bind with CB2 receptors throughout the body.(55) Because of the direct receptor site action, inflammatory responses in the body are more readily elicited.(56) This gives it the ability to treat a huge range of conditions. Beta Caryophyllene has already been shown to help treat colitis, osteoarthritis,(57) diabetes,(58) cerebral ischemia,(59) anxiety and depression,(60) liver fibrosis,(61) and cancer.(62) 

Beta Caryophyllene may even be a hidden source of longevity. In one study, scientists observed that caryophyllene modulated the genetic stress response of Caenorhabditis elegans, a small kind of worm. In doing so, it increased the life expectancy of these creatures by a stunning 22%.(63) Obviously there’s no guarantee that these results will translate to humans, but they are still a pretty exciting start.

Linalool

Linalool may be one of the most relaxing terpenes. The terpene is commonly found in lavender and rosewood, and has a signature herbal aroma. And while it has many biological effects, it is mostly known for its sedative properties. 

Human and animal studies have repeatedly demonstrated that breathing in linalool or lavender extract quiets and helps to inhibit excitatory responses in the nervous system. In mice, linalool has been found to decrease anxiety and aggressive behavior, while increasing positive social interactions.(64) These “anticonflict” effects have been further backed up by other studies.(65) 

Linalool has also demonstrated anticonvulsant effects(66) and antidepressant properties in similar animal studies.(67) Linalool can also act as a powerful analgesic when paired with CBD.(68)

Aside from promoting relaxation and relief, linalool can function as a great defense mechanism. The powerful terpene has been shown to reduce DNA damage,(69) exert antioxidant and antibacterial effects,(70) and fight cancer in humans.(71)

Humulene

Humulene is the characteristic terpene in hops, the bitter flowers that are frequently used to flavor beer. It can also be found in sage, and ginseng. As such, humulene often produces an earthy, bitter, and hoppy aroma. Humulene has very pronounced anti-inflammatory properties, making it a good potential treatment for local or systemic inflammation.(72)

Humulene has powerful anti-inflammatory effects.(73) In animal studies, the terpene has been used to decrease allergic inflammation of airways,(74) and promote healing in skin wounds.(75) 

Humulene has also demonstrated antitumor activity,(76) and antibacterial effects.(77)

It is occasionally reported that humulene works as an appetite suppressant. However, there is little scientific evidence to back up that claim. Regardless of if it keeps you sated or not though, there is still plenty to love about humulene.

Entourage Effects

Each strain of hemp contains a unique terpene profile. These varying terpene levels give different strains unique smells, tastes, and medicinal properties. While each terpene has a unique set of effects, they may also combine to produce even more significant entourage effects.(78) 

The idea behind entourage effects is that different hemp compounds can work synergistically together. So, while either of two terpenes might not produce an effect in isolation, the combination of the two could actually produce a big effect. It’s also important to note that terpenes can vary in effect when combined with different cannabinoids. For example, we tend to see CBD and linalool provide analgesic properties, while THC and linalool tend to create an overall stronger sedative effect.(79)

Terpenes can also interact with cannabinoids or flavonoids to produce further entourage effects. More research is still needed, putative benefits of hemp entourage effects include enhanced treatment of depression, anxiety, addiction, epilepsy, cancer, and infections.(80)

The Future of Terpenes

It may be tempting to start chasing specific terpenes, but a more organic approach will probably yield better results. Nature produces thousands of terpenes across hundreds of thousands of plant varieties. And all of these terpenes have unique flavors, wellness benefits, and potentials for interactions or entourage effects. 

In the future, we may know enough about terpenes and cannabinoids to formulate ultra-targeted blends for specific conditions. As of now, however, we are likely unable to match the diversity or creativity of the natural terpene blends that exist in hemp plants. 

Terpenes are at the nexus of science and holistic wellness. People all around the world have been using these compounds to support wellness for thousands of years, and that isn’t changing any time soon. As we use modern scientific methods to validate, understand, and explore terpenes, we may learn how to use a wider variety of plants to treat an even greater range of ailments.

Contributions By: 

Ashton Hayes, Sales Operations Manager, Open Book Extracts 

References

 

1) Zhou, F., Pichersky, E. More is better: the diversity of terpene metabolism in plants. Current Opinion in Plant Biology. 2020;55: 1-10.

2) Breitmaier, E. Terpenes: Flavors, Fragrances, Pharmaca, Pheromones. Wiley-VCH. 2016.

3) Ibid

4) Raguso, R.A., Pichersky, E. Why do plants produce so many terpenoid compounds? New Phytologist Trust. 2016;220:655-658

5) Booth J.K., Bohlmann J. Terpenes in Cannabis sativa – From plant genome to humans. Plant Science. 2019; 284: 67-72.

6) Raguso, R.A., Pichersky, E. Why do plants produce so many terpenoid compounds?

7) Ibid

8) Tsunetsugu Y, Park BJ, Miyazaki Y. Trends in research related to “Shinrin-yoku” (taking in the forest atmosphere or forest bathing) in Japan. Environ Health Prev Med. 2010; 15(1):27-37.

9)  Ibid

10) Seo, S.C., Park, S.J. et al. Clinical and immunological effects of a forest trip in children with asthma and atopic dermatitis. Iran J Allergy Asthma Immunol. 2015; 14(1): 28-36.

11) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402865/

12) Franklin, L et al. Terpene based pesticide treatments for killing terrestrial arthropods including, amongst others, lice, lice eggs, mites and ants. 2001.

13) Booth J.K., Bohlmann J. Terpenes in Cannabis sativa – From plant genome to humans.

14) Cox-Georgian D, Ramadoss N, Dona C, Basu C. Therapeutic and Medicinal Uses of Terpenes. Medicinal Plants. 2019 Nov 12:333–59.

15) Booth JK, Page JE, Bohlmann J. Terpene synthases from Cannabis sativa. PLoS One. 2017 Mar 29;12(3):e0173911.

16) Ibid

17) Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. Eur. J. Med. Chem. 2018;157:198–228.

18) Borges R.S., Ortiz B.L.S., Pereira A.C.M., Keita H., Carvalho J.C.T. Rosmarinus officinalis essential oil: A review of its phytochemistry, anti-inflammatory activity, and mechanisms of action involved. J. Ethnopharmacol. 2019;229:29–45.

19) Salehi B, Upadhyay S, Erdogan Orhan I, Kumar Jugran A, L D Jayaweera S, A Dias D, Sharopov F, Taheri Y, Martins N, Baghalpour N, Cho WC, Sharifi-Rad J. Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature. Biomolecules. 2019 Nov 14;9(11):738.

20) Rivera-Yanez C.R., Terrazas L.I., Jimenez-Estrada M., Campos J.E., Flores-Ortiz C.M., Hernandez L.B., Cruz-Sanchez T., Garrido-Farina G.I., Rodriguez-Monroy M.A., Canales-Martinez M.M. Anti-Candida Activity of Bursera morelensis Ramirez Essential Oil and Two Compounds, alpha-Pinene and gamma-Terpinene-An In Vitro Study. Molecules. 2017;22:2095.

21) Kovac J., Simunovic K., Wu Z., Klancnik A., Bucar F., Zhang Q., Mozina S.S. Antibiotic resistance modulation and modes of action of (-)-alpha-pinene in Campylobacter jejuni. PLoS ONE. 2015;10:e0122871.

22) van Zyl R.L., Seatlholo S.T., van Vuuren S.F. The biological activities of 20 nature identical essential oil constituents. J. Essent Oil Res. 2006;18:129–133.

23) Rufino A.T., Ribeiro M., Judas F., Salgueiro L., Lopes M.C., Cavaleiro C., Mendes A.F. Anti-inflammatory and chondroprotective activity of (+)-alpha-pinene: Structural and enantiomeric selectivity. J. Nat. Prod. 2014;77:264–269.

24) Porres-Martinez M., Gonzalez-Burgos E., Carretero M.E., Gomez-Serranillos M.P. In vitro neuroprotective potential of the monoterpenes alpha-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z. Nat. C. 2016;71:191–199.

25) Zhang Z., Guo S., Liu X., Gao X. Synergistic antitumor effect of alpha-pinene and beta-pinene with paclitaxel against non-small-cell lung carcinoma (NSCLC) Drug Res. 2015;65:214–218.

26) Kusuhara M., Urakami K., Masuda Y., Zangiacomi V., Ishii H., Tai S., Maruyama K., Yamaguchi K. Fragrant environment with alpha-pinene decreases tumor growth in mice.

27) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

28) Woo J., Yang H., Yoon M., Gadhe C.G., Pae A.N., Cho S., Lee C.J. 3-Carene, a phytoncide from pine tree has a sleep-enhancing effect by targeting the GABA(A)-benzodiazepine receptors. Exp. Neurobiol. 2019;28:593–601.

29) Kasuya H., Okada N., Kubohara M., Satou T., Masuo Y., Koike K. Expression of BDNF and TH mRNA in the brain following inhaled administration of alpha-pinene. Phytother. Res. 2015;29:43–47.

30) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

31) Burcu GB, Osman C, Asli C, et al. The protective cardiac effects of Beta-myrcene after global cerebral ischemia/reperfusion in C57BL/J6 mouse. Acta Cir Bras. 2016;31:456–462.

32) Rufino AT, Ribeiro M, Sousa C, et al. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. European Journal of Pharmacology. 2015; 750.

33) Mitic-Culafic, M. Zegura, B. et al. Protective effect of linalool, myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cells. Food and Chemical Toxicology. 2009; 47(1):260-266.

34) Paula-Freire LI, Molska GR, Andersen ML, et al. Ocimum gratissimum essential oil and its isolated compounds (Eugenol and Myrcene) reduce neuropathic pain in mice. Planta Med. 2016;82:211–216.

35) Rao VS, Menezes AM, Viana GS. Effect of myrcene on nociception in mice. J Pharm Pharmacol. 1990;42:877–878.

36) Jansen, C., Shimoda, L., Kawakami, J. K., Ang, L., Bacani, A. J., Baker, J. D., Badowski, C., Speck, M., Stokes, A. J., Small-Howard, A. L., & Turner, H. Myrcene and terpene regulation of TRPV1. 2019. Channels (Austin, Tex.), 13(1), 344–366.

37)  do Vale, T.G., Furtado, E.C. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba. Phytomedicine. 2019; 9(8): 709-714.

38) Jing L, Zhang Y, Fan S, et al. Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity. Eur J Pharmacol. 2013;715(1-3):46-55.

39) Wang, X., Li, G., & Shen, W. (2018). Protective effects of D-Limonene against transient cerebral ischemia in stroke-prone spontaneously hypertensive rats. Experimental and therapeutic medicine, 15(1), 699–706.

40) Hakim IA, Harris RB, Ritenbaugh C. Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin. Nutr Cancer. 2000; 37(2):161-168.

41) Miller JA, Lang JE, Ley M, et al. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. Cancer Prev Res (Phila). 2013;6(6):577-584.

42) Hirota R, Roger NN, Nakamura H, Song HS, Sawamura M, Suganuma N. Anti-inflammatory effects of limonene from yuzu (Citrus junos Tanaka) essential oil on eosinophils. J Food Sci. 2010;75(3):H87-H92.

43) Yu L, Yan J, Sun Z. D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways. Mol Med Rep. 2017;15(4):2339-2346.

44) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

45) Russo, E.B., Marcu J. Chapter Three – Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Advances in Pharmacology. 2017;80:67-137.

46) Sayyah M, Nadjafnia L, Kamalinejad M. Anticonvulsant activity and chemical composition of Artemisia dracunculus L. essential oil. J Ethnopharmacol. 2004;94(2-3):283-287.

47) Valente J, Zuzarte M, Gonçalves MJ, et al. Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L. essential oil. Food Chem Toxicol. 2013;62:349-354.

48) 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.

49) Grassmann J, Hippeli S, Spitzenberger R, Elstner EF. 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;12(6-7):416-423.

50) Ito K, Ito M. The sedative effect of inhaled terpinolene in mice and its structure-activity relationships. J Nat Med. 2013;67(4):833-837.

51) Okumura N, Yoshida H, Nishimura Y, Kitagishi Y, Matsuda S. Terpinolene, a component of herbal sage, downregulates AKT1 expression in K562 cells. Oncol Lett. 2012;3(2):321-324. doi:10.3892/ol.2011.491

52) Tosun I, Akyuz Z, Guler NC, et al. Distribution, virulence attributes and antifungal susceptibility patterns of Candida parapsilosis complex strains isolated from clinical samples. Med Mycol. 2013;51(5):483-492.

53) Macedo EM, Santos WC, Sousa BP Neto, et al. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation. Braz J Med Biol Res. 2016;49(7):e5103.

54) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

55) Finlay DB, Sircombe, KJ, et al. Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors. Front. Pharmacol. 2020.

56) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

57) Rufino AT, Ribeiro M, Sousa C, et al. 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. 2015;750:141-150.

58) Basha RH, Sankaranarayanan C. β-Caryophyllene, a natural sesquiterpene, modulates carbohydrate metabolism in streptozotocin-induced diabetic rats. Acta Histochem. 2014;116(8):1469-1479.

59) Chang HJ, Kim JM, Lee JC, Kim WK, Chun HS. Protective effect of β-caryophyllene, a natural bicyclic sesquiterpene, against cerebral ischemic injury. J Med Food. 2013;16(6):471-480.

60) 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;135:119-124.

61) Calleja MA, Vieites JM, Montero-Meléndez T, et al. The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation [published correction appears in Br J Nutr. 2013 Feb 14;109(3):583.

62) Legault J, Pichette A. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol. 2007;59(12):1643-1647.

63) Pant A, Mishra V, Saikia SK, et al. Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans [published correction appears in Exp Gerontol. 2016 Dec 1;85:128]. Exp Gerontol. 2014;57:81-95.

64) Linck VM, da Silva AL, Figueiró M, Caramão EB, Moreno PRH, Elisabetsky E. Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice. Phytomedicine. 2010;17(8-9):679–683.

65) Umezu T, Nagano K, Ito H, Kosakai K, Sakaniwa M, Morita M. Anticonflict effects of lavender oil and identification of its active constituents. Pharmacology Biochemistry and Behavior. 2006;85(4):713–721.

66) de Sousa DP, Nóbrega FFF, Santos CCMP, de Almeida RN. Anticonvulsant activity of the linalool enantiomers and racemate: investigation of chiral influence. Natural Product Communications. 2010;5(12):1847–1851.

67) Guzman-Gutierrez, S.L., Gomez-Cansino, R., et al. Antidepressant activity of Litsea glaucescens essential oil: Identification of β-pinene and linalool as active principles. Journal of Ethnopharmacology. 2012; 143(2): 673-679.

68) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

69) Mitic-Culafic, M. Zegura, B. et al. Protective effect of linalool, myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cells.

70) Jaradat, N., Adwan, L., et al. Variability of Chemical Compositions and Antimicrobial and Antioxidant Activities of Ruta chalepensis Leaf Essential Oils from Three Palestinian Regions. Biomed Res Int. 2017.

71) Iwasaki K, Zheng YW, Murata S, et al. Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer. World J Gastroenterol. 2016;22(44):9765-9774.

72) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

73) Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM, et al. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007;569:228–236.

74) 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;158(4):1074-1087.

75) 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;158(4):1074-1087.

76) Legault, Jean, et al. “Antitumor activity of balsam fir oil: production of reactive oxygen species induced by α-humulene as possible mechanism of action.” Planta medica 69.05 (2003): 402-407.

77) zizan N, Mohd Said S, Zainal Abidin Z, Jantan I. 2017. Composition and antibacterial activity of the essential oils of Orthosiphon stamineus Benth and Ficus deltoidea Jack against pathogenic oral bacteria. Molecules 22(12): 2135

78) Hartsel, J.A., Makriyannis, A. Cannabis Sativa and Hemp. Nutraceuticals. 2016.

79) Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

80) Ibid

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