Have you ever coughed or sneezed so hard that your back went out?  “Slept wrong” where you wake up with a nasty kink in your neck or shoulder and have limited range of motion?

As we age, we start paying more attention to our health.  Sometimes it’s because our health is not as optimal as we desire.  Sometimes it’s because we see the health of the people around us deteriorate with age. We were told that if we eat right and exercise, we should live a long, healthy, and happy life.  What about the stress and anxiety that comes with life? Eating right and exercising helps the physical self, but what about the mental self?

Massage therapy addresses both, offering self-care for not only the physical body, but also for the mental self.  As we get older, our bodies take on the stresses of life, and we can seek massage to help us with our pain and even depression. 1 Eighty-nine percent of those who receive massage therapy agree that massage can be effective in reducing pain. 3   

The primary reason people receive massage is for health and wellness such as pain management, soreness relief, tension relief, injury rehabilitation, overall wellness, and improved quality of life.  As preventative care, massage therapy can help improve our sleep and our mood. Studies have also shown that massage therapy is an effective method of deflecting common seasonal challenges, 2 such as Seasonal Affective Disorder (SAD).

Cannabis and Massage

Massage therapy has become mainstream.  Massage with cannabis therapeutics is the next “big thing.”

Any massage therapist living in a state with cannabis legalization or medical marijuana legislation (including CBD-only laws) can tell you about a lot of positive and promising anecdotal results from massage therapy with cannabis topicals.  The “green spa rush” is becoming more mainstream, and more spas and practitioners are providing hemp or marijuana topicals in their massages.

Aestheticians are adding cannabinoids to their skin care services.  Hair stylists have inquired about the potential benefits of adding cannabinoid hair products to their client services.  While individual practitioners may not care, their clients are inquiring because they hear about the potential benefits people are receiving from the cannabis plant and are interested. Some may have heard the term terpenes and the entourage effect.  Unfortunately, studies researching massage therapy and the use of cannabis topicals are not available. However, research which I’ll look at later in this article, is available about effects of cannabis on skin and muscles.

Cannabis sativa L. is one of the oldest plants cultivated by man.  Historical records show the use of cannabis topicals to help with conditions ranging from hair growth to inflammation to skin bruises and burns.  A Persian Physician, Al-Razi, was the first to report in the early 10th century that topical treatment with cannabis leaves would stimulate hair growth. 4 In the 1700s, several physicians recorded their findings with the cannabis root ball.  Records indicate cannabis root ball is most often extracted with boiling water and applied topically to treat gout and arthritis 5.  In the 12th century, the Persian Philosopher, Ibn Sina (Avicenna), wrote in the Canon of Medicine that “the compress with the boiled roots of cannabis decrease fever.” 6  The Argentineans also found relief of fever from malaria by using cannabis topicals that included root ball.  The 18th century Persian medical text Makhzan-al-Adwiya describes topical preparations, including the leaves, juice, bark, and flowers. 7 Cannabis root has also been used topically to treat skin burns in a variety of ways, including raw root, as a juice, and mixed with fat (butter). 8

Massage Therapy Research

Massage therapy not only feel good but also IS GOOD for you.  We already know about many therapeutic benefits of massage, and the benefits continue to be researched and studied. In a 2010 study, scientists at Cedars-Sinai investigated the physical effects of massage therapy.  The study showed that even one massage session, boosts in the immune system, including a sizeable decrease in arginine vasopressin, a hormone that contributes to aggressive behavior; a decrease in the stress hormone cortisol; and an increase in lymphocytes—cells that help the immune system defend the body from disease. 9,10  This is proof that massage therapy should be part of your health and wellness regimen throughout your lifespan.  

Other recent massage research has shown the effectiveness of massage for anything from treating pain, including but not limited to low back pain, 11 post-operative pain, 12 the symptoms of carpal tunnel syndrome, 13 pain in cancer patients, 14 pain from fibromyalgia, 15 pain from osteoarthritis of the knee, 16 and pain from rheumatoid arthritis. 17 Massage also helps reduce headache frequency. 18 Massage therapy is becoming more mainstream as people are finding it helps not only when we are in pain, but for overall wellness and quality of life.  

Adding Cannabis to Massage Therapy

Throw cannabis into the picture. What do we know?  The endocannabinoid system (ECS) is the largest neurotransmitter system in the human body and regulates all 11 major organ systems to create homeostasis. The ECS is a “key and lock” system, where our naturally produced endocannabinoids, and phyto-cannabinoids from the cannabis plant, are the “key” as they “lock” into the two main cannabinoid receptors 1 and 2 (CB1 and CB2).  

CB1 receptors are primarily located in the brain and tissues of the central nervous system (CNS), including the spinal cord, reproductive organs, lungs, and the spleen. CB2 receptors are primarily located in the peripheral nervous system (PNS), the organs, and peripheral tissues, including our skin, muscles, and immune system.  CB2 receptors help regulate inflammatory responses.

The ECS of the skin has been implicated in the regulation of skin cell proliferation, survival, and differentiation, the delicate balance of which is a key determinant of proper cutaneous homeostasis. 19 Cannabis topicals (such as lotions, creams, salves, ointments, and oils) activate CB2 receptors in the skin.  This activation has been shown to help with localized pain, spasms, and various skin diseases and conditions without intoxicating effects.

These receptors are activated by phytocannabinoids of the cannabis plant.  As of now there are over 200 cannabinoids. The CBD only fad has hit hard, and many do not realize CBD only has a small bell curve of efficacy.  Full plant medicine is far superior than single isolate. Many of these cannabinoids interact synergistically creating an “entourage effect” 20 and affect the body in a mechanism like the body’s own endocannabinoid system which magnifies the therapeutic benefits. Explained by Project CBD, the medicinal impact of the whole plant is greater than the sum of its parts.

Terpenes vs Terpenoids

Terpenes and Terpenoids are the flavor and fragrance components common to the human diet produced in flowers, fruit, leaf and sap of plants. They are not exclusive to the cannabis plant. There are over 200 reported terpenes and terpenoids in cannabis. 21 The basics difference between the two is that terpenes contain carbon (C) and hydrogen (H), while terpenoids not only contain C and H, but also contains oxygen (O).  They are the essential oils of the plant, and just like all cannabinoids, they are secreted from the trichomes of the flower. Trichomes are the microscopic, mushroom-like sticky resonated glands of the plant. Terpenoids, particularly monoterpenoids, are highly bioavailable via inhalation. 22 Terpenoids have been designated Generally Recognized as Safe (GRAS) by the US Food and Drug Administration, the Food and Extract Manufacturers Association (FEMAs), and other world regulatory agencies. They are quite potent and effect animal and even human behavior when inhaled. 23   In his review, Dr Russo, a board-certified neurologist and psychopharmacology researcher, explains that it is the phytocannabinoid-terpenoid relationship that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, and several other ailments.  I will go over a handful of common terpenoids and studies behind them. The therapeutic effects of added terpenoids to a massage oil may not only come from inhalation of the fragrant molecules, it may come from penetration through the skin. 24

Alpha-Pinene

Alpha-Pinene, a bicycle monoterpene, is the most widely encountered terpenoid in nature. 25 Alpha-Pinene is an anti-inflammatory. 26 A bronchodilator in humans at low levels and has a high bioavailability rate of 60% absorption after human pulmonary administration with rapid metabolism and redistribution. 22

• One study found alpha-pinene is a wide spectrum antibiotic. 27
• Pinene increased mouse motility after inhalation by 13.77%. 28
• Another study found inhalation of α-pinene in mice at 10 μL/L concentration produced an
  anxiolytic effect in the elevated plus maze, with general brain distribution. 29
• Chronic inhalation over 5 days, anxiolytic effects were maintained. 30

Beta-Carophyllene

Beta-Carophyllene is common to black pepper, is a sesquiterpenoid, and is most common in cannabis extracts. If offers great promise as a therapeutic compound in dermatological applications such as contact dermatitis. 55 β-Caryophyllene synergizes with THC to impart antipruritic effects and gastric cytoprotection, and with CBD to impart anti-inflammatory benefits. 23

• One study found β-Caryophyllene is an anti-inflammatory. 31
• Another study confirmed β-Caryophyllene activity at CB2 receptors in rodent models of nociception and pain. 32
• Another study showed CB2 agonist, likely including caryophyllene, reduced cocaine administration and improved scores of depression and anxiety in animal models. 33

Limonene

Limonene is a monoterpene most common to citrus rinds and is the second most widely distributed terpenoid in nature. 25 It has a high bioavailability rate of 70% absorption after human pulmonary administration. 34

• A study found limonene to be a strong anxiolytic, boosting serotonin levels in prefrontal cortex, and dopamine in hippocampus. 35
• Another study found orange terpenes, primarily limonene, boosted mouse motility after inhalation by 35.25%, while decreasing activity after caffeine 33.19%. 28
• A study done in Japan found depressed patients exposed to citrus scent experienced normalization of Hamilton Depression Scores (HADS), allowing discontinuation of antidepressants in 9 out of 12 hospitalized patients.  Immune stimulation was also documented. 36

Linalool

Linalool in a monoterpenoid and is commonly extracted from lavender. Linalool has established sedative antidepressant, anxiolytic, and immune potentiating effect. 37 It is also the only terpenoid that had a study focused on the percutaneous absorption from a massage oil and demonstrated the practicality of this application. 24

• Linalool decreased mouse motility after inhalation by 73%. 28
• One study found linalool is likely suspect in therapeutic capabilities of lavender essential oil to alleviate skin burns without scarring. 38
• Another study found the local anesthetic effects of linalool. 39
• Another study found in mice, an essential oil mix including linalool, limonene, and pinene, increased permeation of estradiol through the skin. 40
• Another study found a decrease in morphine opioid usage after inhalation versus placebo in gastric banding in morbidly obese surgical patients. 41

Myrcene

Myrcene is a monoterpene and the most prevalent terpene in modern cannabis chemovars in the United States and is anti-inflammatory. 42

• One study found myrcene is analgesic in mice but can be blocked by naloxone. 43
• Another study found myrcene sedative, used as a sleep aid in Germany. 44
• Another study found myrcene acts as a muscle relaxant in mice, and prolonged barbiturate sleep time. 45

This short list is only a little insight in the world of terpenoids.  The cannabis terpenoid activity table below (Table 2) is from Dr Ethan Russo’s review titled: Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects. 23  The United States is lacking clinical trials that examine the phytocannabinoid-terpenoid interactions.

Cannabis and the Skin

The skin is the largest organ of the body and the first line of defense against injury and infection and contributes to homeostasis. The skin naturally produces endocannabinoid molecules such as anandamide (AEA) and 2_AG.  Phytecs, a biotechnology company researching and developing innovative approaches targeting the human endocannabinoid system (ECS), does an excellent job explaining the different layers of the skin (epidermis, immune cells, hair follicles, sebaceous glands, sweat glands, and sensory nerves) and how cannabinoids effect the ECS in each layer on the Phytecs website: http://www.phytecs.com/tour-the-ecs/the-ecs-in-skin/ .

In 2015, a multinational study showed keratinocytes are part of the peripheral endocannabinoid system. 46 Dr. Jeanette Jacknin M.D. presented at the 2018 American Academy of Dermatology annual meeting.  She explained that the researchers showed a unique signaling mechanism of CB1 receptors, which has important implication in epidermal differentiation and skin development.

Several studies show the effectiveness of cannabis for a variety of skin conditions, 47 such as pruritus, 48-50 atopic dermatitis, 51-53 contact dermatitis, 54-56 acne, 56-59 and the treatment of burns. 60-61 There are also studies on how cannabinoids have helped with the treatment of melanoma, 62 anti-aging, 63 skin tumor growth, 64 pain and faster healing from epidermolysis bullosa, 65 and even cancer. 19, 66-69  

One study investigated the plant cannabinoids Delta-9 tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and cannabigerol (CBG) for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors. The results of the study showed cannabinoids, specifically CBN, have potential as a component in topical applications, inhibiting keratinocyte proliferation via, and therefore supporting a potential role for cannabinoids in the treatment of psoriasis. 69-70

Pain relief and management is on most of my clients’ minds when they come to see me.  Pain usually means inflammation. As we are currently in the middle of an opioid epidemic, finding alternatives to opioids is critical.  More and more studies are showing cannabis can provide pain relief without causing feelings of intoxication:

• One study found topically administered cannabinoid agonists may reduce pain without the psychoactive effects of internal consumption of cannabis. 71  
• Another study found general anti‐inflammatory effects of CBD application to skin, making it a potential treatment for acne, other inflammatory skin disorders, and possibly even wound healing.19, 57
• Another study found “topical medical cannabis” helped patients with Pyoderma Gangrenosum (a rare inflammation skin disorder that causes painful sores and ulcers) heal faster from there open wounds.  Also, patients felt analgesic effects within five minutes of applying the topical on the open sores. 65
• A study found topically administered cannabinoid agonists may reduce pain without the side effects of opiates. 72

Cannabis and Muscles

What about the muscles, a main concern of massage therapists?  We know the endocannabinoid system is involved in metabolic regulation and glycemic control. Skeletal muscle plays an important role in metabolic regulation and glycemic control. CB1 receptors have been detected in skeletal muscle 73 and studies suggest blockage of CB1 may have direct effects on skeletal muscle modulating energy homeostasis. 74-75

Studies regarding the ECS and muscles are not as plentiful as studies dealing with the skin.  You can find studies such as “The role of the endocannabinoid system in skeletal muscle and metabolic adaptation to exercise: potential implications for the treatment of obesity” 76 and studies that look at the effects of a high-fat diet and CB1 receptor blockade. 77 It is not a surprise that much less data is available on the effects of cannabis on skeletal muscles than on other tissues, given the current restrictions on research due to its Schedule I classification under the Controlled Substance Act (CSA). 78

Drawback to Cannabis Topicals

Using cannabis topicals does have a few negatives. We may not know all the ingredients in the different topicals because regulations are not standard.  Ingredients may be different for hemp-derived topicals, cannabis health and beauty aids (CHABA – marijuana-derived topicals with not more than 0.3% THC in WA state), 79 or marijuana-derived topicals (stronger cannabis topicals in Washington). A person can be allergic to some of the ingredients, such as nut-based oils. Some people can be allergic to the terpenes, such as linalool.  

Some cannabis-infused topicals have added preservatives or perfumes that people can be sensitive to.  Unfortunately, we do not know how the cannabis was grown. Is it clean? Is it free of metals and toxins? Is it pesticide free? If not, do you want to rub it all over yourself or someone else?

Conclusion

Studies on the skeletal muscle ECS are not as common as studies for the skin ECS. Currently, there are no published studies on massage therapy and the use of cannabis topicals. Further studies on the entourage effect and the phytocannabinoid-terpenoid relationship are much needed and are very promising for a better future for mankind.

Anecdotal evidence suggests adults who incorporate massage therapy with cannabis topicals, that include terpenoids, into a regular and consistent health care regimen can find a better quality of life and relief from a multitude of health issues without a high feeling.  Many of my fellow massage therapists’ clients are seeing their skin get “stronger” and repair itself faster. They are feeling pain and inflammation relief, so their quality of life is better without “big pharma” side effects. They feel like their muscles relax faster while on the massage table and the benefits from massage therapy last longer than without the cannabis topicals.   

Massage therapy is good for you, but if you add a cannabis-infused topical to that massage, it will be an even better experience over time, physically and mentally.  With all the positive experiences and possible potential, massage therapy with cannabis topicals has become intriguing and it justifies the need for future studies.

Have you booked your next massage yet?  What are you waiting for?

References

1. Hou, W.H., Chiang, P.T., Hsu, T.Y., Chiu, S.Y., Yen, Y.C. (2010). Treatment effects of massage therapy in depressed people: a meta-analysis. J Clin Psychiatry. 71(7):894-901.
2. Gitlin L.N., Kales H.C., Lyketsos C.G. Managing behavioral symptoms in dementia using nonpharmacologic approaches: an overview. JAMA. 2012; [PubMed]
3. 2017 American Massage Therapy Association Consumer Surveys
4. Lozano, Indalecio. (2001) The Therapeutic Use of Cannabis sativa (L.) in Arabic Medicine.  Journal of Cannabis Therapeutics, Vol. 1 (1).  Retrieved from www.cannabis-med.org/data/pdf/2001-01-4_0.pdf
5. Marcandier M. [Hemp Treaty]. In French. Chez Nyon: Paris, 1758;138
6. Ibn Sina A. Kanun fi at-Tibb (Canon of medicine) [in Arabic]. 2ndvol. Manuscript from the collection of the Institute of Manuscripts: Baku, Azerbaijan, copied 1143
7. Russo G 2006, A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol Medical Hypotheses. Online. Available at http://analytica1360. com/wp-content/uploads/2011 /08/Russo_Tale_of_Two_ Cannabinoids_Med_Hypoth_2006.pdf
8. Ryz NR, Remillard DJ, Russo EB. Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain. Cannabis Cannabinoid Res. 2017;2(1):210-216. Published 2017 Aug 1. doi:10.1089/can.2017.0028
9. Massage Therapy Journal. (2012) Power of Touch, 26 https://www.amtamassage.org/uploads/cms/documents/client_tearout_web_su12.pdf
10. Rapaport MH, Schettler P, Bresee C. A preliminary study of the effects of a single session of Swedish massage on hypothalamic– pituitary–adrenal and immune function in normal individuals.  [PMC free article]
11. Preyde M. (2003) Effectiveness of massage therapy for subacute low back pain: a randomized controlled trial. Journal of Soft Tissue Manipulation, 8, 4 – 10.
12. Piotrowski, M., Paterson, C., Mitchinson, A., Kim, H. M., Kirsh, M., Hinshaw, D. B. (2003) Massage as Adjuvant Therapy in the Management of Acute Postoperative Pain: A Preliminary Study in Men. Journal of the American College of Surgeons, 197(6), 1037-1046.
13. Field, T., Diego, Miguel, Cullen, Christy, Hartshorn, Kristin, Gruskin, Alan, Hernandez-Reif, Maria, Sunshine, William. (2004). Carpal tunnel syndrome symptoms are lessened following massage. Journal of Bodywork and Movement Therapies. 8:9-14. http://www.massagetherapyfoundation.org/pdf/Massage%20and%20carpal%20tunnel%20syndrome.pdf
14. American College of Physicians. (2008) Massage Therapy May Have Immediate Positive Effect On Pain And Mood For Advanced Cancer Patients. Science Daily 16 September. http://www.sciencedaily.com/releases/2008/09/080915174534.htm.
15. Castro-Sánchez, A.M., Matarán-Peñarrocha, G.A., Granero-Molina, J., Aguilera-Manrique, G., Quesada-Rubio, J.M., Moreno-Lorenzo, C. (2011). Benefits of massage-myofascial release therapy on pain, anxiety, quality of sleep, depression, and quality of life in patients with fibromyalgia. Evid Based Complement Alternat Med. 2011:561753.
    Released February 23, 2017
16. Perlman AI, Sabina A, Williams AL, Njike VY, Katz DL. (2006) Massage Therapy for Osteoarthritis of the Knee. Arch Intern Med. 166(22):2533-8.
17. Sefton JM, Yarar C, Berry JW, et al. Six weeks of massage therapy produces changes in balance, neurological and cardiovascular measures in older persons. International Journal of Therapeutic Massage & Bodywork.2012; 5(3):28-40. Helmick CG., et al. Estimates of the Prevalence of Arthritis and Other Rheumatic Conditionsin the United States. Arthritis & Rheumatism. 2008 January; 58:15-25.
18. Quinn C, Chandler C, Moraska A. Massage Therapy & Frequency of Chronic Tension Headaches. (2002) American Journal of Public Health. 92(10):1657-61.
19. Biro T, Toth BI, Hasko G, Paus R, Pacher P. The endocannabinoid system of the skin in health and disease: Novel perspectives and therapeutic opportunities. Trends Pharmacol Sci 2009;30(8):411–420. [PubMed]
20. Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z et al. (1998). An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol 353: 23–31.
21. Mehmedic, Z., Chandra, S., Slade, D., Denham, H., Foster, S., Patel, A. S., et al. (2010).
    Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations
    from 1993 to 2008*. Journal of Forensic Sciences, 55(5), 1209–1217. http://doi.org/10.
    1111/j.1556-4029.2010.01441.x
22. Falk, A. A., Hagberg, M. T., Lof, A. E., Wigaeus-Hjelm, E. M., & Wang, Z. P. (1990).
    Uptake, distribution and elimination of alpha-pinene in man after exposure by inhalation. Scandinavian Journal of Work, Environment and Health, 16(5), 372–378.
23. Russo, E. B. (2011). Taming THC: Potential cannabis synergy and phytocannabinoid terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344–1364. http://
    doi.org/10.1111/j.1476-5381.2011.01238.x.
24. Jäger W, Buchbauer G, Jirovetz L, Fritzer M (1992). Percutaneous absorption of lavender oil from a massage oil. J Soc Cosmet Chem 43 (Jan/Feb): 49–54.
25. Noma, Y., & Asakawa, Y. (2010). Biotransformation of monoterpenoids by microorganisms,
    insects, and mammals. In K. H. C. Baser & G. Buchbauer (Eds.), Handbook of essential oils:
    Science, technology, and applications (pp. 585–736). Boca Raton, FL: CRC Press.
26. Gil, M. L., Jimenez, J., Ocete, M. A., Zarzuelo, A., & Cabo, M. M. (1989). Comparative
    study of different essential oils of Bupleurum gibraltaricum Lamarck. Pharmazie,
    44(4), 284–287.
27. Nissen L, Zatta A, Stefanini I, Grandi S, Sgorbati B, Biavati B et al. (2010). Characterization and antimicrobial activity of essential oils of industrial hemp varieties (Cannabis sativa L.). Fitoterapia 81:413–419.
28. Buchbauer G, Jirovetz L, Jager W, Plank C, Dietrich H (1993). Fragrance compounds and essential oils with sedative effects upon inhalation. J Pharm Sci 82: 660–664.
29. Kasuya, H., Okada, N., Kubohara, M., Satou, T., Masuo, Y., & Koike, K. (2015). Expression
    of BDNF and TH mRNA in the brain following inhaled administration of alpha-pinene.
    Phytotherapy Research, 29(1), 43–47. http://doi.org/10.1002/ptr.5224.
30. Satou, T., Kasuya,H., Maeda, K., & Koike, K. (2014). Daily inhalation of alpha-pinene in mice: Effects on behavior and organ accumulation. Phytotherapy Research, 28(9), 1284–1287.
31. Basile AC, Sertie JA, Freitas PC, Zanini AC (1988). Anti-inflammatory activity of oleoresin from Brazilian Copaifera. J Ethnopharmacol 22: 101–109.
32. Katsuyama, S., Mizoguchi, H., Kuwahata, H., Komatsu, T., Nagaoka, K., Nakamura, H.,
    et al. (2013). Involvement of peripheral cannabinoid and opioid receptors in betacaryophyllene-induced antinociception. European Journal of Pain (London, England), 17(5), 664–675. http://doi.org/10.1002/j.1532-2149.2012.00242.x.
33. Bahi, A., Al Mansouri, S., Al Memari, E., Al Ameri, M., Nurulain, S. M., & Ojha, S. (2014).
    β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant
    to anxiety and depression in mice. Physiology & Behavior, 135C, 119–124. http://doi.org/
    10.1016/j.physbeh.2014.06.003.
34. Falk-Filipsson, A., Lof, A., Hagberg, M., Hjelm, E. W., & Wang, Z. (1993). d-limonene
    exposure to humans by inhalation: Uptake, distribution, elimination, and effects on
    the pulmonary function. Journal of Toxicology and Environmental Health, 38(1), 77–88.
35. Carvalho-Freitas, M. I., & Costa, M. (2002). Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biological & Pharmaceutical Bulletin, 25(12), 1629–1633.
36. Komori T, Fujiwara R, Tanida M, Nomura J, Yokoyama MM (1995). Effects of citrus fragrance on immune function and depressive states. Neuroimmunomodulation 2: 174–180.
37. Russo, E. B. (2001). Handbook of psychotropic herbs: A scientific analysis of herbal remedies for psychiatric conditions. Binghamton, NY: Haworth Press.
38. Gattefosse, R.-M. (1993). Gatefosse’s aromatherapy (R. W. Tisserand, Trans.). Essex: C.W.
    Daniel.
39. Re L, Barocci S, Sonnino S, Mencarelli A, Vivani C, Paolucci G et al. (2000). Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse neuromuscular junction. Pharmacol Res 42: 177–182.
40. Monti D, Chetoni P, Burgalassi S, Najarro M, Saettone MF, Boldrini E (2002). Effect of different terpene-containing essential oils on permeation of estradiol through hairless mouse skin. Int J Pharm 237: 209–214.
41. Kim JT, Ren CJ, Fielding GA, Pitti A, Kasumi T, Wajda M et al. (2007). Treatment with lavender aromatherapy in the post-anesthesia care unit reduces opioid requirements of morbidly
    obese patients undergoing laparoscopic adjustable gastric banding. Obes Surg 17: 920–925.
42. Lorenzetti BB, Souza GE, Sarti SJ, Santos Filho D, Ferreira SH (1991). Myrcene mimics the peripheral analgesic activity of lemongrass tea. J Ethnopharmacol 34: 43–48.
43. Rao VS, Menezes AM, Viana GS (1990). Effect of myrcene on nociception in mice. J Pharm Pharmacol 42: 877–878.
44. Bisset NG, Wichtl M (2004). Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on A Scientific Basis, 3rd edn. Medpharm Scientific Publishers: Stuttgart; CRC Press: Boca Raton, FL
45. do Vale TG, Furtado EC, Santos JG Jr, Viana GS (2002). Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown. Phytomed 9: 709–714.
46. Chiurchiù V, Battistini L, Maccarrone M. Endocannabinoid signaling in innate and adaptive immunity. Immunology. 2015;144(3):352–364. [PubMed]
47. Kupczyk, et al 2009. Cannabinoid system in the skin – a possible target for future therapies in dermatology Experimental Dermatology. 8:669-679
48. Stander et al Stander, S., Reinhardt, H.W., and Luger, T.A. [Topical cannabinoid  agonists: an effective new possibility for treating chronic pruritus]. Der Hautarzt. 2006; 57: 801–807. [PubMed]
49. Szepietowski, J.C., Szepietowski, T., and Reich, A. Efficacy and tolerance of  the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary  study. Acta Dermatovenerologica Croatica. 2005; 13: 97-103
50. Todurga, Z.G., Gunduz, O., Karadag, C.H., and Ulugol, A. Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids. Acta Neuropsychiatr. 2016; 28: 321–326.
51. Pulvirenti N, et al. Topical adelmidrol 2% emulsion, a novel aliamide, in the treatment of mild atopic dermatitis in pediatric subjects: a pilot study. Acta Dermatovenerol. Croat. 2007;15:80–83. [PubMed]
52. Leonti, M., Casu, L., Raduner, S. et al.Falcarinol is a covalent cannabinoid CB1  receptor antagonist and induces pro‐allergic effects in skin. Biochem Pharmacol. 2010; 79: 1815–1826
53. Nam G, Jeong SK, Park BM.  Ann Dermatol. 2016 Feb;28(1):22‐9. doi: 10.5021/ad.2016.28.1.22.  Epub 2016 Jan 28. Selective Cannabinoid Receptor‐1 Ag Model. Namazi MR1. Cannabinoids,  loratadine and allopurinol as novel additions to the antipsoriatic ammunition. J Eur Acad Dermatol Venereol. 2005 May;19(3):319‐22.
54. Gaffal E, Cron M, Glodde N, Tüting.   T.Allergy. 2013 Aug; 68(8): 994‐1000. doi:  10.1111/all.12183. Epub 2013 Jul 29. Anti‐inflammatory activity of topical THC in DNFB mediated mouse allergic contact dermatitis independent of CB1 and  CB2 receptors.
55. Karsak M, et al. Attenuation of allergic contact dermatitis through the endocannabinoid system. Science. 2007;316:1494–1497. [PubMed]
56. Lambert DM. Allergic contact dermatitis and the endocannabinoid system: from mechanisms to skin care. ChemMedChem. 2007;2:1701–1702.[PubMed]
57. Olah A, Toth BI, Borbiro I, et al. Cannabidiol exerts sebostatic and anti-inflammatory effects on human sebocytes. J Clin Invest. 2014;124(9):3713–3724. [PubMed]
58. Ali A, Akhtar N. The safety and efficacy of 3% Cannabis seeds extract cream for reduction of human cheek skin sebum and erythema content. Pak J Pharm Sci. 2015;28(4): 1389-95
59. Dobrosi N, Tóth BI, Nagy G, Dózsa A, Géczy T, Nagy L, Zouboulis CC, Paus R, Kovács L, Bíró T. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling. FASEB Journal. 2008;22(10):3685-95.
60. Qin, N., Neeper, M. P., Liu, Y., Hutchinson, T. L., Lubin, M. L., & Flores, C. M. (2008).
    TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal
    root ganglion neurons. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 28(24), 6231–6238. http://dx.doi.org/10.1523/JNEUROSCI.0504-08.2008.28/24/6231 [pii]
61. Russo, E. B. (2014). The pharmacological history of Cannabis. In R. Pertwee (Ed.), Handbook of Cannabinoids. (pp. 23–43). Oxford, United Kingdom: Oxford University Press.
62. Blazquez C, et al. Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J. 2006;20:2633–2635. [PubMed]
63. A. J. Hampson, M. Grimaldi, J. Axelrod, and D. Wink, “Cannabidiol and (−)∆9-Tetrahydrocannabinol Are Neuroprotective Antioxidants,” Proceedings of the National Academy of Sciences of the United States of America 95, no. 14 (1998): 8268–8273.
64. Casanova ML, et al. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J. Clin. Invest. 2003;111:43–50.[PMC free article] [PubMed]
65. Maida MD V, Corban MD J, et al. Topical Medical Cannabis: Treatment for Wound Pan – Three Cases of Pyoderma Gangrenosum. Journal of Pain and Sympton Management. 2017; 54(5): 732-736
66. Guzman M. Cannabinoids: potential anticancer agents. Nat Rev Cancer. 2003;3:745–755. [PubMed]
67. Sarfaraz S, Adhami VM, Syed DN, Afaq F, Mukhtar H. Cannabinoids for cancer treatment: progress and promise. Cancer Res. 2008;68:339–342.[PubMed]
68. Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther 2015;97(6)575–586. [PubMed]
69. Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J. Dermatol. Sci. 2007;45:87–92. [PubMed]
70. Hashim PW, Cohen JL, Pompei DT, Goldenberg G. Topical cannabinoids in dermatology. Cutis 2017;100(1):50-52. [PubMed];
71. Dogrul A, Gul H, Akar A, Yildiz O, Bilgin F, Guzeldemir E.  Topical cannabinoid antinociception: synergy with spinal sites. Pain. 105(1-2):11-6. [PubMed]
72. Jorge, Feres, et al 2011, Topical preparations for pain relief: efficacy and patient adherence Journal of Pain Research, 4:11-24
73. Mendizabal-Zubiaga J, Melser S, Bénard G, et al. Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration. Front Physiol. 2016;7:476. Published 2016 Oct 25. doi:10.3389/fphys.2016.00476
74. Viveros MP, Bermúdez-Silva FJ, Lopez-Rodriguez AB, Wagner EJ. The Endocannabinoid System as Pharmacological Target Derived from Its CNS Role in Energy Homeostasis and Reward. Applications in Eating Disorders and Addiction. Pharmaceuticals (Basel). 2011;4(8):1101–1136. Published 2011 Aug 10. doi:10.3390/ph4081101
75. Arrabal S, Lucena MA, Canduela MJ, et al. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle. PLoS One. 2015;10(12):e0145244. Published 2015 Dec 15. doi:10.1371/journal.pone.0145244
76. Heyman E1, Gamelin FX, Aucouturier J, Di Marzo V. The role of the endocannabinoid system in skeletal muscle and metabolic adaptations to exercise: potential implications for the treatment of obesity. Obes Rev. 2012;13(12):1110-24.
77. Crespillo A1, Suárez J, Bermúdez-Silva FJ, Rivera P, Vida M, Alonso M, Palomino A, Lucena MA, Serrano A, Pérez-Martín M, Macias M, Fernández-Llébrez P, Rodríguez de Fonseca F. Expression of the cannabinoid system in muscle; effects of a high-fat diet and CB1 receptor block. Biochem J. 2011;433(1):175-85 [PubMed]
78. Drug Enforcement Administration – Controlled Substance Act by schedule. https://www.deadiversion.usdoj.gov/schedules/orangebook/e_cs_sched.pdf
79. WA State Legislative.  RCW 69.50.575 Cannabis Health and Beauty Aids https://app.leg.wa.gov/rcw/default.aspx?cite=69.50.575