Why I Love Cannabis Topicals: Clinical Pearls for Topical Cannabis Use

Why I Love Cannabis Topicals: Clinical Pearls for Topical Cannabis Use

 In Clinical Pearls
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JAKE F. FELICE, ND, LMP 

The purpose of this article is to describe one clinician’s experience with medical cannabis.   

Why Cannabis Topicals? 

Non-steroidal anti-inflammatory drugs (NSAIDS) and opiates represent the mainstay of pharmacological treatment for pain. Their use is increasing over time1–3 and they are associated with very significant morbidity and mortality.4–7 Viable alternatives to opiates and NSAIDS are desperately needed. Medical cannabis possesses very low toxicity, can be used along with opiates, is effective for pain, is generally well tolerated, and is associated with significant decreases in the use of both NSAIDS and opiates.8–11  

Cannabis topicals are an ideal introduction to the world of medical cannabis for cannabis-naïve patients. One reason is that topical products, even the ones containing tetrahydrocannabinol (THC), do not give patients a head high. Also, because cannabis topicals bypass the digestive system, they avoid first-pass metabolism in the liver and therefore pose no risk for potential herb-drug interactions.   

Topical cannabis products include infused oils, lotions, and balms that can be applied to the skin. They are an affordable and increasingly accessible modality for pain relief, itch, and inflammation. New transdermal innovations, including transdermal patches, are fast arriving in the cannabis and cannabidiol (CBD) markets. Consumers throughout all 50 states now have access to hemp-derived cannabis topical products via online purchasing.   

This paper focuses on clinical pearls and applications that this plant has taught me over the last 15 years. For those readers who are interested in a more in-depth look at the research than is covered in this paper, please see my online article “Topical Cannabis: Research Review.”10  

The skin is the largest organ of the body, yet its importance is often neglected by clinicians. It acts as a barrier and is our first line of defense. Skin is responsible for critical transmission of biologic information, exchanging and receiving data from events in the external environment, and transmitting them to our internal organs and immune system. This biologic information travels via neural, endocrine, and immune cell messaging, as well as via the endocannabinoid system (ECS) to regulate local and global homeostasis.12   

A large percentage of my patients use topical cannabis products combined with oral cannabis products, and report positive results when combining these delivery methods. This makes sense given the synergistic coordination between peripheral, spinal, and central sites of the ECS in the central nervous system.13–19 Additionally, it is likely that additive or synergistic effects are occurring not only between different cannabinoids, such as THC and CBD, but also between topical cannabinoids and topical opiates.18 

Applications & Clinical Pearls 

Topical cannabinoids may significantly improve skin barrier function,20 which is an essential feature in addressing itch.21 Certain phytocannabinoids that enhance sebum production may be effective in treating dry-skin syndrome.22 Evidence from cell-culture, human, and animal studies also demonstrates potential applications for topical cannabinoids in the following areas: 

  • Acne22-24  
  • Wound healing25-27   
  • Myositis28  
  • Psoriasis29  
  • Eczema20,30,31   
  • Arthritis32-35   
  • Multiple sclerosis36 
  • Contact dermatitis37-39 
  • Atopic dermatitis37 
  • Neuropathic pain40-42 
  • Post-operative pain17  

Additional properties of topical cannabinoids derived from in-vitro and animal studies include inhibitory effects on sebocyte proliferation23 and differentiation, tumorigenesis, inflammation, sensation of pain, and itch.12,21 

Topical cannabis products are dose-dependent, meaning that a critical amount (concentration) of cannabinoids contained in topical preparations is essential for achieving optimal relief.10 Also, the more cannabinoids one applies to the skin, the more effective they are. Cannabinoid concentration is an important consideration when making product recommendations to patients; ie, they should be informed of this concentration-dependent attribute when they are shopping online for the most effective products.   

It is also important to explain to patients that topical cannabis products are not miracle drugs. They should be informed that cannabis topicals are mildly effective for pain and are typically short-acting, providing relief that typically lasts between 4 and 5 hours. Frequently, multiple applications may be necessary for maximum relief.     

Patients can be reassured that, according to the limited available human research, topical cannabis products are generally well tolerated.43,44 Because absorption of topicals can be enhanced by carrier ingredients such as ethanol,45,46 attention to the carriers with which a topical cannabis product is delivered is important in order to ensure efficient transmission across the skin barrier.   

One easy way to enhance absorption of cannabinoids across the skin barrier is to use an alcohol-based tincture of cannabis as a spray. In addition, applying copaiba oil or castor oil to the skin after using the cannabis spray may help drive the cannabinoids through the epidermis. These oils have been shown in animal models to penetrate well and possess anti-inflammatory and pain-relieving properties in their own rights.47,48 An anti-inflammatory oil can offer potential additive and synergistic effects when given along with cannabinoids. “Driving” agents such as dimethyl sulfoxide (DMSO) may also be considered.49 DMSO also has anti-inflammatory properties,46 though it may not be as well tolerated as a cannabis topical.   

Shock wave therapy or ultrasound can also enhance absorption of topical cannabis by helping drive the topical through the epidermis immediately following its application.50,51 This might be a consideration for clinicians who already have this equipment in their offices. 

CBD in Sunscreens 

Research indicates that the ECS plays a role in the detection of tissue injury.52 Interestingly, the ECS is also involved in protecting skin from ultraviolet (UV) radiation.53,54 Specifically, topical cannabinoids may offer protection after UV sun exposure.55 A recent study described dose-dependent protective effects of CBD on UV-exposed melanocytes and keratinocytes.56 Because CBD does not exhibit absorption in the UVB spectra, this effect was thought to be due to the scavenging of reactive oxygen species (ROS) rather than the blocking of UV exposure.56 

Topical CB2 Agonism 

Beta-caryophyllene in Topicals 

Stimulation of cannabinoid receptor-2 (CB2) has been shown in mice to reduce neuropathic pain.57 Beta-caryophyllene is a terpenoid in cannabis that acts as a CB2 receptor agonist and has been demonstrated to specifically diminish neuropathic pain in animals.58 Beta-caryophyllene has also been shown to contribute to the entourage effects of cannabis.59 I have personally found products rich in beta-caryophyllene to be advantageous for pain, especially when there is an element of neuropathic pain involved.  

Although I am unaware of any peer-reviewed research specifically examining the effects of topical cannabis products containing high levels of beta-caryophyllene, the animal research gives us reason to consider these in topical formulations. This is an area that will benefit from future research. 

The high concentration of beta-caryophyllene in oils such as copaiba oil60 makes them ideal as carrier oils for topical cannabis products. Black pepper and rosemary also contain large amounts of beta-caryophyllene, thus can be added as support herbs to a topical botanical formula containing hemp or cannabis.59 Many cannabis products come with certificates of analysis (COAs), and patients can be instructed in how to search for and read COAs online at the manufacturers’ websites.  

Echinacea 

Another botanical compound that stimulates the CB2 receptor is Echinacea. Its alkylamide molecules bind to the CB2 receptor, even at low nanomolar concentrations.61  

Multiple naturopathic physicians have found that Echinacea can positively impact neuropathic pain in shingles. Incorporating Echinacea into a tincture with cannabis may therefore be helpful as a topical when treating this condition. The vesicles that occur during shingles do not react well to lotions or creams due to their fragility, and the fragile, sensitive skin barrier can be disrupted by the pressure required to apply these products. A topical spray can be applied to the area so that the patient does not have to touch the skin directly.  

I have also had numerous patients report moderate relief from flank pain during the passage of kidney stones after applying topical cannabis to the skin overlying the site of the pain. 

Conclusion 

Because topical cannabis products are generally well tolerated and do not cause a head high, these products can be an ideal choice for introducing patients to the therapeutic benefits of cannabis. Topicals are affordable, easy to apply, well tolerated, and do not adversely interact with systemic pharmaceutical drugs. While it is apparent that much more human research is needed to fully assess the potential benefits and limitations of the topical application of cannabinoids, their low toxicity along with high potential for benefit provides a good rationale for clinicians to consider topical cannabis lotions, creams, salves and patches in their treatment regimens.   

References: 

  1. Centers for Disease Control and Prevention. Opioid Overdose. Understanding the Epidemic. Last reviewed March 17, 2021. CDC Web site. https://www.cdc.gov/drugoverdose/epidemic/. Accessed March 28, 2021. 
  1. Davis JS, Lee HY, Kim J, et al. Use of non-steroidal anti-inflammatory drugs in US adults: Changes over time and by demographic. Open Heart. 2017;4(1):e000550.  
  1. Phillips JK, Ford MA, Bonnie RJ, eds. Trends in Opioid Use, Harms, and Treatment. In: Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use. Washington DC: National Academies Press; 2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK458661/. Accessed March 28, 2021. 
  1. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999;340(24):1888-1899.  
  1. Frech EJ, Go MF. Treatment and chemoprevention of NSAID-associated gastrointestinal complications. Ther Clin Risk Manag. 2009;5(1):65-73.   
  1. Centers for Disease Control and Prevention. Drug Overdose Deaths. Last reviewed March 3, 2021. CDC Web site. https://www.cdc.gov/drugoverdose/data/statedeaths.html. Accessed March 28, 2021. 
  1. Liu S, Scholl L, Hoots B, Seth P. Nonfatal Drug and Polydrug Overdoses Treated in Emergency Departments – 29 States, 2018–2019. MMWR Morb Mortal Wkly Rep. 2020;69(34):1149-1155.  
  1. Corroon JM Jr, Mischley LK, Sexton M. Cannabis as a substitute for prescription drugs – A cross-sectional study. J Pain Res. 2017;10:989-998.  
  1. Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668-1673.  
  1. Felice JF. Topical Cannabis: Research Review. August 5, 2020. NDNR. Available at: https://ndnr.com/uncategorized/topical-cannabis-research-review/. Accessed March 28, 2021. 
  1. Corroon J, Felice JF. The Endocannabinoid System and its Modulation by Cannabidiol (CBD). Altern Ther Health Med. 2019;25(S2):6-14. 
  1. Slominski AT, Zmijewski MA, Skobowiat C, et al. Sensing the environment: regulation of local and global homeostasis by the skin’s neuroendocrine system. Adv Anat Embryol Cell Biol. 2012;212:v, vii, 1-115.  
  1. Palazzo E, Luongo L, de Novellis V, et al. The role of cannabinoid receptors in the descending modulation of pain. Pharmaceuticals (Basel). 2010;3(8):2661-2673.  
  1. Kress M, Kuner R. Mode of action of cannabinoids on nociceptive nerve endings. Exp Brain Res. 2009;196(1):79-88.  
  1. Pertwee RG. Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol. 2009;156(3):397-411.  
  1. Paus R, Schmelz M, Bíró T, Steinhoff M. Frontiers in pruritus research: Scratching the brain for more effective itch therapy. J Clin Invest. 2006;116(5):1174-1185.  
  1. Zhu CZ, Mikusa JP, Fan Y, et al. Peripheral and central sites of action for the non-selective cannabinoid agonist WIN 55,212-2 in a rat model of post-operative pain. Br J Pharmacol. 2009;157(4):645-655.  
  1. Yesilyurt O, Dogrul A, Gul H, et al. Topical cannabinoid enhances topical morphine antinociception. Pain. 2003;105(1-2):303-308.  
  1. Dogrul A, Gul H, Akar A, et al. Topical cannabinoid antinociception: Synergy with spinal sites. Pain. 2003;105(1-2):11-16.  
  1. Yuan C, Wang XM, Guichard A, et al. N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: Results of a randomized, double-blind, controlled study in 60 patients. Clin Interv Aging. 2014;9:1163-1169.  
  1. Elmariah SB, Lerner EA. Topical therapies for pruritus. Semin Cutan Med Surg. 2011;30(2):118-126.  
  1. Oláh A, Markovics A, Szabó-Papp J, et al. Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment. Exp Dermatol. 2016;25(9):701-707.  
  1. Oláh A, Tóth BI, Borbíró I, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. J Clin Invest. 2014;124(9):3713-3724.  
  1. Nickles MA, Lio PA. Cannabinoids in Dermatology: Hope or Hype? Cannabis Cannabinoid Res. 2020;5(4):279-282.  
  1. Klein M, de Quadros De Bortolli J, Guimarães FS, et al. Effects of cannabidiol, a Cannabis sativa constituent, on oral wound healing process in rats: Clinical and histological evaluation. Phytother Res. 2018;32(11):2275-2281.  
  1. Maida V. Medical Cannabis in the Palliation of Malignant Wounds – A Case Report. J Pain Symptom Manage. 2017;53(1):e4-e6.  
  1. Maida V, Corban J. Topical Medical Cannabis: A New Treatment for Wound Pain – Three Cases of Pyoderma Gangrenosum. J Pain Symptom Manage. 2017;54(5):732-736.  
  1. Sánchez Robles EM, Bagües Arias A, Martín Fontelles MI. Cannabinoids and muscular pain. Effectiveness of the local administration in rat. Eur J Pain. 2012;16(8):1116-1127.  
  1. Szachowicz-Petelska B, Łuczaj W, Wroński A, et al. The Differential Effect of Cannabidiol on the Composition and Physicochemical Properties of Keratinocyte and Fibroblast Membranes from Psoriatic Patients and Healthy People. Membranes. 2021;11(2):111.  
  1. Wohlman IM, Composto GM, Heck DE, et al. Mustard vesicants alter expression of the endocannabinoid system in mouse skin. Toxicol Appl Pharmacol. 2016;303:30-44.  
  1. Eberlein B, Eicke C, Reinhardt HW, Ring J. Adjuvant treatment of atopic eczema: Assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol. 2008;22(1):73-82.  
  1. Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20(6):936-948.  
  1. Lodzki M, Godin B, Rakou L, et al. Cannabidiol-transdermal delivery and anti-inflammatory effect in a murine model. J Control Release.  2003;93(3):377-387.  
  1. Schuelert N, McDougall JJ. Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 2008;58(1):145-153.  
  1. Schuelert N, Johnson MP, Oskins JL, et al. Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain. 2011;152(5):975-981.  
  1. Giacoppo S, Galuppo M, Pollastro F, et al. A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. Daru. 2015;23:48.  
  1. Yarbrough KB, Neuhaus KJ, Simpson EL. The effects of treatment on itch in atopic dermatitis. Dermatol Ther. 2013;26(2):110-119.  
  1. Gaffal E, Cron M, Glodde N, Tüting T. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors. Allergy. 2013;68(8):994-1000.  
  1. Gaffal E, Cron M, Glodde N, et al. Cannabinoid 1 Receptors in Keratinocytes Modulate Proinflammatory Chemokine Secretion and Attenuate Contact Allergic Inflammation. J Immunol. 2013;190(10):4929-4936.  
  1. Xu DH, Cullen BD, Tang M, Fang Y. The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities. Curr Pharm Biotechnol. 2019;21(5):390-402.  
  1. Hesselink JM, Hekker TA. Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. J Pain Res. 2012;5:437-442.  
  1. Lever IJ, Pheby TM, Rice ASC. Continuous infusion of the cannabinoid WIN 55,212-2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity. Br J Pharmacol. 2007;151(2):292-302.  
  1. Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat. 2005;13(2):97-103.  
  1. Phan NQ, Siepmann D, Gralow I, Ständer S. Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. J Dtsch Dermatol Ges. 2010;8(2):88-91. [Article in English, German]  
  1. Stinchcomb AL, Valiveti S, Hammell DC, Ramsey DR. Human skin permeation of Delta8-tetrahydrocannabinol, cannabidiol and cannabinol. J Pharm Pharmacol. 2004;56(3):291-297.  
  1. Percy EC, Carson JD. The use of DMSO in tennis elbow and rotator cuff tendonitis: A double-blind study. Med Sci Sports Exerc. 1981;13(4):215-219.  
  1. Alvarenga MOP, Bittencourt LO, Mendes PFS, et al. Safety and effectiveness of copaiba oleoresin (C. reticulata ducke) on inflammation and tissue repair of oral wounds in rats. Int J Mol Sci. 2020;21(10):3568.  
  1. Vieira C, Evangelista S, Cirillo R, et al. Effect of ricinoleic acid in acute and subchronic experimental models of inflammation. Mediators Inflamm. 2000;9(5):223-228.  
  1. Horita A, Weber LJ. Skin penetrating property of drugs dissolved in dimethylsulfoxide (DMSO) and other vehicles. Life Sci. 1964;3(12):1389-1395.  
  1. Maier M, Staupendahl D, Duerr HR, Refior HJ. Castor oil decreases pain during extracorporeal shock wave application. Arch Orthop Trauma Surg. 1999;119(7-8):423-427.  
  1. Dedes V, Tzirogiannis K, Polikandrioti M, et al. Radial extra corporeal shockwave therapy versus ultrasound therapy in the treatment of plantar fasciitis. Acta Inform Med. 2019;27(1):45-49.  
  1. Akopian AN, Ruparel NB, Jeske NA, et al. Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia. Trends Pharmacol Sci. 2009;30(2):79-84.  
  1. Gegotek A, Biernacki M, Ambrozewicz E, et al. The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation. J Dermatol Sci. 2016;81(2):107-117.  
  1. Gęgotek A, Atalay S, Domingues P, Skrzydlewska E. The Differences in the Proteome Profile of Cannabidiol-Treated Skin Fibroblasts following UVA or UVB Irradiation in 2D and 3D Cell Cultures. Cells. 2019;8(9):995.  
  1. Atalay S, Dobrzyńska I, Gęgotek A, Skrzydlewska E. Cannabidiol protects keratinocyte cell membranes following exposure to UVB and hydrogen peroxide. Redox Biol. 2020;36:101613.  
  1. Gohad P, McCoy J, Wambier C, et al. Novel cannabidiol sunscreen protects keratinocytes and melanocytes against ultraviolet B radiation. J Cosmet Dermatol. 2020 Sep 16. doi: 10.1111/jocd.13693. [Epub ahead of print] 
  1. Sheng WS, Chauhan P, Hu S, et al. Antiallodynic Effects of Cannabinoid Receptor 2 (CB 2 R) Agonists on Retrovirus Infection-Induced Neuropathic Pain. Pain Res Manage. 2019;2019:1-12.  
  1. Aly E, Khajah MA, Masocha W. β-caryophyllene, a CB2-receptor-selective phytocannabinoid, suppresses mechanical allodynia in a mouse model of antiretroviral-induced neuropathic pain. Molecules. 2019;25(1):106.  
  1. Russo EB. Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.  
  1. Ames-Sibin AP, Barizão CL, Castro-Ghizoni CV, et al. β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats. J Cell Biochem. 2018;119(12):10262-10277.  
  1. Raduner S, Majewska A, Chen JZ, et al. Alkylamides from Echinacea are a new class of cannabinomimetics: Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J Biol Chem. 2006;281(20):14192-14206.

Jake F. Felice, ND, LMP is a cannabis author, clinician, educator, and consultant whose vision is to advance the science and practical application of cannabis for medical and recreational markets around the world. Dr Felice provides world-class educational experiences by speaking authentically about hemp and cannabis. He consults with healthcare providers, industry, and the general public. His Category 1 CME courses for doctors, nurses, and pharmacists has been translated into 4 languages. Dr Felice is the founder of Cannabis Matrix Consulting, LLC, and he maintains a regular cannabis blog at drjakefelice.com. 

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