cbd oil as a topical.for skin cancer

Topical Cannabinoids in Dermatology

Drs. Hashim and Goldenberg are from the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Cohen is from AboutSkin Dermatology and DermSurgery, both in Englewood, Colorado; the Department of Dermatology, University of Colorado Denver, Aurora; and the Department of Dermatology, University of California at Irvine. Dr. Pompei is from Baruch College, City University of New York, New York.

The authors report no conflict of interest.

Correspondence: Gary Goldenberg, MD, Department of Dermatology, Icahn School of Medicine at Mount Sinai Medical Center, 5 E 98th St, New York, NY 10029 ([email protected]).

Topical cannabinoids are increasingly utilized by dermatology patients for a range of disorders; however, the acceptance of these over-the-counter products has far outpaced scientific investigation into their safety and efficacy. Here, we review the studies of topical cannabinoids in skin conditions and assess their current place in dermatology practice.

Practice Points

  • Topical cannabinoids are advertised by companies as treatment options for numerous dermatologic conditions.
  • Despite promising data in rodent models, there have been no rigorous studies to date confirming efficacy or safety in humans.
  • Dermatologists should therefore inquire with patients about the use of any topical cannabinoid products, especially around the time of planned procedures, as they may affect treatment outcomes.

References

  1. Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389-462.
  2. 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.
  3. 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;20:936-948.
  4. Schicho R, Storr M. Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 2012;89:149-155.
  5. Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002;54:161-202.
  6. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199-215.
  7. Svizenska I, Dubovy P, Sulcova A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures—a short review. Pharmacol Biochem Behav. 2008;90:501-511.
  8. Stander S, Schmelz M, Metze D, et al. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005;38:177-188.
  9. Kim HJ, Kim B, Park BM, et al. Topical cannabinoid receptor 1 agonist attenuates the cutaneous inflammatory responses in oxazolone-induced atopic dermatitis model. Int J Dermatol. 2015;54:E401-E408.
  10. Nam G, Jeong SK, Park BM, et al. Selective cannabinoid receptor-1 agonists regulate mast cell activation in an oxazolone-induced atopic dermatitis model. Ann Dermatol. 2016;28:22-29.
  11. Gaffal E, Cron M, Glodde N, et al. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors. Allergy. 2013;68:994-1000.
  12. Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68:515-521.
  13. Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34:672-680.
  14. Wilsey B, Marcotte T, Deutsch R, et al. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14:136-148.
  15. Wilsey B, Marcotte T, Tsodikov A, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008;9:506-521.
  16. Abrams DI, Couey P, Shade SB, et al. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90:844-851.
  17. Dogrul A, Gul H, Akar A, et al. Topical cannabinoid antinociception: synergy with spinal sites. Pain. 2003;105:11-16.
  18. Yesilyurt O, Dogrul A, Gul H, et al. Topical cannabinoid enhances topical morphine antinociception. Pain. 2003;105:303-308.
  19. Phan NQ, Siepmann D, Gralow I, et al. Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. J Dtsch Dermatol Ges. 2010;8:88-91.

The prevalence of topical cannabinoids has risen sharply in recent years. Commercial advertisers promote their usage as a safe means to treat a multitude of skin disorders, including atopic dermatitis (AD), psoriasis, and acne. Topical compounds have garnered interest in laboratory studies, but the purchase of commercial formulations is limited to over-the-counter products from unregulated suppliers. In this article, we review the scientific evidence behind topical cannabinoids and evaluate their role in clinical dermatology.

Background

Cannabis is designated as a Schedule I drug, according to the Controlled Substances Act of 1970. This listing is given to substances with no therapeutic value and a high potential for abuse. However, as of 2017, 29 states and the District of Columbia have laws legalizing cannabis in some capacity. These regulations typically apply to medicinal use, though several states have now legalized recreational use.

Cannabinoids represent a broad class of chemical compounds derived from the cannabis plant. Originally, this class only comprised phytocannabinoids, cannabinoids produced by the cannabis plant. Tetrahydrocannabinol (THC) is the most well-known phytocannabinoid and leads to the psychoactive effects typically associated with cannabis use. Later investigation led to the discovery of endocannabinoids, cannabinoids that are naturally produced by human and animal bodies, as well as synthetic cannabinoids. 1 Cannabidiol is a phytocannabinoid that has been investigated in neurologic and anti-inflammatory conditions. 2-4

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Cannabinoids act as agonists on 2 principal receptors— cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2)—which are both G protein–coupled receptors (Figure). 5 Both have distinct distributions throughout different organ systems, to which cannabinoids (eg, THC, cannabidiol, endocannabinoids) show differential binding. 6,7 Importantly, the expression of CB1 and CB2 has been identified on sensory nerve fibers, inflammatory cells, and adnexal structures of human skin. 8 Based on these associations, topical application of cannabinoids has become a modality of interest for dermatological disorders. These formulations aim to influence cutaneous morphology without producing psychoactive effects.

Signaling pathways associated with cannabinoid receptor activation. CB1 indicates cannabinoid receptor type 1; CB2, cannabinoid receptor type 2; AC, adenylyl cyclase; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; MAPK, mitogen-activated protein kinase.

Topical Cannabinoids in Inflammatory Disorders

Atopic dermatitis has emerged as an active area of investigation for cannabinoid receptors and topical agonists (Table 1). In an animal model, Kim et al 9 examined the effects of CB1 agonism on skin inflammation. Mice treated with topical CB1 agonists showed greater recovery of epidermal barrier function in acutely abrogated skin relative to those treated with a vehicle preparation. In addition, agonism of CB1 led to significant (P < .001) decreases in skin fold thickness among models of acute and chronic skin inflammation. 9

Nam et al 10 also examined the role of topical CB1 agonists in mice with induced AD-like symptoms. Relative to treatment with vehicle, CB1 agonists significantly reduced the recruitment of mast cells (P < .01) and lowered the blood concentration of histamine (P < .05). Given the noted decrease in the release of inflammatory mediators, the authors speculated that topical agonsim of CB1 may prove useful in several conditions related to mast cell activation, such as AD, contact dermatitis, and psoriasis. 10

The anti-inflammatory properties of topical THC were evaluated by Gaffal et al. 11 In a mouse model of allergic contact dermatitis, mice treated with topical THC showed decreases in myeloid immune cell infiltration, with these beneficial effects existing even in mice with deficient CB1 and CB2 receptors. These results support a potentially wide anti-inflammatory activity of topical THC. 11

Topical Cannabinoids in Pain Management

The effects of smoked cannabis in treating pain have undergone thorough investigation over recent years. Benefits have been noted in treating neuropathic pain, particularly in human immunodeficiency virus–associated sensory neuropathy. 12-15 Smoked cannabis also may provide value as a synergistic therapy with opioids, thereby allowing for lower opioid doses. 16

In contrast, research into the relationship between topical application of cannabinoids and nociception remains in preliminary stages (Table 2). In a mouse model, Dogrul et al 17 assessed the topical antinociceptive potential of a mixed CB1-CB2 agonist. Results showed significant (P < .01) and dose-dependent antinociceptive effects relative to treatment with a vehicle. 17 In a related study, Yesilyurt et al 18 evaluated whether a mixed CB1-CB2 agonist could enhance the antinociceptive effects of topical opioids. Among mice treated with the combination of a cannabinoid agonist and topical morphine, a significantly (P < .05) greater analgesic effect was demonstrated relative to topical morphine alone. 18

Studies in humans have been far more limited. Phan et al 19 conducted a small, nonrandomized, open-label trial of a topical cannabinoid cream in patients with facial postherpetic neuralgia. Of 8 patients treated, 5 noted a mean pain reduction of 87.8%. No comparison vehicle was used. Based on this narrow study design, it is difficult to extrapolate these positive results to a broader patient population. 19

Bad Report Card: Herbal Remedies for Skin Cancer

—Dear internet: Thanks for the inaccurate information about alternative skin cancer treatments.

By Mary L. Carter
Reviewed by Michael Leapman, MD

According to previous estimates, about 85% of U.S. patients with skin disease have used alternative therapies, such as herbal, vitamin, and mineral supplements. Although the majority of patients with skin cancer undergo conventional treatment under the direction of a dermatologist, some patients will instead use alternative botanical treatments exclusively. 1

Take Note
  • Patients who insist on trying alternative therapies often delay taking prescription products with proven efficacy.
  • Eight common herbals for skin disease all received identical poor grades in a recent analysis.
  • Physicians should discuss these products with their patients and warn them of their possible risks.

Unfortunately, there’s little reproducible evidence that supports the efficacy of these botanicals in skin cancer, and patients who opt for unproven alternative treatments often delay initiating conventional care that has proven efficacy. 1 The U.S. Food and Drug Administration (FDA) doesn’t regulate herbal supplements, but it does address the problem of deceptive cancer cures on its website. 2

Janet Y. Li, MD, and Jeremy T. Kampp, MD, from the Division of Dermatology, University of Washington School of Medicine in Seattle, recently published the results of their literature review of common topical herbal treatments that are advertised as skin cancer cures, which began with a search of the following terms in turn: “nonmelanoma skin cancer,” “basal cell carcinoma,” “squamous cell carcinoma,” and “melanoma.” 1 The authors then applied evidence levels and grades of recommendation as determined by the Oxford Center for Evidence-Based Medicine.

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Do any of these herbal supplements really work?

Drs. Li and Kampp reviewed several herbal supplements for skin cancer, in addition to providing background information on each of them. Here’s what they reported for 8 popular supplements. (Unfortunately, for those who believe in these products, the authors’ findings can only be described as sobering.)

Black salve

Bloodroot and zinc chloride, the primary ingredients in black salve, cause localized tissue necrosis. Black salve is currently marketed, against the FDA’s warning to desist, by a non-US based company as a cure for melanoma and nonmelanoma skin cancer. Sanguinarine, which is the active ingredient in bloodroot, has been shown in mouse models to induce apoptosis and cytotoxicity in melanoma cells, but no clinical trials have studied its efficacy and safety. However, there are many case reports of serious adverse effects from black salve skin cancer therapy.

Of the published case reports on black salve treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma lesions in 13 patients, 8 BCC lesions and 1 SCC lesion attained a complete response (6 were biopsy proven). Two cases each of residual and progressed BCC, and metastases in 2 melanomas, 1 SCC, and 1 BCC, were seen. Almost all patients experienced serious side effects, such as pain, ulceration, and scarring.

Rating: Given the inconsistent evidence and the severity of adverse effects, black salve scored a D recommendation.

Solasodine rhamnosyl glycosides

These glycosides are derived from the Solanaceae family, which includes tomatoes, potatoes, bell peppers, and eggplant. They attach to the surface of cancer cells, but not normal tissue, and initiate apoptosis. Creams containing solasodine rhamnosyl glycosides are licensed in Australia and the U.K. but aren’t approved for use in the U.S.

A case series (86 patients total) and 1 randomized control trial (RCT) (N=94) were found in the literature. In the case series of 86 patients followed for 3 months, complete regression was seen in 100% of BCC, SCC, and actinic keratosis cases after roughly 5 weeks of treatment. In the 8-week RCT in 94 patients with BCC, 66% of patients using cream containing solasodine glycosides showed histologically confirmed clearance of BCC; however, 22% of these patients had a recurrence of BCC at the study’s 1-year follow-up. No serious adverse effects were reported.

Rating: Solasodine glycosides, because of the inconsistent results associated with them, scored a D recommendation.

Frankincense

Derived from the Boswellia tree, frankincense contains boswellic acid, which induces apoptosis, as shown in animal studies. In humans, only 1 case study, in a middle-aged man with 2 BCC lesions, was reported in the current literature review. After 4 months’ treatment with frankincense oil, 1 lesion on the patient’s arm completely resolved and 1 on his chest showed focal residual BCC. Treatment-associated allergic contact dermatitis has been reported.

Rating: Because only 1 case study could be found, frankincense received a D recommendation.

Cannabis

Cannabinoids have shown melanoma and nonmelanoma antitumor effects in preclinical studies of mouse and human melanoma cell lines. Among the results, synthetic cannabinoids lead to apoptosis, impaired angiogenesis, and inhibition of epidermal growth factor receptor, as well as decreased adhesion of melanoma cells to brain endothelial cells and impaired transendothelial migration of melanoma cells. Tetrahydrocannabinol (THC) was shown to induce apoptosis in melanoma cells and decrease cell viability, and also demonstrated decreased melanoma cell proliferation, angiogenesis, and metastasis.

Rating: Various brands of cannabis oil are promoted to heal a wide array of medical diseases, from multiple sclerosis to depression, but there are no clinical trials to support any claims. This dearth of clinical evidence therefore earned topical use of cannabinoids a D recommendation.

Black raspberry

In the only skin cancer study thus far, use of black raspberry extract after ultraviolet B exposure reduced the number and size of skin cancer tumors in mice. However, no clinical trials in humans have been conducted, and no adverse effects associated with black raspberry have been reported.

Rating: Because there’s no clinical evidence, use of black raspberry extract scored (you guessed it) a D recommendation.

Milk thistle

Silibinin, a flavonoid isolated from milk thistle seed, induces apoptosis in mouse BCC cell lines and inhibits BCC tumor growth in mice. Even though milk thistle or its active compounds have been reported as skin cancer therapy, no clinical trials in humans have been conducted. No adverse effects associated with topical milk thistle have been reported.

Rating: As with several of the other skin cancer herbals evaluated, Drs. Li and Kampp found no clinical evidence of the effectiveness of milk thistle or its active compounds. It, too, gets a D recommendation.

St. John’s wort

Hypericin is an active ingredient in St. John’s wort that induces apoptosis in human melanoma cell lines and SCC cells when given before photodynamic therapy. One pilot study conducted in 34 patients showed, after weekly treatment with St. John’s wort extract and photodynamic therapy for 6 weeks, a complete clinical response in 50% of 8 patients with actinic keratosis, 28% of 21 patients with BCC, and 40% of 5 patients with SCC in situ. However, no RCTs have studied the efficacy or safety of St. John’s wort in treating skin cancer.

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Rating: The jury is still out due to inconclusive evidence of efficacy. Therefore, topical use of St. John’s wort in skin cancer scored yet another D.

Tumeric

Curcumin, a derivative of turmeric, induces apoptosis and inhibits in vitro melanoma cell migration and invasion in preclinical studies. However, no clinical studies show that curcumin is efficacious in treating nonmelanoma skin cancer. Allergic contact dermatitis, contact urticaria, and pruritus have been reported with the use of topical turmeric.

Rating: Another D recommendation, again thanks to the lack of clinical evidence.

False, false, false

Despite some support from preclinical data, there’s little to no clinical evidence supporting the use of any of these botanicals for the treatment of skin cancer. So why do patients continue to purchase them? As the authors state, “Many websites and patient testimonials cite a mistrust of physicians as a reason to turn to alternative therapies, often ignoring potentially devastating consequences. It is important for physicians to be aware of these alternative therapies and to maintain an open dialog with patients.”

Physicians and other healthcare professionals, they suggest, “should warn their patients that although some encouraging results have been reported with herbal preparations, those positive results have not been reproducible and are not robust enough to replace current standard therapies . . . these botanicals may cause indiscriminate local tissue destruction . . . and produce an incomplete cure and a delay in diagnosis that allows for further local progression of disease at best and metastasis at worst.”

How to Use Rick Simpson Oil (RSO)

A message from our Clinical Director on the benefits and uses of Rick Simpson Oil (RSO), a highly concentrated form of medical cannabis.

A message from our Clinical Director:

As the medical cannabis industry grows, patients are able to choose from a variety of products and dosage forms. One particularly potent dosage form is an oil called Rick Simpson Oil, or RSO for short. Rick Simpson was diagnosed in 2003 with skin cancer. He decided to make a concentrated THC oil to use as a treatment. He applied the oil topically for several days. When he removed the bandages after this period of time, the skin cancer was gone!

Today, RSO is available as a potent THC, CBD, or mixed ratio of THC:CBD concentrate. The oil is a full plant extract and is typically thick and sticky. RSO can be used in a variety of ways. It can be used topically, orally, sublingually, you can cook with it, and depending on how it is extracted, it can be smoked. I do not, however, recommend smoking it in case you do not know how it was extracted and what solvents were used in the process. If it was extracted with a highly flammable solvent then you definitely do not want to smoke it!

To use RSO topically, apply a small amount to the affected area and cover with a bandage. You can reapply a few times daily, just be sure to change the bandage each time. You can also mix each dose with a little coconut oil to help thin it out so it is easier to apply.

To use RSO orally, you can place your grain of rice-sized dose (or less if you are just starting out – see below for dosing) directly on a cracker or a piece of bread and eat it. RSO is very sticky and tacky, so I suggest not chewing it directly, as it could get stuck in your teeth and leave an unpleasant taste in your mouth.

To use RSO sublingually, simply place your dose under your tongue or inside your cheek and let it get absorbed. This method allows it to be absorbed right into the bloodstream for fast effects.

Finally, you can cook with RSO just as you would with your canna-butter or canna-oil. Cooking with RSO is very easy as it is already activated and ready to go, no decarboxylating necessary!

To start using RSO, you want to start with ½-1 grain of rice sized drop. Take this dose every 8 hours for 1 week or so. For the next couple of weeks (until about week 5) if you are ready, try increasing the dose until you reach 1gram per day, in divided doses. After about 12 weeks, you should consider backing down the dose until you are only using what is needed for maintenance. This can range from 1-2 grams per month. Do not abruptly stop using RSO, as you may experience withdrawal symptoms. Instead, back down slowly.

The main side effect from RSO is sedation. The body heals bests in a state of rest so this is a good thing. Please do not try RSO and then go driving or operating machinery. Always discuss using RSO or any cannabis product with your healthcare provider first. RSO is a very potent medicine and should be taken responsibly. It can have wonderful benefits when used properly. Its versatility makes it a great tool in your medicine toolbox.