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cannabidiol

  • Currently, the most talked about natural ingredient in the dietary supplement industry is probably CBD. It’s also the ingredient about which the most misinformation is being disseminated. One YouTube video may say it’s the cure for all ills, while another website may say that it’s not safe, and might even make you high. It really is a travesty that there is so much hype and unreliable personal opinion being expressed about CBD. In an effort to provide some clarity, this article will share science-based information about hemp, CBD and phytocannabinoids.

    Defining CBD
    Cannabidiol, or CBD, is a naturally-occurring compound found in plants. It belongs to a family of compounds called cannabinoids or, more specifically, phytocannabinoids — which means cannabinoids from plants (phyto = plant). Actually, there are over 100 different phytocannabinoids, and hemp provides a primary source. Other common plants, such as oregano and basil, also contain phytocannabinoids. It may be that, when you eat Italian foods, one of the reasons you may enjoy them so much (besides the delicious taste), is that the phytocannabinoids they contain help you feel good.

    The most well-known of the phytocannabinoids, aside from CBD, is tetrahydrocannabinol, or THC. THC is the psychoactive compound found in marijuana that makes you high. To be clear, CBD and the other phytocannabinoids are not psychoactive, and will not make you high. They have other benefits, but they are not psychoactive.

    Full-Spectrum Phytocannabinoids
    While CBD is the most prevalent phytocannabinoid in hemp, it isn’t the only one. In fact, cannabinoids work together to create a greater overall synergistic activity. In scientific literature, the name for this is “the entourage effect.” This is similar to the way that various vitamins and minerals work together synergistically. If you’re just using isolated CBD, you’re not getting the benefits of the entourage effect.

    A full-spectrum hemp extract, on the other hand, provides a full array of naturally-occurring phytocannabinoids, including a defined amount of CBD. That’s what you want: full-spectrum phytocannabinoids, not CBD isolate. It should also be noted that CBD isolate is less expensive than full-spectrum, as well as less effective.

    The Endocannabinoid System
    While most people can probably name a couple of body systems, like the immune and cardiovascular systems which consist of defined organs and other structures, the vast majority of people are unaware of the endocannabinoid system (ECS). The ECS is a different type of system, composed of a series of receptors which occur throughout the nervous system and, consequently, throughout every system in the body. The ECS plays a major role in regulating many physical and cognitive processes in the body.

    In addition, the body produces endocannabinoids, which are its own internal cannabinoids. These activate the ECS receptors to initiate a cascade of powerful and important effects. Likewise, phytocannabinoids work with endocannabinoids to support and provide healthy functioning of the ECS. Just as every other system in the body needs nutritional support to stay healthy, the ECS needs such support as well. Supplementation with phytocannabinoids can help in the nourishment of the ECS.

    Research On CBD/Phytocannabinoids
    Regarding the benefits of cannabinoids let me start by saying that most CBD research is actually done on full-spectrum phytocannabinoids with a defined amount of CBD, not CBD isolate. So, that’s what I’m going to talk about. CBD/ phytocannabinoid research had been done on a broad range of health issues, with significant variations in dosage. In this article, we’ll focus on a few primary benefits associated with specific amounts of phytocannabinoids.

    Relaxation And Sleep
    Americans have a serious need to relax. Almost one-third of adults report that stress has a strong impact on their physical and mental health — and 42 percent of those report feeling nervous or anxious. In addition, about 46 percent of adults surveyed have reported lying awake at night due to stress. Essentially, stress just keeps their mind going and going, making it difficult to shut down for the night. Since the ECS plays an important role in the regulation and maintenance of all body systems, and phytocannabinoids support the ECS, it’s not surprising to learn that in human clinical research, 25 mg of phytocannabinoids daily have been shown to help calm stress and stress-induced anxiety, as well as help improve sleep.

    A large, retrospective series of case studies1 was conducted in which the vast majority of 103 adult subjects with stress/anxiety and sleep complaints were given 25 mg phytocannabinoids per day in capsule form. If stress/anxiety complaints predominated the 25 mg dose was given in the morning after breakfast. If sleep complaints predominated, the dose was given in the evening after dinner. The results were that, on average, stress/anxiety and sleep improved for the majority of patients and these improvements were sustained over time. At the first monthly assessment following the start of phytocannabinoid supplementation, 79.2 percent and 66.7 percent of subjects experienced an improvement in stress/anxiety and sleep, respectively.

    Other published case studies found similar results when phytocannabinoids were supplemented. In a case study2 with a young girl with stress/anxiety, 25 mg of phytocannabinoids at bedtime resulted in a steady improvement in the quality and quantity of her sleep. Likewise, in a case study3 with a 27-year old man who had stress/anxiety and sleep issues, the subject reported that 24 mg of phytocannabinoids daily resulted in improvements in stress/anxiety as well as settling into a regular pattern of sleep.

    There are other studies in a variety of populations4,5,6,7,8,9,10,11 in which phytocannabinoids have been successfully used at higher doses for stress/anxiety and sleep, but no studies in which phytocannabinoids have been used in lower doses.

    Pain/Inflammation
    An emerging area of phytocannabinoid research is inflammation and pain. Now before exploring the data, keep in mind that inflammation commonly occurs in a non-disease state. Inflammation occurs in everyone, every day. Higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains are associated with experiencing more inflammation.12 Colder temperatures are associated with experiencing more inflammation.13 Physical overexertion — like exercising extra hard at the gym — may result in temporary inflammation and pain.14,15 So, when talking about pain and inflammation, these are the type of applications we're considering. Now, onto a review of phytocannabinoid research on inflammation and pain.

    In research, there are various markers of inflammation. That is, there are inflammatory chemicals produced by our cells which contribute to the inflammatory process, and which can be measured. In one laboratory study,16 researchers sought to quantify the anti-inflammatory effects of cannabinoids, including phytocannabinoids, in cells that produced inflammatory markers. The results were that the cannabinoids successfully reduced inflammatory markers. Similar results were seen in other laboratory research with cannabinoids/phytocannabinoids and inflammation.17,18,19 Other laboratory research suggests that phytocannabinoids may also have application for pain.20,21

    In addition to laboratory research, there is also human research in which various doses of phytocannabinoids have been used in different inflammation/pain situations. In double-blind, placebo-controlled research with 62 subjects, supplementation with 200 mg/day phytocannabinoids significantly reduced levels of resistin, a type of protein that promotes several proinflammatory cytokines.22 In other human research,23 50-100 mg/day of phytocannabinoids resulted in pain reduction in most subjects tested.

    Furthermore, 2,409 phytocannabinoid users were recently surveyed regarding why they used phytocannabinoids. The results, published in a scientific journal,24 were that almost 62 percent of the phytocannabinoid used reported using phytocannabinoids for specific health applications. The top three were pain, anxiety, and mood. Almost 36 percent of respondents reported that phytocannabinoids effectively addressed their issue(s) "very well by itself," while only 4.3 percent reported "not very well." Of course, this survey in and of itself does not constitute direct evidence of the effectiveness of phytocannabinoids of temporary pain applications, but when taken together with the other research cited it certainly provides interesting insights into the popular use of phytocannabinoids.

    Conclusion
    Much of the aforementioned research was conducted using a daily dose of 25 mg of phytocannabinoids. Nevertheless, you may find products on the market that contain 10 mg or even 5 mg of CBD/phytocannabinoids. Many people have asked me if these lower doses will do them any good. My answer is maybe, but since there's no research showing that doses lower than 25 mg have efficacy, I would recommend sticking with 25 mg dose for a greater likelihood of success.

    References

    1. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol (CBD) in Anxiety and Sleep: A large case series. Unpublished. n.d. 10 pgs.
    2. Shannon S, Opila-Lehman J. Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Perm J. 2016 Fall;20(4):108-11.
    3. Shannon S, Opila-Lehman J. Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report. Integrative Medicine. 2015;14(6):31-5.
    4. Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A, Borgwardt S, Martin-Santos R, Seal ML, O'Carrol C, Atakan Z, Zuardi AW, McGuire P. Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Int J Neuropsychopharmacol. 2010 May;13(4):421-32.
    5. Crippa JA, Derenusson GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, Simoes MV, Bhattacharyya S, Fusar-Poli P, Atakan Z, Santos Filho A, Freitas-Ferrari MC, McGuire PK, Zuardi AW, Busatto GF, Hallak JE. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011 Jan;25(1):121-30.
    6. Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, Quevedo J, Roesler R, Schroder N, Nardi AE, Martin-Santos R, Hallak JE, Zuardi AW, Crippa JA. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011 May;36(6):1219-26.
    7. Das RK, Kamboj SK, Ramadas M, Yogan K, Gupta V, Redman E, Curran HV, Morgan CJ. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology (Berl). 2013 Apr;226(4):781-92.
    8. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 1981 Aug-Sep;21(S1):417S-27S.
    9. Zuardi AW, Crippa JA, Hallak JE et al. Cannabidiol for the treatment of psychosis in Parkinson's disease. J Psychopharmacol, 2009;23(8):979.83.
    10. Chagas MH, Eckeli AL, Zuardi AW, Pena-Pereira MA, Sobreira-Neto MA, Sobreira ET, Camilo MR, Bergamaschi MM, Schenck CH, Hallak JE, Tumas V, Crippa JA. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J Clin Pharm Ther. 2014 Oct;39(5):564.6.
    11. Pesantez-Rios G, Armijos-Acurio L, Jimbo-Sotomayor R, Pascual-Pascual SI, Pesantez-Cuesta G. [Cannabidiol: its use in refractory epilepsies]. Rev Neurol. 2017 Aug 16;65(4):157.60. [Article in Spanish]
    12. Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE, Hu FB. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004 Oct;80(4):1029.35.
    13. Halonen JI, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Associations between outdoor temperature and markers of inflammation: a cohort study. Environ Health.2010 Jul 23;9:42.
    14. Suzuki K, Peake J, Nosaka K, et al. Changes in markers of muscle damage, inflammation and HSP70 after an Ironman Triathlon race. Eur J Appl Physiol. 2006 Dec;98(6):525.34.
    15. Rowlands DS, Pearce E, Aboud A, et al. Oxidative stress, inflammation, and muscle soreness in an 894-km relay trail run. Eur J Appl Physiol. 2012 May;112(5):1839.48.
    16. Couch DG, Tasker C, Theophilidou E, Lund JN, O'Sullivan SE. Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon. Clin Sci(Lond). 2017 Oct 25;131(21):2611.26.
    17. Koay LC, Rigby RJ, Wright KL. Cannabinoid-induced autophagy regulates suppressor of cytokine signaling-3 in intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2014 Jul 15;307(2):G140.8.
    18. Kozela E, Juknat A, Kaushansky N, Rimmerman N, Ben-Nun A, Vogel Z. Cannabinoids decrease the th17 inflammatory autoimmune phenotype. J Neuroimmune Pharmacol. 2013 Dec;8(5):1265.76.
    19. De Filippis D, Esposito G, Cirillo C, Cipriano M, De Winter BY, Scuderi C, Sarnelli G, Cuomo R, Steardo L, De Man JG, Iuvone T. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS One. 2011;6(12):e28159.
    20. Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011 Sep 1;51(5):1054.61.
    21. Xiong W, Cui T, Cheng K, Yang F, Chen SR, Willenbring D, Guan Y, Pan HL, Ren K, Xu Y, Zhang L. Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J Exp Med. 2012 Jun 4;209(6):1121.34.
    22. Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, O'Sullivan SE, Tan GD. Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care. 2016 Oct;39(10):1777.86.
    23. Cunetti L, Manzo L, Peyraube R, Arnaiz J, Curi L, Orihuela S. Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. Transplant Proc. 2018 Mar;50(2):461.4.
    24. Corroon J, Phillips JA. A Cross-Sectional Study of Cannabidiol Users. Cannabis Cannabinoid Res. 2018 Jul 1;3(1):152.61.

  • Eating CBD gummies from Every Day Optimal is one of the easy ways of dosing with cannabidiol. Each gummy from this brand contains 10, 15 to 25 milligrams of cannabidiol, making it easier for you to get your recommended dose by simply eating the number of gummies that you dose requires. CBD gummies belong to a group of CBD infused products called “edibles” and as the term implies, you eat these to get your dose of this hemp derivative.

    There’s no question that CBD edibles have made self-administering CBD easier. Does the ease of self-administration with the edibles translate to faster absorption? Can CBD gummies get you instant relief?

    How Does CBD Work?
    Cannabidiol or CBD is one of the active compounds found in hemp, which is a strain of the cannabis sativa plant family. Although marijuana does contain trace amounts of CBD, this compound is most abundant in industrial hemp. Early research into CBD have suggested that it has various potential medical applications. Studies indicate that CBD may be a viable treatment and therapeutic option for a wide range of medical conditions.

    So how exactly does CBD work?
    Many have been using CBD for the treatment and management of various health issues. Despite this, however, data on the exact mechanism of action of CBD is limited. CBD belongs to a group of compounds called cannabinoids and such compounds trigger reactions in the body by attaching to receptors. The body itself produces its own cannabinoids, which can also attach to its cannabinoid receptors called CB1 and CB2 receptors1.

    CB1 receptors, which are found mostly in the brain, are responsible for the body’s movement and coordination, for pain, mood, logical thinking and a number of other functions. The other cannabinoid receptor, CB2, regulates the body’s inflammatory and pain reactions. It was initially thought that CBD attaches to these two receptors to trigger positive responses. However, recent studies suggest that CBD actually encourages the body to produce its own cannabinoids and then attach to the CB1 and CB2 receptors.

    Benefits of Supplementing with CBD

    Once the body’s own cannabinoids are produced and subsequently attaches to the CB1 and CB2 receptors, it results in the following benefits.

    Better circulation. Experts have observed that CBD has the ability to relax the veins in a phenomenon called vasodilation2. This allows the blood to circulate freely around the body, which in turn has a number of other health benefits. Vasodilation relieves some of the stress from the heart, thus may be effective in preventing certain heart conditions. The vasodilating properties of CBD may also help mitigate the effects of hypertension.

    Pain management and anti-inflammatory properties.Many users of CBD swear by its ability to relieve chronic pain and relieve inflammation. Studies are still underway to fully understand how CBD does the job, but many are already enjoying its benefits, particularly those who would rather go with a natural product that does not cause stress the liver.

    Mood regulation. Other users of CBD take regular doses to help mitigate and manage their anxiety and depression. Studies are also underway to determine the extent and long term effects of CBD’s anxiolytic properties.

    Can CBD Gummies Give You Quick Relief?
    The simple answer is yes however people will react differently. CBD has been observed to be highly bioavailable and that it crosses the blood-barrier easily. Some studies are being conducted to see if it is possible for CBD to serve as transport for certain drugs to be absorbed into the system faster and more efficiently. Once you pop a CBD gummy into your mouth, your saliva and chewing action will start breaking it down. While chewing, some of the CBD will be instantly absorbed via the mucous membranes inside the mouth. More of the CBD in the gummies will be absorbed quickly once it hits the intestines as the stomach enzymes further breaks down the gummies.

    Consuming CBD in general, whether in the form of tinctures or edibles, can give you quick results. The real question should be, what is the right CBD dose for your needs and how often should you self-administer throughout the day. This is of course, a subject for another discussion.

    1. https://www.nature.com/articles/0803273
    2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228270/

  • Cannabis has been a popular topic recently, with a clear consensus that there are wide health benefits to the plant, and evolving laws that are increasing its availability. Recognized commonly for its use in chronic pain and inflammation, its benefits in treating a variety of skin conditions is a less familiar topic. This article will focus on cannabidiol (CBD) only, i.e. the part of the plant not containing tetrahydrocannabinol (THC), which is the psychoactive part that gets you high.

    CBD's effect on skin goes beyond its anti-inflammatory effects, and is not only helpful in treatment but prevention as well.

    Dr. Phillip Blair, MD, Ret. COL spoke on this topic at the recent Cannabis World Conference and Business Exposition in Los Angeles. An international consultant on medical uses of CBD, Dr. Blair geared this presentation to the effects CBD can have on such conditions as acne, psoriasis, and even skin cancer. This was the inspiration for this article.

    How Does It Work?
    Benefits of CBD for the skin include the following mechanisms:
    • Neuro-regulation
    • Immune modulation—includes decreasing pro-inflammatory cytokines TNF, IL1 and IL6 and increasing anti-inflammatory cytokines IL4 and IL10
    • Effects on hunger, stress, and sex hormones
    • Ability to restore balance to the Endocannabinoid System (ECS)

    What is Cannabidiol?
    Cannabidiol (pronounced Can’na-bi-die’-ol) is a derivative of the cannabis or hemp plant that contains a number of beneficial natural chemicals such as cannabinoids and terpenes, providing a synergistic or "entourage effect." This means that when added together, the effects are not simply additive, but create a more potent effect overall.

    Over-the-counter cannabidiol, legal in all 50 states, contains less than .3 percent tetrahydrocannabinol (THC). In states where licensed, plants and their derivatives that contain more than .3 percent THC require a medical license and are purchased at a dispensary. That is a changing requirement, though, beyond the scope of this article. THC is the chemical in the plant that has direct mind- and mood-altering effects; i.e., it gets you high. Non-THC CBD also can have positive effects on mind and mood, but without the "high" effect.

    Cannabidiol and the Skin
    Cannabidiol (CBD) has been shown to have positive effects on a variety of skin conditions, its mechanism of action going beyond the commonly accepted anti-inflammatory properties of CBD. The most common modes of administration for skin care are orally and topically. Conditions treated include acne, eczema, psoriasis, skin cancer, wound healing, and aging skin.

    The Endocannabinoid System and Acne
    Acne is generally a result of overactive sebaceous glands. The body's endocannabinoid system (ECS) which plays a key role in the regulation of sebum production1 responds to both endocannabinoids (made naturally in our body) and phytocannabinoids (found in the cannabis plant). Balancing the ECS is key here.

    CBD works three different ways to regulate a sebaceous cell:

    • Stops inflammatory lipids like arachidonic acid
    • Stops the extra production of the cell types in sebaceous cells that lead to overproduction of sebaceous material
    • Provides an anti-inflammatory effect2

    There are other factors, too, which facilitate acne beyond the sebocyte factor. One is the over-production of testosterone which induces lipid synthesis, with excessive secretion and cell growth. CBD was shown to inhibit this lipid syntheses.2 Another factor is the overgrowth of bacteria called Propionibacterium. CBD has been shown to exhibit antibacterial properties and potentially inhibit its growth.2,3

    Eczema
    Eczema is a common skin condition characterized by a red, itchy rash, most commonly appearing on the face, back of the knees, wrists, hands, or feet, but may affect other areas as well. Eczema affects about 10 percent to 20 percent of infants and about 3 percent of adults and children in the US.

    Newer research indicates that that skin conditions like eczema and acne develop when there is an imbalance in the ECS,4 and suggests that the cannabinoids can help repair this imbalance by interacting with cannabinoid receptors. One study of 2500 patients with eczema experienced significant reductions in redness, scaling, itching, chafing, and thickening after regular topical use of a cannabinoid-containing cream. This study also resulted in 38.3 percent of the patients experiencing a complete resolution of itching symptoms.5

    Psoriasis
    Psoriasis is an autoimmune disorder which includes pathological overproduction of skin cells. The cytokine, Interleukin-17 (IL-17) is known to be largely responsible for psoriasis. CBD reduces the production of inflammatory cytokines IL-17 and IL-6 and increases the production of an anti-inflammatory cytokine, IL-10.6 This is a great boon to psoriasis sufferers, who have had to cover up with clothing, or take strong and expensive medications. They can now use a product that not only treats their unsightly rash, but has side benefits instead of side effects.

    Skin Cancer
    Many studies show promising results of cannabis on cancer cells. One study found that activating the cannabinoid receptors induced cell death in tumorigenic epidermal cells, while the non-cancerous epidermal cells remained unaffected.7 Dr. Blair discussed his experience with a 50-year-old man with recurring basal cell cancer. He had the cancer removed and covered the area with CBD under a band-aid. The patient experienced complete healing at two months with no signs of recurrence.

    Wound Healing
    There is considerable anecdotal evidence related to cannabis and wound healing. A few studies suggest that activation of the endocannabinoid system plays a role in this process.8 Dr. Blair showed some before and after photos of a patient with a wound on his arm, showing significant healing within 12 weeks.

    Anti-aging Skin Care
    There are an increasing number of CBD-containing skin care products, owing largely to its anti-inflammatory effects, which can counter the effects of aging.

    Dosing and Application
    For skin conditions, CBD can be taken orally, in capsules, gel caps or tinctures, or topically, as a cream or oil. Dosing should start at 15 mg of CBD twice a day orally, adjusting the dose upward as needed. It not unusual to go up to 60 mg. For a location-specific condition like eczema or skin cancer, you can apply the topical cannabis directly on the affected area. For nonspecific topical application, CBD oil can be applied to the back and covered with a band-aid as protection. Any improvements are typically seen in about two weeks after the first dose.

    A number of troublesome and heretofore difficult to treat skin conditions have been resolved successfully with its use. And this is just one of a growing wave of uses of CBD.

    We thank Dr. Phillip Blair for supplying both the inspiration and a portion of the material for this article.

    References:

    1. Dobrosi N, et al. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling. FASEB J. 2008;22(10):3685¡V95.
    2. Olah A, et al. Cannabidiol exerts sebostatic and anti-inflammatory effects on human sebocytes. The Journal of Clinical Investigation. 2014;124(9): 3713¡V24
    3. Kozela E, et al. Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype. Journal of Neuroimmune Pharmacology. 2013;8(5): 1265¡V76
    4. Appendino G, et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod. 2008;71(8):1427¡V30.
    5. Eberlein, B., Eicke, C., Reinhardt, H.W., and Ring, J. (2008, January). Adjuvant treatment of atopic eczema: assessment of an emollient containing Npalmitoylethanolamine (ATOPA study). Journal of the European Academy of Dermatology and Venereology: JEADV, 22(1), 73¡V82.
    6. Biro, T., Toth, B.I., Hasko, G., Paus, R., and Pacher, P. (2009). The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends in Pharmacological Sciences, 30(8), 411¡V20.
    7. M. Llanos Casanova, et al. Inhibition of Skin Tumor Growth and Angiogenesis in Vivo by Activation of Cannabinoid receptors. JCI. 2003;111(1): 43¡V50.
    8. Ramot Y, Sugawara K, Zakany N, Toth BI, Biro T, Paus R. (2013) A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ. PeerJ 1:e40 https://peerj.com/articles/40/