Cosmetics & Personal Care

An effective phytocannabinoid alternative to CBD
25th March 2020

By Maria Célia H. Reimberg, R&D Supervisor at Beraca Chemicals

Maria Célia H. Reimberg, R&D Supervisor at Beraca Chemicals, describes the action of a natural non-hemp-based phytocann

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Maria Célia H. Reimberg, R&D Supervisor at Beraca Chemicals, describes the action of a natural non-hemp-based phytocannabinoid that exhibits anti-inflammatory and endorphin production activity, making it suitable for use on sensitive skin.

Sensitive skin is an irregular condition that causes several issues regarding the skin aspect including rash, itch redness, dryness, and discomfort. It is caused by the reactivity of the skin to environmental conditions and / or external and inner factors, including immunological and individual susceptibility. The prevalence of reported sensitive skin worldwide is very high – 14% for normal population1.
 
Regarding skin´s self-defense, one of several mechanisms is related tothe endocannabinoid system, formed by a net of lipidic signals that can modulate both neural and inflammatory functions through a bidirectional interaction with different receptors2:
CB1 – One of the most common receptors in the entire nervous system – moderators of your memory, mood, motor function, perception of pain and responsible for responsible for the psychoactive properties of cannabis when THC binds to them
 
CB2 – Most often found on the cells of our immune system – mediates immunomodulatory and
Inflammatory properties
 
The CB1 and CB2 receptors are distributed throughout the body, but particularly for CB2, it´s found in higher density on the peripheral tissues(epidermis and dermis). The CB2 receptor is activated by endogenous (endocannabinoids) or exogenous ligands (generally agonists). As an example of exogenous ligands, we can point out thephytocannabinoids.
 
The most known phytocannabinoid is the cannabidiol (CBD), an active derived from hemp that has an affinity for both receptors and is known by its anti-inflammatory activity, however it´s use is still controversy due to the fact that may contain tetrahydrocannabinol (THC), related to psychotropic effect and with almost no studies regarding its possible side effects.
 
As an alternative to cannabidiol (CBD), another natural phytocannabinoid is theβ-caryophyllene2, present in the BERACARE CBA, a blend of amazon oils, from Beraca,which can modulate cell signs and consequently, attenuate inflammatory effects (decreasing levels of cytokines such as IL-1β and IL-6) with no activity in the CB1 receptor.
 
The β-caryophyllene is a CB2 receptor agonist2. When it interacts with the CB2 receptor, it naturally acts through the interaction with the surface molecules and the inhibition of the Toll-type receptors, which is a type-I protein family, a part of the innate immune process3.
 
It is important to note that the action on Toll-type receptors leads to pro-inflammatory cytokines expression, thus these cytokines are not delivered and, consequently, persistent anti-inflammatory activity is formed.
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Figure 1. The effects of BERACARE CBA on (a) IL-1β and (b) IL-6 production in human skin culture in the presence or absence of lipoteichoic acid (LTA) at 100µM.

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Besides the activity of β-caryophyllene for CB2, it also occurs a secondary activation related toβ-endorphin, that is a neurotransmitter (also presented in the skin)related to immunological functions4,5, that are produced as a cutaneous immune response. The β-endorphins are peptides formed by 31 amino-acids and produced in the brain, present in skin cells and delivered by opioid receptors6. These compounds are resistant to enzymatic degradation and act directly on the immune system. One of the main effects of β-endorphins in the body is its analgesic effect.
 
Particularly for skin cells, β-endorphins production is directly related to comfort, calm, and relaxing, helping in the tissue’s reepithelization and recovery (skin healing)7.
 
To study the β-caryophyllene – CB2 activity, efficacy tests were performed in preclinical assays (ex vivo) forits anti-inflammatory activity, based on human skin culture that underwent inflammatory stress (actions on interleukins IL-1β and IL-6), and foritsβ-endorphin production.
 
The Amazon oil complex (β-caryophyllene rich) showed a reduction in inflammatory interleukins secretion and mediation of the immune system by the CB2 receptor activation, with a direct impact on tissue repair and maintenance of the skin balance. The balance – or skin homeostasis – allows the improvement of the natural cutaneous tissue ability of the recovery process8,9.
 
The complex was able to act on the skin inflammatory response control, with a significant 55.4% and 25.2% reduction in the inflammatory interleukins IL-1β and IL-6 respectively, besides a 92.9% significant increase of β-endorphins production. Thus, these results indicate an anti-inflammatory activity that may favor both skin healing and reepithelization, according to the Graphs 1 and 2 respectively.
 
Finally, efficacy tests have proven important benefits of the Beracare CBA for beauty. The ingredient will help to mitigate the effects of premature aging related to inflammatory stress and it can support the re-epithelization and healing process due to the increased β-endorphin production10.
 
Beracare CBA is an ingredient with wellness and de-stressing properties,promoting various skin benefits such as calming, improved healing activity and providing comfort. In addition, the product is a safe alternative to CBD, with the versatility of applications in different cosmetic products.
Bibliography:
  1. Berardesca. E.; Farage, M. and Maibach, H. Sensitive skin: an overview. Review Article. International Journal of Cosmetic Science. 35; 2-8, 2013.
  2. Sharma, C. et al. Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Curr. Pharm. Des.; 22 (21):3237-64. 2016
  3. Tóth, K. F. et al. Review: Cannabinoid signaling in the skin: therapeutic potential of the “C(ut)annabinoid” system. Molecules. 24; 918. 2019
    1. Jean-Gilles, L. et al. Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immunecells. Acta Physiol. 214;63-74; 2015.
  4. Choi, J.E. and Di Nardo, A. Skin Neurogenic Inflammation. Sem. Immunopathol. May;40(3):249-259. 2018.
  5. Martins, R. et al. Receptores opioides até o contexto atual. Rev. Dor, SP. Jan-Mar; 13(1): 75-9; 2012.
  6. Elewa, R. et al. Neuropeptides and skin aging. Horm. Mol. Biol. Clin. Invest. Dec; 16(1):29-33, 2013.
  7. Landén, N.X. et al. Transition from inflammation to proliferation: a critical step during wound healing. Cell. Mol. Life Sci.; 73: 3861-3885, 2016.
  8. Iribarne, M. et al. Cannabinoid receptors in conjunctival epithelium: identification and functional properties. IOVS, Oc.; vol. 49; 10. 2008.
  9. Su, T. et al. Cannabinoid CB2 receptors contribute to upregulation of β-endorphin in inflamed skin tissues by electroapuncture. Molecular Pain. 7:98, 2011.
  10. Arizuka, N. et al. The effect of β-caryophyllene on nonalcoholic steatohepatitis. J. Toxicol. Pathol. 30:263-273; 2017.
  11. Dahham, S. et al. The anticancer, antioxidant and antimicrobial properties of the sesquiterpene β-caryophyllene from the essential oil of Aquilariacrassna. Molecules. 20; 11808-11829. 2015.
  12. Wang, X. et al. The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis. J. Invest. Dermatol. 123:124-131; 2004.
  13. Said, A. et al. Inflammatory conditions distinctively alter immunological functions of Langerhans-like cells and dendritic cells in vitro. Immunology. 144; 218-230; 2014.
  14. Zhang, T. et al. Cytokines, Inflammation and Pain. Int. Anesthesiol. Clin. 45(2):27-37. 2007.



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