Nourishing cannabis stem cells

Many end customers enjoy skin care and see it as their little daily ritual for greater wellbeing. But what if an ingredient can objectively ensure this? Òscar Expósito reports on the latest research results.

Cannabis sativa stem cells

Kannabia Sense stimulates the skin microbiota to produce in-situ a postbiotic which boosts the synthesis of oxytocin in keratinocytes. The molecules generated in the keratinocytes activate the oxytocin production in sensory neurons, communicating with the rain and leading to a well-being response. Therefore, it positively activates the so-called Microbiota-Skin-Brain Axis. This active made from cannabis sativa plant stem cells and has been obtained through the Phyto-Lipidic Fractions technology and enriched in plant terpenes and polyphenols while avoiding the production of the cannabinoids THC and CBD.

In Vitro efficacy

In vitro 1: Characterisation of bacterial in-situ postbiotic Screening analyses were performed on the bacterial SuperNatant (bSN). Their composition was evaluated with the aim to link this specific metabolic profile with this activation of ‘pleasure’ neurochemicals. The active was added to separate cultures of skin commensal microbiota (Cutibacterium acnes and Staphylococcus epidermidis). The resulting bacterial culture supernatants were combined in a 1:1 ratio (bSN) (Fig. 2). The bSN treated with the active produced less total proteolytic content and biofilm forming exopolysaccharides and had lower antioxidant activity. Compared to untreated controls, the postbiotic generated contained less metabolites related to microbial stress and was full of balanced, healthy, and beneficial molecules for the skin.

In vitro 2: Analysis of Microbiota- Skin-Brain Axis networks The active was added to separate cultures of commensal microbiota (CutiÒscar bacterium acnes and Staphylococcus epidermidis)1. The resulting bacterial culture supernatants were combined in a 1:1 ratio (bSN)2 and added to a human keratinocyte culture (NHEK)³. Oxytocin levels produced by the NHEK were analysed and compared, allowing us to determine if the in-situ postbiotic (the bSN), which is low in microbial stress markers and rich in beneficial compounds, can stimulate the NHEK to synthesize more relaxing molecules, such as oxytocin⁴. Next, the supernatant of treated NHEK (kSN) was added to sensory neurons and the levels of oxytocin were analysed⁵. The production levels of oxytocin of untreated sensory neurons were compared with those treated with the active and with those treated with bSN or with kSN⁶. In these six steps (Fig. 2), the effect of the active in positively activating the Microbiota-Skin-Brain Axis was confirmed.

The oxytocin levels were analysed in both keratinocytes and sensory neurons:

• Oxytocin levels in Keratinocytes (NHEK - Step 4): The active increased the oxytocin synthesis on NHEK by up to 1.5-fold vs untreated control, and the bacterial supernatant (bSN) increased the oxytocin synthesis on NHEK by up to three times fold vs control (Fig. 3).
• The ingredient activates the oxytocin production in keratinocytes, but its effect is much higher by indirect activation through the stimulation of skin microbiota.
• Oxytocin levels in sensory neurons (Step 6): The active increased the oxytocin synthesis on sensory neurons through the sequential activation of cutaneous microbiota and keratinocytes. The bacterial supernatant (bSN) increased the oxytocin production, while the keratinocytes’ supernatant (kSN) was able to increase it even more, eight times more vs untreated control (Fig. 4).
• The active centers its mechanism on activating the cascade of reactions from the skin microbiota to the brain.

In Vivo Efficacy

In vivo 1: Evaluation of Skin Well-Ageing effect The first in vivo test was performed on a 40-volunteer panel (46-64 years old) vs placebo, with two daily applications for 28 days.

• Mood wrinkles: The anti-wrinkle effect of the active was evaluated on a subgroup of 30 volunteers by Bio3D Structured-light Scanner, a refined 3D digitalizing system based on structured light projection which uses 290 pictures per second to prevent movement effects and allows very high-resolution images. The measured parameters were area and length of the ‘emotional wrinkles’ after 28 days (Fig.5).
• The area and length of wrinkles were reduced, down 44% and 28% in Marionette lines, and down 27% and 32% in frown lines.
• Skin hydration: The application of a cream containing 1% active for 28days significantly increased the skin hydration levels by 19% vs placebo, and up 56% vs initial time (36 volunteers).
• Skin radiance: A cream containing 2% active was applied for 28 days. Their skin gloss and radiance increased significantly, by 18% vs placebo and by 50% vs initial time (30 volunteers).

In vivo 2: Evaluation of Emotional Modulation

A cream with 2% active was applied twice daily by a 30-volunteer group (46-69 years old) vs placebo.

• Analysis of brain activation by functional Magnetic Resonance Imaging (fMRI): The volunteers’ brain activity was analysed, in a subgroup of 20 volunteers, by functional Magnetic Resonance Imaging (fMRI), a sophisticated technique that measures the changes in brain activity associated with changes in blood flow and related to the neuronal activation of specific areas.
• A series of correlation coefficient weighted matrices for every pairwise brain region was developed, where red areas indicated strong brain activation, and blue areas indicated a low brain activation. From such matrices, 3D brain models were elaborated to illustrate which brain areas were activated and connected. 132 brain regions were analysed.
• The active demonstrated a higher positive brain activation vs placebo at 15 minutes after application, while producing an even higher positive activation of the brain pleasure zones at 28 days (Fig. 6).
• The active demonstrated a higher activation of brain regions and connections, significantly greater than placebo, with those areas associated with touch, affective processes and regions especially involved in the response to oxytocin.
• Kannabia Sense showed an activation profile similar to that of oxytocin, demonstrating its ability to activate the neuroendocrine skinbrain axis, similar to touch and massage, with an emotional effectiveness as well. The activated brain pleasure regions are related to a greater social predisposition and attractiveness of the person.
• Modulation of mood state: The emotions generated in the 30 volunteers after applying a cream containing 2% active ingredient were also analysed. Their positive emotions increased up to a 29% vs placebo, and they reported feeling happier, more relaxed and confident (Fig. 7).

Conclusion

The prebiotic treatment Kannabia Sense stimulates the skin microbiota to produce a positive in-situ postbiotic that ignites the synthesis of cutaneous oxytocin. This process activates the brain pleasure centres, induces a better self perception and positive emotional and induces a better self-perfection and positive emotions, which are visible in a healthier and prettier skin. The ingredient has a wide range of cosmetic applications: well-ageing, anti-ageing, delicate facial treatments, restoring night creams, and uplifting massage lotions. This cannabis raw material is a step forward in neuro-cosmetics due to an innovative mechanism of action which brings new benefits for the human skin while being respectful with the skin microbiota. 

References:

¹ Misery L, et al. 2010. PRURITUS Chapter 34 Psychosomatics and Psychiatry pag. 219.

² Denda M. 2015. The epidermis as the third brain. Dermatologica sinica, 33:70-73.

³ Bocheva G, et al. 2019. Neuroendocrine Aspects of Skin Aging, Int J Mol Sci., 7:20.

⁴ Slominski A, et al. 2012. Sensing the environment by the skin’s neuroendocrine system. Adv Anat Embryol Cell Biol, 212:1-115.

⁵ Nordlind K, et al. 2007. The skin as a mirror of the soulexploring the possible roles of serotonin. Exp Dermatol, 17(4):301-11. 

⁶ Slominski A, et al. 2015. On the role of skin in the regulation of local and systemic steroidogenic activities. Steroids, 103:72-8.

⁷ Prescott S, et al. 2017. The skin microbiome-impact of modern environments on skin ecology, barrier integrity and immune reprogramming, World Allergy Organ J, 10(1):29.