Cannabinoids in Dermatology

Cannabinoids in Dermatology

While current research has mainly been focused on the role cannabinoids in pain management, neurological conditions, mood disorders and cancers, new studies are demonstrating how cannabinoids could be utilised to treat skin conditions and are emerging as a promising new area of interest. Here we explore further the potential of cannabinoids in the management of skin conditions.

The skin is the largest organ in the body and plays a number of vital roles which include

barrier functions, maintaining fluid balance, regulation of body temperature, production of hormones and immunological and metabolic functions. Our skin can reflect our general underlying health and can be a marker for a large number of systemic diseases. Poorly controlled skin conditions can have a profound effect on both physical and psychological wellbeing.

Our skin contains cannabinoid receptors and cannabinoid signalling influences several aspects of skin function, with dysregulation likely to contribute to the pathogenesis of several skin diseases. Significant attention is currently being directed towards the therapeutic potential of CB1 and CB2 agonists. In many pre-clinical studies, cannabinoids have been shown as potentially effective in treating a wide variety of skin conditions which include acne, allergic contact dermatitis, atopic dermatitis, hidradenitis suppurativa, Kaposi sarcoma, pruritus, psoriasis, skin cancer and the cutaneous manifestations of systemic sclerosis.

CBD has been demonstrated as a potential promising therapeutic agent for the treatment of acne vulgaris due to a combination of lipostatic, antiproliferative, and anti-inflammatory properties. CBC, CBDV and THCV have also been shown to significantly reduce arachidonic acid induced ‘acne-like’ lipogenesis with additional anti-inflammatory actions. CBG and CBGV may both have properties that could be useful in the treatment of dry-skin conditions. A small human, single blinded study found that cannabis seed extracts improved acne symptoms among participants when compared to control.

Topical cannabinoid receptors agonists may prove to be a potential treatment pathway for atopic dermatitis. Studies in mice treated with topical CB1 agonists demonstrated greater recovery of epidermal barrier function and decreased skin fold thickness compared to those treated with a vehicle preparation. Results from this study, which examined the role of topical CB1 agonists in mice with induced atopic dermatitis like symptoms found that CB1 agonists significantly reduced the recruitment of mast cells and lowered histamine levels, suggesting that topical agonists of CB1 may prove useful in several conditions related to mast cell activation, such as atopic dermatitis, contact dermatitis, and psoriasis.

Topically applied THC has been shown to improve contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This may have important implications for the future development of cannabinoids for the treatment of inflammatory skin diseases.

Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory molecule and acts by down-modulating mast cells following activation of the cannabinoid CB2 receptor. In this animal study PEA was shown to reduce some of the features of late stage contact allergic dermatitis. PEA has also been shown to be effective and well-tolerated in the treatment of itch associated with a range of conditions including atopic dermatitis and lichen simplex and may additionally play a role in improving scaling, dryness and itching. Several studies have shown that anandamide exerts anti-pruritic effects and that CB1 and CB2 agonists can help to reduce itch via activation of receptors present on cutaneous sensory nerve fibres, mast cells, and keratinocytes.

There is new evidence that signs of analgesia induced in models by transdermal administration of an opioid can be enhanced by transdermal co-administration of a low dose of a CB1 and CB2 receptor agonists. Results from this study demonstrated an antinociceptive interaction between topical opioids with topical cannabinoids. THC has been shown to enhance the potency of both fentanyl and buprenorphine patches which may in time lead to the design of an effective combination analgesic patch.

Postherpetic neuralgia is a frequent adverse event in herpes zoster patients and difficult to treat. In a small, non-randomised open label human study investigators compared a trial of topical cannabinoid cream in patients with facial postherpetic neuralgia against a control and found that 5 out of total of 8 patients noted a mean pain reduction. This was a small-scale study with narrow design but nonetheless highlights an interesting area for future research.

Psoriasis is characterised in part by epidermal keratinocyte hyper-proliferation. In preclinical trials, cannabinoids (including THC, CBD, CBG and CBN) have all been demonstrated to inhibit keratinocyte proliferation in vitro, thus supporting a potential role for topical cannabinoids in the treatment of psoriasis.

A growing number of preclinical and animal studies indicate that cannabinoids from plant, synthetic and endogenous origin are capable of effectively decreasing tumour growth and invasion. Cannabinoids have been demonstrated to modulate key cell signalling pathways involved in the control of cancer cell proliferation and survival. In vitro and in vivo cancer models have shown that cannabinoids can modulate tumour growth via both CB1 and CB2 receptors and that the anti-tumour effects appear to be largely dependent on cancer type and drug dose/concentration.

Both melanoma and non-melanoma skin cancer (NMSC) cells express CB1 and CB2 receptors and the endocannabinoid system is being discovered as playing a vital role in melanoma and NMSC development and progression. Preclinical data so far indicates that cannabinoid receptor agonists may be appropriate therapeutic targets for melanoma that phyto- and synthetic cannabinoids are capable of decreasing NMSC growth in different tumour models.

This animal study looked at the effects of treatment with a cannabinoid derivative on malignant melanoma tumours and a significant decrease in tumour size was detected in mice treated with CBD when compared with the control group. The authors concluded that further studies are necessary to evaluate this potentially new and novel treatment of malignant melanoma.

Topical cannabinoid creams may additionally play an important role in reducing pain and speeding up healing time and may be particularly useful for skin conditions such as pyoderma gangrenosum, as demonstrated in this small Canadian study. Again, whilst being a small study with narrow design this does highlight a need for further research within this area.

The topical delivery of cannabinoids can be problematic due to the highly lipophilic nature of the compounds, which rely on fatty substrates for absorption and have low penetration when placed directly onto the skin. One possible solution is using nanoparticle encapsulation which slowly delivers cannabinoids into the skin for maximum penetration and benefit to patients. This recent animal study demonstrated the efficacy of nanoparticles for delivering cannabinoids into the skin and improving symptoms of cutaneous lupus erythematosus.

Given the pace of current research and the emerging evidence base, the future looks promising for cannabinoid-based products as potential new treatment pathways for a wide range of skin conditions. Some of these may be turn out to be life changing treatments for patients who have failed to respond to more conventional therapies.

However, we must be reminded that our current understanding of the role of the cannabinoid system in the skin is still largely confined to relatively small, pre-clinical trials and as always, caution is needed around new and novel treatments. There should now be a focus on larger scale, clinical studies to further assess the mechanisms, safety, and efficacy of cannabinoids in the treatment of dermatologic diseases.

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