Cannabis as a Treatment for Psoriasis and Pruritus

Psoriasis

Psoriasis is achronic inflammatoryskin disease with complex etiopathogenesis. Expertsbelievepsoriasisoccursdue to genetic inheritance, including streptococcal infection and related molecular mimicry and immunological disturbances. Psoriasis ischaracterizedby benign, uncontrolled epithelial skin cell growth (keratinocyte hyperproliferation), and psoriatic patients tend to produce new skin cells quickly. These skin cells reach the skin surface before maturation. Overtime, the uncontrolled buildup of immature skin cells on the skin surface causes itching with raised flaky scales. The psoriatic patient may suffer redness, swelling, pain or discomfort at the site of inflamed skin (psoriatic lesion). Although some symptoms may vary from one person to another, symptoms such as itching (pruritus), burning sensation or soreness, dry and cracked skin are common among all patients. Psoriasis affects approximately 2% of the Western population.

As psoriasis is aninflammatory disorder, it occurs as a result ofT-cell activationin response to various molecular factors. Activated CD4+T-cells in the psoriatic lesionacceleratekeratinocyte proliferation by stimulating interferon- release. Additionally, the role ofT helper cellsand pro-inflammatory cytokines are well demonstrated by research evidence.

Due to autoimmunity, less than 25% of psoriatic patients develop psoriatic arthritis, which is characterized by painful swelling and stiffness of the joints. Progressive, untreated or inadequately treated psoriasis may lead to permanent joint damage in psoriatic patients. Immunologically, the pathogenesis of psoriasis mimics certain T-cell mediated chronic disorders.

To treat psoriasis, the treatment approach should stop the skin cells from growing rapidly. Nonetheless, this is not a permanent solution to relieve the symptoms. Immuno-modulating drugs, such as biologics, can calm down the immune system crosstalk and treat the symptoms temporarily, albeit with an unacceptable degree of adverse events including deadly, life-threatening infections.

Pruritus

Pruritus (itching) is a common symptom for several localized and systemic diseases. Localized inflammatory conditions associated with skin disorders, such as eczema and psoriasis, could contribute to pruritus. Skin itching iscommonin about of70-90%of psoriatic patients, and at least30%of psoriatic patients suffer generalized itching.

Despite the fact that it is less intensive, most psoriatic patients feel pruritus is a bothersome symptom that negatively affects their quality of life and contributes to mental stress and low self-esteem, as well as depression and anxiety which correlate with the level of stigmatization. Patients suffering from asevere formof psoriasis tend to experience intense pruritus.

The association between psoriasis and pruritus is poorly understood; it is believed to be evoked by serotonin, proteases,IL-2, IL-31 and prostanoidsbut notby histamine inpsoriatic patients.

The ECS in the Skin

Mother Nature gifted us with a unique, skin-specific endocannabinoid system within the subcutaneous dermis, in addition to central and peripheral distribution. Research studies have demonstrated the beneficial effects of endocannabinoid system activation in the treatment of skin disorders. Oneexperimental studyfound that certain cannabinoid agonists inhibit rapid skin cell proliferation (keratinocytes), which has potential implications in psoriasis treatment.

Recent studies enthrallingly demonstrated the existence of a functional endocannabinoid system in the skin and its functional role in skin cell differentiation, proliferation, growth, apoptosis and hormonal or other mediator production of various skin cell types and appendages, including hair follicles and sebaceous glands.

The main role of the cutaneous ECS is to regulate or control the optimal proliferation, differentiation and survival of the skin cells as well as the immunocompetence or tolerance of skin cells. A disruption of this delicate balance or homeostasis might result in several skin-related problems, such as systemic sclerosis, hair growth disorders, allergic dermatitis, acne, seborrhea, psoriasis and related itching and pain and skin cancer.

This evidence has shown that phytocannabinoids inhibit keratinocyte proliferation, and pave a pathway for the treatment of psoriasis.

Cannabis for Psoriasis

Psoriasis is an inflammatory disorder with etiology of epidermal keratinocyte hyperproliferation. Although epidermal keratinocyte proliferation is not the sole contributor of psoriatic skin events, it may have a circumstantial role in the disease process. Cannabinoid receptors in the human skin have remarkable affinity to anandamide, an endogenous CB receptor ligand that inhibits epidermal keratinocyte differentiation or proliferation.

Other studieshave observed the human keratinocyte proliferation inhibitory effects of cannabinoids via non-CB1/CB2 mechanisms. The possible non receptor-mediated mechanism suggested by thesestudiesare the dual-modulatory role of the endocannabinoid system on cholinergic and anti-inflammatory pathways, which may have potential therapeutic implications in anti-psoriatic treatment.

Upon investigating the effects of four active phytocannabinoids including THC, CBG, CBD and cannabinol the study found all of these compounds were equally effective in inhibiting the rapidly proliferating human keratinocytes.One studyconcluded that cannabis may not completely inhibit the rapid growth of keratinocyte hyperproliferation, but rather slow it down; which aids wound healing and treats psoriasis.

Dysregulated release of pro-inflammatory cytokines by the immune cells and altered immune response worsens psoriasis prognosis. In addition to suppression of keratinocyte hyperproliferation, the anti-inflammatory benefits of cannabinoids play akey rolein modulating immune response in psoriasis pathophysiology. Cannabinoids modulate the dysfunctional immune response by correcting the cytokine release through regulation of T-helper subset cells such as Th1 and Th2, and also bydecreasinganti-inflammatory molecules such as TNF-, GM-CSF, IL-12 and IFN- levelsvia CB1receptor-dependent mechanisms. The cannabinoids influence on cytokine releasegreatly dependson the type of cannabinoid, and its concentration. Not just the pro-inflammatory molecules, cannabinoids (THC) have been shown toinhibitthe molecular/gene expression (mRNA) of IL-1, IL-1, IL-6 and TNF- via cannabinoid receptors independent mechanisms.

In chronic inflammatory conditions like psoriasis,suppressionof IL-6 can ...