Psoriasis is a chronic inflammatory skin disease with complex etiopathogenesis. Experts believe psoriasis occurs due to genetic inheritance, including streptococcal infection and related molecular mimicry and immunological disturbances. Psoriasis is characterized by 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 an inflammatory disorder, it occurs as a result of T-cell activation in response to various molecular factors. Activated CD4+ T-cells in the psoriatic lesion accelerate keratinocyte proliferation by stimulating interferon-γ release. Additionally, the role of T helper cells and 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 (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 is common in about of 70-90% of psoriatic patients, and at least 30% 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 a severe form of psoriasis tend to experience intense pruritus.
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. One experimental study found 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 studies have observed the human keratinocyte proliferation inhibitory effects of cannabinoids via non-CB1/CB2 mechanisms. The possible non receptor-mediated mechanism suggested by these studies are 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 study concluded 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 a key role in 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 by decreasing anti-inflammatory molecules such as TNF-α, GM-CSF, IL-12 and IFN-γ levels via CB1 receptor-dependent mechanisms. The cannabinoids’ influence on cytokine release greatly depends on the type of cannabinoid, and its concentration. Not just the pro-inflammatory molecules, cannabinoids (THC) have been shown to inhibit the molecular/gene expression (mRNA) of IL-1α, IL-1β, IL-6 and TNF-α via cannabinoid receptors’ independent mechanisms.
In chronic inflammatory conditions like psoriasis, suppression of IL-6 can reduce tissue injury. Synthetic cannabinoids have been shown to downregulate IL-6 and IL-8 synthesis via non-CB1/CB2-mediated mechanisms, and attenuate the inflammatory processes. This CB receptor-independent benefit might be attributed to anandamide activity, which by nature suppresses IL-2 and PPAR-γ expression and also cytokine-induced inflammation. Dysregulated cytokine (IL-12 and IFN-γ) release may reduce FAAH activity and disrupt the endocannabinoid system that collectively contributes to the pathogenesis of various ailments. In such conditions, phytocannabinoid administration could restore the ECS to normalcy, and suppress inflammation.
More clinical research is needed to confirm these findings; still, this evidence provides ground to the argument that cannabis may be a viable and effective alternative to treat psoriasis.
Cannabinoids are potentially anti-inflammatory in nature, and possess inhibitory effects on the proliferation of several tumorigenic cell lines via inhibitory effects of cannabinoid receptors.
In addition to analgesic, immuno-modulating and anti-inflammatory effects, other entourage effects of cannabis such as anti-allergic, anti-microbial, and antioxidant properties might be helpful to treat psoriasis symptoms effectively.
For psoriatic and other skin disorder patients, smoking cannabis is not recommended. Instead, they should consider using topical skin applications such as oils and balms. Studies have suggested that topical-formulated cannabinoids are readily absorbed through the skin, and hence it could be easily employed as oils or balms to treat skin disorders.
Topical cannabis oils and balms are also equally effective in controlling immature skin cell production and inflammation. With its potent anti-inflammatory potential, cannabis can ease painful inflammation during episodic psoriatic flares.
Phytocannabinoids for Pruritus
A scientific review of three clinical trial studies suggested delta-9-tetrahydrocannabinol was effective for treatment of cholestatic (liver disease) pruritus in patients who were unresponsive to conventional therapies. Topical administration of synthetic cannabinoids remarkably reduced experimentally-induced itching (pruritus), in addition to pain and acute burning sensations, which are common in psoriatic episodes.
A Polish study reported that the topical application of cannabinoid-based cream reduced abnormal dryness of skin (xerosis) and pruritus in uremic patients. With just three weeks of topical application, complete disappearance of pruritus was observed in 38% of patients and remarkable reduction of symptoms was observed in the rest of the patients in the study. Interestingly, 81% of the patients reported complete reduction of skin dryness after topical cannabinoid treatment. Co-existence of abnormal skin dryness and pruritus are highly common in psoriasis patients, and some dermatologists now believe cannabinoids may be a newer, promising and effective therapeutic option for the management of xerosis and pruritus.