Psoriasis: What the Skin Shows and the Science Behind It

Anyone living with psoriasis usually describes the same experience: the skin begins to flake, red plaques appear, and they sometimes itch or cause pain. In many cases, flare-ups come and go in cycles that seem completely unpredictable. However, what modern medicine now understands is that psoriasis does not start in the skin — it manifests on it.

Psoriasis is one of the most common inflammatory skin diseases, with a significant genetic component present in about 30% of cases. It can emerge at any stage of life, though it is most frequent between ages 30 and 40. Despite its visible manifestations, it is crucial to reinforce: psoriasis is not contagious, even though it is still frequently surrounded by social stigma.

Millions of people worldwide live with the disease, highlighting not only its clinical relevance but also its impact on public health.

Due to its appearance, psoriasis is often confused with other dermatological conditions, such as dermatitis. However, there are key differences: while dermatitis tends to present with moisture-rich lesions and, in early stages, tiny blisters (vesicles), psoriasis is characterized by drier, thicker, scaly plaques with a reddish base. When scratched, the skin typically flakes even more, revealing this signature pattern.

Psoriasis is a chronic, immune-mediated inflammatory disease in which the immune system becomes dysregulated, maintaining a persistent inflammatory state even without a clear external trigger (Lowes et al., 2014).

In practice, this means the body reacts as if it were under constant threat, keeping inflammation continuously active. To understand this, it helps to imagine how the skin functions under normal conditions.

In healthy skin, the cells of the epidermis (keratinocytes) follow an organized renewal cycle. They form in the deepest layers, mature over approximately 28 days, and reach the surface to form a stable protective barrier.

In psoriasis, this cycle loses its rhythm.

This imbalance happens because the body begins broadcasting inflammatory signals as if there were a constant wound needing repair. It is as if the skin is in a continuous state of “regeneration” — even when it is completely unnecessary.

This phenomenon is central to understanding the disease: it is not just accelerated growth, but disorganized and uncontrolled growth.

Cells multiply within days, without enough time to mature properly. They rush to the surface while still immature and pile up, forming the thick, scaly plaques characteristic of the condition.

But this acceleration does not happen in a vacuum. It is sustained by a continuous inflammatory process. Immune cells — especially T lymphocytes from the Th1 and Th17 pathways — release cytokines such as TNF-α, IL-17, and IL-23. These molecules act as inflammation amplifiers while simultaneously driving further keratinocyte proliferation.

These cytokines act as true “biological switches,” keeping the system turned on indefinitely. In simpler terms, they are “alert messengers,” telling the skin to stay inflamed and keep producing cells, even when it is no longer required.

This creates a cycle that is incredibly difficult to break: Inflammation accelerates cell renewal, and cell renewal perpetuates inflammation.

The skin enters a state of constant hyperactivity.

This dynamic becomes clearer when we observe the structure of the skin affected by psoriasis. This integrated overview is essential because it shows that there is no single point of origin for the disease, but rather an entire system out of balance.

Figure 1. Pathophysiology of Psoriasis

Schematic representation of cellular and inflammatory changes, including immune activation, vascular dilation, and keratinocyte proliferation.

• When looking at the illustration, you can follow this process almost like a sequence:
  
• Increase in immune cells in the dermis → triggers inflammation
• Inflammatory mediators released
• Blood vessels dilate (explains redness)
• Epidermis thickens due to accelerated cell proliferation
• On the surface, cellular accumulation turns into visible flaking

This visualization helps us understand that psoriasis is not a superficial problem. It begins in deeper skin layers and involves multiple systems at once: immune, vascular, and cellular.

Perhaps the most crucial takeaway is realizing that this is not a linear sequence — it is a self-reinforcing feedback loop.

Because of this, psoriasis is not just a localized or cosmetic issue. Today, it is well established that it is associated with a systemic inflammatory state. Patients with psoriasis face a higher risk of developing metabolic syndrome, cardiovascular diseases, and significant metabolic alterations (Griffiths & Barker, 2007).

This means the inflammation is not restricted to the skin — it circulates throughout the body, affecting other systems and contributing to chronic comorbidities. Furthermore, the impact goes beyond the biological. This often-silent emotional toll also acts as an aggravating factor, creating a vicious cycle between the skin and the nervous system.

The presence of visible, recurrent, and often unpredictable lesions can directly impair quality of life, leading to increased anxiety, stress, and depressive symptoms.

Figure 2: Skin Lesions in Psoriasis

Clinical images help recognize the pattern: well-defined, reddish plaques covered with whitish scales, frequently located in friction-prone areas such as the elbows, knees, and scalp.

These lifestyle and psychological factors, in turn, heavily influence the disease:

Chronic stress is recognized as one of the primary triggers for flare-ups. It modulates the immune system and promotes the maintenance of the inflammatory state.

Alcohol consumption — while not a direct cause — is associated with worsening lesions. It can intensify systemic inflammation, compromise skin barrier function, reduce treatment response, and negatively impact compliance.

Other triggers include infections, skin trauma, smoking, and the use of certain medications (e.g., lithium).

When we piece together all these immunological, cellular, metabolic, and behavioral factors, it becomes clear that psoriasis is not just an excess of inflammation.

Above all, it is a failure of regulation.

The problem is not merely the inflammation itself, but the body’s inability to turn it off. The organism loses its capacity to balance signals that would normally be kept under control. The inflammation does not stop. Cell renewal does not slow down. The system remains locked in the “on” position.

It is precisely this realization that is shifting how science approaches treatment. If the root problem is regulatory, simply blocking inflammation might not be enough. We may need to understand which internal systems participate in this balance and how they can be modulated. Among these, one system has taken center stage in recent years: the cutaneous endocannabinoid system.

Core idea: Psoriasis does not start on the surface; it is the visible expression of a system that has lost control.

If the Problem Is Systemic, Why Do We Only Treat the Surface?

Conventional treatments — topical corticosteroids, immunosuppressants, and biologics — primarily aim to reduce inflammation. Many are highly effective.

However, they come with a major limitation: they predominantly work by suppressing the inflammatory response without necessarily restoring the skin’s natural physiological mechanisms of balance. This means that, in many cases, control depends on continuous use. Once stopped, inflammation can rebound precisely because the underlying regulatory system remains misaligned.

It is within this landscape that novel therapeutic approaches are being investigated.

The Skin Is Not Passive: It Responds

For a long time, the skin was considered merely a physical barrier. Today, we know it is a highly active organ capable of producing inflammatory mediators, interacting with the immune system, and regulating its own homeostasis. Furthermore, the skin communicates directly with the nervous and endocrine systems, functioning as a true neuroimmunoendocrine organ.

And here enters a central concept of modern biology:

THE ENDOCANNABINOID SYSTEM (ECS)

The system that regulates the skin that few people know about.

The skin possesses receptors and biochemical pathways that make up the endocannabinoid system — a signaling network involved in regulating inflammation, cell proliferation, pain, and immune response.

This system is composed of:

• CB1 and CB2 receptors
• Endocannabinoids produced by the body itself
• Enzymes responsible for their synthesis and degradation

More recently, this concept has been expanded into the endocannabinoidome, which includes other molecular targets such as TRP channels and PPAR-γ nuclear receptors, broadening the complexity and functional reach of this network (Cristino et al., 2020; Di Marzo & Piscitelli, 2015).

Figure 3 – Overview of the Cutaneous Endocannabinoid System

Schematic representation of the main elements of the endocannabinoid system across cellular compartments of the skin. Source: Montagner & De Salas-Quiroga, 2023

Figure 3 shows that the ECS acts as an integration hub, connecting immune response, cellular activity, and sensory perception in the skin.

At the center are the primary endocannabinoids produced by our own bodies — such as anandamide (AEA) and 2-AG — which act as signaling molecules. They are released locally and interact with receptors present across multiple skin components. These receptors (especially CB1 and CB2) are not restricted to a single region. They appear in immune cells, the epidermis, sebaceous glands, hair follicles, and even sensory nerve endings. Following the arrows in the figure helps us understand this action functionally:

In the epidermis: ECS activation is associated with reduced cell proliferation and controlled keratinocyte differentiation — two areas directly compromised in psoriasis.

In immune cells: The system modulates inflammation, reducing the release of inflammatory mediators.

In nerve endings: ECS activation is linked to decreased pain and itching (pruritus) — symptoms frequently reported by patients.

In sebaceous glands and hair follicles: It influences lipid production, hair growth, and cell apoptosis, proving that the system manages overall skin homeostasis, not just inflammation.

The ECS does not act in an isolated or piecemeal fashion. It functions as a master regulator of the skin — fine-tuning, balancing, and modulating responses.

This regulatory capacity is exactly what is capturing scientific attention when addressing conditions like psoriasis, where the main problem is not a lack of response, but an excess of it.

Where Does Cannabis Come In?

If the body already possesses a system wired to respond to these molecules, the entire premise changes. It is no longer just about “putting cannabis on the skin.” Instead, the question becomes: How do the compounds in cannabis interact with a system that already exists inside the body?

Cannabinoids like cannabidiol (CBD) and cannabigerol (CBG) have chemical structures capable of interacting with these receptors and modulating their functions. They don’t create an artificial effect — they tune a physiological system that is out of whack.

In vitro and clinical studies show that cannabinoids can directly modulate pathways involved in psoriasis, including keratinocyte proliferation and the production of inflammatory cytokines (Wilkinson & Williamson, 2007; Puaratanaarunkon et al., 2022).

CBD and CBG: Different Molecules, Complementary Responses

Cannabidiol (CBD) is currently the most thoroughly researched compound in dermatology. It acts as a multifunctional modulator:

• Reduces pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β
• Inhibits hyperproliferation of keratinocytes
• Exerts antioxidant action, reducing cellular oxidative stress
• Modulates TRPV1 and PPAR-γ (involved in inflammation and cell differentiation)

In practice, CBD strikes directly at the two core pillars of psoriasis: inflammation and dysregulated cell renewal.

Cannabigerol (CBG) — while less studied in human clinical trials — presents a promising pharmacological profile in preclinical research:

• Strong affinity for CB2 receptors (linked to immune response)
• Modulation of TRP channels involved in pain and inflammation
• Activation of PPAR-γ, impacting inflammatory gene regulation
• Relevant antimicrobial effects on the skin

This array of actions positions CBG as a potential, more direct modulator of cutaneous immune inflammation.

A simple way to understand the synergy:

CBD acts primarily as a mediator — smoothing out excesses, calming inflammation, controlling overgrowth, realigning signals.

CBG plays a more active role in specific pathways — an “active peacemaker” targeting immune responses, helping contain severe immune flares.

The “Blend” Concept: When Cannabinoids Work Together

If each molecule has a distinct role, does it make sense to use only an isolated cannabinoid? Latest science suggests not necessarily.

Cannabis operates as an integrated pharmacological system. When combined, CBD and CBG work hand-in-hand, hitting multiple pathways at once. This is known as the entourage effect (Russo, 2011), where different compounds of the plant — including terpenes, flavonoids, and acidic cannabinoids — modulate and enhance each other’s biological impacts.

In skin health, this translates to:

• Broader anti-inflammatory action
• Simultaneous modulation of different receptor types
• More balanced effect on cell proliferation and immune response
• Why Topical Use Makes Sense for Regulation

Since these compounds target receptors right inside the skin, the route of administration is a game-changer. Topical application offers:

• Localized action directly on affected tissue
• Reduced systemic exposure
• Higher interaction with the cutaneous endocannabinoid system

However, there is a technical formulation challenge. Cannabinoids like CBD and CBG are highly lipophilic (fat-soluble) molecules, making it difficult for them to pass through the skin barrier naturally. Therefore, efficacy depends heavily on formulation technology.

Advanced strategies currently being studied to boost penetration include:

• Nanoemulsions
• Liposomes
• Controlled-release delivery systems

We are no longer talking about just applying a trendy ingredient to the skin. We are talking about modulating a complex biological system using molecular synergy and targeted pharmaceutical technology.

When Theory Meets Practice: Cannabis in Action on the Skin

One of the most notable clinical trials was published in 2022 in the Journal of the European Academy of Dermatology and Venereology. This randomized, double-blind, placebo-controlled trial followed 51 patients with mild plaque psoriasis using a 2.5% CBD ointment over 12 weeks (Puaratanaarunkon et al., 2022).

The study utilized a “split-body” design: each patient applied CBD ointment to a lesion on one side of the body and a placebo to the other side, allowing direct comparison within the same organism.

Results were compelling:

• Significant reduction in the Psoriasis Local Assessment Score (LPSI)
• Noticeable improvement in flaking within the first few weeks
• Clear trend toward reduction in size of CBD-treated lesions
• Excellent tolerability with no relevant adverse effects

The authors detailed that CBD acts directly on core disease mechanisms, including inhibition of keratinocyte proliferation and modulation of inflammatory cytokines like TNF-α and interleukins — the very pathways that feed chronic psoriasis.

Figure 4 – Comparative clinical evolution between a lesion treated with cannabidiol (CBD) and a placebo over 12 weeks.

Observing these clinical timelines reveals more than cosmetic improvement; it shows a fundamental shift in how the skin behaves over time.

In the CBD group, thick, scaly plaques progressively transitioned into a smoother, more homogeneous surface, with visible reductions in inflammation early on. Placebo-treated areas showed less consistent and less intense responses.

The visible improvement mirrors what molecular science predicts:

• Reduced inflammation
• Decreased flaking (slowed cell proliferation)
• Reorganization of the skin surface

It is not just “less red” skin — it is skin returning to a balanced state of health.

Broader Dermatological Evidence

Even before this controlled trial, a study by Palmieri et al. (2019) published in Clinical Therapeutics observed similar positive outcomes with topical CBD in patients with chronic inflammatory skin disorders. Over three months of twice-daily application, researchers recorded improved skin hydration, reduced itching, and decreased inflammation, with zero major side effects reported.

These results highlight that CBD does not simply “dry out” a lesion or temporarily mask symptoms. It interfaces with broader cutaneous processes, supporting inflammatory regulation, barrier function balance, and healthy cellular renewal.

The Cellular Level: Slowing Down the Clock

A classic study published in the Journal of Dermatological Science demonstrated that phytocannabinoids, including CBD and CBG, are capable of inhibiting human keratinocyte proliferation (Wilkinson & Williamson, 2007).

Because psoriasis hinges on skin cells multiplying at a chaotic, hyper-accelerated rate, the proven ability of cannabinoids to scale back this proliferation means they strike at the literal structural foundation of plaque formation.

Interestingly, the authors noted that this effect does not rely solely on classical CB1 and CB2 receptors — it recruits other pathways such as TRP channels and nuclear receptors, validating the reality of the expanded endocannabinoidome.

A New Era for Applied Biotechnology

As outlined in a recent review in Phytochemistry Reviews (Atti et al., 2023), preclinical data heavily support this therapeutic potential, while expanding clinical trials continue to show efficacy in conditions ranging from psoriasis and dermatitis to acne, alongside improvements in skin hydration and elasticity.

Looking at this complex landscape, it is easy to see why reducing cannabis to just “a few drops of CBD oil” is an oversimplification that falls short of modern science. Cannabinoids are not a magic, single-target bullet — they are a multi-target network.

In this context, the skin is not a passive canvas. It is a biologically active system equipped with its own tools for self-regulation.

Dermatology is now beginning to embrace these cannabinoid strategies with clinical precision, backed by an increasingly robust body of work. We are no longer looking at an isolated trend, but at an expanded, integrated, and highly sophisticated therapeutic frontier.

The ultimate challenge rests on delivery: ensuring these fat-soluble molecules penetrate efficiently through the skin’s barrier. Through the lens of applied biotechnology — where advanced formulation science meets human physiology — cannabis is earning its rightful, proven place in modern skincare and dermatology.

Conclusion

In the end, perhaps psoriasis teaches us something much larger than just a lesson about the skin.

It shows us what happens when a system loses its ability to regulate itself.

And science, step by step, is beginning to respond — not merely with blocks and suppression, but with modulation.

Cannabis fits into this story precisely at this intersection.

Not as a simplified solution, not as a passing trend, but as part of a biological language that the body itself already recognizes.

Between molecules, receptors, and systems, what is emerging is not a single, magic-bullet answer, but a completely new way of approaching treatment:

More integrated. More precise. Closer to our own natural physiology.

And perhaps that is what will shift the question moving forward. It is no longer about “what to put on the skin,” but rather how to give the skin back its own capacity to find balance.

Bibliography / References

• Lowes, M. A., Suárez-Fariñas, M., & Krueger, J. G. (2014). Immunology of psoriasis. Annual Review of Immunology, 32, 227–255. https://doi.org/10.1146/annurev-immunol-032713-120225
• Griffiths, C. E. M., & Barker, J. N. W. N. (2007). Pathogenesis and clinical features of psoriasis. The Lancet, 370(9583), 263–271.
• Cristino, L., Bisogno, T., & Di Marzo, V. (2020). Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nature Reviews Neurology, 16(1), 9–29.
• Di Marzo, V., & Piscitelli, F. (2015). The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics, 12(4), 692–698.
• Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344–1364.
• Puaratanaarunkon, T., et al. (2022). Topical cannabidiol‐based treatment for psoriasis: A dual‐centre randomized placebo‐controlled study. Journal of the European Academy of Dermatology & Venereology, 36(9).
• Palmieri, B., et al. (2019). A therapeutic effect of CBD-enriched ointment in inflammatory skin diseases and cutaneous scars. La Clinica Terapeutica, 170(2), e93–e99.
• Wilkinson, J. D., & Williamson, E. M. (2007). Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. Journal of Dermatological Science, 45(2), 87–92.
• Atti, et al. (2023). Cannabinoids in dermatology: a review of the evidence. Phytochemistry Reviews.
• Montagner, P., & De Salas-Quiroga, A. (2023). Tratado de Medicina Endocanabinoide (1st ed.). WeCann Endocannabinoid Global Academy. https://wecann.academy
• Lab Deltha. Psoríase: fisiopatologia. https://labdeltha.com.br/psoriase/
• Varella, D. Psoríase pode ser confundida com outros problemas de pele. https://drauziovarella.uol.com.br/dermatologia/psoriase-pode-ser-confundida-com-outros-problemas-de-pele/

By Dr. Lih Vitória – Geneticist Biomedic, Cannabinoid Specialist, and PhD Candidate in Nanotechnology