Psoriasis and Psoriatic Arthritis
Psoriatic Inflammation Explained: How Cannabinoids and Terpenes Could Help
Article by Justin L Scharton, Independent Researcher
Article written on January 15 2025
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Disclaimer:
This information is provided for informational purposes only and is not intended to diagnose, treat, or cure any condition. Always consult a licensed medical professional before making changes to your healthcare regimen.
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Psoriasis
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Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. The epidermal cells, immune cells, and sensory neurons contribute to the development and progression of psoriasis.(97E)
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Psoriatic Arthritis (PsA)
Psoriatic Arthritis (PsA) is a chronic inflammatory disease that affects the joints, skin, and nails, and causes permanent joint damage and disability.(98E) TNF-α, IL-23 and IL-17 are the cytokines targeted for treating PsA.(99E)
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Immune Cells and Cytokines Involved in Psoriasis
(IL-17, IL-22, IL-23, TNF-a, α7nAChR, CD4+ T-cells, NK Cells, Macrophages, Dendritic Cells)
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IL-17
- Role: Central to psoriatic inflammation, driving keratinocyte activation and inflammatory cascade.(1F)
- Produced by:
1. CD4+ T Helper Cells (Th17 Subset) (1F)
2. Natural Killer (NK) Cells (1F)
- The terpene fenchone can reduce IL-17. (92D)
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IL-22
- Role: Promotes keratinocyte proliferation and inflammation; often co-expressed with IL-17. (2F)
- Produced by:
1. CD4+ lymphocytes: subsets Th1, Th17, Th2 (23F)
2. Natural killer T (NKT) cells (3F)
3. Innate lymphoid cells (ILC) (3F)
4. Less commonly by CD8+ lymphocytes (3F)
IL-23
- Role: Drives the expansion and stabilization of Th17 cells, leading to increased IL-17 (and other inflammatory cytokine) secretion that worsens psoriasis. (4F)
- Produced by:
1. Macrophages (4F)
2. Dendritic cells (4F)
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TNF-alpha
TNF-a has a complicated role in cutaneous psoriasis. TNF-a inhibitors (etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab) are used for treating both cutaneous psoriasis and psoriatic arthritis. These inhibitors can also have a paradoxical effect by causing cutaneous psoriasis eruptions to happen. TNF-a induced psoriasis can be difficult to treat.(5F)
TNF-a is produced by cells such as activated macrophages, T lymphocytes, monocytes, neutrophils, mast cells, endothelial cells, fibroblasts, and osteoclasts.(98E)
Terpenes that reduce TNF-a: alpha-pinene,(12C) linalool,(62C) b-caryophyllene,(81C) eucalyptol,(38D) a-phellandrene,(50D) a-bisabolol,(62D) fenchone,(92D) and cedrol.(8E)
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alpha-7 nicotinic acetylcholine receptor (α7nAChR)
α7nAChR is upregulated in psoriatic lesions, mainly in keratinocytes and macrophages. Increasing acetylcholine with agonists (PNU-282987) reduces inflammatory cytokines, normalized keratinocyte proliferation/differentiation, and reduced STAT3/NF-κB signaling. Antagonists (Methyllycaconitine) worsened psoriasis.(6F)
Terpenes that may help through acting as acetylcholinesterase inhibitors: a-pinene, b-caryophyllene, caryophyllene oxide, +/- limonene, humulene, geraniol, and delta-3 carene. (37E,52C)
Terpenes that may worsen psoriasis through inhibiting acetylcholine: Thymol (from thyme) and Carvacrol (from oregano) are α7 nAChR inhibitors.(17E) Terpineol is an anticholinergic.(11D) Linalool inhibits the release of Acetylcholine (ACh) at the neuromuscular junction.(55C)
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CD4+ T Helper Cells (Th17 Subset)
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Produce: IL-17 (7F) and IL-22 (9F)
Driven/maintained by: IL-23 (7F,4F)
Role in Psoriasis: Major contributors to the inflammatory loop via the IL-17/IL-23 axis. IL-23/IL-17 pathway may be a therapeutic target for the treatment of chronic inflammatory diseases.(8F)
Receptors on CD4 T-cell: CB1, CB2, TRPA1, TRPV2, TRPM8. (35A)(77A) (80A)(94E)(95E)
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Natural Killer (NK) Cells
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Subsets: NK-17 and NK-22 (10F)
Produce: IL-17 and IL-22 (10F)
Potential Role in Psoriasis: Although less studied than Th17 cells, these NK subsets may amplify inflammation via similar cytokine profiles.(10F)
Receptors on NK-cells: CB1, CB2, TRPV2 (35A)(77A)(80A)
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Macrophages and Dendritic Cells
Produce: IL-23 (4F)
Role: Trigger and sustain the Th17 response, which in turn leads to increased IL-17 and IL-22 secretion.(4F)
Receptors on macrophages: CB1, CB2, TRPA1, TRPV1, TRPV2, TRPV4 (35A)(77A)(78A)(80A)(91E)(92E)(93E)
Receptors on dendritic cells: CB1, CB2, TRPA1, TRPV1, TRPV2 (35A)(77A)(78A)(80A)(92E)
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Possible treatments for psoriasis and psoriatic arthritis with cannabinoids and terpenes
TNF-a inhibitors like etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab are often prescribed to treat psoriasis and psoriatic arthritis. Corticosteroids to shut the immune system down are also used.(5F) These medications do come with a lot of side effects.
Now let’s look at how we can target specific receptors and cytokines to help treat psoriasis. We can directly target IL-17 and TNF-a with the terpene fenchone.(92D) Other terpenes that inhibit TNF-a, while also increasing acetylcholine are limited to a-pinene and b-caryophyllene.(12C, 52C, 81C) The other terpenes mentioned in the above list would only affect one of those receptors, and a few have anticholinergic effects.
The cannabinoid CBG is known to reduce skin inflammation.(75B)
The immune cells themselves can be regulated through their specific TRP, CB1, and CB2 receptors. CBD and THC are the easiest to obtain, and can affect most of the immune receptors. If we want to maximize how many immune cells are being activated, a mix of CBG, CBD, THC, THCA, and THCV would activate all of the cannabinoid and TRP receptors on the immune cells.
Mixing those cannabinoids along with the terpenes fenchone, a-pinene, and b-caryophyllene looks like they would be the most effective combination to help treat cutaneous psoriasis and psoriatic arthritis. The cutaneous type would likely benefit from both a systemic and topical application.
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Psoriasis treatment with capsaicin and TRPV1 overexpression
TRPM2 and TRPV1 are both overexpressed in psoriasis.(11F) TRPM2 is not easy to target, but TRPV1 is very easy with both cannabinoids and capsaicin. TRPV1 agonists with down regulate the overexpression of TRPV1.(79E) A study using capsaicin to treat psoriasis found that there was a greater reduction in scaling, erythema, burning, stinging, itching, and redness of the skin.(12F)
Psoriatic arthritis would likely benefit from capsaicin. There were no studies on psoriatic arthritis like there was on cutaneous psoriasis to show if there was upregulated TRPV1 in psoriatic arthritis. Eating or drinking spicy foods or drinks could help with pain reduction, and topical application would get to the cutaneous lesions directly. Both topical and systemic capsaicin could be helpful to those that can handle the heat.
For those that cannot use capsaicin, terpenes that are TRPV1 agonists are only b-myrcene, and nerolidol.(68C) Cannabinoids that are TRPV1 agonists are CBD, CBG, CBC, CBN, THCV, CBGV, CBDV, CBDA, CBGA, and THCVA. (3A,19A,20A,21A)
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