Rosacea

Article by Justin L Scharton, Independent Researcher

Article written on January 12 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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     Rosacea is a chronic inflammatory skin disease, and the cause is unknown. Receptor gene expression and immunoreactivity differs between different subtypes of Rosacea as shown below (80E):

 

Erythematotelangiectatic rosacea (ETR)

 

• Elevated TRPV2 and TRPV3 in the dermis (80E)

• Increased TRPV1 gene expression (80E)

 

Papulopustular rosacea (PPR)

 

• Enhanced TRPV2 and TRPV4 immunoreactivity (80E)

• Upregulated TRPV2 gene expression (80E)

 

Phymatous rosacea (PhR)

 

• Increased dermal TRPV3 and TRPV4 (80E)

• Higher TRPV1 and TRPV3 gene expression (80E)

• Decreased TRPV2 staining in the epidermis (80E)      

 

     If certain receptors show increased gene expression but are not actually present in the dermis (as shown above), they won’t serve as pharmacological targets. Even when a gene is upregulated, it doesn’t always lead to the production of functional receptors because cells often prioritize certain gene expressions over others.

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Will TRPV2, 3, and 4 in rosacea downregulate from desensitization?

 

     Unfortunately, no research has been done to see if TRPV2, TRPV3, and TRPV4 would down regulate with frequent use of agonists to cause desensitization. Research has only been done on TRPV1 becoming downregulated with using agonists,(79E) as shown in the section on shingles. 

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Erythematotelangiectatic rosacea (ETR)

 

     Symptoms of ETR include flushing (transient erythema), persistent central facial erythema (background erythema), appearance of telangiectasias (dilated small blood vessels), stinging and burning sensations, and scaling. Some triggers like, heat exposure, hot temperature, exercise, spicy foods, and alcohol ingestion can cause increased vasodilation of the facial skin.(81E)

 

     Current medical treatments for ETR are using brimonidine 0.33% gel, with intermittent use of laser/light-based therapy.(81E)  Brimonidine tartrate is a highly selective alpha2-adrenergic receptor agonist that is typically used for glaucoma and ocular hypertension.82E Alpha 1 and alpha 2 adrenergic receptor activation causes vasoconstriction,83E to reduce the vasodilation from ETR.(81E)

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Papulopustular rosacea (PPR)

 

     Papulopustular rosacea has the signs of central facial erythema and a variable number of small erythematous papules and pustules.(84E) Medication management could include azelaic acid. A study compared that to metronidazole, and found that “The use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea.”(85E) Azelaic acid (AzA) has profound anti-inflammatory, antioxidative effects, and is bactericidal against a range of Gram-negative and Gram-positive microorganisms.86E Azelaic acid is an inhibitor of tyrosinase, mitochondrial respiratory chain enzymes and DNA synthesis.(87E)

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Phymatous rosacea (PhR)

 

     Phamatous (Gr. phyma, growth) rosacea most commonly affects the nose (rhinophyma), and has skin thickening and hyperplasia of sebaceous glands.(84E) Treatment can include Isotretinoin (13-cis-retinoic acid), which is a synthetic retinoid derived from retinol (vitamin A).(88E) Isotretinoin is an anti-inflammatory and sebum-suppressive agent. A study with people with rosacea treated with Isotretinoin had a reduction of inflammatory lesions by 50% within 2 weeks, and by over 95% within 8 weeks.(89E)

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Can cannabinoids and terpenes help or hurt rosacea?

 

     This section is showing the possible outcomes of certain cannabinoids and terpenes that could affect rosacea based on specific receptors for 3 of the subtypes of rosacea. Here are the receptors that we are working with:

 

Erythematotelangiectatic rosacea (ETR) - Receptor targets: TRPV2, TRPV3, and alpha2-adrenergic agonists (80E,81E,82E)

 

Papulopustular rosacea (PPR) -  Receptor targets: TRPV2 and TRPV4 (80E)

 

Phymatous rosacea (PhR) - Receptor targets: TRPV3 and TRPV4 (80E)

 

TRPV2 agonists: THC, CBD, CBG, CBGV, CBDV, THCA, CBN. (3A,19A)

 

TRPV3 agonists: CBD, CBGV, CBGA, THCV (3A,19A)

 

Terpenes that are TRPV3 agonists: camphor, menthol, dihydrocarveol, 1,8-cineol,(38A) 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol, (+)-borneol,(39A) and eugenol. (36A)

 

TRPV4 agonists: CBG, CBN, CBDV, THCV, CBGV, CBGA (3A,54A)

 

Terpenes that interact with the adenosine A2A receptor: +/- limonene,(89B) and humulene.(6D)

 

TRPM8: eucalyptol is a TRPM8 agonist.(33D)

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     There is currently no published research on whether cannabinoids or terpenes help or harm rosacea. It is possible to create a topical blend by mixing shea butter with cannabis oil and terpenes; however, this is strictly for educational exploration, not a proven treatment.

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TRPV3 and vasodilation

 

     Starting off, we do know that the cannabinoids, CBD, CBGV, CBGA, THCV are agonists of TRPV3 (3A,19A), and that could lead to some different possible outcomes. TRPV3 activation can cause vasodilation through triggering the release of Adenosine Triphosphate (ATP), calcitonin gene-related peptide (CGRP), nitric oxide (NO), and prostacyclin (PGI2).(42A,43A) Rosacea has a problem with vasodilation already,(81E) Further activation with cannabinoids or terpenes could possibly worsen aspects of rosacea, especially redness and inflammation.

 

     Another possibility could be that the cannabinoids would modulate the flow of ions through those receptors, that would reduce the inflammation through TRPV3 and/or other anti-inflammatory properties. The terpenes that activate TRPV3 would likely be more of an irritant.

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Does limonene and humulene activate alpha-2 adrenergic receptor for vasoconstriction?

 

     It is possible to try other receptors with terpenes to cause more vasoconstriction. Limonene and humulene are agonists of the alpha-2 adrenergic receptor,(6D) and activation of that receptor will cause vasoconstriction. A-2 agonist like brimonidine 0.33% gel has been used for treating Erythematotelangiectatic rosacea.(81E) Brimonidine tartrate is a highly selective alpha2-adrenergic receptor agonist that is typically used for glaucoma and ocular hypertension.(82E) It is not known which terpene would activate alpha-2 adrenergic receptors more effectively, but some of us cannabis users would point to humulene to be more of a vasoconstrictor.

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TRPM8 for vasoconstriction and cooling

 

     TRPM8 activation will cause a cooling sensation,(55A) which could lead to vasoconstriction.90E Eucalyptol is a TRPM8 agonist.(33D) This terpene could possibly cause some relief for rosacea through TRPM8 activation causing both a cooling sensation and vasoconstriction.

 

 

 

Cannabis and terpene infused shea butter for rosacea?

 

     Shea butter infused with both CBD and CBN would target all 3 subtypes of rosacea, or specific cannabinoids can be used for each subtype. Terpenes like humulene, eucalyptol, and possibly limonene could further enhance the cooling and vasoconstrictive properties of the cannabinoids. It is also possible that either the cannabinoids or terpenes could make some of the symptoms worse with rosacea. Caution is advised!