Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases
Abstract
:1. Introduction
2. The Endocannabinoid System: A Brief Overview
2.1. Classic Cannabinoid Receptors
2.2. Endocannabinoids
2.3. Enzymes Involved in Biosynthesis and Degradation of Endocannabinoids
2.4. Further Receptor Targets of Cannabinoids
3. The Endocannabinoid System in the Skin
3.1. Distribution of Components of the Endocannabinoid System in the Skin
3.1.1. Classic Endocannabinoid System
3.1.2. Extended Endocannabinoid System
3.2. The Endocannabinoid System as a Regulator of Skin Homeostasis
3.2.1. Influence on Melanogenesis
3.2.2. Influence on Wound Healing
Cannabinoid Receptor Knockout Models
Role of CB2 Receptor Activation—Results from In Vivo Experiments
Effects of ACEA and Adelmidrol
Role of FAAH—Results from In Vivo Experiments
Role of the Endocannabinoid System in Cell Migration—Results from In Vitro Experiments
On the Path to Clinical Use
3.2.3. Influence on Cutaneous Barrier Function
3.2.4. Influence on Sebocyte Biology
3.2.5. Influence on Hair Follicle Biology
3.2.6. Influence on the Photoexposed Epithelium
3.2.7. Influence on Cutaneous Pain
3.2.8. Influence on Keratinisation
3.2.9. Influence on Skin Ageing Processes
3.3. Regulation of the Endocannabinoid System in Skin Diseases
3.3.1. Endocannabinoids and Classic Cannabinoid Receptors
3.3.2. Extended Endocannabinoid System
TRP Channels
GPR55, GPR119 and GPR18
PPARs
4. Selected Skin Diseases—Pharmacotherapy and Effect of Cannabinoids
- A Brief Historical Overview on Anti-Inflammatory Effects of Cannabinoids
- A Brief Overview on Anti-Pruritic Effects of Cannabinoids
4.1. Androgenetic Alopecia
4.1.1. Current Therapies of Androgenetic Alopecia
4.1.2. Preclinical Findings on the Effect of Cannabinoids in Androgenetic Alopecia
4.2. Atopic Dermatitis
4.2.1. Current Therapies of Atopic Dermatitis
4.2.2. Preclinical Findings on the Effect of Cannabinoids in Atopic Dermatitis
4.3. Allergic Contact Dermatitis
4.3.1. Current Therapies of Allergic Contact Dermatitis
4.3.2. Preclinical Findings on the Effect of Cannabinoids in Allergic Contact Dermatitis
4.4. Psoriasis
4.4.1. Current Therapies of Psoriasis
4.4.2. Preclinical Findings on the Effect of Cannabinoids in Psoriasis
4.5. Acne
4.5.1. Current Therapies of Acne
4.5.2. Preclinical Findings on the Effect of Cannabinoids in Acne
4.6. Systemic Sclerosis
4.6.1. Current Therapies of Systemic Sclerosis
4.6.2. Preclinical Findings on Effects of Cannabinoids in Skin Fibrosis/Systemic Sclerosis
4.7. Dermatomyositis
4.7.1. Current Therapy of Dermatomyositis
4.7.2. Preclinical Findings on Effects of Cannabinoids in Dermatomyositis
4.8. Epidermolysis Bullosa
4.8.1. Current Therapies of Epidermolysis Bullosa
4.8.2. Case Reports on Cannabinoid Effects on Epidermolysis Bullosa
4.9. Pyoderma Gangrenosum
4.9.1. Current Therapies of Pyoderma Gangrenosum
4.9.2. Case Report on Cannabinoid Effects on Pyoderma Gangrenosum
4.10. Beneficial Effects of Cannabinoids in Other Disorders
4.10.1. Acute Inflammation
4.10.2. Keratin Disorders
4.10.3. Scars and Keloids
5. Clinical Trials with Cannabinoids
5.1. Acne Vulgaris
5.2. Acute Inflammation
5.3. Androgenetic Alopecia
5.4. Asteatotic Eczema
5.5. Atopic Dermatitis
5.6. Atopic Eczema
5.7. Dermatomyositis
5.8. Hidradenitis Suppurativa
5.9. Neurogenic Flare Reaction
5.10. Postherpetic Neuralgia
5.11. Pruritus (Chronic)
5.12. Pruritis (Uremic)
5.13. Psoriasis
5.14. Scalp Inflammation (Scalp Psoriasis/Seborrhoeic Dermatitis)
5.15. Systemic Sclerosis
5.16. Urticaria (Chronic Spontaneous)
5.17. Venous Leg Ulcers
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Endocannabinoid/ Receptor | Disease | Regulation | Species | Cells/Tissue | Ref. |
---|---|---|---|---|---|
AEA | TPA-induced acute ear inflammation | ↔ | mouse | inflamed ear versus control ear | [170] |
oxazolone-induced contact dermatitis | ↔ | mouse | oxazolone-treated ear versus control ear | [171] | |
DNFB-induced contact dermatitis | ↑ | mouse | DNFB-exposed ear samples | [3] | |
psoriasis vulgaris and psoriatic arthritis | ↑ | human | human plasma | [172] | |
psoriasis | ↓ | human | keratinocytes from patients | [7] | |
bleomycin-induced skin fibrosis | ↑ | mouse | fibrotic versus control skin | [169] | |
2-AG | TPA-induced acute ear inflammation | ↑ | mouse | inflamed ear versus control ear | [170] |
oxazolone-induced contact dermatitis | ↑ | mouse | oxazolone-treated ear versus control ear | [171] | |
DNFB-induced contact dermatitis | ↑ | mouse | DNFB-exposed ear samples | [3] | |
mite antigen-induced dermatitis | ↑ | mouse | skin lesions versus healthy skin | [5] | |
psoriasis vulgaris and psoriatic arthritis | ↑ | human | human plasma | [172] | |
psoriasis | ↓ | human | keratinocytes from patients | [7] | |
bleomycin-induced skin fibrosis | ↑ | mouse | fibrotic versus control skin | [169] | |
CB1 | DNFB-induced contact dermatitis | ↓ | mouse | DNFB-exposed ear samples | [3] |
psoriatic arthritis | ↑ | human | granulocytes from patients | [172] | |
psoriasis vulgaris | ↔ | human | granulocytes from patients | ||
atopic dermatitis | ↓ | human | itchy lesional skin | [173] | |
psoriasis | ↓ | human | itchy lesional skin | ||
seborrheic keratosis | ↓ | human | seborrhoeic keratosis affected tissue | [156] | |
streptozotocin-induced type 1 diabetes | ↓ | mouse | skin tissue | [166] | |
CB2 | DNFB-induced contact dermatitis | ↑ | mouse | DNFB-exposed ear samples | [3] |
incised wounds | ↑ | mouse | various cell types | [175] | |
psoriatic arthritis | ↔ | human | granulocytes from patients | [172] | |
psoriasis vulgaris | ↑ | human | granulocytes from patients | ||
atopic dermatitis | ↓ | human | itchy lesional skin | [173] | |
psoriasis | ↓ | human | itchy lesional skin | ||
dermatomyositis | ↑ | human | lesional skin and PBMCs | [8] | |
imiquimod-induced psoriasis | ↑ | mouse | psoriatic skin lesion | [178] |
Receptor | Disease | Regulation | Cells/Tissue | Ref. |
---|---|---|---|---|
TRPV1 | erythematotelangiectatic rosacea | ↑ | affected skin | [179] |
phymatous rosacea | ↑ | affected skin | ||
atopic dermatitis | ↑ | pruritic lesional skin | [173] | |
psoriasis | ↑ | pruritic lesional skin | ||
TRPV2 | erythematotelangiectatic rosacea | ↑ | affected skin | [179] |
papulopustular rosacea | ↑ | affected skin | ||
phymatous rosacea | ↓ | affected skin | ||
atopic dermatitis | ↑ | pruritic lesional skin | [173] | |
psoriasis | ↓ | pruritic lesional skin | ||
TRPV3 | erythematotelangiectatic rosacea | ↑ | affected skin | [179] |
papulopustular rosacea | ↑ | affected skin | ||
phymatous rosacea | ↑ | affected skin | ||
atopic dermatitis | ↓ | pruritic lesional skin | [173] | |
psoriasis | ↑ | pruritic lesional skin | ||
TRPV4 | phymatous rosacea | ↑ | affected skin | [179] |
chronic idiopathic pruritus | ↑ | pruritic skin | [180] | |
GPR55 | psoriasis vulgaris, psoriatic arthritis | ↑ | granulocytes from patients | [172] |
GPR119 | acne | ↓ | sebaceous glands | [99] |
PPARα | actinic keratosis | ↓ | affected skin | [181] |
lichen planopilaris | ↔ | lymphocytic scarring alopecias | [149] | |
atopic dermatitis | ↓ | eczematous skin | [182] | |
melasma | ↓ | affected skin | [183] | |
psoriasis | ↓ | pruritic lesional skin | [173] | |
systemic sclerosis | ↓ | fibrotic skin tissue | [184] | |
PPARγ | actinic keratosis | ↔ | affected skin | [181] |
lichen planopilaris | ↓ | lymphocytic scarring alopecias | [149] | |
photoageing in human skin | ↓ | photoaged or acutely UV-irradiated human skin | [185] | |
atopic dermatitis | ↓ | atopic lesions | [186] | |
psoriasis | ↓ | psoriatic lesions | ||
psoriasis | ↓ | pruritic lesional skin | [173] | |
systemic lupus erythematosus | ↓ | circulating CD14+ monocytes | [187] | |
systemic sclerosis | ↓ | lesional skin fibroblasts | [98] | |
systemic sclerosis | ↓ | fibrotic skin tissue | [184] | |
PPARδ | psoriasis | ↑ | psoriatic lesions | [188] |
lichen planopilaris | ↔ | lymphocytic scarring alopecias | [149] |
Substance | Disease/ Condition | Study Design | Formulation | Outcome | Ref. |
---|---|---|---|---|---|
PEA | asteatotic eczema | randomised, monocentric, double-blind, comparative trial | Physiogel® A.I. Cream 1; combination with AEA | higher capacitance of skin surface; improved skin barrier function; reduction of pruritus | [400] |
atopic dermatitis | randomised, investigator-blinded, split-body trial | Physiogel® A.I. Cream 1 | faster healing; reduction of flares | [17] | |
atopic eczema | multinational, multicentre, observational, non-controlled, prospective cohort study | Physiogel® A.I. Cream 1 | reduction of skin dryness, excoriation, lichenification, scaling, erythema and pruritus | [406] | |
randomised, interventional, double-blind trial | Levagen®+ 2 | no results posted yet | [407] | ||
chronic pruritus | randomised, prospective, controlled, open-label, noninterventional study | Physiogel® Calming Relief A.I. Body Lotion | no significant improvement of pruritus and quality of life | [419] | |
postherpetic neuralgia | open observational study; no placebo control | Physiogel® A.I. Cream 1 | reduction of pain and pruritus | [418] | |
uremic pruritis | preliminary observational study; no placebo control | Derma Membrane Structure®; combination with AEA | reduction of pruritus and xerosis | [420] | |
CBD | acne vulgaris | randomised, double-blind, placebo-controlled phase II study | BTX 1503 liquid formulation | no results posted yet | [389] |
andro- genetic alopecia | case series study | CBD-rich hemp oil extract | enhanced hair regrowth | [394] | |
atopic dermatitis | randomised, double-blind, placebo-controlled, phase II study | BTX 1204 liquid formulation | no significant improvement | [16,402] | |
double-blind, placebo-controlled interventional study | JW-100 (topical formulation containing CBD and aspartame) | improvement in ISGA 3 scale | [18] | ||
observational study | topical CBD | decrease in itch; improvement in eczema | [403] | ||
chronic spon- taneous urticaria | placebo-controlled, open- label, single center, phase IIa study | oral CBD | no results posted yet | [427] | |
psoriatic arthritis | randomised, double-blind, placebo-controlled trial | oral CBD | pain reduction | [421] | |
scalp psoriasis/ seborrheic dermatitis | observational study | REVITA.CBD® SHAMPOO 4 | reduction of arborizing vessels, twisted capillaries, scales, erythema, itching and burning | [423] | |
Lenabasum | dermato- myositis | randomised, single-center, double-blind, placebo-controlled phase II study | oral JBT-101 | reduction of CDASI 5 | [408,409] |
randomised, multicenter, double-blind, placebo-controlled, phase III study | oral JBT-101 | reduction of CDASI 5 (patients without muscle weakness); improvement in TIS 6 (patients with muscle weakness) | [410,411] | ||
healthy volunteers 7 | randomised, open-label, placebo-controlled study | oral anabasum | inhibition of neutrophil infiltration; resolution of inflammation | [221] | |
systemic sclerosis | randomised, placebo- controlled phase II trial | oral lenabasum | improvement in CRISS 8 | [424,425] |
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Ramer, R.; Hinz, B. Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases. Cells 2022, 11, 4102. https://doi.org/10.3390/cells11244102
Ramer R, Hinz B. Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases. Cells. 2022; 11(24):4102. https://doi.org/10.3390/cells11244102
Chicago/Turabian StyleRamer, Robert, and Burkhard Hinz. 2022. "Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases" Cells 11, no. 24: 4102. https://doi.org/10.3390/cells11244102