Adapalene
A third-generation synthetic retinoid originally developed for acne that has significant anti-aging benefits. Adapalene is more stable than tretinoin (resistant to light and oxygen degradation) and better tolerated because it selectively binds to RAR-beta and RAR-gamma receptors rather than all three subtypes. The 0.1% concentration became available OTC in 2016 (Differin), making it the most accessible prescription-strength retinoid.
Concentration & Usage
OTC: 0.1% gel, apply pea-sized amount once nightly to clean, dry skin. Prescription: 0.3% gel for more resistant acne. Can be applied to slightly damp skin with less irritation than tretinoin. Results visible at 8-12 weeks.
Application
Topical (gel, cream, lotion). More stable than tretinoin — can tolerate some benzoyl peroxide layering (Epiduo combines both).
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Mechanism of Action
Adapalene selectively binds RAR-beta and RAR-gamma (minimal RAR-alpha affinity), reducing inflammatory signaling compared to pan-RAR agonists. It normalizes follicular epithelial differentiation and reduces corneocyte cohesion in the pilosebaceous unit, preventing microcomedo formation. Adapalene inhibits AP-1 transcription factor (c-Fos/c-Jun dimerization), suppressing IL-6, TNF-alpha, and neutrophil chemotaxis. It promotes comedolysis by accelerating desquamation of existing comedones. For anti-aging, it stimulates fibroblast collagen I and III via RAR-beta/gamma, with comparable efficacy to tretinoin. Its lipophilic naphthoic acid structure confers superior follicular penetration and light stability.
Ingredient Interactions
Like all retinoids, adapalene benefits from ceramide moisturizers to manage irritation. Apply ceramide cream after adapalene has absorbed for 5-10 minutes.
Unlike retinol and tretinoin, adapalene is chemically stable with benzoyl peroxide. This is the basis of the prescription product Epiduo. Can be layered or used in a combined formulation.
See our full Ingredient Interactions Guide for more combinations and timing strategies.
Regulatory Status
0.1% available OTC in the US and many countries (Differin gel). 0.3% prescription-only. Approved by FDA for acne.
Risks & Safety
Common
Dryness, peeling, redness — generally less than tretinoin. Initial purging for 4-6 weeks.
Serious
Avoid in pregnancy (retinoid class).
Rare
Allergic contact dermatitis, severe peeling.
Compare Adapalene With
Research Papers
8Published: May 29, 2024
AI Summary
Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older.
Published: November 30, 2006
AI Summary
Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy ofretinoids like tretinoin and retinol.
Published: March 19, 2024
AI Summary
Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib-induced skin disorder.
Published: November 22, 2021
AI Summary
Acne vulgaris is an inflammatory disease of the pilosebaceous unit of the skin that primarily involves the face and trunk and affects approximately 9% of the population worldwide (approximately 85% of individuals aged 12-24 years, and approximately 50% of patients aged 20-29 years). Acne vulgaris ca
Published: May 31, 2023
AI Summary
Disease-induced irritation combined with topical medication-induced irritation results in dryness and enhanced inflammation leading to lower compliance and increased skin healing time. TEWL for the treatment group remained significantly lower than the control at all timepoints and significantly improved from baseline by week 12.
Published: December 26, 2023
AI Summary
Hormonal treatments, such as the combined contraceptive pill, are also effective and there is growing evidence for the use of spironolactone for women with persistent acne. Although acne is associated with psychiatric disorder, the mental health effects of isotretinoin remain controversial.
Published: August 31, 2023
AI Summary
Photoaging due to cumulative lifetime ultraviolet light exposure is the greatest contributing factor to facial aging. With the continued growth of the population of individuals aged ≥65 years and over, demand for safe and effective photoaging treatments will likely increase.
Published: December 10, 2022
AI Summary
Among the representatives of retinoids, tretinoin is considered the most effective agent with proven antiaging effects on the skin and can be found in formulations approved as medicines for topical treatment of acne, facial wrinkles, and hyperpigmentation.
Frequently Asked Questions
What is Adapalene used for?
A third-generation synthetic retinoid originally developed for acne that has significant anti-aging benefits. Adapalene is more stable than tretinoin (resistant to light and oxygen degradation) and better tolerated because it selectively binds to RAR-beta and RAR-gamma receptors rather than all three subtypes. The 0.1% concentration became available OTC in 2016 (Differin), making it the most accessible prescription-strength retinoid.
What are the side effects of Adapalene?
Common: Dryness, peeling, redness — generally less than tretinoin. Initial purging for 4-6 weeks. Serious: Avoid in pregnancy (retinoid class). Rare: Allergic contact dermatitis, severe peeling.
How is Adapalene administered?
Adapalene is administered via topical (gel, cream, lotion). more stable than tretinoin — can tolerate some benzoyl peroxide layering (epiduo combines both)..
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Azelaic Acid
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Azelaic Acid
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Bakuchiol
A plant-derived compound from Psoralea corylifolia seeds that provides retinol-like benefits without retinoid chemistry. Bakuchiol does not bind to retinoic acid receptors — it achieves similar gene expression changes through a completely different mechanism, making it safe during pregnancy and for skin too sensitive for any retinoid. Clinical studies show comparable improvements in wrinkles and pigmentation to 0.5% retinol.
Bakuchiol
A plant-derived compound from Psoralea corylifolia seeds that has been clinically shown to provide retinol-like anti-aging effects without retinoid side effects. A 2019 British Journal of Dermatology study directly compared bakuchiol to retinol and found comparable improvement in fine lines, pigmentation, and photodamage — but with significantly less scaling and stinging. It is the most evidence-backed 'retinol alternative' for those who cannot tolerate retinoids.
Benzoyl Peroxide
The most effective OTC acne treatment and one of the few topical treatments that kills acne-causing bacteria (C. acnes) without promoting antibiotic resistance. Benzoyl peroxide works through oxidation — it releases oxygen into pores, creating an environment where anaerobic bacteria cannot survive. It is one of three first-line acne treatments (alongside adapalene and salicylic acid) recommended by dermatological guidelines.