Adapalene is a third-generation topical retinoid available in 0.1% and 0.3% concentrations, primarily used to treat mild to moderate acne vulgaris. It works by modulating keratinocyte differentiation and proliferation, preventing microcomedone formation, and it exhibits anti-inflammatory properties by inhibiting inflammatory mediators.⁴ Common side effects include skin irritation, dryness, redness, and a transient burning or stinging sensation, particularly during the initial weeks of therapy.⁴ Adapalene is contraindicated during pregnancy due to potential teratogenic risks associated with retinoids.⁵ (Please see Table 1)

304119 Table 1.

Initially approved by the U.S. Food and Drug Administration (FDA) as a prescription medication, adapalene 0.1% gel became the first retinoid approved for OTC use in 2016 for individuals aged 12 years and older.⁶

Azelaic acid is a naturally occurring dicarboxylic acid utilized topically at a 20% concentration for the treatment of mild to moderate acne vulgaris.⁷ Its mechanism of action includes antimicrobial activity against C. acnes, anti-inflammatory effects through the inhibition of reactive oxygen species, and normalization of keratinization by reducing the production of keratohyalin granules in the pilosebaceous duct.⁷ Common adverse effects are generally mild and transient, including burning, stinging, tingling, dryness, and redness at the application site.⁷

The U.S. FDA approved azelaic acid 20% cream in 1995 for the topical treatment of mild to moderate inflammatory acne vulgaris.⁸

Benzoyl peroxide (BPO) is a widely utilized over-the-counter topical agent for the treatment of acne vulgaris, particularly effective against mild to moderate forms. Available in concentrations ranging from 1% to 10%, BPO exhibits multiple mechanisms of action. Primarily, it serves as a potent antimicrobial by releasing reactive oxygen species that oxidize bacterial proteins, effectively reducing C. acnes populations.⁹ Additionally, BPO possesses keratolytic properties, promoting the desquamation of the follicular epithelium, which aids in preventing comedo formation.⁹ Its mild anti-inflammatory effects further contribute to its efficacy in acne management.⁹ Common adverse effects associated with BPO include skin irritation, dryness, peeling, redness, and a burning or stinging sensation at the application site. Notably, BPO has a bleaching effect, which can discolor hair, clothing, and bedding upon contact.⁹

The U.S. FDA has approved benzoyl peroxide for over-the-counter use in acne treatment products. However, recent testing has identified elevated levels of benzene, a known carcinogen, in a small number of BPO-containing products, leading to voluntary recalls of those specific items.¹⁰

Salicylic acid is a beta-hydroxy acid that penetrates the skin to exfoliate and unclog pores, making it effective against comedonal acne.¹¹ It also exhibits anti-inflammatory properties by suppressing the NF-κB pathway, reducing inflammation associated with acne lesions.¹² Common side effects include skin irritation and dryness.¹¹ The U.S. FDA has approved salicylic acid for over-the-counter use in acne treatment products.¹³

Sulfur is applied topically in concentrations between 1% and 10%, exhibits keratolytic and antibacterial properties, aiding in the treatment of mild to moderate acne.¹⁴ It helps to shed dead skin cells and reduce excess oil, preventing pore blockage.¹⁴ Adverse effects may include malodor and dry skin.¹⁴ Sulfur is FDA-approved for acne treatment.

Zinc, administered orally as zinc gluconate (200 mg/day) or zinc sulfate (400–600 mg/day), has bacteriostatic properties and inhibits chemotaxis, potentially reducing tumor necrosis factor-alpha production.¹⁵ It is used for mild to moderate acne and may be beneficial in severe inflammatory cases.¹¹ Side effects can include gastrointestinal disturbances such as nausea, vomiting, and diarrhea.¹¹ While zinc oxide is FDA-approved for use in over-the-counter skin products like sunscreens and skin protectants, oral zinc supplements are not specifically approved for acne treatment.

Alpha hydroxy acids (AHAs), such as glycolic and lactic acids, are typically used at concentrations around 10% for their exfoliative capabilities.¹⁶ They promote epidermolysis, disperse basal layer melanin, and increase collagen synthesis within the dermis, aiding in the treatment of mild acne. Adverse effects may include redness, swelling, burning, and pruritus.¹⁶ AHAs are FDA-approved for use in cosmetic products.¹⁷

Sodium sulfacetamide, often combined with 5% sulfur, acts by inhibiting C. acnes proliferation through competitive antagonism of para-aminobenzoic acid, halting bacterial DNA synthesis.¹⁸ It is effective for inflammatory lesions and comedones.¹¹ Side effects can include mild transient dryness and itching.¹¹ While this combination is not technically FDA-approved for acne treatment, the presence of sulfur allows for labeling as such.

Niacinamide, applied topically in concentrations of 2–5%, possesses anti-inflammatory properties, reduces sebum production, and improves skin barrier function.¹⁹ It is effective for mild to moderate acne vulgaris.¹¹ Generally well-tolerated, rare cases of skin irritation have been reported.¹¹ Niacinamide is available OTC but is not FDA-approved specifically for acne treatment.

Resorcinol combined with sulfur is a topical acne treatment commonly formulated with 2% resorcinol and 8% sulfur. Resorcinol functions as a keratolytic agent, promoting the shedding of the outer skin layer to prevent pore blockage and reduce comedo formation.²⁰ It also exhibits antimicrobial properties, contributing to its effectiveness against acne-causing bacteria.²⁰ Sulfur complements this action by further aiding in the removal of dead skin cells and absorbing excess oil, thereby reducing the likelihood of clogged pores.¹⁴ This combination is particularly effective for treating mild to moderate acne, including blackheads and whiteheads.¹¹ Common side effects may include skin irritation, redness, peeling, and dryness.²⁰ These effects are generally mild and can often be managed by adjusting the frequency of application. Resorcinol-sulfur formulations are available over the counter in various forms, such as creams and lotions, but they are not specifically approved by the FDA for acne treatment.

Hydrocolloid patches are non-medicated, adhesive dressings originally developed for wound care but have gained popularity for managing superficial acne lesions. These patches are composed of hydrocolloid material that absorbs excess fluid from pimples, creating a moist environment that promotes faster healing. At the same time, the patches protect the area from external contaminants and physical irritation while concealing the acne lesion.²¹ By maintaining this occlusive barrier, hydrocolloid patches can help reduce inflammation and prevent further infection.²¹ Some hydrocolloid patches are infused with active ingredients like salicylic acid or tea tree oil to enhance their acne-fighting properties, but the primary mechanism remains fluid absorption and protection. Adverse effects are minimal but can include skin irritation, especially in individuals with sensitive skin or when the adhesive is too strong.²¹

Hydrocolloid patches are widely available over the counter and are generally recognized as safe for use; however, they are not specifically approved by the FDA for acne treatment.

Blue light therapy, utilizing wavelengths between 405 and 420 nanometers, is a non-invasive treatment for mild to moderate inflammatory acne.²² It works via targeting C. acnes. These bacteria produce porphyrins, which, when exposed to blue light, generate reactive oxygen species that destroy the bacterial cells.²² Additionally, blue light may exert anti-inflammatory effects by modulating cytokine production, thereby reducing inflammation associated with acne lesions.²²

FDA-approved blue light therapy devices are available for at-home use, offering a convenient, non-pharmacologic option for individuals seeking alternative or adjunctive acne treatments. While generally well-tolerated, potential side effects include skin irritation, redness, dryness, and, in rare cases, changes in pigmentation.²² The FDA has approved light-emitting diode (LED) devices (blue, red, and combination light devices) for at-home use.

Melaleuca alternifolia, commonly known as tea tree oil, is an essential oil derived from the leaves of the Australian tea tree. It is widely recognized for its antimicrobial and anti-inflammatory properties, making it a popular OTC remedy for mild to moderate acne, including cystic lesions. The primary active component, terpinen-4-ol, exhibits broad-spectrum antibacterial activity, effectively targeting acne-causing bacteria such as C. acnes and Staphylococcus aureus.²³ Additionally, tea tree oil has been shown to reduce inflammation, which can help alleviate the redness and swelling associated with acne lesions.²³ However, side effects include skin irritation in some individuals, and allergic contact dermatitis has been reported.²³ To minimize the risk of adverse reactions, it’s recommended to perform a patch test before applying tea tree oil to larger areas of the skin.

Tea tree oil is generally recognized as safe (GRAS) by the U.S. FDA for topical use, but it is not specifically approved for acne treatment. It is available in various formulations, including pure essential oils, gels, creams, and cleansers.

Rosemary essential oil, derived from the leaves of Rosmarinus officinalis, has garnered attention for its potential benefits in acne management. Its efficacy is primarily attributed to bioactive constituents such as 1,8-cineole, α-pinene, camphor, and camphene, which exhibit significant antibacterial activity against C. acnes.²⁴ Studies have demonstrated that rosemary essential oil can disrupt the bacterial cell wall and membrane, leading to cell death.²⁴ Beyond its antimicrobial effects, rosemary essential oil possesses anti-inflammatory properties that may alleviate the redness and swelling associated with acne lesions.²⁴ These combined actions suggest its utility in treating mild to moderate acne. Despite its potential benefits, rosemary essential oil can cause allergic contact dermatitis in some individuals.²⁵

While rosemary essential oil is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration for use in food, it is not specifically approved for acne treatment.

Green tea extract, derived from the leaves of Camellia sinensis, has garnered attention for its potential benefits in managing mild to moderate acne. Rich in polyphenolic compounds, particularly epigallocatechin-3-gallate (EGCG), green tea exhibits notable antioxidant and anti-inflammatory properties.²⁶ The antibacterial effects of green tea extract further enhance its role in acne management.²⁶ EGCG has been shown to inhibit the growth of C. acnes by disrupting bacterial membranes and reducing pro-inflammatory cytokine production.²⁷ Moreover, green tea’s antioxidant capacity helps protect the skin from oxidative stress, which can exacerbate acne.²⁶

Green tea extract is available over the counter in various formulations, including creams, lotions, and cleansers. Although it is not specifically approved by the FDA for acne treatment, it is recognized as safe for use in cosmetic products.

Kaolin and bentonite clays are natural minerals widely used in OTC skincare products, particularly facial masks and cleansers, for managing mild acne. Kaolin, a hydrated aluminum silicate, is known for its gentle absorbent properties, making it suitable for sensitive skin.²⁸ Bentonite, primarily composed of montmorillonite, exhibits strong absorptive capabilities due to its negative charge, allowing it to attract and remove positively charged toxins, bacteria, and excess oils from the skin.²⁹ Clinical studies have demonstrated that masks containing these clays can significantly reduce sebum production, decrease the number of open and closed comedones, and improve overall skin texture.²⁸ However, potential adverse effects include skin dryness and irritation, particularly with overuse or in individuals with naturally dry or sensitive skin.

While kaolin and bentonite clays are GRAS for topical use, they are not specifically approved by the FDA for acne treatment.

Witch hazel (Hamamelis virginiana) is a botanical extract commonly incorporated into OTC skincare products, particularly toners and astringents, aimed at managing mild acne. Its efficacy is primarily attributed to its rich content of tannins and flavonoids, which confer astringent and anti-inflammatory properties.³⁰ These compounds help reduce skin oiliness by constricting pores and diminishing inflammation, potentially alleviating acne symptoms.³⁰ Despite its widespread use, witch hazel may cause adverse effects such as skin irritation, dryness, or allergic contact dermatitis, particularly in those with sensitive skin.³¹ These reactions may be exacerbated by formulations containing alcohol, which is often present in witch hazel extracts and can further dry out the skin.

While witch hazel is GRAS for topical use and is available over the counter, it is not specifically approved by the U.S. FDA for acne treatment.

Retinol and retinyl palmitate are vitamin A derivatives commonly found in OTC acne products at concentrations ranging from 0.01% to 1%. These ingredients promote epidermal cell turnover and prevent clogged pores, targeting key steps in acne pathogenesis.³² Retinol converts into retinoic acid in the skin, while retinyl palmitate acts as a gentler precursor, making it better suited for sensitive skin.³²

Though not FDA-approved specifically for acne, both are widely used in mild to moderate cases.

Manuka honey, derived from the Leptospermum scoparium plant, is increasingly used in skincare for its natural antimicrobial and wound-healing properties.³³ Its efficacy in acne treatment is primarily attributed to methylglyoxal (MGO), a compound with strong antibacterial activity against C. acnes and Staphylococcus aureus.³³ It also maintains a moist wound environment and has anti-inflammatory effects, which may help reduce redness and swelling associated with mild acne.

Though available over the counter and marketed for various skin concerns, Manuka honey is not FDA-approved specifically for acne treatment.

Microneedle patches are emerging OTC acne treatments designed to deliver active ingredients, commonly salicylic acid and niacinamide, directly into the epidermis through tiny, dissolvable needles. This targeted delivery allows deeper penetration compared to traditional topicals, enhancing the effectiveness of exfoliants like salicylic acid and anti-inflammatory agents like niacinamide.³⁴ These patches are typically used as single-use spot treatments for localized acne lesions, particularly papules and pustules. However, mild side effects such as redness, irritation, or transient discomfort at the application site may occur.²⁴

Though available OTC and widely marketed in cosmeceuticals, these devices are not FDA-approved specifically for acne treatment.

C. acnes bacteriophage therapy is an emerging approach in acne treatment that utilizes viruses (phages) capable of selectively infecting and lysing C. acnes, especially type I strains associated with acne pathogenesis.³⁵ Phages can also help reverse bacterial resistance by targeting multidrug efflux pumps that serve as phage receptors, potentially restoring antibiotic sensitivity.³⁵ Some bacteriophages show long-term stability, especially when formulated with appropriate stabilizers or in semisolid vehicles, but they generally require refrigeration and optimized buffer conditions to maintain efficacy. Some products are already available as over-the-counter preparations. This therapy has shown promise for mild to moderate acne, as it directly modulates the skin microbiome without harming commensal organisms.

Although bacteriophage therapy is promising and is being incorporated into skincare regimens, much remains to be elucidated and there is no FDA-approved product in this category for acne at this time.

Topical nitric oxide (NO) therapies, particularly formulations like NO 4% gel, represent an innovative approach to acne treatment through controlled nitric oxide release. NO-releasing nanoparticles have demonstrated strong antimicrobial activity against C. acnes, significantly reducing bacterial viability.³⁶ In addition to their bactericidal effects, these agents also suppress pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-8, thereby addressing both microbial and inflammatory components of acne pathophysiology.³⁶

Clinical studies have shown efficacy in patients with mild to moderate acne, with reductions in lesion counts and inflammatory markers. Reported adverse effects include nasopharyngitis, headache, and dysmenorrhea.³⁷

Although topical nitric oxide is available in some OTC formulations and as cosmeceuticals, these agents are not yet FDA-approved for acne.

Oxygen therapy for acne is a non-invasive treatment typically administered in medical spas or clinical settings rather than through OTC products. Its proposed mechanism involves the generation of reactive oxygen species (ROS), which exert potent antimicrobial effects by disrupting microbial membranes, including those of C. acnes.³⁸ Additionally, oxygen therapy promotes wound healing and skin rejuvenation by stimulating angiogenesis through the upregulation of vascular endothelial growth factor (VEGF) and other pro-healing cytokines.³⁹ This therapy is generally marketed for mild to moderate inflammatory acne and is often combined with other facial treatments.

Some newer topical formulations use oxygen and carbon dioxide in nanobubble suspensions to enhance transdermal gas absorption. These nanobubbles are taken up by the skin’s outer layers, where carbon dioxide promotes local vasodilation, improving blood flow and tissue oxygenation via the Bohr effect, while oxygen supports cellular repair and antimicrobial activity.⁴⁰

While adverse effects are rare and generally unreported, its clinical efficacy remains under investigation, and it has not received FDA approval specifically for acne treatment.

Topical probiotics and postbiotics are emerging as promising adjunctive treatments for mild to moderate acne. Various formulations typically contain live or lysed commensal bacteria or their metabolites, designed to restore skin microbiome balance, suppress C. acnes overgrowth, and reduce inflammation. Key mechanisms include enhancing barrier function, producing antimicrobial peptides, and modulating both innate and adaptive immune responses.⁴¹

While this category of therapy is generally considered safe, concerns include the potential for allergic reactions, antibiotic resistance gene transfer, and, though rare, bacteremia particularly in immunocompromised individuals.^42,43

There are a number of these products available OTC but none are FDA-approved specifically for acne.

Bakuchiol is a plant-derived compound extracted from Psoralea corylifolia and is gaining popularity as a botanical alternative to retinoids in acne management. It exhibits anti-inflammatory, antibacterial, and antioxidant properties that contribute to its efficacy in treating mild to moderate acne.⁴⁴ Mechanistically, bakuchiol downregulates C. acnes proliferation and inhibits inflammatory pathways involved in acne pathogenesis, including NF-κB signaling.⁴⁴

Although structurally distinct from retinoids, bakuchiol mimics many of their effects, such as promoting cell turnover and reducing hyper keratinization, but with fewer reports of irritation or photosensitivity.⁴⁵ It also has demonstrated effectiveness in reducing hyperpigmentation and fine lines, making it a popular dual-purpose ingredient in acne and anti-aging regimens.⁴⁴ Bakuchiol is available OTC in various cosmetic formulations, but concentrations are not standardized across products. The most common adverse effect reported is allergic contact dermatitis, though this remains relatively rare. While promising, bakuchiol is not FDA-approved specifically for the treatment of acne.

Topical cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has emerged as a novel anti-inflammatory and sebostatic agent for acne. Its therapeutic potential is primarily attributed to its ability to inhibit intracellular adenosine uptake, which enhances endogenous adenosine signaling, a known pathway involved in reducing inflammation.⁴⁶ Additionally, CBD modulates the activity of sebaceous glands, decreasing sebum production and limiting the proliferation of C. acnes, thereby addressing key pathogenic mechanisms in acne development.⁴⁷ Formulations typically contain 1–5% CBD, though standardized concentrations are lacking across OTC products. While generally well-tolerated, reports of cannabinoid abuse accompanied by acne have been noted.⁴⁸

Despite increasing commercial availability in OTC skincare, topical CBD is not FDA-approved for acne treatment.

Apple cider vinegar (ACV) is a popular home remedy used for managing mild acne, typically applied topically in diluted concentrations of 5 to 10%. Its therapeutic potential stems from its acetic acid content and associated low pH, which may exert antimicrobial effects by creating an inhospitable environment for acne-associated microbes and disrupting microbial membranes.⁴⁹ Despite its widespread use, ACV lacks clinical trials supporting its efficacy in acne. Furthermore, its acidic nature poses safety concerns. Case reports have documented chemical burns, particularly in children, due to improper or undiluted use. ACV can also enhance the leaching of nickel from metal containers, potentially leading to contact dermatitis in nickel-sensitive individuals.⁴⁹ Though available OTC and widely accessible, ACV is not FDA-approved for acne treatment.

Not applicable

YM has no relevant disclosures. PL reports being on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oréal, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn Biologics, AbbVie, Almirall, Amyris, Apogee, Arcutis, ASLAN, Astria Therapeutics, Boston Skin Science, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs, Concerto Biosci, Dermavant, Eli Lilly, Galderma, Kenvue, LEO Pharma, Lipidor, L’Oréal, Merck, Micreos, MyOR Diagnostics, Pelthos Therapeutics, Phyla, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Soteri Skin, Stratum Biosciences, Sun Pharma, Theraplex, Thimble Health, UCB, Unilever, Verdant Scientific, Verrica, Yobee Care. Stock options with Alphyn Labs, Codex Labs, Concerto Biosci, Soteri Skin, Stratum Biosciences, Thimble, Yobee Care, Verdant Scientific. In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member emeritus of the National Eczema Association.