The Chemistry of Beauty: How Retinoids Enhance Skin Health

Understanding retinoidsRetinoids in dermatologyRetinoids for anti-agingThe future of retinoids in skincareConclusionReferences Further reading 

Retinoids are vitamin A derivatives responsible for regulating several physiological activities with profound importance in dermatology and skincare. They are the most widely utilized active ingredient in topical skin rejuvenation therapies. The various forms of retinoids have found a plethora of applications in dermatological and cosmetic care over the years. They are widely used to treat various skin conditions, including acne, wrinkles, skin cancer, ichthyosis, and psoriasis.

Understanding retinoids

The retinoid family includes various synthetic compounds of vitamin A and its natural derivatives. This consists of retinoic acid, retinyl esters, and retinaldehyde.

According to the molecular characteristics, retinoids are classified into three generations – first, second, and third. The former comprises natural retinoid compounds, including retinal and tretinoin, while the latter consists of synthetic monoaromatic compounds wherein benzene is replaced by cyclohexane, for example, acitretin and etretinate. The third-generation retinoids are polyaromatic and are created due to the cyclization of the polyene side chain. This group includes adapalene, arotinoid, and tazarotene.

Moreover, one of the primary physiologically active metabolites of vitamin A is ATRA (all-trans-retinoic acid). ATRA and other retinoids activate many cellular kinases in a highly cell-specific manner. There seems to be some limitation to the efficacy of ATRA in the skin because of ATRA-mediated resistance resulting from many multifactorial pathways.

Retinoids regulate the proliferation and differentiation of cells, thereby promoting skin healing. They attach to retinoic acid receptors via direct ligand-receptor binding and activate them to induce the transcription of retinoic acid‐responsive genes. This process is mediated by nuclear hormone receptors and CRBP (cytosolic binding proteins). CRBP and CRABP, or cytosolic retinoic acid-binding proteins, are the two types of retinoid receptors.

Retinol enhances the activity of fibroblasts, keratinocytes, Langerhans cells, and melanocytes. It interacts with receptors within keratinocytes and stimulates its proliferation. This then enhances the protective function of the epidermis and decreases transepidermal water loss. Further, it prevents the deterioration of shield collagen and blocks the action of metalloproteinases that break down the extracellular matrix. Furthermore, it promotes angiogenesis in the dermal papillary layer and improves the remodeling of reticular fibers.

Retinoids in dermatology

Retinoids are the most widely utilized active ingredient in topical skin rejuvenation therapies. They are widely used to treat various skin conditions, including acne, wrinkles, skin cancer, ichthyosis, and psoriasis. Disorders of pigmentation like melasma can also be treated using retinoids. By using new RAMBAs (retinoic acid metabolism-blocking agents), the regulation of endogenous ATRA concentration and its natural stereoisomers may lead to the development of new cancer therapeutic approaches as well as dermatological disease treatments.

According to the American Academy of Dermatology (AAD), common retinoids that can be used in various forms (gel, lotion, or cream) to manage acne are – adapalene, tretinoin, tazarotene, and tazarotene. They can be used alone or in combination with other products. Adapalene is thought to be the least effective acne treatment, although it is well-tolerated among other forms of retinoid. Tretinoin is known to have a moderate level of tolerance and efficacy. Although tazarotene has the highest efficiency, skin irritation makes it intolerable. Comparing adapalene 0.1% gel to tretinoin 0.025% gel, a meta-analysis comprising five randomized controlled trials revealed that the former was more tolerable and comparatively effective in treating acne.

Every group in a 12-week randomized trial comparing tazarotene 0.1% gel and adapalene 0.3% gel experienced a clinically significant decrease in the overall number of lesions. Adapalene treatment resulted in a 61% reduction in acne lesions, compared to a 57% reduction in the tazarotene group. The 0.3% gel of adapalene was as effective as the 0.1% gel of tazarotene. Adapalene users, however, reported less irritation.

Retinoids can also play an important role in treating hyperpigmentation caused by acne or other skin conditions. Hyperpigmentation is a common condition in people of color. Asians, Hispanics, and Blacks usually suffer from various forms of hyperpigmentation, including acne lesions and hyperpigmented macules.

Retinoids can also treat hyperpigmentation in conjunction with other topical medications and procedures, such as superficial chemical peels. Primary acne lesions can get better weeks before PIH (post-inflammatory hyperpigmentation) gets better, so helping patients set realistic expectations will help them feel less frustrated.

The chronic, complex disease known as psoriasis disrupts keratinocyte development and proliferation. Psoriasis has long been treated with retinoid therapy. This makes it possible to comprehend retinoic acid's function in skin physiology and disease on a deeper level.

It has been demonstrated that treating basal cell carcinomas (BCCs) with derivatives of retinoic acid is beneficial. An early study found that topical 0.05% tretinoin effectively regressed BCCs. However, once treatment ended, recurrence rates were high. Clinical investigations showed more promise for tazarotene creams.

Tazarotene, a derivative of retinoic acid, was shown in a clinical investigation to be beneficial in the treatment of BBCs. There was a regression of basaliomatous cells, which was linked to higher apoptosis and decreased proliferation. Fenretinide, another retinoid, is carcinogenic to skin tumor cells as well as other cancerous cells.

Retinoids for anti-aging

Skin aging due to chronology or inherent factors happens as time passes. Clinically, there are fine wrinkles, and the skin looks dry and atrophic. However, it is acknowledged that external or environmental variables have a bigger impact on the look of skin, making them appropriate targets for "antiaging" therapy.

Sunlight's ultraviolet radiation (UVR) is widely acknowledged to be the main environmental element causing extrinsic aging or photoaging. There is a dose-response association between pack-years of smoking and wrinkles, indicating that tobacco use is an independent risk factor for accelerated skin aging. It is well known that air pollution contributes to extrinsic skin aging, causing wrinkles and dyspigmentation.

Retinoids play a crucial role in the anti-aging process of the skin. The various forms of retinoids have found a plethora of applications in dermatological and cosmetic care over the years. Retinol helps in the management of wrinkles, fine lines, and skin textures. Retinyl esters and retinaldehyde have stabilizing properties and can facilitate the treatment of wrinkles.

The effectiveness of 0.05% and 5% tretinoin cream on numerous actinic keratosis and photoaged skin was examined in a study. Improvement in skin photoaging was observed after the treatment.

The future of retinoids in skincare

An area of investigation that has led to novel medicines in acne therapy is combination therapies with topical retinoids. The utilization of combination therapy with topicals has proven to be helpful from the perspective of a multimodal mechanism of action. It potentially minimizes the necessity for oral medication and systemic exposure. New topical retinoids and these agents being coupled with other well-proven topical therapies will come as no surprise, given the prevalence of acne in both adults and children. Formulating compounds in new vehicles that support the stability of products and lessen their adverse effects is also of interest.

Despite several decades of biochemical and clinical research, there are still several obstacles to using retinoids to prevent and treat skin cancer. First, there are new retinoid compounds that haven't been well-tested for their potential to treat skin cancer. The clinical translations of basic research findings are not fully informed. To minimize adverse effects and maximize the utility of retinoids in the treatment of skin cancer, rational medication combinations incorporating these chemicals may be essential.

Therefore, the identification of therapeutic biomarkers to assess retinoid response and anticipate resistance may be a promising area of research in the future, perhaps leading to the selection of patients most likely to benefit from retinoid therapy.

Conclusion

Over the years, first-generation tretinoin—which is still a popular therapeutic option for many dermatologists—has given way to topical retinoids. The third and fourth-generation retinoids, which have improvements in potency, tolerability, photostability, and other indications, were discovered as a result of ongoing research into these drugs.

Characterizing the molecular genetics of retinoid response and applying this understanding to treatment design, prognostication, and patient selection optimization can be productive research directions. Such studies can help direct the use of retinoids in dermatology in the future, ushering in the era of precision medicine.

References

Further Reading 

The Best CBD Face Creams of 2024

We include products we think are useful for our readers. If you buy through links on this page, we may earn a small commission. Here’s our process.

Healthline only shows you brands and products that we stand behind.

Our team thoroughly researches and evaluates the recommendations we make on our site. To establish that the product manufacturers addressed safety and efficacy standards, we:

We do the research so you can find trusted products for your health and wellness.

While you may be familiar with cannabidiol (CBD) oils, gummies, and even salves and balms, CBD beauty products are a little newer to the scene.

But do products like night creams really benefit from being infused with CBD oil? And is CBD gentle enough for the delicate skin on your face?

Keep reading to find out more about CBD face creams and our top CBD face cream picks.

When it comes to CBD for skin care, the research is still ongoing. But what’s known so far is somewhat promising.

Here’s what the research says about CBD’s effects on the skin.

It may have anti-inflammatory effects

According to a 2014 study, CBD’s anti-inflammatory properties may play a role in controlling sebum, or oil, production. Bye bye, oily T-zone!

Emerging evidence also suggests that CBD may help treat acne due to its anti-inflammatory effects.

A research review from 2020 suggested CBD may help protect against oxidative stress, which causes cell damage. But the conclusion is based only on in vitro (aka test tube) studies and not clinical trials with actual people.

It may help treat several skin conditions

One 2018 research review concluded CBD may help treat skin conditions, including:

However, the review authors recommended additional high quality randomized, controlled trials to further look into the effects of CBD on the skin.

Another review from 2019 suggested CBD may also help with wound healing. In addition, a 2020 review noted CBD’s therapeutic potential for treating skin issues like eczema and acne.

Again, there’s a need for further study since most of the data included in the reviews are based on in vitro and animal studies.

Some clinical studies suggest topical CBD can provide pain relief, which may be helpful for people with sensitive, easily irritated skin or chronic facial wounds. But again, more high quality studies are needed to validate this.

According to a small 2019 study that followed 20 participants with irritating skin conditions, applying THC-free CBD to the affected area significantly improved skin health without causing side effects. While this was promising, more high quality clinical trials are needed.

We chose these products based on criteria we think are good indicators of safety, quality, and transparency. Each product in this article:

As a part of our selection process, we also considered:

Where available, we’ve included special discount codes for our readers.

Pricing guide

Best CBD face cream for eczemaMedterra Manuka Care Cream

Manuka honey is a particular type of honey that may have antibacterial properties. It may help alleviate the symptoms of eczema, a painful skin condition that causes severely dry, itchy skin.

In addition to manuka honey and CBD isolate, this cream also includes more than 20 botanicals to help soothe the skin. Reviews for the cream are generally positive. People say it helps with eczema as well as many other skin conditions.

In addition to offering assistance programs for veterans and people on long-term disability, Medterra is also U.S. Hemp Authority Certified.

Best CBD cream for dry skinNeurogan CBD Face Cream

This rich moisturizer from Neurogan features a blend of skin-soothing ingredients, like shea butter, sunflower oil, jojoba seed oil, and aloe leaf juice, to help hydrate and nourish your skin and target uneven texture and dryness.

The brand recommends using it every day.

At time of publish, 36 out of 36 reviewers gave this moisture-rich CBD face serum 5 out of 5 stars. They say it smells great, glides on smoothly, and even helps with redness.

Best calming CBD face maskCBDfx CBD Face Mask

This soothing sheet mask is designed to soothe, tone, and hydrate stressed skin.

There are five scents to choose from, each of which is formulated with a unique blend of ingredients, like aloe vera, charcoal, cucumber, lavender, and rose.

CBDfx recommends applying this mask after cleansing and drying the skin and leaving it on for 10 minutes to allow your skin to absorb the active ingredients.

Customers note that this mask leaves their skin feeling soft and smooth. Some also report that it works well for sensitive skin and can help with issues, like redness and puffiness.

Best CBD face cream for daily useZatural CBD Face Cream

Zatural’s daily face cream is designed to prevent dryness and target the signs of aging, like fine lines, wrinkles, and age spots.

Each bottle contains 300 mg of broad-spectrum CBD and a blend of skin-soothing ingredients, including jojoba seed oil, white tea extract, and hyaluronic acid. The company recommends applying the product after cleansing and toning, morning and night.

Customers note that this moisturizer helps brighten the skin and doesn’t have a greasy feel. One reviewer even says that the cream helped with redness and was gentle enough to use on sensitive skin.

Because there are so many companies selling CBD — and some of them are not so great — you need to be able to sort the good from the bad.

And when it comes to products intended to go on your face, you also need to look for stuff that’s compatible with your skin type and concerns.

Here’s what to consider:

Potency

Because the skin doesn’t absorb topical CBD products that easily, it’s important to choose potent products for optimal results. Look for creams that contain at least 3 mg of CBD per mL of product.

CBD type

You’ll find products with one of three types of CBD:

While full-spectrum CBD contains some THC, isolate and broad-spectrum don’t. Additionally, both full- and broad-spectrum CBD contain additional therapeutic compounds, like terpenes.

Third-party testing

There’s no regulatory body that guarantees the safety of over-the-counter (OTC) CBD products. But a reputable CBD company will get its products tested by a third-party lab and have COAs readily available for customers to view.

Be sure the COA lists the CBD and THC potency, as well as the level of contaminants, like heavy metals and pesticides.

Hemp source and other ingredients

Companies should be transparent about where they source their hemp. Ideally, go with a product made from all-natural, U.S.-grown hemp.

And if it’s for your face, make sure other ingredients won’t irritate sensitive skin.

Using topicals, like CBD face cream, is pretty self-explanatory. Rub them onto the skin and massage the area until the cream gets absorbed, just like you would with any non-CBD cream.

CBD creams vary in potency, but it’s generally OK to use the same amount you would with a non-CBD face cream.

CBD face creams are generally safe to use over and over again, but make sure to do a patch test before applying them to your entire face — especially if you have reactive skin.

Because topically applied CBD isn’t absorbed into your bloodstream quite like ingested CBD, creams are unlikely to cause side effects or interact with medication.

However, talk with your doctor before using a CBD face cream, just in case.

Does CBD face cream do anything for your skin?

CBD may have anti-inflammatory effects and help treat certain skin conditions. But there’s still a lot we don’t know about CBD for skin care, so it’s difficult to say for certain.

Does CBD face cream work for eczema?

Initial research suggests CBD creams may help soothe dry, itchy skin that occurs because of eczema. But most of the research has been on human or animal skin samples, not actual people.

Anecdotally, people report that it helps with this skin condition.

Does CBD face cream have anti-aging properties?

Because CBD has antioxidant properties, it may help reduce fine lines and wrinkles and help to smooth skin texture, if that’s something you want. But more research is needed to fully understand the aging support effects of CBD creams.

Just like how CBD may help with sleep issues and chronic pain, it may also be helpful for the skin.

When shopping for CBD face creams, carefully scan the ingredients list and look for anything that might not agree with your skin. Be sure to choose a product from a reputable brand that conducts third-party testing.

Is CBD legal? The 2018 Farm Bill removed hemp from the legal definition of marijuana in the Controlled Substances Act. This made some hemp-derived CBD products with less than 0.3% THC legal at the federal level. However, CBD products containing more than 0.3% THC still fall under the legal definition of marijuana, making them illegal at the federal level. Some states have legalized CBD, so be sure to check state laws, especially when traveling. Also, keep in mind that the FDA has not approved nonprescription CBD products, and some products may be inaccurately labeled.

Steph Coelho is a freelance writer with chronic migraine who has a particular interest in health and wellness. When she’s not click-clacking away on her keyboard, she’s probably nose-deep in a good book.