Topical and Transdermal CBD Research

There are many CBD products available today that are designed to be applied directly to the skin. The skin is the largest organ in the body, whose main function is to provide a barrier between the environment and the inside of the body. The skin protects us from many things, including UV radiation, allergens, chemicals, and microorganisms like bacteria, viruses, and fungi. It also keeps things like water and nutrients inside of our body. Skin plays a really important role in health, but many people experience skin problems, as well as localized pain and inflammation. Topical and transdermal CBD may be helpful in the treatment of many of these conditions. 

Cannabis has a long history of being applied directly to the skin. Ancient texts describe mixing cannabis flowers with honey which was applied to wounds, as well applying it to skin to treat conditions including bruising and pain¹. More recently, superficially applied cannabis has been approved in various US states to treat conditions including severe pain, psoriasis, lupus, and nail-patella syndrome². CBD and THC are the dominant cannabinoids in cannabis, but due to the psychoactivity and legal restriction of THC, the majority of currently available topical and transdermal cannabis products only contain CBD, sometimes with other minor cannabis components. CBD can also pass through the skin much more readily than THC, with up to 10x greater skin permeation³, supporting application to the skin as a therapeutic route.  

Topical vs Transdermal

The terms topical and transdermal are often used interchangeably, but do they have the same meaning? And how do CBD products fit into these definitions?

The term topical usually refers to products that are minimally absorbed past the skin into the deeper tissues, with a negligible amount passing into the bloodstream. Topical products are designed to minimally penetrate the skin layer, whereas transdermal products are designed to pass through the skin to deeper and distant tissues, with a considerable amount being absorbed into the bloodstream. These are usually formulated with chemical penetration enhancers that allow a deeper penetration. Topical products will provide superficial and local effects, while transdermal products will provide effects that are felt locally but also throughout the body.

The majority of CBD products are described as topical and can be used to treat site specific pain and inflammation as well as skin conditions. A smaller number of CBD products are described as transdermal. Topical CBD products can be used in the treatment of skin conditions, superficial pain, neuropathic pain, and inflammation, whereas transdermal CBD products are being explored as an alternative to oral ingestion, as they bypass the first pass metabolism by the liver, and for treatment of pain and inflammation in deeper tissues⁴.

While these definitions seem clear, even in the scientific literature the terms are often used interchangeably and without distinction. For example, in a 2016 article, CBD applied to the skin is described as being both topical and transdermal⁵, and the same interchange of terms is seen in a 2020 article⁶. This lack of distinction is understandable, in that transdermal products do, in fact, need to be applied topically to the skin. The only way to truly distinguish between topical and transdermal applications is to actually measure the permeation of the product, which is done infrequently. As such, this article will review the research and applications of both topical and transdermal CBD.

Skin Endocannabinoid System

CBD interacts with the endocannabinoid system (ECS) in the skin, known as the dermatological or cutaneous endocannabinoid system. Abnormal functioning of the cutaneous ECS has been linked to common skin disorders including atopic dermatitis, fibrotic disorders, and psoriasis, as well as to the sensation of pain. The two primary endogenous cannabinoids (that is, cannabinoids made by the body) are anandamide (AEA) and 2-arachidonylglycerol (2-AG), both of which are made by the epidermis, hair follicles, and sebaceous glands of the skin. Moreover, the two main ECS receptors, CB1 and CB2, are found in all skin types. Sensory neurons in the skin also contain CB1 and CB2 receptors. The cutaneous ECS is associated with many functions, including pain sensation, inflammation, cell proliferation, and sebum production, providing multiple potential applications for CBD applied to the skin^7,8. 

Research Evidence

While research on the clinical applications of topical and transdermal CBD is limited, it does show promise in the treatment of several conditions. Here are some of the research highlights:

1. Peripheral Neuropathy: CBD applied to the skin has been found to reduce the symptoms of peripheral neuropathy in humans. Topically applied CBD oil reduced intense pain, sharp pain, cold, and itchy sensations in patients with symptomatic peripheral neuropathy when used daily for four weeks in a randomized placebo-controlled study⁶. A recent review article noted the potential for CBD to be used in the treatment of peripheral neuropathy, although human research is limited⁹.
2. Myofascial Pain: CBD applied to the skin has been found to reduce symptoms of myofascial pain in humans. CBD ointment applied twice daily for two weeks directly to the skin over the masseter muscle in the jaw in patients with myofascial pain due to temporomandibular jaw disorder resulted in reduced pain and muscle activity, as measured by surface electromyography in a placebo-controlled study¹⁰.  
3. Arthritis: CBD applied to the skin over a joint has been found to decrease arthritis associated inflammation and pain in an animal model. Application of CBD containing transdermal gel for four consecutive days to rats with experimentally induced knee arthritis resulted in decreased joint swelling, pain, and markers of inflammation⁵. 
4. Inflammation: CBD applied to the skin has been found to reduce inflammation in an animal model. Pre-treatment with transdermal CBD prevented the development of edema in a mouse model of inflammation¹¹. 
5. Pain/Palliative Care: Topical CBD has been found to reduce pain in palliative care patients. In a recent survey, 24% of palliative care outpatients reported using CBD on a regular basis, with topical application being most common. Most patients reported improvements in pain¹².
6. Dermatology: CBD has shown to be beneficial in the treatment of many dermatological conditions in research with humans, rodents, and human skin cells. In humans, application of a CBD enriched ointment on the skin of 20 patients with psoriasis, atopic dermatitis, or scars resulted in improved hydration, transepidermal water loss, and elasticity when used twice daily for three months. Other improvements were noted in some patients, including reduced skin blemishes, scars, papules, pustules, and psoriasis¹³. Also in humans, a small study of three pediatric patients found that topical CBD applied as an oil, cream, or spray by their parents reduced pain and blistering and improved wound healing in patients with epidermiolysis bullosa¹⁴. In animals, CBD was found to reduce inflammation in a mouse model of ear irritation¹⁵, as well as research with human skin cells, which found that CBD inhibited the release of mediators involved in inflammation and wound injury¹⁶. Research with human skin cells has also found that CBD reduces sebum production and inflammation, suggesting a possible application in the treatment of acne¹⁷.

Other Ingredients

Topical and transdermal CBD products come in a variety of forms including lotions, creams, gels, and ointments, all of which include a variety of other ingredients. While we can’t review all of these, there are some ingredients that consumers should avoid, as well as some that have been shown to be beneficial. 

It is generally accepted that products applied to the skin should be free from parabens, artificial fragrances, sodium lauryl/laureth sulfate, toluene, phthalates, formaldehyde, diethanolamine, and triclosan. These should all be avoided in CBD topical and transdermal products.

CBD products are often formulated with other ingredients that may be helpful in the treatment of pain, inflammation, and dermatological conditions. Terpenes that are also found in the cannabis plant, such as linalool (lavender), limonene (lemon), camphor, and menthol may be included for their natural fragrances and soothing effects, along with other skin soothing ingredients such as aloe and yuzu. Arnica may be included for pain, bruising, and arthritis. Products should also be naturally sourced from organic plant ingredients.

For transdermal CBD, skin penetration enhancers may be used. Enhancers will increase penetration by disrupting the skin’s outer layer, the stratum corneum⁴. A recent study found that CBD is better absorbed when prepared as a gel consisting primarily of propylene glycol, as compared to liquid paraffin, virgin olive oil, or polyethylene glycol¹⁸. CBD has also been found to accumulate in muscle under the skin when combined with ethanol and a carbomer gel, in an “ethasomal formulation.”¹¹Natural terpenes, which are widely found in plants including cannabis, are widely being explored as natural skin permeation enhancers, with research showing that terpenes such as limonene and menthol (among others) can increase the penetration of products such as CBD into the skin¹⁹. These terpenes are also often found in topical products where they would be expected to increase skin permeation. 

How to Use

There are two ways to use topical and transdermal CBD products. First, they can be used on their own for the treatment of superficial pain, neuropathic pain, inflammation and skin conditions, although it should be noted that transdermal products may be formulated with ingredients such as ethanol that could aggravate certain dermatological conditions. Used this way, topical products are expected to exert a primarily local and superficial effect while transdermal products are expected to penetrate more deeply into the tissues and also to be absorbed into the bloodstream with circulation throughout the body. Second, topical products can be used in conjunction with orally ingested CBD, which would allow for both local and systemic effects. This approach would not be recommended for transdermal products, which are essentially designed as an alternative, rather than an adjunct, to oral ingestion. For patients who are using CBD to treat multiple conditions (for example, anxiety and neuropathic pain), combining topical and orally ingested CBD could provide greater benefit than using a single product. 

Summary

CBD can be applied to the skin for the treatment of several conditions, including pain, inflammation, and skin disorders. Two types of products are available, topical and transdermal, which differ in their depth of permeation into the skin and deeper tissues. Topical and transdermal products are formulated with additional ingredients, which should be carefully evaluated for their benefits and general safety. Overall, while more research on the clinical uses of topical and transdermal CBD is definitely needed, they do show potential for therapeutic use, which is not surprising given the extensive endocannabinoid system in the skin. 

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