Effects of THC and CBD: Absorption Through the Skin

The use of cannabis to treat a number of conditions has been proven beneficial, including the ability to manage pain, inflammation, epilepsy, sleep disorders, symptoms of multiple sclerosis, and more. The active ingredients in cannabis are called cannabinoids, and while there are over 100 different types of cannabinoids in marijuana plants—presenting in different concentrations and proportions—two cannabinoids, in particular, have been identified as having a therapeutic effect: tetrahydrocannabinol (THC) and cannabidiol (CBD).

Cannabinoids interact with receptors found on cells throughout the body. These receptors are part of the endocannabinoid system and provide a variety of endogenous signaling pathways to help us maintain homeostasis. Cannabinoid receptors are categorized as CB1 receptors, which are found in the brain and spinal cord, or CB2 receptors, which are widely dispersed among the peripheral nervous system, digestive system, and immune cells. Modulation of regulatory pathways through the use of cannabinoids is a growing strategy for supporting analgesic, neuroprotective, anti-inflammatory, and antibacterial activity.

The specific effects of THC and CBD on cannabinoid receptors depends on receptor localization, specific function, and signaling mechanism. Therefore, the route through which cannabinoids are administered matters. While smoking is a traditional mechanism of cannabis delivery, it makes it hard to control dose and provide the optimal therapeutic effect. Researchers are now investigating alternative modalities, including the absorption of cannabinoids through the skin. Let’s take a closer look at the therapeutic benefits of THC and CBD, as well as novel transdermal modalities.

What Are the Therapeutic Mechanisms of THC and CBD?

THC is primarily associated with the psychoactive effects of cannabis by stimulating both CB1 and CB2 receptors, but especially those in the brain. Aside from psychoactive activity, well-known effects of THC include modulating pain, enhancing appetite and digestion, and triggering emotional processes. Of course, THC is also associated with a range of adverse events (such as drowsiness, confusion, or psychosis) which may limit its tolerability in clinical applications.

CBD, on the other hand, is the major non-psychoactive, therapeutic component of cannabis. CBD helps to counteract the “high” from THC through anti-inflammatory, anti-anxiety, and anti-psychotic activity. CBD acts by limiting CB1 receptor activity (effectively blocking messages of pain and sensitivity to stimuli) and weak inverse agonism of CB2 receptors, in which CBD binds to CB2 receptors but induces the opposite response of THC. However, CBD has little affinity for cannabinoid receptors in general. Researchers propose that CBD interacts with serotonin, vanilloid, and adenosine receptors, among others, to mediate anti-inflammatory pathways.

The role of cannabinoids in inflammation and pain is of particular importance. Evidence shows that the endocannabinoid system is involved in the pathophysiology of pain, and endocannabinoids (the endogenic molecules that interact with cannabinoid receptors) inhibit the expression of pro-inflammatory compounds. This provides a promising route for managing inflammatory disorders: cannabinoid receptor agonists can be used to block pain and attenuate inflammation, while further inducing dopamine release in the brain to reduce the perception of pain.

What Are Novel Modalities of Cannabinoid Delivery?

One challenge of eliciting the benefits of medical cannabis is consistent delivery and control of active components (THC and CBD). Although inhalation and oral administration of cannabis are the most common routes, pharmaceutical companies are now exploring and fully prioritizing different routes of cannabinoid delivery beyond traditional modalities. Oromucosal, topical-transdermal, and rectal routes are of significant interest among researchers.

Another reason for pursuing alternative administration routes to smoking cannabis—besides inconsistency of delivery and dosing and the variable dynamics of the individual user—is due to the fact that cannabinoids tend to combine with fats but less so with aqueous solutions, and they are susceptible to degradation when exposed to light and temperature. In other words, the formulation of cannabis-based therapeutics plays an important role in the stability of the drug.

Not only is stability a concern in medical cannabis, but the pharmacokinetics—the way drugs are distributed and metabolized by the body—vary as a function of the route of administration. In this case, absorption shows the most variability in how cannabinoids move into, throughout, and out of the body. Topical or transdermal absorption is affected both by the intrinsic capacity of cannabinoids to dissolve in lipids and by the inherent organ tissue characteristics, specifically the protective lipid layers of cells.

What Are the Advantages of Transdermal Administration of CBD and THC?

Delivery of cannabis-based products via skin patches, gels, oils, creams, and sprays is comparable to the efficacy of oral-dosage forms but avoids the first-pass metabolism effect associated with the oral route. This improves drug bioavailability, meaning the components are more available in the blood stream and thus have a more profound effect. Another advantage of transdermal administration is that it allows for a steady infusion of cannabinoids delivered over time, which minimizes the adverse effect of a higher peak concentration and improves tolerability and adherence.

Most importantly, topical administration has the potential to treat localized symptoms and is ideal for skin conditions, arthritis, and peripheral neuropathic pain. Other indications for the transdermal administration of CBD include reduction of deep tissue joint and muscle inflammation and wound-healing activities. It also holds promise for the treatment of epilepsy, fragile-X syndrome, osteoarthritis, and other conditions. Finally, a hydrophilic form of THC is being used to reduce intraocular pressure in glaucoma.

Topical-transdermal administration of CBD can be mixed with other anti-inflammatory products or penetration enhancers, such as silicon fluids, oleic acid, emu oil, and argan oil, and can be administered through micro needling formulations. While possible side effects include local irritation and low skin penetration, in comparative studies, transdermal administration of CBD has demonstrated better absorption than the oral route within the same pathological model, indicating the overall efficacy of this novel delivery approach.


Bruni N, Della Pepa C, Oliaro-Bosso S, Pessione E, Gastaldi D, Dosio F. Cannabinoid delivery systems for pain and inflammation treatment [published online September 27, 2018]. Molecules. doi:10.3390/molecules23102478

Urits I, Borchart M, Hasegawa M, Kochanski J, Orhurhu V, Viswanath O. An update of current cannabis-based pharmaceuticals in pain medicine [published online February 5, 2019]. Pain Ther. doi:10.1007/s40122-019-0114-4