CRx MAGAZINE

Summer 2020

Beyond the Smoke: Transdermal Patches Offer New Path to Cannabinoid Delivery

As the use of cannabis as medicine continues to grow, so do innovative methods of administration. One recent advancement is the development of transdermal patches that deliver THC and other cannabinoids through the skin into the bloodstream. However, transdermal patches aren’t exactly novel; transdermal administration of prepared treatments in the form of salves, potions, and patches to manage specific ailments can be traced back to ancient Egyptian and Babylonian medicine.1

Yet it wasn’t until the 1970s that methods of precise and reproducible administration through transdermal delivery systems were patented and recognized to have measurable systemic effects. For instance, Scopolamine (hyoscine) patches for the treatment of motion sickness were the first transdermal patches to be widely prescribed starting in 1979.1 Since then, the variety of transdermal patches on the market has expanded to include those for hypertension treatment, hormone replacement therapy, nicotine therapy, and cannabis consumption.

While sometimes discussed as though they’re interchangeable, transdermal and topical administration aren’t the same. Transdermal delivery of medications produces clinical and systemic effects, such as local anesthesia and anti-inflammatory activity, deep within or beneath the skin, whereas topical delivery treats superficial skin problems through a relatively local action. Transdermal patches (also known as transdermal delivery systems or TDDS) work by creating a “drug concentration gradient,” meaning there’s a high concentration of a drug on one side (the patch) and a low concentration of drug on the other side (under the skin). As the active ingredients start to interact with the skin, the drug moves into the area of lower concentration in an attempt to reach equilibrium. As the drug moves deeper into the skin, it enters the bloodstream and causes systemic effects. Because it enters the bloodstream directly, it doesn’t go through first-pass liver metabolism.

Options
There are two types of patches: matrix and reservoir.

Matrix patches are a mixture of the active drug (in this case, cannabinoid extracts), a transdermal adhesive, an excipient (a “vehicle” in drug delivery), and natural skin permeation enhancers. The mixture is applied in a uniform layer to a plastic release liner that’s removed when the patch is placed on the skin. After the matrix cures, a backer is placed on top (this is the neutral-colored material that shows on the skin; the matrix is between two layers). Application requires peeling off the plastic release liner and sticking the backing to the skin, putting the matrix between the backing and the skin. Matrix patches offer a tapered release of the active ingredient, starting with higher concentrations and releasing less and less active ingredient as the drug concentration gradient comes to equilibrium.1

Reservoir patches have a peel-off liner and an adhesive, but they hold the active ingredient in a reservoir covered by a permeable release membrane. This membrane helps control the rate at which the active ingredient penetrates the skin. This ensures that the active ingredient is released at a steady, controlled pace.2

According to Jeremy Riggle, PhD, chief science officer of Mary’s Medicinals, a manufacturer of widely available transdermal cannabinoid patches, the key to transdermal delivery of any drug is overcoming the barrier function of the skin. “Patches must be engineered to disrupt the structure of the stratum corneum (the outermost layer of the skin) just enough to permit the delivery of cannabinoids through the skin and into the bloodstream,” Riggle says. There are a number of different types of permeation enhancers, some of which may cause skin irritation, so it’s important to choose a product that lists all of the ingredients, not just the active cannabinoids.

Plusses of the Patch
The benefits associated with transdermal cannabis administration include the following:

Systemic relief. Because cannabinoids are absorbed directly into the bloodstream when administered transdermally, they can provide whole-body relief instead of spot relief such as that felt when cannabinoids are applied topically.
Time-released relief. Transdermal delivery releases a consistent amount of cannabinoids slowly over several hours. Effects of transdermal patches are usually felt within 15 minutes and last until the cannabinoids have all crossed the skin barrier, about four to six hours, or about 45 minutes after removal of the patch.
Specific cannabinoid profiles. Made from cannabis extracts, transdermal patches can deliver very specific cannabinoids and precise cannabinoid ratios because they are specifically and accurately dosed from the outset. For instance, patches can be CBD only, cannabinol (CBN) only, THC only, 1:1 CBD:THC ratios, and more. This targeted approach can be better for certain conditions when specific cannabinoids are required to elicit specific medicinal effects, eg, using a CBN patch for sleep.
Discretion. One of the most common reasons people use transdermal patches is because they often go unnoticed. They’re usually a neutral color and worn on the inside of the wrist or the top of the foot. There’s no odor. And because the patch lasts for hours, there’s no reason to take frequent doses.
Dose control. Because the amount of cannabinoids in a patch is consistent, it’s easy to increase or decrease the dose. For a lower dose, matrix patches can be cut in half; if undesired effects occur, the patch can be removed. On the other hand, if the desired effects aren’t being felt with one patch, a second patch can be used.
Bioavailability. When cannabis is smoked or eaten, up to 70% may be lost to vaporization and/or metabolism. Transdermal delivery is more effective, with almost 100% of the cannabinoid content entering the bloodstream. As with any medicine, the dose required for relief by an individual is based on age, body composition, condition, and other factors.
Safety. Using patches avoids risk of exposure to potentially dangerous combustion byproducts and first-pass liver metabolism from smoking or consuming edibles.

Conditions Benefiting From Transdermal Cannabinoid Administration
According to Riggle, “transdermal cannabinoid patches are a low-risk, high-reward proposition for a number of conditions.” That said, there isn’t much hard science to support this mode of administration. As with most of research in medical cannabis, the majority of the studies investigating the benefits of transdermal delivery of cannabinoids is preclinical, based on animal models, and highly preliminary. However, there’s promising work being conducted. In 2015, a study of inflammation and pain behavior in rats showed that the transdermal administration of CBD resulted in reduced joint swelling and reduced acute pain scores. The authors concluded that the data suggest CBD’s therapeutic potential for relief of arthritis pain and inflammation.3

Other conditions that lend themselves to transdermal cannabinoid therapy are anxiety and sleep. Although there aren’t any studies on efficacy specific to transdermal delivery, it stands to reason that consistent, prolonged exposure to cannabinoids such as CBD and CBN can be an effective way to manage anxiety and sleep disturbances.

While the main reason people use transdermal cannabis patches is for pain relief, they can be used for any condition for which other forms of cannabinoid therapy would be applicable. The low, slow delivery of cannabinoids such as THC and CBD can provide all-day (or -night) symptom relief without the intoxicating effects. This can allow patients to remain highly functional and productive while experiencing the pain relief offered by cannabis.

Availability
There are a number of manufacturers of cannabinoid patches. State and federal regulations present logistical challenges because THC can’t be moved across state lines. Therefore, manufacturers of patches containing THC must have individual operations in each state in which they sell products. Moreover, patches containing THC can be sold only through dispensaries. This leads to questions about consistency and quality of these types of products. Patches that contain only CBD are more readily available and can even be purchased online.

Conclusion
Easy, accurate, safe, and effective, transdermal patches of THC, CBD, or a combination of cannabinoids may be the best mode of administering medical cannabis therapy. For patients hesitant to try smoking, vaping, or edibles because of safety or stigma, transdermal patches offer a safe, discreet way to try cannabis therapy.

As with any cannabis therapy, it’s important that patients keep a detailed diary of time, dose, and effects. Specific to transdermal patches, patients should note changes in pain or anxiety over time to determine how long the patch lasts.

One caveat to transdermal patches is the cost. Quality patches with strong adhesives and highly functional permeation enhancers can cost as much as $10 per patch. For patients new to cannabis therapy, starting with a matrix patch that can be cut in half or even in fourths can be a way to stretch therapy dollars. In this case, it’s particularly important to note when cannabis effects begin and when they wear off to make changes in timing and dosing as needed.

— Bonnie Johnson, MS, RDN, HCP, is a registered dietitian nutritionist, food industry consultant, speaker, and certified cannabis consultant. She spends much of her volunteer time educating a variety of audiences about the benefits and potential risks of using cannabis to treat chronic pain, anxiety, insomnia, and other ailments. As a consultant, she works with the food and cannabis industries to bring science-based education to health care professionals and category-changing products to market.

References

1. Pastore MN, Kalia YN, Horstmann M, Roberts MS. Transdermal patches: history, development and pharmacology. Br J Pharmacol. 2015;172(9):2179-2209.

2. Shaw JE, Theeuwes F. Transdermal dosage forms. In: Prescott LF, Nimmo WS, eds. Rate Control in Drug Therapy. New York, NY: Churchill Livingstone; 1985:65-70.

3. Hammell D, Zhang L, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain‐related behaviours in a rat model of arthritis. Eur J Pain. 2016;20(6):936-948.

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