Both THC and CBD act on a system of receptors in your body called cannabinoid receptors. You have cannabinoid receptors throughout your body and, so far, researchers have identified two major types: CB1 (found primarily in the central nervous system, including parts of the brain and spinal cord) and CB2 (found mainly in immune system tissues). Interestingly, both have been found in skin. Researchers have also found that while THC can bind to and activate both types of receptors, CBD seems to modulate and somewhat block the effects of CB1 and CB2 receptors. So, any effect that CBD has on CB receptors may actually be more related to regulating and even counteracting some of the actions of THC and other cannabinoids in the brain.
Nevertheless, how do we account for all the people out there (like me) who use these products and feel like they’re doing something? Beyond the placebo effect, it’s possible that something else in the cream could be doing the heavy lifting here. These products don’t just contain CBD, Dr. Tishler points out. In fact, many of them also come with ingredients like arnica, menthol, or camphor, which may all provide a more immediate sensation of soothing or pain relief. So it could be those ingredients (or just the act of massaging the balm into your skin) that makes you feel better.
What is CBD?
In fact, the most compelling research they found for using cannabinoids for pain came from a large review and meta-analysis published in JAMA in 2015. For the study, researchers looked at results from 79 previous studies of cannabinoids and various medical conditions, including chronic pain. However, of those studies, only four involved CBD (without THC)—none of which were looking at pain. So although we might assume that CBD is doing something to help address pain—according to the studies involving the whole cannabis plant—we don’t have great evidence to prove it.
That said, we don’t always know exactly what’s in the CBD products out there due to a lack of regulation. Until recently, CBD was regulated as a Schedule 1 substance, meaning that the federal government believed it had a high potential for abuse and no accepted medical value. But the FDA approval of Epidiolex last year and the passage of the Farm Bill in December 2018 changed things by lifting the federal ban on commercial hemp production (hemp also contains CBD in lower amounts than cannabis). But it also made things more confusing because we’re still waiting on actual CBD regulations from the FDA. In the meantime, companies are treating hemp-derived CBD as if it’s perfectly legal, Dr. Tishler says.
And even though the lotion was applied topically in the rat study, it wasn’t applied locally to the knee. Instead, the researchers were really using the topical application to get it into the rats’ bloodstream, or what’s called systemic administration. But you’d likely need a different dose for it to be effective locally (if you applied it just to your aching shoulder, for instance) in a human. We have no idea what that dose should look like.
CBD and other cannabinoids are large, complex molecules that do not penetrate the skin efficiently without the use of technologies that improve their penetration. As such, topical formulations of CBD or oils derived from Cannabis may require very high doses to reach therapeutic blood levels, or may not cross the skin and into the bloodstream at all.
Challenge: Topical Administration
Addressing Limitations of Current Treatments
Challenge: CBD degradation to THC in the stomach
Potential Benefit of Zygel:
Zygel is a unique permeation-enhanced CBD transdermal gel. Transdermal therapeutics are applied locally and absorbed through the skin directly into the systemic circulation, resulting in a lower incidence of gastrointestinal side effects, and avoidance of first-pass liver metabolism, which potentially enables lower dosage levels of active pharmaceutical ingredients and rapid, reliable absorption with increased bioavailability. Other potential benefits of transdermal delivery compared with oral administration may include fewer drug-drug interactions.
Potential Benefit of Zygel:
Zygel is pharmaceutically manufactured in a cGMP (Current Good Manufacturing Practice) facility that will comply with rigorous efficacy and safety standards established by global regulatory agencies and is not extracted from the Cannabis plant. We believe that producing CBD this way ensures that we can provide consistent potency and efficiently scale manufacturing to meet the needs of the markets that we are targeting, without the cost and logistical requirements of growing and harvesting Cannabis .