A Study to Investigate the Bioavailability and Skin Absorption of CBD and THC From GT4 Technology in Healthy Adults The bioavailability of cannabinoids differs greatly for different routes of There’s a lot of hype around CBD-infused skin products and its benefits. But more research is needed before experts recommend it for use. Topical application of CBD may be more beneficial than smoking.
A Study to Investigate the Bioavailability and Skin Absorption of CBD and THC From GT4 Technology in Healthy Adults
The bioavailability of cannabinoids differs greatly for different routes of administration. When applied topically to the skin, they are absorbed through the skin or hair follicles while interacting with receptors to provide localized effects. To gain more information on the potential of this route of administration in therapeutic applications, this open-label study will investigate the skin absorption and bioavailability of CBD and THC delivered trans-dermally.
|Condition or disease||Intervention/treatment||Phase|
|Biological Availability Skin Absorption CBD THC||Combination Product: CBD and THC with GT4 technology||Phase 1|
The global use of cannabis for both recreational and medical purposes has deep historical origins. Medicinal cannabis has traditionally been used to treat nausea, inflammation, vomiting and pain. The use of cannabis is widespread, with over 147 million people worldwide consuming cannabis annually ). While cannabis regulations for recreational use have traditionally followed the prohibitionist model, Canadian legalization is expected to loosen the barriers to access and research of its potential medicinal and therapeutic benefits.
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two naturally occurring phytocannabinoids found in cannabis. THC is the main psychoactive compound of cannabis and gives users a distinguished “high” feeling, whereas CBD studies have shown it does not have any mind-altering effects. Differences in molecular interactions and structural properties are responsible for the varied pharmacological effects of THC and CBD. Both Δ9-THC and CBD exert their effects by interacting with the receptors of the endocannabinoid system (ECS), CB1 and CB2, with varying affinities.
The ECS plays an integral role in regulatory functions implicated in health and disease as well as in downregulating stress signals that cause pain and inflammation. Endocannabinoid receptors are ubiquitous in the body, and due to their extensive presence, the ECS is referred to as a ‘bridge between mind and body. Cutaneously, the role of the ECS is to regulate skin cell proliferation, survival, and differentiation. CB1 receptors are found mainly in the brain and central nervous system and are involved in coordination, movement, pain, memory and mood, whereas CB2 receptors are found mainly in peripheral organs and are linked with reducing inflammation, pain and tissue damage. Differential activation of CB1 and CB2 receptors, whether individually or simultaneously, could lead to varied physiological effects.
The differences in neurological outcomes between THC and CBD may be linked to their contrasting interactions with the CB1 receptor. THC is a potential partial agonist of the CB1 receptor, and it produces its effects through direct binding. CBD, on the other hand, is a negative allosteric modulator of CB1 and it induces a conformational change to inhibit other agonists from binding. The binding of CB1 receptors is also responsible for the antinociceptive activity of THC, which makes it an effective analgesic agent. In addition, THC has been shown to improve food intake and weight gain in wasting conditions such as cancer, Crohn’s disease and AIDS, as well as in the treatment of glaucoma, nausea, multiple sclerosis, epilepsy and inflammation in a series of preclinical and clinical studies. CBD, on the other hand, shows immense therapeutic potential without the psychoactive effects of THC. It has shown promise in the treatment of anxiety, epilepsy, schizophrenia, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and sleep management. Studies have shown that CBD and THC acting together can be more potent than their individual effects. Oral supplementation of THC alone is not as effective as their combination, which has been shown to significantly relieve neuropathic pain. CBD can also lower the psychoactive effects of THC and thus produce their combined benefits by enhancing THC tolerability.
The bioavailability of cannabinoids differs immensely for different routes of administration. When taken orally, CBD and THC are digested in the stomach and intestines. Further the CBD and THC will undergo first-pass metabolism after digestion. When taken sublingually, they bypass first-pass metabolism, which increases their bioavailabilities. When inhaled, CBD and THC are immediately absorbed through the lungs resulting in a faster response and higher bioavailability in comparison with oral products. When applied topically to the skin, they are absorbed through the epidermis or hair follicles while interacting with receptors to provide localized effects. A common route of administration for recreational purposes is inhalation through smoking as it yields very high concentrations rapidly, but this is not ideal due to risks such as toxicity and loss of activity through combustion. To take advantage of the lungs’ efficient drug delivery and avoid the harm associated with smoking, inhalation can be achieved via aerosolization or vaporization. Systemically, the bioavailability of inhaled CBD using these two methods has been reported to be 31%, and the peak plasma concentration was reached within 10 minutes. The terminal half-life of CBD following inhalation was found to be 27-35 hours, following intravenous injection it was 18-33 hours and following oral administration it was 2-5 days. The terminal half-life of THC after inhalation was found to be 21-31 hours and following intravenous injection it was 24 hours. Bioavailability of oral CBD was found to be around 6%, and bioavailability for oral THC was shown to be 4-12%.
The pharmacokinetics of CBD and THC after transdermal administration have not been extensively studied. When applied with the GT4 technology, the CBD and THC are expected to be absorbed through the stratum corneum and other epidermal layers, the basement membrane and into the dermis rapidly. Once in the dermis CBD and THC can enter the capillary bed aided by increased blood flow and then the systemic circulation. In addition to avoiding the negative effects of inhalation, transdermal administration is superior to oral ingestion as this route provides a way to avoid gastrointestinal involvement and first pass metabolism. Further, transdermal delivery may generate more constant plasma levels. It can also be designed for targeted delivery where the IP and specific tissues within the cutaneous ECS can interact. Pharmaceuticals with the GT4 technology have had over 1,000 prescriptions filled in the United States to deliver 10% gabapentin and 5% naproxen sodium for treatment of severe muscular skeletal pain. This technology has allowed physicians to treat severe pain without or with significantly less opioids. To date, no adverse events have been reported.
The objective of this open-label study is to investigate the bioavailability and skin absorption of CBD and THC delivered using GT4 technology in a healthy adult population. Participants will be healthy men and women between the ages of 25-65 and will be occasional cannabis users. They will have used cannabis at least once in the past 6 months and 4 times in their lifetime but no more than 3 times per week. Participants must have experienced psychotropic effects related to cannabis without having severe adverse events. In the area of application, participants must not have received laser hair removal, shaved, or waxed within 14 days or have any acute or chronic skin diseases or dermatological conditions to avoid interfering with the test product. Participants must not be using medicinal cannabis. They must not be receiving any treatments that may confound results, such as prescribed medications, over-the-counter medications, supplements, and food/drinks that will interact with the test product or that contain CBD and THC. Based on the short half lives of CBD and THC, recreational users must refrain from cannabis for 48 hours. The inclusion and exclusion criteria in this study ensure a homogeneous population of participants who are healthy, stable, and have no comorbidities.
CBD for Skin: What to Know
Cannabidiol (CBD) is a natural compound found in Cannabis sativa plants, which include marijuana and hemp plants. Lately, there’s a lot of hype around skin products infused with CBD. You can find it in cosmetics like creams, lotions, balms, oils, face masks, shampoos, and even bath bombs.
You may have heard that CBD is good for acne, certain skin disorders, and fine lines and wrinkles. But does it really work? Is it safe to use? Ongoing studies on CBD’s uses and benefits are in early stages, so experts say there needs to be more large-scale research to know for sure.
Popular Claims on Benefits
While there isn’t in-depth research available to prove benefits for any skin conditions, scientists are looking for answers, and some early studies have shown some promise.
One small study looked at CBD’s effects on 20 people with the skin conditions psoriasis or eczema, as well as the scars they may leave. Participants used a CBD-enriched skin ointment twice daily for 3 months. They showed some improvements like reduced inflammation. No irritation or allergic reactions were reported, but the study had many limitations.
Experts say there needs to be more research on proper dosage, long-term benefits, and side effects to know if it’s safe and effective, especially if you plan to use it as part of your daily skin routine.
Potential Side Effects and Risks
CBD products in general often make misleading claims, the FDA notes. Since CBD products don’t need a prescription and are easily available, many people may think CBD is mostly harmless. But this isn’t necessarily true. According to the FDA, there are possible risks to look out for when you use CBD.
CBD, especially if taken by mouth, can damage your liver. There’s not yet information on whether CBD products can have the same effect when you apply it on your skin. For instance, it’s not clear yet how much CBD gets absorbed through your skin.
If you use CBD skin products, you may develop a rash. It could be from the CBD or other ingredients in the products you use.
If you’re pregnant or breastfeeding, the FDA warns against CBD use in all forms whether it’s a cream or an oral capsule. The FDA is studying the safety of CBD products, including cosmetics, food, and supplements.
Before you try any CBD products, make sure to read the product labels carefully for active ingredients. Even so, it can be hard to know exactly what’s in the product, including how much CBD it contains. If you have questions, talk to your doctor about it.
Is It Legal?
There are no laws against using CBD in beauty or skin care products. CBD doesn’t contain any THC (tetrahydrocannabinol) that’s found in high levels in marijuana. So you can’t get high on it. But some skin products may add THC along with CBD. Some experts find this concerning.
It’s illegal to market CBD if it’s added to foods or sold as a dietary supplement.
Experts want to see more reliable research before they recommend CBD for your skin. But if you do decide to use CBD-infused skin products and notice a reaction, tell your doctor about it. If you have skin problems, talk to a dermatologist for diagnosis and treatment options.
FDA: “What You Should Know About Using Cannabis, Including CBD, When Pregnant or Breastfeeding,” “What You Need to Know (And What We’re Working to Find Out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD.”
AAD: “The Truth About Skin Care Products with CBD.”
La Clinica Terapeutica: “A Therapeutic Effect of CBD-Enriched Ointment in Inflammatory Skin Diseases and Cutaneous Scars.”
Mayo Clinic: “Psoriasis,” “Atopic dermatitis (eczema).”
National Institutes of Health: “Cannabis (Marijuana) and Cannabinoids: What You Need To Know.”
Harvard Health Publishing: “Cannabidiol (CBD) — what we know and what we don’t.”
Do CBD Ointments Benefit Your Skin or Brain?
Topical application of CBD may be more beneficial than smoking.
- What Is CBD?
- Find a therapist near me
Humans have been rubbing oily extracts of the cannabis plant into our skin for a very long time. The plant is mentioned several times (as “kaneh-bosem,”) in the Old Testament (as per Yahweh’s instruction to Moses in Exodus 30:23) as an ingredient in holy anointing oil. At that time in history, the word messiah simply meant “the anointed one.” Even if this reference is not historically accurate, marijuana was an important medicinal plant to our ancestors.
Today, over-the-counter gels containing CBD are for sale everywhere. Do these products offer any health advantages for your skin? The answer, thus far, is yes. Recent studies using rats suggest that transdermal CBD has beneficial anti-inflammatory effects on the skin. If this is also true for humans, then CBD ointments should provide relief to people who suffer from dermatitis (eczema), rosacea, seborrheic dermatitis, and psoriasis. The application of CBD to the skin of mice increased the proliferation and wound-repair chemicals in keratinocytes, which are the epidermal cell that produces keratin. The authors concluded that their results support the use of topical CBD for the treatment of atopic dermatitis and keratin disorders as well as for enhancing wound healing.
With regard to whether topical CBD can influence the brain, a number of factors become important. The challenge in applying any drug to the skin is that the drug must first penetrate the dead superficial layer of skin in order to become absorbed into the blood. The amount of CBD that gets into the blood is greater if the skin is abraded, burned, or inflamed; obviously, these are not ideal conditions for regular use.
So, can CBD get across the skin and into the blood? Yes. A much more important question is whether it can reach an adequate level in the blood in order to affect your brain function. Once the CBD is absorbed into the blood it will distribute first to the body fat. Thus, for the majority of big adults who carry extra body fat, the amount of CBD that gets into the blood will be quickly absorbed into the fat and not the brain. Therefore, you may need to apply a lot of gel.
A recent study examined the ability of THC to get across the skin and reported that levels of THC were undetectable after being applied via a topical cream. However, CBD is ten times more permeable in the skin than THC. If CBD is embedded in a transdermal patch, or in a transdermal gel, which is designed to enhance absorption, then it can gain access to the blood. A recent study applied the gel twice a day to the skin for 12 weeks (that’s a long exposure) and reported a significant decrease in the level of anxiety in children with Fragile X syndrome. It’s important to note that children are smaller and have less body fat and would require that less CBD reach the blood in order to affect the brain.
There is still very little human data on this topic that is reliable. When CBD was applied as a transdermal gel to the skin of guinea pigs, the level of CBD peaked at 6.3 ng/mL of plasma after about 12 hours. When CBD was applied in a transdermal gel to the skin of rats, the level of CBD reached almost 400 ng/ml of plasma and the authors reported a reduction in anxiety and impulsivity. You can easily see that the challenge is getting enough into the blood.
The application of CBD dissolved in transdermal gels offers some unique advantages. Oral absorption of CBD is not as efficient as inhalation and is associated with gastrointestinal side effects. For some people, inhalation is not an option. These preliminary studies encourage further studies of the usefulness of topical application as compared to oral or inhalation methods in humans.
- What Is CBD?
- Find a therapist near me
© Gary L. Wenk, Ph.D. is the author of Your Brain on Food, (3rd Edition, 2019; Oxford University Press) and is a member of the Governor’s Medical Marijuana Advisory Committee for the State of Ohio.
Casares L et al (2020) Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1 REDOX BIOLOGY, vol 28, Article No: UNSP 101321
Gonzalez-Cuevas G et al (2018) Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle. NEUROPSYCHOPHARMACOLOGY Vol 43, p 2036