CBD in Cosmetics: A Practical Primer

Read this article in its entirety in the September 2020 digital edition. . .

Disclaimer: The present article explores the use of CBD in cosmetics and personal care. It is offered solely for your consideration and further exploration. Readers are advised to research the rules and regulations set forth by the proper authorities in relevant operating districts to ensure CBD-containing products are compliant. In no way does the author or Cosmetics & Toiletries assume any responsibility or liability in relation to the use of CBD in cosmetics.

The global cannabidiol (CBD) cosmetics market is expected to increase at a compound annual growth rate of more than 30% from 2020 to 2024 to reach $3.1 billion (USD), according to Market Reports World.¹ As a point of clarity, the CBD used in cosmetics is derived from the low-THC, industrial grade and non-psychotropic form commonly referred to as hemp although CBD is generally present in low quantities the higher-THC containing marijuana plant. Cannabis refers to the overall genus of both hemp and marijuana plants.

Unfortunately, the U.S. Food and Drug Administration (FDA) is walking a winding and complex path toward the regulation of CBD’s use and consumption. One reason for this is because compounding precedents have been set. For example, the approval of Epidiolex^a in 2018 as a prescription drug, with CBD identified as the active pharmaceutical ingredient (API), affects the addition of this chemical to any food, dietary supplement,² prescription, OTC drug or cosmetic. Furthermore, a 1940s court ruling against Helene Curtis³ set a precedent that disallows cosmetic companies to claim a product contains CBD. At that time, a shampoo claiming “plus egg” was deemed false and misleading because the ingredient was present at levels too low for cosmetic benefits. Since CBD is an approved drug, claiming that a product contains CBD presumes the material is present at levels for drug-like effects, unless companies can prove both its cosmetic benefits and non-drug effects.

For these reasons, the INCI name Cannabidiol is used instead, and CBD-containing cosmetics must not make any drug claims; e.g., anti-inflammatory. As an aside, the use of CBD in other drugs, whether prescription or OTC, requires pre-approval by the FDA.

In addition, although the Farm Bill⁴ passed by the U.S. Congress in 2018 removed cannabis containing less than 0.3% delta-9 tetrahydrocannabinol (D⁹-THC) from the Controlled Substances Act, significant confusion and misunderstanding have prevented the mainstream use of CBD in U.S. Commerce. Also, while most states support the Farm Bill, making it perfectly legal to grow hemp in those states, others do not. This makes it illegal to grow or even transport hemp within or across those state boundaries—even if the destination is a Farm Bill-supporting state. According to one industry expert, the bill is even hung up in semantics over the Latin word for hemp. At press, the most updated source of information from the FDA attempting to clarify the regulation of cannabis and cannabis-derived products including CBD is found in a Q&A posted on the FDA’s website.⁵

The Farm Bill will expire in October 2021 and it is expected that the U.S. Department of Agriculture (USDA) will address the many thousands of comments submitted to the agency (this author’s included) during the rule-making process. Significant factors contributing to this confusion are the FDA’s firm stance prohibiting the consumption of CBD in food and beverage products,⁵ issues and stigma resulting from the recreational use of marijuana, and a general reluctance of large-scale producers to risk litigation until there is more clarity, research and standards to support its use.

Politics aside, the good news for formulation chemists and manufacturers is that the price of CBD has declined greatly over the last 12 months. This is mainly due to oversupply and excess of product on the market. CBD isolate, for example, was typically priced around $6 per gram in May 2019 and almost one year later, it sells for approximately one-fifth of that price. Furthermore, additional studies continue to demonstrate the potential efficacy and cosmetic benefits of products containing cannabis, as will be discussed later.

The present article explores the cultivation of hemp, how CBD is derived from it, quality control considerations and full-spectrum vs. CBD isolate. It also presents recent research supporting the benefits of CBD in cosmetics, and product formulation and dosing. It is intended as a primer to highlight key aspects of CBD sourcing and use in cosmetics.

Cultivation of Hemp

Cannabis is one of the oldest known medicinal plants. Archaeological evidence shows it entered Europe from Asia sometime around 500 B.C. All cannabinoids, regardless of THC content, originate from the same species, Cannabis sativa L.—a member of the Cannabaceae family.

One of the most troublesome issues for hemp farmers is that both THC and CBD originate from the same precursor molecule, cannabigerolic acid (CBGA) (see Figure 1). As the plant reaches maturity, both CBD and THC are produced enzymatically from the same molecule.⁶ Thus, getting the harvest timing right can prove difficult to economically produce hemp with THC levels below the permitted 0.3% threshold while also maximizing CBD production, typically around 8%. If the THC limit is exceeded, the farmer must destroy the crop; and if the crop is harvested too early, the farmer risks low CBD yield and financial burden. Weather, soil, fertilizer and plant genetics can also affect yields, further compounding the issue.

Processing Hemp into Raw Oil and Distillate

After hemp is harvested, it is typically dried to about 10-12% moisture using natural or mechanical means. After drying, the flowers are separated from the fan leaves and stalks, since these typically contain a higher quantity of cannabinoids and terpenes. Sometimes the plant parts are ground to increase surface area and enhance extraction recovery. Indeed, recent internal testing has found that milling can increase the extraction yield by more than 10%.

The major steps for processing and purifying hemp are shown in Figure 2. While various methods are used, ethanol-based extraction is the most common; note that the FDA has approved only one extraction method for the production of CBD for drug indications.⁷ After extraction, the resulting crude hemp oil, which is generally around 60-70% pure CBD molecule, is winterized to remove undesirable fats and lipids. If these are not removed, the final product will be cloudy and opaque—which is generally considered a sign of poor quality and sold at a lower value.

Winterization is accomplished by dissolving the crude oil in food-grade alcohol, freezing to precipitate the solids, then filtering with micron-sized media. After this, the ethanol is recovered using rotary evaporators, or rotovaps, and decarboxylated by heating for a known temperature and time. The decarboxylation step, shown in the second reaction in Figure 2, removes carbon dioxide from the aromatic ring of the cannabidiolic acid (CBDA) naturally produced by the plant to produce cannabidiol (CBD).

The final step is to purify the mixture via distillation, which typically raises the CBD molecule purity to more than 90% and creates the final product, commonly referred to as the distillate. Before the distillate is created, the terpenes are removed at lower distillation temperatures. Many types of distillation equipment are available; here, the author’s lab uses wiped, thin-film equipment for efficiency, speed and short residence time in the vapor phase to minimize possible product degradation (see Short Path Distillation Demo on Page DM8 of your digital magazine).

Quality Control in Wholesale Supply

Quality assurance testing for CBD is generally regulated at the state level. In California, a state that follows one of the most rigorous testing standards in the nation, Phase 3 testing became mandatory on January 1, 2020.⁸ Depending on the final product type and route of use, testing is usually conducted for cannabinoid levels (also referred to as potency), residual solvents and pesticides, heavy metals, terpenes, foreign matter, homogeneity, mycotoxins (Type B1, B2, G1 and G2) and microbes (A. fumigatus, A. flavus, A. niger, A. terreus, Escherichia coli and Salmonella spp.).

The resulting data is included in the product’s Certificate of Analysis (COA), which should be evaluated in detail before purchasing from a producer. After the product is purchased, it should be stored in a dark, cool environment to minimize product breakdown and ideally used as soon as possible after acquisition. Once it is incorporated into the final product, it should be tested again to ensure the accuracy of content and labeling.

When a lab report measures values in the COA report, these usually include references to the limit of quantification (LOQ) and the limit of detection (LOD). The LOD is the lowest quantity of a substance that can be observed by the instrument in comparison with a blank sample. The LOQ, on the other hand, is similar but takes into account predefined statistical parameters for bias and precision; this value is generally higher than the LOD.⁹ When interpreting results, the LOQ should be considered as the lowest concentration at which the compound may be reliably detected, and well below the action limit to ensure a margin of safety.

There are several things to look for in the COA. Be sure the COA batch number is traceable to your product and that its purity is sufficiently high; it is recommended that the CBD distillate is 85-90% pure, and isolate should be above 99%. Also, the date of the COA should be fairly recent (within 30 days)—considering that CBD approved by the FDA only has a shelf-life of three months.⁸ Studies show that CBD degradation mechanism is first order with a half-life of about eight months.¹⁰ Research performed in the 1970s found CBD to be extremely light sensitive but the authors assert that “cannabis or extracts are reasonably stable for one to two years if stored in a dark room at room temperature.”¹¹

Furthermore, harmful compounds should be absent or below action limits. Regarding this point, a complete discussion of relevant test methods and regulatory limits is beyond the scope of this article but several key points can be made. First, cannabis is a known bioaccumulator and can uptake and concentrate metals from the soil. Thus, naturally occurring arsenic in soil may pose a problem in some areas of Northern America,¹² so this an important test.

Also, pesticides approved by the U.S. Environmental Protection Agency (EPA) such as myclobutanil (also known as Eagle 20, Masalon and/or Nova), which is a commonly used fungicide for grapes, stone fruits, strawberries, apples and other crops, can impact hemp cultivation. If used near hemp crops in areas of unfavorable wind conditions, residual myclobutanil may be flagged during testing since it has an action limit of 9 µg/g—equivalent to one part per million. Chemical solutions can be used to remove residual pesticides if necessary. Fortunately, the EPA significantly limits the use of allowable pesticides for hemp cultivation to just eight relatively benign types, including neem oil and insecticidal soaps.¹³

Lastly, the COA analysis should originate from a reputable lab as results can vary drastically. This is currently a problem in the industry. In 2019, for example, one round-robin test of several Northern California labs for potency and residual pesticides in THC distillate showed wide inconsistencies. The false negative rate, indicating a compound to be present but not reported, was greater than 70% and the potency for THC registered higher than 15%.¹⁴ Aside from basic ISO certifications, there is no accreditation program in place to certify or approve the testing lab—so it’s a case of caveat emptor, “buyer beware.”

A Note on Terpenes

Terpenes are volatile molecules found in all plants that impart unique aroma profiles. They are present in essential oils, which have been used for many thousands of years. There are more than 200 terpenes found in cannabis¹⁵ and they participate in what is known as the entourage effect—a synergistic effect where the outcome is enhanced by the presence of both cannabinoid and terpene molecules.¹⁶

Due to the complexities of 200+ known terpenes interacting with 100+ known cannabinoids at varying concentrations, it is difficult to accurately assess the exact therapeutic mechanism in “whole plant” cannabis medicine. However, most agree the effect is valuable and may be missing when isolated CBD is used in the absence of terpenes; this will be discussed further later.

When crude oil is distilled, as in the last step of Figure 2, the terpenes are removed prior to distillation. They are generally collected and retained in one or two fractions and may have medicinal qualities by themselves. In vape pens, they are reintroduced to the distillate to give it flavor and to reduce viscosity. Some products may have a “skunky” pot smell, however, if not properly refined. Residual chlorophylls are particularly offensive—and the reason why marijuana brownies can taste awful. This can be caused by ethanol extraction where the temperature is too high and/or filtration is defective.

Full-Spectrum vs. CBD Isolate

There are no legal or formal scientific definitions for the terms full-spectrum, broad-spectrum oil, distillate or isolate as they refer to CBD. However, it is widely recognized that full-spectrum refers to extracts or distillates that contain mostly CBD along with lesser minor cannabinoids such as THC, cannabichromene (CBC), cannabigerol (CBG), cannabidiol acid (CBDA) and cannabidivarin (CBDV). The lesser cannabinoids are generally present at 1% or less and if psychoactive, as in the case of THC, they will not alter the user’s faculties at such low concentrations. In fact, the presence of these lessor cannabinoids is important since, as noted, they are believed to work in a beneficial and synergistic manner.

Broad-spectrum refers to oil or distillate from which the THC has been removed to the lowest practical quantity, presumably to meet legal requirements that vary from country to country and state to state. Finally, isolate refers to the purified crystal precipitate form of CBD, which is typically high in purity—usually in excess of 99% CBD molecule. Interestingly, there is no THC version of the isolate since the molecule is unable to crystallize unless it is in the acid form, THCA.

CBD Activity and Safety

On a molecular level, cannabinoids become functionally active by binding to what are referred to as the CB1 and CB2 cannabinoid receptors in the body’s endocannabinoid system. CB1 receptors are found on brainstem neurons¹⁷ and glial cells. CB2 sites are found in the spleen tissue.¹⁸ These receptors were first described by Maccarrone et al. in 200319 and reviewed in detail by Biro et al. in 2009.²⁰

The quantitative polymerase chain reaction (qPCR) technique has long been used to determine if particular genes are expressed in in vitro skin cultures. To date, 163 genes have been identified in skin, ranging from inflammation, pigmentation, wound healing, anti-aging and hydration, to name a few.²¹ Interestingly, researchers have found that more than 100 genes are regulated by CBD in a manner dependent upon the concentration, solvent and duration of the test. This approach offers an interesting means to target formulations with intended effects in real skin tissue.

Several dozen peer-reviewed research papers report the benefits of CBD for skin. Examples include combating inflammation,^22-24 acne,⁹ pain²⁵ and melanoma;²⁶ acting as an analgesic to promote wound healing²⁷ and relieving itch^{13, 28}—although note that the FDA has not approved CBD for these or any other topical treatment applications.

In human trials, Palmieri et al. found the topical application of CBD to effectively reduce psoriasis, eczema (atopic dermatitis) and tissue scarring. Also observed were significant improvements in hydration, elasticity and the Psoriasis Area Severity Index (PASI).²⁹ Likewise, Wilkinson showed CBD to act on psoriasis in cultured human epidermal keratinocytes.³⁰

Studies also have indicated that CBD can regulate epidermal differentiation through the CB1 receptor^{31, 32} and reduce histamine responses in human skin.^{33, 34} Other work documents its use in treating inflammatory acne vulgaris due to its ability to decrease the proliferation of human sebocytes, as shown in vitro.³⁵ Chelliah et al. even reports on the topical application of CBD to treat the rare, blistering skin disorder of Epidemolysis bullosa, finding that patients healed faster and experienced less pain and blistering.³⁶

Furthermore, the safety of CBD also is well-established. No adverse effects levels (NOAEL) were reported by Max, et al., for example.³⁷ Also, Human Repeat Insult Patch Tests (HRIPT) showed no irritation or allergic response in 52 subjects.³⁸

Formulation Considerations

CBD distillate, rather than crude oil, is used most commonly in modern formulations. At room temperature, CBD distillate is a thick, sticky mass resembling honey. To facilitate transfer and measurement, it is usually heated to about 90°C before use. To formulate products such as balms, salves and body butters, CBD distillate is readily soluble in most vegetable oils including medium-chain triglycerides, which are found in coconut and palm oils, as well as olive, grapeseed, almond, avocado and sunflower oils. It also is compatible with common emollients including Butyrospermum parkii (shea) butter, Mangifera indica (mango) seed butter and Simmondsia chinensis (jojoba) oil, among others.

For emulsions, glyceryl monostearate, polyethylene glycol and polysorbates are compatible with most cannabinoids. Quillaja saponaria extract from the soap bark tree also offers a natural alternative for clean beauty formulations. Cetearyl alcohol can be used with CBD distillate as an emulsion stabilizer, while sodium stearoyl lactylate can be used to improve viscosity and volume.

Many vendors also add essential oils to CBD distillate that contain terpenes such as pinene, myrcene, limonene, linalool and b-caryophyllene. As described above, the effects of these compounds in combination with cannabinoids are not well-understood, but their synergies may be important to achieve the desired outcome. The pioneering neurologist Ethan Russo wrote a comprehensive review³⁹ on the potential effects between cannabinoids and terpenes. He identified studies where linalool and CBD distillate appeared to help skin healing and scarring;⁴⁰ and where limonene,⁴¹ linalool and pinene⁴² combined with CBD distillate were effective in acne therapy. Researchers have also observed that essential fatty acids such as a- and g-linolenic acid, oleic acids and phytosterols (b-sitosterol) can be combined with CBD distillate to impart the added function of improving skin elasticity and hydration by inhibiting enzyme 5-a-reductase, which inhibits excessive skin sebum secretion, ^{43, 44} independent of the cannabinoids present.

As mentioned previously, especially after processing, the final CBD-containing product should be retested to ensure accuracy and agreement with the labeling value.

CBD Delivery

CBD is a highly lipophilic molecule (logK_o/w ≈ 6)45 that tends to accumulate in the stratum corneum rather than penetrate into the deeper strata.⁴⁶ For this reason, researchers have evaluated other methods of delivery, including gels made with carbomer^b,⁴⁷ encapsulation and transdermal patches (discussed below), or in combination with hyaluronic acid,⁴⁸ argan oil⁴⁹ and boswellic acid⁵⁰ to enhance absorption.

In a study with carbomer gel,³⁹ researchers found that transdermal dosing from 0.62 mg to 6.2 mg per day of CBD had an excellent correlation with plasma levels and was effective in reducing arthritic inflammation and swelling. A high dose of 62 mg per day did not fit the pharmacokinetic modeling and the authors postulate a saturation threshold was reached or exceeded.

. . .Read more in the September 2020 digital edition. . .

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^a Epidiolex (cannabidiol), by GW Pharmaceuticals, is the first and currently only FDA-approved prescription CBD used to treat seizures associated with Lennox-Gastaut syndrome and Dravet syndrome.

^b Carbopol 980 (INCI: Carbomer), Lubrizol.