CBD has already become a familiar term, despite people being unsure of the exact nature of CBD oils and their relationship to Cannabis sativa.
In April’s SPC article CBD & skin: A scientific history, Rouah Al-Wakeel introduced CBD and the endocannabinoid system (ECS), explaining how its primary function is to maintain the body’s equilibrium[1].
She went on to write about cannabinoids in skin, mentioning the many cannabinoid receptors found in skin and how skin naturally synthesises its own endocannabinoids (anandamide and 2-AG).
These two skin cannabinoids bind to skin cannabinoid receptors and surpress cellular proliferation, trigger cell differentiation and control the release of inflammatory mediators.
Skin endocannabinoids can also initiate lipid production and reduce pain and itching[2].
The current literature indicates that CBDs may be beneficial for acne and atopic dermatitis, however, studies tend to be small and so non-conclusive[3].
The shortage of authoritative studies has divided scientific opinion and left many toxicologists feeling that there is insufficient information on the pharmacokinetics and toxicity of topical CBD.
Dermal absorption of CBD from cosmetics, even after repeated use, would be expected to be low, because of its lipophilic nature, however more studies are needed to be certain.
To help address the need for good scientific information, The International Cannabis and Cannabinoids Institute (ICCI), has been established. It is bringing together global experts from academia, health care and industry to research the various uses of medical cannabis and investigate anecdotal claims about health benefits.
It is expected that its studies will continue to fuel the trend for cannabinoids (phytocannabinoids), CBD oil, synthetic cannabinoids and their derivatives in cosmetics.
Sources of CBD are set to rise
More CBD is used in food supplements than in cosmetics however, the demand for CBD in skin care is growing. It is estimated that the legal usages of Cannabis sativa will rise to over $60 billion in the next few years[4], driven by the lessening of legal constraints on hemp cultivation.
The US 2018 Farm Bill now fully legalises the cultivation and sale of hemp, subject to state and federal regulations. Consequently, cannabis is now grown legally in over ten USA states[5] (with more states expected to follow).
The regulations controlling cannabis cultivation are being readdressed globally and everyone wants a slice of this lucrative market.
Cosmetic grade hemp and CBD oil may be coming into Europe from almost anywhere. It could have originated in countries from China to Chile, from North Korea to New Zealand as well as from Russia and the US.
Choosing from the myriad of cannabis products
This upsurge in the availability of cannabis related materials has left cosmetic formulators choosing from over 100 different natural Cannabis sativa-derived cannabinoids and extracts, not to mention synthetic cannabinoids, which begs the question; which cannabinoids can and should, cosmetic formulators be using?
Al-Wakeel pointed out that the medical potency of the different commercial CBD products relates to their composition in terms of both concentration and constituent cannabinoids. She mentioned "the entourage effect", where efficacy can be boosted through synergy with other natural companion substances and she described the three main commercial CBD products as follows:
Full Spectrum: All the natural Cannabis sativa cannabinoids with <0.3% the psychoactive Tetrahydrocannabinol (THC);
Broad Spectrum: With just the following cannabinoids: Cannabidiol (CBD), Cannabinol (CBN), Cannabidivarin (CBDV), Cannabigerol (CBG) and Cannabichromene (CBC);
And Isolate: >99% CBD.
If only the situation was as simple as just choosing from the three above. The true situation is even more complicated.
Before considering the potency or better still, the cosmetic value of a cannabis-derived cosmetic ingredient, it is important to know the law.
In the EU, it is essential to know if the CBD was derived from the correct part of an EU registered cultivar grown by a licensed grower? Because despite strict EU regulations stating "cosmetic ingredients must be made using industrial hemp varieties (low in THC), which are registered on the European Commission’s Plant Variety Database and have been grown by licenced growers", cannabis materials from other cultivars are finding their way into EU markets.
Low or no THC
As I write this article under coronavirus lockdown, Switzerland allows cosmetics with CBD, if the THC content is less than 1%.
European countries have their own restrictions. France insists there is zero THC in CBD isolates and thinking logically, isolates should be just pure CBD.
Austria and Luxembourg allow CBD products with a THC content of up to 0.3% and CBD is totally illegal in Slovakia and Lithuania.
As there is so much contradictory information about the THC levels allowed in the EU, I asked Amanda Isom at Bloom Regulatory to clarify the situation.
She said, “It is a common misconception that the CBD used in cosmetics destined for the EU must contain less than 0.2% THC. From a practical point of view, it will only be feasible to use industrial varieties of cannabis (hemp), for which the level of THC in the plant must be below 0.2%."
However, THC is actually prohibited in cosmetic products and so cosmetics need to avoid containing THC.
Isom went on to say: "Using CBD and cannabis materials in a cosmetic is a complex area. Not only must companies ensure compliance with the specific sector legislation for the destination market, but they must also be mindful of local legislation on controlled substances. And this often hinges on issues of purity and traceability."
Materials from Cannabis sativa flowering or fruiting tops are not permitted
It is especially important to know the part(s) of the plant used to make the CBD as EU regulations demand that cosmetic grade CBD originates only from seed and or the leaves.
It is worth mentioning in passing that the United Nations Conventions on International Drug Control, define controlled cannabis as "the flowering or fruiting tops of the cannabis plant". They do not include materials derived from Cannabis sativa seed or leaves, as controlled substances.
This position is mirrored in the EU cosmetic regulations - and will be the UK regulations immediately post Brexit, which allow cosmetics to contain CBD, "however it shall be prohibited from use in cosmetic products, if it is prepared as an extract or tincture or resin of Cannabis in accordance with the Single Convention"[6].
CBD can therefore originate from the seeds and or the leaves of the plant, provided no material from cannabis fruiting tops is present.
To be certain of compliance to EU cosmetic regulations, only use CBD from supply chains that can demonstrate the biomass originated just from the leaves of EU approved cultivars <0.2% THC, as anything else could be deemed illegal.
CBD is not a controlled substance
The US definition of marijuana in the Controlled Substances Act (CSA) has been amended to exclude hemp and its derivatives. They define hemp as follows: "Cannabis sativa and any part of that plant, including the seeds and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 % on a dry weight basis."
To reduce confusion, the WHO Expert Committee on Drug Dependence have requested that the conventions state that CBD preparations are not under their international drug control[7].
FDA & EU Regulations concerning CBD
Meanwhile, the US Food and Drug Administration (FDA) has only approved pharmaceutical-based CBD and does not consider CBD as a food or dietary supplement. The FDA is genuinely concerned about companies selling products containing cannabis and cannabis-derived compounds in ways that violate the Federal Food, Drug and Cosmetic Act (FD&C Act).
It says it is taking steps to aid the lawful marketing of appropriate cannabis and cannabis-derived products but remains committed to protecting public health.
Companies who are not thoroughly checking the levels of THC and the origins of their cannabis and cannabis-derived ingredients are risking severe penalties.
The FDA and the Federal Trade Commission (FTC) are acting. They have already sent warning letters to US companies marketing CBD dietary products with overstated health claims[8].
Remembering too, that the cosmetic use of CBD in Europe needs to satisfy (EU) Regulation No 1223/2009 (the Cosmetics Regulation), which defines a cosmetic product as any substance or mixture intended to be placed in contact with external parts of the human body for the purposes of cleaning, perfuming, changing its appearance, protecting, keeping in good condition or correcting body odours. Claims evoking pain and itch reduction, activating cell differentiation and controlling the release of inflammatory mediators, would not be appropriate for a cosmetic.
It is worth mentioning again here that the cannabis listed in the Single Convention is material from the flowering and fruiting tops (and not the cosmetic grade materials deriving from the seed and or the leaves) as Annex II of the EU Cosmetic Regulation includes any substance referred to in Tables I and II of the Single Convention on Narcotic Drugs of 1961 (the Single Convention) as substances, which are prohibited from use in cosmetics.
CBD quality
CBD oils can be all described as concentrated Cannabis sativa leaf/seed extracts, which are then dissolved in edible oil(s). It is not the purity but the impurities in CBD oils that matter.
Hemp is a phytoremedial crop used to repair ground contamination[9] so some of the hemp, which is illegally finding its way into supply chains, will have been grown on soils contaminated with toxic substances. Heavy metals, and pollutants such as monocyclic and polycyclic hydrocarbons (known carcinogens) etc, along with pesticides and other agrochemicals, can all become contaminants.
There is no recognised quality standard or extraction procedure for CBD. For safety, the grade and suitability of the solvents need to be known. Ethanol and isopropyl alcohol are amongst the most popular solvents used and others including supercritical CO2 extracted Cannabis sativa are also available.
Extracts may be further refined by chilling (winterisation) and filtering to remove precipitate material before dissolving in the edible oils.
With no safety standard certification for cannabis-based products, the situation is open to abuse. The BBC consumer programme Trust Me, I’m a Doctor sent 12 popular CBD oil products to the ICCI for analysis, who, in collaboration with the University of Prague, found that three of the products contained less CBD than was claimed. One, professed to contain 2.75% CBD, contained only 1.7% CBD. Another, which should have had 5%, only contained 2.9% CBD. A third product claiming to contain 500mg in 10ml of CBD (5% CBD), comprised of just 0.00075%.
When the ICCI looked at the quality of CBD products available in the EU they were concerned that the levels of THC were not listed and hydrocarbons, pesticides and other recognised impurities could be present[10].
An independent 2019 report commissioned with FERA Science confirms its concerns[11].
The results showed levels of contamination amongst UK CBD products – all of which were imported. They found heavy metals rhodium, manganese, chromium, and copper along with polycyclic aromatic hydrocarbons (PAH), including benzo[a]anthracene, chrysene, benzo[b]fluoranthene, and benzo[a]pyrene). Some CBD products also had polychlorinated biphenyls (both dioxin-like and non-dioxin like PCBs), and furans.
Crime adds to supply chain risk for cannabis-based cosmetic materials
The lucrative CBD market is swamped with material. As a result, very few of the supply chains currently operating across Europe are compliant. Back in 2017, the United Nations Office on drugs and crime estimated that globally there were 183 million cannabis users and that cannabis was being grown illegally in 135 countries[12].
Highly sophisticated underground supply chains have developed over the decades of abuse. The likely involvement of hardened criminals means, more than ever, suppliers’ documents stating that a CBD/Cannabis sativa-based ingredient was made only from the leaf and or seed of an EU registered plant variety, cannot be assumed to be reliable. Documents can be easily falsified as food scandals, when horse meat was found in beef products, prove[13].
Even in the most tightly managed systems, documents alone are not proof of compliance. Blockchain shared ledgers secures digital information but if the digital information contains misinformation then blockchain simply secures the lie.
Also, when brands are challenged by the authorities, being confused about the legal status of CBD is not an acceptable defence in the eyes of the law.
Large fines mean it has never been more important to know the source of the CBD. Brands must be confident in their supply chain and have recourse, in the event of non-compliance to CBD regulations.
With the US supplying 40% of the global market share and Asian sales expected to reach US$1.7bn by 2025[14], CBD will be entering the EU market in increasing amounts.
No brand would openly admit to using illegal, unethical, unsustainable sources. However, all the while the authorities allow isolates to be imported with only a CAS number, no certificate of origin or supporting paperwork to confirm the cultivar, illegal Cannabis sativa products will enter and be used in the EU.
Transparency and traceability in global supply chains
Isom points outs that "the horizontal link between the EU Cosmetics Regulation and the International Single Convention on Narcotic Drugs means that it is not permissible to use the flowering tip of the cannabis plant in cosmetics, even if it is obtained from Hemp varieties. Therefore, in order to be able to demonstrate compliance, it is especially important to not only obtain CBD that is not processed from the flowering tip part of the plant but also to be able to show the full traceability from the processed extract to use in the final product."
Technology is available to give traceability throughout the entire supply chain from crop-to-shop. The digital revolution has made track-and-trace part of consumers’ everyday experience for parcel deliveries.
As already mentioned, digital documents can be secured using blockchain distributed ledger systems. Smart phones are allowing consumers to instantly access information shared via the cloud. Sadly, in practice, very few brands feel the need to use these technologies.
One exception is the UK based company, TTS Pharma[15]. It finds itself alone in seriously investing in vertical integration to control every step from farm to product. Unlike products from unregulated sources, TTS Pharma products provably satisfy the UK and European regulations. It has established its own fully traceable track-and-trace supply chain system (CHOtrak). It therefore knows that the seed is on the EU Approved list and cultivation followed ethical and organic practices.
Labelling legal CBD using DNA Technology
The 2020 Covid-19 (SARS-CoV-2) pandemic has turned almost everyone into virologists and molecular biologists and thanks to the media, the terms RNA and PCR have become commonplace. Hundreds of thousands of people have undergone the swab test for Covid-19, where samples were taken from their nose or from the back of their throat. In this test, coronaviral RNA is extracted from the swabs and mixed with the enzyme, reverse transcriptase (RT), which converts coronaviral RNA, into its complementary, cDNA nucleic acid sequences. The coronaviral cDNA is then amplified by the Polymerase Chain Reaction (PCR).
Amazingly, the exponential nature of PCR enables some test methods to detect down to as little as just 40 copies of coronavirus SARS-CoV-2 RNA per ml. This same PCR technology is being used to secure a wide range of supply chains from textiles to electronic components destined for fighter jets; and is now being used to authenticate CBD.
PCR selective DNA amplification
The PCR reaction is a powerful, everyday laboratory tool that enables, not just traces of coronaviral cDNA to be amplified but also to reveal traces of incriminating DNA found at crime scenes. This same technology can be adapted to enable the use of DNA as molecular tags. Because PCR is so sensitive, these DNA molecular tags can tag CBD throughout supply chains at concentrations of just parts per billion.
PCR amplification begins when double stranded DNA is melted into its two separate DNA strands. Primer sequences, in the assay media, bind to the single strands and enable the enzyme, DNA Polymerase to catalyse the replication of both strands. The resulting two new double strands of DNA can then be melted into their single strands ready for the next cycle to begin again. In this manner PCR exponentially increases the amount of target DNA.
Primers are short nucleic acid sequences, which are complementary to the three-prime end sequences on the target, DNA. Due to their specificity, in the case of the Covid-19 test kits, only coronavirus SARS-CoV-2 cDNA is amplified.
Similarly, when authenticating molecular tagged CBD, the primers included in the assay will be those specific to the target DNA tags ensuring they are the only DNA amplified. DNA polymerase catalyses up to 155 nucleotides per second. Super-fast PCR can achieve amplification of short DNA sequences in less than 15 seconds.
Fluorescent dyes included in PCR reagents make these tests even more sensitive. In the case of Covid-19, samples testing positive for the virus are those which show increasing fluorescence reaching a validated threshold.
SigNature DNA tagging legal cannabis
The use of DNA tagging for cannabis has been developed and implemented by Applied DNA Sciences, using its SigNature DNA molecular tags. These molecular tags are the auditors’ friend as they forensically authenticate the material at every stage of its journey from farm to face cream.
SigNature DNA has been used to authenticate materials in global supply chains, not just for the textiles and electronic components mentioned earlier, but the tags are also used to authenticate items as diverse as pharmaceuticals, fertilisers, leather, down, inks and a wide range of polymers.
These SigNature DNA molecular tags act much like a bar code as unique identifiers associated to original points or a specific claim being made by a manufacturer or brand. DNA item identification can be included in Blockchain shared documents, using Applied DNA’s CertainT platform. The physical presence of the SigNature DNA code on a molecular tagged consignment indisputably links the material to accompanying digital documents. Transparent track and trace informatician be achieved by sharing the GPS located portable PCRs’ results via the cloud[16].
CBD is expected to continue to be popular in cosmetics; especially with the ICCI encouraging anecdotal claims to be investigated.
Unfortunately, along with the huge profit potential of the fast-growing CBD market, comes huge risk. Unscrupulous players have joined the enthusiasts and global cosmetic brands making CBD products. Even law-biding producers will be tempted to deceive, if for example, THC tests show they have accidentally grown a Schedule I controlled substance, which by law must be destroyed.
After decades of illegal cannabis use, and lack of scientifically supported facts, the regulations controlling cosmetic the use of Cannabis sativa are unusually strict.
In the EU, cosmetic phytocannabinoids must only come from the seeds and or leaves of registered cultivars, which have been cultivated by licensed growers. All the while authorities continue to allow isolates with only a CAS number and no documented evidence of their origin to enter the EU, unacceptable risks are being put on the Responsible Person and brands, before being passed onto the consumer.
Brands looking to remove the risk of prosecution should therefore only purchase from suppliers using track and trace systems such TTS Pharma. The same DNA technologies detecting coronavirus can be used to authenticate CBD oils.
Applied DNA Sciences' uses SigNature DNA molecular tags as part of its CertainT platform, which offers forensically verifiable supply chain transparency, providing sources of identification for Blockchain or other digital systems.
By combining the new DNA and digital technologies, supply chains can be made fully transparent - from 'field to face cream'. Formulators should only be using cosmetic Cannabis sativa derived materials with fully transparent supply chains.
References
1. Al-Wakeel, R., 2020. CBD & skin: A scientific history. SPC April, pp64-66.
2. Bíró, T., Tóth, B.I., Haskó, G., Paus, R. and Pacher, P., 2009. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends in pharmacological sciences, 30(8), pp.411-420.
3. Nickles, M.A. and Lio, P.A., 2020. Cannabinoids in Dermatology: Hope or Hype? Cannabis and Cannabinoid Research.
4. Grand View Research. Feb 2020. Legal Marijuana Market Size, Share & Trends Analysis Report By Marijuana Type (Medical, Adult Use), By Product Type, By Medical Application (Cancer, Mental Disorders), And Segment Forecasts, 2020 – 2027 www.grandviewresearch.com/industry-analysis/legal-marijuana-market.
5. FDA Website: Testimony of Amy Abernethy, MD, PhD. Principal Deputy Commissioner - Office of the Commissioner before the United States Senate. Hemp Production and the 2018 Farm Bill July 25, 2019 https://www.fda.gov/news-events/congressional-testimony/hemp-production-and-2018-farm-bill-07252019
6. EU COSing https://ec.europa.eu/growth/tools-databases/cosing/index.cfm?fuseaction=search.details_v2&id=96287
7. WHO Website: https://www.who.int/medicines/access/controlled-substances/Annex_1_41_ECDD_recommendations_cannabis_22Jan19.pdf
8. FDA Website: https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd
9. Linger, P., Müssig, J., Fischer, H. and Kobert, J., 2002. Industrial hemp (Cannabis sativa L.) growing on heavy metal contaminated soil: fibre quality and phytoremediation potential. Industrial Crops and Products, 16(1), pp.33-42.
10. https://www.bbc.co.uk/programmes/articles/sDNZjp3h8lxzv8k8KLYNvW/what-s-really-in-cannabis-based-health-products
11. Private communication
12. WDO Expert Committee on Drug Dependence Pre-Review. Cannabis plant and Cannabis Resi. Section 5 Epidemiology. 2018.
https://www.who.int/medicines/access/controlled-substances/Section5epidemiologyCannabisPlant.pdf?ua=1
13. Lawrence, F. Where did the horsemeat scandal begin? The Guardian.15th Feb. 2013. https://www.theguardian.com/uk/2013/feb/15/horsemeat-scandal-the-essential-guide.
14. Grand View Research Aug. 2019 https://www.prnewswire.com/news-releases/cbd-skin-care-market-size-worth-1-7-billion-by-2025--cagr-32-9-grand-view-research-inc-300908941.html
15. TTS Pharma Ltd. www.ttspharma.com
16. Applied DNA Sciences https://adnas.com/certaint-platform/
