The cannabis and hemp industry is moving at such an alarming rate that the analytical testing community is struggling to keep up with it. It is estimated that the demand for medicinal and adult recreational cannabis-based products, containing Tetrahydrocannabinol (THC) and Cannabidiol (CBD) compounds will exceed $25 billion in the US by 2025.
Authored By: Robert Thomas, Scientific Solutions
Introduction
However, because the FDA has only been involved in this process when an investigational new drug (IND) has been submitted to conduct human clinical trials (e.g. Epidiolex™ for treating seizures in young children), regulating the industry to make sure products are safe for human consumption has been left to individual states. In addition, CBD-only products, which are dominating todays’ marketplace, are for all intents and purposes, unregulated by the federal government at this time.
Unfortunately, many of the states where it is legal do not have the necessary experience and background to fully-understand all the safety, quality and toxicological issues regarding the cultivation and production of cannabis and hemp products on the market today. Besides the need to characterize its potency (CBD and THC content) and other beneficial compounds such as terpenoids, one of the most important contaminants to measure is the level of heavy metals, because cannabis and hemp will avidly accumulate trace elements from the growing medium, soil, fertilizers and even the metallic equipment used during the preparation and processing of the various concentrates and oils. For that reason, it’s critically important to monitor heavy metals in cannabis and hemp to ensure that products are safe for human consumption.
Regulating Cannabis and Hemp
The lack of federal oversight with regard to heavy metals in medicinal cannabis products in the US has meant that it has been left to the individual states to regulate its use. Medical cannabis is legal in 34 states, while 12 states including Washington, DC allow its use for adult recreational consumption. However, the cannabis plant is known to be a hyper-accumulator of heavy metals in the soil so it is critical to monitor levels of elemental contaminants to ensure cannabis products are safe to use. Unfortunately, there are many inconsistencies with heavy metal limits in different states where cannabis is legal. The vast majority of states define four heavy metals (Pb, As, Cd and Hg). Some base their limits directly in the cannabis, while others are based on human consumption per day. Others take into consideration the body weight of the consumer, while some states do not even have heavy metal limits. Certain states only require heavy metals in the cannabis plant/flower, while some give different limits for the delivery method such as oral, inhalation or transdermal (1). This makes it extremely complicated because currently all regulations apply only in the state where the cannabis is grown, processed and sold. And since the federal government still considers cannabis a Schedule I drug (same as heroin), there can be no interstate commerce with regard to cannabis products. However in 2020, it will be legal to grow hemp anywhere in the US for the production of CBD-based and other industrial products (Note: hemp is a variant of the cannabis plant, which contains <0.3% THC), so it will be interesting to see how the Dpt of Agriculture regulates the industry at the federal level, when cannabis is regulated by the individual states.
What Can be Learned from the Pharmaceutical Industry?
So clearly there is a need for more consistency across state lines, particularly as the industry inevitably moves in the direction of being federally regulated. The cannabis industry can learn a great deal from the pharmaceutical industry, as it went through this process over 20 years ago, when it updated its 100-year old qualitative sulfide precipitation test for an undefined suite of heavy metals (2) to eventually arrive at a list of 24 elemental impurities in drug products using plasma spectrochemical techniques.
These procedures were described in the ICH Guideline Q3D on Elemental Impurities: Step 5 (3), together with United States Pharmacopeia (USP) Chapters <232> Elemental Impurities: Limits (4), and <233> Elemental Impurities: Procedures (5). These new directives defined maximum PDE (permitted daily exposure) limits, based on well-established elemental toxicological data for drug delivery methods (inc. oral, parenteral and inhalation), together with the analytical methodology to carry out the analysis. This meant that pharmaceutical manufacturers were required to not only understand the many potential sources of heavy metals in raw materials and active ingredients, but also to know how the manufacturing process contributed to the elemental impurities in the final drug products.
The beginning of the journey to regulate elemental impurities in pharmaceuticals in the late 1990s can be likened to the production of cannabis and hemp derived products today, where the source of elemental contaminants is not fully understood. In particular, the elemental toxicological guidelines to regulate the cannabis industry are being taken very loosely from a combination of methods and limits derived by the pharmaceutical, dietary supplements, food, environmental and cosmetics industries. Even though the process of manufacturing cannabis products might be similar in some cases to drugs and herbal medicines, the consumers of cannabis and hemp products are using them very differently and in very different quantities, particularly compared to pharmaceuticals, which typically have a maximum daily dosage. The bottom line is that heavy metal toxicological data generated for pharmaceuticals over a number of decades cannot simply be transferred to cannabis, hemp and their multitude of products.
An added complication is that the cannabis and hemp plant can not only absorb heavy metals from the soil, but also from contaminants in fertilizers, nutrients, pesticides and the growing medium as well as from other environmental pathways. Additionally, the process of cutting, grinding and preparing the cannabis/hemp flowers for extraction can often pick up elemental contaminants from the stainless steel manufacturing equipment. Finally the cannabinoid extraction process will extract different amounts of heavy metals, depending on the solvent and/or the extraction process used and could possibly end up in the finished products. In addition, some cultivators will use nutrients containing metal-based bud/flower enhancers, which would not be picked up by the state regulatory process. It’s also worth pointing out that the equipment used to deliver these products to consumers such as inhalers, and vaporizers can mean the user is exposed to additional sources of elemental contaminants from inside these devices, apart from what’s in the cannabinoid compound itself.
Phytoremediation Properties of Cannabis and Hemp
Cannabis and hemp are known to be hyper-accumulators of contaminants in the soil. That is why they have been used to clean up toxic waste sites where other kinds of remediation attempts have failed. In the aftermath of the Chernobyl nuclear melt down in the Ukraine in 1986, industrial hemp was planted to clean up the radioactive isotopes that had leaked into the soil and ground waters. Of course Chernobyl is an extreme example of heavy metal and radionuclide contamination, but as a result of normal anthropogenic activities over the past few decades including mining, smelting, electroplating, gasoline exhaust, energy production, use of fertilizers, pesticides, waste treatment plants, lead-based paint and plumbing materials etc., heavy metal pollution has become one of the most serious environmental problems today. And with all the diverse and varied conditions used for growing cannabis, it will be very difficult to eliminate all these potential sources of pollution in order to reduce their impact on the plant’s biology.
So there is no question that the current suite of four heavy metals being required by state-based regulators is totally inadequate to ensure cannabis products are fit for human consumption. Based on evidence in the public domain, there are about 15 heavy metals found in natural ecosystems (soil, water, air) that could be potential sources of contaminants accumulated by the plant, including Pb, As, Hg, Cd, Ni, V, Co, Cu, Se, Ba, Ag, Sb, Cr, Mo, Mn, Zn, Fe. They might not all have a negative impact on the health of the plant during cultivation but the chances that they will end up in the flowers and the final manufactured products are very high. Their levels of toxicity would need to be investigated further, but there is a case to be made that the majority of them could be the future basis of a federally-regulated panel of elemental contaminants in cannabis and hemp (6). For this reason, it is critically important to characterize all the potential sources of elemental contamination including the cultivation of the cannabis/hemp plant as well as the cannabinoid manufacturing process.
Testing Procedures
As a result of the high likelihood of heavy metals being present in hemp and cannabis products, the correct sampling and testing procedures is absolutely critical, so the analytical result of the sample being presented to the instrument is indicative of the cannabis plant being grown. The most suitable and widely used technique is considered to be Inductively Coupled Plasma Mass Spectrometry (ICP-MS), which is a very sophisticated multielement analytical technique that can easily measure down to ppt (parts per trillion) detection levels. However, it requires an analytical chemist with a high level of knowledge and expertise to fully-understand the nuances of ultra-trace elemental analysis, including lab cleanliness, sources of contamination, sample preparation, digestion techniques, instrumental method development, interference corrections, calibration routines, use of reference materials and validation procedures. In other words, in the hands of an inexperienced user it could easily generate erroneous results. For that reason, the expertise of the testing lab and the people running the instrumentation is of prime importance.
The pharmaceutical industry went through this learning curve when they were first required to use plasma spectrochemistry after 100 years of using the qualitative colorimetric sulfide precipitation test. As the leader of the heavy metals task force on the ACS Reagent Chemicals Committee, I had become very familiar with the demands of the pharmaceutical community, as my committee worked very closely with the USP to align our updated ACS test for heavy metals with the new USP plasma-based methodologies described in Chapters 232 and 233. It was very clear that pharmaceutical manufacturers were just not familiar with working at the ultra-trace level required by ICP-MS. This became the incentive to write my last book entitled “Measuring Elemental Impurities in Pharmaceutical Materials: A Practical Guide,” which was available in the spring of 2018 (7). After I published this book, I then turned my attention to the cannabis and hemp industry and started talking to cultivators, growers, producers, processors regulators and testing labs to get a better understanding of what the industry needs with regard to its heavy metals’ testing requirements. As a result of that background research, I began the process of writing a new book, which will focus on heavy metals in cannabis and hemp with the objective of having it available by the late summer of 2020 (8). This article represents an overview of some of the initial findings of my research.
Final Thoughts
Our environment has been severely polluted by heavy metals, which has compromised the ability of our natural ecosystems to foster life and render its intrinsic values. Heavy metals are known to be naturally occurring compounds, but anthropogenic activities introduce them in extremely large quantities into our agricultural ecosystems. Nowhere is this more evident than in the delicate balance of growing and cannabis and hemp for commercial, medicinal and recreational uses. Unfortunately, the demand for cannabinoid-based products is moving so fast that the scientific community is not keeping up with it; whether it’s the medical research required to understanding the biochemistry that is fundamental to treating a particular disease or ailment the testing of the products to make sure they are safe for human consumption. There is clear evidence that the industry is not completely removing the elemental contaminants from commercially-available products as indicated by products recalled for high levels of heavy metals. There was a case recently where the FDA issued a product recall against a CBD oil producer from Florida that was selling a CBD tincture which had 10x higher Pb levels than the maximum allowable limit (9). Another example was of a recent lawsuit against a CBD manufacturer, that claimed their product was Pb-free, but on further testing found it was above the legal limit for Pb, Cu and Ni (10). There have been many other similar stories reported in the US over the past 12 months.
So it’s clear the industry is both exciting and chaotic at the same time, but because of its unparalleled growth there appears to be very little incentive to bring in sensible regulations. At the bare minimum, there needs to be a more comprehensive suite of elemental contaminants tested and to set the maximum limits on toxicological data based on the manner and the quantity that cannabis products are consumed. For that reason, I firmly believe that researchers who are trying to raise the bar now will be rewarded when the FDA eventually starts to regulate the industry. However, in the meantime, I’m firmly committed to educating state regulators to better understand the potential sources of heavy metals in cannabis and hemp and to helping testing labs improve the quality of their data.
Further Reading
- Marijuana Policy by State: https://www.mpp.org/states/
- United States Pharmacopeia General Chapter <231> Heavy Metals Test in USP National Formulary (NF), https://www.usp.org/chemical-medicines/elemental-impurities-updates
- ICH Guideline Q3D on Elemental Impurities: Step 5, European Medicine Agency Website: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use_en-13.pdf)
- United States Pharmacopeia General Chapter <232> Elemental Impurities – Limits: First Supplement to USP 40–NF 35, 2017, https://www.usp.org/chemical-medicines/elemental-impurities-updates
- United States Pharmacopeia General Chapter <233> Elemental Impurities – Procedures: Second Supplement to USP 38–NF 33, 2015, https://www.usp.org/chemical-medicines/elemental-impurities-updates
- Marijuana Toxicity: Heavy Metal Exposure Through State-Sponsored Access to “la Fee Verte”, D. Gauvin et.al., Pharmaceutical Reg Affairs, 7:1, 2018
- Measuring Elemental Impurities in Pharmaceuticals: A Practical Guide, R. J. Thomas, CRC Press, Boca Raton. FL, US, 2018, ISBN: 9781138197961, https://www.routledge.com/Measuring-Elemental-Impurities-in-Pharmaceuticals-A-Practical-Guide/Thomas/p/book/9781138197961?utm_source=crcpress.com&utm_medium=referral
- Measuring Heavy Metal Contaminants in Cannabis and Hemp: A Practical Guide, R. J. Thomas, CRC Press, Boca Raton, FL, ISBN: 9780367417376, Available September, 2020, https://www.routledge.com/Measuring-Heavy-Metal-Contaminants-in-Cannabis-and-Hemp/Thomas/p/book/9780367417376
- Marijuana contaminated with heavy metals, pesticide recalled in testing lab investigation, A. Biolchini, Michigan live, August, 30, 2019, https://www.mlive.com/news/2019/08/marijuana-contaminated-with-heavy-metals-pesticide-recalled-in-testing-lab-investigation.html
- Lawsuit over heavy metals in CBD products ‘raises more questions than answers, E. Watson, May 11, 2020, Food Navigator, https://www.foodnavigator-usa.com/Article/2020/05/11/Lawsuit-over-heavy-metals-in-CBD-products-raises-more-questions-than-answers-says-attorney-Hemp-Authority-seal-gains-traction#
Robert Thomas, CSci, CChem, FRSC
——————————————————————-
Principal Consultant
Scientific Solutions: Serving the Writing Needs of the Scientific Community
4615 Sundown Road
Gaithersburg, MD 20882
Office: 301-570-2811
Cell: 301-717-0900
Fax: 301-570-2811
Email: robert.james.thomas@verizon.net
Website: www.scientificsolutions1.com
