On a daily basis, the average person around the world is subjected to doses of heavy metals and other contaminants from a variety of sources. One of the most insidious sources of routes of exposure is through food, beverages, and other sources of oral consumption (that is, nutraceuticals, pharmaceuticals, and so on). The World Health Organization contends that food may be the source of the largest contribution to the intake of contaminants. Many agricultural products may naturally contain heavy metal and other contaminant compounds, from either natural biochemical processes or from bioaccumulation from the environment. Other products become contaminated by natural, agricultural, or industrial sources or poor hygiene methods of production and storage. Finally, there are food and beverage products that are intentionally adulterated or counterfeited with materials containing contamination. In this column, we look at different sources of potential contamination exposure that may be of concern to both the cannabis industry and the cannabis consumer from the perspective of an analytical industry professional with decades of experience in metals analysis. The guest author of this installment, Robert Thomas, has worked as an analytical chemist in the field of trace element analysis for more than 45 years, including 24 years for an inductively coupled plasma-mass spectrometry (ICP-MS) manufacturer and 19 years as principal of his own consulting company.
The cannabis and hemp industry is moving at such an alarming rate that the scientific and 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 U.S. by 2025 (1,2). However, because the U.S. Food and Drug Administration (FDA) has only been involved in this process when an investigational new drug (IND) has been submitted to conduct human clinical trials (for example, Epidiolex from GW Pharmaceuticals), 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 today’s marketplace, are for all intents and purposes, unregulated by the federal government at this time.
Unfortunately, many of the state regulators (including state cannabis commissions and department. of agriculture personnel) 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. This article, therefore, focuses on the importance of measuring elemental contaminants (heavy metals) in cannabis and hemp and, in particular, how they might be better regulated to ensure that products are safe for human medicinal and recreational consumption. It is universally recognized that the toxicity effects of heavy metals have been well-documented in the public domain because they have such a serious impact on human health, particularly for young children and adults with compromised immune systems (3,4). Note: Much of the information in this article has been sourced from my new book, Measuring Heavy Metals in Cannabis and Hemp: A Practical Guide, which will be published in the summer of 2020 (5).
Regulating Cannabis and Hemp
The lack of federal oversight with regard to heavy metals in medicinal cannabis and hemp products in the U.S. 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 the District of Columbia allow its use for adult recreational consumption (6). 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 (7). Unfortunately, there are many inconsistencies with heavy metal limits in different states where cannabis is legal. Some states define four heavy metals while others specify up to nine. Some are based on 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. Some states only require the measurement of heavy metals in the cannabis plant or flower, while others give different limits for the delivery method such as oral, inhalation, or transdermal (via the skin).
What Can be Learned from the Pharmaceutical Industry?
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 almost 25 years ago when it updated its 100-year-old semiquantitative (at best), sulfide colorimetric test for an undefined suite of heavy metals to eventually arrive at a list of 24 elemental impurities in drug products using plasma spectrochemical techniques. This new list included maximum permitted daily exposure (PDE) limits, based on well-established elemental toxicological data for drug delivery methods (including oral, parenteral, and inhalation), together with the analytical methodology to carry out the analysis.
These procedures were described in United States Pharmacopeia (USP) chapters 232, 2232, and 233 (8–10) for elemental impurities in pharmaceutical raw materials, drug compounds, and dietary supplements. This meant that pharmaceutical and nutraceutical 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 seriously regulate elemental impurities in pharmaceuticals in 1995 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.
- The Global State of the Hemp Industry, Hemp Business Journal, a division of New Frontier Data Analytics (2019).
- Cannabis Consumer Report, New Frontier Data Analytics (2019).
- “Preventing Lead Poisoning in Young Children,” U.S. Department of Health and Human Services, Public Health Services, Centers for Disease Control (1991).
- R. Thomas, Spectroscopy 34(2), 22–32 (2019).
- R.J. Thomas, Measuring Heavy Metals in Cannabis and Hemp: A Practical Guide (CRC Press, Boca Raton, Florida, to be published in summer 2020).
- Marijuana Policy by State: https://www.mpp.org/states/.
- M.A. Khan, et.al., J. Chem. Soc. Pak. 30(6), 805–809 (2008).
- General Chapter <232> “Elemental Impurities in Pharmaceutical Materials– Limits,” 2nd supplement to United States Pharmacopeia 37–National Formulary 32 (USP37–NF32) (United States Pharmacopeial Convention, Rockville, Maryland, 2014).
- General Chapter <2232> “Elemental Contamination in Dietary Supplements,” 2nd supplement to United States Pharmacopeia 37–National Formulary 32 (USP37–NF32) (United States Pharmacopeial Convention, Rockville, Maryland, 2014).
- General Chapter <233> “Elemental Impurities in Pharmaceutical Materials – Procedures,” 2nd supplement to United States Pharmacopeia 37–National Formulary 32 (USP37–NF32) (United States Pharmacopeial Convention, Rockville, Maryland, 2014).
- W. Chen, et. al., J. Environ. Qual. 37(2), 689–95 (2008).
- B. Whittle, C.A. Hill, I.R. Flockhart, D.V. Downs, P. Gibson, and G.W. Wheatley, US Patent Number, US7344736B2, “Extraction of pharmaceutically active components from plant materials,” GW Pharmaceuticals.
- D.V. Gauvin, et.al., Pharmaceutical Reg. Affairs 7(1), 202. doi: 10.4172/2167-7689.1000202 (2018).
- P. Soudek et. al., in Advanced Science and Technology for Biological Decontamination of Sites Affected by Chemical and Radiological Nuclear Agents, N. Marmiroli, B. Samotokin, and M. Marmiroli, Eds. (IOS Press, Amsterdam, and Springer in conjunction with the NATO Public Diplomacy Division, 2007) pp. 139–158.
- R. Ahmad et. al., Clean Soil Air Water 44(2), 195–201 (2016), https://doi.org/10.1002/clen.201500117.
- D.V. Gauvin, et.al., Pharmaceut Reg. Affairs 7(1),1–99 (2018).
- R. Pappas, et al., J. Anal. Toxicol. 38, 204–211 (2014.
- P. Ziarati, Z. Mousavi, and S. Pashapour, J. Med. Discovery 2(1), jmd16006; doi:10.24262/jmd.2.1.16006 (2017).
- P. Olmedo, et. al., Environ. Health Perspect. 26(2), https://doi.org/10.1289/EHP2175 (2018).
- M. Halstead, et.al., J. Anal. Toxicol. in press (2019).
- P. Atkins, Cannabis Science and Technology 1(4), 40–49 (2018).
- R.J. Thomas, Measuring Elemental Impurities in Pharmaceuticals: A Practical Guide (CRC Press, Boca Raton, Florida, 2018).
About the Guest Author
Robert Thomas is the principal of Scientific Solutions, a consulting company that serves the training, application, marketing, and writing needs of the trace element user community. He has worked in the field of atomic and mass spectroscopy for more than 45 years, including 24 years for a manufacturer of atomic spectroscopic instrumentation. He has served on the American Chemical Society (ACS) Committee on Analytical Reagents (CAR) for the past 19 years as leader of the plasma spectrochemistry, heavy metals task force, where he has worked very closely with the United States Pharmacopeia (USP) to align ACS heavy metal testing procedures with pharmaceutical guidelines. Rob has written almost 100 technical publications.
About the Columnist
Patricia Atkins is a Senior Applications Scientist with SPEX CertiPrep and a member of both the AOAC and ASTM committees for cannabis.
How to Cite This Article
R. Thomas, Cannabis Science and Technology 2(5), 22-30 (2019).