Understanding Sources of Heavy Metals in Cannabis and Hemp: Benefits of a Risk Assessment Strategy – Part 4

Part 4: Production, packaging, and delivery of cannabis consumer products?

Part 1 of this series of articles highlighted the pharmaceutical risk assessment approach from a historical perspective to better understand sources of heavy metal contaminants in drug products. Part 2 explored why the cannabis industry could benefit from a similar strategy and in particular how the cultivation process likely contributed to sources of metal uptake from the soil and growing environment. Part 3 examined the critically important step of extracting cannabinoids from the biomass, the flower, and other parts of the plant.

This final installment will explore potential elemental sources in the production, packaging, and delivery of cannabis consumer products.

Manufacture of cannabis products

Once the cannabinoid product has been manufactured, serious consideration must be given to the selection and composition of diluent mineral oils, flavoring compounds, and recipe ingredients. For example, raw materials such as fillers, excipients, dissolution compounds – which are added to these products – could possibly be contaminated with heavy metals. For that reason, it is critically important to carry out quality control testing of all components. Even if there are no heavy metals in the cannabinoid extract, it could exceed the regulated limits because of contaminated additives or ingredients. In fact, a recent study by researchers at the University of Illinois showed that cacao beans grown in certain countries in Latin America contained abnormally high levels of cadmium. Chocolate made from these beans could easily end up in cannabis consumer products such as brownies and cookies¹ It is also worth emphasizing that many cannabinoid products (in particular CBD derived from hemp) are being sold and labelled as dietary supplements, which is attracting the attention of federal regulators, because it violates the Federal Dietary Supplement Health and Education Act (DSHEA) and could potentially put the health and safety of consumers at risk.

Packaging, storage and container systems

It is also important to characterize the material used for packaging the products, particularly if they are in liquid form. This was a major consideration when the pharmaceutical industry was carrying outs its risk assessment study, because drug products are often stored for long periods of time, which could potentially allow them to degrade or become contaminated from the packing material. For example, some low-quality borosilicate glasses and inexpensive plastic containers are notorious for elemental contamination, which could leach out into the product during storage. In fact, researchers at the Florida Department of Agriculture found abnormally high levels of lead in CBD extracts, which had been leaching out over time, and was most likely coming from the lead-based ink used in the graduated dropper bottles. One sample resulted in lead levels 36 times higher than the state’s maximum action limit of 0.5 parts per million (ppm)². In addition, a recent study presented at a cannabis science conference showed that rolling papers contained abnormally high levels of lead³.

Delivery devices

It is worth pointing out that, historically, most consumers of recreational cannabis have delivered their cannabinoids via the smoking route. Smoke chemistry has been predominantly investigated in tobacco products, but many studies over the past ten years have highlighted the qualitatively similar carcinogenic chemicals contained within both tobacco and cannabis smoke^{4, 5}.

In a recent study, the International Organization for Standardization and Health Canada analyzed tobacco and cannabis cigarettes. The heavy metals contained in both smoked products included mercury, cadmium, lead, chromium, nickel, arsenic, manganese, and selenium⁶. Quantitatively, there were lower heavy metal concentrations in cannabis smoke condensates, mainly because the cannabis supply was grown hydroponically. In addition, the soilless growth medium of the cannabis plants required water and water-soluble hydroponic vegetable fertilizers, which contain nitrogen in the form of nitrates. So, with no soil-based heavy metals present in the growing cycle of the cannabis, it was the liquid nutrients and fertilizers used in the hydroponic systems that contributed most to the heavy metal levels. There is a great deal of information in the public domain about heavy metals in tobacco and tobacco products, such as nicotine and electronic nicotine delivery (END) devices^{7, 8}.

Vaping systems

However, the more common way of inhaling cannabis products today is via vaping sticks, carts, or pens. The demand for these vaping devices is growing so fast that they are very loosely regulated, which is attracting manufacturers with very little regard for safety. There are literally millions of these devices out in the marketplace where the cannabis flower, extract or oil is heated up to about 200-300 °C and the aerosol is vaporized into the consumer’s mouth.

The problem with this mode of delivery is that many of the components inside these vaping devices are metal, including the tank, coil, mouthpiece, and battery terminals, which are typically made from materials such as stainless steel (iron, chromium, nickel, cobalt), brass (copper, zinc, lead), chromel (chromium, nickel), inconel (nickel, chromium, and iron), Nichrome (nickel, chromium) and soldered battery connectors (lead, antimony, tin). At these kinds of temperatures, dissolved metals or even fine metallic particles can easily be delivered to the consumer’s air pathways and lungs via the mouth⁹. Unfortunately, there is no standardized test for these elemental contaminants in the vaped aerosol, so even though the cannabis flower, oil or extract in the tank might contain elemental impurity levels below the regulated limits, the vaping mechanism is generating an entirely new panel of pollutants, which is escaping the scrutiny of state regulators¹⁰. The list above demonstrates that most of the metals under discussion here have much higher toxicity (e.g., lower permitted daily exposure) when inhaled compared to being consumed orally.

This is of great concern, because unlike delivery through the mouth and gastro-intestinal digestion system, the lungs and respiratory system were designed to allow us to breathe. They bring oxygen from the air into our bodies and send carbon dioxide out. Air enters the respiratory system through the nose or the mouth. If it goes in through the nostrils there are tiny hairs called cilia that protect the nasal passageways and other parts of the respiratory tract, filtering out dust and other particles that enter the nose. There is no such filtering system in the mouth, so if any metal particulates make it into the aerosol there is no mechanism to stop them entering through the respiratory system into the lungs, where they can do serious damage, particularly if vaping is carried out on a regular basis over extended periods of time. This fact makes it critically important to characterize the metal contaminants in the aerosol, not just in the tank. Unfortunately, this is not straight forward because the vaping aerosol condensate, which is a mixture of hydrophobic and hydrophilic liquids must be trapped and collected before it gets introduced into the ICP-mass spectrometer for quantitation. This involves using a modified smoking machine, which can mimic the inhalation profile of a typical cannabis vaping consumer, which is very different to someone who uses a nicotine vaping system. The bottom line is that it requires specialized equipment and a person with a high level of knowledge and experience in working in the ultra-trace element environment¹¹. In 2019 a nationwide outbreak of e-cigarette and vaping use-associated lung injuries (EVALI) led to 3000 people developing pneumonia-type symptoms and 68 deaths, mainly from illicit THC vaping devices containing vitamin E acetate¹². As most state-based regulations only specify lead, arsenic, cadmium, and mercury they would fail to identify the other elements if they were present in the vaping aerosol because there is no requirement to test for them in most states. The last thing the industry wants is for another EVALI-type crisis by not paying enough attention to these additional elemental contaminants.

Note: Smoking cannabis using water pipes (bongs) is another way of delivering cannabinoids to consumers, but they are beyond the scope of this series of articles. However, it should be noted that most of these devices are typically made from low quality materials like borosilicate glass, ceramic or plastic which often have metallic impurities associated with them and could potentially leach out of the material over extended periods of use.

In conclusion

It took the pharmaceutical industry over 20 years to fully-understand all the sources of elemental impurities in the manufacture of drug products. The sector finally accomplished this by classifying the impurities’ toxicity impact and the risks of finding these impurities throughout the entire manufacturing process. It is clear that the cannabis industry has a great deal to learn about this process. The way to minimize heavy metals in cannabis and cannabis products is to first understand and characterize the cultivation process. Unfortunately, this is often very challenging, particularly if the plants are being grown outdoors. However, by carefully selecting the right cultivars, understanding the soil chemistry and the use of high purity fertilizers, nutrients, and water, the industry can minimize the plants’ uptake of elemental contaminants. Moreover, by optimizing the extraction and purification method, processors have the ability to reduce levels of heavy metals in the final cannabinoid extracts. Very often there are many choices when selecting an extraction technology, depending on the desired extract or the products being made for a therapeutic outcome. It is clear that elemental contaminants can be minimized by optimizing the entire production process, including extraction solvent, temperature/pressure/flow conditions, and the other purification techniques, including evaporation, distillation, and filtration. However, this must also be extended to include the packaging and delivery systems, which are all important areas to characterize in order to ensure that cannabis consumer products are free of heavy metals and safe for human consumption.

A final word of caution! The insatiable consumer appetite for cannabis products in the US is being fulfilled from outside the country. Yunnan Province in southern China is now producing CBD-products for the US market¹³. This should not be surprising, considering the US industry cannot produce enough to supply the huge demand. What is more disturbing is that the metal refining for the electronics industry in China has produced some of the most contaminated waste sites in the world¹⁴. Experience has warned us that consumer products coming from China are not always of the highest quality. So, it is imperative that no matter where the products are sourced, especially if it is from outside the US, testing the hemp and CBD products for a comprehensive suite of elemental contaminants is critically important.

Our appetite for the cannabis and hemp plant and their medicinal and recreational properties is not likely to diminish in the near future, so we are going to have to balance that with its natural instinct to absorb heavy metal from its growing medium. Hopefully we will not be tempted to sacrifice one for the other and jeopardize consumer safety!

Following the direction of the pharmaceutical industry and implementing a comprehensive risk assessment study is one way of minimizing these risks. It remains to be seen whether this approach will be taken up by individual manufacturers, driven by state regulations, or perhaps even addressed nationally as was done with USP 232 and ICH Q3D and driven through a regulatory/industry consortium established with the goal of providing minimum national standards for cannabis products in any of their forms. Federal scrutiny will clearly impact this decision, but it will be interesting to see how quickly this will happen. Only time will tell!

References

1. How Cadmium Ends Up in Your Chocolate: Lab Worldwide, Feb 12, 2022; https://www.lab-worldwide.com/how-cadmium-ends-up-in-your-chocolate-a-1095283/?cmp=nl-358&uuid=4d1ec37456e7450045207a16777e2bfa
2. Heavy Metals in Hemp Extract Products: A. Beadle, Analytical Cannabis, May 6, 2022, https://www.analyticalcannabis.com/articles/heavy-metals-analysis-in-hemp-extract-products-313875
3. Heavy Metals Contamination: Is Cannabis Packaging to Blame?, R. Newman, Analytical Cannabis, Feb 20, 2020, https://www.analyticalcannabis.com/articles/heavy-metals-contamination-is-cannabis-packaging-to-blame-312246
4. Toxic Metal Concentrations in Mainstream Smoke from Cigarettes Available in the USA, R. Pappas et al. al. Journal of Analytical Toxicology; 38:204–211, 2014, https://dx.doi.org/10.1093%2Fjat%2Fbku013
5. Toxic Metals in Cigarettes and Human Health Risk Assessment Associated with Inhalation Exposure, N. Benson et.al., Environmental Monitoring Assessment, 2017 Nov 8;189(12):619, https://link.springer.com/article/10.1007%2Fs10661-017-6348-x
6. Analysis of Heavy Metals in Cigarette Tobacco, P. Ziarati et. al., Journal of Medical Discovery (2017); 2(1):jmd16006; doi:10.24262/jmd.2.1.16006, http://www.e-discoverypublication.com/wp-content/uploads/2017/02/JMD16006.pdf
7. Analysis of Toxic Metals in Liquid from Electronic Cigarettes, N. Gray et.al., International Journal of Environmental Research and Public Health, 2019;16 https://www.mdpi.com/1660-4601/16/22/4450
8. Lead and Other Toxic Metals Found in E-Cigarette Vapors, P. Olmedo et. al., Johns Hopkins Bloomberg School of Public Health, February 7, 2017, https://www.jhsph.edu/news/news-releases/2017/study-toxic-metals-found-in-e-cigarette-liquids.html
9. Toxic Metal-Containing Particles in Aerosols from Pod-Type Electronic Cigarettes. R.S Pappas, et al., Journal of Analytical Toxicology, 2020, https://doi.org/10.1093/jat/bkaa088
10. Heavy Metals Can Leach into Cannabis Vape Oils and Aerosols, New Study Warns, A. Beadle, Analytical Cannabis, November, 2021, https://www.analyticalcannabis.com/news/heavy-metals-can-leach-into-cannabis-vape-oils-and-aerosols-new-study-warns-313479
11. The Challenges of Measuring Heavy Metal Contaminants in Cannabis Vaping Aerosols. R. Thomas, Analytical Cannabis white Paper, https://cdn.technologynetworks.com/ac/Resources/pdf/the-challenges-of-measuring-heavy-metal-contaminants-in-cannabis-vaping-aerosols-313041.pdf
12. Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products, Center for Disease Control and Prevention (CDC) Website: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html
13. China Cashes in on the Cannabis Boom, New York Times editorial, S. Meyers, May 4, 2019, https:// www.nytimes.com/2019/05/04/world/asia/china-cannabis-cbd.html
14. China: Toxic Trails from Metal Production Harms Health of Poor Communities Amid Soaring Global Demand for Gadgets; G. Shih, Washington Post, January 5, 2020, https://www.business-humanrights.org/en/latest-news/china-toxic-trails-from-metal-production-harms-health-of-poor-communities-amid-soaring-global-demand-for-gadgets-2/