Regulating Heavy Metal Contaminants in Cannabis: What Can be Learned from the Pharmaceutical Industry? Part 4

Potential sources of contamination: the final products

The first installment of the series gave an overview of why testing cannabis and hemp for heavy metal contaminants is so important and how the pharmaceutical industry can play a critical role in preparing the cannabis industry for federal oversight.  Part 2 focused on how growers and cultivators need to actively investigate all potential sources of elemental contamination before they can even hope to minimize them. And, Part 3 highlighted how potential sources from the extraction and manufacturing processes can contribute to the problem. Part four will examine how processors can reduce the chances of elemental contamination, as well as provide examples of how high levels of heavy metals in some CBD products have led to government recalls and litigations because of false advertising of heavy metal content. In addition, we’ll take a look at one CBD manufacturer’s extraction protocols and how it impacted heavy metal levels in its products. Finally, we’ll investigate the effect of smoking/inhaling cannabis products, not only from the perspective of the cannabinoid but also from heavy metal contamination in the smoking/inhaling method/device used. 

Note: The series has been summarized from two chapters in Robert Thomas’ upcoming book, Measuring Heavy Metal Contaminants in Cannabis and Hemp: A Practical Guide, which will be published by CRC Press this September. The book, including its table of contents, is now available for preordering from the publisher’s website.

Product recalls

There is clear evidence in the public domain that heavy metals are not being completely removed from commercially-available cannabinoid products, evidenced by the fact that from time to time we see products recalled for high levels of heavy metals. The following stories, taken from online newspapers and news sites are examples of this.

• There was a case recently where a CBD oil producer from Florida was forced to recall a CBD tincture by the FDA because it had 10x higher Pb levels - 4.7 ppm compared to the maximum allowable limit for Florida which was 0.5 ppm¹.

• And there have been other similar stories reported where a CBD manufacturer claimed their product was “heavy metal” free but on further testing, it was found to be over the legal limit for Pb, Cu, and Ni. This case is currently going through the litigation process².

• Thirteen strains of medical marijuana sold at a licensed medical marijuana center in Michigan were recalled. They failed to meet state maximum allowable limits for heavy metals when tested, because they were contaminated with high levels of Cd and As, according to the Michigan Bureau of Marijuana Regulation MBMR)³.

• Ohio state regulators recently recalled medical marijuana flower because it was packaged for sale at dispensaries before being tested for high levels of heavy metals, in addition to microbes, mycotoxin fungi, and foreign matter⁴.

• Following an inspection by the California Bureau of Cannabis Control (CBCC) a cannabis testing lab had to give up its business license. The inspection uncovered false results for a group of contaminants during cannabis product testing over a four-month period. This was especially detrimental to the California cannabis industry because they were in the process of putting in stricter limits for toxins, such as heavy metals⁵. 

• Medical cannabis regulators in Maryland expanded testing for heavy metals in marijuana products as they warned the public about the risk for possible lead contamination in popular vaping devices. They issued an advisory to notify patients and other stakeholders of potential lead contamination of cannabis liquids in vape cartridges following exposure to heat inside the device⁶. 

• Lead and ethanol contaminants were found in vape cartridges sold in Hawaii. They don't say where these contaminants come from, but the lead most likely comes from the soldered battery connections inside the vaping device, while the ethanol is a carryover from the cannabinoid extraction process. At vaping temperatures of approx 200°C, who knows what these contaminants are doing to someone's lungs, so it’s not surprising that a local doctor thinks they might be linked to a recent spate of lung illnesses⁷.

These stories emphasize that there is a continuing trend of products that are testing above maximum allowable levels for heavy metals, which indicates that growers and processors do not fully understand how heavy metals end up in commercially available cannabinoid products. It should also be pointed out that the majority of states that allow for medicinal cannabis only regulate Pb, As, Cd and Hg. In Part 2 of my series, I show convincing evidence in the public domain that there are probably another 10 heavy metals that could potentially be considered when assessing contamination in cannabis and cannabinoid products. Currently, if these metals found their way into cannabis products, they would escape the scrutiny of most state regulators. 

CBD-Based Drugs

There are many over the counter CBD-based drugs/medications on the market for medicinal purposes, but there is only one CBD prescription drug that is regulated by the FDA.  Epidiolex™ is a prescription CBD-based drug for seizures in young children, which is manufactured by G.W. Pharmaceuticals. And, because it a prescription drug, it is regulated according to USP Chapter 232/233 in the US and to ICH Q3D guidelines in the ROW for 24 elemental impurities Permitted Daily Exposure (PDE) limits (refer to Part 2 for details). However, as the elemental impurities are not listed on the Epidiolex label, the only evidence I could find that indicates the level of heavy metals in the product is with regard to the company’s patent application for their cannabis extraction process⁸. A summary of its production/extraction protocol is shown below, which uses CO₂ with sub-critical fluid extraction conditions at a temperature of 10° C and a pressure of 60 bar. On further investigation of the patent, the final heavy metal content is in the order of 20 ppm, although they do not mention which heavy metals they found.

        - Subcritical extraction conditions: approximately 60 bar pressure at 10°C

• Removal of CO₂ by depressurization to recover crude extract

• Winterization of the crude extract by dissolution in ethanol followed by chilling solution (-20°C up to 52 hours) to precipitate unwanted lipids and waxes

• Removal of unwanted waxy material by cold filtration (20 µm filter)

• Removal of ethanol and water from the filtrate by thin-film evaporation under reduced pressure (60°C with vapor at 40°C - 172 mbar and 72 mbar)

• Final botanical drug substance (CBD extract) stored at -20°C.

By reading through the entire patent, the following text gives their reasons for using this extraction procedure.

….the density of sub-critical CO₂ is low, and remains low even as pressure is increased until the critical point of the system is reached. Thus, whilst the solvating power of sub-critical CO₂ is reduced, a high degree of selectivity can be achieved, as only the most soluble components are efficiently dissolved by the CO₂; in this case the cannabinoid fraction. The result is the production of a relatively simple extract containing, as well as the cannabinoids, only a limited number of non-target compounds (inc. heavy metals), many of which can be removed relatively easily by a simple winterization clean-up step. In contrast, at higher temperatures, there is a significant increase in the density of the CO₂ as it now exists in a supercritical fluid state. This has the effect of greatly increasing the solvating power of the solvent, which whilst generally advantageous in that more cannabinoids are solubilized, thereby giving high yields, in fact, proves disadvantageous because the decreased selectivity of the more powerful solvent results in increased solubility of a range of non-target compounds which makes the resulting extract more difficult to purify.

Using this process, the resulting product specifications are shown in Figure 1: 

Figure 1: Product Specifications for a CBD extract manufacture by GW Pharmaceuticals⁸.