Challenges in Medical Cannabis Analysis
Dr. Donald Land is a tenured professor at the University of California, Davis, and chief scientific consultant at Steep Hill Labs, a leading cannabis science and technology firm.
Dr. Donald Land is a tenured professor at the University of California, Davis, and chief scientific consultant at Steep Hill Labs, a leading cannabis science and technology firm with locations in California, Alaska, Hawaii, Maryland, New Mexico, and Washington State. Dr. Land guides the science and product development groups at Steep Hill. At UC Davis, his research spans the fields of forensic science, biotechnology, and sensor development.
Q: What are the main laboratory tests Steep Hill does for medical cannabis?
A: Steep Hill tests for a number of safety issues. We test for pesticides, mycotoxins, residual solvents, (volatile organics), as well as for microbiological contamination and heavy metals. Then we do potency testing, which is testing for a range of 17 cannabinoids and, in some markets, 43 terpenes. Different jurisdictions require different pesticide lists and other analytes.
Q: What main analytical technologies do you use for the tests?
A: We use ultra-high-pressure (or ultra-high-performance) liquid chromatography and gas chromatography. We generally use triple-quadrupole mass spectrometers as our primary detectors for the very-low-concentration analytes. For the potency targets, which are more in the tenth of a percent range that we are looking in, we still often use mass spectrometry, but also some ultraviolet photodiode array detection in the liquid chromatography for some of those analytes. For heavy metals, it’s inductively coupled plasma mass spectrometry. In microbiology, we use DNA probes as well as turbidity measurements on growth culture and headspace analysis with GC-MS for the volatile organics, residual solvents, and terpenes. Because the pesticide lists are long and variable, we end up having to do two pesticide runs—one on a GC triple quad and one on an LC triple quad.
Q: What are some of the key challenges the medical cannabis analysis industry faces?
A: One of the key challenges is that there’s no federal oversight, no federal guidelines, and no established regulatory limits for cannabis. Therefore, every jurisdiction—and that means not just every state, but in some states every local county and city—can have their own set of rules and lists. It’s not like every place we open a lab we’re doing the same EPA method, or have the same set of EPA regulations that apply as they would in most other industries of this nature. We don’t have that in cannabis. So as lab managers or directors, we have to be very fluid and flexible in our ability to meet those regulatory needs differently in different markets.
Q: What are some of those differences in regulations?
A: Many jurisdictions have regulations that are aimed more toward [cannabis as] an herbal product and then other regulations that are more akin to FDA food and drug and pharmaceutical [regulations], and then others as commodity produce. So one of the challenges is trying to work with jurisdictions to understand that, for example, things that grow in the ground [and are exposed] aren’t going to be sterile. Things that are made with ethanol extractions are going to have small amounts of ethanol residue. Again, because these jurisdictions don’t have the ability to go to some federal standard to say, “This is what you have to do,” they’re all trying to come up with their own on the fly and they’re not prepared or equipped for it, so you end up having a lot of mistakes. That … causes delays that sometimes put businesses out of business because start dates don’t happen on time and regulations aren’t enforceable.
Q: What are some of the issues that have happened because those regulations aren’t enforceable?
A: We had a huge fiasco in the state of Washington that’s still in the process of being resolved, where labs would falsify data or [perform] microbiological testing after sterilizing the samples that [were] brought in. Things like this were going on, on purpose, [to show] elevated levels of potency and decreased levels of contaminants [in order] to gain market share, and it worked. This has been a huge issue in the state of Washington and a lot of states are looking at this and trying to figure out how to avoid that nightmare. The bottom line is that there are no teeth in the state regulations that enforce people to be good actors, and they didn’t have any proper oversight to even catch bad actors. That’s all now in the works, but it’s taking months and months to finalize. In the meantime, we’ve been told of evidence that you can track certain batches that fail at one lab, go down the street to another lab, and get passed into the market and sold to the consumer.
We’ve seen pesticide issues in Colorado. Colorado decided to not deal with the issue of trying to establish all of the limits and regulations you would need for pesticide regulation and as a consequence they had an exposé not too long ago where significant amounts of product had to be recalled and destroyed because a test for pesticides came up positive on [several products]. There have been a lot of stumbles and falls because regulators are being forced to establish the rules that they normally just enforce. Another challenge is trying to work with the regulators and get them to understand that we have some experience with this, we can give them some guidance, and they’re not out there on their own. We can help them establish fair, reasonably-priced tests that will speak very highly to the safety of the product going onto the shelf. There’s one jurisdiction where their regulation is written to an extent where it implies that pesticide testing would involve a test for every single registered pesticide on the EPA list. I’m not sure that’s possible, and if it is, it’s going to be a very, very expensive test, especially if a lot of those pesticides that you’re testing for aren’t even available in that area. There are a lot of stumbling blocks that need to be resolved.
Q: What about analytical challenges?
A: There are no standard methods [for testing cannabis], so every single method that we run here is a method that I’ve developed specifically to be applicable to cannabis. In most cases, I start with a method that has been developed for some other application and then have to modify it significantly to get it to work with cannabis. One of the reasons for this is the nature of cannabis. Cannabis has around 500 different individual identified compounds in the matrix, and there are literally hundreds of terpenoids and cannabinoids and then dozens of flavonoids. There’s this incredible, rich variety of compounds and very many of them are medicinal and relevant, but standards don’t exist and, in a lot of cases, it’s difficult to tell the difference between them. At the moment, we’re quantitating close to a hundred different analytes either internally or for sale and it’s tough. It definitely makes it interesting for someone who’s trying to get a lab going in this to not have any standard methods that work or that you know will work.
Q: What other method development issues are common in the cannabis industry?
A: Another particularly interesting aspect of the cannabis industry is that most of the instrument manufacturing companies are not willing to touch cannabis and, therefore, when they develop their methods, they develop their methods in the absence of matrix. They buy what standards are available on a DEA-exempt basis, they run their methods with standards and get separation and say they have a method, but when you actually apply it to a sample that has real matrix in it, most of them don’t work because of overlapping peaks with these other hundreds of compounds. It’s a difficult foray to start out in this business and make it very far. There’s a very steep learning curve and it’s not often when running a commercial lab that you have the luxury of doing a lot of method development for brand-new methods on brand-new matrices for which you don’t really have much information to go on. But all of these things definitely make it interesting, and we’ve got a really top-notch science team here and that makes it fun. We’ve had a lot of success. It’s been a journey, but at Steep Hill we have really progressed the science a long way in the past couple of years.
Q: Is there any chance that the federal government will eventually come up with regulations for medical cannabis?
A: The federal government is bound by the DEA’s decisions to continually keep cannabis on the Schedule I list, so no federal government organization works with any cannabis company because by their definition it was illegal, even though state rulings were different. Literally, they are not allowed to discuss it with you or give you advice. If you want to talk to the EPA about cannabis, they don’t want to talk to you about it. We see that changing a little bit. The EPA recently came out with some rules for disposal of cannabis, which provide limited advice. Prior to those rulings and recommendations, it made our life very difficult trying to figure out disposal of tested cannabis as a hazardous material.
Q: What are some of the biggest changes you expect to see in testing going forward?
A: One of the biggest changes I see going forward in this industry is in the microbiological testing world. First there’s the issue of, do you treat [cannabis] as a food, do you treat it like a pharmaceutical, do you treat it like an herbal product—what’s the right way to treat it? That’s an issue where there is no right answer at this point. In some cases it’s used like a pharmaceutical, in some cases it’s used like a food, and in other cases it’s used like an herbal product.
Q: What are some of the challenges you’d expect to see with those changes?
A: For a lot of jurisdictions, the microbiological counts allowed for cannabis would only be able to be reached if it were sterilized, and that’s usually not a very attractive way to go just because of the changes in the nature of the product that go along with the sterilization. But even worse is the fact that it’s becoming popular for the farmers to use what they call “microbiological teas” that are teeming with what you would call good bacteria—foliar spray that makes the plant look nice and green and fresh—and yet you’re spraying bacteria on the plant. Those samples, as you might expect, test through the roof for total aerobic counts, which would make them unfit for just about anything in the pharmaceutical industry. If the person using it is using it in the right format and isn’t immunosuppressed, these teas aren’t necessarily hazardous to the vast majority of people. But there is a subset of people who would be sensitive to them. That throws a wrench into trying to do your ordinary total aerobic count and using that as a guide to whether you need to test further for specific individual organisms. So that method of assessing the cleanliness of cannabis samples may not be as appropriate as, say, a DNA test that would specifically tell you what species or even strains of pathogenic bacteria might be present. [Currently], there’s a question about what’s the best way to test for that kind of microbiological contamination [and] there’s definitely a debate going on now about how to assure the cleanliness of the products that are being sold. That’s what I would say would be the biggest challenge.
Q: What do you expect will change the most in the industry going forward?
A: I’d say everything. Because the industry is so young and … the methods for this particular substance, this particular plant—soon to be a commodity—just don’t exist. So everything’s going to change. I’d say, for the most part, the types of instrumentation, the types of methods, and the type of standard operating procedures that we use are very similar to those in place in other related industries, though the devil is in the details due to the uniqueness of the cannabis plant. At this point in time, it looks like heavy metals testing is pretty much the same and everything else is different.
Q: What are some issues the industry runs into with samples?
A: It’s very expensive to use two pounds of cannabis oil which sells at about $100 a gram and so if you take two pounds of that, that’s about $100,000 just in material. And that’s what these standard EPA pesticide methods call for, is a couple of pounds of fruit or vegetables or whatever [you’re testing]. And that’s a pretty big pill for a producer or a manufacturer to swallow. The dollar value for cannabis wholesale by the pound is, depending on quality and time of the year and so on, somewhere between $1,000 and $3,500 a pound. That’s if you’re selling it in California. The price per pound in the state of New York is double or triple that. It depends on where you are and when you are, but that’s a lot of money any way you slice it.
Q: What are some key differences between the testing required for food and that required for cannabis?
A: Most food, most commodities, most herbal products, and most pharmaceuticals aren’t required to get third-party testing before they go to market. They generally have in-house testing that they use to protect themselves from lawsuits and so on, to make sure that the products they have going out aren’t going to hurt anybody so they don’t get sued. That’s a big incentive but they’re not required to go to a third-party tester, they just do their own and make sure they have the documentation that they need to back it up if something does go wrong. But in the cannabis industry those lawsuits do don’t go that far because with the federal status still being illegal, anything that makes it up into the federal court system generally gets tossed out on that basis, so that makes it less risky for people to [engage in risky behaviour such as using] pesticides that haven’t been approved. For the most part, people have been operating without licenses, without training or education on how to use pesticides.
On top of that, one single plant can produce on the low end, two to three pounds of usable cannabis, whereas the high end is maybe ten pounds or even more per single plant. So again, at a couple thousand dollars a pound, we’re talking each single plant being worth many thousands if not tens of thousands of dollars. If you have a few heads of lettuce in the corner of the farm that aren’t doing well, it doesn’t behoove you to spend a lot of money on pesticides to try to save them. But if you’ve got one sick [cannabis] plant infested with some pest or other, you’ve got thousands and thousands of dollars of financial incentive to do whatever you have to do to try and save that plant and save as much of the product as you can. That is one of the reasons why cannabis is unlike any of those other things.
The second reason that cannabis is special is that it’s very often inhaled and at this point in time, nobody but the insiders in the tobacco industry have any idea what kinds of problems and issues there are with inhaling certain pesticides and other toxins for lack of a better word, especially under heated conditions. So, the information is not out there for people to figure it out because [cannabis is] federally illegal and yet here we are with a substance that’s inhaled where there’s a huge financial incentive to put pesticides [on the product] even if it’s illegal and unsafe.
Then the third important reason that cannabis is different is that it is used by a lot of people as a means of relaxing and destressing and so on, similar to a glass of wine or two after dinner or after work, but then there’s the other class of people who truly use it as a medicine. There are people who are taking it for seizures, dementia, arthritis, because they’re on chemotherapy—all of these different uses. Because of the nature of the product and the way it interacts with this endocannabinoid system that more or less touches all the other systems in the human body, and generally has a positive effect, those people often have suppressed immune systems and other issues, and that also makes it special and different from other commodities. That’s another reason that you might want to have third party testing.