Cannabis Analytics Assist in Laboratory Accuracy

How did you become interested in cannabis?

Mark Lewis: Well, I’m a bit older. MTV ruled the land of information for teenagers when I was in high school. That meant that garbage in from MTV pretty much resulted in the actions that came out.

Spring break, head bangers ball, and rap city. I was a big fan of NWA and The Ghetto Boyz. So in 1991, when Dr. Dre’s album “The Chronic” dropped, I was all in. Every song was about chronic. In 1992, I attended the Dr. Dre / Ghetto Boyz concert. Most of the crowd threw joints onto the stage. After that, I was reading High Times, hunting for seeds in every bag, and officially an “activist.”

What led you to get into the analytical side of the cannabis industry?

Lewis: My favorite subject in high school was chemistry. In fact, I used to wear a 100% hemp t-shirt with only the tetrahydrocannabinol (THC) molecule on the front. I remember, my chemistry teacher taught me that the name and the molecule did not match. LOL, so the t-shirt was wrong. Then, in 1994, I attended Indiana University at Bloomington for one year and discovered “kind bud” for the first time. We had to keep our nugs in the black plastic 35 mm film cases to contain the smell. I was always curious as to why I preferred the taste or smell of one over another, and also why some plant’s highs were more enjoyable than others. Some of the “weed” was great for football practices, while others were good for studying. So, I continued my focus on chemistry and after receiving my bachelors in chemical engineering, I chose to earn a PhD in chemistry with a focus on natural products.

Can you tell us a little about Napro Research (1)?

Lewis: Napro was founded to support the research I was conducting in my garage because analytical laboratories that tested cannabis had real struggles getting the chemistry right. Some laboratories wouldn’t disclose the solvents they were using to extract the natural products. During many conversations with various laboratories, it became clear that the services they were offering were flawed. So, we started Napro with one gas chromatography system coupled with flame ionization detection and mass spectroscopy (GC–FID/MS) and one liquid chromatography system coupled with a photodiode-array detector (LC–PDA). In 2015, Napro published the first peer-reviewed validated methodology for characterizing the terpenoids and cannabinoids in cannabis. [https://pubmed.ncbi.nlm.nih.gov/26651562/ This paper became the industry standard—not only for laboratories, but also for instrument manufacturers. During that time, we developed many different services that were all rooted in great chemistry—from quality control specs for finished products, to quality control for testing laboratories, report formats (PhytoFacts), to deep endocannabinoid research, and product formulation. Napro is focused on biotechnology, production, new product innovation, laboratory services, and education.

What does Napro Research use to collect data?

Lewis: Napro uses all of the common instrumentation: GC-FID, GC–MS, LC–PDA, LC–MS, inductively coupled plasma-mass spectroscopy (ICP-MS), spectrometers, flash columns, and many other standard analytical instruments.

What is PhytoFacts and PhytoVerify?

Lewis: PhytoFacts provide intuitive data visualizations and insights for the chemometric characterization. They display a complete chemical profile for flowers and concentrates, and incorporate the PhytoPrint, which is an advanced terpenoid visualization.

PhytoVerify is a proprietary track and trace software that is based on chemistry instead of the cultural definitions such as Indica, Sativa, and hybrid. Supply chains are getting more sophisticated, and streamlining production is front and center for Napro. Thus, all plants, plant components, biomass, extract batches, and so forth are all sorted in the background of PhytoVerify by their chemical classification (see PhytoFacts). This means that regardless of “common name” or “strain name” flowers, trim, kief, and so on are all batched based on their chemical profiles. Limonene-dominant, high-THC is batched with other limonene-dominant, high-THC varieties, and so on. Because we service the most sophisticated breeding programs in the world, the software really helps to expedite searches based on chemistry. One of our breeding partners has more than 1300 parental lines in development. Could you imagine how difficult it would be to create common names and keep all those chemistries organized?

Can you describe some of your ideas and findings from your publication, “Pharmacological Foundations of Cannabis Chemovars” (2)?

Lewis: First, working with Dr. Ethan Russo was a fantastic experience. It was great to lean on his breadth and depth of clinical knowledge while tying it together with analytical chemistry and truly exotic hybrids. Dr. Russo has been a preeminent advocate for maximizing the therapeutic value of the plant and I was fortunate to be able to collaborate with him on this paper. The most valuable aspect of the paper and the underlying research was the invention of hybrids that all tasted and smelled the same, but had very different cannabinoid profiles (and vice versa). These cultivars enable Napro to deeply research the entourage effect compound by compound, as well as help to provide the world with a comprehensive toolkit for properly researching plant formulations. This was a first-of-its-kind and reflects the type of groundbreaking work on which we are focused day in and day out.

What research opportunities are you involved in for terpenes and cannabinoids?

Lewis: There is no end to the opportunities in sight, especially with the toolkits and families of plants discussed above and in the Pharmacological Foundations paper, because all of the major terpenes are represented in a host of hemp and cannabis cultivars. The future is looking quite science-fictiony for the cannabis industry. From teatrahydrocannabivarinic acid (THCVA) and cabbabidivarinic acid (CBDVA) to cannabichromenic acid (CBCA) and other rare cannabinoids. I’m excited for researchers to get their hands on these cultivars.

Can you describe what cannabis chemovars are?

Lewis: A chemovar is a term coined by Arno Hazekamp and is simply defining a plant based on the chemistry in the final harvested product. The classification system developed for the PhytoFacts report format is essentially a chemovar sorting system. For example, if a given chemovar’s class code is LXX1G, then it’s a limonene-dominant, type I (mostly tetrahydrocannabinolic acid [THCA]), and the ‘G’ denotes cannabigerolic acid (CBGA) as the second most abundant cannabinoid. That’s the plant’s chemistry and referencing plants by their chemical makeup invites calling the plant a chemovar. As for another example, TCX3V is a hemp chemovar with terpinolene and b-caryophyllene as dominant terpenes, a type III (mostly cannabidiol [CBD]), and the second most abundant cannabinoid is CBDVA.

What kind of testing methods do you use for cannabis and hemp? How did you standardize your methods to help organize the testing industry (3)?

Lewis: See the methodology paper by Giese and colleauges from 2015v(4).

Do you see inaccuracies in laboratories testing for THC and other cannabinoids?

Lewis: Yes, in some cases, we work directly with compliance laboratories to ensure the quality of their products and troubleshoot root cause for the emergence of errors.

Do you have any advice for those looking to get into the cannabis industry?

Lewis: Be professional and know that many changes are coming to support a more sophisticated supply chain, marketplace, and perhaps most importantly, regulatory framework (that is, Food and Drug Administration [FDA]). Tailored experiences, product safety, mood enhancement, chemical properties, and a focus on satisfaction are the future of product development.

What kind of policies or legal measures do you hope to see in the next few years for the cannabis industry in regard to testing and certifications?

Lewis: First, it would be great if legislators could be educated enough to realize that hemp and cannabis are the same plant with different chemistries. The separation of these into two different silos has created a new “designer” black market that is dangerous to the public. Instead, these two plants should be regulated by the same agencies and a THC limitation put into place to address public health concerns. This could gain cannabis and hemp a generally recognized as safe (GRAS) certification that could then help awareness and safe access. (Please do not demonize me for suggesting a THC limitation; I am extremely well informed because of the depth and breadth of our research.) It doesn’t take much to get people high, but it also doesn’t take many “bad experiences” to ruin it for the rest of us. So, go full speed, have fun, but keep the THC at a reasonable level. You can always take a few more hits, or even a lot more hits, but if too many kids have bad trips because they got a hold of a 1000 mg edible, we’re in trouble. These are the kinds of negative consequences that could shutter the marketplace.

Is there anything else you would like to add?

Lewis: Another idea for a safer marketplace would be to explore requiring a CBD “buffer” to be included in THC plants as has been proposed by the European drug policy group, Transform, and explored by various regulatory authorities. Federal law required car manufacturers to include seatbelts into all new cars beginning in 1968 and 16 years later, New York became the first state to mandate that drivers use a seatbelt. Today, all but one state requires adult front seat occupants to wear a seatbelt—use has climbed from 14% in the early 1980s to over 90% today. A CBD buffer is much like a seatbelt; it allows you to enjoy THC and all of its positive effects and simultaneously protect yourself from certain adverse events. We drive cars regularly and despite strong early opposition to mandatory seat belt laws, today, most drivers understand the role of the seatbelt in protecting them on the road.

References

1. https://www.naproresearch.com
2. https://pubmed.ncbi.nlm.nih.gov/29161743/
3. https://terpenesandtesting.com/phytofacts-standardizing-the-way-we-talk-about-terpenes/
4. https://phytofacts.info/resources/methods.pdf.

Mark Lewis of Napro Research works to support the research and development of plant-based therapeutics and related technologies through cannabinoid genetics. His targeted breeding program provides patented and award-winning chemovars to farmers and others interested in advancing the market. He created the chemometric visualization tool PhytoFacts and co-authored the paper “Pharmacological Foundations of Cannabis Chemovars” paper with Dr Ethan Russo that highlights examples of Napro’s breeding accomplishments which serve as a critical foundation for further research.