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Busting the THC Myth: When it Comes to the Best User Experience, Terpenes Reign Supreme

By Mark Lange, PhD
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The scent of pine from your Christmas tree. The fragrance of a ripe summer peach at the farmer’s market. The whiff of eucalyptus and lavender that greets you when you enter a spa.

Aroma is a keystone in how we experience the world. In any given environment, aroma can help shape your mood, solidify memories and instantly transport you to another place or time.

I have focused my career on studying the fascinating compounds that are often behind these powerful aromas: terpenes. They form the largest class of natural products (compounds produced by living organisms), found in nearly all living beings. There are around 50,000 currently known terpenes in nature — with potentially thousands yet to be discovered.

Terpene-rich plants you might be most familiar with are lavender, mint, oranges (in the peel), and yes, cannabis. In recent years, terpenes have rightfully become a central discussion in the recreational cannabis world. This is because terpenes — not THC level, not “Indica-Sativa” classification — are a key determinant of cannabis’s effect, both psychoactive and non-psychoactive. But the current lack of prioritization and understanding of the crucial role terpenes play may put the collective quality of U.S. cannabis at risk.

At this crucial inflection point for legal cannabis, on its path to becoming a $70 billion dollar global industry by 2028, we need to ensure that everyone across the cannabis space, from breeders to testers, growers and consumers, understands which traits to prioritize for a cannabis world brimming with diversity and predictable effects.

What the cannabis industry has to lose 

What do we lose if the cannabis industry continues to scale without a clear understanding of the compounds that define the uniqueness of each variety?

There is a ripple effect across the ecosystem. For cannabis testing labs, focusing on only twenty of the most dominant terpenes means we are missing out on tapping into potentially over a hundred of less common terpenes in cannabis. For the cannabis consumer, lack of understanding on the breeding and testing side may make it difficult to find cannabis that delivers on its promised effect time and time again. And, most detrimentally for breeders, not understanding the direct correlation between genetics and the formation of terpenes means we will have increasingly fewer terpene profiles and combinations to work with, especially when the industry-dominant focus has been on cannabinoid potency.

Let’s explore some misconceptions related to potency. In recent years, many breeders have prioritized high THC levels over genetic diversity. Consumers often associate high THC levels and that telltale strong “skunky” aroma with a strain’s quality and effect, when in reality, these are poor indicators of potency. (In fact, recent research indicates that this specific cannabis aroma is caused by a family of sulfur compounds.) Terpene profiling is a much more accurate way to determine a variety’s given effect. In focusing too much on increasing THC, breeders miss out on the true potency powerhouse: tapping into the terpene diversity that’s out there.

Terpenes are responsible for giving flowers (including cannabis), fruits and spices their distinctive flavors and aromas. Common terpenes include limonene, linalool, pinene and myrcene.

To illustrate the impact of breeding practices that prioritize crop yield over product quality, I first have a question for you: When was the last time you enjoyed a really good tomato?

If you’re lucky enough to have a great farmer’s market nearby, maybe you purchased an heirloom tomato at peak freshness last August. It was likely fragrant, flavorful and didn’t need much preparation to be enjoyable.

Or maybe you can’t remember the last time you’ve eaten a good tomato, as the last standard grocery store tomato you purchased was watery, tasteless and essentially scentless.

Tomatoes are a prime example of what is unfortunately true for a whole host of traditional crop plants in the U.S. When yield is the goal, flavor and aroma profiles often suffer. The culprit: lack of genetic diversity in the breeding process. The tragedy of the tomato serves as a harbinger for the cannabis industry — and we can draw parallels to what we’ve seen happen to cannabis.

What the cannabis industry should do: Tap into the diversity that’s out there

An important aspect of preventing cannabis from going the way of the tomato is to better understand the genes that generate these different terpene profiles. Different cultivars with varying aromas will hold different collections of genes. We as an industry must learn more about which terpenes correlate with desirable aromas, and then access already existing genetic diversity.

We have just begun to scratch the surface of the potential of terpenes in cannabis. With the right alignment across the industry and a stronger focus on genetics in breeding, we will see the rise of completely unique cannabis varieties. They will smell like lavender, lilac, orange peel or even brand-new aromas that have yet to be discovered. To ensure this future, we need to prioritize the right traits and the right genetics.

A Conversation with the Founders of Veda Scientific: Part Two

By Aaron G. Biros
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This is the second piece in a two-part conversation with the founders of Veda Scientific, CEO Leo Welder and CSO Aldwin M. Anterola, PhD. To read part one, click here.

In part one, we chatted about their backgrounds, their approach to cannabis testing, their role in the greater industry and how they came into the cannabis industry.

In part two, we’re going down a few cannabis chemistry rabbit holes and realizing that what we don’t know is a lot more than what we do know. Join us as we delve into the world of volatile compounds, winemaking, the tastes and smells of cannabis, chicken adobo and much more.

Aaron: Alright so you mentioned the GCxGC/MS and your more advanced terpene analysis. How do you envision that instrument and that data helping your customers and/or the industry? 

Leo: Some of the things that we envision will help is a better understanding of what compounds and what ratios will lead to desirable outcomes, things like better effects, aroma and flavor. By better understanding these things it’ll help the industry create better products.

I have a personal connection to this. My wife has some insomnia and she’s always had to take various forms of OTC pharmaceuticals to help with sleep. She tried using a 1:1 vape pen and it was a miracle worker for her for several months. The local dispensary had a sale on it, and she bought some extra. Unfortunately, even though she used it the same way as before, she got very serious anxiety, which obviously didn’t help her sleep. Every time she used the vapes from this same batch, she felt the same extreme anxiety. Sadly, she now had a lot of this product that she couldn’t use because it kept her awake rather than helping her sleep, so she went back to trying other OTC solutions. That’s a problem for both consumers and the industry at large. If people find something that works and provides a desired effect, they need to be able to rely on that consistency every time they purchase the product, leading to similar outcomes and not exaggerating the problem. That’s why I think consistency is so important. We’re taking two steps forward and one back when we have inconsistent products. How do we really grow and expand the availability of cannabis if we lose trust from our consumer base? What a lab can do and what we can do is provide data to cultivators and manufacturers to create that consistency and ultimately allow the market to expand into other demographics that are currently wary and less tolerant of that variance.

Vials of cannabis samples being prepped for collaborative research with the CESC

On a similar note, we have been having a lot of discussions with the CESC [Clinical Endocannabinoid System Consortium] down in San Diego. They are an advanced cannabis research group that we have been working with for over a year. We’ve started looking at the idea of varietals. To be more specific, because I’m not a wine connoisseur, varietals are the pinot noirs, the cabernets and sauvignon blancs of the industry. In the cannabis industry, consumers have indica and sativa, though we still argue over what that concept really means, if anything. But for the sake of argument, let’s say we have this dichotomy to use as a foundational decision tool for consumers- call it the red and white wine of the cannabis industry. How inaccessible would wine be if we just had red or white? Imagine if you went to a dinner party, really liked the wine you were drinking, and the host could only tell you that it was a red wine. You can’t go to a wine store and expect to find something similar to that wine if the only information you have is “red.” At a minimum, you need a category. So that’s what varietals are, the categories. The data that we can produce could help people in the industry who identify and establish the varietals based on their expertise as connoisseurs and product experts to find what those differences are chemically. Similarly, we’re also looking at appellation designations in California. So, we want to help provide tools for farmers to identify unique characteristics in their flower that would give them ability to claim and prove appellation designation.

Aldwin: The GCxGC/MS allows us to find more things besides the typical terpene profile with 20 or 40 terpenes. It allows us to go beyond those terpenes. The issue sometimes is that with a typical one-dimensional GC method, sure you could probably separate and find more terpenes, but the one dimension is not enough to separate everything that coelutes. And it’s not just terpenes. Some terpenes coelute with one another and that’s why people can see this inconsistency. Especially if you use a detector like an FID, we can see the compound limonene on the chromatogram, but there’s another terpene in there that is unknown that coelutes with limonene. So, this instrument is helping us get past the coeluting issue and solve it so that we know what peaks represent what terpenes.

The other bonus with our GCxGC/MS is that the coeluting compounds that were masked behind other terpenes are now revealed. There is a second dimension in the chromatogram where we can now detect some compounds in cannabis that would be hiding behind these large peaks if it were just a one-dimensional GC. Besides terpenes, we’ve found esters, alkanes, fatty acids, ketones, alcohols and aldehydes, as well as thiols. The terpenes are so plentiful in cannabis that these other compounds present at lower levels cannot be seen with just one-dimensional GC. There are just so many compounds in cannabis that the ones in small amounts are often masked. My analogy to highlight the importance of these minor compounds is like a dish; I am from the Philippines and I like chicken adobo. My father does it differently from my mom and someone else will do it differently in a different region. The base of the sauce is vinegar and soy sauce, but some people will do it differently and maybe add some bay leaf, garlic, pepper, or a touch of another spice. It’s still chicken adobo, but it tastes differently. Just like in cannabis, where yes, you have the same amount of THC in two different plants, but it’s still giving you a different experience. Some people say it’s because of terpenes, which is true in a lot of cases, but there are a lot of other volatile compounds that would explain better why certain dishes taste different.

2-D chromatogram showing four peaks separated by the GCxGC. With a traditional 1-D chromatogram, these peaks would coelute and not separate.

Leo: There’s been some recent developments too here that show it’s very significant. It’s like the difference between bland and spicy. And it could be the thiol. We identified a thiol in cannabis at the same time as other scientists reported an article that just came out on this subject.

Aldwin: Thiols are sulfur containing compounds that produce very powerful odors, giving cannabis the skunky smell. Skunks also produce thiols. It is very potent; you only need a little bit. It turns out that yes, that paper described thiols and we also saw them in our GCxGC/MS. These are the kinds of things that the GCxGC can show you. Those very tiny amounts of compounds that can have a very powerful impact. That’s one that we know for sure is important because it’s not just us that’s finding out that GCxGC can detect this.

Not everything is about THC or the high amount of the compounds in the flower. This paper and our concurrent findings indicated that the skunkier smelling strains contained very small amounts of thiols and you can recognize their presence quite readily. It’s not a terpene, but it’s producing a distinct flavor and a powerful smell.

Aaron: Okay, so why is this useful? Why is it so important?

Leo: I would say two things in particular that we know of that are issues currently, both related to scents. We mentioned this earlier. We do know that farmers with breeding programs are trying to target particularly popular or attractive scent profiles, whether it be a gas or fruity aroma. Right now, when they get the flower tested and review the terpene profile, it isn’t enough information to help them identify what makes them chemically distinct. We hear time and again that farmers will say their terpene profile is not helpful in identifying specific scents and characteristics. They are looking for a fingerprint. They want to be able to identify a group of plants that have a similar smell and they want a fingerprint of that plant to test for. Otherwise, you have to sniff every plant and smell the ones that are most characteristic of what they’re targeting. For larger operations, walking through and smelling thousands of plants isn’t feasible.

Once we can identify that fingerprint, and we know which compounds in which ratios are creating the targeted aroma, we can run tests to help them find the best plants for breeding purposes. It’s about reproducibility and scalability.

Another value is helping people who are trying to categorize oils and strains into particular odor categories, similar to the varietals concept we’ve been talking about. Currently, we know that when manufacturers send multiple samples of oils with the same or similar scent to be tested, the results are coming back with significantly different terpene profiles. There is not enough data for them to chemically categorize products. It’s not that their categories are wrong, it’s just that the data is not available to help them find those boundaries.

Those are two issues that we know from conversations with customers that this particular piece of equipment can address.

Aldwin: Let’s start from what we find, meaning if you are using the GCxGC/MS, we are finding more terpenes that nobody else would be looking at. We have data that shows, for example, that certain standards are accounting for 60% or so of total terpene content. So a large percent is accounted for, but there is still quite a bit missing. For some strains there are terpenes that are not in common reference standards. Being able to know that and identify the reason why we have different terpenes in here unaccounted for is big. There are other things there beyond the standard terpenes.

Dr. Anterola working with the GCxGC/MS

What excites me sometimes is that I see some terpenes that are known to have some properties, either medical or antibacterial, etc. If you find that terpene looking beyond the list, you’ll find terpenes that are found in things like hardwood or perfumes, things that we don’t necessarily associate with the common cannabis terpenes. If you’re just looking for the limited number of terpenes, you are missing some things that you might discover or some things that might help explain results.

Leo: It’s also absolutely necessary for the medical side of things. Because of the federal limitations, cannabis hasn’t been researched nearly enough. We’re missing a lot of data on all of the active compounds in cannabis. We are finally starting to move into an era where that will soon be addressed. In order for certain medical studies to be successful, we need to have data showing what compounds are in what plants.

Drs. John Abrams and Jean Talleyrand of the CESC launched the Dosing Project in 2016. They have been studying the impact of cannabis flower for indications such as pain mitigation and sleep improvement, and now more recently mood, and appetite modulation. They categorize the THC & CBD content as well as flower aroma into 3 cannabinoid and 3 odor profiles. They are able to acquire quite a bit of data about how odor correlates with the outcomes. Because they were initially limited in terms of underlying natural product content data, they contacted us when they found out we acquired this equipment in 2020, and have stated that they are certain the data we will now be producing will take their research to the next level of understanding.

Aldwin: For quality control you are looking at specific things that would reflect properties in cannabis. There should be a 1:1 correspondence between properties observed and what we are measuring. The current assumption is that the terpenes we are looking at will tell us everything about how people would like it, with regards to flavor and smell preference. But we know for a fact that the limited terpenes most labs are measuring do not encapsulate everything. So, it is important for QC purposes to know for this particular strain or product, which everyone liked, what is it in there that makes everybody like it? If you just look at the typical terpene profile, you’ll find something close, but not exact. The GCxGC/MS shows us that maybe there’s something else that gives it a preferred property or a particular smell that we can explain and track. In one batch of flower, the consumer experiences it a certain way, and for another batch people experience it another way. We’d like to be able to understand what those differences are batch to batch so we can replicate the experience and figure out what’s in it that people like. That’s what I mean by consistency and quality control; the more you can measure, the more you can see.

Aldwin: Speaking to authenticity as well, in a breeding example, some growers will have this strain that they grew, or at least this is what they claim it to be, but what are the components that make those strains unique? The more analytes you can detect, the more you can authenticate the plant. Is this really OG Kush? Is this the same OG Kush that I’ve had before? Using the GCxGC/MS and comparing analytes, we can find authenticity in strains by finding all of the metabolites and analytes and comparing two strains. Of course, there is also adulteration- Some people will claim they have one strain that smells like blueberries, but we find a compound in it that comes from outside of cannabis, such as added terpenes. Proving that your cannabis is actually pure cannabis or proving that something has added terpenes is possible because we can see things in there that don’t come from cannabis. The GCxGC/MS can be used as a tool for proving authenticity or proving adulteration as well.  If you want to trademark a particular strain, we can help with claiming intellectual property. For example, if you want to trademark, register or patent a new product, it will be good to have more data. More data allows for better description of your product and the ability to prove that it is yours.

Leo: One thing that I think is a very interesting use case is proving the appellations. It is our understanding that California rolled out a procedure for growers to claim an appellation, but with strict rules around it. Within those rules, they need to prove uniqueness of growing products in specific regions. The GCxGC/MS can help in proving uniqueness by growing two different strains in two different regions, mapping out the differences and seeing what makes a region’s cannabis unique. It’s valuable for growers in California, Oregon, Colorado to be able to prove how unique their products are. To prove the differences between cannabis grown in Northern California versus plants grown along the Central Coast. And of course, for people across the world to be able to really tell a story and prove what makes their cannabis different and special. To be able to authenticate and understand, we need to have more comprehensive data about properties in those strains. It could be terpenes, it could be esters or thiols. That’s what we’re excited about.

Aaron: From your perspective, what are some of the biggest challenges and opportunities ahead for the cannabis industry?

Aldwin: Getting ready for federal legalization is both a challenge and opportunity. A challenge because when it is federally legal, there will be more regulations and more regulators. It is also a challenge because there will be more businesses, more competition, that might get into the industry. It is opening up to other players, much bigger players. Big tobacco, mega labs and massive diagnostic testing companies might participate, which will be a challenge for us.

But it’s also an opportunity for us to serve more customers, to be more established at the federal level, to move to interstate commerce. The opportunity is to be ready here and now while other people are not here yet.

Another challenge and opportunity is education. Educating consumers and non-consumers. We have to realize and accept that cannabis is not for everybody, but everyone is a stakeholder, because they are our neighbors, parents or part of the medical establishment. It would be a disservice not to educate the non-consumers.

The medical establishment, they don’t have to be consumers but they need to know about cannabis. They don’t know as much as they should about cannabis and they need to know more, like how it could affect their patients for better or for worse, so they know how to help their patients better. There could be drug interactions that could affect the potency of other drugs. They need to know these things. Educating them about cannabis is a challenge. It’s also an opportunity for us to now come in and say that cannabis is here to stay and be consumed by more and more people, so we better know how to deal with it from a medical perspective.“This bucking bronco of a growth style will throw a lot of people off. We need to figure out what we can grab on to and ride out these waves.”

Law enforcement needs to be educated too. What THC level in the blood indicates impairment? It is still a challenge because we’re not there yet, we don’t have that answer quite yet. And it’s an opportunity to help educate and to find more answers for these stakeholders, so we can have regulations that make sense.

Leo: To Aldwin’s point, the biggest opportunity comes along with federal legalization as well as expanding the customer base beyond the traditional market. Since adult use was legalized in CA, we haven’t yet seen the significant expansion of the consumer population. We’re primarily seeing a legal serving of the market that already existed before legalization.

The reality is cannabis can be used in different ways than what we think of. We know it has medical benefits and we know it is enjoyed recreationally by people looking for high THC content and the highest high. But there is also this middle ground, much like the difference between drinking moonshine and having a glass of wine at dinner. The wine at dinner industry is much bigger than the mason jar moonshine industry. That’s really where the opportunity is. What’s the appeal to the broader market? That will be a big challenge, but it’s inevitable. It comes from everything we’ve talked about today, consistency in products, educating people about cannabis, normalizing it to a certain degree, varietals and appellations.

As an entrepreneur, I’m looking at this from a business perspective. Everyone talks about the hockey stick growth chart, but it is a very wavy hockey stick. I expect to see very significant growth in the industry for a while, but it will have a lot of peaks and valleys. It’ll essentially be whiplash. We are seeing this in California right now, with sky high prices in flower last year down to bottom of the barrel prices this year. We have to all figure out how to hang on. This bucking bronco of a growth style will throw a lot of people off. We need to figure out what we can grab on to and ride out these waves. The good ones will be fun and the bad ones will be painful and we know they are coming again and again and again. That’s the biggest challenge. People say ‘expect tomorrow to look a lot like today,’ but you really can’t expect tomorrow to look anything like today in the cannabis industry. Tomorrow will be totally different from today. We need to figure out, within all this chaos, what can we hang on to and keep riding the upward trajectory without getting thrown off the bronco.

A Conversation with the Founders of Veda Scientific: Part One

By Aaron G. Biros
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Leo Welder, CEO of Veda Scientific, founded the business with Aldwin M. Anterola, PhD in July of 2019. A serial entrepreneur with experience in a variety of markets, he came to the industry with an intrigue for cannabis testing and analysis. After teaming up with Dr. Anterola, co-founder and chief science officer at Veda Scientific, they came together with the purpose of unlocking possibilities in cannabis. From the beginning, they set out with a heavy scientific interest in furthering the industry from a perspective of innovation and research.

Through discussing their clients’ needs and understanding their complex problems, the two realized they wanted to start a lab that goes well beyond the normal regulatory compliance testing. Innovation in cannabis looks like a lot of things: new formulations for infused products, better designs for vaping technology or new blends of genetics creating unique strains, to name a few. For the folks at Veda Scientific, innovation is about rigorous and concentrated research and development testing.

With the help of some very sophisticated analytical chemistry instruments, their team is working on better understanding how volatile compounds play a part in the chemometrics of cannabis. From varietals and appellations to skunky smells, their research in the chemistry of cannabis is astounding – and they’ve only begun to scratch the surface.

In this two-part series, we discuss their approach to cannabis testing, their role in the greater industry as a whole and we go down a few cannabis chemistry rabbit holes and find out that what we don’t know is a lot more than what we do know. In part one, we get into their backgrounds, how they came into the cannabis industry and how they are carving out their niche. Stay tuned for part two next week where we delve deep into the world of volatile compounds, winemaking, the tastes and smells of cannabis and chicken adobo.

Aaron G. Biros: Tell me about how you and your team came to launch Veda, how you entered the cannabis space and what Veda’s approach is to the role of testing labs in the broader cannabis industry. 

Leo Welder, CEO of Veda Scientific

Leo Welder: I’m an entrepreneur. This is my third significant venture in the last fifteen years or so. So, I was intrigued by cannabis legalization broadly, because it is such a unique time in our history. I was always interested in participating in the industry in some way, but I didn’t see where would be a good fit for me. I used to meet monthly with a group of friends and fellow entrepreneurs for dinner and discussions and one member started working on the software side of the industry. He mentioned the testing element of cannabis in one of our meetings. I latched on to that and was intrigued by the concept of testing cannabis. I began to research it and found the role that testing plays in the cannabis industry is really significant. I found out that regulators rely pretty heavily on labs to make sure that products are safe, labels are accurate and that consumers have some protections. So, I thought that this is a space that I thought I could really find a calling in.

So, from that point I knew I needed to find a subject matter expert, because I am not one. I have business skills and experience in some technical fields but I am not a cannabis testing expert by any means. So, with that I started to look at a few different markets that I thought may have opportunity for a new lab, and I came across Aldwin’s business; he had a cannabis testing lab in Illinois at that time. I reached out to him, talked to him about my vision for the space and his thoughts and his vision and we really started to come together. From there, we researched various markets and ultimately chose to approach Santa Barbara County as our first foray together into the cannabis testing market.

Aldwin M. Anterola: As Leo mentioned, he was looking for a subject matter expert and I am very much interested in plant biochemistry. Which means I like to study how plants make these compounds that are very useful to us. For my PhD [in plant physiology], I was studying how cell cultures of loblolly pine produce lignin. Our lab was interested in how pine trees produce lignin, which is what makes up wood. Wood comes from phenolic compounds. You’ve probably heard of antioxidants and flavonoids – those are phenolic compounds. After my PhD, I wanted to do something different so I decided to work with terpenes.

I picked a very important terpene in our field, an anti-cancer compound called Taxol, produced from the bark of the yew tree. You have to cut trees to harvest it. We have ways of synthesizing it now. But at that time, we were trying to figure out how the tree produces that terpene. Of course, I’m interested in any compound that plants make. My interest in terpenes led me to cannabinoids which turn out to be terpenophenolics, thus combining the two interests in my professional field.

Aldwin M. Anterola, PhD, Co-Founder and Chief Science Officer at Veda Scientific,

So that’s the scientific and intellectual side of why I became interested in cannabis, but practically speaking I got into cannabis because of a consulting offer. A company was applying for a cultivation license, wanted to have a laboratory component of their business in their application, and hired me to write that part of their application. I was very familiar with HPLC, and had a GC/MS in the lab. I also have a background in microbiology and molecular biology so I can cover every test required at that time, and I knew I could research the other analytical techniques if necessary.

So, they did not get the license, but I figured I’d take what I wrote, once I received permission, and set up an independent laboratory together. But it’s hard to run a lab and be a professor at the same time. Also, the busines side of running a lab is something that I am not an expert in. Fortunately, Leo found me. Before that, I really got excited about this new industry. The concept of cannabis being now accessible to more people is so interesting to me because of how new everything is. I wanted to be involved in an industry like this and help in making it safe while satisfying my curiosity in this new field of research. As a scientist, those are the things that excite us: the things we didn’t have access to, we can now do. It opens up a whole new room that we want to unlock. It was my intellectual curiosity that really drove me. This opened up new research avenues for me as well as other ventures if you will. How can I be more involved? I thought to myself.

SIU boasts an impressive cannabis program, thanks largely to Dr. Anterola’s work there.

Back in 2014, I introduced cannabis research to our university [Southern Illinois University] and set up an industrial hemp program, which was DEA-licensed I gathered faculty that would be interested in studying hemp and cannabis and we now have a whole cannabis science center at the university. I teach a course in cannabis biology and because I also teach medical botany to undergraduate students, I was able to introduce [premed] students to the endocannabinoid system. Anyway, I can go on and on.

Outside of that I became involved with the AOAC and ASTM, and became a qualified assessor for ISO 17025:2017. I have been a member of the American Chemical Society since 2000 but there were no cannabis related activities there yet until relatively recently. But when they had the new cannabis chemistry subdivision, I am happy to participate in there as well . There are many avenues that I took to begin dabbling with cannabis, be it research, nonprofits, teaching, testing and more. Cannabis has basically infiltrated all areas of what I do as an academic.

Leo: I read his resume and I was like this is the guy! So back to your question, what’s Veda’s role as a testing lab in this space? What are we trying to build? We spent a lot of time trying to figure out what we wanted to be in this space. We came to understand that labs are not the tip of the spear for the market; that would be the growers, the retailers and the processors. We are a support, a service. We see ourselves as a humble, but competent guide. We provide the data for the tip of the spear, the people pushing the industry forward with support, data and the services to make sure they have the tools they need to build these great companies and great products with good cultivation practices and more, leading everyone to the next level of the cannabis industry. Our job is to support innovation, to provide quality compliance testing, to of course ensure safety, while also providing great R&D to these innovative companies.

Aldwin: I’d like to add a bit to that thought. Okay so that’s who we are, but what are we not? Because as Leo said I had a testing lab before we met [Advanced Herbal Analytics]. From there, I approach it as safety testing, making sure that before it gets to the end consumer, we are sort of like gate keepers keeping consumers safe. That’s one side to it, but we are not the people who are trying to make sure that none of the products get to the market. For some, that’s how we’re treated as.

People often look at testing labs like the police. We are not the people trying to limit products to market. Our approach is not to find faults. There is another way of being a testing lab that is less about finding faults in products and more about finding uniqueness. What makes your product different? With this new approach, we are much more focused on helping the best products make it to the shelves.

Aaron: Given that all state licensed labs have to provide the same tests as the other labs in that state, how does Veda differentiate itself?

Leo: Location was the first thing. We picked Santa Barbara County intentionally. We knew that some of the biggest operators, some of the most forward-thinking innovators were setting up shop here. Looking down the road, not just this year or next year but very long term, we wanted to start building a great, sustainable company. We wanted to build a brand that those kinds of companies would be receptive to. Building better and greater products. There’s one other lab in the county and that’s it. Whereas there are clusters of labs in other parts of the state. Part of the draw to Santa Barbara for us was that it is such a small, tight-knit community. We have worked very hard to build relationships in our community and to understand their challenges, helping them however we can.

Location and relationships. Getting to know the challenges that different size customers face, be it our greenhouse customers versus outdoor customers, or large-scale operations versus smaller manufacturing operations, the challenges are all different. Some people care about turnaround times, some more about R&D. If we understand our client’s problems, then we can provide better service. We see ourselves as problem solvers. We lean heavily on our technical team members like Aldwin, who not only have tremendous amounts of experience and education, but also great networks to utilize when a customer needs help, even when it falls outside of our local expertise.

The GCxGC/MS instrument, used for Veda’s advanced R&D testing

Last but certainly not least is the advanced R&D testing that we do. When we first started, we started talking to farmers and manufacturers trying to understand their challenges. What data were they not getting? How would a testing lab better serve them? So, we started investing strategically in certain instruments that would allow us to better serve them. We’ll get into this later as well, but we invested in a GCxGC/MS, which allows us to get more visibility into things beyond the typical panels, like more terpenes and other volatile compounds including thiols and esters. We did that because we knew there is value in that. The data our customers were getting prior just wasn’t enough to put together really great breeding programs or to manufacture really consistent products, you know, to move toward that next level of innovation in the industry.

Aldwin: Leo mentioned advanced R&D and it’s basically the same approach that I mentioned before. It’s not just telling you what you can and cannot do. It’s about asking them what do you want to do and what do you want from a lab? If we have a problem, let’s see if we can solve it. That’s how the GCxGC/MS came into play because we knew there was a need to test for many terpenes and other volatile compounds. The common complaint we received was why two terpene profiles differ so much from each other, even from the same genetics.

This is something that would actually give the customer, the cultivator or the manufacturer: data about their product that they can actually use. For consistency, for better marketing and other reasons. We are trying to help them answer the questions of ‘how can I make my product better?’

You know, for example, clients would tell us they want something that has a specific taste or smells a certain way. Nobody is telling them what makes the flavor or smell. There is a need there that we can fill. We are trying to provide data that they, the customers, need so that they can improve their breeding programs or their formulations. Data they can use, not just data they need in order to comply with regulations. They would ask us what we can do. We listen to our customers and we try and help as best we can. We don’t know every answer. We are discovering there is a lot more to terpenes than what you can find on a traditional one dimensional gas chromatogram. Some of the terpene data that our clients had previously is not really actionable data, which is where the GCxGC/MS is helping us.


In part two, we delve deep into the world of volatile compounds, winemaking, the tastes and smells of cannabis and chicken adobo. Click here to read part two. 

Leaders in Cannabis Formulations: Part 4 – LifeTonic

By Aaron Green
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Russell is the CEO of NES Technology Holdings, a technology development and marketing company that operates Vapor Distilled and LifeTonic Brands. NES Technology Holdings has invented a technology portfolio of more than 160 granted and pending patents that cover inventions across several high-value industries, including cannabis, beverage, fragrance and nutraceuticals. The company is currently in license acquisition diligence processes with 7 of world’s 10 largest fragrance companies and has received a joint venture offer from a $3 billion fragrance company to produce perfumes with its extraction technology. It is also launching ionized cannabis beverage products that provide effects as quickly as alcohol in Nevada and Colorado this fall.

Vapor Distilled invented and commercialized an evaporative extraction process with 40 international patents granted and pending that, along with CO2 extraction, is one of only two fundamentally new extraction processes invented in the last 50 years. Instead of using solvents or hydrocarbons to extract oils from plants, evaporative extraction directly evaporates essential oils from plants and condenses the evaporated compounds into an extract. The process takes less than two seconds to complete and extracts higher levels of volatile terpenes than existing extraction methods. Vapor Distilled has built a fleet of commercial-scale extraction machines and has supplied some of the cannabis industry’s largest brands. The company is currently licensing its evaporative extraction technology within the perfume industry and is marketing an aroma hop extract to replace the dry hopping step when making beer.

LifeTonic invented a drug delivery technology with 56 patents pending and granted, that turns oil-based plant compounds like CBD and THC into electrically charged cannabinoid ions that dissolve completely in water without emulsifiers or additives. When cannabinoids are ionized, absorption is significantly enhanced and their effects can be felt in minutes. The effects of a LifeTonic ionized CBD beverage can be felt by most people in less than 5 minutes, whereas the effects of a LifeTonic ionized THC beverage can be felt by most people in less than 8 minutes. For reference, typical onset times for cannabis beverages are 30 minutes or longer. LifeTonic beverage technology will allow cannabis beverages to work as quickly as alcohol, enabling cannabis to become a social drink.

Russell Thomas, CEO of Vapor Distilled and LifeTonic

We spoke with Russell Thomas, CEO of Vapor Distilled and LifeTonic about his cannabinoid evaporation process and rapid onset beverage technologies. Thomas is a career entrepreneur and inventor with 21 years of experience inventing and protecting intellectual property. Russell’s team has generated more than 160 granted and pending patents. Prior to entering the cannabis industry, Thomas worked in the cleantech industry.

Aaron Green: How did you get involved in the cannabis industry?

Russell Thomas: I came to the cannabis industry from the cleantech industry where I worked on technologies that improved the fuel economy of vehicles. I saw opportunities in the cannabis industry to improve cannabis extraction, which was one of the most important supply chain verticals in cannabis. Every product, from edibles to beverages and vape products, requires a cannabis extract. Any product that needs to be accurately dosed requires an extract. The old way of making edible products with cannabis butter was simply not viable as the industry matured, and most people were rapidly moving away from smoking cannabis and embracing vape products. Even with the entire industry almost completely dependent on extraction, no fundamental innovation was occurring. The primary ways that cannabis was being extracted were chemically intensive. The cleaner methods, such as CO2 extraction, were slow and expensive for terpene recovery. I saw this as a great opportunity to provide a better solution within a primary funnel of the cannabis supply chain.

We commercialized an extraction technology that evaporates cannabinoids directly from plant material in the form of vapor, and then recondenses that vapor back into an essential oil. The entire process takes less than two seconds to complete and preserves fragile terpenes. That technology, called Evaporative Extraction, is the foundation of Vapor Distilled.

Green: What timeframe was that roughly?

Thomas: We capitalized our company in 2015 and began selling wholesale extracts in 2017.

Green: Can you talk more about the evaporative extraction process?

Thomas: Our process works in a similar way to a cannabis vaporizer, but on a massive scale. Our extract is literally recondensed cannabis vapor. In one step, we extract, refine, and activate cannabinoids. On one end, plant material goes in the machine, and on the other end, extract and depleted plant material comes out. Our total extraction time is less than two seconds if you measure the time from when the plant material goes into the extractor and when the extract is condensed.

The LifeTonic logo

A continuous feed of dry plant material is introduced into a heated air stream. The air stream pneumatically conveys the plant material through a series of turbulent, heated evaporation chambers. Upon entering the evaporation chambers, volatile plant compounds are instantaneously distilled from the plant material. A centrifugal separator removes the depleted plant material from the air stream. The air stream is rapidly cooled, causing the volatile plant compounds to condense into an essential oil.

We achieve nearly total activation of THCA to THC simultaneously during extraction and, on average, we extract approximately two to four times more terpenes than a conventional extraction process. The cannabis industry is rampant with exaggeration about terpenes, but we are the only cannabis company negotiating a joint venture with a $3 billion fragrance company to produce perfumes, and I think that says a lot about our process.

Green: Is the extract coming out then as an oil?

Thomas: Our extract comes out of our machines as a fully-activated, high-terpene content, full spectrum oil. Unlike the THC crude that emerges from other processes, our extract requires no further distillation, activation or refinement. You can put it straight into a product.

Green: How about terpene recovery?

Thomas: This is by far what we do best. We excel with the recovery terpenes and volatile compounds from plant material. From day one, we noticed that our evaporative extraction process yields about two to four times more terpenes by mass compared to traditional extraction methods.

While we started as a cannabis company, we recently received a compelling joint venture offer from a $3 billion fragrance company to produce perfume products with our technology. We are also under NDA with 7 of the world’s 10 largest fragrance companies to complete diligence processes to license our extraction technology.

As part of our licensing diligence process, we are performing paid fragrance extraction research for three multi-billion-dollar fragrance companies. Our evaporative extracted fragrance extracts are presenting a broader and more complete range of volatile compounds compared reference samples. We are also seeing substantially improved yield of volatile fragrance compounds. Combined, this gives us the advantage of being able to produce more extract at a lower cost, while also producing a superior product. This combination is how licensees can take market share away from any fragrance company that does not have access to our technology, and it is why we are seeing so much rapid traction in this area.

We have also extracted hops with our technology. If you’ve ever smelled a traditional hops resin, it smells good, but the smell doesn’t fill the room. If you put just a drop of our hops extract on any surface, the entire room will smell strongly of a premium IPA beer. It’s so potent you don’t want to get it on your hands or clothes because you will smell like beer for hours. It’s powerful and wonderful stuff!

Green: What is your business model?

Thomas: At our core, we are a technology development and licensing company. We first identify what we believe to be critical verticals and bottlenecks in high-value industries, then we develop and patent highly differentiated and disruptive technology solutions that we believe exist nowhere else. We then demonstrate both market fit and viability at scale through proof-of-concept sales of branded and high-profile, white-labeled products produced with our unique technologies. Finally, we systematically license and exit the various portions our IP portfolio though the orchestration of highly competitive bidding processes that promote both defensive and strategic acquisitions of our technologies. We are currently at the final phase of our model with licensing our extraction technology, and we are receiving offers as part of a competitive bidding process.

Green: Okay, let’s change gears here and start talking more about LifeTonic and your cannabinoid ionization technology. Can you talk high level about the onset times of cannabinoids in different matrices and media?

Thomas: Through LifeTonic, we invented 56 international patents granted and pending cannabinoid ionization technology that compresses the normal onset time of cannabis beverages from 30 minutes down to just a few minutes. Our cannabinoid ionization technology can also be used as a rapid onset vape alternative when sold in a breath spray format. We are currently selling hemp-based versions of these products through LifeTonic.com, and we are bringing THC versions of these products to market in Nevada and Colorado this fall and winter under the brand name LifeTonic.

All conventional and even nano-emulsified cannabis edibles and beverages take a long time to work. A cannabis chocolate can take 45 minutes to two hours before the effects kick in. Cannabis gummies are faster, but it still takes half an hour to 45 minutes to feel the effects. The very best nano-emulsified cannabis beverages take about a half an hour to work on average, if you are lucky. That long of a time delay effectively eliminates the social aspect of consuming cannabis, so most people instead choose to vaporize or smoke cannabis.

If you look at the largest investments that have been made across cannabis, some of the most prominent have been made by alcohol companies. Constellation Brands invested nearly $4 billion into Canopy Growth, with a mission to find an alternative to alcohol in cannabis. Molson Coors has partnered with Hexo and AB InBev has partnered with Tilray, both with that same mission. Even after all this effort and investment, cannabis beverages represent just a sliver of the market because current cannabis-based beverages take too long to work. The fastest ones on the market, on average, take around a half hour to kick in.

Imagine going to a bar and knowing that every time you got a shot of tequila or a shot of whiskey it’s going to take thirty minutes or more for the effects to even begin to kick in. That would be terrible. That would be the end of social drinking. Unfortunately, that is how a conventional cannabis beverage works.

You can’t really get a social drinking experience with cannabis yet, so most people vape it because it’s fast. But a lot of people don’t want to smoke something; in fact, they don’t want to inhale at all. So, we saw beverages as a huge opportunity. How do we make cannabis beverages work as fast as alcohol? That’s what our ionization technology delivers. From all the people we’ve surveyed – hundreds of people – they say that they reliably feel an onset within about seven to eight minutes with our technology. That is just about as fast as a shot of tequila or whiskey.

“With our partners, we will be featuring LifeTonic beverage products on tap in a cannabis cocktail lounge right off the Las Vegas strip, where social consumption rules are welcoming.”What we’ve done is very different from available nanoemulsion technologies. All those technologies try to mix oil and water, and oil and water don’t mix. In a nanoemulsion, you mix cannabis, a carrier oil, an edible detergent and water, and then you run it all through an ultrasonic homogenizer that breaks the cannabinoids and oil into microscopic droplets suspended in water. There are a lot of styles of nanoemulsions, from spray-dried nanoemulsions to liquid liposomal encapsulations, and they all confer certain absorption benefits when compared to straight-up oil absorption. But still, even the microscopic oil droplets suspended in water are quite large compared to what we have done, and still take quite a long time to digest.

We looked at the cannabis molecule and we said, “You know what? If we can put a strong negative charge on it, if we can ionize it, then we can make it behave more like a dissolvable salt instead of an oil.” When we treat it this way, the cannabis molecule dissolves completely in the water without emulsifiers or additives. When something is dissolved, there is no nano-emulsion droplet size. It is single molecules dissolved water. A single ionized cannabinoid molecule is about 1,000 times smaller than an average nano-emulsion droplet – and this greatly enhances absorption. The onset speed of ionized cannabinoids compared to nanoemulsions is measurable as just a few minutes instead of a half hour or more.

We have 56 granted and pending patents on LifeTonic’s ionization technology. We can ionize THC, CBD, CBG and CBD – most cannabinoids are compatible. There are also several herbal products that are compatible with our ionization technology, like the curcuminoids in turmeric, which are normally very hard to get into water. We can also ionize the eugenol that is in cloves. Ionized eugenol is an intoxicant, so we have big plans for alcohol alternatives outside of cannabis.

We’re using this technology to enter the Nevada cannabis market with one of the largest dispensary chains and cannabis product manufacturers in Nevada. With our partners, we will be featuring LifeTonic beverage products on tap in a cannabis cocktail lounge right off the Las Vegas strip, where social consumption rules are welcoming. We’ll craft every kind of cocktail you can imagine, only without alcohol. All these beverages will work in a matter of minutes to provide the first true social drinking experience with cannabis. After you enjoy a beverage, you may purchase a package of ionized THC beverage powder sachets in the cannabis cocktail lounge or at any of the dispensaries within our distribution network. You can pour the powder into any beverage, and it becomes a friendly, fast-acting THC beverage that will get you high, but not leave you with a hangover. We will also be selling a breath-spray format that works almost as quickly as vaping.

Green: What kind of validation studies have you done?

Thomas: We have conducted several broad market studies for our ionized products and almost all people report a profound onset within a few minutes. We have not completed a formalized clinical trial, but we are closing a major funding round that will allow us to do so. We plan to begin controlled pre-clinical trials focused mainly on ionized CBD because it’s far easier to get FDA approval for clinical trials on CBD than for THC. Our studies will monitor a couple dozen volunteers with a functional MRI and watch the change in the brain using our oral spray and beverage products compared against a standard CBD tincture control. We know that we’re going to see fast action because everybody who uses it says that a feeling develops in minutes.

Green: What geographies are you active in and exploring?

Thomas: CBD and hemp products from our extraction technology have been sold in every US state and parts of Europe. Additionally, hemp-based CBD and CBG versions of our ionized products and ionized turmeric products have been sold in several states through our LifeTonic.com, our ecommerce site. We have also sold white labeled versions of our ionized products through partner brands. We will be launching THC versions of our ionized products with our partners Nevada this fall. We expect THC versions to also be available in Colorado this winter.

Green: So, you are creating the powders on site?

Thomas: Yes. We manufacture ionized CBD, CBG, eugenol and turmeric beverage powders on site. We also manufacture and fast acting ionized sprays. These products are sold through our own retail site and we white label for other brands. Per our long-term licensing strategy, these sales establish market viability through sales. Selling products and establishing market viability prior to licensing significantly increases the value of our licenses and exits. It’s very important to answer the question: Do people buy it and do people love it? So far, we like the feedback!

On the THC side, we manufacture ionized products through partners in each cannabis state that we enter. We manufacture the ionizing base here in Colorado, then we ship it to other states where our partners add the THC and package it in LifeTonic-branded packaging. The analogy is that we sell a proprietary Coca-Cola formula without the caffeine, then our partners add the caffeine and bottle it in Coca-Cola branded bottles. In this way, we ensure that the hardest part of our process is controlled house to ensure consistency and quality across all states. It also allows us to be a non-plant touching business, since we only sold upstream base products that did not contain THC. We pick the best manufacturing and distribution partner in each cannabis state and grow from there.

Green: What’s the one thing you’re most interested in learning about?

Thomas: Increasing the bioavailability of cannabis. I have been most passionate about making cannabis work as quickly as alcohol and giving people an alternative to inhaling it through smoking or vaping. That’s definitely what we’ve been most excited about as a company.

Green: Okay, great. That concludes the interview!

Thomas: Thank you Aaron!

Pesticide Remediation by CPC

By Arpad Konczol, PhD
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Like any other natural product, the biomass of legal cannabis can be contaminated by several toxic agents such as heavy metals, organic solvents, microbes and pesticides, which significantly influence the safety of the end products.

Let’s just consider the toxicological effects. Since cannabis products are not only administered in edible forms but also smoked and inhaled, unlike most agricultural products, pesticide residue poses an unpredictable risk to consumers. One example is the potential role of myclobutanil in the vape crisis.

Unfortunately, federal and state laws are still conflicted on cannabis-related pesticides. Currently, only ten pesticide products have been registered specifically for hemp by the U.S. Environmental Protection Agency. So, the question arises what has to be done with all pf the high-value, but also contaminated cannabis, keeping in mind that during the extraction processes, not only the phytocannabinoids get concentrated but the pesticides as well, reaching concentrations up to tens or hundreds of parts per million!

Currently, there are three different sets of rules in place in the regulatory areas of Oregon, California and Canada. These regulations detail which pesticides need to be monitored and remediated if a certain limit for each is reached. Because the most extensive and strict regulations are found in Canada, RotaChrom used its regulations as reference in their case study.

Centrifugal Partition Chromatographic (CPC) system

To illustrate that reality sometimes goes beyond our imagination, we evaluated the testing results of a THC distillate sample of one of our clients. This sample contained 9 (!) pesticides, of which six levels exceeded the corresponding action limits. The most frightening, however, regarding this sample, is that it contained a huge amount of carbofuran, a category I substance. It is better not to think of the potential toxicological hazard of this material…

The CPC-based purification of CBD is a well-known and straightforward methodology. As the elution profile on the CPC chromatogram of a distillate shows, major and minor cannabinoids can be easily separated from CBD. At RotaChrom, this method has been implemented at industrial-scale in a cost effective and high throughput fashion. In any case, the question arises: where are the pesticides on this chromatogram? To answer this, we set ourselves the goal to fully characterize the pesticide removing capability of our methodologies.

Our results on this topic received an award at the prestigious PREP Conference in 2019. The ease of pesticides removal depends on the desired Compound of Interest.

Here is a quick recap on key functionalities of the partition chromatography.

  • Separation occurs between two immiscible liquid phases.
  • The stationary phase is immobilized inside the rotor by a strong centrifugal force.
  • The mobile phase containing the sample to be purified is fed under pressure into the rotor and pumped through the stationary phase in the form of tiny droplets (percolation).
  • The chromatographic column in CPC is the rotor: cells interconnected in a series of ducts attached to a large rotor
  • Simple mechanism: difference in partition

Let’s get into the chemistry a bit:

The partition coefficient is the ratio of concentrations of a compound in a mixture of two immiscible solvents at equilibrium. This ratio is therefore a comparison of the solubilities of the solute in these two liquid phases.

The CPC chromatogram demonstrates the separation of Compounds of Interest based on their unique partition coefficients achieved through a centrifugal partition chromatography system.

CPC can be effectively used for pesticide removal. About 78% of the pesticides around CBD are very easy to remove, which you can see here:

In this illustration, pesticides are in ascending order of Kd from left to right. CBD, marked with blue, elutes in the middle of the chromatogram. The chart illustrates that most polar and most apolar pesticides were easily removed beside CBD. However, some compounds were in coelution with CBD (denoted as “problematic”), and some compounds showed irregular Kd-retention behavior (denoted as “outliers”).

If pesticides need to be removed as part of THC purification, then the pesticides that were problematic around CBD would be easier to remove and some of the easy ones would become problematic.

To simulate real-world production scenarios, an overloading study with CBD was performed, which you can see in the graph:

It is easy to see on the chromatogram that due to the increased concentration injected onto the rotor, the peak of CBD became fronting and the apparent retention shifted to the right. This means that pesticides with higher retention than CBD are more prone to coelution if extreme loading is applied.

To be able to eliminate problematic pesticides without changing the components of the solvent system, which is a typical industrial scenario, the so-called “sweet spot approach” was tested. The general rule of thumb for this approach is that the highest resolution of a given CPC system can be exploited if the Kd value of the target compounds fall in the range of 0.5-2.0. In our case, to get appropriate Kd values for problematic pesticides, the volume ratio of methanol and water was fine-tuned. Ascending mode was used instead of descending mode. For the polar subset of problematic pesticides, this simple modification resulted in an elution profile with significantly improved resolution, however, some coelution still remained.

In the case of apolar pesticides, the less polar solvent system with decreased water content in ascending mode provided satisfactory separation.

Moreover, if we focus on this subset in the three relevant regulatory areas, the outcome is even more favorable. For example, myclobutanil and bifenazate, dominant in all of the three regulatory regions, are fully removable in only one run of the CPC platform.

Based on these results, a generic strategy was created. The workflow starts with a reliable and precise pesticide contamination profile of the cannabis sample, then, if it does not appear to indicate problematic impurity, the material can be purified by the baseline method. However, if coeluting pesticides are present in the input sample, there are two options. First, adjusting the fraction collection of the critical pesticide can be eliminated, however the yield will be compromised in this case. Alternatively, by fine-tuning the solvent system, a second or even a third run of the CPC can solve the problem ultimately. Let me add here, that a third approach, i.e., switching to another solvent system to gain selectivity for problematic pesticides is also feasible in some cases.

In review, RotaChrom has conducted extensive research to analyze the list of pesticides according to the most stringent Canadian requirements. We have found that pesticides can be separated from CBD by utilizing our CPC platform. Most of these pesticides are relatively easy to remove, but RotaChrom has an efficient solution for the problematic pesticides. The methods used at RotaChrom can be easily extended to other input materials and target compounds (e.g., THC, CBG).

How to Develop Quality Cannabis Products with Advanced Analytical Testing

By Vanessa Clarke, Melody Lin
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A thorough cannabis product development process goes far beyond extracting and packaging. Performing advanced analytical testing at each and every stage allows producers to know the quantity, quality and behaviour of compounds in samples. Here are the four key stages from flower to consumption.

Stage 1: Flower

Developing a quality cannabis product begins with knowing the composition of compounds in your starting material. The best analytical tests utilize a metabolomics approach. Metabolomics is a suite of techniques that include a variety of instruments to run samples through in order to receive compositional data. In this stage, LC-qTOF and GC-MS are the best instruments to track all the compounds in the starting plant material. Essentially, metabolomics establishes a fingerprint of the compounds in a plant sample. This is beneficial because producers have to understand how their chosen cannabis plant differs from other cultivars and how it would potentially behave in their desired end product formulations.

Stage 2: Concentrate

After the plant material has gone through an extraction process, producers want to know precisely what is in the extract. Are there compounds that should not be there and are all the desired compounds present? The best way to test the quality of cannabis oils is again to use metabolomics (e.g. via LC-qTOF). This test reveals all the compounds in the sample in order to help the producer determine the purity and consistency of molecules beyond just THC and CBD.

When testing cannabis isolates, it is best to use NMR spectroscopy and X-ray diffraction. NMR characterizes and assesses the purity of single compounds or mixtures in solution or solid state. X-ray diffraction provides information about the crystal structure, chemical composition and the physical properties of the cannabis sample to help the producer prove the identification of desired compounds. Establishing that the concentrates are pure and aligned with what the producer intended to extract is key in this stage of product development.

Stage 3: Formulation

Designing an appropriate drug delivery formula is a universal challenge producers face at this stage of product development. Where nanoemulsion or other carrier approaches are being used, formulation characterization allows producers to understand how their active compounds behave in simulated physiological environments as well as how stable their products are over time. Specifically, nanoparticle sizing and assessing size changes over time can help a formulation scientist ensure the highest quality product is being mixed, and that the desired effect will be imparted on the consumer/patient.

Stage 4: Smoke/Vapor

Many producers might not consider this final stage, but it is critical for all inhalable cannabis products and devices. Using a smoke analyzer and metabolomics testing can identify and quantify compounds present within the formed smoke or vapor from pre-roll joints to vape devices. This is not only important for preventing the production of toxic by-products, but it can help producers create an optimal smoking experience for consumers.

One area that is often an afterthought is quality compliance testing. Despite a number of groups using the required tests well during development, many forget to continue the same robust testing on end products. In the current cannabis product development landscape, there is little guidance on how compliance testing should be conducted on every product “batch.” With these advanced analytical tests, producers can confidently develop compliant, stable and quality cannabis products.

 

The Craft of Extraction: Like Beer Making, It’s All About Control

By Jeremy Diehl
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Any brewmaster from the more than 7,000 U.S. craft breweries will tell you one of two things: That their art is a science, or that their science is an art. The answer might depend upon the brewer’s individual approach, but a combination of experience, process, precise measurement and intuition is exactly what’s required to create great beer. In a very similar way, the cannabis industry has its own version of the brewmaster: Extraction technicians.

A cannabis extraction technician deploys knowledge from multiple science disciplines to apply industrial solvents, heat and pressure to plant matter through a variety of methods with the aim to chemically extract pure compounds. Extraction techs use their passion for the cannabis and hemp plants, combined with chemistry, physics, phytobiology and chemical engineering to help create a result that’s not quite art, but not quite completely science. By manipulating plant materials, pressure, heat and other variables, the extraction technician crafts the building block for what will become an edible, tincture or extract.

Similarly, brewmasters use their knowledge of multiple science disciplines like chemistry and microbiology, as well as different brewing processes and a variety of ingredients to develop creative recipes that result in consistent, interesting beers. The brewmaster’s work is both science and art, as well. And they also manipulate plant materials, pressure, heat and other variables to achieve their desired results.

Author Jeremy Diehl collects cannabis extract from equipment for testing

“I would certainly consider brewing to be an art and a science, but it takes a very disciplined approach to create consistent, yet ever evolving beers for today’s craft market,” says Marshall Ligare, PhD. Research Scientist at John I. Haas, a leading supplier of hops, hop products and brewing innovations. “We work to ensure brewers can create something different with every new beer, as well as something that helps create an experience as well as a feeling.”

In both brewing and extraction, the art comes in the subjective experience of the craftsman and his or her ability to curate the infinite possibilities inherent in each process. However, both are a science in their requirement of establishing production methodologies that guarantee a consistent, reliable product experience every time to win customer loyalty (and regulatory compliance). In the same way hops determine recipes for beer flavors, the cannabis plant determines extraction recipes, especially considering the role that terpenoids play in the quality, flavor and effects of the end product.

The development of new and appealing cannabis products is beginning to mimic the vast variety of craft beers now found all over the world. In the same way beer connoisseurs seek out the perfect stout, lager or IPA, discriminating cannabis consumers now search for that gem of a single-origin, specialty-strain vaporizer oil or irresistible dab extract.

“I see an exciting new day for quality-focused, craft extraction that tells a story, not only of where the cannabis plant might have been grown and how, but also the care that was taken in the processing of that strain into smokable or edible oil,” says John Lynch, Founder of TradeCraft. “Imagine the impact in the marketplace when product-makers figure out how to do seasonal one-offs where engaged connoisseurs are willing to pay a premium for the art behind limited releases.”

In the same way hops determine recipes for beer flavors, the cannabis plant determines extraction recipes

In either process, you’re essentially creating art with science. Each process works with different strains. Each is concerned with chemical and flavor profiles. Each has its own challenges. In both worlds, quality depends upon consistency. You’re creating art, but you need to replicate that art over and over – which can only occur with strict control of the process. Brewmasters seek control of things like yeast quantity and health, oxygen input, wort nutritional status and temperature, among other things. In their pursuit, extraction technicians seek to control temperature, pressure and flow rate–as well as all the ways these variables interact with each other. What enables this control in both efforts is the equipment used to achieve results.

“A modern brewhouse is very much like a scientific laboratory,” Ligare says. “Brewers treat their setup with the same care and attention a scientist gives to their lab equipment, and are equally concerned with precision, cleanliness and the purity of the result. With each new beer, they want to develop a process that can be controlled and replicated.”

The key to creating a precise process is to use instrument-grade extraction machinery that performs to specifications – and allows you to repeat the process again and again. The value of using high-quality instrumentation to manage and monitor either the brewing or extraction process cannot be overstated. Although it seems counterintuitive, this is where the “craft” comes into play for both brewing and cannabis extraction. Precise instrumentation is what allows the brewer or extraction “artist” to manipulate and monitor the conditions required to meet recipe standards. Along with the quality of the ingredients (hops, cannabis, hemp, etc.), the quality of the equipment utilized to create the product is one critical element impacting the end result. “Imagine the impact in the marketplace when product-makers figure out how to do seasonal one-offs where engaged connoisseurs are willing to pay a premium for the art behind limited releases.”

In cannabis extraction, a second crucial decision is determining which solvent is the best solution for the recipe you’re using and the end result you’re hoping to achieve. This decision is a part of the “craft” of extraction, and determined according to a combination of criteria. There’s no question that each solvent has a business case it serves best, and there is ongoing debate about which approach is best. But overwhelmingly, the solvent that best serves the most business needs is CO2 due to its inherent versatility and ability to have its density tuned to target specific compounds.

“Control is what makes or breaks any craft product,” says Karen Devereux, Vice President of Northeast Kingdom Hemp. “We’re based in Vermont and love how Vermont is known for its quality craft beer, cheese and maple syrup. We wanted to bring that craft approach to hemp extraction, and everyone knows that any craft endeavor is focused on the details and getting them right again and again. You can’t do that without controlling every aspect of the process.”

Greater control of the process can also open up worlds of discovery. The inherent “tunability” of CO₂ enables the extraction technician to target specific compounds, enhancing the potential for experimentation and even whimsy. This can lead to entirely new products much in the way a brewer can control his process to create new, interesting beers.

American portrait photographer Richard Avedon famously declared that art is “about control,” describing the artistic process as “the encounter between control and the uncontrollable.” The same can be said for beer making and cannabis extraction. The more precisely you can control variables, the more options you’ll have for yourself and your customers. The more choices you’ll have with regard to different recipes and products. And the more loyalty you’ll ultimately generate among fans of your products.

Soapbox

Confront Poor Medicinal Cannabis Policies to Save Lives

By Dr. Jordan Zager
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For me, the opioid epidemic was never a theoretical crisis. The mounting lives lost to overdoses weren’t just numbers in news reports to me, but names. A high school lab partner, little league teammates, a cook at my first restaurant job and others in my hometown were lost to the epidemic. By the time I graduated high school, seven people in my life died due to complications arising from opioid use.

What’s not lost on me now, after earning my PhD in plant biochemistry and founding a startup focused on bringing consistency and scientific credibility to the cannabis industry, is how a stigma around medicinal cannabis seems like such a contributing factor in their deaths.

Cannabis, although fully illegal in only eight U.S. states, still qualifies as a Schedule 1 drug on the federal level, legally equivalent to LSD or heroin. Crystal methamphetamine and cocaine as Schedule 2 drugs have lower penalties and even have federally approved medical applications. This is where we’ve failed as a broader scientific community.

The reason is this: Medicinal cannabis produced from the same genetic replicates, but grown in separate locations, or even different seasons, will possess different bioactive compounds. In short, their effect on patients will be different depending on the various bioactive compounds produced by the plant. Prescription medications do not come with that major caveat.

Dr. Jordan Zager, CEO and co-founder of Dewey Scientific

There’s a quality assurance problem, compounded by a lack of science that’s been shackled by the criminalization of cannabis since 1937.

We do know that the primary benefits of cannabis are three-fold: First, there’s pain management, as 28 well conducted randomized clinical trials (RCTs) have documented that cannabinoid agents are effective analgesics for chronic pain. Second, while potentially psychologically addictive, so people may desire the “high” produced by cannabis, THC is not chemically addictive and does not create a biological desire for the drug, much like the craving induced by the absence of, say, cocaine or heroin has on regular users. And finally, patients cannot overdose.

As a scientific community, there are three things we need to start doing today to change the narrative around medicinal cannabis and help bring this safer alternative therapy to more people. We need to provide a larger body of evidence about the benefits. We need to drive increased consistency in cannabis products themselves. And we need to confront stigmas rooted in misinformation. The sooner we can succeed here, the sooner we can hope for a day when we see fewer devastating opioid overdoses and deaths.

I am driven by a vision for a future when people can have access to safe, trusted and consistent cannabis for their medical and recreational uses, and we as a society are able to fully realize the therapeutic benefits of this amazing plant. As scientists, my colleagues and I are committed to doing our part to bring the credibility and advancements that will help this vision become a reality.

Using tools rooted in science–including functional genomics and secondary metabolite pathway expression profiling–cultivators can learn to fully “know” the plants they grow and hone in on producing the same bioactive compounds and in the same ratios that show medicinal promise. Cultivators can learn the genetic effect that their facility has on their genetics and why those genetics lead to a different chemical profile when grown elsewhere. Together, we can identify the driving factors of what makes a variety help with whatever ailment you are trying to treat.

I’m buoyed by data that shows states that have legalized and provided access to recreational cannabis have between 20% and 35% fewer reported opioid deaths, and lower rates of opioid prescriptions. But more needs to be done. I plan to become a more vocal voice, advocate for sound science, consistency in medical cannabis and better access to natural plant-based medicines without the stigma of yesteryear.

The time has come for our policy makers to step up. We cannot afford to just be observers when the cost of remaining on the sideline is measured in lives.

Beyond THC: Encouraging Cannabinoid and Terpene Production with LEDs

By Andrew Myers
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For years, tetrahydrocannabinol (THC) got all the attention. While THC certainly delivers its own benefits (such as relaxation and pain relief), there’s a whole host of other – and often overlooked – compounds found in cannabis with important benefits as well. THC is truly only the tip of the iceberg when it comes to cannabis’s potential.

As the cannabis industry evolves with changing consumer tastes and developing medical research, growers may employ techniques to boost cannabinoid and terpene profiles in their harvests – beyond merely focusing on THC. Advanced LEDs allow growers to elicit specific biological responses in cannabis crops, including increased concentrations of these naturally occurring chemical compounds.

The Foundation of Cannabis’s Effects
Whether used medicinally or otherwise, cannabis has changed our society and many of our lives – and there’s a collection of naturally occurring chemical compounds, known as cannabinoids and terpenes, to thank.

  • The cannabinoids THC and CBD are the most common and well-researched, however they are accompanied by more than 200 additional compounds, including cannabinol (CBN), cannabigerol (CBG) and tetrahydrocannabivarin (THCV), among others.
  • The cannabis plant also contains terpenes. These structures are responsible for giving flowers (including cannabis), fruits and spices their distinctive flavors and aromas. Common terpenes include limonene, linalool, pinene and myrcene.

Both cannabinoids and terpenes are found in the cannabis plant’s glandular structures known as trichomes. Look closely, and you’ll notice trichomes coating the cannabis flowers and leaves, giving the plant an almost frosty appearance.

macropistil/trichome
A macro view of the trichomes and pistils on the plant

Trichomes – which are found across several plant species – are a key aspect of a cannabis plant’s survival. The specific combination of metabolites produced by trichomes may attract certain pollinators and repel plant-eating animals. Moreover, trichomes (and specifically THC) may act as the plant’s form of sunscreen and shield the plant from harmful ultraviolet rays.

While they play an essential part in the cannabis plant’s lifecycle, trichomes are volatile and easily influenced by a range of environmental factors, including light, heat, physical agitation and time. Therefore, environment is a defining variable in the development of these important structures.

How LEDs Support Cannabinoid and Terpene Development in Crops
Spectrally tunable LEDs give indoor cannabis growers unparalleled control over their crops. As research has expanded about plants’ responses to the light spectrum, growers have discovered they are able to elicit certain physiological responses in the plant. This phenomenon is called photomorphogenesis. At its root, photomorphogenesis is a survival tactic – it’s how the plant responds to miniscule changes in its environment to increase the chances of reaching full maturity and, eventually, reproducing. While cultivated cannabis plants won’t reproduce at an indoor setting, growers can still use the light spectrum to encourage strong root and stem development, hasten the flowering process and the development of bigger, brightly colored flowers.

It makes sense that using the proper light spectrums may also have an impact on the production of specific cannabinoids and terpenes – an important factor when responding to highly specific consumer needs and desires, both within medical and adult-use markets.

Here are a few more reasons why utilizing full-spectrum LEDs can lead to higher quality cannabis:

  • Lower Heat, but the Same Intensity.
    When compared to HPS, fluorescent and other conventional lighting technologies, LEDs have a much lower heat output, but provide the same level of intensity (and often improved uniformity). This represents an enormous advantage for cannabis cultivators, as the lights can be hung much closer to the plant canopy without burning trichomes than they would be able to with other lighting technologies.
  • UV Light. Cannabinoids and terpenes are part of the cannabis plant’s natural defense mechanism, so it makes sense that lightly stressing plants can boost cannabinoid and terpene numbers. Some studies illustrate an increase in UV-B and UV-A light can lead to richer cannabinoid and terpene profiles.1 It’s a fine line to walk, though – too much UV can result in burned plants, which leads to a noticeable drop in cannabinoids.
  • Full-Spectrum Capabilities. The cannabis plant evolved over millions of years under the steady and reliable light of the sun. Full-spectrum is the closest thing to natural sunlight that growers will be able to find for indoor growing – and they’ve been shown to perform better in terms of cannabinoid development. A 2018 study titled “The Effect of Light Spectrum on the Morphology and Cannabinoid Content for Cannabis Sativa L.,” explored how an optimized light spectrum resulted in increased expression of cannabinoids CBG and THCV.2

This is the most important tip for indoor growers: your plants’ environment is everything. It can make or break a successful harvest. That means cultivators are responsible for ensuring the plants are kept in ideal conditions. Lights are certainly important at an indoor facility, but there are several other factors to consider that can affect your lights’ performance and the potency of your final product. This includes your temperature regulation, humidity, the density of plants within the space, CO2 concentration and many other variables. For the best results, your lights should be fully aligned with other environmental controls in your space. Nothing sabotages a once-promising crop like recurrent issues in the indoor environment.

solsticegrowop_feb
Indoor cultivation facilities often use high powered lights that can give off heat

Cannabinoids and terpenes take time to develop – so cultivators will want to avoid harvesting their plants too early. On the other hand, these compounds begin to degrade over time, so growers can’t wait too long either.

Cultivators seeking potent cannabinoid and terpene profiles must find a happy medium for the best results – and the best place to look is where cannabinoids and terpenes develop: the trichomes. With a microscope, cultivators can get up close and personal with these sparkly structures. Younger plants begin with clear trichomes, which eventually become opaque and change to amber. Once your plants show amber-hued trichomes, they’re ready for harvest.

The truth here is that there’s no perfect formula to elicit show-stopping cannabinoids and dizzying terpenes with every harvest. A lot of cannabis cultivation is based around trial-and-error, finding what works for your space, your business and your team. But understanding the basics around indoor environmental controls like lighting and temperature – and how they can affect the development of cannabinoids and terpenes – is an excellent place to start. Using high quality equipment, such as full-spectrum LED lighting can boost both cannabinoid and terpene production, resulting in richer, more potent and higher quality strains.


References:

  1. Lyndon, John, Teramura, Alan H., Coffman, Benjamin C. “UV-B Radiation Effects on Photosynthesis, Growth and Cannabinoid Production of Two Cannabis Sativa Chemotypes.” August 1987. Photochemistry and photobiology. Web. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1751-1097.1987.tb04757.x?&sid=nlm%3Apubmed
  2. Magagnini G., Grassi G., Kotiranta, S. “The Effect of Light Spectrum on the Morphology and Cannabinoid Content of Cannabis sativa L.” 2018. Medical Cannabis and Cannabinoids. Web: https://www.karger.com/Article/FullText/489030
IR Spectrum of 2,4-Dichlorophenol in different physical states
From The Lab

Gas Chromatography/Infrared Spectroscopy: A Tool For the Analysis of Organic Compounds in Cannabis

By John F. Schneider
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IR Spectrum of 2,4-Dichlorophenol in different physical states

Editor’s Note: The author will be teaching a 1/2 day short course on this topic at PITTCON in Philadelphia in March 2019.


The combination of gas chromatography and infrared spectroscopy (GC/IR) is a powerful tool for the characterization of compounds in complex mixtures. (1-5) Gas chromatography with mass spectroscopy detection (GC/MS) is a similar technique, but GC/MS is a destructive technique that tears apart the sample molecules during the ionization process and then these fragments are used to characterize the molecule. In GC/IR the molecules are not destroyed but the IR light produced by molecular vibrations are used to characterize the molecule. IR spectrum yields information about the whole molecule which allows the characterization of specific isomers and functional groups. GC/IR is complementary to GC/MS and the combination results in a powerful tool for the analytical chemist.

A good example of the utility of GC/IR vs GC/MS is the characterization of stereo isomers. Stereo isomers are mirror images such as a left hand and a right hand. In nature, stereo isomers are very important as one isomers will be more active then its mirror image. Stereo isomers are critical to medicinal application of cannabis and also a factor in the flavor components of cannabis.

GC/MS is good at identifying basic structure, where GC/IR can identify subtle differences in structure. GC/MS could identify a hand, GC/IR could tell you if it is a left hand or right hand. GC/MS can identify a general class of compounds, GC/IR can identify the specific isomer present.

Why GC/IR?

Gas chromatography interfaced with infrared detection (GC/IR), combines the separation ability of GC and the structural information from IR spectroscopy. GC/IR gives the analyst the ability to obtain information complementary to GC/MS. GC/IR gives the analyst the power to perform functional group detection and differentiate between similar molecular isomers that is difficult with GC/MS. Isomer specificity can be very important in flavor and medical applications.

 IR Spectrum of 2,4-Dichlorophenol in different physical states

IR Spectrum of 2,4-Dichlorophenol in different physical states

Gas chromatography with mass spectrometry detection (GC/MS) is the state-of-the-art method for the identification of unknown compounds. GC/MS, however, is not infallible and many compounds are difficult to identify with 100 % certainty. The problem with GC/MS is that it is a destructive method that tears apart a molecule. In infrared spectrometry (IR), molecular identification is based upon the IR absorptions of the whole molecule. This technique allows differentiation among isomers and yields information about functional groups and the position of such groups in a molecule. GC/IR complements the information obtained by GC/MS.

Interfaces

Initial attempts to couple GC with IR were made using high capacity GC columns and stopped flow techniques. As GC columns and IR technology advanced, the GC/IR method became more applicable. The advent of fused silica capillary GC columns and the availability of Fourier transform infrared spectrometry made GC/IR available commercially in several forms. GC/IR using a flow cell to capture the IR spectrum in real time is known as the “Light Pipe”. This is the most common form of GC/IR and the easiest to use. GC/IR can also be done by capturing or “trapping” the analytes of interest eluting from a GC and then measuring the IR spectrum. This can be done by cryogenically trapping the analyte in the solid phase. A third possibility is to trap the analyte in a matrix of inert material causing “Matrix Isolation” of the analyte followed by measuring the IR spectrum.

Infrared Spectroscopy

The physical state of the sample has a large effect upon the IR spectrum produced. Molecular interactions (especially hydrogen bonding) broadens absorption peaks. Solid and liquid samples produce IR spectra with broadened peaks that loses much of the potential information obtained in the spectra. Surrounding the sample molecule with gas molecules or in an inert matrix greatly sharpens the peaks in the spectrum, revealing more of the information and producing a “cleaner” spectrum. These spectra lend themselves better to computer searches of spectral libraries similar to the computer searching done in mass spectroscopy. IR spectral computer searching requires the standard spectra in the library be of the same physical state as the sample. So, a spectrum taken in a gaseous state should be searched against a library of spectra of standards in the gaseous state.

IR of various phases:

  • Liquid Phase – Molecular interactions broaden absorption peaks.
  • Solid Phase – Molecular interactions broaden absorption peaks.
  • Gas Phase – Lack of molecular interactions sharpen absorption peaks.
  • Matrix Isolation – Lack of molecular interactions sharpen absorption peaks.

IR Chromatograms

GC/IR yields chromatograms of infrared absorbance over time. These can be total infrared absorbance which is similar to the total ion chromatogram (TIC) in GC/MS or the infrared absorbance over a narrow band or bands analogous to selected ion chromatogram. This is a very powerful ability, because it gives the user the ability to focus on selected functional groups in a mixture of compounds.

Conclusion

Gas chromatography with infrared detection is a powerful tool for the elucidation of the structure of organic compounds in a mixture. It is complementary to GC/MS and is used to identify specific isomers and congeners of organic compounds. This method is greatly needed in the Cannabis industry to monitor the compounds that determine the flavor and the medicinal value of its products.


References

  1. GC–MS and GC–IR Analyses of the Methoxy-1-n-pentyl-3-(1-naphthoyl)-Indoles: Regioisomeric Designer Cannabinoids, Amber Thaxton-Weissenfluh, Tarek S. Belal, Jack DeRuiter, Forrest Smith, Younis Abiedalla, Logan Neel, Karim M. Abdel-Hay, and C. Randall Clark, Journal of Chromatographic Science, 56: 779-788, 2018
  2. Simultaneous Orthogonal Drug Detection Using Fully Integrated Gas Chromatography with Fourier Transform Infrared Detection and Mass Spectrometric Detection , Adam Lanzarotta, Travis Falconer, Heather McCauley, Lisa Lorenz, Douglas Albright, John Crowe, and JaCinta Batson, Applied Spectroscopy Vol. 71, 5, pp. 1050-1059, 2017
  3. High Resolution Gas Chromatography/Matrix Isolation Infrared Spectrometry, Gerald T. Reedy, Deon G. Ettinger, John F. Schneider, and Sid Bourne, Analytical Chemistry, 57: 1602-1609, 1985
  4. GC/Matrix Isolation/FTIR Applications: Analysis of PCBs, John F. Schneider, Gerald T. Reedy, and Deon G. Ettinger, Journal of Chromatographic Science, 23: 49-53, 1985
  5. A Comparison of GC/IR Interfaces: The Light Pipe Vs. Matrix Isolation, John F. Schneider, Jack C. Demirgian, and Joseph C. Stickler, Journal of Chromatographic Science, 24: 330- 335, 1986
  6. Gas Chromatography/Infrared Spectroscopy, Jean ‐ Luc Le Qu é r é , Encyclopedia of Analytical Chemistry, John Wiley & Sons, 2006