There is a significant increase in demand for all cannabinoid products across the board—including CBD, THC, CBG and THCV—from recreational users, consumer packaged goods and pharmaceutical companies. And the next great race is on for the hottest arrival to scientific cannabis therapeutics: rare cannabinoids.
Research shows rare cannabinoids are poised to be the future of cannabis investing, providing better health benefits in addition to impacting the pharmaceutical, CPG, nutraceuticals, cosmetics and pet care markets significantly. According to recent reports, the biosynthesis of rare cannabinoids will be a $25 billion market by 2025 and $40 billion by 2040.
The companies that will revolutionize this market are ones with the highest quality and lowest prices, which means that biosynthetic cannabinoid companies will be the leaders in investment and capturing market share. We will also see a major consolidation in this market amongst the grow, harvest and extraction companies, increasing efficiencies and driving down costs.
What are rare cannabinoids and why should we care?
Rare cannabinoids such as CBG, CBN, THCV, THCA and others have significantly better and more specific health benefits than just CBD on its own. Biotech companies like ours, Biomedican, which has a patent-pending biosynthesis platform, can produce pharmaceutical grade, non-GMO, bioidentical, synthetic cannabinoids with 0.0% THC at 70-90% less cost. Producing 0.0% THC means that rare cannabinoids can be added into nutraceuticals, CPG and cosmetics/lotions with zero changes in current cannabis regulations. Also, we produce the same exact product every time (not possible through plants), which is extremely important for pharmaceutical companies conducting clinical trials.
Why are rare cannabinoids important?
The human body contains different cannabinoid receptors that help regulate critical processes, including learning, memory, neuronal development, appetite, digestion, inflammation, overall mood, sleep, metabolism and pain perception. This considerable involvement of cannabinoid receptors, critical to many physiological systems, underscores their potential as pharmaceutical targets.
Pharmacological research has uncovered several medical uses for cannabinoids, which bind to cannabinoid receptors. They’ve been shown to help with pathological conditions such as pediatric epilepsies, glaucoma, neuropathic pain, schizophrenia and have anti-tumor effects as well as promote the suppression of chemotherapy-induced nausea. This ongoing research is becoming more prevalent and has the potential to uncover therapeutic uses for an array of cannabinoids.
In addition to the medical field, other prominent sectors have adopted the use of cannabinoids. There is an increasing demand for cannabinoids in inhalables, the food industry and in hygienic and cosmetic products. Veterinary uses for cannabinoids are also coming to light. The use of naturally occurring cannabinoids reduces the need for synthetic alternatives that may produce harmful off-target effects.
So how does this affect the investing market?
Where there is demand, significant and growth investments follow. All the major players from nutraceuticals, CPG, cosmetics and pet care companies are driving the demand for rare cannabinoids. We are seeing a major investment shift from commodity-based prices for cannabis and CBD to the new biosynthesis technology which offers significantly better health benefits and higher profit margins. Those unique qualities of rare cannabinoids open an enormous opportunity to create new drugs and food supplements for treating various medical conditions and improving the quality of life. This creates a massive global opportunity for all companies in these categories differentiating their products from competitors.
There will be big winners and losers in these markets, but at the end of the day, the highest quality and lowest cost producers will capture most of these markets. Biomedican has the highest quality, highest yields and lowest cost of production in the industry. Which we believe will make us the clear leader in the biosynthesis rare cannabinoid markets.
Which rare cannabinoid to invest in first?
Early reports indicate THCV (not to be confused with THC) could contain a variety of health benefits: it may help with appetite suppression/weight loss, possibly treat diabetes as well the potential to reduce tremors and seizures caused by conditions like multiple sclerosis, Parkinson’s disease and ALS.
There has been an explosion of interest in THCV due to its potential health benefits. We are seeing major players in the nutraceutical, health food and pharmaceutical industries clamoring to add THCV to their product lines. Companies can now produce THCV through biosynthesis, creating a pharmaceutical-grade, organic, bioidentical compound at 70-90% less than wholesale prices. This is exactly what the largest players in the market want: a pharmaceutical-grade, consistent product at significantly less cost. The current prices and quality have limited THCV production, but new breakthroughs in biosynthesis have solved those issues, so we expect a tsunami of orders for THCV in 2021.
Remediation of delta-9 tetrahydrocannabinol (d9-THC) has become a hot button issue in the United States ever since the Drug Enforcement Agency (DEA) released their changes to the definitions of marijuana, marijuana extract, and tetrahydrocannabinols exempting extracts and tetrahydrocannabinols of a cannabis plant containing 0.3% or less d9-THC on a dry weight basis from the Controlled Substances Act. That is because, as a direct consequence, all extracts and tetrahydrocannabinols of a cannabis plant containing more than 0.3% d9-THC became explicitly under the purview of the DEA, including work-in-progress “hemp extracts” that because of the extraction process are above the 0.3% d9-THC limit immediately upon creation.
The legal ramifications of these changes to the definitions on the “hemp extracts” marketplace will not be addressed. Instead, this article focuses on the amount of d9-THC that is available in the plant material prior to extraction and tracks a “hemp extract” from the point it falls out of compliance to the point it becomes compliant again and stresses the importance of accurate track-n-trace protocols at the processing facility. The model developed to support this article was intended to be academic and was designed to follow the d9-THC portion of a “hemp extract” through the lifecycle of a typical CO2-based extract from initial extraction to THC remediation. A loss to the equipment of 2% was used for each step.
For this exercise, a common processing scenario of 1000 kg of plant material at 10% cannabidiol (CBD) and 0.3% d9-THC by weight was modeled. This amount, depending on scale of operations, can be a facility’s total capacity for the day or the capacity for a single run. 1000 kg of plant material at 0.3% d9-THC has 3 kg of d9-THC that could be extracted, purified, and diverted into the marketplace. CO2 has a nominal extraction efficiency of 95%, meaning some cannabinoids are left behind in the plant material. The same can be said about the recovery of the extract from the equipment. Traces of extract will remain in the equipment and this little bit of material, if unaccounted for, can potentially open an operator up to legal consequences. Data for the initial extraction is shown in Image 1.
As soon as the initial extract is produced it is out of compliance with the 0.3% d9-THC limit to be classified as a “hemp extract”, and of the 3 kg of d9-THC available, the extract contains approx. 2.8 kg, because some of the d9-THC remains in the plant material and some is lost to the equipment.
Dewaxing via Winterization and Solvent Removal
Dewaxing a typical CO2 extract via winterization is a common process step. For this exercise, a wax content of 30% by weight was used. A process efficiency of 98% was attributed to the wax removal process and it was assumed that 100% of the loss can be accounted for in the residue recovered from the equipment rather than in the removed waxes. Data for the winterization and solvent recovery are shown in Image 2 and 3.
Two things occur during winterization and solvent removal, non-target constituents are removed from the extract and there is compounded loss from multiple pieces of process equipment. These steps increase the concentration of the d9-THC portion of the extract and produce two streams of noncompliant waste.
Decarboxylation & Devolatilization
Most cannabinoids in the plant material are in their acid form. For this exercise, 90% of the cannabinoids were considered to be acid forms. Decarboxylation is known to produce a mass difference of 87.7%, i.e. the neutral forms are 12.3% lighter than the acid forms. Heat was modeled as the primary driver and a process efficiency of 95% was used for the conversion rate during decarboxylation. To simplify the model, the remaining 5% acidic cannabinoids are presumed destroyed rather than degraded into other compounds because the portion of the cannabinoids which get destroyed versus degrade into other compounds varies from process to process.
Devolatilization is the process of removing low-molecular weight constituents from an extract to stabilize it prior to distillation. Since the molecular constituents of cannabis resin extracts vary from variety to variety and process to process, the extracts were assumed to consist of 10% volatile compounds. The model combines the decarboxylation and devolatilization steps to account for complete decarboxylation of the available acidic cannabinoids and ignores their weight contribution to the volatiles collected during devolatilization. Destroyed cannabinoids result in an amount of loss that can only be accounted for through a complete mass balance analysis. Data for decarboxylation and devolatilization are shown in Image 4.
As the extract moves along the process train, the d9-THC concentration continues to increase. Decarboxylation further complicates traceability because there is both a known mass difference associated with the process and an unknown mass difference that must be calculated and justified.
A two-pass distillation was modeled. On each pass a portion of the extract was removed to increase the cannabinoid concentration in the recovered material. Average data for distilled “hemp extracts” was used to ensure the model did not over- or underestimate the concentration of the cannabinoids in the distillate. The variables used to meet these data constraints were derived experimentally to match the model to the scenario described and are not indicative of an actual distillation. Data for distillation is shown in Image 5.
After distillation, the d9-THC concentration is shown to have increased by 874% from the original concentration in the plant material. Roughly 2.2 kg of the available 3 kg of d9-THC remains in the extract, but 0.8 kg of d9-THC has either ended up in a waste stream or walking out the door.
Chromatography – THC Remediation Step 1
Chromatography was modeled to remove the d9-THC from the extract. Because there are several systems with variable efficiency rates at being able to selectively isolate the d9-THC peak from the eluent stream, the model used a 5% cut-off on the front-end and tail-end of the peak, i.e. 5% of the material before the d9-THC peak and 5% of the material after the d9-THC peak is assumed to be collected along with the d9-THC. Data for chromatography is shown in Image 6.
After chromatography, a minimum of three products are produced, compliant “hemp extract”, d9-THC extract, and noncompliant residue remaining in the equipment. The d9-THC extract modeled contains 2.1 kg of the available 3 kg in the plant material, and is 35% d9-THC by weight, an increase of 1335% from the distillation step and 11664% from the plant material.
CBN Creation – THC Remediation Step 2
For this exercise, the d9-THC extract was converted into cannabinol (CBN) using heat rather than cyclized into d8-THC, but a similar model could be used to account for this scenario. The conversion rate of the cannabinoids into CBN through heat degradation alone is low. Therefore, the model assumes half of the available cannabinoids in the d9-THC extract are converted to CBN. The entirety of the remaining portion of the cannabinoids are assumed to convert to some form of degradant rather than a portion getting destroyed. Data for THC destruction is shown in Image 7.
Only after the CBN cyclization step has completed does the product that was the d9-THC extract become compliant and classifiable as a “hemp extract.”
Throughout the process, from initial extraction to the final d9-THC remediation step, loss occurs. Of the 3 kg of d9-THC available in the plant material only 2.1 kg was recovered and converted to CBN. 0.9 kg was either lost to the equipment, destroyed in the process, attributable to the mass difference associated with decarboxylation, or was never extracted from the plant material in the first place. All of these potential areas of product loss should be identified, and their diversion risk fully assessed. Not every waste stream poses a risk of diversion, but some do; having a plan in place to handle waste the DEA considers a controlled substance is essential. Without a track-n-trace program following the d9-THC and identifying the potential risk of diversion would be impossible. The point of this is not to instill fear, instead the intention is to shed light on a very real issue “hemp extract” producers and state regulators need to understand to protect themselves and their marketplace from the DEA.
Plant genetics are an important consideration for cultivators planning to grow cannabis crops. Genetics can affect how well a plant grows in a particular environment under various conditions and have a major impact on the production of cannabinoids, terpenes as well as other molecules and traits expressed by the plant.
Front Range Biosciences is a hemp and cannabis genetics platform company, leveraging proprietary next generation breeding and Clean Stock® tissue culture nursery technologies to develop new varieties for a broad range of product applications in the hemp and cannabis industries. FRB has global reach through facilities in Colorado, California and Wisconsin, and a partnership with the Center for Research in Agricultural Genomics in Barcelona, Spain. FRB is headquartered in Lafayette, Colorado.
We spoke with Jonathan Vaught, Ph.D., CEO and co-founder of Front Range Biosciences. Jonathan co-founded Front Range in 2015 after a successful career in the diagnostics and food testing industries.
Jonathan Vaught: This was a collaborative project between the BioServe group at the University of Colorado Boulder, which is a part of their aerospace engineering program. They do research on the International Space Station, and they have for quite some time. We partnered with them and another company, Space Technology Holdings, a group that’s working on applications of space travel and space research. We teamed up to send tissue culture samples to the space station and let them sit in zero gravity at the space station for about a month, and then go through the reentry process and come back to Earth. We brought them back in the lab to perform some genomic analyses and try to understand if there’s any underlying genetic changes in terms of the plants being in that environment. We wanted to know if there was anything interesting that we could learn by putting these plant stem cells and tissue cultures in an extreme environment to look for stress response, and some other possible changes that might occur to the plants by going through those conditions.
Aaron: That’s an interesting project! Are there any trends that you’re following in the industry?
Jon: We’re excited to see ongoing legalization efforts around the world. We’ve seen continued progress here in the United States. We still have a long way to go, but we’re excited to see the additional markets coming onboard and regulations moving in the right direction. Also, we’re excited to see some of the restorative justice programs that have come out.
Aaron: How did you get involved at Front Range Biosciences?
Jon: It really starts with my background and what I was doing before Front Range Biosciences. I’ve spent more than 15 years developing commercializing technologies in human diagnostics, food safety and now agriculture.
I started my career during graduate school in biotech at the University of Colorado at Boulder, where I helped develop some of the core technology for a human diagnostic startup company called Somalogic here in Colorado. I went to work for them after finishing my dissertation work and spent about six years there helping them grow that company. We ended up building the world’s largest protein biomarker discovery platform primarily serving pharmaceutical companies, hospitals and doctors, with personalized medicine and lab tests for things like early detection of chronic illness, cancer, heart disease and inflammation.
I then went to another startup company called Beacon Biotech, that was interested in food safety. There I helped develop some similar technologies for detecting food-borne illness — things like salmonella, listeria and E. coli. That was my introduction to big food and big agriculture. From there, I went to help start another company called Velocity Science that was also in the human diagnostic space.
Along the way, I started a 501(c)3 nonprofit called Mountain Flower Goat Dairy, a dairy and educational non-profit that had a community milk-share, which included summer camps and workshops for people to learn about local and sustainable agriculture. I became more and more interested in agriculture and decided to take my career in that path and that’s really what set me up to start Front Range Biosciences.
Aaron: Do you have any co-founders?
Jon: I have two other co-founders. They both played various roles over the last four years. One was another scientist, Chris Zalewski, PhD. He currently works in the R&D department and helps oversee several different parts of the company including pathology and product development. My other co-founder, Nick Hofmeister served as chief strategic officer for the last few years, and has helped raise the majority of our funding. We’ve raised over $45 million dollars, and he played a big role in that.
Aaron: What makes you different from other cannabis seed companies?
John: We’ve built the first true cannabis genetics platform. What I mean by that is we built a platform that allows us to develop and produce new plant varieties that support both the hemp and the cannabis markets. To us, it’s all cannabis. Hemp and cannabis are scientifically the same plant. They just have different regulatory environments, different products and different markets, but we stay focused on the plant. Our platform is built on several different pillars. Genetics are one of the core pieces, and by genetics I mean, everything from molecular based breeding to marker assisted breeding to large germplasm collections. We collect different varieties of germplasm, or seed, from all over the world and use those to mix and match and breed for specific traits. We also have large nursery programs. Another one of our pillars of the platform includes greenhouse nursery production — everything from flowering cannabis plants to producing cannabis seeds to cloning and producing mother plants and rooted cuttings or clones.
Then tissue culture is another part of the platform, it’s basically the laboratory version of a greenhouse nursery. It’s housed in a sterile environment and allows us to produce plants that are clean and healthy. It’s a much more effective, modern way to manage the nursery. It’s part of our clean stock program, where we start clean, stay clean, and you can finish clean. It’s really built on all of those different pieces.
We also have capabilities in analytical chemistry and pathology, that allow us to better understand what drives performance and the plants, and both different regions as well as different cannabinoid products or terpene products. All of the science and capabilities of the platform are what allow us to create new varieties faster, better, stronger.
Aaron: It sounds like you’re vertically integrated on the front-end of cannabis cultivation.
Jon: Absolutely, that’s a great way to think about it.
The last piece I’d say is that we have areas of research and development that cover the full span of multiple product lines. We think about it from an ingredient perspective. Cannabinoids and terpenes are certainly what drive a large part of the cannabis market in terms of edibles, smokable flower, vapes and extracts and the different effects and flavors that you get. We also are looking at other ingredients, like plant-based protein and hemp as a viable protein source and the ability for hemp to produce valuable fiber for textiles, as well as industrial building materials and applications.
Lastly, there are additional small molecules that we’re working on as well from a food ingredients perspective. There are all kinds of interesting compounds. Everybody talks about the cannabinoids and terpenes, but there are also things like flavonoids, and some other very interesting chemistries that we’re working on as well.
Aaron: What geographies are you currently in?
Jon: Colorado and California primarily and we have a small R&D partnership in Barcelona.
Aaron: Do you have plans for expansion beyond that?
Jon: Our current headquarters are out of Colorado, and most of our Colorado operations right now are all hemp. Our hemp business is national and international.
We work with a licensed cannabis nursery partner in California which is our primary focus for that market, but we will be expanding the cannabis genetics and nursery program into Colorado next year. From a regulated cannabis perspective, that’s the first move. Beyond that, we’re in conversations with some of the multi-state operators and cannabis brands that are emerging to talk about how to leverage our technology and our genetics platform across some of the other markets.
Aaron: How do you think about genetics in your products?
Jon: Genetics means a lot of things to different folks depending on your vantage point and where you sit in the supply chain. Our business model is based on selling plants and seeds. At the end of the day, we don’t develop oils, extracts and products specifically, but we develop the genetics behind those products.
For us, it’s not only about developing genetics that have the unique qualities or ingredients that a product company might want like CBD, or other minor cannabinoids like THCV for example, but also about making sure that those plants can be produced efficiently and effectively. The first step is to introduce the ingredient to the product. Then the second step is to make sure that growers can grow and produce the plant. That way they can stabilize their supply chain for their product line. Whether it’s for a smokable flower product, or a vape product, or an edible product, it’s really important to make sure that they can reproduce it. That’s really how we think about genetics.
Aaron: What is a smart plant? That’s something I saw on your website.
Jon: It’s really about plants that perform under specific growing regions, or growing conditions. For example, in hemp, it’s one thing to produce CBD or CBG. It’s another thing to be able to produce it efficiently in five different microclimates around the U.S. Growing hemp in Florida or Alabama down on the Gulf Coast versus growing on the Pacific Northwest coast of Washington, or Oregon are two very different growing conditions that require smart plants. Meaning they can grow and thrive in each of those conditions and still produce the intended product. Generally, the different regions don’t overlap. The genetics that you would grow in Pacific Northwest are not going to do as well as some better selected varieties for the South East.
It’s not only different outdoor growing regions, but it’s different production styles too. When you think about regulated cannabis the difference between outdoor and indoor greenhouse is mixed light production. Even with hydroponic type growing methods, there are lots of different ways to grow and produce this plant and it’s not a one size fits all. It’s really about plants that perform well, whether it’s different regions in the United States in outdoor production or different indoor greenhouses with mixed lights and production methods.
Aaron: You market CBG hemp as a product line. What made you start with CBG? Is that a pull from the market or something you guys see trending?
Jon: So I think it’s a little bit of both. We offer CBD dominant varieties and CBG dominant varieties of hemp. We also now have other cannabinoids in the pipeline that we’ll be putting out in different varieties next year. Things like CBC as well as varins, or propyl cannabinoids. Also things like CBDV, CBCV, or CBGV, which are the propylcannabinoid versions of the more familiar compounds.
There was a lot of market demand for CBG. It was a fairly easy cannabinoid to produce as a single dominant cannabinoid similar to CBD or THC. There’s a lot of up-and-coming demand for some of the other minor cannabinoids. Up until a few years ago, CBD was considered a minor cannabinoid. It wasn’t until Charlotte’s Web in the Sanjay Gupta story that it became a major cannabinoid. So I think we see some level of market pull across the category.
On the flip side of that, we have one of the world’s largest R&D teams and consolidated expertise in terms of cannabis. We see the potential for minor cannabinoids, and even terpenes and other compounds like flavonoids to have wide ranging implications in human health. Everything from wellness products, to active pharmaceutical ingredients, to recreational products. From our perspective, that’s the reason why we’re pushing these ingredients. We believe that there are a lot of good products that come out of this work and the genetics that produce these minor cannabinoids.
Aaron: Okay, great. And then last question, is there anything you’re interested in learning more about?
Jon: I think the most exciting thing for me, given my background in clinical diagnostics and human health, is to see more data around how all of these different compounds of the plant can support improved wellness, health and nutrition. I think we’ve only scratched the tip of the iceberg. This type of research and data collection takes years, even decades, especially to see outcomes over time of people using these products. I’m really excited to see more of that and also hopefully be able to make stronger conclusions about some of the benefits that can be had from this plant.
Aaron: That’s the end of the interview, thanks Jon!
Editor’s Note: Part 3 will be an interview with Liz Conway, Regional President of Florida at Parallel. In part 4 we’ll sit down with Stephanie Gorecki, vice president of product development at Cresco Labs.
Cannabis infused products manufacturing is quickly becoming a massive new market. With companies producing everything from gummies to lotions, there is a lot of room for growth as consumer data is showing a larger shift away from smokable products to ingestible or infused products.
This is the second article in a series where we interview leaders in the national infused products market. You can find the first piece here. In this second piece, we talk with Mike Hennesy, vice president of innovation at Wana Brands. Mike started with Wana in 2014 after moving to Colorado and leveraged his science background to transition into product development and innovation where he has helped develop one of the best-known brands in Colorado.
Next week, we’ll sit down with Liz Conway, Regional President of Florida at Parallel. Stay tuned for more!
Aaron Green: Thank you for taking the time today. Just to start off, can you walk me through how you got involved at Wana Brands?
Mike Hennesy: Thanks Aaron. I got involved in the cannabis industry pretty intentionally. After graduating college in 2012, I was determined to get involved. I moved to Colorado from the east coast. I’m originally from Virginia. I moved out here in 2013 and started with Wana in 2014.
I got involved in the sales side of the business originally – as the company was just starting to emerge into the legal recreational market – and oversaw growth here at Wana during significant changes in the industry. Over time, my role transitioned into innovation and R&D where I am leaning on my background in science.
I now lead new product development and education as Vice President of Innovation, and I’m also completing a master’s degree in cannabis science and therapeutics.
Aaron: So, what does innovation mean to you?
Mike: Innovation for the cannabis industry is pretty unique and interesting. We are just beginning to unpack the pharmacopeia of the cannabis plant as well as starting to understand our own bodies endocannabinoid system.
Innovation spans from genetics of plants and how they are grown to how you deliver cannabinoids to the body and what different ratios and blends of cannabinoids and terpenes you are actually putting in there. So, innovation is not a one size fits all category for cannabis.
Aaron: Sounds like an interesting role! At Wana Brands, and in your role in innovation, how do you think about differentiating in the market with your products?
Mike: I would describe the way we perceive differentiation as going beyond simple developments, such as product forms or new flavors. We see the future of product development trending towards what active ingredients and in what ratios we are putting into products. For example, what kinds of cannabinoids and terpenes are we using? What kinds of drug delivery systems might we be harnessing? How do we put all of these ingredients and technologies into a product to make it more effective?
A simple way to think about all of this is: how is our product going to work better for the consumer? Because that is really the key here. Tasting great is important, but we are delivering a product that provides an experience. We want to continue to make a better experience and a better way for customers to enhance their life.
Aaron: I think that leads nicely into our next question, which is, when you’re thinking about creating a new product for the consumer, what’s your process for creating a new product?
Mike: We have a very full pipeline of new products, and many of these ideas come from networking and speaking with innovators and following the research and science for inspiration and direction. We take this information and start brainstorming as a team. We have a decade of experience in the cannabis space that provides us with a unique lens on how we apply new research to our product development.
From there, we build a product development pipeline of potential ideas and start to prioritize, looking at the feasibility of each of these ideas and their market readiness. Sometimes we have a great idea for a product, but a lack of consumer knowledge may mean we don’t move forward with launching.
Aaron: Can you expand a bit on what you mean by education and how you guys think about education to the end consumer?
Mike: Since product innovation must move with consumer knowledge and cannabis is so new, education is critical. We have a very robust education platform with topics that range from cannabis 101 to the endocannabinoid system, to lessons on terpenes and CBD, as well as trainings on our products themselves. We have both bud tender-facing and consumer-facing trainings. The consumer trainings are on our website, and bud tender trainings are hosted through dispensaries.
Aaron: Is that training electronic training or written material?
Mike: Both, but the primary platform is online in the form of interactive training courses. We also have printed flip book training material in dispensaries and offer in-person presentations, but with the pandemic, we’ve been heavily leaning on the online training content.
Aaron: Alright. So, we’re going to take a different direction here on questions. From your perspective, at the innovation level, can you walk me through your experience with your most recent product launch?
Mike: Most recently, we launched the line of Wana Quick Fast-Acting Gummies. I am extremely excited and proud of this line. They have absolutely exploded in popularity!
The idea for these products started a few years ago as we were learning cannabinoids are not very bioavailable. This means most of the cannabinoids that you consume from an edible do not end up in the bloodstream. Edibles also have a delayed onset and undergo a conversion of THC in the liver, called first pass metabolism, that gives a heavier sedating high. This slow onset and difference in effects with edibles can be a turn off for some consumers, leading us to the idea of developing a fast acting gummie that works differently.
It was about two years of research looking at technologies developed by pharma and nutraceutical companies to improve bioavailability and bypass first pass metabolism. We started looking into nano-emulsions and encapsulation of cannabinoids that help with bioavailability and reduce the onset time. These technologies envelop the cannabinoids like a disguise that tricks the body into absorbing the oily compounds more easily. The encapsulation bypasses the liver and is absorbed into the bloodstream quickly, so their effect starts within five to fifteen minutes. Since they are not processed in the liver, they deliver delta-9 THC instead of 11-hydroxy-THC, giving an effect I describe as a “smoker’s high.”
We trialed and tweaked many technologies before we landed on one that is truly effective and worked with our line of gummies. With this revolutionary technology inside, we then crafted delicious flavors and a new triangular shape to differentiate them from our classic gummies. Because they take effect so quickly and only last about three hours, we thought the Quick Fast-Acting Gummies were the perfect product to use during happy hour. So, we have Happy Hour inspired flavors like Pina Colada, Strawberry Margarita and Peach Bellini.
We launched in March, and already right now, these SKUs in Colorado are #4, #7 and #11 out of all edibles sold in Colorado. And overall, Wana produces eight out of the ten top SKUs in Colorado. That’s according to BDSA, so a pretty impressive achievement!
Aaron: Okay, great, I’d say so! The next question here goes deeper in the supply chain. How do you go about sourcing for the ingredients?
Mike: I am going to start with the cannabis side of things. As I mentioned earlier, cannabis is unique. It is not just one ingredient. It’s many different compounds like the cannabinoids THC, CBD and others, but also terpenes and other beneficial compounds. To make the most effective edibles we partner with growers that care about their genetics, how they are growing, and how they are extracting to create high quality cannabis extracts.
We also understand terpenes are so important in the entourage effect, and that different terpene blends synergize with cannabinoids to produce different effects. Some can be energizing while others are more relaxing. Wana has innovated the terpenes we use by formulating proprietary blends of thirty terpenes or more that replicate indica, sativa and hybrid strains.
We did this by strain hunting the best cannabis in each class and analyzing the strains to understand their profiles. Then using organic, botanically derived terpenes, we build blends in the ratios they are found in the plant and reintroduce them into our edibles. This means Wana edibles match the terpenes that you will find in cannabis, unlike other products that just use distillates where the terpenes are degraded and lost in extraction. This also means we can replicate these blends with our partners in other states, so when you consume a Wana indica or sativa product you’re going to have the same terpene blends and the same experience and feeling every time.
Beyond cannabis and terpenes, we are extremely selective in all of our ingredients. And in the near future we’re implementing an optimized recipe that is all-natural, with no high-fructose corn syrup, as well as moving towards organic ingredient sourcing.
Aaron: Can you give me an example in your role of a challenge that you run into frequently?
Mike: I think that is the exciting thing about working in R&D and new products: there is always a new challenge. I guess I would say if you are not making mistakes, you are not really trying to push the envelope in product development.
We are working with plant matter, terpenes and encapsulation technologies, things that don’t always taste good, and putting them all into edibles. That means we frequently run into the challenge of figuring out how to put the right ingredients for effect in a product, but still make it taste delicious. We are very selective in what ingredients we use and how we’re introducing them to make sure the product still tastes good. We oftentimes come across a great technology—such as a terpene blend or a quick onset delivery system—that does the job, but is not optimal for a gummie recipe, such as the resulting consistency or taste.“These developments are all heading in the direction of delivering consistent repeatable experiences for consumers, which is what I see as the future of cannabis.”
Aaron: Would it be correct to say that formulation is a common thing you run up against in terms of challenges?
Mike: Yes, especially because a lot of the ingredients and technologies we are working with are new. There isn’t a guidebook for how to incorporate encapsulated cannabinoids into a gummy, for example.
That’s the novel aspect of a lot of this: how do you take a terpene blend that’s designed to mimic the cannabis plant and put it in your gummies? What’s the right way to introduce it so they’re not degraded by heat? Formulating with cannabis is about problem solving, and is the backbone to what we do in R&D
Aaron: We’re getting towards the end of the conversation here. And these questions are more geared towards you individually. So, what trends are you following in the industry right now?
Mike: I’ve got to have my eyes on a lot of things. That’s how you innovate in this industry!
I would say No. 1 is still terpenes. We are already innovating there, but I think we’re just scratching the surface of where we’re going to go. I think terpenes are going to unlock a lot of potential in cannabis products in the future, and Wana is going to be innovating there, leading the pack.
Next is minor cannabinoids. Through decades of an illicit black-market, the genetics have skewed towards high THC strains, but the cannabis genome actually allows for many other cannabinoids to be formed. Through the right cultivation and breeding programs, we are going to see a lot more CBG, CBN, CBC, and even more rare cannabinoids like THCV and others. These currently rare cannabinoids are going to be important for new product development as we learn more about their therapeutic effects.
Then there is continued innovation on delivery systems and bioavailability, functional ingredient blends and more natural products. These developments are all heading in the direction of delivering consistent repeatable experiences for consumers, which is what I see as the future of cannabis.
Aaron: Awesome. What are you interested in learning more about? This could be cannabis related or business related.
Mike: Well, fortunately, I am working on a master’s degree right now and so I get to learn a lot every day. I am most curious to see where science takes us with the endocannabinoid system. It was pretty much unheard of until a few decades ago, and now we understand that it interacts with almost every other system in the body. It is like missing the elephant in the room when you are talking about human biology. The amount of information that we’re going to unlock about how the ECS interacts and regulates our body is going to continue to revolutionize the industry There’s a lot more to be understood around how different compounds interact with the ECS and affect us, and I think we are going to learn how we can use it to tailor other products for outcomes such as sleep, pain, anxiety, energy and focus.
Aaron: Just a clarification there. What are you working on for your master’s?
Mike: I’m getting a Master’s in Medical Cannabis Science and Therapeutics from the School of Pharmacy at the University of Maryland. It is the very first master’s level program of its kind, and is taught by doctors and pharmacists, so we discuss cannabis as a drug and how it effects the brain and the body. It has been really exciting and I’m looking forward to continuing learning more about this amazing plant!
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.
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.
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.
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
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
By Alison J. Baldwin, Brittany R. Butler, Ph.D., Nicole E. Grimm 1 Comment
With legalization of cannabis for medicinal and adult use occurring rapidly at the state level, the industry is seeing a sharp increase in innovative technologies, particularly in the area of cannabis extraction. Companies are developing novel extraction methods that are capable of not only separating and recovering high yields of specific cannabinoids, but also removing harmful chemicals (such as pesticides) from the concentrate. While some extraction methods utilize solvents, such as hydrocarbons, the industry is starting to see a shift to completely non-solvent based techniques or environmentally friendly solvents that rely on, for example, CO2, heat and pressure to create a concentrate. The resulting cannabis concentrate can then be consumed directly, or infused in edibles, vape pens, topicals and other non-plant based consumption products. With companies continually seeking to improve existing extraction equipment, methods and products, it is critical for companies working in this area to secure their niche in the industry by protecting their intellectual property (IP).
Comprehensive IP protection for a business can include obtaining patents for innovations, trademarks to establish brand protection of goods and services, copyrights to protect logos and original works, trade dress to protect product packaging, as well as a combination of trade secret and confidentiality agreements to protect proprietary information and company “know-how” from leaking into the hands of competitors. IP protection in the cannabis space presents unique challenges due to conflicting state and federal law, but for the most part is available to cannabis companies like any other company.
Federal trademark protection is currently one of the biggest challenges facing cannabis companies in the United States. A trademark or service mark is a word, phrase, symbol or design that distinguishes the source of goods or services of one company from another company. Registering a mark with the U.S. Patent and Trademark Office (USPTO) provides companies with nationwide protection against another company operating in the same space from also using the mark.
As many in the industry have come to discover, the USPTO currently will not grant a trademark or service mark on cannabis goods or services. According to the USPTO, since cannabis is illegal federally, marks on cannabis goods and services cannot satisfy the lawful use in commerce requirement of the Lanham Act, the statute governing federal trademark rights. Extraction companies that only manufacture cannabis-specific equipment or use cannabis-exclusive processes will likely be unable to obtain a federal trademark registration and will need to rely on state trademark registration, which provides protection only at the state-level. However, extractors may be able to obtain a federal trademark on their extraction machines and processes that can legitimately be applied to non-cannabis plants. Likewise, companies that sell cannabis-infused edibles may be able to obtain a federal trademark on a mark for non-cannabis containing edibles if that company has such a product line.
Some extraction companies may benefit from keeping their innovations a trade secretSince the USPTO will not grant marks on cannabis goods and services, a common misconception in the industry is that the USPTO will also not grant patents on cannabis inventions. But, in fact, the USPTO will grant patents on a seemingly endless range of new and nonobvious cannabis inventions, including the plant itself. (For more information on how breeders can patent their strains, see Alison J. Baldwin et al., Protecting Cannabis – Are Plant Patents Cool Now? Snippets, Vol. 15, Issue 4, Fall 2017, at 6). Unlike the Lanham Act, the patent statute does not prohibit illegal activity and states at 35 U.S.C. § 101 that a patent may be obtained for “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof.”
For inventions related to extraction equipment, extraction processes, infused products and even methods of treatment with concentrated formulations, utility patents are available to companies. Utility patents offer broad protection because all aspects related to cannabis extraction could potentially be described and claimed in the same patent. Indeed, there are already a number of granted patents and published patent applications related to cannabis extraction. Recently, U.S. Patent No. 9,730,911 (the ‘911 patent), entitled “Cannabis extracts and methods of preparing and using same” that granted to United Cannabis Corp. covers various liquid cannabinoid formulations containing very high concentrations of tetrahydrocannabinolic acid (THCa), tetrahydrocannabinol (THC), cannabidiol (CBD), THCa and cannabidiolic acid, THC and CBD, and CBD, cannabinol (CBN), and THC. For example, claim 1 of the ‘911 patent recites:
A liquid cannabinoid formulation, wherein at least 95% of the total cannabinoids is tetrahydrocannabinolic acid (THCa).Properly crafted non-disclosure agreements can help further ensure that trade secrets remain a secret indefinitely.
Although the ‘911 patent only covers the formulations, United Cannabis Corp. has filed a continuation application that published as US2017/0360745 on methods for relieving symptoms associated with a variety of illnesses by administering one or more of the cannabinoid formulations claimed in the ‘911 patent. This continuation application contains the exact same information as the ‘911 patent and is an example of how the same information can be used to seek complete protection of an invention via multiple patents.
An example of a patent application directed to solvent-based extraction methods and equipment is found in US20130079531, entitled “Process for the Rapid Extraction of Active Ingredients from Herbal Materials.” Claim 1 of the originally filed application recites:
A method for the extraction of active ingredients from herbal material comprising: (i) introducing the herbal material to a non-polar or mildly polar solvent at or below a temperature of 10 degrees centigrade and (ii) rapidly separating the herbal material from the solvent after a latency period not to exceed 15 minutes.
Claim 12, covered any equipment designed to utilize the process defined in claim 1.
Although now abandoned, the claims of this application were not necessarily limited to cannabis, as the claims were directed to extracting active ingredients from “herbal materials.”
Other patents involve non-toxic extraction methods utilizing CO2, such as Bionorica Ethics GMBH’s U.S. Patent No. 8,895,078, entitled “Method for producing an extract from cannabis plant matter, containing a tetrahydrocannabinol and a cannabidiol and cannabis extracts.” This patent covers processes for producing cannabidiol from a primary extract from industrial hemp plant material.
There have also been patents granted to cannabis-infused products, such as U.S. Patent No. 9,888,703, entitled “Method for making coffee products containing cannabis ingredients.” Claim 1 of this patent recites:
A coffee pod consisting essentially of carbon dioxide extracted THC oil from cannabis, coffee beans and maltodextrin.
Despite the USPTO’s willingness to grant cannabis patents, there is an open question currently regarding whether they can be enforced in a federal court (the only courts that have jurisdiction to hear patent cases). However, since utility patents have a 20-year term, extractors are still wise to seek patent protection of the innovations now.
Another consideration in seeking patent protection for novel extraction methods and formulations is that the information becomes public knowledge once the patent application publishes. As this space becomes increasingly crowded, the ability to obtain broader patents will decline. Therefore, some extraction companies may benefit from keeping their innovations a trade secret, which means that the secret is not known to the public, properly maintained and creates economic value by way of being a secret. Properly crafted non-disclosure agreements can help further ensure that trade secrets remain a secret indefinitely.
Regardless of the IP strategy extractors choose, IP protection should be a primary consideration for companies in the cannabis industry to ensure the strongest protection possible both now and in the future.
As mentioned in Part 1, the physiological effects of cannabis are mediated by a group of structurally related organic compounds known as cannabinoids. The cannabinoids are biosynthetically produced by a growing cannabis plant and Figure 1 details the biosynthetic pathways leading to some of the most important cannabinoids in plant material.
The analytical measurement of cannabinoids is important to ensure the safety and quality of cannabis as well as its extracts and edible formulations. Total cannabinoid levels can vary significantly between different cultivars and batches, from about 5% up to 20% or more by dry weight. Information on cannabinoid profiles can be used to tailor cultivars for specific effects and allows end users to select an appropriate dose.
Routine Analysisvs. Cannabinomics
Several structurally analogous groups of cannabinoids exist. In total, structures have been assigned for more than 70 unique phytocannabinoids as of 2005 and the burgeoning field of cannabinomics seeks to comprehensively measure these compounds.¹
Considering practical potency analysis, the vast majority of cannabinoid content is accounted for by 10-12 compounds. These include Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), Δ9-tetrahydrocannabivarian (THCV), cannabidivarin (CBDV) and their respective carboxylic acid forms. The cannabinoids occur primarily as carboxylic acids in plant material. Decarboxylation occurs when heat is applied through smoking, vaporization or cooking thereby producing neutral cannabinoids which are more physiologically active.
Potency Analysis by HPLC and GC
Currently, HPLC and GC are the two most commonly used techniques for potency analysis. In the case of GC, the heat used to vaporize the injected sample causes decarboxylation of the native cannabinoid acids. Derivatization of the acids may help reduce decarboxylation but overall this adds another layer of complexity to the analysis² ³. HPLC is the method of choice for direct analysis of cannabinoid profiles and this technique will be discussed further.
A sample preparation method consisting of grinding/homogenization and alcohol extraction is commonly used for cannabis flower and extracts. It has been shown to provide good recovery and precision² ³. An aliquot of the resulting extract can then be diluted with an HPLC compatible solvent such as 25% water / 75% acetonitrile with 0.1% formic acid. The cannabinoids are not particularly water soluble and can precipitate if the aqueous percentage is too high.
To avoid peak distortion and shifting retention times the diluent and initial mobile phase composition should be reasonably well matched. Another approach is to make a smaller injection (1-2 µL) of a more dissimilar solvent. The addition of formic acid or ammonium formate buffer acidifies the mobile phase and keeps the cannabinoid acids protonated.
The protonated acids are neutral and thus well retained on a C18 type column, even at higher (~50% or greater) concentrations of organic solvent² ³.
Detection is most often done using UV absorbance. Two main types of UV detectors are available for HPLC, single wavelength and diode array. A diode array detector (DAD) measures absorbance across a range of wavelengths producing a spectrum at each point in a chromatogram while single wavelength detectors only monitor absorbance at a single user selected wavelength. The DAD is more expensive, but very useful for detecting coelutions and interferences.
Chemical Constituents of Marijuana: The Complex Mixture of Natural Cannabinoids. Life Sciences, 78, (2005), pp. 539
Development and Validation of a Reliable and Robust Method for the Analysis of Cannabinoids and Terpenes in Cannabis. Journal of AOAC International, 98, (2015), pp. 1503
Innovative Development and Validation of an HPLC/DAD Method for the Qualitative and Quantitative Determination of Major Cannabinoids in Cannabis Plant Material. Journal of Chromatography B, 877, (2009), pp. 4115
Rebecca is an Applications Scientist at Restek Corporation and is eager to field any questions or comments on cannabis analysis, she can be reached by e-mail, email@example.com or by phone at 814-353-1300 (ext. 2154)
When a cannabis sample is submitted to a lab for testing there is a four-step process that occurs before it is tested in the instrumentation on site:
It is ground at a low temperature into a fine powder;
A solution is added to the ground powder;
An extraction is repeated 6 times to ensure all cannabinoids are transferred into a common solution to be used in testing instrumentation.
Once the cannabinoid solution is extracted from the plant matter, it is analyzed using High Pressure Liquid Chromatograph (HPLC). HPLC is the key piece of instrumentation in cannabis potency testing procedures.
While there are many ways to test cannabis potency, HPLC is the most widely accepted and recognized testing instrumentation. Other instrument techniques include gas chromatography (GC) and thin layer chromatography (TLC). HPLC is preferred over GC because it does not apply heat in the testing process and cannabinoids can then be measured in their naturally occurring forms. Using a GC, heat is applied as part of the testing process and cannabinoids such as THCA or CBDA can change form, depending on the level of heat applied. CBDA and THCA have been observed to change form at as low as 40-50C. GC uses anywhere between 150-200C for its processes, and if using a GC, a change of compound form can occur. Using HPLC free of any high-heat environments, acidic (CBDA & THCA) and neutral cannabinoids (CBD, THC, CBG, CBN and others) can be differentiated in a sample for quantification purposes.
Near infrared (NIR) has been used with cannabis for rapid identification of active pharmaceutical ingredients by measuring how much light different substances reflect. Cannabis is typically composed of 5-30% cannabinoids (mainly THC and CBD) and 5-15% water. Cannabinoid content can vary by over 5% (e.g. 13-18%) on a single plant, and even more if grown indoors. Multiple NIR measurements can be cost effective for R&D purposes. NIR does not use solvents and has a speed advantage of at least 50 times over traditional methods.
The main downfall of NIR techniques is that they are generally less accurate than HPLC or GC for potency analyses. NIR can be programmed to detect different compounds. To obtain accuracy in its detection methods, samples must be tested by HPLC on ongoing basis. 100 samples or more will provide enough information to improve an NIR software’s accuracy if it is programmed by the manufacturer or user using chemometrics. Chemometrics sorts through the often complex and broad overlapping NIR absorption.
Bands from the chemical, physical, and structural properties of all species present in a sample that influences the measured spectra. Any variation however of a strain tested or water quantity observed can affect the received results. Consistency is the key to obtaining precision with NIR equipment programming. The downfall of the NIR technique is that it must constantly be compared to HPLC data to ensure accuracy.
At Eurofins Experchem , our company works with bothHPLC and NIR equipment simultaneously for different cannabis testing purposes. Running both equipment simultaneously means we are able to continually monitor the accuracy of our NIR equipment as compared to our HPLC. If a company is using NIR alone however, it can be more difficult to maintain the equipment’s accuracy without on-going monitoring.
What about Terpenes?
Terpenes are the primary aromatic constituents of cannabis resin and essential oils. Terpene compounds vary in type and concentration among different genetic lineages of cannabis and have been shown to modulate and modify the therapeutic and psychoactive effects of cannabinoids. Terpenes can be analyzed using different methods including separation by GC or HPLC and identification by Mass Spectrometry. The high-heat environment for GC analysis can again cause problems in accuracy and interpretation of results for terpenes; high-heat environments can degrade terpenes and make them difficult to find in accurate form. We find HPLC is the best instrument to test for terpenes and can now test for six of the key terpene profiles including a-Pinene, Caryophyllene, Limonene, Myrcene, B-Pinene and Terpineol.
Quality systems between different labs are never one and the same. Some labs are testing cannabis under good manufacturing practices (GMP), others follow ISO accreditation and some labs have no accreditation at all.
From a quality systems’ perspective some labs have zero or only one quality system employee(s). In a GMP lab, to meet the requirements of Health Canada and the FDA, our operations are staffed in a 1:4 quality assurance to analyst ratio. GMP labs have stringent quality standards that set them apart from other labs testing cannabis. Quality standards we work with include, but are not limited to: monthly internal blind audits, extensive GMP training, yearly exams and ongoing tests demonstrating competencies.
Maintaining and adhering to strict quality standards necessary for a Drug Establishment License for pharmaceutical testing ensures accuracy of results in cannabis testing otherwise difficult to find in the testing marketplace.
Important things to know about testing
HPLC is the most recommended instrument used for product release in a regulated environment.
NIR is the best instrument to use for monitoring growth and curing processes for R&D purposes, only if validated with an HPLC on an ongoing basis.
Quality Systems between labs are different. Regardless of instrumentation used, if quality systems are not in place and maintained, integrity of results may be compromised.
GMPs comprise 25% of our labour costs to our quality department. Quality systems necessary for a GMP environment include internal audits, out of specification investigations, qualification and maintenance of instruments, systems controls and stringent data integrity standards.
Dr. Zacariah Hildenbrand, chief scientific officer and partner at C4 Laboratories, is currently researching some of the lesser-known molecules in cannabis, and he’s on to something. His research focuses on discovering new molecules, determining their therapeutic effects and expanding our understanding of the constituents of cannabis.
Dr. Hildenbrand received his Ph.D. from the University of Texas at El Paso where he researched the molecular architecture involved in hormone-dependent cancers. At the University of Texas Southwestern Medical Center in Dallas, his post-doctoral research contributed to the development of a novel therapy for the treatment of chronic myeloid leukemia, a blood-borne cancer that afflicts small children. He has published over 25 peer-reviewed scientific journal articles and hopes to do the same with his research in cannabis.
After a career of scientific consulting, Dr. Hildenbrand met Ryan Treacy, founder and chief executive officer of C4 Laboratories, in 2015 when Treacy launched the company. In June of 2015, the laboratory began operations, providing Dr. Hildenbrand the opportunity to embark on a new and exciting field of research- cannabis.
They currently collaborate with Dr. Kevin Schug of the Shimadzu Center for Advanced Analytical Chemistry (SCAAC) at the University of Texas, Arlington and together Drs. Schug and Hildenbrand are pursuing a DEA license to expand their current cannabis research. The SCAAC is a $10.0+ million analytical laboratory with instrumentation that only a handful of people in the world has access to.
C4 Laboratories, based in Mesa, Arizona, currently offers a range of services for cannabis analysis including terpene and cannabinoid analytics, microbial, pesticide, fungicide and insecticide testing. In addition to the standard gamut of tests, they also specialize in cultivation analytics like mold and mildew culture testing, viral detection with sentinel plants and comprehensive analysis of environmental conditions.
What makes their company unique is their multidisciplinary effort to characterize the therapeutic compounds found in cannabis, the C4 Cannabinomics Collaborative. We sit down with Dr. Zac Hildenbrand to talk cannabis science, his research and what they hope to accomplish with the C4 Cannabinomics Collaborative.
CannabisIndustryJournal: What is the C4 Cannabinomics Collaborative?
Dr. Zacariah Hildenbrand: The C4 Cannabinomics Collaborative is an open collaboration between growers and scientists to discover new molecules in cannabis and to have a better characterization of individual cannabis strains based on the active constituents found in each sample. We are facilitating the collaboration of some of the world’s best cannabis growers with world-class scientists to find new information about the plant.
What we want to accomplish in this work is identifying novel molecules. Because of the [federal government’s] restrictions in researching cannabis, there is very little peer-reviewed literature on many of the compounds found in cannabis. We want to secondarily find out what those molecules do in the human body and thus make recommendations for strains targeting specific conditions.
We also want to understand the strains currently out there by determining the most established cannabinoids and terpenes via chemotyping. You hear a lot of people talking about the effects of an Indica or Sativa and making recommendations based on that. We want to find chemical signatures based on cannabinoids and terpenes and make recommendations based on that. There are a lot of problems at hand when discussing strain names scientifically. There are nomenclature issues- people calling the same strain different names, people giving multiple names to the same strain to make it appear that their strain portfolios are more diverse.
We can identify the chemical signatures in strains based on the major cannabinoids and terpenes. Based on the terpenes and chemical profile we can determine more accurate recommendations for patients as well as in recreational applications. All of this, again, discovering the new molecules, identifying the current strains, is so we can make more informed decisions regarding cannabis use. It is not a panacea but it is a very robust plant. There are a lot of terpenes with anti-inflammatory responses. Other molecules help with blood flow, sleep, regulating blood glucose, and we all know the cases of CBD helping children with convulsions and epilepsy. We want people to make sure they have the most up-to-date information.
CIJ: How is your collaboration with the SCAAC at UT Arlington contributing to this work?
Dr. Hildenbrand: One of the instruments we use there is a supercritical-fluid-extraction supercritical-fluid-chromatography mass-spectrometer (SFE-SFC-MS). With that instrument, we can do the extraction on the machine with an extreme level of sensitivity. It is ideal for drug discovery and identifying molecules in the parts-per-quadrillion range. This particular instrument allows us to detect molecules with an extreme level of sensitivity without volatizing them during the sample extraction process.
We want to acquire samples of unique cannabis from growers that will work with us to discover new cannabis constituents. We are in the process of getting a DEA license so that we can send products across state lines to the center at UT Arlington to perform the advanced characterization. They have instrumentation that only a handful of people in the world have access to, which gives us the best opportunity to explore the unknown. When we discover new molecules, find out what they do on the molecular level, we can then isolate these compounds and ultimately use this newfound knowledge for the development of effective nutraceuticals.
CIJ: What molecules are you researching right now?
Dr. Hildenbrand: Some of the low-hanging fruit in our research looks at identifying compounds similar to the better-studied compounds such as THC and CBD. THCV has a very similar structure to THC, but has a shorter acyl carbon chain (3 carbons vs. 5).
THCV doesn’t induce a psychoactive response (like THC), but it does improve fat utilization, so it has remarkable potential for medicine. We are looking at what conditions are required for it to occur naturally. Cannabis doesn’t produce THCV in a high amount. 0.7% by weight is the most we have seen in Arizona. In Oregon, where craft cannabis has been refined to a much higher degree, we have heard rumblings of some strains containing up to 3% THCV. We want to find out if this is a possible weight loss tool. Our research in CBDV is very much the same.
CBL is the breakdown product of CBC when it is treated with ultraviolet light. We know absolutely nothing about what CBL does. If we find a strain that produces high amounts of CBC, we can then treat it with UV light and force the conversion to CBL, and then ultimately determine what it does. This is a good example of low-hanging fruit and the versatility of cannabis. Based on the biogenesis of the cannabinoids, we can alter the profile of cannabis products using a series of biochemical reactions.
For example, we have been helping clients in Arizona look for a quality sleep aid in cannabis. Certainly, Indica strains will help, but the molecule CBN helps specifically with sleep abnormalities. As CBN is formed as a byproduct when CBD or THC are oxidized, we see some producers using liquid nitrogen to oxidize CBD, leading to higher CBN levels. I would like to think we are in the age of understanding CBD, THC and the major terpenes,but there are a whole milieu of compounds that require our attention and THCV, CBDV and CBL are just a few that we want to devote our efforts to right away.
CIJ: What are your plans in the immediate future?
Dr. Hildenbrand: We are in the process of finalizing the documents to bring a C4 laboratory into Oregon where we can do quite a bit of research and where we’ll have access to some very unique cannabis. We will offer full compliance testing per ORELAP and OLCC regulations, but we also want to acquire samples (free of charge) from growers that want to collaborate with us to discover new molecules. We’ve been lucky enough to start working with growers like Adam Jacques and Chris West in Eugene, but we also want to be available to other growers who want to contribute to this research.
CIJ: What are your long-term goals with this project?
Dr. Hildenbrand: At a basic level, we hope to expand the current understanding of the cannabis plant. There is a lot of “bro science” and anecdotal claims out there. There is so much that we don’t know about cannabis that we cannot simply rely on anecdotal claims for each strain. We want to bring cannabis into the same light as any pharmaceutical-grade or biomedical research.
We need to be characterizing this plant with the same level of detail as other pertinent molecular therapies. In doing so there are a lot of potential discoveries to be made and we might be able to unlock the future of medicine. A drug like Marinol, for example, has been met with mixed reviews because its only one dimensional. Furthermore, we find that the terpene molecules are tremendously beneficial and this interplay between cannabinoids and terpenes is something that we want to explore further. All and all we wish to further illustrate the therapeutic capacities of cannabis within the contexts of specific ailments and medical conditions, while discovering the medicine of the future.
David Goldstein, co-founder and chief executive officer of PotBotics, launched a medical cannabis recommendation engine called PotBot with the goal to better inform patients to target their conditions with more accurate recommendations based on scientific research. “This is a tool to help move the market away from the thousands of strain names that are mainly just marketing or branding indicators,” says Goldstein. The medical application is designed to inform patients on peer-reviewed data, research on the treatment of their ailments with cannabis and the specific cannabinoids that are necessary for treating their condition. They began development on PotBot in October of 2014, launching the beta version to 400 users in November of 2015. On April 20th, 2016, Goldstein launched officially in the Apple Store, and the program will be available on Android in July.
Rather than focusing on strain names, PotBot focuses on the cannabinoid values to help patients gain an understanding of the correlation between which compounds might best target their condition. “This is a great tool for patients trying to familiarize themselves with what strains might work best,” says Goldstein. “For example, insomnia patients generally need cannabis with higher CBN levels, so we first educate the patient on cannabinoid ranges to shoot for and what strains might help. PotBot would recommend the strain Purple Urple because it is an indica found to have higher CBN values,” adds Goldstein. The program goes into great detail with the patient’s preferences including everything down to consumption methods so they know why it might recommend certain strains.
The recommendation tool is accessible via kiosks at dispensaries, on a desktop version for the computer as well as on the Apple Store for iPads and iPhones. “I do not see it as a way of replacing budtenders, rather supplementing them with knowledge,” says Goldstein. PotBot is designed as a tool to supplement the budtender’s understanding of cannabis, so the budtender does not need to know everything off the top of their head or recommend strains based on anecdotal information, according to Goldstein.
Goldstein’s team at PotBotics performed extensive research prior to launching PotBot, spending two years doing strain testing to develop the program. “There is currently no regulatory body [for strain classification] so we took it upon ourselves to work with the best testing laboratories for truly robust analyses and properly vetted growers to get the most valid data,” says Goldstein. “The current strain classification system and nomenclature is rather unscientific so we focus on cannabinoid values and soon we will be able to incorporate terpene profiles in the recommendation.” Moving away from the common focus on taste, smell and other qualitative values, they focus on medical attributes of cannabinoid profiles because they have the most peer-reviewed research available today.
As an OEM, the company designed the tool to work with each dispensary’s inventory, to provide recommendations for strains that a patient can access on site, however anyone can access the recommendation tool for free at PotBot.com. Goldstein’s company and their mission represent an important development in the cannabis industry; this could begin a key transition from thousands of understudied strain names to a more scientific and calculated method to treating patients’ conditions with cannabis.
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