Terpenes and Testing World Conference 2018
Ethan Carruthers, PharmD, Treasurer of the American Society of Cannabis Pharmacists, attended the first-annual Terpenes and Testing Conference in Silicon Valley, CA on April 10-11, 2018.
Please enjoy his review of the conference and the important take-away points relevant for pharmacists and clinicians working with medical cannabis.
“Collection of Great Minds and Industry Leaders” This year the areas of focus were extraction technology trends, developing a common taxonomy of cultivar and chemovars, the role of cannabinoids and terpenes in cannabis chemistry, grow technologies, and regulatory and analytics. Continue reading to learn more about the science behind medical cannabis.
I. Extraction Technology
Although the vast majority of conference time was spent discussing supercritical & subcritical CO2 (I’ll just call it CO2 from here on out), it was clear that most of the industry is becoming painfully aware of CO2’s limitations and expense. Although CO2 is very selective, in many ways it is either too selective or not enough. CO2 is too selective in that it removes too many desirable components (many terpenes and cannabinoids are completely left behind) and it disproportionately concentrates others by up to 500%. Even under the best circumstances and including a first-stage extraction to preserve terpenes, the extract will not be representative of the starting material in any way, shape, or form- meaning that getting full profile extracts with CO2 is impossible. The second point is that CO2-produced extracts require a tremendous amount of post-extraction work to clean up via winterizing and other techniques. There’s a recent push to integrate older techniques into the newer ones to refine them. One example of this is addition of 5% ethanol (more is not better) in a pulsed manner to the CO2 extraction significantly improved the speed, yields, and terpene profiles compared to the pure CO2 extractions. This is especially prominent in the new super cold ethanol extractions (-20 degrees C) that gets a much better (read: more honest-to-plant and complete) terpene profile, more medically active unknown constituents, and it leaves the undesirables like fats, waxes, chlorophyll, lipids, and other contaminants behind. While CO2 was in many ways the star at the conference, it was clear that its limitations and sheer cost are factors causing many in the industry to look to other techniques.
To my mind the most promising but least covered technique discussed was extraction with R134a Freon. Freon is generally recognized as safe (GRAS) by the FDA and could be adapted to cannabis. The other speakers seemed to ignore this presenter- Dr. George Stantchev, of www.comerg.com- however, R134a is perfect for extracting exactly what you want and leaving out what you don’t want. In addition, it evaporates at -30 degrees C for perfectly clean recapture at just about 100%. Dr. Stantchev showed an incredibly methodical and logical argument to switching to R134a and, although he was somewhat ignored, I think he was taken seriously. The industry is so invested in CO2 right now that it doesn’t have the capacity to move to freon and convince people it’s safer and better. However, I think he will be vindicated and that Freon and/or cold ethanol may be the state of the art in the next decade.
There is a well-recognized problem in the cannabis industry: taxonomy. There is no common taxonomy and the “strain” designations are simply laughable going into the future. For one, strain is not a botanical term and it’s utterly meaningless. So are the terms Indica and Sativa. They are completely and utterly meaningless while also trying to convey something useful: how it MIGHT make you feel. The proper term is cultivar and that is what we should use going forward rather than strain. So, we need a common language for cultivars that convey a layer of meaning on its genomics and its intended effect. Unfortunately, there is no official body to design this taxonomy so it will necessarily be piecemeal.
The Israeli cannabis industry is the one “group” (although they are not monolithic in this sphere) who really want to create a common taxonomy for both cultivars and chemovars. So, what are chomovars? Well, every time you grow a cultivar clone, even under very well conserved conditions, the total chemical profile alters every single batch and most companies have no idea how to control for this. The exceptions to this rule are GW Pharmaceuticals, which bases its consistency on the methods laid out in the Ph. D. thesis of David Potter (pubmed link to articles)– “The Propagation, Characterization, and Optimization of Cannabis Sativa L as a Phytopharmaceutical”.
Another company that’s leading the pack in creating stable cultivars with consistent chemovars is the Dutch company Bedrocan. Those two companies have done the ground work to create really useful and stable cultivars that create stable chemovars every single time. The cannabis industry as a whole should learn from them and also move away from silly-named “strains” towards a new taxonomy-based methodology.
The third area is in the terpenes and cannabinoids themselves and how we use cannabis to create predictable therapeutic outcomes. First, we have to get away from the terpene wheels that predict effects in cannabis that are currently out there. When you see online how a terpene like alpha-limonene does this or that thing, that data was created on the terpene alone or from a very specific extract. The physiological effect these terpenes have when ingested alone is vastly different when they are ingested as a part of a whole-plant cannabis mixture. Another important point is that what you consider the important terpenes from a sensory perspective are NOT necessarily the ones that are most medically relevant.
For example, some Israeli companies have characterized which terpenes are most relevant to the traditional Sativa and Indica experience (i.e. which are most relevant to creating the non-sedating, energizing effects vs the sedating, pain-reducing effects). For the Sativa-like “Daytime” formulation the following five terpenes are most medically relevant: myrcene, ocimene, trans-α-bergamotene, α-guaiene, and trans-β-farnesene. For the Indica-like “Nighttime” formulation the top five terpenes are β-caryophyllene, linalool, fenchol, α-terpineol, and camphor. Now, I know that you were not expecting those to be the top five most medically relevant terpenes for the day vs. night effect- and that is the point. We still need to do the research to find which cannabinoids and terpenes are most medically relevant for a given condition and, to do that, we need a common taxonomy. So, that’s the first step. We need to form a council that everyone will listen to and create that taxonomy just like what was done in organic chemistry over a century ago. Without it, there is no common language and no way to move forward.
Characterizing which terpenes are most medically relevant should be a joint goal of the cannabis industry. Again, the Israeli groups paired with other scattered companies in Israel, Canada, and the US, seem to be taking the lead in this matter. One lead company that is extremely important in all of this is Eybna and they have partnered with many other companies. They have chemically characterized and created HPLC standards for all 144 known cannabinoids and around 200 terpenes. They are creating hitmaps of cannabis cultivars characterizing the full spectrum of cannabinoids and terpenes, and they are pairing them up with patient data. In Israel, if you are a medical cannabis patient, you need to participate in this research, I believe (I have not done the ground work to see how true this is). Eybna pairs up the chemovar data along with condition-specific survey data every month to evaluate which chemovars treat which conditions best. They also are conducting research on which chemovars and their extracts targets specific cancers (cell culture experiments) while evaluating which chemical constituents are most important in creating the cancer-killing effects. Every state with medical cannabis should be using the Israeli survey data to collect patient data every month (or whenever) patients come in to get their medicine. The Israeli groups want to pair this detailed chemical analysis and patient therapeutic data with machine learning to evaluate which constituents are most medically relevant and then eventually design clinical trials using those chemovars. They are years away from reaching this point but the Israelis are a half-decade ahead of everyone else, especially in the US.
In regards to growing cannabis, there are a few schools of thought. Some like it as natural and “organic” (whatever that means) as possible; others aim for the highest yields, and still others want to focus on creating cultivar/chemovar consistency. There are hundreds of arguments about soil vs hydroponic, pesticides vs natural predators, and many other interesting issues. Unfortunately, my lack of knowledge shows here and I found these sessions less interesting. One thing I would say is that for consistency, reducing insect predation, and limiting cultivar contamination, hydroponics seems to be the strongest choice. However, it’s very pricey and has a less ‘natural’ feel in an industry that prides itself in its naturalness. For many, this means going more old school. Honestly, I can see both sides in this debate and, frankly, I think the industry will thrive with the competition of ideas and approaches. That being said, don’t necessarily listen to the folks who say they have the perfect bacteria-fungus mixture to make your stuff grow amazingly. We can only characterize and culture a tiny proportion of the microbes responsible for the symbiotic relationships with roots and the vast majority are unculturable. So, while I think these techniques are useful and will be more so into the future, I wouldn’t bet the farm on them, as it were.
IV. Regulatory and Analytical
The final area of the conference I wanted to discuss were the regulatory and analytics aspects since these seem to be inseparably intertwined. The more and more cannabis comes into the light, the brighter the spotlight of regulation will become. My takeaways here are to make establishing Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP) a strategic priority for your companies, and monitor internal compliance using ISO9000-type internal audits. Developing robust Standard Operating Procedures and documentation practices will take some effort but will pay off in the long run. Companies in the medical cannabis space also will want to look into establishing in-house testing and getting experienced personnel doing your quality work; recruit quality professionals from pharmaceutical and cosmetic backgrounds, as those industries have already gone through these growing pains and understand FDA scrutiny.
Overall, it was a valuable conference to attend and meet many of the players working hard in the cannabis industry. Everyone is passionate about bringing cannabis “into the light” and generating good research and good practices. Many experts from the food, pharmaceutical, and cosmetic industries have a lot to teach those in the cannabis industry. The most important problem to be solved in the near future is getting everyone speaking the same language via a common taxonomy.