By Gursaanj Singh Bajaj and Markus Roggen, Ph.D., Complex Biotech Discovery Ventures (CBDV)
Products based on cannabis extracts are the fastest growing segments in the market. The demand for more cannabis extracts is constantly growing and so is the price pressure on these extracts. In most mature markets, the prices of cannabis and cannabis extracts have been declining, putting pressure on producers to stabilize their profit margins. This trend is usually expected from an established market. If revenue is falling, the only way to protect profits is to reduce costs.
Business people will suggest cutting labor costs or reducing material costs. We are scientists; we will not do such things. We want to point to the waste and inefficiencies in production and how to remove these. We want to help you reduce your cost of production and, possibly, make some better extract along the way.
What’s the issue?
While working in process chemistry and data analytics, many shortcomings can be observed in the production of cannabis throughout the industry. For example, terpenes are lost and cannabinol (CBN) is formed in the drying and decarboxylation process, extraction equipment is slowly breaking to leave behind delta-9-tetrahydrocannabinol (THC) oils in the plant, and badly tuned processes produce low-quality oils that need costly cleanup steps.
Not only do these drawbacks pose big problems to many companies, but most find it difficult, or even impossible, to understand the causes behind them. Though the answer differs for each case and company, drawbacks can be more easily realized if producers took a more comprehensive approach while tracking their process. Knowing what happens to the cannabis material throughout the entirety of the extraction process is extremely valuable. Simply enough, if more is known about the processes and mechanics involved with production, instead of just the material itself, we are able to monitor the processes, analyze them, and find improvement potential.
What can we do?
Data Tracking for Process Control
Extract manufacturers live by “garbage in, garbage out! Quality in, quality out!” How about garbage vs. quality work?
We see many companies put a singular focus on the input material, focusing on aspects such as weight and the profiles for cannabinoids and terpenes. While material input plays an important role in influencing the outcome, it does not do enough to reflect the complexity of all other process inputs involved (i.e. decarboxylation time, extraction pressure, winterization solvent, distillation temperature, etc.). We should also be tracking other important inputs. When considering extraction, by keeping better track of certain aspects of the extractor, such as the set temperatures, pressures, run times and the date, and more obscure aspects like particle size, we gain insights that could lead to minimizing waste production as well as high concentrated outputs. We can also spot instrument degradation early and in turn, minimize loss of efficiency among many other things [Figure 3].
Evidently, there are many other characteristics, both internal and external, in production that should be tracked and analyzed in order to better understand previous outcomes and, hopefully, prepare for future ones.
What should we do?
Data Analysis for Process Improvement
If the production teams keep meticulous track of their process data, and even sprinkle in some well-planned experimental conditions, it becomes possible to improve the process even further. Here is an example of how data was used to improve both the yield of cannabis extraction and the concentration of THC in the extract.
We can correlate how important certain inputs are to a known output through an analytical process known as the Design of Experiments (DOE). We can compute response surfaces to visually evaluate how the combination of input variables (e.g. temperature and pressure) impact the resulting output (e.g. yield and concentration). Figure 1 shows that we can expect the highest concentration of THC to be extracted at the middle ground pressure for separator 1 and higher pressure for separator 2. Whereas, Figure 2 shows that we can expect to have the highest yield at a low pressure for separator 1 and the lowest pressure for separator 2.
Why we should do it?
Data Analytics for the Future
Although, data analytics has found its way into sales processes some time ago, data analytics for production only saw its first applications very recently, and is still not widely accepted. The use of data analytics in cannabis production appears daunting. The usefulness of such analytics is also not directly apparent.
Process data analytics does not need to be hard; there are specialists for it, but it can be very useful if you try it out [check out the free data analytics tool on our website (https://www.cbdvl.com/freedata.html)].
The cannabis industry is in an early phase and we still have room for large improvements. But if we don’t know what we are doing, we cannot make it better.
By keeping track of how much material gets extracted per run and for what duration, we can actually keep track of the efficiency of certain instruments. As the trend suggests in Figure 1, with more experimental runs, less material weight gets extracted per hour, hinting to a failing pump.
Taking the hypothetical scenario where the company has run roughly 85 extraction runs in total, conducting 2 runs a day at 10 hours per run (4 hours used for cleaning and turnover), we can actually calculate the loss of potential extracted material during this span. This amounts to 850 hours.
The area covered in green represents the mass of material that has been extracted (X) whereas the area covered in red represents the mass lost from the failing pump (Y). So the total mass of material that the company could have extracted if they were to have tracked their pump earlier (Z) can be defined as:
So, the lost mass in comparison to the total can be denoted as (W) where
Using some basic geometry as a rough estimate, we see that equates to a 20% loss in yield of oil. This is equivalent to 5.61 kg of oil being lost throughout the span of all extraction. If we were to assume a gram of oil sells at $10 per gram, this amounts to a potential loss $56,000.
Cannabis use dates back to as early as 2700 BCE, where the Chinese Emperor Shen Nung drank it as a tea for its medicinal properties. Over the years, historical evidence of cannabis usage was found in many other countries, and the major application was as medicine. In the 1200’s BCE, Egyptian’s used it to treat Glaucoma, inflammation and enemas. Indians used it in around 1000 BCE as an anesthetic. There are even records from the Middle East, Ancient Greece and Rome, all dating before or in the early common era .
Cannabis made its way to North America in 1611 CE with the Jamestown settlers, a colony in Virginia, where it was commonly known as hemp . Hemp fiber became an important export and in 1619, the Jamestown settlers were required to grow hemp. Centuries later, hemp was still very important and refusing to grow hemp was against the law in many parts of America . Both Thomas Jefferson and George Washington grew hemp on their plantations.
Research into cannabis first stemmed from Dr. William B. O’Shaughnessy, who published a study in 1839, which investigated the plants medicinal effects . This study was the first of its kind for cannabis, and was very controversial at the time of its publication. However, it opened the doors for other researchers to enter the field and begin taking a closer look at this plant. It wasn’t until 1940 when the first cannabinoid was discovered by Dr. Robert S. Cahn, CBN (cannabinol) . Just two years later, Dr. Roger Adams successfully isolated a cannabinoid for the first time and it was CBD (cannabidiol). Dr. Adams is also responsible for the discovery of THC (tetrahydrocannabinol).
Another early scientist of note was Dr. Raphael Mechoulam, who in the 1980’s conducted a study on the treatment of epilepsy with the use of CBD. After treating eight individuals for four months with CBD, he found that half stopped having seizures, while the other half experienced a great reduction in the frequency of their seizures . Today, a study like this would have been seen as an amazing break through. However, when his paper was published it was not advertised as such due to the stigma around cannabis. With all the positive history towards cannabis, both in use as a medicine, and as a fiber, what changed?
The use of cannabis for its medicinal properties, for rope and other fibers was widespread in the early twentieth century. However, the recreational use was not. Smoking cannabis in a joint or in a pipe was popularized by Mexican immigrants, which resulted in a negative response within the U.S., probably affected by the xenophobia experienced at the time . Between 1914-1925, twenty-six states had passed laws prohibiting the plant. With the alcohol prohibition in effect from 1920, opiates and drugs were now the new focus. The use of the media was crucial as they sensationalized stories of drug users and the danger of their addictive effects. To constantly find new ways to portray these stories, the media began associating violent crimes such as murder with cannabis, rather than basing the reasons for the crime on evidence and facts . The release of propaganda such as the movie Reefer Madness in 1936, only added fuel to already concerned individuals about the so-called dangers of cannabis.
With all the negative press in the twentieth century, what changed that made cannabis so popular today? Its increase in popularity can be attributed to people who began to share their own personal experiences with cannabis. Stories, like that of Charlotte Figi, began to shift people’s perspectives towards cannabis. CBD managed to reduce Charlotte’s epileptic seizures from her having 300 a week, to only 2-3 a month . This is not the first instance where cannabis, and specifically CBD, has been seen to help with epileptic seizures, remember the study conducted by Dr. Mechoulam in the 1980’s? What frustrates many, is the time that could have been spent towards more research on the plant, but was wasted due to its criminalization. Now, with it being legalized in various countries, the research is trying to catch up.
The full medical potential of cannabis is unknown. One thing that is clear in the field, we have barely scratched the surface of this plant. With cannabinoids still being discovered, this is only the beginning of the journey.
Cannabis plant material preparation for efficient extraction operations with Fritsch Pulverisette 19
The Fritsch Pulverisette 19 is utilized to finely mill cannabis plant material in preparation for SFE processes. The efficient and precise reduction in particle size optimizes oil output and formulation.
Dr. Markus Roggen and Blake Grauerholz
The fast-growing field of cannabis extraction still holds many process inefficiencies, that can be easily overcome. A bottleneck often encountered is the packing density, or lack thereof, of cannabis plant material in the extraction vessel. Low packing density leads to a decrease in extraction efficiency and increase in output variability. Non-milled cannabis plant material generally experiences packing densities of 100-125 g/L, whereas milled material packs at 225-250 g/L.
The Fritsch Pulverisette 19 is an efficient tool to quickly comminute large volumes of cannabis plant material to a precise particle size. Plant material is fed into the Pulverisette 19 through large funnel for fast throughput. The negative pressure in the milling system ensures a continuous flow through the cutting rotor and the selected sieve cassette for precise particle sizing, and prevents any system clogging. The high throughput of up to 60 L/h is supported by large collection vessels of up to 10 liters. Fast processing is further supported by unrestricted accessibility of the cutting chamber, quickly removable cutting rotor and sieve cassette, and generally easy-to-clean grinding chamber.
In this application note we describe the general process employed at OutCo for sample preparation in their SFE production operation. This will include particle size distribution data and experimental data on extraction yield increases due to particle size reduction.
After testing (Figure 1), we chose the 2mm screen size, as it allows for a high packing density, increased extraction speed, optimized oil constitution, while allowing the operator to constantly feed material into the mill itself, thus increasing work efficiency. The blade speed of 300 rpm was found to be optimal for narrow particle size distribution. Furthermore, this low blade speed avoids thermal damage and loss of volatiles for the sample. It is important that the moisture content of the material being milled is dry, below 15%, as the milling sieve will clog in the presence of moisture. One full extraction load of 4.5 kg can be milled before stopping the machine to clean the sieve and behind the milling wheel to prevent buildup of chlorophyll and cannabis residue. If there is not enough of a single cultivar to facilitate a full extraction run, a blend of strains can be homogenized using the Fritsch mill. Strains selected for a blend should have complimentary flavor profiles and can also be chosen to enhance therapeutic effects.
Other applications OutCo uses the mill for is sample preparation for rosin pressing and milling of flower for pre-roll production. It was found that different particle sizes optimize draw behavior or item stability.
The Fritsch Pulverisette 19 critically supports OutCo’s extraction operations by providing fast milling of powders with precise particle size distribution and minimal degradation of raw material.
What is the difference between terpenes and terpenoids?
According to our growing database, the presence of over 450 terpenes (and counting!) have been found in cannabis and the chemical structure of many of them is still unknown! Interest in the ability of terpenes to influence the flavours, aromas, and potentially therapeutic effects of cannabis products is growing. This leads to more and more companies offering services like terpene isolation and terpene profiling.
But if you’re preparing to catch the terpene train, you might find that getting into specifics starts to get tricky - terpenes are often called “the future of cannabis” while also confused for terpenoids. We’ve also seen terpenoids called “denatured terpenes”, which is inaccurate. Terpenes and terpenoids are everywhere – in our perfumes, cosmetics, shampoo, food – and they can have vastly different properties. In chemistry, nomenclature can tell you a lot about what properties a molecule has and how specific compounds are structured. Thus, staying informed and critical about the information out there is vital for any producer and that is why it can be very useful to understand how terpenes are named and classified.
Let’s start with a little history. The word terpene is usually attributed to the chemist August Kekulé, who was the first to use the term to describe the hydrocarbons found in turpentine as the suffix “ene” illustrates the existence of a carbon-carbon double bound, for example ethene (figure 1). Over time this terminology has changed its meaning to address a broader class of compounds. The term terpene is currently used to characterize isoprene-based secondary metabolites.
Terpenes are generally found as part of essential oils. They are usually the dominant elements of rosin and turpentine. They are hydrocarbons which means that they are made up of only carbon and hydrogens. Furthermore, terpenes are built of multiple 5-carbon isoprene units (figure 1). Terpenes are classified according to the number of these 5-carbon units they contain – that’s where terms like “monoterpene", “sesquiterpene", and “diterpene” come from, a little counter-intuitively, these are made up of 2, 3, and 4 isoprene units respectively (figure 2). Terpenes are usually desirable in food and pharmaceutical products due to their flavouring and fragrances properties. These compounds usually act on receptors and neurotransmitters . The compounds tend to also mix well with lipids and fats. Limonene (figure 2), a monoterpene, for example, is a commonly used cleaning solvent. Terpenes can also be used in drugs to target malaria .
Terpenoids, on the other hand, are modified terpenes that contain additional elements and functional groups. These functional groups contain oxygen. Terpenoids can be “monoterpenoids", “sesquiterpenoids" and “diterpenoids”, mimicking the nomenclatura of terpenes (figure 3). Many terpenoids’ variations are biologically active and are used to cure many illnesses. One of the most known terpenoids are used to repress carcinogenic cells and are also components of drugs like Taxol .
Based on these differences, the use of the terms terpene and terpenoids interchangeably is incorrect. It is important to understand these differences, especially in the cannabis industry, as many compounds present in the plant are still to be discovered and the database is growing every minute. To understand the plants properties and its possible uses and advantages, a critical and accurate view of the plant’s composition is needed.
 Medical Jane (2019, 10). Introduction to Terpenes. Retrieved from https://www.medicaljane.com/category/cannabis-classroom/terpenes/#introduction-to-terpenes
McCreath, S. B., & Delgoda, R. (2017;2016;). Pharmacognosy: Fundamentals, applications and strategies. US: Academic Press.
Donnelly, D. (1991). Natural products of woody plants I and II. Phytochemistry, 30(1), 373-374. doi:10.1016/0031-9422(91)84163-M
 Perveen, S. (2018, 06). Introductory Chapter: Terpenes and Terpenoids. Retrieved from https://www.intechopen.com/books/terpenes-and-terpenoids/introductory-chapter-terpenes-and-terpenoids
Healthy and Concentrated Cannabis Plants: How to Use Acronyms to Optimize Production
Dr. Markus Roggen
This article was first published in the Journal of AOAC International, Vol. 102, no. 2, 2019. The original is viewable as a pdf here.
If you're interested in the work we do and would like to chat more, contact us.
The legal and regulated cannabis industry is a very recent development in the United States (1). Therefore, regulations, oversight, and enforcement have not yet conformed to the level seen in other established industries such as pharmaceutical or food supplement manufacturing. Because of a lack of clear, strict guidance from authorities, cannabis producers and trade groups (e.g., the National Cannabis Industry Association, the National Organization for the Reform of Marijuana Laws, Americans for Safe Access, etc.) are often left on their own to establish robust, consistent, and safe manufacturing processes. Although there are few official methods or policies (2–4), methodical frameworks such as the Hazard Analysis and Critical Control Points (HACCP) can be adopted from related industries to inform cannabis production. This report will detail the improvements made at OutCo’s cannabis facility through the adaptation of HACCP protocols throughout all stages of the cannabis production pipeline.
Now is the time to stop and think about extraction, cultivation methods
Dr. Markus Roggen
This article first appeared in Marijuana Venture on October 30th 2018.
In the last decade, many U.S. states have legalized either medical or recreational cannabis, and Canada followed through with recreational legalization in October.
In anticipation of those events, we have seen a “green rush,” where individuals and companies have been trying to build the largest cultivation, the biggest production or the widest distribution. It makes me wonder if the current green rush and the gold rush of the 19th century have a common ancestor, the “blind rush.” We are at a unique stage in the cannabis industry today; we can continue to blindly follow temptation, or we can stop, think and optimize our path.
Optimization of the Decarboxylation Reaction in Cannabis Extraction
Dr. Markus Roggen, Antonio M. Marelli, Doug Townsend, Ariel Bohman
The production of cannabis extracts and oils for medicinal and recreational products has increased significantly in North America. This growth has been driven by both market demand in newly legalized states and patient demand for a greater diversity in cannabis products.[1,2,3] Most cannabis extraction processes, independent of solvent or instrument choice, undergo a decarboxylation step whereby the carboxylic acid functional group is removed from the cannabinoids. The decarboxylation reaction converts the naturally occurring acid forms of the cannabinoids, e.g. tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), to their more potent neutral forms, e.g. tetrahydrocannabinol (THC) and cannabidiol (CBD). Because the carboxylic acid group is thermally labile, the industry typically applies a heat source, and at times a catalyst, to decarboxylate the cannabinoids
The heat-promoted decarboxylation reaction has been discussed at length within the industry, but an extensive literature search reveals very few papers on the process.[4, 5, 6] The data available represents a large spectrum of reaction conditions, including a range in reaction temperature, time and instrumental setup. As such, there is a lack of universal agreement surrounding the optimal reaction conditions for the decarboxylation process in cannabis extract. This reaction is further complicated by its sensitivity to water, with increased water content promoting the reaction. Additionally, studies show that competing isomerization, oxidation, and decomposition reactions can occur at elevated temperatures. These factors can lead to inconsistent cannabis extract products and an overall lack of quality control in the laboratory.
This article was first published on the Terpenes & Testing blog
Cannabis products are improving in both quality and sophistication every day. Even standardization of active ingredients and medicinal effectiveness is progressing. Our industry is coming out of the shadows and into the limelight and is poised to be an economic driving force in the coming years.
Cannabis product acceptance is rising and the customer base is ever expanding. But there is one tiny detail that we are missing on our products that virtually every food, dietary supplement or medication has tucked away on the bottle cap or the bottom of the package: The best before or expiration date.
By Markus Roggen, Ph.D. (Complex Biotech Discovery Ventures),
Glenn Sammis, Ph.D. (University of British Columbia, Department of Chemistry)
The following is from the Proceedings of the Cannabis Chemistry Subdivision (Spring 2019 Symposia), first published in the July/August 2019 issue of Terpenes & Testing magazine.
During our work in process optimization of cannabis production, we noticed a rate difference of decarboxylation for tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). The noticeable rate difference between the decarboxylation reactions of THCA & CBDA has been noted but is generally overlooked. [1a, 1b] We were curious to study and understand those rate differences. We took a two-pronged approach. First, we investigated the reaction mechanism in-silico. Secondly, we developed an in-process analytical tool to track decarboxylation in real time.
This article was first published in the July/Aug 2019 issue of Terpenes&Testing. Click to see the pdf version.
To keep growing, the cannabis industry must embrace the Dark Side: Big Pharma.
The Big Pharma empire has certainly given us many reasons to be skeptical, starting with Big Pharma’s stakes against cannabis legalization , its financial interest in addictive substances like opioids , artificial price inflation of life- saving drugs , and using patents to prevent innovation.  But the pharmaceutical industry is also known for: developing drugs that drastically reduced the prevalence of certain diseases,  product purity,  extensive clinical trials,  and their relatively low recall rates. 
Big Pharma has been perfecting its mastery of the Force for at least a century, and as a New Republic, turning away from this wealth of insight and experience would make the budding cannabis industry as bad as Jar Jar Binks.  If we don’t learn from the Dark Side, we will be extinguished.
So what does the pharmaceutical industry get right?