Tag Archives: solvent

Cannabis Extracts for the Informed Consumer: Solvent or Solventless

By Nick J. Bucci
1 Comment

As cannabis markets continue to gain traction, inconsistent and largely unpredictable markets have left recreational consumers in an informational fog. Try as the industry may, or may not to inform consumers, the lack of knowledge was evident when an established Colorado hash company opened a second operation in California. Expecting high demand for their solventless concentrates, the demand for their solvent-based counterparts came as a surprise. Initially hoping to eliminate solvent extracts from their product line-up, the company was forced to devote about half their overall production to solvent extracts, until information spreads and attitudes start to change. Over the past year several companies have joined the solventless side of history, but consumer understanding remains largely stagnant. For those immediately overwhelmed by terminology, cannabis extracts, concentrates or hash are all interchangeable terms describing concentrated cannabis. Under these umbrella terms, two distinct categories emerge depending upon whether chemical solvents were or were not used to extract the hash. Hence: solvent or solventless. A brief overview of cannabis concentrates will help consumers to understand the evolution away from solvent extractions and toward a superior solventless future.

ecxtractionfig2
Science and economics merge when considering all the possible uses of concentrated compounds to final product formulations

Before regulated cannabis markets, cannabis extracts had long been in use. These old-world methods of cannabis extraction use very basic solventless techniques to create more potent, concentrated forms of cannabis. Dry sifting is easily the oldest form of cannabis extraction and a prime example of one solventless technique. Something as simple as shaking dried cannabis over metal screens and collecting the residue underneath creates a solventless product called keif. Dark brown bubble-hash, made popular decades ago, is another ancient technique using only ice and water to perform extractions without chemical solvents. After decades of stagnant and limited old-world methods, changes in legislation allowed cannabis sciences to flourish. These old-world hash methods were quickly forgotten, replaced by the astonishing progress of modern solvent extractions.

Tetrahydrocannabinol (THC), just one of hundreds of cannabinoids found in cannabis.

The emergence of solvent extracts revolutionized cannabis around 2011, creating new categories of cannabis products that exploded onto the scene. Not only did solvent extracts produce the most potent and cleanest forms of hash ever seen at this point, it also created new possibilities for hash-oil vape cartridges and cannabis extract infused edibles. These solvent extracts use butane, propane, or other hydrocarbon solvents to extract, or “blast” cannabinoids from the plant. By running solvents through cannabis and then purging or removing leftover, residual solvents, a super-potent, premium hash product is achieved. Regulated markets require testing to ensure only a safe level, if any, of the solvent used in the extraction process remains in the final product. This technology ushered in the first wave of concentrates to medical and recreational markets under the descriptive titles of wax, shatter and crumble. While these effective and affordable products can still be found today, far superior products have largely replaced wax and shatter. Distillation techniques can further purify and isolate THC-a, while removing harmful residual solvents. For a time, Solvent-free was used to describe this ultra-purified distillate, but the needless term has fallen out of use. Solvent-free is still a solvent extraction using chemical solvents, don’t be fooled. Distillation and CO2 extractions have fallen into general disfavor as they destroy the flavorful terpenes and valuable cannabinoids, that when present create an “entourage effect.” This “entourage effect” happens when the medicinal and recreational properties are most effective, pronounced, and impactful due to a full range of terpenes and cannabinoids being present in the final product. With companies manually reintroducing terpenes to their final extracts, it’s an attempt to restore what was lost during solvent extraction processes. Many brands claim to use cannabis derived or food-grade terpenes to infuse or reintroduce terpenes into their purified hash oils. While this adds flavor and taste, especially to distillate cartridges, it’s far from an ideal solution. Armed with this new information, the informed consumer looks for a full profile of terpenes and cannabinoids in their hash.

THC-A crumble, terpene-rich vape oil, THC sap (from left to right).

With terpene preservation a new priority, all aspects of hash making were reevaluated. By using fresh-frozen cannabis flower, solvent extractions quickly reached new heights. Using the same techniques as prior solvent extractions, the cannabis plant is frozen immediately upon harvesting, rather than trimming and drying the crop as usual. Freezing the plant preserves valuable terpenes helping to create a new category for hydrocarbon extracts under the general label of live resins. This live resin, containing vastly greater profiles of terpenes and cannabinoids than earlier waxes, shatters or crumbles is sold as live-resin sauce, sugar, badder, frosting, diamonds and more. Many versions of live resin re-use previous terms that describe consistencies. These live resin solvent extracts outperform the wax, crumble and shatters of old, and are priced accordingly. Some of the best solvent extracts available today use butane to extract hash oil, which forms THC-a crystals and diamonds seen in live resin sauces. Having learned the value of terpenes and cannabinoids, early efforts to purify THC were clearly misled. The industry defining use of fresh-frozen cannabis flowers greatly improved the quality of all extracts having realized the psychoactive effects are largely dependent on the various profiles of cannabinoids and terpenes. Pure THC-a crystals and isolates are easily achieved with solvent extractions but, produce inferior effects both medicinally and recreationally. Discovering the “entourage effect” as described earlier, these elements of cannabis allowed old-world solventless techniques to be re-inspired and reinvigorated with the benefit of healthy genetics and a hearty understanding of past mistakes.

Having gone full circle, solventless techniques are again at the forefront of the cannabis industry, having attained near perfection for our current understanding of cannabis anatomy.

figure1 extract
The increasingly finer mesh works to separate and extract microscopic trichomes

Using the lessons and tendencies of prior extractions, the solventless method, in all its final forms, begin with the same initial process to make ice-water hash oil. Often referred to as solventless hash oil (SHO), fresh-frozen flowers are submerged in ice and water, soaked and agitated before the water is filtered through mesh screens. As these mesh screens are measured by microns, the increasingly finer mesh works to separate and extract microscopic trichomes that break free from the cannabis plant. The 120- and 90-micron mesh screens usually collect pristine trichome heads. After scraping the remaining material from the screens, its sieved onto trays where the hash can dry using modern techniques of sublimation. The results are beyond phenomenal and are sure to shock even life-long cannabis consumers. This technique isolates only the most potent and psychoactive parts of the plant, to produce white to clear solventless ice water hash. When done with precision 6-star ice water hash is formed. The hash can be sold and consumed as is or undergo additional solventless techniques to produce hash-rosin. Not to be confused with live-resins, rosin uses pressure and slight heat to squeeze ice-water hash, into hash-rosin. Some companies have elected to whip their rosins into a solventless badder or allow their hash rosins to undergo a cold cure process that creates textures and varieties like hash rosin sauce. Regardless of the final solventless product, they all begin as ice water extractions. These simple, natural methods of extraction are quickly being adopted by companies known for live resin. As solventless extracts are safer, cleaner and superior in quality to solvent chemical extractions, the race is on as the industry shifts toward a solventless future.

While I’d be happy to never see another solvent extract again, without the miraculous breakthroughs and advances in all aspects of cannabis manufacturing and production we may have not yet arrived where we are today. When using solvents to extract, the trichomes, which contain the full spectrum of terpenes and cannabinoids, are dissolved by the solvent, which is then evaporated off, leaving behind dissolved trichomes. In solventless hash, these trichomes remain whole and are never dissolved or broken down. Instead they are broken free by agitation in ice and water, separating the trichome heads from their less-active stems. These valuable trichomes heads contain everything pertinent and are never destroyed, dissolved or melted like solvent-extractions are forced to do. The benefit of keeping the heads of these trichomes whole results in a far superior product expressing the full profile of terpenes and cannabinoids the way mother nature intended. This natural profile of trichomes lends itself directly to the entourage effect that solvent extracts were found to be missing.

Extraction techniques are not equal and depend upon whether quality or mass production is the aim. Solvent extracts have quickly begun to represent the old-guard of mass-produced cannabis concentrates, with the solventless new-guard focusing on quality, small batch, hash-rosin excellence.

dry cannabis plants

How to Grow Cannabis Plants for Concentrate Production

By Andrew Myers
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dry cannabis plants

While flower is still the most popular way to consume cannabis, the concentrates market is booming. Some predict concentrates will be nearly as popular as flower by 2022, with an estimated $8.5 billion in retail sales. That’s a lot of concentrates and, chances are, cannabis producers are already feeling the pressure to keep up.

Concentrates refer to products made from processing cannabis – often resulting in much higher THC or CBD percentages. The category includes oils, wax, dabs, shatter, live resin and hash. Consumers are increasingly drawn to these cannabis products for their near-immediate and intense effects. They’re often consumed through vaporization, dabbing or sublingual absorption and are sometimes favored by those who want to avoid smoking. Cannabis growers who have traditionally focused on flower yields may decide to prioritize quality and potency levels in order to tap into these changing consumer tastes.

What Growers Should Focus on to Produce High Quality Concentrates
We’ll let you in on a little secret: making good concentrates starts with good flower. If you’re starting with low-quality flower, it’s impossible to create a high-quality concentrate. Whatever qualities inherent to the flower you’re starting with will be amplified post-processing. So, really, the concentrate-making process starts at the seedling level, requiring the right care and attention to coax out the results you’re looking for.

Tetrahydrocannabinol (THC), just one of hundreds of cannabinoids found in cannabis.

But what makes good flower? While this can be a subjective question, those producing concentrates generally look for flowers with big, abundant trichomes. Trichomes are the small, dewy structures found across the cannabis plant on buds, leaves and even the stem. They’re responsible for producing the plant’s cannabinoids and terpenes – the chemical compounds that give a strain its unique benefits, aroma and taste. Evolutionarily, trichomes attract pollinators, deter hungry herbivores and provide some defense against wind, cold and UV radiation.

Generally, trichomes indicate how potent the flower is. Plus, what we’re most often looking for when making concentrates is higher cannabinoid and terpene profiles, while also ensuring absolute safety.

What measures can growers take to produce crops that are ideal for concentrate production? Start with the following:

Avoiding Contaminants
Just like you would wash your fruits and vegetables before consumption, consumers want to be sure there’s no dangerous residuals in the concentrate they are ingesting. Growers can avoid any post-process residuals by taking a few key steps, including:

  • Photo: Michelle Tribe, Flickr

    Cutting out the pesticides. Any pesticides that are on your flowers before they go through processing will show up in your concentrates, often even more – you guessed it – concentrated. This is a serious health concern for consumers who might be sensitive to certain chemicals or have compromised immune systems. It’s dangerous to healthy consumers, too. Rather than spraying hazardous chemicals, growers could consider integrated pest management techniques, such as releasing predatory insects.

  • Limiting foliar spraying. Some growers will use foliar spraying to address nutrient deficiency or pest-related issues through delivering nutrients straight to the leaves. However, this can also result in contaminated concentrates. If you really need to spray, do it during the vegetative stage or investigate organic options.
  • Taking the time to flush the crop. This is a critical step in reducing potential contaminants in your concentrate, especially if you’re using a non-organic nutrient solution or fertilizer. Flushing simply means only giving your plants water during the final two weeks of flowering before harvest, resulting in a cleaner, non-contaminated flower and therefore a cleaner concentrate.

Perfecting the Indoor Environment
When cultivating cannabis indoors, growers are given ultimate control over their crop. They control how much light the plants receive, the lighting schedule, temperature and humidity levels. Creating the ideal environment for your cannabis crop is the number one way to ensure healthy plants and quality concentrates. There are many factors to consider when maintaining an indoor grow:

  • Temperature regulation. Trichomes are sensitive to temperature changes and start to degrade if they’re too hot or too cold. To maintain the best trichome structure, you’ll want to maintain an ideal temperature – for most strains, this falls between an idyllic 68 and 77 degrees.
  • Adequate light. For plants to perform photosynthesis indoors, they’ll need an appropriate light source – preferably one that is full-spectrum. Full-spectrum LEDs are able to closely replicate the sun and provide ample, uniform light to your crop. Another selling point for LEDs is their low heat output, making it much easier for growers to regulate ambient heat.

    dry cannabis plants
    Rows of cannabis plants drying and curing following harvest
  • CO2. Another necessary ingredient for photosynthesis is CO2. Providing your indoor crops with CO2 can boost plant size and yields and, therefore, provides more surface area for trichomes to develop and thrive.
  • Cold snap prior to harvest. Some growers rely on this age-old tactic for one last push before harvest – lowering their temperature for a few days right at the end of the flower cycle. They believe this puts the plants into a defense mode and will produce more trichomes in order to protect themselves.

Following Best Practices Post-Harvest
You made it to harvest – you’re almost done!

When harvesting and storing your plants, handle them with care to reduce damage to trichomes. If you’re planning on immediately making concentrates, you can move forward to the drying and curing process. If you’re going to wait a few weeks before processing, freeze your plants. This will preserve the cannabinoid and terpene profiles at their peak.

As the cannabis industry continues to expand, more consumers are likely to reach for concentrates at their local dispensaries. It makes sense that businesses want to diversify their offerings to satisfy customers looking for the most effective way to consume cannabis. As with any cannabis-derived product, producers will want to prioritize quality and safety – especially in the concentrate market.

Managing Cannabis Waste and Protecting Your Business from Risk

By David Laks
2 Comments

Cannabis producers know that they cannot treat plant waste like common yard waste. They need to develop a detailed waste disposal plan in order get a license to operate.

Failing to follow the approved plan and improperly disposing of dry waste materials and waste products from oil extraction leads to fines, liabilities or even having your license rescinded.

Learning to deal with cannabis waste appropriately is crucial to the success of an operation. There are a number of strict controls in place for dealing with any kind of hazardous waste, which can’t just be sent to a landfill or composting facility.

In the US, the EPA and state governments provide guidelines for disposing of hazardous waste properly, and other countries have federal and local requirements as well. The EPA, like other environmental bodies, differentiates between two types of waste: solid and liquid.

Solid waste disposal: The guideline for identifying solid waste is that it’s “unrecognizable and unusable.” This means no one should be able to look at a bag of waste and know immediately that it is cannabis. Many cannabis operations have a facility on site for grinding down the waste into smaller bits. If the waste is non-hazardous, it is mixed with other non-cannabis organics such as garden trimmings and then composted or sent to the appropriate landfill. If it’s hazardous, it’s mixed with cat litter, sand, plastic or sawdust and sent to the appropriate landfill.

Liquid waste disposal: Liquid waste is a bit more complicated. It must be disposed of properly or sent to a hazardous waste treatment facility. Cannabis operations must partner with a shipping company to dispose of the hazardous waste appropriately, unless they transport it themselves.

It can be confusing to manage the risks of proper disposal of cannabis waste. Keep it simple by following these three tips:

  1. Become an expert in all the legal restrictions – and follow them. Federal restrictions will guide you overall, but local (i.e., state and municipal) restrictions are equally important and may vary.
  2. Seek out experienced, reputable disposal companies – and hire the best one.Look for one that is familiar with handling hazardous waste in general and cannabis waste in particular.
  3. Familiarize yourself with the guidelines for proper tracking, transportation and sign-offs – and follow them.Completing all appropriate documentation ensures you have a paper trail to protect you in the event of an audit. Much of the documentation creates a written record so inspectors can confirm appropriate handling.

Waste disposal policies should be reviewed regularly as state and municipal regulations can change. At the same time, it would be wise to review your environmental insurance policy to ensure your business is covered for any accidental releases.

It can be tempting to take shortcuts – saving both money and time – when it comes to hazardous waste disposal. But properly disposing of hazardous materials can demonstrate your organization’s credibility and financial wellbeing, and it can also save you from unnecessary risk.

From The Lab

I Was Wrong… und das ist auch gut so!

By Dr. Markus Roggen
3 Comments

I was wrong. And that’s a good thing! Based on all available data, I assumed that evaporating ethanol from a cannabis oil/ethanol solution would result in terpene loss. As it turns out, it doesn’t. There are so many beliefs and assumptions about cannabis: Cannabis cures cancer!1 Smoking cannabis causes cancer!2 Sativas help you sleep; Indicas make you creative!3,4 CBD is not psychoactive!5 But are these ‘facts’ backed by science? Have they been experimentally tested and validated?

I postulated a theory, designed experiments to validate it and evaluated the results. Simply putting “cannabis backed by science” on your label does not solve the problem. Science is not a marketing term. It’s not even a fixed term. The practice of science is multifaceted and sometimes confusing. It evolved from the traditional model of Inductivism, where observations are used in an iterative process to refine a law/theory that can generalize such observations.6 Closely related is Empiricism, which posits that knowledge can only come from observation. Rationalism, on the other hand, believes that certain truths can be directly grasped by one’s intellect.7 In the last century, the definition of science was changed from the method by which we study something, such as Inductivism or Rationalism, and refocused on the way we explain phenomena. It states that a theory should be considered scientific if, and only if, it is falsifiable.8 All that means is that not the way we study something is what makes it scientific, but the way we explain it.

I wonder how can we use empirical observations and rational deliberations to solve the questions surrounding cannabis? And more importantly, how can we form scientific theories that are falsifiable? Cannabis, the plant, the drug, has long been withheld from society by its legal status. As a result, much of what we know, in fact, the entire industry has thrived in the shadows away from rigorous research. It’s time for this to change. I am particularly concerned by the lack of fundamental research in the field. I am not even talking about large questions, like the potential medical benefit of the plant and its constituents. Those are for later. I’m talking about fundamental, mundane questions like how many lumens per square centimetre does the plant need for optimal THC production? What are the kinetics of cannabis extraction in different solvents? What are the thermodynamics of decarboxylation? Where do major cannabinoids differ or align in terms of water solubility and viscosity?

The lack of knowledge and data in the cannabis field puts us in the precarious position of potentially chasing the wrong goals, not to mention wasting enormous amounts of time and money. Here’s a recent example drawn from personal experience:Certainly, I cannot be the only one who has made an incorrect assumption based on anecdotes and incomplete data?

Some of the most common steps in cannabis oil production involve ethanol solutions. Ethanol is commonly removed from extraction material under reduced pressure and elevated heat in a rotary evaporator. I expected that this process would endanger the terpenes in the oil – a key component of product quality. My theory was that volatile terpenes9 would be lost in the rotary evaporator during ethanol10 removal. The close values of vapor pressure for terpenes and ethanol make this a reasonably assumed possibility.11 In the summer of 2018, I finally got the chance to test it. I designed experiments at different temperatures and pressures, neat and in solution, to quantify the terpene lost in ethanol evaporation. I also considered real life conditions and limitations of cannabis oil manufacturers. After all the experiments were done, the results unequivocally showed that terpenes do not evaporate in a rotary evaporator when ethanol is removed from cannabis extracts.12 As it turns out, I was wrong.

We, as an industry, need to start putting money and effort into fundamental cannabis research programs. But, at least I ran the experiments! I postulated a theory, designed experiments to validate it and evaluated the results. At this point, and only this point, can I conclude anything about my hypothesis, even if that is that my working theory needs to be revised. Certainly, I cannot be the only one who has made an incorrect assumption based on anecdotes and incomplete data?

There is a particular danger when using incomplete data to form conclusions. There are many striking examples in the medical literature and even the casual observer might know them. The case of hormone replacement therapy for menopause and the associated risks of cardiovascular diseases showed how observational studies and well-designed clinical trials can lead to contradicting results.13 In the thirties of the last century, lobotomy became a cure-all technique for mental health issues.14 Dr. Moniz even won the Nobel Prize in Medicine for it.15 And it must come as no surprise when WIRED states “that one generation’s Nobel Prize-winning cure is another generation’s worst nightmare.”16 And with today’s knowledge is impossible to consider mercury as a treatment for syphilis, but that is exactly what it was used as for many centuries.17 All those examples, but the last one in particular should “be a good example of the weight of tradition or habit in the medical practice, […] of the necessity and the difficulties to evaluate the treatments without error.”18 There is the danger that we as cannabis professionals fall into the same trap and believe the old stories and become dogmatic about cannabis’ potential.

We, as an industry, need to start putting money and effort into fundamental cannabis research programs. That might be by sponsoring academic research,19 building in-house research divisions,20 or even building research networks.21 I fully believe in the need for fundamental cannabis research, even the non-sexy aspects.22 Therefore, I set up just that: an independent research laboratory, focused on fundamental cannabis research where we can test our assumptions and validate our theories. Although, I alone cannot do it all. I likely will be wrong somewhere (again). So, please join me in this effort. Let’s make sure cannabis science progresses.


References

  1. No, it does not. There are preliminary in-situ studies that point at anti-cancer effects, but its more complicated. The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report, Abrams, Donald I., European Journal of Internal Medicine, Volume 49, 7 – 11
  2. No, it does not. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. https://doi.org/10.17226/24625.
  3. No, it does not. The chemical profile of the plant dictates the biological effects on humans, not the shape of the leaf.  Justin T. Fischedick, Cannabis and Cannabinoid Research, Volume: 2 Issue 1: March 1, 2017
  4. Indica and Sativa are outdated terms. Piomelli D, Russo EB. The Cannabis sativa versus Cannabis indica debate: An Interview with Ethan Russo, MD. Cannabis Cannabinoid Res 2016; 1: 44–46.
  5. No, it is. CBD’s supposed “calming effects” is indeed a psychoactive effect. However, it is not intoxicating like THC. Russo E.B., Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.Br. J. Pharmacol. 2011; 163: 1344-1364
  6. As attributed to Francis Bacon.
  7. See the work by philosopher Baruch Spinoza.
  8. As theorized by Karl Popper.
  9. Monoterpenes have a vapor pressure in the low to mid hundreds of Pascals at room temperature.
  10. Vapor pressure of 5.95 kPa at 20˚C.
  11. Furthermore, there is always the possibility of azeotropes in complex mixtures. Azeotropes are mixtures of two or more liquids that have different boiling points individually, but in mixture boil together.
  12. Terpene Retention via Rotary Evaporator Application Note, Heidolph North America
  13. https://www.pharmaceutical-journal.com/research/review-article/establishing-the-risk-related-to-hormone-replacement-therapy-and-cardiovascular-disease-in-women/20202066.article?firstPass=false
  14. https://psychcentral.com/blog/the-surprising-history-of-the-lobotomy/
  15. https://en.wikipedia.org/wiki/António_Egas_Moniz
  16. https://www.wired.com/2011/03/lobotomy-history/
  17. https://www.infezmed.it/media/journal/Vol_21_4_2013_10.pdf
  18. https://www.ncbi.nlm.nih.gov/pubmed/11625051
  19. Canopy Growth funds a professorship of cannabis science at UBC. Tilray collaborates with UCSD on a phase I/II clinical trial.
  20. For examples see: NIBR, PMISCIENCE.
  21. For examples see: CEMI, theAIRnet, Future Sky.
  22. Research that does not lead to short-term stock value spikes but long-term progress

A More Effective and Efficient Approach to Purer Cannabidiol Production Using Centrifugal Partition Chromatography

By Lauren Pahnke
3 Comments

Many physicians today treat their patients with cannabidiol (CBD, Figure 1), a cannabinoid found in cannabis. CBD is more efficacious over traditional medications, and unlike delta-9 tetrahydrocannbinol (THC), the main psychoactive compound in cannabis, CBD has no psychoactive effects. Researchers have found CBD to be an effective treatment for conditions such as cancer pain, spasticity in multiple sclerosis, and Dravet Syndrome, a form of epilepsy.

CBD is still considered an unsafe drug under federal law, but to meet the medical demand, 17 states in the US recently passed laws allowing individuals to consume CBD for medical purposes. A recent survey found that half of medicinal CBD users rely on the substance by itself for treatment. As doctors start using CBD to treat more patients, the demand for CBD is only expected to rise, and meeting that demand can pose challenges for manufacturers who are not used to producing such high quantities of CBD. Furthermore, as CBD-based drugs become more popular, the US Food and Drug Administration (FDA) will likely require manufacturers to demonstrate they can produce pure, high-quality products.

cannabidiol
Figure 1. The structure of cannabidiol, one of 400 active compounds found in cannabis.

Most manufacturers use chromatography techniques such as high performance liquid chromatography (HPLC) or flash chromatography to isolate compounds from natural product extracts. While these methods are effective for other applications, they are not, however, ideal for CBD isolate production. Crude cannabis oil contains some 400 potentially active compounds and requires pre-treatment prior to traditional chromatography purification. Both HPLC and flash chromatography also require silica resin, an expensive consumable that must be replaced once it is contaminated due to irreversible absorption of compounds from the cannabis extract. All of these factors limit the production capacity for CBD manufacturers.

Additionally, these chromatography methods use large quantities of solvents to elute natural compounds, which negatively impacts the environment.

A Superior Chromatography Method

Centrifugal partition chromatography (CPC) is an alternative chromatography method that can help commercial CBD manufacturers produce greater quantities of pure CBD more quickly and cleanly, using fewer materials and generating less toxic waste. CPC is a highly scalable CBD production process that is environmentally and economically sustainable.

The mechanics of a CPC run are analogous to the mechanics of a standard elution using a traditional chromatography column. While HPLC, for instance, involves eluting cannabis oil through a resin-packed chromatography column, CPC instead elutes the oil through a series of cells embedded into a stack of rotating disks. These cells contain a liquid stationary phase composed of a commonly used fluid such as water, methanol, or heptane, which is held in place by a centrifugal force. A liquid mobile phase migrates from cell to cell as the stacked disks spin. Compounds with greater affinity to the mobile phase are not retained by the stationary phase and pass through the column faster, whereas compounds with a greater affinity to the stationary phase are retained and pass through the column slower, thereby distributing themselves in separate cells (Figure 2).

Figure 2- CPC
Figure 2. How CPC isolates compounds from complex, natural mixtures. As the column spins, the mobile phase (yellow) moves through each cell in series. The compounds in the mobile phase (A, B, and C) diffuse into the stationary phase (blue) at different rates according to their relative affinities for the two phases.

A chemist can choose a biphasic solvent system that will optimize the separation of a target compound such as CBD to extract relatively pure CBD from a cannabis extract in one step. In one small-scale study, researchers injected five grams of crude cannabis oil low in CBD content into a CPC system and obtained 205 milligrams of over 95% pure CBD in 10 minutes.

Using a liquid stationary phase instead of silica imbues CPC with several time and cost benefits. Because natural products such as raw cannabis extract adhere to silica, traditional chromatography columns must be replaced every few weeks. On the other hand, a chemist can simply rinse out the columns in CPC and reuse them. Also, unlike silica columns, liquid solvents such as heptane used in CPC methods can be distilled with a rotary evaporator and recycled, reducing costs.

Environmental Advantages of CPC

The solvents used in chromatography, such as methanol and acetonitrile, are toxic to both humans and the environment. Many environmentally-conscious companies have attempted to replace these toxic solvents with greener alternatives, but these may come with drawbacks. The standard, toxic solvents are so common because they are integral for optimizing purity. Replacing a solvent with an alternative could, therefore, diminish purity and yield. Consequently, a chemist may need to perform additional steps to achieve the same quality and quantity achievable with a toxic solvent. This produces more waste, offsetting the original intent of using the green solvent.

CPC uses the same solvents as traditional chromatography, but it uses them in smaller quantities. Furthermore, as previously mentioned, these solvents can be reused. Hence, the method is effective, more environmentally-friendly, andeconomically feasible.

CPC’s Value in CBD Production

As manufacturers seek to produce larger quantities of pure CBD to meet the demand of patients and physicians, they will need to integrate CPC into their purification workflows. Since CPC produces a relativelyduct on a larger scale, it is equipped to handle the high-volume needs of a large manufacturer. Additionally, because it extracts more CBD from a given volume of raw cannabis extract, and does not use costly silica or require multiple replacement columns, CPC also makes the process of industrial-scale CBD production economically sustainable. Since it also uses significantly less solvent than traditional chromatography, CPC makes it financially feasible to make the process of producing CBD more environmentally-friendly.

Suggested Reading:

CPC 250: Purification of Cannabidiol from Cannabis sativa

Introduction to Centrifugal Partition Chromatography

California Manufacturing Regulations: What You Need To Know

By Aaron G. Biros
No Comments

In late November, California released their proposed emergency regulations for the cannabis industry, ahead of the full 2018 medical and adult use legalization for the state. We highlighted some of the key takeaways from the California Bureau of Cannabis Control’s regulations for the entire industry earlier. Now, we are going to take a look at the California Department of Public Health (CDPH) cannabis manufacturing regulations.

According to the summary published by the CDPH, business can have an A-type license (for products sold on the adult use market) and an M-type license (products sold on the medical market). The four license types in extraction are as follows:

  • Type 7: Extraction using volatile solvents (butane, hexane, pentane)
  • Type 6: Extraction using a non-volatile solvent or mechanical method
    (food-grade butter, oil, water, ethanol, or carbon dioxide)
  • Type N: Infusions (using pre-extracted oils to create edibles, beverages,
  • capsules, vape cartridges, tinctures or topicals)
  • Type P: Packaging and labeling only

As we discussed in out initial breakdown of the overall rules, California’s dual licensing system means applicants must get local approval before getting a state license to operate.

The rules dictate a close-loop system certified by a California-licensed engineer when using carbon dioxide or a volatile solvent in extraction. They require 99% purity for hydrocarbon solvents. Local fire code officials must certify all extraction facilities.

In the realm of edibles, much like the rule that Colorado recently implemented, infused products cannot be shaped like a human, animal, insect, or fruit. No more than 10mg of THC per serving and 100mg of THC per package is allowed in infused products, with the exception of tinctures, capsules or topicals that are limited to 1,000 mg of THC for the adult use market and 2,000 mg in the medical market. This is a rule very similar to what we have seen Washington, Oregon and Colorado implement.

On a somewhat interesting note, no cannabis infused products can contain nicotine, caffeine or alcohol. California already has brewers and winemakers using cannabis in beer and wine, so it will be interesting to see how this rule might change, if at all.

CA Universal Symbol (JPG)

The rules for packaging and labeling are indicative of a major push for product safety, disclosure and differentiating cannabis products from other foods. Packaging must be opaque, cannot resemble other foods packaged, not attractive to children, tamper-evident, re-sealable if it has multiple servings and child-resistant. The label has to include nutrition facts, a full ingredient list and the universal symbol, demonstrating that it contains cannabis in it. “Statute requires that labels not be attractive to individuals under age 21 and include mandated warning statements and the amount of THC content,” reads the summary. Also, manufacturers cannot call their product a candy.

Foods that require refrigeration and any potentially hazardous food, like meat and seafood, cannot be used in cannabis product manufacturing. They do allow juice and dried meat and perishable ingredients like milk and eggs as long as the final product is up to standards. This will seemingly allow for baked goods to be sold, as long as they are packaged prior to distribution.

Perhaps the most interesting of the proposed rules are requiring written standard operating procedures (SOPs) and following good manufacturing practices (GMPs). Per the new rules, the state will require manufacturers to have written SOPs for waste disposal, inventory and quality control, transportation and security.

Donavan Bennett, co-founder and CEO of the Cannabis Quality Group

According to Donavan Bennett, co-founder and chief executive officer of the Cannabis Quality Group, California is taking a page from the manufacturing and life science industry by requiring SOPs. “The purpose of an SOP is straightforward: to ensure that essential job tasks are performed correctly, consistently, and in conformance with internally approved procedures,” says Bennett. “Without having robust SOPs, how can department managers ensure their employees are trained effectively? Or, how will these department managers know their harvest is consistently being grown? No matter the employee or location.” California requiring written SOPs can potentially help a large number of cannabis businesses improve their operations. “SOPs set the tempo and standard for your organization,” says Bennett. “Without effective training and continuous improvement of SOPs, operators are losing efficiency and their likelihood of having a recall is greater.”

Bennett also says GMPs, now required by the state, can help companies keep track of their sanitation and cleanliness overall. “GMPs address a wide range of production activities, including raw material, sanitation and cleanliness of the premises, and facility design,” says Bennett. “Auditing internal and supplier GMPs should be conducted to ensure any deficiencies are identified and addressed. The company is responsible for the whole process and products, even for the used and unused products which are produced by others.” Bennett recommends auditing your suppliers at least twice annually, checking their GMPs and quality of raw materials, such as cannabis flower or trim prior to extraction.

“These regulations are only the beginning,” says Bennett. “As the consumer becomes more educated on quality cannabis and as more states come online who derives a significant amount of their revenue from the manufacturing and/or life science industries (e.g. New Jersey), regulations like these will become the norm.” Bennett’s Cannabis Quality Group is a provider of cloud quality management software for the cannabis industry.

“Think about it this way: Anything you eat today or any medicine you should take today, is following set and stringent SOPs and GMPs to ensure you are safe and consuming the highest quality product. Why should the cannabis industry be any different?”

Cannabis-Infused Beer Goes Mainstream

By Aaron G. Biros
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Lagunitas Brewing today unveiled a new beer infused with cannabis, making it the first large national brewery to experiment with cannabis. Lagunitas, now owned by Heineken, announced the launch of their “Supercritical Ale,” an IPA brewed with terpenes extracted from cannabis.

The brewery chose to partner with AbsoluteXtracts and CannaCraft, based in California, for their cannabis extract and will use hops from Yakima, Washington. “We’ve long known about the close connection between cannabis and hops,” reads their website. “Now Lagunitas is excited to partner with a like-minded neighbor in Sonoma County, AbsoluteXtracts, to close the gap further with tandem innovations on the topic.” Hops and cannabis belong in the same taxonomic family, Cannabinaceae, and they also have a number of physical similarities, which helps explain the “close connection” they are referring to. The website says the beer will only be available in California—for now. According to Fortune Magazine, the terpenes come from two strains, Blue Dream and Girl Scout Cookies (known as GSC in some states).

The name “Supercritical” comes from the state that carbon dioxide is best used as a solvent for extracting compounds from plants. Terpenes are responsible for the aromatic properties of plants, giving hops the piney and citrusy flavors that come in IPAs, and giving cannabis the same flavors and smells as well. Limonene, for example, is a cyclic terpene molecule that gives us a citrusy smell and flavor.

Coalition brewing Co.’s Two Flowers IPA

They’re not the first brewery to experiment with cannabis-infused beer; smaller craft breweries have been doing it for some time now. Coalition Brewing Co., based in Portland, Oregon, sells a cannabis-infused beer called Two Flowers IPA, with 3mg of cannabidiol (CBD) in a 12oz glass. Dad and Dudes Breweria, based in Aurora, Colorado, also put out a CBD-infused beer last year, called General Washington’s Secret Stash. According to Westword, Dad and Dudes was the first brewery to receive federal approval for a CBD-infused beer, but since the DEA declared cannabis oil illegal last winter, the Alcohol and Tobacco Tax and Trade Bureau rescinded their approval.

The common denominator between these three beers is that none of them contain THC, the popular psychoactive ingredient in cannabis. Perhaps Lagunitas is taking a safer approach with regard to federal legality by only using terpenes, not CBD, and only offering it in state. Coalition’s Two Flowers IPA is also only available in Oregon, but does, however, contain CBD. Check out the video on Lagunitas’ Supercritical Ale below.

Soapbox

Clear vs. Pure: How Fallacies and Ignorance of Extraction Misrepresent the Cannabis Flower

By Dr. Markus Roggen
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Demand for cannabis extracts, in particular vaping products, is at an all-time high. People want good oil, and they want to know something about the quality of it. It is therefore time to take a step back and consider the process from plant to cartridge. What is the current industry standard for cannabis extraction, what constitutes quality and where might we need to make some adjustments?

Right now, “clear” oil is hot. Customers have been led to believe that a pale gold extract is synonymous with the best possible cannabis concentrate, which is not necessarily the case. Producing a 95% pure THC extract with a translucent appearance is neither a great scientific feat nor a good representation of the whole cannabis flower. Moreover, it runs counter to the current trend of all-natural, non-processed foods and wellness products.

“My carrots are organic and fresh from the farmers market, my drink has no artificial sweeteners and my honey is raw, but my cannabis oil has undergone a dozen steps to look clear and still contains butane.”Cannabis is a fascinating plant. It is the basis of our livelihood, but more importantly, it enhances the quality of life for patients. The cannabis plant offers a plethora of medicinally interesting compounds. THC, CBD and terpenes are the most popular, but there are so many more. As of the most recent count, there are 146 known cannabinoids1. Cannabinoids are a group of structurally similar molecules2, including THC and CBD, many of which have shown biological activity3.

Then there are terpenes. These are the smaller molecules that give cannabis its distinct smell and flavor, over 200 of which have been identified in cannabis4. But wait, there’s more. The cannabis plant also produces countless other metabolites: flavonoids, alkaloids, phenols and amides5. All these components mixed together give the often-cited entourage effect6,7.

Current industry standards for cannabis oil extraction and purification stand in marked contrast to the complexity of the plant’s components. Due to an unsophisticated understanding of the extraction process and its underlying chemistry, cannabis oil manufacturers frequently produce oil of low quality with high levels of contamination. This necessitates further purifications and clean up steps that remove such contaminants unfortunately along with beneficial minor plant compounds. If one purifies an extract to a clear THC oil, one cannot also offer the full spectrum of cannabinoids, terpenes and other components. Additionally, claiming purities around 95% THC and being proud of it, makes any self-respecting organic chemist cringe8.

Precise control of extraction conditions leads to variable, customized concentrates. THC-A crumble, terpene-rich vape oil, THC sap (from left to right).

The labor-intensive, multi-step extraction process is also contrary to “the clean-label food trend”, which “has gone fully mainstream”9. Exposing the cannabis flower and oil to at least half a dozen processing steps violates consumer’s desire for clean medicine. Furthermore, the current practice of calling supercritical-CO2-extracted oils solvent-less violates basic scientific principles. Firstly, CO2 is used as a solvent, and secondly, if ethanol is used to winterize10, this would introduce another solvent to the cannabis oil.

We should reconsider our current extraction practices. We can offer cannabis extracts that are free of harmful solvents and pesticides, give a better, if not full, representation of the cannabis plant and meet the patients’ desire for clean medicine. Realizing extracts as the growth-driver they are11 will make us use better, fresher starting materials12. Understanding the underlying science and learning about the extraction processes will allow us to fine-tune the process to the point that we target extract customized cannabis concentrates13. Those, in turn, will not require additional multi-step purification processes, that destroys the basis of the entourage effect.

The cannabis industry needs to invest and educate. Better extracts are the result of knowledgeable, skilled people using precise instruments. Backroom extraction with a PVC pipe and a lighter should be horror stories of the past. And only when the patient knows how their medicine is made can they make educated choices. Through knowledge, patients will understand why quality has its price.

In short, over-processing to make clear oil violates both the plant’s complexity and consumers’ desires. Let us strive for pure extracts, not clear. Our patients deserve it.


[1] Prof. Meiri; lecture at MedCann 2017

[2] ElSohly, Slade, Life Sciences 2005, 539

[3] Whiting, et. al., JAMA. 2015, 2456

[4] Andre, Hausman, Guerriero, Frontiers in Plant Science 2016, 19

[5] Hazekamp, et. al., Chemistry of Cannabis Chapter 3.24; 2010 Elsevier Ltd.

[6] Ben-Shabat, et al.; Eur J Pharmacol. 1998, 23

[7] Mechoulam, et al.; Nat Prod Rep. 1999, 131

[8] Medical and Research Grade chemicals are generally of purities exceeding 99.9%

[9] Bomgardner, Chemical & Engineering News 2017, 20

[10] Winterization is the industry term for what is correctly referred to as precipitation.

[11] Year-over changes to market shares in Colorado 2015 to 2016: Concentrates 15% to 23%; Flower 65% to 57%, BDS Analytics, Marijuana Market Executive Report, 2017

[12] Further reading about the whole extraction process: B. Grauerholz, M. Roggen; Terpene and Testing Magazine, July/Aug. 2017

[13] Further reading about optimizing CO2 extraction: M. Roggen; Terpene and Testing Magazine, May/June 2017, 35

From The Lab

QuEChERS 101

By Danielle Mackowsky
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Sample preparation experts and analytical chemists are quick to suggest QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) to cannabis laboratories that are analyzing both flower and edible material for pesticides, mycotoxins and cannabinoid content. Besides having a quirky name, just what makes QuEChERS a good extraction technique for the complicated matrices of cannabis products? By understanding the chemistry behind the extraction and the methodology’s history, cannabis laboratories can better implement the technology and educate their workforce.

QuEChERS salt blends can be packed into mylar pouches for use with any type of centrifuge tubes
QuEChERS salt blends can be packed into mylar pouches for use with any type of centrifuge tubes

In 2003, a time when only eight states had legalized the use of medical cannabis, a group of four researchers published an article in the Journal of AOAC International that made quite the impact in the residue monitoring industry. Titled Fast and Easy Multiresidue Method Employing Acetonitrile Extraction/Partitioning and “Dispersive Solid-Phase Extraction” for the Determination of Pesticide Residues in Produce, Drs. Michael Anastassiades, Steven Lehotay, Darinka Štajnbaher and Frank Schenck demonstrate how hundreds of pesticides could be extracted from a variety of produce samples through the use of two sequential steps: an initial phase partitioning followed by an additional matrix clean up. In the paper’s conclusion, the term QuEChERS was officially coined. In the fourteen years that have followed, this article has been cited over 2800 times. Subsequent research publications have demonstrated its use in matrices beyond food products such as biological fluids, soil and dietary supplements for a plethora of analytes including phthalates, pharmaceutical compounds and most recently cannabis.

QuEChERS salts can come prepacked into centrifuge tubes
QuEChERS salts can come prepacked into centrifuge tubes

The original QuEChERS extraction method utilized a salt blend of 4 g of magnesium sulfate and 1 g of sodium chloride. A starting sample volume of 10 g and 10 mL of acetonitrile (ACN) were combined with the above-mentioned salt blend in a centrifuge tube. The second step, dispersive solid phase extraction (dSPE) cleanup, included 150 mg of magnesium sulfate and 25 mg of primary secondary amine (PSA). Subsequent extraction techniques, now known as AOAC and European QuEChERS, suggested the use of buffered salts in order to protect any base sensitive analytes that may be critical to one’s analysis. Though the pH of the extraction solvent may differ, all three methods agree that ACN should be used as the starting organic phase. ACN is capable of extracting the broadest range of analytes and is compatible with both LC-MS/MS and GC-MS systems. While ethyl acetate has also been suggested as a starting solvent, it is incompatible with LC-MS/MS and extracts a larger amount of undesirable matrix components in the final aliquot.

All laboratories, including cannabis and food safety settings, are constantly looking for ways to decrease their overhead costs, batch out the most samples possible per day, and keep their employees trained and safe. It is not a stretch to say that QuEChERS revolutionized the analytical industry and made the above goals tangible achievements. In the original publication, Anastassiades et al. established that recoveries of over 85% for pesticides residues were possible at a cost as low as $1 per ten grams of sample. Within forty minutes, up to twelve samples were fully extracted and ready to be analyzed by GC-MS, without the purchase of any specialized equipment. Most importantly, no halogenated solvents were necessary, making this an environmentally conscious concept. Due to the nature of the cannabis industry, laboratories in this field are able to decrease overall solvent usage by a greater amount than what was demonstrated in 2003. The recommended starting sample for cannabis laboratories is only one gram of flower, or a tenth of the starting volume that is commonly utilized in the food safety industry. This reduction in sample volume then leads to a reduction in acetonitrile usage and thus QuEChERS is a very green extraction methodology.

The complexity of the cannabis matrix can cause great extraction difficulties if proper techniques are not used
The complexity of the cannabis matrix can cause great extraction difficulties if proper techniques are not used

As with any analytical method, QuEChERS is not perfect or ideal for every laboratory setting. Challenges remain in the cannabis industry where the polarity of individual pesticides monitored in some states precludes them from being amenable to the QuEChERS approach. For cannabis laboratories looking to improve their pesticide recoveries, decrease their solvent usage and not invest their resources into additional bench top equipment, QuEChERS is an excellent technique to adopt. The commercialization of salt blends specific for cannabis flowers and edibles takes the guesswork out of which products to use. The growth of cannabis technical groups within established analytical organizations has allowed for better communication among scientists when it comes to best practices for this complicated matrix. Overall, it is definitely worth implementing the QuEChERS technique in one’s cannabis laboratory in order to streamline productivity without sacrificing your results.

OHA Addresses Oregon Growing Pains, Changes Testing Rules

By Aaron G. Biros
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Last week, the Oregon Health Authority (OHA) published a bulletin, outlining new temporary testing requirements effective immediately until May 30th of next year. The changes to the rules come in the wake of product shortages, higher prices and even some claims of cultivators reverting back to the black market to stay afloat.img_6245

According to the bulletin, these temporary regulations are meant to still protect public health and safety, but are “aimed at lowering the testing burden for producers and processors based on concerns and input from the marijuana industry.” The temporary rules, applying to both medical and retail products, are a Band-Aid fix while the OHA works on a permanent solution to the testing backlog.

Here are some key takeaways from the rule changes:

Labeling

  • THC and CBD amounts on the label must be the value calculated by a laboratory, plus or minus 5%.

Batch testing

  • A harvest lot can include more than one strain.
  • Cannabis harvested within a 48-hour period, using the same growing and curing processes can be included in one harvest lot.
  • Edibles processors can include up to 1000 units of product in a batch for testing.
  • The size of a process lot submitted for testing for concentrates, extracts or other non-edible products will be the maximum size for future sampling and testing.

    Oregon Marijuana Universal Symbol for Printing
    Oregon Marijuana Universal Symbol for Printing

Sampling

  • Different batches of the same strain can be combined for testing potency.
  • Samples can be combined from a number of batches in a harvest lot for pesticide testing if the weight of all the batches doesn’t exceed ten pounds. This also means that if that combined sample fails a pesticide test, all of the batches fail the test and need to be disposed.

Solvent testing

  • Butanol, Propanol and Ethanol are no longer on the solvent list.

Potency testing

  • The maximum concentration limit for THC and CBD testing can have up to a 5% variance.

Control Study

  • Process validation is replaced by one control study.
  • After OHA has certified a control study, it is valid for a year unless there is an SOP or ingredient change.
  • During the control study, sample increments are tested separately for homogeneity across batches, but when the control study is certified, sample increments can be combined.

Failing a test

  • Test reports must clearly show if a test fails or passes.
  • Producers can request a reanalysis after a failed test no later than a week after receiving failed test results and that reanalysis must happen within 30 days.
Gov. Kate Brown Photo: Oregon Dept. of Transportation
Gov. Kate Brown
Photo: Oregon Dept. of Transportation

The office of Gov. Kate Brown along with the OHA, Oregon Department of Agriculture (ODA) and Oregon Liquor Control Commission (OLCC) issued a letter in late November, serving as a reminder of the regulations regarding pesticide use and testing. It says in bold that it is illegal to use any pesticide not on the ODA’s cannabis and pesticide guide list. The letter states that failed pesticide tests are referred to ODA for investigation, which means producers that fail those tests could face punitive measures such as fines.

Photo: Michelle Tribe, Flickr
Photo: Michelle Tribe, Flickr

The letter also clarifies a major part of the pesticide rules involving the action level, or the measured amount of pesticides in a product that the OHA deems potentially dangerous. “Despite cannabis producers receiving test results below OHA pesticide action levels for cannabis (set in OHA rule), producers may still be in violation of the Oregon Pesticide Control Act if any levels of illegal pesticides are detected.” This is crucial information for producers who might have phased out use of pesticides in the past or might have began operations in a facility where pesticides were used previously. A laboratory detecting even a trace amount in the parts-per-billion range of banned pesticides, like Myclobutanil, would mean the producer is in violation of the Pesticide Control Act and could face thousands of dollars in fines. The approved pesticides on the list are generally intended for food products, exempt from a tolerance and are considered low risk.

As regulators work to accredit more laboratories and flesh out issues with the industry, Oregon’s cannabis market enters a period of marked uncertainty.