A new analysis of cannabis research spending in the U.S., Canada and the United Kingdom published in Science magazine found that half of the money spent on research goes toward investigating the potential negative side effects and ramifications of misuse of the plant.

The Boston Business Journal, through public records requests, analyzed how Massachusetts has spent its adult-use cannabis tax revenue during the past two fiscal years. Here’s what the analysis found:

Within the cannabis and hemp industries, the utility of CO₂ for extracting cannabinoids and terpenes from dried plant material is widely known and accepted. As an extraction solvent, CO₂ is cheap, clean, nontoxic and nonflammable. However, what may come as a surprise (especially to those new to cannabis and/or hemp processing) are the significant cultivar-to-cultivar differences when performing CO₂ extraction runs. Extraction scientists should consider several key questions when developing cultivar-specific CO₂ extraction protocols.

1. What is the extraction goal?

Prior to creating any new CO₂ extraction protocol, it’s important to consider the desired outcome. Is the goal to extract all the desirable compounds from the biomass as quickly as possible? Is terpene preservation or oil fractionation (a separation process) important? The answers to these questions will determine whether you utilize supercritical or subcritical CO₂ extraction, or a combination of the two.

Supercritical CO₂ extraction takes place at pressures above 1,083 psi and temperatures greater than 88^oF when the CO₂ has reached its critical point where liquid and vapor coexist. Behaving like a gas, supercritical CO₂ expands to fill the volume of the extraction vessel and can freely diffuse through ground cannabis or hemp material within the vessel. Behaving as a liquid, supercritical CO₂ has great solvent power capable of extracting a wide range of compounds from biomass with a greater percent yield in a shorter amount of time compared to subcritical. Because supercritical CO₂ extraction employs higher temperatures and pressures, terpenes and other more volatile compounds may be degraded or lost during the process.

Subcritical CO₂ extraction occurs below the critical point (less than 1,083 psi and lower than 88^oF) where CO₂ is in the form of a liquid. While subcritical CO₂ has decreased solvent power, this can be advantageous, as it allows for more selectivity in the extraction process. Subcritical is ideal for extracting terpenes and other more volatile compounds from cannabis or hemp, and many of the more undesirable components (fats, waxes, and chlorophyll) are not readily soluble in subcritical CO₂. This is useful because subcritical extraction is capable of fractionation, producing oils rich in CBD, THC, and other cannabinoids. The cooler temperatures used in subcritical also mean there is minimal decarboxylation that occurs in the process, preserving the acid forms of CBD and THC (CBDA and THCA) that are naturally present in the plant. The major drawback is time—subcritical CO₂ extraction generally takes two to four times longer than supercritical to get the same yield.

(The best conditions for using a combination of these two methods will be addressed later.)

2. What is the next step for the extracted oil?

A closely related question to the first one: What do you plan to do with the cannabis or hemp oil once it is extracted? Will it undergo winterization to remove waxes? Will it be distilled? Will it need to be decarboxylated for use in food products or oral dosage forms (capsules, lozenges, tinctures)? The post-extraction processing/purification pathway will help guide in the development of your CO₂ extraction process. For example, if you plan to perform thin film distillation on the extracted oil, you could likely get away with doing a higher pressure supercritical CO₂ extraction run, which would result in a faster run time, but the extracted oil would be less refined.

3. What is the cannabinoid composition of my starting material?

This question is key when it comes to CO₂ extraction method development. Studies have demonstrated that THC, CBD, and other cannabinoids have differing solubility in supercritical CO₂, with CBD having higher solubility compared to THC (see “References” sidebar for studies on that subject). While the researchers in these studies determined cannabinoid solubility at a relatively high range of temperatures (greater than 100ºF) and pressures (more than 2200 psi), similar trends in THC and CBD solubility are observed in practice at lower temperatures and pressures.

When extracting using the same parameters for temperature and pressure, we have consistently observed that hemp/CBD-dominant cannabis cultivars extract much more efficiently than high THC cultivars. Of the high-CBD strains we process, total extraction run time is two- to three-fold less than their high-THC counterparts, yet achieves the same yield of raw oil. The raw CO₂ extract from high CBD strains generally is less viscous compared to high THC extracts, making for easier recovery and cleanup.

For high THC cannabis strains, we routinely perform a series of CO₂ extraction runs spanning both sub- and supercritical parameters to fractionate terpenes and cannabinoids. Performing additional extraction runs on the same feedstock also ensures that you recover as much THCA as possible from the biomass and optimize extraction yield. If you plan to perform some type of post-processing on the extracted oil (as described previously, in the answer to the second question), you can save time by performing a single supercritical CO₂ extraction run.

4. How do I develop/optimize a cultivar-specific CO₂ extraction method?

Most manufacturers of CO₂ extraction equipment will provide a set of basic parameters for both sub- and supercritical extraction in their operating instructions. While this is an obvious starting point, we have experienced great success systematically changing time, temperature, and pressure settings to achieve optimal extraction results. To ensure you know how the change is impacting the extraction run, only change one parameter at a time and clearly document the times, temperatures, and pressures observed. With this information, you will be able to correlate method parameter changes to changes in yield and cannabinoid potency. Don’t be afraid to experiment! Most CO₂ extractors operate over a wide range of temperatures and pressures, and it is helpful to collect extraction data covering this range—the ideal parameters for your cultivar may not align with predictions.

While we expect and routinely observe extraction differences between hemp/CBD-dominant cannabis cultivars and high-THC cultivars, we have also noted cultivar-to-cultivar differences within each class. We have witnessed substantial differences in extraction efficiency/oil potency between numerous high-THC cannabis cultivars run using the same extraction parameters. In some cases, these differences were overcome by increasing the extraction pressure or run time, while in others, we re-extracted the same biomass to strip out the remaining THCA.

In comparing extraction efficiency cultivar-to-cultivar, it is very helpful to monitor cannabinoid potency in the extracted oils as well as in the spent hemp/cannabis feedstock. This will help determine when the extraction run is complete as well as determine which parameter changes result in a higher potency oil.

Dr. Rachel Loeber, Ph.D., is chief science officer at Minnesota-based Leafline Labs.

Tom Schultz, CEO and co-founder of Connecticut-based medical cannabis producer CTPharma and longtime Cannabis Business Times columnist and speaker at Cannabis Conference, tragically passed away on Aug. 22 from injuries sustained in a bicycle accident. He was 70 years old.

Schultz was on his weekly bicycle ride, traveling south on High Ridge Road in Pound Ridge, N.Y., when a 2014 Ford Econoline van traveling in the same direction struck him.

“We are heartbroken that Tom has been taken from us tragically and far too soon. He was a friend to all and will be greatly missed,” said Rino Ferrarese, CTPharma COO. “Tom was an inspirational leader who believed that the study of the medical benefits of marijuana and its compounds was truly in its infancy and that the potential to address a multitude of health issues was unlimited.”

In his CBT column, “Technically Speaking,” which he co-authored with Ferrarese, Schultz explored regulatory and standards issues in the cannabis industry, often taking a forward-looking approach in answering complex problems and offering guidance from his experience in the pharmaceutical and over-the-counter (OTC) markets.

“Tom has been contributing, along with his friend and business partner, Rino Ferrarese, to Cannabis Business Times since April 2017, and his vision has helped guide the industry toward higher standards in professionalism, patient care and product quality and consistency,” said Noelle Skodzinski, editorial director for GIE Media’s cannabis group. “Tom was a brilliant thinker and businessperson, with a true and persevering passion for the medical potential of cannabis, as well as for the patients CTPharma has served over the years. He was also a dear friend to me and many of those on our team. We are all mourning his loss and thinking of his family and his extended family at CTPharma at this time.”

In addition to being CEO of CTPharma, which he had successfully guided to conduct FDA-approved cannabis studies, Schultz also was president of Connecticut’s medical cannabis producers’ association and was involved in many charities, including the one he founded, the Canaan Foundation, which works on technology transfer initiatives for schools in Kenya and Cameroon.

Prior to CTPharma, Schultz was a Wall Street lawyer and investment banker turned pharmaceutical executive. He started as a lawyer with Mudge Rose Guthrie Alexander & Ferdon and, later, joined a boutique Wall Street investment banking firm that was acquired by National Westminster Bank.

In 1996, Tom completed a merger of the major producers of witch hazel and assumed the leadership of Dickinson Brands, Inc., the resulting firm. Dickinson markets OTC pharmaceutical products and consumer packaged goods to major retailers across the United States.

“Tom was a leader who served as an example to all of us. His work and knowledge of the cannabis industry will be remembered and missed.” – Michael Fedele

A whip-smart man with a sharp wit, Schultz was a graduate of Yale University, the NYU School of Law, and the Woodrow Wilson School at Princeton.

He is survived by his three children, seven grandchildren, “and a community that will forever miss his guidance,” Ferrarese added.

“Tom Schultz helped make CTPharma a leader in the bio-science component of our industry and as we will discover the full medical potential of marijuana, we will remember that Tom Schultz was on the leading edge of that discovery,” said Michael Fedele, chairman of the CTPharma board. “Tom was a leader who served as an example to all of us. His work and knowledge of the cannabis industry will be remembered and missed.”

Brian MacIver is senior editor for Cannabis Business Times and Cannabis Dispensary magazines.