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is with with Ameritox Ltd., in Greensboro, North Carolina.

An investigation of C18 and phenyl-hexyl column chemistries for definitive identification of 13 synthetic cannabinoid metabolites in patient samples.

The Synthetic Cannabinoid Chemical Arms Race and Its Effect on Pain Medication Monitoring

 presented its last episode in a three-part webinar series, “Cannabis as Harm Reduction Alternative.” The event was hosted by Dr. Marion McNabb, Founder and President of the CCOE with guest speakers Dr. Peter Grinspoon, a primary care provider at Massachusetts General Hospital, and Andrew DeAngelo, co-founder of Harborside and the Last Prisoner Project. The Massachusetts-based CCOE is a nonprofit that brings together many diverse entities to conduct research studies, education programs, and document best practices. This webinar series aimed to translate findings from CCOE’s recent research study into practical applications for clinicians, patients, and policy makers. In this hour-long episode, all three presenters shared their recommendations for evidence-based suggestions for integrating cannabis in reducing harm in light of the ongoing opioid epidemic.

The first part of the webinar provided a summary of results from the 2023 CCOE survey “Cannabis as an Alternative Therapy,” which asked participants about their substance use and cannabis use and interest. Dr. McNabb then explained the current efforts the alleviate the opioid epidemic in Massachusetts and how cannabis can be a tool in these efforts. She stated, “I think this is a great opportunity to start to really destigmatize the role that cannabis can play. And as a result, we have developed some policy recommendations.”

For the second part of the webinar, the presenters provided detailed input and wide-ranging perspectives on these policy recommendations. For the first two policies, recurring themes discussed included the need for data-based decisions, for finding common ground, and for educating all healthcare providers regardless of their views on cannabis. The presenters also shared how they have seen cannabis policies change for better and worse over the past years.

When examining the possibility of donation programs (policy 3), Dr. Grinspoon stated, “I think it really helps people suffering from different addictions, not just opioid addiction, but from alcohol addiction. I think donations are a really good idea. There's no reason not to do them. Medical cannabis can't be another treatment just for the well-to-do; it has to be available to everyone. Poverty is a real risk factor for addiction, but you don't have to be poor to be addicted.” Both presenters agreed that health insurance should cover medical cannabis. DeAngelo described the medical donation programs from the first years that Harborside Health Center, opened in California in 2006, and how policies have changed in less beneficial ways. He stated, “Whatever Massachusetts decides to do with this program on a public policy, learn from California—make it as least restrictive as possible. Don't worry about diversion, worry about access. Because for every day you don't have a program like this in the state, there are people turning to Valium and Percocet and there are people that are perhaps overdosing.”

For research projects to gauge the cost savings assessment and potential of cannabis as a harm reduction tool (policies 4 and 5), DeAngelo stated, “cannabis is a powerful harm reduction tool. It is going to save lives and is going to save money for the state and for insurance companies and for the feds and for the healthcare system overall. You're talking about a medicine that somebody can grow on their balcony, if need be, or hopefully access in not too difficult a way. So when we have data that supports this really powerful harm reduction tool, then it can be used more widely as a harm reduction tool and some of that data can be then used to develop the consensus we need.”

The presenters also discussed the potential effects of cannabis as a Schedule III drug rather than a Schedule I drug. Both Dr. Grinspoon and DeAngelo agreed that descheduling rather than rescheduling would be more beneficial. Rescheduling, DeAngelo noted, would “create a lot more access and a faster road to consensus.” Dr. Grinspoon explained that while rescheduling is a step in the right direction, he questioned how it would help medical cannabis patients be better able to access their medicine. Dr. McNabb shared 

findings from a 2023 survey showing who respondents trusted most to create cannabis policy

, highlighting that more than two thirds stated that trust people with lived experience to make cannabis laws.

In offering one last piece of advice for the policymakers, DeAngelo explained how policies should be integrated at both state and local levels. Dr. Grinspoon stated, “cannabis as a harm reduction tool is really the humane and compassionate thing to do…no matter what, it's going to be an essential component of how we treat a whole range of addictions. We just don't know exactly how to best use it.”

Read a summary of the first episode for a 

, and a summary of the second installment for 

insights into clinical implications for integrating cannabis as a harm reduction tool

The final installment of this webinar series discussed recommendations for new policies integrating cannabis into harm reduction efforts. 

Topic

Cannabis for Harm Reduction: Recommendations for Future Policies

From simple DIY to lessons learned from mainstream agriculture to chemical discoveries, extraction techniques are driving more product innovation.

The search to isolate more and more cannabinoids is driving extraction development. That’s been a trend for years (1).

But there is also a search for better methods of extraction (read: cleaner, greener) and more focus on extracting specific cannabinoids, as their value to human wellness is explored. Newer concentrate products, such as badder and cured resin—made using a solvent within a pressurized closed-loop extraction system—are showing up at dispensaries. They are among the top sellers in the California, Oregon, and Nevada markets (2).

points to the use of extraction methods such as ultrasonic-assisted, microwave-assisted, supercritical fluid, and pressurized liquid extraction processes as greener options than conventional extraction processes, because they reduce the need for synthetic and organic solvents, cut down on operational time, and produce a better-quality extract with a higher yield (3). Less solvent is used, and extraction times are reduced from conventional methods.

That’s all good for the recreational market. But the potential recent rescheduling of cannabis from Schedule I to Schedule III, announced in April 2024, will drive the search for a reproducible, pharmaceutical-quality cannabis product that will drive further innovation.

This installment of the “Tech Innovations” column will discuss new methods and lab processes to do more targeted cannabis extraction. There is also a growing need to accurately measure homogeneity in the cannabis product, especially for medicinal cannabis, and that begins in the extraction process.

Extraction technology in the cannabis industry is becoming part of the global sustainability efforts, with the goal of developing medicinal preparations from the biomass of cannabis. That biomass extraction technology is becoming standard operating procedure for mainstream cash crops, with interesting product payoffs. But the road to getting there in the cannabis industry is full of obstacles.

The amount of research into cannabis waste is extremely small relative to the research into cannabis itself, in part because of the need to control that biomass from getting into the black market. Cannabis biomass has to be destroyed or otherwise disposed of (landfill, composting, anaerobic digestion) instead of recovered as a resource (4).

Waste valorization (5) has been a research interest of Josh Katz, senior research and development scientist at Trulieve (6). “We grow all of this biomass,” Katz explained. “We reduce the volume of the mass by a certain amount, but it's still a gigantic amount of biomass that we either have to throw away or compost or whatever. There's a lot of interesting chemistry out there that can take this spent material and digest it into commercially interesting products that the cannabis industry hasn't even thought of.”

The biomass of cannabis are the so-called non-utilized components of the plant, such as the roots, which can be rich in polyphenols, and other bio-active compounds, which can be used for health promoting products.

To get an idea of what can be created through extraction of biomass, the cannabis industry should take note of how it works for some mainstream cash crops.

The annual yield of banana peels is 60 million tons; orange peels 10 million tons; avocado pits and peels 4 million tons; and wine by-products more than 14.6 million tons, according to researchers (7).

PeelPioneers, in the Netherlands processes citrus peels into oil, D-limonene. Garden of Natural Solution Co., Ltd. uses an ultrasonic extraction method to produce citrus peel extract with antioxidant effects as a cosmetic ingredient (8). Lianyuan Kangbiotech Co., Ltd. extracts various fruits and fruit peels to obtain sweetener, oils, and polyphenols (9).

Keracol, a company formed by the University of Leeds (10), extracts resveratrol, a natural molecule found in the outer skins of red grapes, which is an antioxidant and known to have protective anti-ageing properties.

Biomass extraction progress is coming to cannabis. There is an extraction method for working with biomass that comes from Milestone on their Ethos platform (11). “It doesn’t even extract cannabinoids,” Katz said. “It’s a terpene extractor. It allows you to take flower immediately after harvest, extract the terpenes out of it, dry the biomass out, re-extract the cannabinoids and you can basically make a vape cart out of the biomass of flower that was harvested yesterday.” They have used it in a couple of their products so far, he said. “From a dollars and cents point of view, it's a substantially cheaper route to cannabis-derived terpenes than CO2 extraction is. Throughputs are comparable, and the total terpene content in what comes out is higher than CO2 extraction. It uses a pretty interesting strategy for getting the terpenes out of material that is not unique to cannabis by any stretch of the imagination.”

Aside from biomass, another extraction method in the sustainable camp is pressurized liquid extraction (PLE) (12), a high-throughput and green extraction technique for the sustainable extraction of bioactive compounds from natural sources.

PLE—also called accelerated solvent extraction (ASE), pressurized fluid extraction (PFE), pressurized hot solvent extraction (PHSE), high-pressure solvent extraction (HPSE), high-pressure high-temperature solvent extraction (HPHTSE), and subcritical solvent extraction (SSE) (13)—is one method of extraction that is easy to use and efficient, using elevated temperatures and moderate to high pressures.

PLE works with a reduced amount of solvent, with the ability to extract a wide range of compounds—ideal for a plant like cannabis where there are more than 550 chemical compounds in cannabis, with more than 100 phytocannabinoids being identified in addition to tetrahydrocannabinol (THC) and cannabidiol (CBD) (14).

Compared to a conventional extraction performed at ambient pressure, the PLE high pressure maintains the solvent in liquid-phase. This improves mass transfer of the extraction by increasing the solubility and decreasing limiting factors such as viscosity and surface tension.

As new extraction ideas and technologies gain traction, it’s important to understand that simple THC extraction and infusion into an edible product arose from an at-home DIY process nearly anyone with basic kitchen know-how can whip up.

First important point to know is that preparing cannabis infused foods is not a simple matter of mixing in crushed cannabis to a brownie mix, for example, and loading that mixture into the oven.

The reason is that THC is not water-soluble, and the human body is composed of up to 60% water (15). But THC is fat soluble and can bind to fat molecules, such as those in oils and other fatty ingredients. THC oil can be mixed or baked into product such as a brownie or cake by making it bind with an oil—generally olive oil, butter, or coconut oil.

To begin the extraction process and get the THC to bind with oil, the cannabis is first ground up, then put on a baking sheet and baked at 230 °F for about an hour to decarbolize it and to activate the compounds (THC and CBD). It is then taken out and allowed to cool.

A separate glass jar with a lid is then put into a large pot. The pot is filled up halfway with water. The now decarbed cannabis is put into the jar, the jar is filled up with the chosen oil nearly to the top, and the lid is screwed on fairly tightly. Then the water in the pot is heated to about 190° F and left to simmer for about three hours. It’s left to cool.

The decarbed cannabis is then filtered out of the oil using some sort of strainer (cheesecloth works), and the oil is poured into a container for future use as a cooking oil to make any THC-infused meal or treat.

Extraction from flower into a dab is also a simple procedure. There are YouTube videos demonstrating how anybody can extract rosin using a simple hair straightener and some parchment paper (16). And old tech is the foundation to some new cannabis extraction tech. One example is short path distillation (17). A short path distillation looks very similar in execution to what most people imagine to be a simple distillation apparatus, Katz said. “You have a big flask, you're heating it. It's boiling, compounds are evaporated. You get a vapor, and the vapor contains a mixture of what was in what you started boiling. The composition of that vapor will change over the course of the distillation. And when I say it changes, I mean it has higher or lower relative fraction of the thing that you're interested in, for example, the cannabinoids.”

Short path distillation is a dynamic process, starting roughly at room temperature, then heating up the cannabis. “The more volatile things come off first, such as any residual solvents, and the terpenes. When they stop coming over, there's usually overlap between the first part of the cannabinoids coming over and the last part of the terpenes coming over,” Katz mentioned. “Part of the skill of extraction is knowing when to make the cut at the overlap.”

A wiped film evaporator (18) is a variation of short film distillation that reduces oil exposure to heat. Wiped-film short path molecular distillation is common in the cannabis industry for separating cannabinoids from terpenes and heavy compounds. It’s a process to get cannabinoid-rich distillate from the molecular distillation process without affecting cannabinoid quality.

“With the wiped film distillation process, you have basically set your parameters so that only the thing that you're interested in, distills over,” Katz explained. “Everything that is more volatile than that will get caught in a cold trap. Anything less volatile than that will get passed on to the residue. So wiped film evaporators are an industrialized approach to short path evaporation. A wiped film evaporator allows you to process a lot more oil a lot faster.”

Another high-tech process is the use of a microwave (MW) reactor developed by Ethos Lean specifically for the decarboxylation of the acidic cannabinoids in cannabis inflorescences prepared for extraction into oil. Both of the steps to produce the oily extract with the MW system were carried out in the Ethos Lean's cavity with special accessories: a rotating drum for the decarboxylation process and a glass reactor with a stirrer for the extraction step, according to an article in 

In collaboration with a hospital pharmacy, the efficiency of the MW device was evaluated by comparing the results obtained with those of exhaustive decarboxylation in a conventional oven and ethanol extraction. A comparison was also made with conventional procedures in olive oil. “Thanks to the rotating drum, which is sensitive to dielectric heating, the complete and homogeneous decarboxylation of phytocannabinoids was rapidly achieved (30 min, 120 °C) without releasing the characteristic intense odor into the laboratory,” the article concluded.

Another new method of extraction was discussed at the 2024 Cannabis Science Conference by Anthony Repay, Laboratory Director of Method Testing Labs (20), involving the use of polysorbate 80 to extract cannabis and distill it into solution.

Polysorbate 80 is a synthetic compound that is commonly used as an emulsifier in a variety of foods, cosmetics, and pharmaceutical products. It's made from ethylene oxide, which is petroleum-based compound. “Why on earth would we go with the cosmetics method when we're dealing with something that is inhaled?” Repay said. “It’s about applicable methods, and things that are similar.”

He demonstrated the mixing process via a video during his presentation, showing where there was a significant association with polysorbate 80 percentage and cannabinoid concentration in a 1-in-10 dilution. “So as the relative percentage of polysorbate 80 in the solution increases, there's a corresponding increase in the amount of Delta-9 THC extracted,” he explained. “Based on this data, we can conclude that there's a statistically significant relationship between the concentration of polysorbate 80 and the extraction of Delta-9 THC, confirming the success of the extraction process.”

“For me, I think we need to get to a point where we get to an extraction efficiency and really see where it starts to tail off,” Repay expressed. “But I'd love to see at what level we start to see a true extraction efficiency where it comes into a linear kind of an algorithmic growth,” he mentioned. “The microbes, like 

 or others, showed no significant impact by increasing concentration of polysorbate 80. At the end of the day, I think we all agree that science needs more data points.”

The news coming down from the US Drug Enforcement Administration (DEA) in late April 2024 about rescheduling cannabis (21) appeared at first to be a shot in the arm for the industry. While it is generally welcomed news, and practically speaking, is likely to be years away from implementation, it will cause tech innovators from cultivators to extractors to keep a wary eye on what it means to their operations, and to the designs of the processors and equipment they use.

With a rescheduled cannabis, making compliant cannabis products using one of the currently available extractors could be a dodgy prospect if science, the regulatory process, and physicians who may soon be able to prescribe cannabis, try to understand different medical cannabis extract products. “Unfortunately, the labs are going to continue to be in a position where they have to make a choice between maintaining scientific integrity, or doing what they need to do to chase regulations that may or may not make sense, but in a way to keep their doors open,” explained Susan Audino, a chemist/chemometrician and independent consultant to chemical and biological laboratories, during the 2024 Cannabis Science Conference which took place in Kansas City, Missouri. “‘So how do I cut corners to meet these regulations that don't make any sense and still maintain a customer base so I can be not just a profitable business, but an open business?’ I see that conflict is going to continue.”

“Opening up this opportunity for research will begin to provide more data to support the contentions from the medical field right now that are using cannabis at any level,” Audino said. “Right now, we know that it works. But if I asked to see the empirical data to demonstrate why and how it works, there's been a teeny tiny amount of information out there, if any. So, I hope rescheduling will open up the opportunity for better research to improve the vast knowledge of empirical data to help support what we've been working with and knowing for a long time.”

But there is still an issue about how regulators do their job right now.

For example, with Delta-8, regulators are looking at the input—what is left over from the synthesis of Delta-8—not the output, Audino said. “That's the detrimental part to the regulatory structure and the interface between regulations and laboratory testing,” Audino explained. “They have to be in alignment. Regulations need to be founded and justified by appropriate science, not the other way around. Because right now science is chasing its tail.”

“We don't know what is going to be rescheduled,” Katz said. “Because Delta-9 THC is a tetrahydrocannabinolic acid (THCA). It's going to be really hard to say if we should change our workflows until we know what is actually going to get rescheduled. I understand why everybody's up in arms right now, because it seems like the sluice gate has been open. But I just caution people not to get too squirrely.”

Hodes, D. New Extraction Technologies Lining Up to Be Game-Changers. 

https://www.cannabissciencetech.com/view/new-extraction-technologies-lining-be-game-changers

Best Selling Cannabis Concentrates in California 

https://www.headset.io/the-best-selling-cannabis-products/california-concentrates

Lazarjani, M.P., Young, O., Kebede, L. et al. Processing and Extraction Methods of Medicinal Cannabis: A Narrative Review. 

https://doi.org/10.1186/s42238-021-00087-9

Baroutian, S.; Bror, R.; Randhawa, P.; Robertson, K.; Star, C. Opportunities and challenges in waste management within the medicinal cannabis sector. 

 https://doi.org/10.1016/j.indcrop.2023.116639

https://www.aiche.org/topics/energy/waste-valorization.

Laibach, N, Chapter 5. Extraction of Valuable Components From Waste Biomass. Waste to Food. 2022, 147-168.

 https://doi.org/10.3920/978-90-8686-929-9_5

https://www.milestonesci.com/microwave-extraction-systems/ 

Alvarez-Rivera, G.; Ballesteros, D.; Bueno, M.; Ibañez, E.; Mendiola, J.; Chapter 13 - Pressurized Liquid Extraction. 

 https://doi.org/10.1016/B978-0-12-816911-7.00013-X

Barp, L.; Moret, S.; Visnjevec, A. Pressurized Liquid Extraction: A Powerful Tool to Implement Extraction and Purification of Food Contaminants. 

Parker, L.; Rock, E. Constituents of Cannabis Sativa. 

, 2020, 1-13. doi: 10.1007/978-3-030-57369-0_1

https://www.usgs.gov/special-topics/water-science-school/science/water-you-water-and-human-body#:~:text=Up%20to%2060%25%20of%20the,bones%20are%20watery%3A%2031%25

https://www.youtube.com/results?search_query=rosin+extraction+and+simple+hair+straightener

https://precisionextraction.com/2021/05/guide-to-short-path-distillation/

Addo, P.; Bilodeau, S.; Gladu-Gallant, F.; Lefsrud, M.; MacPherson, S.; Orsat, V.; Paris, M.; Sagili, S. Optimization of Wiped-Film Short Path Molecular Distillation for Recovery of Cannabinoids from Cannabis Oil Using Response Surface Methodology. 

https://doi.org/10.1016/j.indcrop.2023.116442

Barge, A.; Binello, A.; Carnaroglio, D.; Cravotto, G.; DiFranco, M.; Gandlevskly, N.; Rosso, E.; Visinoni, F. A New Prototype Reactor for the Fast Microwave-Assisted Decarboxylation and Extraction of Cannabinoids in Olive Oil from Cannabis Inflorescences. 

 https://doi.org/10.1016/j.scp.2023.101303

https://www.linkedin.com/in/anthony-repay-m-s-2b201696/ 

Miller, Z.; Goodman, J.; Mustian, J.; Whitehurst, L. US Poised to Ease Restrictions on Marijuana in Historic Shift, But It’ll Remain Controlled Substance 

https://apnews.com/article/marijuana-biden-dea-criminal-justice-pot-f833a8dae6ceb31a8658a5d65832a3b8

 has written for many cannabis publications, and organized or moderated sessions at national and international cannabis trade shows. He was voted the 2018 Journalist of the Year by Americans for Safe Access, the world’s largest medical cannabis advocacy organization.

Hodes, D., Extraction Tech Inspires New Product Development, 

A look at how extraction techniques are driving more product innovation and whether the rescheduling of cannabis will affect extraction.


Extraction Tech Inspires New Product Development

When it comes to packaging, there are several variables that need to be considered. Some of these points to take note of are cost, safety, and if it's environmentally friendly. All these things play a role in the sustainability of packaging. In this interview, Raphael Wechsler, Founder of Wroots Botanicals LLC, Sustainability Lead for Studio Voltaire LLC, and former Director of Partnerships and Operations and Sustainability Committee Chair for the Cannabis Association of New York, discusses the challenges of cannabis packaging and its sustainability in the industry.

How does your experience and education give you a unique understanding of cannabis packaging and sustainability?

 I have unique views on this subject because I have served in different roles whereby I have gained perspectives from business and brand owners, cultivators, academics, policy and regulatory, and consumer perspectives. Additionally, even though it may sound completely irrelevant, working in corporate finance in Iceland or technology with Apple, you gain a broad knowledge, experience, and perspective capability to see things through different lenses. Every dimension needs to be considered and the more diverse your experience is, the greater the vantage points, and—very importantly—the more you can understand what drives decision making in each universe. From an evidence-based decision-making model, your dataset is more expansive, and you are exposed to more ideas at the margin. These may seem nonsensical today, but if they are given the respect they deserve, in time they can be game changers—I’ll dive into some of these later.

What are some regulations and standards for cannabis packaging?

 First and foremost, packaging regulations are designed around the intent of serving the public with such aspects including labeling that is clear, details about cannabinoid content such as tetrahydrocannabinol (THC) or cannabidiol (CBD) in grams per serving, warnings such as the impairment of driving ability with consumption, and labeling that does not entice children. For example, a brand cannot create images or artwork on a mylar bag for edibles making it look like it belongs in a drug store candy section. Another example, and I have some unique views on this, but if we look at regulations in the NortheastUS, all packaging for any product with THC/A must be child resistant.

What are the main elements of sustainable cannabis packaging?

Sustainable cannabis packaging, to me, is domestically or locally sourced, designed and made by a company that itself is sustainable and treats its employees well with sustainable incentives, is made from materials that have a traceable audit with public results, has a low packaging weight to contents ratio, obviously is nontoxic, in most cases is child-resistant, and has a clear way to either reuse or ensure true recyclability.

What are some current and upcoming innovations in cannabis packaging?

 I must be transparent in terms of my model for ideal packaging: a banana peel, an orange peel, or, put differently, how nature packages. The beginning and end of life are where I start because like most packaging, the product is quickly consumed but the packaging and impact remain. Having said this, the innovations that excite me the most are non-petroleum based, or created without great waste whether it be plastic, glass, or metal. Specifically, carbon-based packaging built by materials that are grown rather than extracted and manufactured, is the ideal. Examples include hemp, hemp-based polymers, polyhydroxyalkanoates (PHA)

 mycelium, seaweed, plastic captured from our oceans, and pulp from sustainably grown materials such as bamboo or wood. On top of that, and this is an area I am particularly passionate about, is in reusable packaging; because ultimately single use cannabis packaging is what we should all work to replace or ban. Ever eat at a restaurant? I’m pretty sure the glass you drank out of, the plate your food was on, and the silverware that put food in your mouth were all previously used by hundreds of people.

How sustainable is packaging in the cannabis/hemp industry currently?

 As I read this question, I can’t help but think of the dedicated members of the sustainability committee I had the privilege to chair, their expressions ready to burst with ideas and insights. The short, hard, and tough pill to swallow is: in general, it is not [sustainable] and there are several real reasons for this. To start, let’s do some quick math. If we take one cannabis product in dried whole flower, which would include pre-rolls, and look at a developed market such as Massachusetts, together they account for about a 63% share of retail sales (1). If we take a common stock keeping unit (SKU) such as a 1/8 oz or 3.5 grams (an eighth) that comes in a virgin plastic polypropylene (PP) or high-density polyethylene (HDPE) dram jar made in China, that brings with it a slew of environmental problems:

a) Packaging Weight to Content Ratio: a plastic jar will on average weigh around 70 grams to store 3.5 grams of plant material.

b) Sourcing and Sustainability Standards: Being produced with little to no sustainability oversight in China and then shipped to the US is, no matter how you look at it, terrible for the environment.

c) Lifecycle: The cannabis product will likely be consumed somewhere between 1-5 days, but the plastic packaging will remain, for all intents and purposes, forever.

In this interview, Raphael Wechsler, Founder of Wroots Botanicals LLC, Sustainability Lead for Studio Voltaire LLC, and former Director of Partnerships and Operations and Sustainability Committee Chair for the Cannabis Association of New York, discusses the challenges of cannabis packaging and its sustainability in the industry.

Sheng Feng

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