GCS CEO, Christopher Tasker, BSc, MRes, explores how the oversupply of hemp biomass has led to producers finding new ways of monetising products. He discusses the emergence of delta-8-THC and the need for professional supervision of this kind of chemistry.
In the ever-evolving battle for profitability in the cannabis industry, everything and anything is being explored to differentiate from the competition and appease investors. CBD aka “cannabidiol” has been a buzzword for some time now in health and wellness circles.
The initial green rush seen in CBD production has seen a lull in the last two years. After the global loosening of CBD regulations, crop production skyrocketed. After hearing the successes of their CBD-producing colleagues, massive investments were made into upscaling CBD production globally. This global push to cash in on the green rush has caused an over-supply of hemp biomass.
The global oversupply has meant a depression in the prices of CBD biomass. This depression in prices and oversupply of biomass has meant that producers have had to explore alternative means of monetizing their products. The efficiency of hemp production as a source of CBD is debatable. Hemp is indeed a fine crop but with average yields of CBD between 1 to 8 per cent, a huge amount of refining is required to extract the precious cannabinoids. As is common with many hemp farms cultivating for CBD, the numerous other beneficial saleable products of the hemp crop have been overlooked.
Delta variants of THC
The delta-8 -tetrahydrocannabinol (delta-8-THC) trend has emerged as a solution to this oversupply of CBD biomass. An interesting chemical property of CBD meant that chemists could convert the unwanted CBD into isomers of THC.
What is an isomer I hear you say? Isomers are two or more compounds with the same formula but a different arrangement of atoms in the molecule and different properties. THC or Tetrahydrocannabinol is a compound that most in our industry will be familiar with. The molecular formula of THC is C₂₁H₃₀O₂. For the non-chemistry speakers, this means the THC molecule consists of 21 carbon atoms, 30 hydrogen atoms, and 2 atoms of oxygen. The subtle difference between the two forms of THC boils down to as little as the positioning of a double bond. Some of you may have noticed that this is also the chemical formula for CBD.
Figure 1. The chemical structures of ∆8-THC and ∆9-THC. ∆8-THC has a double bond between the carbon atoms labeled 8 and 9. ∆9-THC has a double bond between the carbon atoms labeled 9 and 10.
The delta-8-tetrahydrocannabinol that we are discussing today, is an isomer of THC. This base chemistry means that delta-8-THC can be synthesized from CBD which also shares this same C₂₁H₃₀O₂ structure (US EPA National Center for Environmental Assessment, 2009).
Figure 2. The chemical structure of cannabidiol (CBD)
With tonnes of waste CBD biomass flooding the market, creative chemists have been left with a high volume of CBD to play with and supported by some very relieved hemp producers. The emergence of the delta-8-THC trend has been triggered by some clever chemistry that advocates argue is a legal method of exploiting a loophole in the 2018 United States Farm Bill.
Both forms of THC share a very similar pharmacological profile and the marketability of the delta-8 form has been that it is less potent than delta-9-THC. This is true, delta-8-THC exhibits a lower psychotropic potency to delta-9-THC, a ratio of roughly 2:3 (Hollister and Gillespie, 1973). In the interests of brevity, this article will not delve deeply into the effects of delta-8-THC, but in short, the physiological effects are very similar to that of delta-9-THC. Of note is that research into most of these minor cannabinoids is yet to fully gain pace, so in actuality we know very little about these molecules and the true extent of their effects in the body. In the real world, most of these products that are claimed to contain delta-8-THC remain extremely difficult to verify.
A key drawback to this trendy new product is that there is likely more inside the product than just the delta-8-THC. Depending on the process used, any number of additional products may be formed and left residually in the product. In combination with lagging regulatory oversight in this market, it is very difficult to verify the legitimacy of these products. Although there is a legitimate chemical basis for these conversions and the utilisation of waste CBD, we are falling foul of several of the same issues we have previously seen in over-the-counter (OTC) CBD products. This new trend is almost a scaling up of many of the issues we witnessed when CBD first emerged into the legal space. Verifying these products is extremely difficult not just for consumers but also for analysts.
Figure 3. The many chemical conversion possibilities for CBD and their respective formation conditions (Golombek et al., 2020).
Like many processes in the field of cannabinoid chemistry, there are a host of other factors and products to consider. Something that we have discussed before at GCS is the presence of residual solvents in cannabis products. The same concerns ring true for the formation of delta-8-THC from CBD. Strong acids and solvents are required that if not appropriately neutralized can find themselves being consumed by unsuspecting members of the public. Be under no illusion, delta-8-THC is a molecule of great therapeutic potential, but this is by no means transferrable to the products that are being sold OTC to consumers.
It is fair to say that products that are being manufactured en masse using loopholes to maintain profitability are not the most reliable of sources. The driver here is profit, and with all the best intentions in the world, analysing and regulating this grey area of the market is invariably difficult. It has been a fantastic way to reutilise what would potentially be a waste product. However, chemistry of this kind needs to be professionally supervised.
The process for converting CBD into delta-8-THC can become extremely murky and there are numerous methods of balancing and refining the process. Everything from the purity of CBD through to the ratio of acid used in the conversion process. As with many chemical processes, if not appropriately controlled there are potentially explosive outcomes from uninformed production. In the eyes of many, delta-8-THC is a synthetic product made using CBD isolated from hemp. The claim that it is legal is a point of legal contention.
This issue highlights once again the disconnect between the academic perspective and the perspective of industry actors. The competitiveness of cannabis means that more and more companies are looking for loopholes to exploit or as some might describe it, finding a niche. What is clear though is that our industry is running out of ideas. Companies repeatedly look towards the plant for new trends and opportunities. People hold the greatest potential in the cannabis industry. To promote innovation and differentiation we have created a range of educational tools that empower companies to make informed and independent business decisions.
Global Cannabinoid Solutions
GCS have a Global network of cannabis academics to solve Industry problems. Existing knowledge is shared and developed to create unique and innovative education tools. You can explore its range of educational products and see how you can strengthen our industry, your business and society.
Golombek, P. et al. (2020) ‘Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature’, Toxics. Multidisciplinary Digital Publishing Institute (MDPI), 8(2). doi: 10.3390/TOXICS8020041.
Hollister, L. E. and Gillespie, H. K. (1973) ‘Delta-8- and delta-9-tetrahydrocannabinol; Comparison in man by oral and intravenous administration’, Clinical Pharmacology & Therapeutics, 14(3), pp. 353–357. doi: 10.1002/cpt1973143353.
US EPA National Center for Environmental Assessment (2009) The Merck index: An encyclopedia of chemicals, drugs, and biologicals: Benzo[a]pyrene. Edited by M. O’Neil, MJ; Smith, A; Heckelman, PE; Obenchain, JR; Gallipeau, JR; D’Arecca. US EPA National Center for Environmental.
Biologists identify “hacks” cannabis uses to make cannabinoids
The research provides insight into how trichomes create high quantities of cannabinoids without the plant poisoning itself.
Previously, it was unknown how cannabis naturally creates high quantities of cannabinoids and terpenes. Now, new research from biologists at the University of British Colombia has defined the “high efficiency” hacks that the plant’s cells use to do this.
A number of biotechnology companies are now using yeast or cell cultures to create synthetic cannabinoids. The process allows for the mass production of cannabinoids to create a high volume of products in order to keep up with consumer demand.
In a new study, published in the journal Current Biology, plant biologists uncovered the microenvironments in which THC is produced and transported in cannabis trichomes, shedding light on several critical points in the pathway of making THC or CBD within the cell.
University of British Columbia botanist who led the research, Dr Sam Livingston, commented” “This really helps us understand how the cells in cannabis trichomes can pump out massive quantities of tetrahydrocannabinol (THC) and terpenes—compounds that are toxic to the plant cells at high quantities – without poisoning itself.
“This new model can inform synthetic biology approaches for cannabinoid production in yeast, which is used routinely in biotechnology.
“Without these ‘tricks’ they’ll never get efficient production.”
Livingston, along with co-author Dr Lacey Samuels, used rapid freezing of cannabis glandular trichomes to immobilise the plant’s cellular structures and the metabolites in situ.
This enabled them to investigate cannabis glandular trichomes using electron microscopes that revealed cell structure at the nano level, showing that the metabolically active cells in cannabis form a “supercell” that acts as a tiny metabolic biofactory.
Until now, synthetic biology approaches have focused on optimising the enzymes responsible for making THC and CBD – like building a factory with the most efficient machinery to make as much product as possible. However, these approaches haven’t developed an efficient way to move intermediate substances from one enzyme to another, or from inside the cell to the outside of the cell where final products can be collected.
This research helps to define the subcellular “shipping routes” that cannabis uses to create an efficient pipeline from raw materials to end products without accumulating toxins or waste products.
Dr Samuels stated: “For more than 40 years, everything that we thought about cannabis cells was inaccurate because it was based on dated electron microscopy.”
“This work defines how cannabis cells make their product. It’s a paradigm shift after many years, producing a new view of cannabinoid production. This work has been challenging, partly the result of legal prohibition and also due to the fact that no protocol for the genetic transformation of cannabis has been published.”
New partnership to commercialise synthetic THCV and rare cannabinoids
Open Book Extracts has partnered with developers of a proprietary chemical synthesis platform that produces ultra-pure, high quality, sustainable cannabinoids, Nalu Bio.
Open Book Extracts (OBX) has entered into a research, development and commercialisation partnership with Nalu Bio.
The partnership will allow Nalu Bio to advance its THCV production method from research and development to commercial-scale manufacturing using its proprietary and scalable synthesis platform.
With a 76,000 sf. NSF- and ISO 9001-certified research and production facility near Durham, North Carolina, OBX and Nalu Bio plan to begin initial production of THCV in September 2022 with market-ready compounds available before the end of the year.
CTO of Nalu Bio, Matthew Roberts, commented: “Our THCV is produced in highly scalable reactors at factory-scale, using low-cost, safe and effective starting materials. Nalu Bio and OBX are both innovators in their respective fields, and this partnership is mutually beneficial for two industry leaders.
“Nalu Bio prides itself on partnering excellence, and we’re excited to deliver high-quality, safe, and low-cost cannabinoid ingredients and products to the market.”
Nalu Bio’s vision for the synthesis and cost-effective mass production of cannabinoids mimics the history of aspirin – the therapeutic value of aspirin for pain relief was discovered, and while initially derived from willow bark, it is now mass produced at factory-scale with higher quality and dosage consistency, which has benefited billions of consumers worldwide as it has become the most commonly used drug in the world.
THCV will be the first cannabinoid available at commercial scale through this partnership, allowing OBX and Nalu Bio to offer the highest quality, most consistent dosage of THCV.
Both OBX and Nalu Bio envision a range of additional cannabinoids to be released through this partnership,including a broad range of cannabinoids from hemp and natural sources, such as CBD, CBN, CBC, CBG, CBT, CBDa, CBGa, CBDV, and THCV.
OBX CEO, Dave Neundorfer, commented: “I am excited about the value Nalu Bio and OBX will bring to the cannabinoid therapeutics market. This partnership is well-positioned to meet the needs of the growing synthetic cannabinoid market and deliver potentially life-changing products to consumers worldwide.”
Greece welcomes first medical cannabis plants from Israel
Mother plants have arrived in Greece, marking the beginning of production for Tikun Europe.
Tikun Europe has welcomed the first mother plants from Israel and will now begin cultivation in the company’s facility at Korinthos, Greece.
Transportation of the plants was carried out by Skyserv Ground Handling Services. The shipment of the plants was made in specially designed containers under controlled environment ensuring the best possible conditions throughout the transportation from Israel to their final destination.
Cultivation will take place in Tikun Europe’s vertically integrated greenhouse unit, with an area of 21,000 m 2 and it anticipates an annual production capacity of 10 tonnes of dry flower.
CEO of Tikun Europe, Nikos Beis, said: “We welcome the first mother plants to our facilities in Greece. Their arrival marks the beginning of production at the factory in Korinthos, which takes us one step closer to the realisation of our commitment.
“Our factory, being the largest pharmaceutical facility in its industry in Europe, is committed to creating innovative, high-quality medical cannabis products.
“A new era is beginning for our country with the operation of our Tikun Europe facility, paving the way for Greece to become one of the main players in the field of production and export of medical cannabis products.”
The plants will be used for propagation under strict protocols that will ensure the preservation of the unique characteristics of the mother plants to the future generations. The facility is expected to reach its full capacity levels gradually in the near future, to deliver a wide variety of finished medical cannabis dosage forms.
The company’s greenhouse and production units are designed to comply with the GACP/EU-GMP standards, and it holds all the necessary licenses and certifications in order for its operation.
COO and vice president of the board of Tikun Europe, Dimitris Giannopoulos, stated: “After completing the construction of our production facility in Korinthos, today signifies another important milestone, that brings us one step closer to the beginning of cultivation of medical cannabis plants in the country.
“The main challenge and opportunity now become the development and production of a complete portfolio of high quality finished medical cannabis products to meet the needs of patients in Greece and in Europe”.
Commercial director of Skyserv Ground Handling Services, Martha Georgila, stated: “We are very happy that Tikun Europe trusted Skyserv to implement the first transport of mother plants in Greece.
“Following all transportation protocols for that type of merchandises, along with the specific storage conditions that were required during their stay at the airport area, we managed to keep them intact until their departure to the company’s factory in Korinthos.”