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ElSohley Award Lecture 2020

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Overview of cannabis research by Complex Biotech Discovery Ventures.

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ElSohley Award Lecture 2020

  1. 1. Collaborative Research for Fundamental Insight into Cannabis Production Dr. Markus Roggen
  2. 2. Fundamental Collaboration • Who am I? • What is cannabis? • Where am I now? • What have I done?
  3. 3. Who am I? • Born in Germany • Germans only drink beer • Highschool with focus on chemistry and math • One guy used cannabis, but he was from a different school • M/Sci Chemistry from Imperial College, London (2008) • Voted “university hardest to find drugs at”
  4. 4. Who am I? • PhD Organic Chemistry at ETH Zürich with Prof. Carreira (2012) • Switzerland!!! • PostDoc Physical Organic Chemistry at Scripps with Prof. Blackmond (2013) • Colorado just legalized, wrong state • Trip to Berlin to visit brother (2014) • Finally learn what cannabis smells like
  5. 5. What is Cannabis?
  6. 6. What is Cannabis?
  7. 7. Where am I now? Complex Biotech Discovery Ventures CBDV is a young research venture that seeks to add fundamental scientific insight to the field of cannabis production. We seek to support the cannabis industry by establishing a centralized hub in Vancouver, BC for collaborative research focused on: • Process Design • Process Optimization • Process Analytics • Formulation Research
  8. 8. Where am I now? Collaborative Research CBDV collaborates with academic, industry and private groups around the globe. Some highlights of those collaborations are: • University of British Columbia, Vancouver • Loyalist College, Belleville • Vialpando, LLC by Dr. Monica Vialpando • Veridient Science by Dr. Linda Klumpers • Fritsch Milling • PerkinElmer
  9. 9. What have I done? I don’t know what cannabis is, so I try to understand it from first principle • In-process analytics for reaction control • Kinetic studies to understand mechanisms • Computational studies to understand mechanisms • Chemometrics and data analytics for process control and optimization • Process development, like crystallization Fundamental Cannabis Chemistry
  10. 10. Processing Extracts Decarboxylation is one of the most critical processing steps. O OH OH O O OH H C O O heat THCA THC
  11. 11. How do You Decarboxylate? There is a lack of universal agreement regarding reaction conditions. • Oven heating • Hot plate • Microwave • Oil bath • Other?
  12. 12. Don’t Decarboxylate to Long Problems of excess heating: • Availability of instruments • Higher costs of production • Side reaction and degradation • Lower yields 0 10 20 30 40 50 60 70 80 0 0.5 1 1.5 2 2.5 3 3.5 0 1000 2000 3000 4000 5000 6000 THC THC(%) CBN&d8-THC(%) d8-THC CBN Elapsed Time (Minutes)
  13. 13. Reaction Monitoring of Decarboxylation Current • Subjective determination of reaction completeness • Reactionary approach • Inconsistent batches • Lack of quality & process control vs. Optimal • Rapid • Simple • Accurate • Small sample volume
  14. 14. In-Process Analytics Infrared spectroscopy is a useful tool for reaction monitoring. BG62-64 T0 BG62-64 T80 Name Sample 023 By Administrator Date Thursday, July 12 2018 Sample 041 By Administrator Date Thursday, July 12 2018 Description 1750 8001600 1400 1200 1000 0.23 -0.01 -0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16 0.18 0.20 0.22 cm-1 A _ Start THCA 20.87 % End THCA 1.56 %
  15. 15. Monitoring THCA In-Process 0 5 10 15 20 25 30 35 0 10 20 30 40 50 60 70 80 THCA(%) Elapsed Time (Minutes)
  16. 16. Monitoring THCA In-Process 16 26 36 46 56 66 76 16 26 36 46 56 66 76 Predicted%THC Reference % THC
  17. 17. Monitoring THCA In-Process 0 5 10 15 20 25 30 35 0 10 20 30 40 50 60 70 80 THCA(%) Elapsed Time (Minutes)
  18. 18. Monitoring THCA In-Process Why bother? Optimization Precision Decarboxylation
  19. 19. O OH OH O O OH H C O O heat THCA THC HO OH OH O HO OH H C O O heat CBDA CBD FAST SLOW Decarboxylation Observation Not all Decarboxylations are equal
  20. 20. Computational Studies Steric vs. Electronic: Exploring the Rate Difference in THCA and CBDA Decarboxylation 1T-S1 1C-S1 Bot View THCA CDBA Top View
  21. 21. Computational StudieskJ/mol 0 50 100 150 200 0 1 2 3 4 5 61T 1C 1C-S1(MeOH) 1C-S3(MeOH) 1C-TS2(MeOH) 1T-TS2(MeOH)
  22. 22. Computational Studies Key Findings: • Rate determining step is the intermolecular protonation • Rate difference is due to steric rather than electronic effects 1C-TS2(MeOH)
  23. 23. Computational Studies 1: Work by Alex Siegel, presented at Emerald Conference 2020 • Δ9-THC isomerizes to Δ8-THC under heat or acid • Δ10-THC and Δ6a,10a-THC have also been found1 • What other THC isomers are possible? O OH O OH O OH O OH Δ9-THC Δ8-THC Δ10-THC Δ6a,10a-THC
  24. 24. Extraction Data Analytics • Big data analytics for cannabis extraction Different Cultivars Some grouping for cultivars
  25. 25. Extraction Data Analytics • Big data analytics for cannabis extraction Change axis to extraction speed Pump is degrading
  26. 26. SFE Design of Experiment SFE optimized for single separator Cannabinoid Concentration EC2 C1C3
  27. 27. SFE Design of Experiment SFE optimized for single separator Cannabinoid Concentration
  28. 28. SFE Design of Experiment SFE optimized for single separator Cannabinoid Yield
  29. 29. Unknown unknowns CBDV’s Metabolite Database • 24 compound categories • 762 compounds • 75 cannabinoids • 416 terpenes Database available to collaborators! info@cbdvl.com
  30. 30. Post-Processing: Crystallization • The process of solidifying atoms or molecules into highly organized structures • Commonly used in the hemp industry to purify CBD • Current standard procedures use pentane or petroleum ether
  31. 31. Post-Processing: Crystallization
  32. 32. Post-Processing: Crystallization
  33. 33. Post-Processing: Crystallization 0.22 0.24 0.26 0.28 0.3 0.32 0.34 0.36 0.38 0.4 15 17 19 21 23 25 27 29 Concentration(g/mL) Temperature (C) Meta stable zone width for CBD in petroleum ether Sol. T (pure) MSZT (pure)
  34. 34. 0.22 0.24 0.26 0.28 0.3 0.32 0.34 0.36 0.38 0.4 15 17 19 21 23 25 27 29 Concentration(g/mL) Temperature (C) Meta stable zone width for CBD in petroleum ether Sol. T (pure) MSZT (pure) Sol. T (curde) MSZT (crude) Post-Processing: Crystallization
  35. 35. Thank You Thanks go to our collaborators: • Blake Grauerholz, OutCo • Taylor Trah, OutCo • Dr. Allison Justice, Hemp Mine • Ariel Bohman, PerkinElmer • Dr. Toby Astill, PerkinElmer • Barry Schubmehl, Fritsch Milling • Antonio Marelli, Imperial College • Weiying He, UBC
  36. 36. Expertise CEO: Dr. Markus Roggen Dr. Roggen has been actively involved in the cannabis industry for over 5 years in executive positions overseeing production, R&D and process optimization for multiple producers. Dr. Roggen is also a trusted advisor and mentor for multiple startups, startup accelerators and organizations. Co-Founder: Prof. Glenn Sammis Prof. Sammis is an Associate Professor in the Chemistry Department at the University of British Columbia. He has built an internationally recognized research group working on the development of novel synthetic methods for the preparation of natural products and pharmaceuticals. CBDV Team Our team covers a wide range of expertise, including analytical chemistry, process chemistry, engineering physics, data science and statistics.
  37. 37. Dr. Markus Roggen markus@cbdvl.com

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