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Collaborative Research for
Fundamental Insight into
Cannabis Production
Dr. Markus Roggen
Fundamental Collaboration
• Fundamental Questions
• Collaboration, Current
• Fundamental Research
• Collaboration, Future
Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?
A Mature Market Demands Cannabis Extracts
Concentrates may surpass flower as the #1 product in the US.
2017 2022
Flower
Concentrates
Edibles
Other
Source: Arcview & BDSAnalytics Cannabis Intelligence Briefing
A Mature Market Demands Cannabis Extracts
NorthAmerica’s expansion (2015: $5bn to 2018: $11bn) reduces cannabis price
Type of Cannabis Extracts
There is a dizzying array of products available and various extraction methods.
• Hash, Rosin
• Shatter, wax
• Distillate, Isolate
• Crude, HTFSE, …
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
CBDV’s 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
Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?
Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?
Processing Extracts
Decarboxylation is one of the most critical processing steps.
How do You Decarboxylate?
There is a lack of universal agreement regarding reaction conditions.
• Oven heating
• Hot plate
• Microwave
• Oil bath
• Other?
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)
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
In-Process Analytics
Infrared spectroscopy is a useful tool for reaction monitoring.
BG62-64 T0
Name
Sample 023 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 %
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)
Monitoring THCA In-Process
16
26
36
46
56
66
76
16 26 36 46 56 66 76
Predicted%THC
Reference % THC
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)
Monitoring THCA In-Process
Why bother?
Optimization Precision Decarboxylation
Decarboxylation Observation
Not all Decarboxylations are equal
Collaboration: Computational Studies
Steric vs. Electronic: Exploring the Rate Difference in THCA and CBDA
Decarboxylation
1T-S1 1C-S1
Bot View
THCA CDBA
Top View
Collaboration: Computational Studies
kJ/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)
Collaboration: Computational Studies
Key Findings:
• Rate determining step is the intermolecular protonation
• Rate difference is due to steric rather than electronic effects
1C-TS2(MeOH)
Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?
What is Cannabis?
• Indica vs. Sativa
Phylos Bioscience
What is Cannabis?
• Indica vs. Sativa
• Strain names
What is Cannabis?
• Indica vs. Sativa
• Strain names
• High THC vs. high CBD
John S. Abrams, PhD; The
CESC
Chemovars
• Indica vs. Sativa
• Strain names
• High THC vs. high CBD
• Chemovars
Chemovars
Hazekamp, et al.; Cannabis and Cannabinoid Research 2016, 1.1
• Indica vs. Sativa
• Strain names
• HighTHC vs. high CBD
• Chemovars
Chemovars
Orser C, Johnson S, Speck M, HilyardA,Afia I (2018)TerpenoidChemoprofiles Distinguish Drug-type
Cannabis sativa L. Cultivars in Nevada. Nat ProdChem Res 6: 304.
• Indica vs. Sativa
• Strain names
• HighTHC vs. high CBD
• Chemovars
Chemovars
• Indica vs. Sativa
• Strain names
• High THC vs. high CBD
• Chemovars
DiscOmic by Digamma Consulting
Unknown unknowns
CBDV’s Metabolite Database
Unknown unknowns
CBDV’s Metabolite Database
• 24 compound categories
• 762 compounds
Unknown unknowns
CBDV’s Metabolite Database
• 24 compound categories
• 762 compounds
• 75 cannabinoids
• 416 terpenes
Known unknowns
Solubility data from literature & in-house data
Solubility of cannabinoids in supercritical CO2 at 326K
K.H. Perrotin-Brunel et al. / J. of Supercritical Fluids 55 (2010) 603–608
Known unknowns
Solubility data from literature & in-house data
% Decarb
THC/THCA
S.M. 7h 22h
SuperCrit 8.0% 25% 10%
SubCrit 14% 25% 14%
CBG/total
Canna.
S.M. 7h 22h
SuperCrit 2.9% 6.% 2.9%
SubCrit 3.0% 13% 4.9%
Unknown knowns
DoE surfaces of solubility
Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?
Collaboration: Extraction Optimization
For what:
• Yield per Run YpR
• Yield per Week YpW
• Cannabinoid Conc. CC
• Terpene Content TC
• Recovery Rec
• …
With what:
• Temperature T
• Pressure P
• Time t
• Flow Rate FR
• Particle Size PS
• …
Size does Matter
Small and even particle size enables:
• Higher packing density
• Improved extraction efficiency
20
22
24
26
28
30
32
34
Non-Ground Food
Blender
2 mm 6 mm 10 mm
%Recovery
Cannabinoid Recovery by Size
75
80
85
90
95
Non-Ground Food
Blender
2 mm 6 mm 10 mm
%Recovery
Terpene Recovery by Size
Collaboration: Extraction Optimization
Temperature (˚C)
Pressure (psi)
Yield THC (g)
34
60 1100
1900
47
1500
0
Collaboration: Extraction Optimization
Temperature (˚C)
Pressure (psi)
Yield THC (g)
34
60 1100
1900
47
1500
0
Collaboration: Extraction Optimization
Temperature (˚C)
Pressure (psi)
Yield THC (g)
34
60 1100
1900
47
1500
0
Collaboration: SFE Database
Collaboration: SFE Database
Collaboration: SFE Database
Collaboration: SFE DoE
SFE optimized for single separator
Cannabinoid Concentration
Collaboration: SFE DoE
SFE optimized for single separator
Cannabinoid Yield
Fundamental Collaboration
• Fundamental Questions
• Collaboration, Current
• Fundamental Research
• Collaboration, Future
Collaborative Data Analysis
cbdvl.com/freedata
• Free extraction data analysis file
• Basic analysis tools
• Send back for in-depth analysis (info@cbdvl.com)
Collaborative Data Analysis
cbdvl.com/freedata
• Free extraction data analysis file
• Basic analysis tools
• Send back for in-depth analysis (info@cbdvl.com)
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
CBDV Team
Luiz Geraldo – VP Finance
Currently pursuing his MBA, Luiz is an Industrial
Engineer and has 5 years of experience in strategy
and operations consulting and strategic planning.
Gursaanj Singh Bajaj – Data Science Associate
Gursaanj is an Astrophysics major in the
department of Physics and Astronomy at UBC, with
a background in data analysis. He will be going into
his 4th year of his undergraduate degree.
Kendra Payne – VP Business Operations
Experienced Program Manager/Coordinator and
Senior Administrator with a demonstrated history of
working in the education management and
biotechnology industries. Skilled in Biotechnology,
Project Coordination and Life Sciences.
Callum MacPhee – Business Associate
Callum is a going into his fourth year at the
University of British Columbia and is pursuing
a Bachelor of Commerce.
Sajni Shah – Research Associate
Currently studying Chemical Biology in the
Department of Chemistry at UBC. She is
going into her final year of her undergraduate
studies.
Klara Wyse – Marketing Associate
Klara is a Media Studies and Urban Studies
student at UBC, going into their fourth year.
Dr. Markus Roggen markus@cbdvl.com

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Cannabis Science Conference 2019: CBDV Fundamental Collaboration

  • 1. Collaborative Research for Fundamental Insight into Cannabis Production Dr. Markus Roggen
  • 2. Fundamental Collaboration • Fundamental Questions • Collaboration, Current • Fundamental Research • Collaboration, Future
  • 3. Fundamental Questions • What to produce? • Which cannabis cultivar is the right one? • How to grow cannabis? • How to process cannabis? • How to extract cannabis? • How to formulate cannabis extracts? • How to treat patients with cannabis products?
  • 4. A Mature Market Demands Cannabis Extracts Concentrates may surpass flower as the #1 product in the US. 2017 2022 Flower Concentrates Edibles Other Source: Arcview & BDSAnalytics Cannabis Intelligence Briefing
  • 5. A Mature Market Demands Cannabis Extracts NorthAmerica’s expansion (2015: $5bn to 2018: $11bn) reduces cannabis price
  • 6. Type of Cannabis Extracts There is a dizzying array of products available and various extraction methods. • Hash, Rosin • Shatter, wax • Distillate, Isolate • Crude, HTFSE, …
  • 7. 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. CBDV’s 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. Fundamental Questions • What to produce? • Which cannabis cultivar is the right one? • How to grow cannabis? • How to process cannabis? • How to extract cannabis? • How to formulate cannabis extracts? • How to treat patients with cannabis products?
  • 10. Fundamental Questions • What to produce? • Which cannabis cultivar is the right one? • How to grow cannabis? • How to process cannabis? • How to extract cannabis? • How to formulate cannabis extracts? • How to treat patients with cannabis products?
  • 11. Processing Extracts Decarboxylation is one of the most critical processing steps.
  • 12. How do You Decarboxylate? There is a lack of universal agreement regarding reaction conditions. • Oven heating • Hot plate • Microwave • Oil bath • Other?
  • 13. 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)
  • 14. 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
  • 15. In-Process Analytics Infrared spectroscopy is a useful tool for reaction monitoring. BG62-64 T0 Name Sample 023 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 %
  • 16. 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)
  • 17. Monitoring THCA In-Process 16 26 36 46 56 66 76 16 26 36 46 56 66 76 Predicted%THC Reference % THC
  • 18. 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)
  • 19. Monitoring THCA In-Process Why bother? Optimization Precision Decarboxylation
  • 20. Decarboxylation Observation Not all Decarboxylations are equal
  • 21. Collaboration: Computational Studies Steric vs. Electronic: Exploring the Rate Difference in THCA and CBDA Decarboxylation 1T-S1 1C-S1 Bot View THCA CDBA Top View
  • 22. Collaboration: Computational Studies kJ/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)
  • 23. Collaboration: Computational Studies Key Findings: • Rate determining step is the intermolecular protonation • Rate difference is due to steric rather than electronic effects 1C-TS2(MeOH)
  • 24. Fundamental Questions • What to produce? • Which cannabis cultivar is the right one? • How to grow cannabis? • How to process cannabis? • How to extract cannabis? • How to formulate cannabis extracts? • How to treat patients with cannabis products?
  • 25. What is Cannabis? • Indica vs. Sativa Phylos Bioscience
  • 26. What is Cannabis? • Indica vs. Sativa • Strain names
  • 27. What is Cannabis? • Indica vs. Sativa • Strain names • High THC vs. high CBD John S. Abrams, PhD; The CESC
  • 28. Chemovars • Indica vs. Sativa • Strain names • High THC vs. high CBD • Chemovars
  • 29. Chemovars Hazekamp, et al.; Cannabis and Cannabinoid Research 2016, 1.1 • Indica vs. Sativa • Strain names • HighTHC vs. high CBD • Chemovars
  • 30. Chemovars Orser C, Johnson S, Speck M, HilyardA,Afia I (2018)TerpenoidChemoprofiles Distinguish Drug-type Cannabis sativa L. Cultivars in Nevada. Nat ProdChem Res 6: 304. • Indica vs. Sativa • Strain names • HighTHC vs. high CBD • Chemovars
  • 31. Chemovars • Indica vs. Sativa • Strain names • High THC vs. high CBD • Chemovars DiscOmic by Digamma Consulting
  • 33. Unknown unknowns CBDV’s Metabolite Database • 24 compound categories • 762 compounds
  • 34. Unknown unknowns CBDV’s Metabolite Database • 24 compound categories • 762 compounds • 75 cannabinoids • 416 terpenes
  • 35. Known unknowns Solubility data from literature & in-house data Solubility of cannabinoids in supercritical CO2 at 326K K.H. Perrotin-Brunel et al. / J. of Supercritical Fluids 55 (2010) 603–608
  • 36. Known unknowns Solubility data from literature & in-house data % Decarb THC/THCA S.M. 7h 22h SuperCrit 8.0% 25% 10% SubCrit 14% 25% 14% CBG/total Canna. S.M. 7h 22h SuperCrit 2.9% 6.% 2.9% SubCrit 3.0% 13% 4.9%
  • 38. Fundamental Questions • What to produce? • Which cannabis cultivar is the right one? • How to grow cannabis? • How to process cannabis? • How to extract cannabis? • How to formulate cannabis extracts? • How to treat patients with cannabis products?
  • 39. Collaboration: Extraction Optimization For what: • Yield per Run YpR • Yield per Week YpW • Cannabinoid Conc. CC • Terpene Content TC • Recovery Rec • … With what: • Temperature T • Pressure P • Time t • Flow Rate FR • Particle Size PS • …
  • 40. Size does Matter Small and even particle size enables: • Higher packing density • Improved extraction efficiency 20 22 24 26 28 30 32 34 Non-Ground Food Blender 2 mm 6 mm 10 mm %Recovery Cannabinoid Recovery by Size 75 80 85 90 95 Non-Ground Food Blender 2 mm 6 mm 10 mm %Recovery Terpene Recovery by Size
  • 41. Collaboration: Extraction Optimization Temperature (˚C) Pressure (psi) Yield THC (g) 34 60 1100 1900 47 1500 0
  • 42. Collaboration: Extraction Optimization Temperature (˚C) Pressure (psi) Yield THC (g) 34 60 1100 1900 47 1500 0
  • 43. Collaboration: Extraction Optimization Temperature (˚C) Pressure (psi) Yield THC (g) 34 60 1100 1900 47 1500 0
  • 47. Collaboration: SFE DoE SFE optimized for single separator Cannabinoid Concentration
  • 48. Collaboration: SFE DoE SFE optimized for single separator Cannabinoid Yield
  • 49. Fundamental Collaboration • Fundamental Questions • Collaboration, Current • Fundamental Research • Collaboration, Future
  • 50. Collaborative Data Analysis cbdvl.com/freedata • Free extraction data analysis file • Basic analysis tools • Send back for in-depth analysis (info@cbdvl.com)
  • 51. Collaborative Data Analysis cbdvl.com/freedata • Free extraction data analysis file • Basic analysis tools • Send back for in-depth analysis (info@cbdvl.com)
  • 52. 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
  • 53. CBDV Team Luiz Geraldo – VP Finance Currently pursuing his MBA, Luiz is an Industrial Engineer and has 5 years of experience in strategy and operations consulting and strategic planning. Gursaanj Singh Bajaj – Data Science Associate Gursaanj is an Astrophysics major in the department of Physics and Astronomy at UBC, with a background in data analysis. He will be going into his 4th year of his undergraduate degree. Kendra Payne – VP Business Operations Experienced Program Manager/Coordinator and Senior Administrator with a demonstrated history of working in the education management and biotechnology industries. Skilled in Biotechnology, Project Coordination and Life Sciences. Callum MacPhee – Business Associate Callum is a going into his fourth year at the University of British Columbia and is pursuing a Bachelor of Commerce. Sajni Shah – Research Associate Currently studying Chemical Biology in the Department of Chemistry at UBC. She is going into her final year of her undergraduate studies. Klara Wyse – Marketing Associate Klara is a Media Studies and Urban Studies student at UBC, going into their fourth year.
  • 54. Dr. Markus Roggen markus@cbdvl.com