Introduction to Cannabis Chemistry

Moving Sustainable Medicines Forward™
Product Diversity in the
Medical Cannabis Arena
Jeffrey C. Raber, Ph.D.
© 2017 The Werc Shop, LLC
www.TheWercShop.com
Chemicals of Medical Cannabis
• 1269 known chemical compounds in/on Cannabis
• Cannabinoids (144 known in Cannabis)
– THC, CBD, CBN, CBG, CBC, THCV, etc.
– THCA, CBDA, CBGA, CBCA, etc.
– Diverse array of therapeutic effects
• Terpenes & Terpenoids (150 known in Cannabis)
– Limonene, Linolool, Pinene, Myrcene, b-Carophyllene
– Smell attributes and diverse therapeutic effects
• Flavonoids (50 known in Cannabis)
– Apigenin, Cannflavin-A, Kaempferol, Vitexin, Orientin
– Very strong anti-oxidants – diverse therapeutic effects
Most Common in Compositions
• Cannabinoids
– THCA, THC, CBDA, CBD, CBGA, CBG, CBN
– Some on plant ratios of 2:1, >20:1, 3:2
– Edibles = array of ratios, common 1:1 THC:CBD
• Terpenes & Terpenoids
– Limonene, Linalool, Pinenes,
b-Myrcene, b-Caryophyllene
– Diverse effects – modulates cannabinoids
– Ensemble Effect – they are all important
Broad Based Medical Utility
• Numerous potential ailments can be alleviated
Izzo, et. al., Trends in Pharmacological Sciences 10, 515-27 (Oct 2009)
Whole Plant is Superior Medicine
• Single chemical entity not very effective
– Marinol® (Dronabinol) – only THC
• Two chemicals have better effect than just 1
– Sativex® - approximately 1:1 THC:CBD
• Cannabis Plant has many compositions!
– MORE THAN JUST THC and CBD!!
– Ensemble Effect hugely important
• What is the Cannabis Composition
– More than 1+1 = 2 – Synergy Factor
– Wildly different from product to product
Marinol® is a trademark of Solvay Pharmaceuticals, Inc. Sativex® is a trademark of GW Pharmaceuticals, Inc.
Cannabinoids – A Broad Term
• Phytocannabinoids
– Cannabis sativa L. Produced
• THCA, CBDA, CBGA, CBCA, etc.
Cannabinoids – A Broad Term
• Processed Cannabinoids
– Decarboxylation has occurred
• Processing, Storage, Vaporization
Plant Production of Cannabinoids
Plant Production of Cannabinoids
THESE ARE WHAT THE PLANTS PRODUCE!
Decarboxylation With Heat
Product Type Diversity
• Plant Material
–Flower, Trim, Kief
• Concentrates
–Shatter, Distillate, Rosin
• Sublinguals
–Tinctures, Tablets/Mints
• Oral Products
–Drinks, Chocolate, Brownies, Cookies
How Is The Product Made
• Plant Material
–Cultivation Conditions
–Drying, Curing, Trimming, Packaging
• Infused Products
–Direct plant material infusion
–From concentrate form
–Does the product get heated
• Impact of terpenes on these methods
Different Consumption Methods
• Inhalation
– Combustion or Vaporization
• Sublingual
– No first pass metabolism
• Topical
– What else is present
• Oral Products
– Matrix effects, absorption rates
Concentrate Process is Key
• How is the concentrate created
–Plant material quality
–How many process steps are used
• Primary Methods
–Water, Hydrocarbon, Alcohol, CO2
• Which components remain in final form?
• Secondary refinements
–Winterization, Distillation
Diverse From Plant to Product
• How is the final product created
–Often relies heavily on concentrate
• Formulation Uniformity
–Homogeneity of product formation
• Different processes yield different
chemicals present in the products
–Not only consumption routes, but what
molecules are being consumed
Plant Types are Diverse Too
•
•
•
•
Consumption Method Diversity
Processing Diversity
Product Type Diversity
All Products Start from Plant Material
–What defines a strain
–Production process handling
–Packaging and Storage conditions
Understanding Cannabis Complexity
• Analyzing terpenes with GC-FID
• Unique method of fingerprinting each varietal
• Not all strains are the same or offer same effects
Terpenes – Complex and Unknown
Linalool: Floral smelling, is believed to provide some anti-cancer
effects and is known to cause severe sedation.
Limonene: Has a citrus scent and may possess anti-cancer,
anti-bacterial, anti-fungal and anti-depression abilities.
Pinenes: Pine odor, bronchodilator that opens the lungs to more
THC absorption. It also increases focus, self-satisfaction, and
energy.
b-Caryophyllene: Sweet, woody, clove taste responsible for
anti-inflammatory and neuroprotective effects through CB2
receptor activation.
What are the Ensemble Effects??
Overview of Data & Analysis
• Over 2200 flowers & 300 concentrates
• Subsets used to simplify analysis
• Average flower THC = 16%
• Average flower CBD = 0.7%
• Terpenes are the major differentiator
• THC is NOT the major determinant
• Product forms can be very different
Scatter Plot Many Strains
According to Morphological Distinction
Lots of overlap – no distinction
Hybrid
Hybrid
Sativa
Sativa
Sativa
Sativa
Sativa
Sativa
Sativa
Sativa
Sativa
Hybrid
Hybrid
Sativa
Sativa
Sativa
Hybrid
Hybrid
Sativa
Hybrid
Sativa
Sativa
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Sativa
10
8
6
4
t[2]
Hybrid
Indica
Sativa
Hybrid
Hybrid Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Indica
Hybrid
Indica
Indica
Indica
Hybrid
Hybrid
Hybrid
Hybrid
Indica
Hybrid
Indica
Hybrid
Indica
Indica
Indica
Indica
Indica
Hybrid
Indica
Indica
Hybrid
Indica
Hybrid
Indica
Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Indica
Indica
Hybrid
Indica
Indica
Indica
Hybrid
Indica
Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
HybridHybrid
Indica
Indica
Hybrid
Indica
Indica
Indica
Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Indica
Hybrid
Hybrid Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Indica
Indica
Hybrid
Indica
Hybrid
Indica
Hybrid
Hybrid
Indica
Indica
Indica
Hybrid
Hybrid
Hybrid
Hybrid Indica
Indica
Hybrid
Hybrid
Hybrid
Indica
Hybrid
Indica
Hybrid
Indica
Hybrid
Sativa
Hybrid
Hybrid
Indica
Sativa
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Hybrid
Sativa
Hybrid
Sativa
Sativa
Hybrid
Sativa
Sativa
Indica
Hybrid
Indica
Hybrid
Hybrid
Hybrid
Sativa
Sativa
Hybrid
Sativa
Hybrid
Indica
Sativa
Indica
Indica
Indica
Indica
Sativa
Hybrid
Indica
Sativa
Hybrid
Indica
Hybrid
Indica
Sativa
Indica
Sativa
Hybrid
Hybrid
Sativa
Sativa
Hybrid
Indica
Sativa
Hybrid
Hybrid
Hybrid
Sativa
Hybrid
Hybrid
Hybrid
Sativa
Sativa
Hybrid
Hybrid
Hybrid
Sativa
Sativa
Hybrid
Sativa
Indica
Sativa
Hybrid
Sativa
Indica
Indica
Hybrid
Hybrid
Hybrid
Sativa
Indica
Hybrid
Sativa
Sativa
Hybrid
Indica
Sativa
Indica
Hybrid
Hybrid
Hybrid
Hybrid
Indica
Sativa
Sativa
Hybrid
Indica
Indica
Hybrid
Indica
Sativa
Sativa
Indica
Indica
Sativa
Indica
Indica
Sativa
Hybrid
Sativa
Hybrid
Indica
Hybrid
Sativa
Indica
Hybrid
Indica
Hybrid
Sativa
Hybrid
Sativa
Hybrid
Hybrid
Indica
Indica
Indica
Hybrid
Hybrid
Indica
Indica
Indica
Hybrid
Hybrid
Sativa
Indica
Hybrid
Indica
Indica
Indica
Sativa
Sativa
Hybrid
Hybrid
Hybrid
Sativa
Indica
Hybrid
Hybrid
Indica
Indica
Hybrid
Sativa
Indica
Indica
Indica
Hybrid
Indica
Indica
Hybrid
Hybrid
Indica
Indica
Sativa
Indica
Hybrid
Indica
Indica
Hybrid
Hybrid Hybrid
Hybrid
Indica
Indica
Indica
Sativa
Indica
Indica
Hybrid
Indica
Hybrid
Hybrid
Indica
Indica
Indica
Indica
Indica
Hybrid
Hybrid
Hybrid
Indica
Indica
Hybrid
Hybrid
Indica
Indica
Hybrid
Hybrid
Hybrid
Sativa
Indica
Indica
Hybrid
Hybrid
Hybrid
Hybrid
2
0
-2
-4
-6
-8
-7
-6
-5
-4
-3
-2
-1
0
1
2
3
4
5
6
7
8
t[1]
SIMCA-P+ 12 - 2013-09-21 13:38:20 (UTC-8)
9
10
Names Present >5 Times
Jack
Herer
Jack
Herer
Jack
Trainwreck
Herer
Jack
Herer
Jack
Herer
Jack
Herer
Jack Herer
Jack
Herer
Jack
Herer
Jack
Herer
Skywalker
Trainwreck
Trainwreck
Trainwreck
Jack Herer
JackJack
Herer
Jack
Herer
Jack
Herer
Trainwreck
Jack
Herer
Herer
Jack
Herer
Trainwreck
Jack Herer
Trainwreck
JackJack
Herer
Herer
Jack
Herer
Pineapple
Kush
Trainwreck
Trainwreck
Trainwreck
Trainwreck
Larry OG
Trainwreck
NY Sour
Diesel
Fire
OG
Blue Dream Haze
Jack Herer WA
Black
Mamba
OG Kush
OG Kush
Skywalker
OG
Black
OG
SFV
Kush
Mamba
1st
OG
Generation
Diablo
Skywalker
Green
Crack
Mack-10
Kush
Blue Cheese
SourOG
Diesel
OG
Kush
AK-47
True
OG
True
OG
SFV
Neptune
OG
OG
TrueOG
OG OG
Jupiter
Fire
OG
Neptune
OG
Skywalker
Skywalker
Tahoe
OG
Tahoe
SFV
OG
OG
ChemDawg
Tahoe
OG
Mack-10
Fire
Neptune
Charlie
Neptune
OG
OG
Kush
Sheen
Black
OG
Mamba
OG
Skywalker
NY
Sour
Diesel
Tahoe
Skywalker
OG
Diablo
Diablo
Kush
Kush
Alien
OG
OG
Kush
Charlie
Black
Mamba
Sheen
OG
Mack-10
True
Skywalker
OG
OG
Herojuana
1st
Generation
Diablo
ChemDawg
OG
Kush
OG
True
Herojuana
OG
Skywalker
OG
Diablo
Charlie
1st
OG
Generation
Sheen
OG
Diablo
Afghan
Kush
True
Skywalker
OG
Green
Crack
Skywalker
Neptune
Skywalker
OG
Skywalker
OG
1st
1st
Generation
OG
Generation
Skywalker
Diablo
Diablo
OG
Herojuana
1st
Generation
Diablo
Diablo
Fire
OG
Skywalker
OG
Harlequin
Skywalker
Jupiter
OG
Black
OG
Mamba
Green
Crack
Diablo
Tahoe
Larry
1st
OG
OG
True
Generation
OG
1st
Fire
OG
Generation
OG
1st
Diablo
Generation
Diablo
Diablo
OG
Kush
Jupiter
OG
Kush
Blue
Dream
Alien
OG
Tahoe
Sour
Jupiter
OG
OG
OG
Skywalker
Black
Platinum
Mamba
OG
AK-47
Sour
Skywalker
Neptune
OG
Skywalker
Fire
Neptune
OG
OG
Ghost
OG
OG
Kush
OG
Black
OG
True
Fire
Mamba
OG
OG
Green
Afghan
Crack
Kush
1st
Larry
Andre
Generation
OG
OG
OG
Herojuana
the
Larry
Herojuana
Giant
Skywalker
Diablo
OG
OG
Strawberry
Cough
AK-47
SFV
OG
True
OG
True
Diablo
Kush
OG
OG
Kush
OG
Sour
Fire
True
Neptune
Diesel
OG
OG
Fire
Tahoe
OG
OG
OG
Kush
Afghan
Green
Kush
Crack
OG
Neptune
Herojuana
Skywalker
Andre
Platinum
OG
the
OG
Giant
OG
Afghan
Sour
Diesel
Kush
OG
OG
Skywalker
Herojuana
Kush
Mack-10
OG
Mack-10
Kush
OG
Skywalker
OG
Pineapple
Afghan
Green
Green
Crack
Kush
Blue
Crack
Cheese
Skywalker
Fire
Jupiter
Tahoe
Fire
Charlie
Fire
OG
OG
1st
OG
OG
OG
Skywalker
Skywalker
Generation
Sheen
1st
OG
Generation
1st
Diablo
OG
Generation
Herojuana
Diablo
Diablo
Sour
Diesel
Fire
True
OG
Charlie
Charlie
OG
OG
Kush
Sheen
Fire
Sheen
Diablo
OG
OG
Kush
Pineapple
Blackberry
OG
Blue
Kush
Blue
Dream
Strawberry
Kush
Dream
Cough
OG
Larry
Herojuana
Andre
Sour
Diablo
the
OG
Sour
Kush
Giant
OG
Blue
Strawberry
Blue
Dream
Dream
Fire
OG
Cough
Sour
Diesel
Platinum
Fire
Platinum
OG
OG
Charlie
Sheen
OG
Grand
Green
Daddy
Crack
Purple
Platinum
Afghan
Grand
OG
Kush
Daddy
OG
SFV
Kush
OG
Purple
SFV
OG
Sour
Diesel
Tahoe
Andre
Blue
OG
the
Dream
Giant
Ghost
OG
Ghost
Bubba
Skywalker
OG
Kush
OG
SFV
OG
Green
Blue
Green
Crack
Cheese
Crack
SFV
Neptune
OG
OG
Black
Mamba
NY
Pineapple
Sour
Ghost
Diesel
Blue
Kush
OG
Dream
Blue
Blue
Dream
Cheese
NY
OG
Haze
Sour
Kush
Trainwreck
Girl
Haze
Fire
Diesel
Scout
OG
Skywalker
Cookies
1st
Generation
Diablo
Diablo
Kush
Ghost
Green
Strawberry
Green
Blue
Pineapple
Blue
OG
LA
Crack
Dream
Crack
Cheese
Confidential
Cough
Alien
Blue
Skywalker
Kush
Dream
OG
SFV
Sour
Platinum
OG
Sour
Diesel
Kush
Diesel
OG
OG
Skywalker
Herojuana
Alien
OG
OG
1st
Skywalker
Generation
OG
Diablo
Green
Bubba
Dream
Crack
Blackberry
Kush
Berry
Kush
SFV
OG
1st
Generation
Diablo
Harlequin
Green
Dream
Crack
Tahoe
Berry
Platinum
Sour
Sour
OG
SFV
Fire
Diesel
OG
OG
Fire
Fire
OG
OG
Black
Mamba
Strawberry
Jack
Alien
Herer
Cough
OG
Headband
Grand
Daddy
Purple
Grand
Blackberry
Blackberry
Sour
Blue
Sour
Bubba
Platinum
Daddy
Diesel
Dream
Diesel
LA
Skywalker
Kush
Kush
Kush
Purple
Confidential
Haze
Bubba
Blue
Pre
NY
Cheese
OG
'98
Sour
Girl
Bubba
Scout
Diesel
Diablo
OG
Cookies
Kush
OG
Girl
Scout
Blue
Cookies
Platinum
Alien
Dream
OG
Blue
Pre
Sour
OG
'98
Dream
Diesel
Bubba
Sour
Sour
Diesel
Diesel
Grand
Green
OG
Daddy
Crack
Green
Pineapple
Sour
Kush
Purple
Crack
Diesel
LA
Purple
Confidential
Kush
Kush
True
Andre
OG
the
Giant
Headband
ChemDawg
Sour
Diesel
Sour
NY
ChemDawg
Diablo
Diesel
Sour
LA
Diesel
OG
Confidential
Purple
Strawberry
Pre
Cough
'98
ChemDawg
Bubba
Girl
Scout
Cookies
Blue
Grand
Pre
Dream
'98
Sour
Daddy
Bubba
Diesel
NY
Purple
Sour
Diesel
SFV
OG
Velvet
Girl
Blue
OG
Scout
Kush
Dream
NY
Tahoe
Cookies
Sour
Platinum
OG
LA
OG
Diesel
Confidential
Purple
Kush
ChemDawg
Bubba
Sour
Kush
Diesel
Harlequin
Pineapple
Purple
Blackberry
Alien
Kush
Kush
OG
Bubba
Kush
Girl
Scout
Cookies
Harlequin
Blue
Blue
Blue
Blue
Dream
Dream
Dream
Dream
LA
OG
Confidential
Haze
Kush
Sour
Girl
Haze
LA
Diesel
LA
Scout
Confidential
OG
Confidential
Cookies
Trainwreck
Blackberry
Velvet
Girl
Platinum
Blackberry
Tahoe
Kush
Blue
Scout
Dream
Dream
OG
Sour
Bubba
Cookies
Berry
Kush
Larry
Sour
OG
Haze
Tahoe
OG
OG
OG
Grand
Blackberry
Daddy
Velvet
Harlequin
Pre
Purple
'98
Kush
Pre
Bubba
LA
ChemDawg
Confidential
'98
Bubba
Sour
Diesel
Blue
Velvet
Cheese
Blackberry
Kush
Sour
Bubba
Diesel
Platinum
Kush
LA
NY
Sour
Confidential
Bubba
Sour
Diesel
Diesel
Harlequin
Pineapple
Velvet
Grand
LA
Kush
Daddy
Confidential
Bubba
LA
Fire
Confidential
Purple
Kush
OG
Sour
Diesel
Diesel
Andre
the
Velvet
Blue
Grand
Blue
Blackberry
Dream
Blue
Kush
Dream
Pineapple
Daddy
Sour
Dream
Diesel
Kush
Purple
ChemDawg
Sour
Diesel
Velvet
Kush
Blue
Dream
Afghan
ChemDawg
Haze
Sour
Kush
OG
Strawberry
AK-47
Purple
Kush
Pre
Dream
Cough
Blue
'98
Bubba
LA
Berry
Bubba
Dream
Headband
Confidential
Kush
Platinum
Headband
Sour
Bubba
Diesel
WA
Harlequin
Velvet
Purple
Dream
Kush
Kush
Berry
ChemDawg
Harlequin
Harlequin
OG
Headband
Kush
Grand
Pre
Purple
AK-47
Daddy
'98
ChemDawg
Kush
Bubba
Blue
Purple
Blue
Girl
Dream
Dream
Scout
Cookies
Girl
Blue
Scout
Blue
Dream
Purple
Grand
Cookies
Dream
Girl
Kush
Daddy
Scout
Purple
Cookies
Girl
Scout
Cookies
Grand
Alien
OG
Daddy
Headband
Afghan
Tahoe
Purple
OG
Kush
Sour
Diesel
WAGiant
Larry
LA
OG
Dream
Pineapple
Confidential
Blue
Berry
Dream
Kush
Platinum
Pre
'98
Bubba
Bubba
Jack
Velvet
Herer
Strawberry
Kush
Platinum
Bubba
Cough
ChemDawg
Girl
Scout
Headband
LA
Cookies
Confidential
ChemDawg
Harlequin
Blue
LA
Confidential
Dream
Sour
Sour
Diesel
Girl
Diesel
NY
Scout
Sour
Cookies
Diesel
Harlequin
Girl
Scout AK-47
Cookies
Blue
Dream
Girl
Scout
Sour
Diesel
Cookies
ChemDawg
LA
Sour
Confidential
Diesel
WA
Blue
Dream
Girl
Scout
Cookies
Harlequin
Sour
Diesel
WA
Larry
Bubba
OG
Kush
Sour
Skywalker
OGAfghan
Headband
Harlqeuin
Afghan
GirlKush
Scout
Cookies
Dream
Blue Blue
Dream
Sour
Diesel
BlueKush
Dream
Haze
Girl
Scout
Cookies
5
4
3
2
t[2]
1
0
-1
-2
-3
-4
• Linalool and Limonene
• Terpinolene and Nerol
-5
-6
-5
-4
-3
-2
-1
0
1
2
3
4
5
t[1]
SIMCA-P+ 12 - 2014-06-23 14:07:19 (UTC-8)
6
7
Loading Plot for All Strains
0.40
Terpinolene
±-Phella0erene
±-Terpinene
Menthol
0.35
0.30
Sabinene Hydrate
±-Guaiene (t)
0.25
p[2]
0.20
”3-Carene
0.15
0.10
±-Cedrene
trans-Ocimene
(t)
²-Pinene
CBG cis-OcimeneFarnesene
Caryophyllene oxide
Isoborneol
CBN
THC
0.05
-0.00
-0.05
-0.10
±-terpineol
Camphor
CBD
±-Pinene
²-Eudesmol
Guaiol
Geraniol
Limonene
t-2-Pinanol (t)
Nerol
(+) Fenchol
Borneol
Camphene
²-Caryophyllene
±-Humulene
Linalool
Elemene (t)
Germacrene B (t)
Valencene (t) (t)
Selina-3,7(11)-diene
Myrcene
±-Bisabolol
-0.15
-0.10
-0.05
-0.00
0.05
0.10
0.15
0.20
0.25
p[1]
SIMCA-P+ 12 - 2013-09-15 12:35:07 (UTC-8)
0.30
Scatter Plot of 4 Popular Strains
6
Some clustering, some variation
OG Kush
Trainwreck
OG Kush
Jack
Herer
Jack
Herer
WA
OG
Kush
OG
Kush
Jack
Herer
Jack Herer
OG
Kush
OG Kush
JackHerer
Herer
Jack
Jack Herer
OG
Trainwreck
OG
OGKush
Kush
OGKush
Kush
Jack
Jack
Herer
Herer
Jack
Herer
Trainwreck
Jack Herer
Herer WA
OG
Kush
Jack
OG
Kush
OG
Kush
OG
Kush
JackTrainwreck
Herer
OG Kush
Jack
Herer
Jack
Herer
Jack
Trainwreck
Herer
Jack
Herer
OG Kush
Jack
Herer
Trainwreck
OG
Trainwreck
OGKush
Kush
Trainwreck
OG
Kush
Sour
Jack
Herer
JackTrainwreck
Herer
Sour Diesel Sour Diesel
Trainwreck
Sour Diesel
Diesel WA
Jack
Herer
Trainwreck
Sour
Diesel
Trainwreck
Jack
Herer
Sour
Diesel
Jack Herer
Trainwreck
Sour
SourDiesel
Diesel
Sour
Diesel
Trainwreck
Trainwreck
Sour
Sour
Diesel
Diesel
Sour
Diesel WA
OG
Sour
Kush
Diesel
Sour
Diesel
OG
Sour
Kush
Sour
Diesel
Diesel
OG
Kush
Diesel
OGSour
Kush
Sour
Diesel
Sour
Diesel
Sour
Diesel
Sour
Diesel
Sour
Diesel
Jack HererSour
WA
Sour
OG
Kush
Diesel
Diesel
Jack
Herer
Sour
Sour
Diesel
Diesel
Sour
Sour
Diesel
Diesel
WAWA
OG
Kush
Sour
Diesel
OG
Kush
Sour
Diesel
OG Kush
Sour
Diesel
Sour
Diesel
OG Kush
Sour
Diesel
SourDiesel
Diesel
Sour
OG Kush
Jack
Herer
4
t[2]
2
0
-2
-4
Trainwreck
-6
-8
-7
-6
-5
-4
-3
-2
-1
0
1
2
3
4
5
6
7
t[1]
SIMCA-P+ 12 - 2014-06-22 19:25:42 (UTC-8)
8
9
Concentrates
5
TWS-C-034
t[2]
0
TWS-C-035
TWS-C-170
-5
-10
TWS-C-071
TWS-C-085
TWS-C-079
TWS-C-081
TWS-C-268
TWS-C-061
TWS-C-060
TWS-C-227
TWS-C-307
TWS-C-036
TWS-C-276
TWS-C-064
TWS-C-052
TWS-C-306
TWS-C-269
TWS-C-077
TWS-C-053
TWS-C-270
TWS-C-326
TWS-C-083
TWS-C-087
TWS-C-067
TWS-C-272
TWS-C-037
TWS-C-073
TWS-C-084
TWS-C-080
TWS-C-065
TWS-C-327
TWS-C-328
TWS-C-271
TWS-C-086
TWS-C-273
TWS-C-263
TWS-C-017
TWS-C-277
TWS-C-050
TWS-C-088
TWS-C-224
TWS-C-078
TWS-C-100
TWS-C-099
TWS-C-091
TWS-C-260
TWS-C-275
TWS-C-038
TWS-C-068
TWS-C-066
TWS-C-063
TWS-C-076
TWS-C-092
TWS-C-044
TWS-C-062
TWS-C-043
TWS-C-009
TWS-C-012
TWS-C-004
TWS-C-082
TWS-C-232
TWS-C-001
TWS-C-089
TWS-C-093
TWS-C-262
TWS-C-055
TWS-C-265
TWS-C-070
TWS-C-302
TWS-C-330
TWS-C-264
TWS-C-090
TWS-C-323
TWS-C-314
TWS-C-013
TWS-C-072
TWS-C-005
TWS-C-244
TWS-C-002
TWS-C-331
TWS-C-278
TWS-C-074
TWS-C-166
TWS-C-006
TWS-C-008
TWS-C-054
TWS-C-010
TWS-C-011
TWS-C-309
TWS-C-246
TWS-C-167
TWS-C-225
TWS-C-057
TWS-C-094
TWS-C-332
TWS-C-300
TWS-C-310
TWS-C-075
TWS-C-014
TWS-C-226
TWS-C-315
TWS-C-322
TWS-C-261
TWS-C-333
TWS-C-007
TWS-C-279
TWS-C-325
TWS-C-003
TWS-C-318
TWS-C-311
TWS-C-134
TWS-C-132
TWS-C-229
TWS-C-231
TWS-C-289
TWS-C-288
TWS-C-163
TWS-C-301
TWS-C-243
TWS-C-259
TWS-C-329
TWS-C-290
TWS-C-045
TWS-C-266
TWS-C-058
TWS-C-049
TWS-C-069
TWS-C-169
TWS-C-168
TWS-C-305
TWS-C-242
TWS-C-303
TWS-C-312
TWS-C-048
TWS-C-032
TWS-C-304
TWS-C-234
TWS-C-101
TWS-C-321
TWS-C-317
TWS-C-337
TWS-C-228
TWS-C-319
TWS-C-015
TWS-C-051
TWS-C-040
TWS-C-046
TWS-C-033
TWS-C-316
TWS-C-324
TWS-C-308
TWS-C-233
TWS-C-334
TWS-C-320
TWS-C-335
TWS-C-241
TWS-C-056
TWS-C-158
TWS-C-018
TWS-C-336
TWS-C-291
TWS-C-313
TWS-C-258
TWS-C-041
TWS-C-042
TWS-C-016TWS-C-230
TWS-C-274
TWS-C-039
-15
TWS-C-059
-14
-12
-10
-8
-6
-4
-2
0
2
4
t[1]
SIMCA-P+ 12 - 2014-06-23 14:12:58 (UTC-8)
6
Concentrates Are Different
6
TWS-C-274
TWS-C-016
Trainwreck
Jack Herer
Jack Herer
WA
TWS-C-230
Jack
Herer
Trainwreck
Jack Herer
Jack Herer
TWS-C-041
TWS-C-042
Jack
Herer
Trainwreck
Jack
Herer
TWS-C-335
Jack
Herer
Jack
Herer
TWS-C-336
Jack
Herer
Jack
Herer
Jack
Jack
Jack
Herer
Herer
Herer
Trainwreck
TWS-C-313 TWS-C-045
Jack
Herer
Trainwreck
Trainwreck
Jack
Herer
TWS-C-315
Jack
Trainwreck
Herer
Jack
Jack
Herer
HererHerer TWS-C-258
Jack
Jack
Herer
TWS-C-090
Trainwreck
TWS-C-324
TWS-C-018
TWS-C-046
Trainwreck
Trainwreck
Trainwreck
Jack Herer
TWS-C-320
TWS-C-322
TWS-C-321
TWS-C-233
TWS-C-054
TWS-C-033
Trainwreck
TWS-C-158
TWS-C-032
TWS-C-308
TWS-C-058
TWS-C-319
TWS-C-043
TWS-C-134
TWS-C-044
TWS-C-333
TWS-C-334
Trainwreck
TWS-C-317
TWS-C-080
TWS-C-093
TWS-C-037
TWS-C-163
TWS-C-241
TWS-C-051
TWS-C-074
TWS-C-072
TWS-C-014
TWS-C-325
Jack
Herer
WA
TWS-C-069
TWS-C-337
TWS-C-327
TWS-C-266
TWS-C-301
TWS-C-092
TWS-C-316
TWS-C-332
TWS-C-017
TWS-C-291
TWS-C-330
TWS-C-078
OG Kush
TWS-C-242
TWS-C-318
TWS-C-246
TWS-C-303
TWS-C-263
TWS-C-304
TWS-C-132
TWS-C-049
TWS-C-328
TWS-C-006
TWS-C-005
TWS-C-003
TWS-C-009
TWS-C-331
TWS-C-007
TWS-C-279
TWS-C-312
TWS-C-010
TWS-C-166
TWS-C-228
TWS-C-300
TWS-C-008
TWS-C-012
TWS-C-038 TWS-C-064
Sour
Diesel
TWS-C-314
TWS-C-070
Sour
TWS-C-229
Diesel
TWS-C-076
TWS-C-056
TWS-C-234
TWS-C-226
TWS-C-323
TWS-C-048
TWS-C-011
TWS-C-004
TWS-C-244
TWS-C-062
TWS-C-001
TWS-C-089
TWS-C-068
OG
Kush
TWS-C-310
Sour
OG
OG
Diesel
OG
Kush
Kush
Kush
TWS-C-066
TWS-C-243
TWS-C-082
OG
Kush
TWS-C-277
TWS-C-169
OG
Kush
TWS-C-167
TWS-C-002
TWS-C-065
TWS-C-326
Sour
OG
Diesel
Kush
TWS-C-013
Jack
Sour
TWS-C-290
TWS-C-231
Herer
Diesel
Sour
Diesel
Sour
Jack
TWS-C-259
Diesel
Herer
OG
Kush
TWS-C-273
Sour
Diesel
OG
OG
Kush
Kush
Sour
OG
Kush
Diesel
TWS-C-086
TWS-C-040
TWS-C-015
TWS-C-168
Sour
Diesel
TWS-C-302
TWS-C-077
Sour
TWS-C-289
Sour
TWS-C-311
Diesel
Diesel
TWS-C-083
TWS-C-329
Sour
OG
Sour
Kush
Diesel
OG
Diesel
Kush
OG
TWS-C-063
TWS-C-091
Kush
TWS-C-073
TWS-C-087
OG
Sour
Sour
Kush
Sour
TWS-C-075
Diesel
Diesel
Diesel
WA
TWS-C-050
TWS-C-084
OG
Sour
Sour
Kush
Sour
Trainwreck
TWS-C-057
TWS-C-261
Sour
OG
Sour
Diesel
Diesel
OG
Diesel
Kush
Diesel
Diesel
Kush
TWS-C-100
TWS-C-099
TWS-C-305
OG
Sour
Kush
Sour
Diesel
Diesel
OG
Kush
TWS-C-271
Sour
OG
Diesel
WA
Kush
TWS-C-260
WA
Trainwreck
Sour
OG
Diesel
Kush
OG
Kush
TWS-C-224
TWS-C-288
Sour
Diesel
OG
Kush
TWS-C-055
TWS-C-101
TWS-C-225
Sour
TWS-C-278
Diesel
WA
TWS-C-309
TWS-C-088
TWS-C-275
TWS-C-272
OG
TWS-C-262
Kush
TWS-C-307
TWS-C-079
TWS-C-264
TWS-C-067
TWS-C-052
TWS-C-265
TWS-C-060
TWS-C-094
TWS-C-232
TWS-C-276
TWS-C-081
TWS-C-270
TWS-C-227
TWS-C-061
TWS-C-053
TWS-C-036
TWS-C-306
TWS-C-269
TWS-C-071
TWS-C-085
TWS-C-268
4
t[2]
2
0
-2
-4
-7
-6
-5
-4
-3
-2
-1
0
1
2
3
4
5
t[1]
SIMCA-P+ 12 - 2014-06-25 12:21:46 (UTC-8)
6
7
What Profiling Tells Us
• Indica/Sativa/Hybrid designation is not medically
meaningful – may indicate plant’s morphology,
but not physiological impacts on the patient
• New chemotype classifications needed
• Multivariant data analysis useful with cannabis
• Misnaming of strains in CA appears rampant
• Terpenes are major differentiators in this CA
data set – sample set bias is likely (high THC)
• Phenotypes and differing cultivation conditions
lead to additional complexities
Repeatable Consumption
• Inhalation Apparatus
– Combustion versus Vaporization
• Pre-rolled versus hand-rolled
• Temperature of heat source
• Hand held vaporizer versus table top
• Inhalation Operation
– Strength of inhale
– Inhalation duration
• Edible and topical products should be
consistent in production, then use
THC Oral Metabolism
• Swallowed
(not felt)
• Felt
psychoactive
• Excreted
Non-psychoactive
Absorptivity Considerations
• Rate of entering the blood stream
– Inhalation, sublingual, oral
– Each edible product can be very different
– What else has been eaten with the medicine?
• Oral Metabolites
– 11-OH, about 5 times as potent as THC
Pharmacokinetics
• How chemicals are
absorbed and
processed through
the body over a
period of time –
how long the drug
is effective.
Pharmacokinetics
Oral vs. Inhaled THC
Typical metabolite profile of
orally consumed THC
11-Hydroxy-THC
0
100
THC
11-Nor-9-carboxy-THC
200
300
Time in minutes
400
Typical metabolite profile of
inhaled THC
11-Hydroxy-THC
500
0
100
THC
11-Nor-9-carboxy-THC
200
300
Time in minutes
400
500
Inhalation Device Considerations
• Different chemicals delivered each way
– Long Path vs. Short Path
– Chilled, Cold Water, Ice Cubes
– Heating Source Temperature
– Rolled cigarette delivers about 30-40% efficiency
• Patient inhalation strength and duration
• Patients should standardize their own
delivery devices and delivery methods
• We must educate patients on their devices
What is Available When?
• Combustion & Vaporization - HEAT
–Neutral cannabinoids form
• THC, CBD, CBG, CBC
–Trace cannabinoids can be inhaled
• THCA, CBDA, CBN, other derivatives
–Terpenes
• Tinctures, Oral and Topicals
–Exactly what is put in the formulations
• No changes due to further heating
Definition of “Repeatable”
• What is a repeatable dose?
– Pharmaceutical specification is 3% of label claim
– OTC specification is 10% of label claim
– Dietary Supplement is 15% of label claim
• Tolerance of dose is based on the
safety, toxicity and effectiveness
– Does a little more or little less matter?
• How sensitive is each patient to cannabis?
– Toxicity concerns generally low
• Goal is Minimum Effective Dose (MED)
Repeatable Consumption
• Amount of THC/CBD delivered to patient
varies for many different reasons!!
• Patients First Need to Select a
Standardized Delivery Method
– May take some trial and experimentation
• Delivery method
– Oral
– Topical
– Inhalation
Complex Combinations
• Finding a Solution is Difficult
Cannabis Is Diversity
• Ingredients and Production
• Patient Needs
• Use Patterns
• Lack of Standards
• Supply Chain Shifts
Cannabis Based Medicine Cabinet