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Chemical and Genetic Variation in Cannabis Strains
Jonathan Page, PhD
University of British Columbia &
Anandia Labs
• Presenter: Jonathan Page• Relationships with commercial interests:
– Founder, CEO and shareholder of a plant biotech and testing company, Anandia Laboratories Inc., that tests cannabis with ACMPR LPs
Presenter Disclosure
Mitigating Potential Bias
• No commercial entity had any involvement in the development of educational materials.
• The steering committee had full control over the program development. • Needs assessment results, past event evaluations, and supporting
documentation were used by the Steering Committee to identify key topics, content and select speakers.
• All faculty members completed the University of Toronto, Faculty of Medicine, Office of Continuing Education and Professional Development Faculty & Planning Committee Disclosure Declaration Form and disclose any identified potential conflicts to participants in accordance with the CFPC standards of Conflicts of Interest and Transparency to Learners.
• Generic names will be used.• Potential faculty conflicts of interest were reviewed and addressed by the
steering committee.
Mitigating Potential Bias
• No commercial entity had any involvement in the development of educational materials.
• The steering committee had full control over the program development. • Needs assessment results, past event evaluations, and supporting
documentation were used by the Steering Committee to identify key topics, content and select speakers.
• All faculty members completed the University of Toronto, Faculty of Medicine, Office of Continuing Education and Professional Development Faculty & Planning Committee Disclosure Declaration Form and disclose any identified potential conflicts to participants in accordance with the CFPC standards of Conflicts of Interest and Transparency to Learners.
• Generic names will be used.• Potential faculty conflicts of interest were reviewed and addressed by the
steering committee.
WHAT IS A STRAIN?
• The term “strain” has been used for different cannabis types because the plant has (mostly) been ignored by formal horticultural naming conventions
• Cultivar (Cultivated Variety) is used for most other crop plants
• Chemovar (Chemical Variety) has been suggested for some cannabis types
CANNABIS STRAIN DIVERSITY
Patients, growers, LPs and dispensaries differentiate two types:
“Indica”• short plant with broad leaves• Sedative and “body stone”
“Sativa”• tall plant with narrow leaves• Stimulating and cerebral effects
“INDICA” VS “SATIVA”
CANNABIS GENOTYPING
Hemp“Indica”
“Sativa”
Sawler et al, 2015
CANNABIS: THE MIXTURE IS THE MEDICINE
Pain relief,appetite,
antinausea,antispasticity…+ psychoactivity
O
OH
THC
CBDO
OHOH
HO
CBD
Myrcene
Linalool
Cannabinol
Limonene
THE CANNABINOIDS
• Group of ~100 metabolites; found only in cannabis• Cannabinoids are prenylated polyketides =
terpenophenolics
THE TERPENES
• Group of 40,000+ metabolites; found in all plants• Often called terpenoids or isoprenoids
-Pinene
-Caryophyllene
Myrcene Limonene Linalool
OH
-Humulene
Monoterpenes
Sesquiterpenes
ETABOLITE PROFILING: CANNABINOIDS + TERPEN
CBCA
THCA
CBDA
CBGA
Time (min)
0
50000
100000
150000
200000
250000
5 6 7 8 9 10 11 12 13 14 15 16 17 18
Monoterpenes
Sesquiterpenes
-Pinene
Myrcene
Limonene
Linalool-Humulene
-Caryophyllene
Time (min)
Cannabinoids
THC AND CBD LEVELS IN CANNABIS STRAINS (2015)• Data from March 2015
• ~210 strains available for 15 MMPR LPs
0
2
4
6
8
10
12
14
16
18
20
0 5 10 15 20 25 30 35
CB
D (%
dry
wei
ght)
THC (% dry weight)
Average17.5% THC0.3% CBD
THC AND CBD LEVELS IN CANNABIS STRAINS (2018)
Estimated 300+ strains available in March 2018
Trends:• More strain diversity• Higher CBD levels• Higher THC levels• More options for mixed THC:CBD (Chemotype II strains)
COMPETING HYPOTHESES ABOUT CANNABISPHARMACOLOGY
Posit that the effects of cannabis are mediated by:
1) THC (dominant active principle)2) THC and CBD (Health Canada)3) The collective and interactive effects of THC, CBD and
other cannabis compounds (e.g. minor cannabinoids and terpenes)
Decreasing support for the 1st hypothesis• Patient reports of strain‐specific effects • Preclinical pharmacology
THE “ENTOURAGE EFFECT”
Why do patients report that cannabis strains differ in their effects, when they typically contain high levels of THC?
• Minor cannabinoids? Other chemicals?
• Terpenes are volatile compounds responsible for the distinct smell of cannabis (pine, lemon, berry…)
• Co‐occur with cannabinoids in trichomes
• The complex mixture of cannabinoids and terpenes together may form a metabolic “entourage” that is responsible for the bioactivity of cannabis (Russo, 2011)
• Note: this remains a hypothesis that requires testing!
EVIDENCE OF STRAIN‐SPECIFIC EFFECTS IN HUMANS
Therapeutic Satisfaction and Subjective Effects of DifferentStrains of Pharmaceutical‐Grade Cannabis. Brunt et al. 2014 – J Clin Psychopharm• 102 adults, pharmaceutical cannabis• Psychometric (VAS): alertness, anxiety, irritability, appetite, sociability…• Q’s: Indication, strain, administration, frequency, dose, nature & degree of effect
3 strains• 19% THC/less than 1% CBD (n = 48)• 12% THC/less than 1% CBD (n = 29)• 6% THC/7.5% CBD (n = 25)
Results• No strain effects on dose (occasion, cumulative)• No strain effects on therapeutic satisfaction• Differences in subjective effects
EVIDENCE OF STRAIN‐SPECIFIC EFFECTS IN HUMANS
Brunt et al. 2014
• Strains are not recognized by horticultural authorities but represent a widespread naming convention for cannabis
• 100s of strains are available to ACMPR patients• Strains are genetically distinct• “Indica” and “Sativa” classifications are dubious• Strains vary in their cannabinoid and terpene chemistry,
providing some suggestion for strain‐specific effects• However, there is very little evidence from trials to support
strain differences• More research is needed!
SUMMARY AND CONCLUSIONS