chemical and genetic variation in cannabis strains...evidence of strain‐specific effects in humans...

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