Medical Marijuana in Canada, 2014: Panacea

or Blowing Smoke

Dr. Paul Daeninck

Mr. Brent Zettl

Presenter Disclosure

•Presenter: Brent Zettl

•Relationships with commercial interests: • President and CEO of Prairie Plant Systems Inc. and

CanniMed Ltd.

• Mr. Zettl has 14 years of experience in the Canadian Medical Marijuana industry.

• Prairie Plant Systems Inc. has been working with and providing medical marijuana to Health Canada since 2000.

• The parent company has provided product for clinical trials and has on-going clinical trials.

• Generic names will be used and will speak to the regulations, science and production as a whole.

Mitigating Potential Bias

Botany of Cannabis • Cannabis sativa • Cannabaceae family • Close relative of Humulus (hop plant used in beer) • Origin in Central Asia • Annual herb • Dioecious (separate female and male plants)

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Female Cannabis Flowers

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The discovery of THC: 50th anniversary in April 2014!

• THC was first discovered by Raphael Mechoulam and Yehiel Gaoni (Weizmann Institute, Israel)

• Their landmark paper “Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish” was published April 20, 1964 in The Journal of the American Chemical Society Page, 2014

The (phyto)cannabinoids • THC is just one of a large group of plant metabolites called the

cannabinoids; found only in cannabis

• There are more than 110 known cannabinoids

• The major cannabinoids are:

ElSohly & Slade, 2005

9-Tetrahydrocannabinol (THC)

• THC produces many of the psychoactive effects of cannabis

• Also the main therapeutic compound present: • Analgesic*

• Antiemetic*

• Appetite stimulant*

• Antispastic activity* *Reported in literature Gaoni and Mechoulam, 1964; Joy et al, 1999

Cannabidiol (CBD)

• Non-psychoactive cannabinoid in cannabis • Second most important cannabinoid after THC • Cannabidiolic acid (CBDA) is the precursor • Present in hemp and some medicinal strains • Anti-inflammatory, neuroprotective, anxiolytic, anti-

epileptic, antipsychotic*

• May attenuate memory-impairment effects of THC • Role in treating pediatric epilepsy (Dravet syndrome)

*Reported in literature

Hampson et al, 1998; Leweke et al, 2012; Mechoulam et al, 2007; Pertwee, 2008

Cannabinoid receptors: CB1 and CB2

• THC is an agonist at both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2)

• CB1 and CB2 are G-protein coupled receptors (GPCRs) • CB1 is presynaptic • CB1 is the most abundant receptor in the human

brain!

Pertwee, 2001; Mackie, 2008

Patient Symptoms where conventional

treatments have failed

Compassionate end-of-life care

or specified medical

conditions

A physician completes a medical document on behalf of patient for access to medicinal marihuana

The patient then sends in the original medical document and an application form

to the Licensed Producer of their choice.

The Licensed Producer then validates the client’s medical

document and application form and adds them as a

client. Once the client orders product, it is then shipped via secured courier to their door.

Medical Marijuana Current

MMPR Process

(Effective June 30, 2013) http://www.laws-lois.justice.gc.ca/eng/regulations/SOR-2013-119/

Medical Marijuana… How is it different than street marijuana?

• A System of Accountability:

• Grown under strict Good Production Practices (GPP) guidelines enforced by Health Canada

• Tested for the presence of microbials, mycotoxins, & metals

• Pesticide use?

• Delivered to the patient in a safe manner (i.e. secure courier or XPressPost with proof of signature)

• Concentrations of cannabinoids require to be captured on the label (usually THC and CBD)

• Recall ability given lot designation

Cannabis Strains • Thousands of cannabis strains exist

• 13 licensed producers listed 118 strains (May 1st, 2014)

• Most strains were developed for recreational use and still use common names

• high THC (15-20%)

• very low CBD (<1%)

• Varying amounts of minor cannabinoids (CBC, THCV, etc.)

• Patients report that cannabis strains differ in their effects

• Patients and cannabis growers generalize into two types:

• Indica – sedative

• Sativa – stimulating

• The difference between Sativa and Indica may relate to species or subspecies of Cannabis, but this is not clear

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Relates to ratio of THC and CBD

What to look for in a Licensed Producer

• Safety (testing for microbials and mycotoxins – should be able to present lot back-up information if required)

•Consistency (every product will be the same from one order to the next)

•Reliability (production/product inventory availability)

•Knowledgeable (regulatory compliance, documentation and registration)

•Adverse Event Record Keeping (Every LP must have a system to capture adverse events)

Metals Quality Control Testing

Natural Health Products (NHP)

Division of Health Canada regulates

the allowable amounts of Heavy

Metals contaminant in

the MM product

Contaminants Tolerance

(µg/Kg/bw/day)

Arsenic < 0.14

Cadmium < 0.09

Lead < 0.29

Mercury < 0.29

Microbial Quality Control Results

Microbiological Analysis

Pre-Irradiation

Post-Irradiation

Specification

Total Coliforms < 1.8 MPN/g < 1.8 MPN/g < 3 MPN/g

Total Aerobic/ Anaerobic Bacteria

200 CFU/g 0 CFU/g < 100 CFU/g

Escherichia coli Absent Absent Absent

Salmonella Absent Absent Absent

Staphylococcus aureus Absent Absent < 100 CFU/g

Yeasts and Molds 22,000 CFU/g < 33 CFU/g < 100 CFU/g

Toxic Molds

Aspergillus 2333 CFU/g Absent

ID and Report Penicillium 4000 CFU/g Absent

Acremonium 1667 CFU/g Absent

Chaetomium 7667 CFU/g Absent

MPN: most probable number; CFU: colony forming units

Potency Quality Control

The profile of the MS-17/338 cultivar includes mainly THC and THCA, with minimal CBD (specification < 0.5% CBD)

Navigating the Health Canada Website

• 13 Licensed Producers to date (650 applicants as of May 1, 2014)

• Patient confusion over who to choose o What distinguishes one LP to another? o Does every LP grow under the same

conditions? o Is the product safe? o What does “Jack the Ripper” and “Green Kush” mean? o Supply availability?

How to Apply – The Patient’s Process

1. Patient visits their Physician to discuss treatments for their indication.

2. Patient and Physician decide on medical marijuana as treatment.

3. Physician fills out a generic medical document (or a specific LP’s medical document).

4. The Patient then submits their medical document along with their application form directly to an LP.

5. Once the LP registers the Patient, the Patient goes online to purchase their medicine.

The Medical Document must include:

1. Patient’s name and DOB

2. Daily quantity of dried marijuana to be used by the Patient and period of use

3. Health Care Practitioner’s name, profession, business address, phone number, province authorized to practice in and license number

4. Attestation that the information contained is correct and complete

5. Physician signature (original only)

Medical Document

Licensed Producer Mailing

Address

Product choice

Health Care Practitioner Information

Patient Information

Written Order Physician

Attestation and Signature

The LP’s Patient Registration Process

1. Patient’s original application form and medical document are received.

2. LP ensures that all documentation has been submitted and contacts the Physician’s office to confirm details (prescription amount, authorization, etc.)

3. Once documentation is confirmed, LP registers the Patient in their computer system.

4. LP notifies the Patient that they are registered and they may now purchase their medicine.

Questions?

References Elsohly, M.A. and Slade, D. (2005). Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sciences, 78, 539-548

Gaoni, Y. and Mechoulam, R. (1964). Isolation, structure, and partial synthesis of an active constituent of hashish. Journal of the American Chemical Society 86, 1646-1647.

Hampson, A.J., Grimaldi, M., Axelrod, J. and Wink, D. (1998). Cannabidiol and (-) 9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences 95, 8268-8273.

Joy, J.E., Watson, S.J., and Benson, J.A. (Eds.). (1999). Marijuana and Medicine: Assessing the Science Base. National Academies Press.

Leweke, F.M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C.W., Hoyer, C., Klosterkotter, J., Hellmich, M. and Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry 2, e94.

Mackie, K. (2008). Cannabinoid Receptors: Where they are and what they do. Journal of Neuroendocrinology 20 (Suppl.1), 10-14.

Mechoulam, R., Peters, M., Murillo-Rodriguez, E. and Hanus, L.O. (2007). Cannabidiol—recent advances. Chemistry and Biodiversity 4, 1678-1692.

Page, J. (2014). Introduction to cannabis, cannabinoids and the endocannabinoid system. CCIC Conference.

Pertwee, R.G. (2001). Cannabinoid receptor ligands. Tocris Reviews 16, 1-8.

Pertwee, R.G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology 153, 199-215.