Medical Marijuana in Canada, 2014: Panacea or Blowing Smoke Dr. - - PowerPoint PPT Presentation

Medical Marijuana in Canada, 2014: Panacea

• r 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

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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

• r specified

medical conditions

A physician completes a medical document on behalf

• f 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
• r 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
• What distinguishes one LP to another?
• Does every LP grow under the same

conditions?

• Is the product safe?
• What does “Jack the Ripper” and “Green Kush” mean?
• 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

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.