Throughout 2015 the Canadian Cancer Survivor Network (CCSN) will offer a series of webinars designed to provide you with information to help build your knowledge and understanding of medical marijuana use in Canada. The first webinar in this series features a presentation and Q&A session with Dr. Paul Daeninck , MD, MSc, FRCPC.

1. Medical Marijuana in
Canada
A Practical Understanding
of Its Use for Cancer
Patients
Paul Daeninck, MD MSc FRCPC
Departments of Internal & Family Medicine
University of Manitoba and CancerCare Manitoba

2. Objectives
At the end of this event, participants will
learn about:
1. The basic facts about medical cannibis
2. The role of medical cannabis for cancer
patients

3. Ma-fen is used for waste
diseases and injuries; it clears
blood and…it undoes
rheumatism. If taken in excess
it produces hallucinations and a
staggering gait. If taken over
a long term it causes one to
communicate with spirits and
lightens one’s body
Ancient Chinese Herbal, c. 2700 BC

4. Russo et al, 2008
Cannabis in History
Food and oil (seeds)
Fibre
(stems)
Drug /
Medicine
(flowers)

5. W.B. O’Shaughnessey, Irish MD
observed use in India 1839
– found a “tincture of hemp”
to be effective analgesic,
muscle relaxant and anti-
seizure treatment
Provided cannabis to
pharmacists in England in
1842

7. Cannabis in History
Production by Lilly and others to
1930s
1937: US Tax Act
1970: Controlled substance
1970s-80s research supported
July 2001: Cdn gov’t medicinal use
Apr 2014: MMPR established

8. Medline-indexed publications on cannabis and cannabinoids
1962-2006
0
200
400
600
800
1000
1200
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Year
Numberofpapers
Medline-indexed publications on cannabis &
cannnabinoids
1962-2006

10. Cannabis sativa

11. Time
Nov 22/2010

12. HOW DOES CANNABIS WORK?

13. Cannabis sativa
Marijuana (dried leaves / flowering heads)
Isolated pure compounds
Non-cannabinoids Cannabinoids
Psychoactive
Δ9-THC
Δ8-THC
cannabinol (weak)
Active, not
psychoactive
cannabidiol
Inactive
> 60
compounds
> 400 chemical
compounds
> 70 types of
cannabinoids
Most potent
psychoactive
ingredient
Marijuana: What’s in it?
Kalant H. Pain Res Manage 2001;6:80-91

14. 1) Neurotransmitter (NT) released
from vesicles within the
presynaptic neuron activates the
postsynaptic neuron
2) Activation of postsynaptic neuron
leads to synthesis and release of
endocannabinoid
3) The endogenous CB1 ligand
diffuses back to and binds to the
presynaptic CB1 receptor
4) The CB1 receptor activates a
G-protein, which lead to
presynaptic events that result in
inhibition of NT release
5) Exogenous drugs directly activate
CB1 receptors to stimulate the
endogenous cannabinoid system,
enhancing its function
5
1
2
4
3

15. Female flowers (“buds”) are rich in cannabinoids (e.g. THC)
Smoked
Herbal cannabis
Joints, pipes
Vaporized
Herbal cannabis heated to release cannabinoids but
prevent burning
Oral / buccal
Tinctures (alcoholic extracts)
Edible products (cookies and brownies)
Sublingual spray (nabiximols by prescription)
Topical
Balms, lotions and salves
Use of medicinal cannabis

17. WHO IS USING CANNABIS?

18. Disease Prevalence Author(s)
HIV/AIDS 15-40%
Sidney 2001, Braitstein 2002, Ware
2002, Woolridge 2005, Prentiss 2006
Epilepsy 21% Gross 2004
Chronic noncancer
pain (CNCP)
15% Ware 2003
Multiple sclerosis (MS) 10-12% Page 2005, Clark 2006, Chong 2006
Who uses cannabis as
medicine?

19. Who uses cannabis as
medicine?
2% use cannabis for medical purposes
>37,000 people registered with MMAR
No prospective prevalence studies done in:
Cancer est 15-25%
Pall Care unknown
Ogborne, CMAJ 2000
Health Canada information

21. Hazekamp et al, J Psycho Drugs, 2013

22. Hazekamp et al, J Psycho Drugs, 2013

23. Hazekamp et al, J Psycho Drugs, 2013

24. WHY ARE PATIENTS ASKING
FOR CANNABIS?
WHAT IS THE EVIDENCE?

25. On-label indications:
Nausea and vomiting from chemotherapy
Chronic pain (neuropathic pain in MS and
cancer)
Anorexia associated with HIV / AIDS
Off-label indications/emerging evidence for:
Neuropathic/nociceptive/
mixed pain
Chronic daily headache
Fibromyalgia
Anorexia and cachexia
Spasticity
Epilepsy
Cannabinoid indications
PTSD
Anxiety
Insomnia
Spasticity (MS)
Lower urinary tract
symptoms (MS)
Improving bladder symptoms
associated with MS

26. Pharmacology of cannabis
Izzo, 2009

27. Cannabinoid receptors and pain
Cannabinoid receptors active in
inflammatory and neuropathic pain models
Cancer pain models involve both CB1 & CB2
receptors
bone pain
inflammatory pain
neuropathic pain

30. Cannabinoids & cancer pain
Farquhar-Smith WP Curr Opin Support Palliat Care 2009;3:7-13

31. Nabiximols in cancer pain
Cannabis extract:
THC 2.7 mg/CBD 2.5 mg per 0.1 mL
minor CBs, terpenoids, sterols & plant components
Used in several pain studies (MS, NP, RA)
Conditional approval for use
in Canada, UK (cancer/neuropathic pain)

32. Agent N= Indication Duration/Type Outcome/References
Sativex
GWCA0101
177 Intractable cancer pain 2 wks Improvements in NRS analgesia
vs placebo (p=0.0142),
Tetranabinex NSD (Johnson et al,
2010)
Sativex
GWCA0701
360 Intractable cancer pain 5 wks/DB CRA of lower & middle dose
cohorts improved over placebo
(p=0.006) (Portenoy et al, 2012)
Adapted from: Russo EB, Hohmann AG. Role of cannabinoids in pain management. In: Deer T,
Gordin V, editors. AAPM Textbook of Pain Medicine. New York: Springer; 2011.
Nabiximols in cancer pain
Nabiximols
Nabiximols

33. Nabiximols: mean pain scores
Johnson et al. JPSM 2010;39:167-179.
Nabiximols

34. Portenoy et al. J Pain 2012: 13:438-449
Nabiximols: improvement in pain

35. Nabiximols: less sleep disruption
Baseline Scores: Placebo=4.6 (n=91); 4 Sprays=4.1 (n=91); 4&10 Sprays=4.3 (n=178)
Courtesy of Dr. Stephen Wright, GW Pharma

36. Cannabinoids in nausea
20 pts, RCT, P vs THC, X-over
10 or 15 mg/m2 po q4h x 3, various
tumours
Chemotherapy not specified
Anti-emetic effect seen in 14/20 THC vs
0/22 P (p<0.001)
No patients vomited while “high”
Sallan et al, NEJM 1975 293: 795-797

37. Martin BR & Willey JL. J Support Onc 2004;2: 305-16
Cannabinoids in nausea

38. Inhaled marijuana
Three studies, associated with chemo
administration
Some new users, many previous
cannabis users
All studies showed benefit, but high
incidence of side effects
25-35% pts prefer marijuana
Vinciguerra et al, N Y State J Med 1988 88:525
Chang et al, Ann Int Med 1979 91:819
Levitt et al, JCO 1984 abstract C-354

39. Jatoi A et al. J Clin Oncol 2002;20:567-573
Nelson K et al. J Pall Care 1994;10:14-18
Timpone JG et al. AIDS Res Hum Retroviruses 1997;13:305-15
Struwe M et al. Ann Pharmacother 1993;27:827-31
Beal JE et al. J Pain Symptom Manage 1995;10:89-97
Beal JE et al. J Pain Symptom Manage 1997;14:7-14
Appetite and weight loss

40. Cannabinoids and Anxiety
Epidemiological studies
demonstrate the most common
reason for use of cannabis is to
reduce feelings of stress, tension
and anxiety
Several reports suggest many
individuals self medicate anxiety
with cannabis
Hollister, 1986; Tournier et al., 2003
Van Dam et al, 2012; Agosti et al, 2002
Hill et al, 2008; Dlugos et al, 2012

41. Cannabinoids and anxiety:
clinical studies
A small study examined efficacy of
nabilone (1 mg nabilone, 3 times a
day for 28 days) in neurotic
anxiety. Significant benefit was seen
after 4 days of treatment vs placebo
Reduced somatic and depressive
symptoms seen in these patients
Fabre and McLendon, 1981

42. Cannabinoids and anxiety:
clinical studies
Oral preparations of very low dose
cannabis could produce sedation
and diminish anxiety independent of
psychoactivity
Cannabidiol, another constituent of
cannabis has anti-anxiety effects,
although seen experimentally-
induced anxiety
Graham and Li, 1976

43. Federal Government Signs Off
On Study Using Marijuana To
Treat Veterans' PTSD
http://www.huffingtonpost.com/2014/03/17/ptsd-medical-
marijuana-study_n_4980702.html
Marijuana May Hold Promise
As Treatment For PTSD
http://www.huffingtonpost.com/2014/11/22/cannabis-
ptsd_n_6199254.html

44. 20 Medical Studies That Prove
Cannabis Can Cure Cancer
http://www.collective-evolution.com/2013/08/23/20-medical-studies-that-prove-
cannabis-can-cure-cancer/#sthash.H5ypYS6a.dpuf
Cannabis Cures Cancer
https://dl.dropboxusercontent.com/u/27713298/Web/cure/How_It_Works.html
Run From The Cure: How Cannabis
Cures Cancer And Why No One Knows
Cannabis sativa hemp, the miracle plant, contains the cure for cancer and
other ailments By Rick Simpson - Friday, March 7 2008
http://www.cannabisculture.com/articles/5169.html

45. MARIJUANA DOES
NOT CURE CANCER

46. Cannabinoids as anticancer agents
Guzman M. Nature Rev Cancer 2003:3;745-755

47. Enhancing the Activity of Cannabidiol
and Other Cannabinoids In Vitro
Through Modifications to Drug
Combinations and Treatment Schedules
October 2013 vol. 33 no. 10 4373-4380
KATHERINE ANN SCOTT, SINI SHAH, ANGUS GEORGE
DALGLEISH and WAI MAN LIU

49. Cannabinoids and cancer
treatment
THC delivered to the tumour bed 3-6 days after resection
cell growth effects noted
no survival benefit (mean 24 wks)
no psychoactive effects
Treatment was safe, sets stage for further investigation

50. HOW DOES ONE OBTAIN
MEDICAL MARIJUANA IN
CANADA?

51. Why is authorizing cannabis so
difficult?
Multiple symptoms are affected by cannabis
Pain
Spasticity
Sleep
Anxiety
Doses used are hard to quantify
It is recreational drug with a great deal of stigma
Data on risks and benefits do not meet regulatory
standards
No teaching in medical school or training programs

52. Prescription cannabinoids
Dronabinol (Δ-9 tetrahydrocannabinol – THC) (2.5 - 10mg)
Oral capsule
Approved for chemotherapy-induced nausea and vomiting and
anorexia associated with HIV/AIDS
Nabilone (0.25 - 1.0mg)
Oral capsule
Approved for chemotherapy-induced nausea and vomiting
Nabiximols (2.5mg THC + 2.7mg CBD)
Oromucosal spray
Approved in Canada for multiple sclerosis-associated
neuropathic pain, spasticity and advanced cancer pain

53. http://www.cmpa-acpm.ca/cmpapd04/docs/resource_files/web_sheets/2013/com_w13_005-e.cfm
“Physicians must be familiar with the
existing program for patients currently
accessing medical marijuana and must
also familiarize themselves with the new
regulations.
Physicians are expected to know and
comply with the regulations and policies
of their College.”

56. Precautions and
contraindications
Contraindications:
Psychosis/schizophrenia
Unstable heart disease
Ask about:
History of legal issues/criminal charges
Screening for other drug use
Prior recreational cannabis use
Validate that use of cannabis is‘medical’

57. Other concerns
Psychosis
Sedation
Anxiety
Dependence
Cardiovascular
effects
Nausea
Cognition
Interactions
Respiratory effects
Pregnancy

58. Medical cannabis: 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 as well as 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

59. Health Canada website
14 Licensed Producers to date
Patient confusion over who to choose
What distinguishes one LP over another?
Is the product safe?
What does “Jack the Ripper” and “Green
Kush” mean?
Supply availability?
http://www.hc-sc.gc.ca/dhp-
mps/marihuana/info/list-eng.php

60. Cannabis Strains
Thousands of cannabis strains exist
14 licensed producers listed >120 strains
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.)
Page, 2014

61. Cannabis Strains
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
Page, 2014

62. Summary
Cannabis has been used for medical purposes
for centuries
Indications for cannabinoid use are varied, but
evidence is still lacking
Any physician can authorize the use of medical
marijuana, but is not compelled to do so