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Webinar Information:
At this webinar you will learn:
• Basic facts about medical cannabis in Canada
• The role of medical cannabis for cancer patients
• How to access medical cannabis under the current Health Canada process
Presenter Information:
Dr. Paul Daeninck is an oncologist and palliative care consultant with CancerCare Manitoba and is an Assistant Professor at the University of Manitoba. He is the Chair of the Symptom Management and Palliative Care disease site group at CancerCare Manitoba and the President–elect of the Board of Directors of the Canadian Consortium for the Investigation of Cannabinoids (CCIC). He has a research and clinical interest in the use of cannabis and cannabinoids in patients with cancer and cancer-related conditions.
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linearity concept of significance, standard deviation, chi square test, stude...
Medical Marijuana - Does it Have a Role in the Treatment of Cancer Patients?
1. Medical marijuana
Does it have a role in the
treatment of 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. Basic facts about medical cannabis in
Canada
2. The role of medical cannabis for cancer
patients
3. How to access medical cannabis under the
current Health Canada process
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. A few definitions…
Cannabis: plant material, cannabis sativa,
cannabis indica, hemp, marijuana
Cannabinoid: group of active compounds
found in cannabis (e.g., THC, CBD, CBG, etc)
Endocannabinoid system: includes
receptors (CB1, CB2), ligands (2-AG),
enzymes (FAAH)
7. 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
> 80
compounds
> 400 chemical
compounds
> 70 types of
cannabinoids
Most potent
psychoactive
ingredient
Cannabis: What’s in it?
Kalant H. Pain Res Manage 2001;6:80-91
active in several conditions
8. 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
Cappendijk S Modulators of Drug Dependence Phenomena 2010
Mackie K Ann Rev Pharmacol Toxicol 2006,46:101-122
9. Endocannabinoids
Immune function
Inflammation
Appetite
Metabolism and energy
homeostasis
Cardiovascular function
Digestion
Bone development and
bone density
Pain
Reproduction
Psychiatric disease
Psychomotor behavior
Memory
Wake/sleep cycles
Regulation of stress and
emotional state
Learning
Evidence supports the role of endocannabinoids in:
11. Who uses cannabis as
medicine?
2% use cannabis for medical purposes (2000)
>37,000 people registered with MMAR (Mar 2013)
approx 6% cancer Dx
>50,000 people registered with MMPR (Mar 2016)
>98,000 registrants with ACMPR (Sept 2016)
No epidemiology studies done in cancer or
palliative care patients
Ogborne, CMAJ 2000
Health Canada information
20. What is the evidence?
Pain
Pre-clinical
Clinical
Evidence
++
+++
21. Pre-clinical data: Pain
Robust in vitro evidence cancer pain
responds to cannabinoid treatment
Use in bone pain/neuropathic pain has
strongest evidence
Direct use of agonists/antagonists and
prevention of enzyme degradation
Peripheral application effective, few A/E
22. Clinical data: Pain
Trial evidence supports oral use in cancer
pain, in addition to usual therapy
Small studies using smoking/vaporization
None using edibles or oils
Reduction in use of pain meds noted
Few A/E
23.
24. Conclusions of reviews
Studies small, short in duration, modest
effect size
“cannabinoids are safe, demonstrate a
modest analgesic effect and provide a
reasonable treatment option for chronic
non-cancer pain”
25. CPS neuropathic pain
guideline revision
Add additional agents
sequentially if partial but
inadequate pain relief
Tramadol or Controlled-release opioid analgesic
Fourth-line agents†
Cannabinoids
TCA Gabapentin or pregabalin SNRI ‡
†methadone, lamotrigine, topiramate, valproic
acid, lidocaine.
‡Do not add SNRIs to TCAs
Pain Res Manage 2014;19(6):328-335
26. What is the evidence?
Nausea
Pre-clinical
Clinical
Evidence
++
+++
27. Martin BR & Willey JL. J Support Onc 2004;2: 305-16
Cannabinoids in nausea
28. CBs may be superior to conventional therapies in low-
medium emetogenic setting
Patient preference for CBs ranged from 38-90% (P 4-20%)
CBs produced significantly more A/E effects (good & bad),
more pt withdrawals
“In selected patients, cannabinoids may be useful as
mood enhancing adjuvants for the control of
chemotherapy related sickness”
BMJ 2001, 323:1-8
29. 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
30. What is the evidence?
Appetite/wt loss
Pre-clinical
Clinical
Evidence
++
+
31. Marijuana flips
appetite switch in
brain
Sudden attacks of 'the
munchies’ triggered by
changes in hormone pro-
opiomelanocortin (POMC)
release by neurons
doi:10.1038/nature.2015.16957
doi: 10.1038/nature14260
32. 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
33. Dronabinol: taste alterations
Pilot trial to improve taste, smell changes in advanced
cancer patients
THC 2.5 mg BID or TID vs placebo x 18 days, n=21
Questionnaires / interviews revealed significant
improvement in taste / smell, increased appetite and
protein intake
QoL measures found improved relaxation, quality of
sleep
Adverse effects same in both groups
TD Brisbois Clarkson et al, Ann Oncol 2011; 22: 2086-93
34. What is the evidence?
Neuroprotection
Pre-clinical
Clinical
Evidence
+/-
+
35.
36. What is the evidence?
Insomnia
Pre-clinical
Clinical
Anxiety
Pre-clinical
Clinical
Evidence
-
++*
++
-
*secondary finding
37. Cannabinoids and anxiety
Oral cannabinoids used for nausea
produces sedation and reduces
anxiety
Very low dose cannabis can
produce sedation, diminish anxiety
without getting high
Cannabidiol can exert anti-anxiety
effects, although only demonstrated
in acute, experimentally-induced
anxiety
Tramer et al, BMJ 2001; 323:1-8
Graham and Li, Cannabis and Health, 1976
Bergamaschi et al, Neuropsychopharmcol 2011; 36: 1219-26
38.
39. 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
40. What is the evidence?
Cancer
Pre-clinical
Clinical
Clinical trials
Evidence
+++
nil
- In Progress
Cannabis is not a cure for
cancer
42. 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
43. 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)
Oils and edible products (cookies, brownies, etc.)
Sublingual spray (nabiximols by prescription)
Topical
Balms, lotions and salves
Medicinal cannabis products
44.
45. Health Canada website
36 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
46. Cannabis strains
Thousands of cannabis strains exist
34 licensed producers listed >300 strains
Most strains were developed for recreational use
and still use common names
high THC (15-20%), very low CBD (<1%)
mod CBD (9-15%), low THC (1-4%)
THC=CBD
Oils (THC>CBD, THC=CBD, THC<CBD)
Varying amounts of minor cannabinoids (CBC, THCV,
etc.), terpenoids, flavonoids
Page, 2014
47. Medical cannabis: Is it different
than street marijuana?
Grown under strict Good Production Practices (GPP)
guidelines enforced by Health Canada
Most producers have industrial size “grow-ops”
Products tested for microbials, mycotoxins, metals and
pesticides
Delivered to the patient in a safe and secure manner
Concentrations of cannabinoids captured on label
(usually THC and CBD)
Recall ability given lot designation
51. PatientCompassionate end-
of-life care or
specified medical
conditions A physician
completes a
medical
document on
behalf of
patient for
access to
medicinal
marijuana
Current ACMPR process
53. Patient
Current ACMPR process
The Licensed Producer
validates the client’s medical
document / application form and
adds them as a client. Once the
client orders product, it is then
shipped via secured courier to
their door.