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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
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
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
Russo et al, 2008
Cannabis in HistoryFood and oil (seeds)
Fibre (stems)
Drug / Medicine(flowers)
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
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
Medline-indexed publications on cannabis and cannabinoids1962-2006
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ap
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Medline-indexed publications on cannabis &
cannnabinoids
1962-2006
Cannabis sativa
Time
Nov 22/2010
HOW DOES CANNABIS WORK?
Cannabis sativa
Marijuana (dried leaves / flowering heads)
Isolated pure compounds
Non-cannabinoids Cannabinoids
PsychoactiveΔ9-THC
Δ8-THC
cannabinol (weak)
Active, not
psychoactivecannabidiol
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
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
43
Female flowers (“buds”) are rich in cannabinoids (e.g. THC)
Smoked
Herbal cannabisJoints, 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
WHO IS USING CANNABIS?
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?
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
Hazekamp et al, J Psycho Drugs, 2013
Hazekamp et al, J Psycho Drugs, 2013
Hazekamp et al, J Psycho Drugs, 2013
WHY ARE PATIENTS ASKING
FOR CANNABIS?
WHAT IS THE EVIDENCE?
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
Pharmacology of cannabis
Izzo, 2009
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
Cannabinoids & cancer pain
Farquhar-Smith WP Curr Opin Support Palliat Care 2009;3:7-13
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)
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
Nabiximols: mean pain scores
Johnson et al. JPSM 2010;39:167-179.
Nabiximols
Portenoy et al. J Pain 2012: 13:438-449
Nabiximols: improvement in pain
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
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
Martin BR & Willey JL. J Support Onc 2004;2: 305-16
Cannabinoids in nausea
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
Jatoi A et al. J Clin Oncol 2002;20:567-573Nelson K et al. J Pall Care 1994;10:14-18Timpone JG et al. AIDS Res Hum Retroviruses 1997;13:305-15Struwe M et al. Ann Pharmacother 1993;27:827-31Beal JE et al. J Pain Symptom Manage 1995;10:89-97Beal JE et al. J Pain Symptom Manage 1997;14:7-14
Appetite and weight loss
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
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
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
Federal Government Signs Off
On Study Using Marijuana To
Treat Veterans' PTSDhttp://www.huffingtonpost.com/2014/03/17/ptsd-medical-
marijuana-study_n_4980702.html
Marijuana May Hold Promise
As Treatment For PTSDhttp://www.huffingtonpost.com/2014/11/22/cannabis-
ptsd_n_6199254.html
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 Cancerhttps://dl.dropboxusercontent.com/u/27713298/Web/cure/How_It_Works.html
Run From The Cure: How Cannabis
Cures Cancer And Why No One KnowsCannabis 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
MARIJUANA DOES
NOT CURE CANCER
Cannabinoids as anticancer agents
Guzman M. Nature Rev Cancer 2003:3;745-755
Enhancing the Activity of Cannabidiol
and Other Cannabinoids In Vitro
Through Modifications to Drug
Combinations and Treatment SchedulesOctober 2013 vol. 33 no. 10 4373-4380
KATHERINE ANN SCOTT, SINI SHAH, ANGUS GEORGE
DALGLEISH and WAI MAN LIU
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
HOW DOES ONE OBTAIN
MEDICAL MARIJUANA IN
CANADA?
Why is authorizing cannabis so
difficult?
Multiple symptoms are affected by cannabisPain
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
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
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.”
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’
Other concerns
Psychosis
Sedation
Anxiety
Dependence
Cardiovascular
effects
Nausea
Cognition
Interactions
Respiratory effects
Pregnancy
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
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
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
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
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
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