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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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