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Medical marijuana Does it have a role in the
treatment of cancer patients?
Paul Daeninck, MD MSc FRCPC
Departments of Internal & Family MedicineUniversity of Manitoba and CancerCare Manitoba
Objectives
At the end of this event, participants will learn about:1. Basic facts about medical cannabis in Canada2. The role of medical cannabis for cancer patients3. How to access medical cannabis under the current Health Canada process
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)
A few definitions…
Cannabis: plant material, cannabis sativa, cannabis indica, hemp, marijuanaCannabinoid: group of active compounds found in cannabis (e.g., THC, CBD, CBG, etc)Endocannabinoid system: includes receptors (CB1, CB2), ligands (2-AG), enzymes (FAAH)
TimeNov 22/2010
How does cannabis work?
Cannabis sativa
Marijuana (dried leaves / flowering heads)
Isolated pure compounds
Non-cannabinoids Cannabinoids
PsychoactiveΔ9-THCΔ8-THCcannabinol (weak)
Active, notpsychoactivecannabidiol
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;6:80-91active in several conditions
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
Cappendijk S Modulators of Drug Dependence Phenomena 2010 Mackie K Ann Rev Pharmacol Toxicol 2006,46:101-122
Endocannabinoids
Immune functionInflammationAppetiteMetabolism and energy homeostasisCardiovascular functionDigestionBone development and bone density
PainReproductionPsychiatric diseasePsychomotor behaviorMemoryWake/sleep cyclesRegulation of stress and emotional stateLearning
Evidence supports the role of endocannabinoids in:
Who is using medical
cannabis?
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 2000Health Canada information
Market data from Health Canada
Hazekamp et al, J Psycho Drugs, 2013
Hazekamp et al, J Psycho Drugs, 2013
Time Nov 22/2010
Why are people
asking for cannabis?What is the evidence?
On-label indications:Nausea and vomiting from chemotherapyChronic pain (neuropathic pain in MS and cancer)Anorexia associated with HIV / AIDS
Off-label indications/emerging evidence for:
Neuropathic / mixed painChronic daily headacheAnorexia / cachexiaSpasticityEpilepsy
Cannabinoid indications
PTSD Anxiety Insomnia Spasticity (MS) Bladder spasms (MS) Fibromyalgia
Symptom prevalence in cancer patients
PainDepressionAnxietyConfusion (delirium)FatigueBreathlessness (dyspnea)
NauseaConstipationAnorexia
35 - 96% 3 - 77%13 - 79% 6 - 93%32 - 90%10 - 70% 6 - 68%23 - 65%30 - 92%
Solano et al, JPSM 2006; 31: 58-69
Symptoms responsive to cannabinoids
PainDepressionAnxietyConfusion (delirium)FatigueBreathlessness (dyspnea)
NauseaConstipationAnorexia
What is the evidence?
Pain Pre-clinical Clinical
Evidence++ +++
Pre-clinical data: Pain
Robust in vitro evidence cancer pain responds to cannabinoid treatmentUse in bone pain/neuropathic pain has strongest evidenceDirect use of agonists/antagonists and prevention of enzyme degradation Peripheral application effective, few A/E
Clinical data: Pain
Trial evidence supports oral use in cancer pain, in addition to usual therapy Small studies using smoking/vaporizationNone using edibles or oilsReduction in use of pain meds notedFew A/E
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”
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
What is the evidence?
Nausea Pre-clinical Clinical
Evidence++
+++
Martin BR & Willey JL. J Support Onc 2004;2: 305-16
Cannabinoids in nausea
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
Inhaled marijuana
Three studies, associated with chemo administrationSome new users, many previous cannabis usersAll studies showed benefit, but high incidence of side effects25-35% pts prefer marijuana
Vinciguerra et al, N Y State J Med 1988 88:525Chang et al, Ann Int Med 1979 91:819Levitt et al, JCO 1984 abstract C-354
What is the evidence?
Appetite/wt loss Pre-clinical Clinical
Evidence+++
Marijuana flips appetite switch in
brainSudden attacks of 'the munchies’ triggered by
changes in hormone pro-opiomelanocortin (POMC)
release by neurons
doi:10.1038/nature.2015.16957doi: 10.1038/nature14260
Jatoi A et al. J Clin Oncol 2002;20:567-573 Nelson 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
Dronabinol: taste alterationsPilot trial to improve taste, smell changes in advanced cancer patientsTHC 2.5 mg BID or TID vs placebo x 18 days, n=21Questionnaires / interviews revealed significant improvement in taste / smell, increased appetite and protein intakeQoL measures found improved relaxation, quality of sleep Adverse effects same in both groups
TD Brisbois Clarkson et al, Ann Oncol 2011; 22: 2086-93
What is the evidence?
Neuroprotection Pre-clinical Clinical
Evidence+/-+
What is the evidence?
Insomnia Pre-clinical ClinicalAnxiety Pre-clinical Clinical
Evidence-
++*
++-
*secondary finding
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; 323:1-8Graham and Li, Cannabis and Health, 1976Bergamaschi et al, Neuropsychopharmcol 2011; 36: 1219-26
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 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
What is the evidence?
Cancer Pre-clinical Clinical Clinical trials
Evidence+++nil
- In Progress
Cannabis is not a cure for cancer
What should one know
about obtaining medical
cannabis in Canada?
Prescription cannabinoidsDronabinol (Δ-9 tetrahydrocannabinol – THC) (2.5 - 10mg)
Oral capsuleApproved for chemotherapy-induced nausea and vomiting and anorexia associated with HIV/AIDS
Nabilone (0.25 - 1.0mg)Oral capsuleApproved for chemotherapy-induced nausea and vomiting
Nabiximols (2.5mg THC + 2.7mg CBD)Oromucosal sprayApproved in Canada for multiple sclerosis-associated neuropathic pain, spasticity and advanced cancer pain
Female flowers (“buds”) are rich in cannabinoids (e.g. THC)Smoked
Herbal cannabis-joints, pipesVaporized Herbal cannabis heated to release cannabinoids but prevent burningOral / buccalTinctures (alcoholic extracts)Oils and edible products (cookies, brownies, etc.)Sublingual spray (nabiximols by prescription)TopicalBalms, lotions and salves
Medicinal cannabis products
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
Cannabis strains
Thousands of cannabis strains exist34 licensed producers listed >300 strainsMost strains were developed for recreational use and still use common nameshigh THC (15-20%), very low CBD (<1%)mod CBD (9-15%), low THC (1-4%)THC=CBDOils (THC>CBD, THC=CBD, THC<CBD)Varying amounts of minor cannabinoids (CBC, THCV, etc.), terpenoids, flavonoids
Page, 2014
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
Precautions and contraindications
Contraindications: Psychosis/schizophreniaUnstable heart diseasePregnancyAge under 21-25 (cognitive development)
Ask about:History of legal issues/criminal chargesScreening for other drug usePrior recreational cannabis use
Adverse effects
DrowsinessDry mouthDelirium/psychosisCognitionHyperemesis
DependenceInteractionsRespiratory effectsSpermatogenesisNeurodevelopment
Patient Symptoms where conventional
treatments have failed
Compassionate end-of-life care or specified medical conditions
Current ACMPR process
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
Patient
Current ACMPR process
The patient sends an application form to the Licensed Producer of
their choice.
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.
Licensed Producer
Mailing Address
Product choice
Health Care Practitioner Information
Patient Information
WrittenOrder
Physician Attestation, Signature
Summary
Cannabis & cannabinoids active in supportive care for cancer patientsClinical benefits in: pain, nausea, appetiteMore research is needed
