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Medical Marijuana and Clinical Oncology in 2022
"The Good the Bad and the Potentially Ugly"
1
FIRST DISCLAIMER
2
Some disclaimers
No financial or other intellectual conflicts of interest to report
Slides/materials have been derived from the internet and various other educational resources-special
thanks to Dr Kerba University of Calgary
To paraphrase our current prime minister “Some may have
smoked but of course they never inhaled!”
3
What we hope to exploretoday
• History
• Biology, pharmacology, and neuropharmacology of cannabinoids
• Individual products and their mechanism of effect
• Some of the current evidence for use
• Potential concerns : drug interactions, college and provincial recommendations,
other possible issues
• Some Considerations: If you do take the endorsement plunge
4
A Brief History
5
History of cannabisasamedicine for cancer
• First reported medical use>3000 yearsago
• Siberian Ice Maiden: 5th century BC
• Traditional Indian medicine
http://siberiantimes.com
• Analgesic, sedative, anxiolytic, appetite-
Introduced into UKby O’Shaughnessyin 1842
• British physician working inIndia
• Analgesic,anti-convulsant
• Fell out of favour in1930s
• Plant material too variable
• Shelf-life short andunpredictable
• Replacedby pure opiates and morereliable
synthetic drugs
• Removedfrom UK/USPharmacopeia1932 & ’41
• Prohibition 1930s related to bad publicity and
“Reefer Madness”
• Until recently-illegal in Canada since the 1970’s 6
7
Some Terminology
• Cannabis-is the botanical term for the plants
Cannabis sativa or Cannabis indica
• Marijuana -is a cultural term for the cannabis
plant - refers to the dried leaves, flowers, stems,
and seeds
• Medical marijuana/cannabis-marijuana that is
recommended/ endorsed by a medical
professional for the treatment of a variety of
medical conditions
8
Plant Biology and Forms
9
Cannabismaybeendogenous, synthetic or derived fromplants
• Phytocannabinoids
• derived from plants: Cannabissativa
• dried leaves and flowering heads(marijuana)
• also resin of upper leaves & flowering beds
(hashish)
• Synthetic cannabinoids
• synthetic THC:dronabinol,nabilone
• many other forms (someillicit)
• Endogenous:Endocannabinoids - anandamide
• alter intracellular signaling
• ?function is to modulate painresponse and
a variety of other physiological functions
10
Cannabissativa
Marijuana (dried leaves/ flowering heads)
Isolated purecompounds
Non-cannabinoids Cannabinoids
Psychoactive
Δ9-
THC
Δ8-THC
cannabinol (CBN)(weak)
Active, not
psychoactive
Cannabidiol (CBD)
Inactive
>60
compounds
>400 chemical
compounds
>70 types of
cannabinoids
Most potent
psychoactive
ingredient
Phytocannabinoids
Kalant H. PainResManage2001;6:80-91
Dr Marc KerbaTBCCJune12th 2019
11
Forms of phytocannabanoids
(plant-derived cannabis)
• Inhaled leaf (smoked or vaporized)
• rapid onsetbut short duration(2-4 hrs)
• Buccalspray: Nabiximols (Sativex)
• 1:1 THC:CBD,TGAregistered forMS
• Ingested forms
• cannabisoil
• oral drops
• oral capsule(liposomalformulation)
• onset30-90 mins, duration 4-12hrs
• Concentration of THC,CBD,other constituents
vary widely but customizable with commercial
preparations ie THC/CBD ratio
12
The synthetic products maybe less than ideal
13
Who Currently Uses Marijuana/Cannabinoids
14
Marijuana/Cannabinoids are commonly used
In North America, marijuana/cannabinoids are the 3rd most
commonly used substances after alcohol and tobacco:
Probably 22 Million Users in the last 30 days
(8% of people 12 years and older)
2014 National Survey of
Drug Use and Health
15
Some homegrown Canadian statistics- pun intentional
• More than 200 types of medical cannabis are available from Canadian licensed
producers
• The highest % of THC studied is 9.4%, but many current products around 15%.
• 43 % of adults reported prior lifetime usage- 12% within the past year.
• Average user consumed cannabis 2 -3 x week - 40% actually consuming >14
grams / week.
16
Why Do North Americans Use Marijuana/Cannabinoids?
Among North Americans who used marijuana in the past year:
17
SOURCE: Pew Charitable Trust, 2013 (reference list).
47%
30%
23%
For Fun For Medical Reasons For Fun and for Medical Reasons
Why do North Americans Use Medical Marijuana/Cannabinoids?
DISORDER THAT REQUIRES
TREATMENT
% CITING AS REASON FOR MJ
USE
Chronic Pain 58.2%
Mental Health Disorders 22.9%
Sleep Disorders 21.3%
Neurological Disorders 16.6%
HIV 1.6%
Cancer 1.5%
Glaucoma 1.3%
18
SOURCE: Reinarman et al., 2011 (reference list).
Who Uses Marijuana/Cannabinoids-1 ?
• Joe (23 years old)
• First used at a party age 15,
continued using through
college
• Now uses when he goes out
or is playing video games with
friends
• Also uses when stressed out
• On average, uses about 4-5
times/week
19
Who Uses Marijuana/Cannabinoids-2 ?
• Maria & Terry
(46 & 48 years old)
• Used in college; stopped
when she got pregnant
• Now smoke socially and
when they go to concerts
• Maria uses when work
stresses her out
• Terry uses for pain stemming
from chronic neuropathy
20
Who Uses Marijuana/Cannabinoids-3 ?
• Elise (78 years old)
• Never used marijuana until she
turned 63
• First used to improve appetite
during chemotherapy for
breast cancer
• Cancer has now metastasized
to her spine.
• Conventional painkillers don’t
work well; now uses several
times a day for pain relief
21
Meanwhile in Colorado, Oregon , California and
more northern climes
22
Colorado – The impact- of some early aspects
of legalization was actually studied
23
Colorado – Some Initial Impacts (2014)
• Traffic fatalities involving operators testing positive for marijuana increased 100%
from 2007 to 2012
• Increase in youth current marijuana users in 2012, to 10.47% of youth from
7.55% -nationally. Colorado, now ranked 4th in the nation, 39% higher than the
national average
• School drug related suspensions/expulsions increased 32% from school years
2008/2009 through 2012/2013
• A 57% increase in marijuana-related emergency room visits from 2011 through
2013
• Hospitalizations related to marijuana increased 82% from 2008 to 2013
24
Did US legalization produce increased compassionate
care danda
use of cannabinoids/marijuana?
<5%
■ Less than 5% of users
had
cancer, HIV/AIDS,
or life-threatening diseases
■ 90% are registered
for ailments such
as general pain or headaches
25
US legalization-Increased compassionate care use
versussimply increased access to marijuana?
>80%
■ Most card holders in
CA and CO are white
men between the
ages of 17 -35
■ No true history of chronic
illness
■Often history of Alcohol
and Drug Use
26
• Wearenow in alegalizedenvironment
• Bill C45the “CannabisAct” receivedRoyalAssent June21st2018
(Thank-you Wilson-Raybould...)
• Legalto purchase cannabis from retailors authorizedby provinces
– Oils
– Dry or freshleaves
– Seeds
– Plants
– Edibles -pending
• Legal to purchase from any federally licensed producer
And What about Canada-1? Regulation-BillC-45
Dr Marc Kerba TBCCJune 12th 2019 27
AndWhatAboutCanada-2?USE2018National CannabisSurvey
https://www150.statcan.gc.ca/n1/en/pub/11-627-m/11-627-m2018009-eng.pdf?st=-trqVQWI
Dr Marc Kerba TBCCJune 12th 2019
28
Canadian veterans' affairs-it was a marijuana growth
powerhouse before funding was cut
29
Cannabinoid Neurobiology
30
Phylogenetically the endocannabinoids system
evolved long before the actual plants appeared
• The endocannabinoid system appears to help regulate numerous
aspects of normal physiologic function, including cognition,
coordination, memory, appetite, pain perception, heart rate,
gastrointestinal mobility, intraocular pressure and immune function
31
CB1 and CB2 receptors
• CB1 receptors are the most widely expressed, located mainly in the
central and peripheral nervous systems, plus a few other locations
including cardiovascular, visual and gastrointestinal systems.
• CB2 receptors have a more limited distribution, being located
primarily in the immune system, including lymphatic tissue, spleen,
macrophages and the immune cells of the CNS
• Psychotropic effects are largely due to activation of the CB1 receptors,
while the CB2 receptors in the periphery affect immune cells and play
a role in inflammation and the immune response
32
33
Where THC acts in the brain
34
WARNING if you are under age 25: Possible mis-wiring
of the early brain: THC disrupts cortex development in
fetus (Tortoriello et al., The EMBO J 2014)
• THC reorganizes wires in the developing and adult nervous
systems (Kano et al, 2009, Keimpema et al, 2010)
• THC disrupts development and maintenance of connections
critical for highly ordered executive and cognitive functions
(Kittler et al, 2000).
35
? Explains the documented effects of cannabinoids on the
brain of adolescents
• The cerebellum plays a role in balance, psychomotor
speed, language generation, rhythm production,
inhibition, attention, and memory
36
Adolescent Marijuana Users Have Enlarged Brain
Cerebellum: Association with Poor Executive Function
Source: Medina KL, Nagel BJ, Taper SF. Abnormal cerebellar morphometry in abstinent adolescent marijuana users.
Psychiatry Research: Neuroimaging 182: 152-159, 2010.
Following one month of abstinence, adolescent MJ users had significantly larger posterior
cerebellar vermis volumes than non-using controls. These greater volumes are associated
with poorer executive and cognitive functioning. . Chronic adolescent MJ users have
shown significantly poorer sustained attention, cognitive inhibition, and abstract
reasoning
37
Howcannabinoidswork:postulated non-psychotropiceffects
Cannabinoid Pharmacology
39
Some cannabinoid pharmacology
•THC identified in 1964
•Smoking:
o1 cigarette contains 0.5 to 1g
of cannabis
o20% absorbed by lungs
oOnset 15 minutes, duration 3
to 4 hours
Oral consumption:
oProlonged but poor
absorption-average 10-15%
oOnset 3-4 hours, duration 6
to 8 hours
•Converted to
metabolites
o11-hydroxy-THC
o11-nor-carboxy-THC
• Accumulates in fat
stores
oT1/2 = 20-30 hours
• Removal from body:
o1/3 excreted as urine
o2/3 eliminated in feces
40
Vaporization of medical cannabis
• Cannabinoids
vaporize at a temp
lower than combustion
• Increasingly popular
• Lower % of noxious
chemicals
• Volcano unit costs
around $450
http://www.volcanovaporizer.com/products-page/complete-sets/ Accessed 08/31/2012
41
A reversal of potency problems- “It’s not your dad’s ‘pot’ anymore”
• Marijuana growers have worked hard to make the drug as potent
as possible.
• In 1960s-70s average THC concentrations were 1-2%. Today, they
are as high as 20%
42
Cannabinoid Physiology and Psychological Effects
43
Potential effects of cannabis
• Low-dose
• mild euphoria, relaxation, sociability, reduced anxiety
• temporal slowing
• High-dose
• agitation, anxiety, depersonalisation
• dry mouth and eyes
• tachycardia
• psychomotor function impairment
• paranoia, hallucinations, psychosis
• Long-term
• possible impaired verbal reasoning, memory, attention
• addictive potential (< opioids), mild withdrawal syndrome
Longo NEJM 2014
44
However adverse events in cancer patients appear
tolerable and possibly transient for most patients
45
Practical Considerations in Medical Cannabis Administration And Dosing
MacCalluma et al, European Journal of Internal Medicine 49 (2018) 12–19
Cannabis and psychosis
• There is reasonable evidence that heavy cannabis use, and perhaps
acute use in sensitive individuals, can induce an acute psychosis
(Paranoia)
• Scientific literature documents that heavy marijuana use can
precipitate schizophrenic episodes but it is unknown if usge can cause
the underlying psychotic disorder
• At a population level, assuming a causal relationship, elimination of
cannabis might reduce the incidence of schizophrenia by
approximately 8%,
46
Marijuana and abuse/dependence
• SUD falls on a continuum of alcohol and drug use
47
PROBLEMATIC SUBSTANCE USE
Risky Substance
Use
Substance Abuse
Substance
Dependence
SUBSTANCE USE DISORDERS (SUD)
Marijuana abuse/dependence
• Most individuals use marijuana without developing
SUD.
• However, because usage is so widespread, more people
end up using marijuana problematically than other
drugs.
• In LA County, marijuana use accounted for more
substance use disorders treatment admissions (23.3%)
than any other drug, including alcohol (22%).
SOURCES: Los Angeles County DPH, 2011; NIDA, 2012a (reference list).
48
Cannabis use disorder-How might the addictive risk
compare?
DRUG
LIFETIME RISK OF
DEPENDENCE
Nicotine 32%
Heroin 23%
Cocaine 17%
Alcohol 15%
Marijuana 9%
49
SOURCE: Bostwick, 2012 (reference list).
Cannabis withdrawal syndrome
• A true clinical entity noted in heavy users
• 3 (or more) of the following signs and symptoms
develop within approximately 1 week:
• Irritability, anger, or aggression.
• Nervousness or anxiety.
• Sleep difficulty (e.g., insomnia, disturbing dreams).
• Decreased appetite or weight loss.
• Restlessness.
• Depressed mood.
• At least 1 of the following physical symptoms causing
significant discomfort: abdominal pain,
shakiness/tremors, sweating, fever, chills, or
headache.
50
Cannabinoid hyperemesis syndrome
Impressyourcolleagueswithyourdiagnosticacumen
• First described in 2004
• Associated with chronic, heavy use of cannabis -presumably
recreational or medical
• Patient presents to emerg →complaint-recurrent episodes of
severe nausea, retching and cyclical vomiting in the absence of
other pathology
• Pathgnomic history→temporary relief from hot
showers/baths triggers compulsive showering!
• Symptoms stop after cannabinoid cessation but may recur
within weeks of resuming
Schreck B., et al. Cannabinoid hyperemesis syndrome: review of the literature
DrugAlcohol Depend. (2017) 182 27–32.
Potential Indications Including Oncology
52
Resurgencein interest in cannabisas treatmentforcancerover last 20 years
• Non-legal use in community: anecdotes
• Researchsince 1980s (esp. Israel)
• Identified endogenous cannabinoids with influenceon
neurologic, immune, gastro-intestinal systems
• Synthetic THCdeveloped
• FDAapproved: nauseaand vomiting due to chemotherapy
• Dronabinol 1986 ,Nabilone2010)
• Subsequently approved in various jurisdictions
• Clinical trials launched in a variety of countries
• Medical prescribing permitted in a number of countries
including Europe, Canada, Australia, Israel etc
53
Medline-indexedpublicationson cannabisor cannabinoids AND
cancerhave increased dramatically since the 1970‘s
160
140
120
100
80
60
40
20
0
Number
of
papers
Y
ear
54
Alberta’a own contributions-What’s That, Bud?
Dr Marc Kerba TBCCJune 12th2019 55
Dr Marc Kerba TBCCJune12th2019
Malignancy
All respondents
(n=1987)
Anylifetime use
(n=834)
Usein last 6
months(n=356)
Breast 428 166 (39%) 65 (15%)
Lung 171 78 (46%) 43 (25%)
Genitourinary 286 107 (37%) 43 (15%)
Brain/H&N 240 105 (44%) 42 (18%)
Gastrointestinal 345 152 (44%) 70 (20%)
Hematologic 290 135 (47%) 55 (19%)
Skin 28 13 (46%) 3 (11%)
Gynecologic 129 52 (40%) 24 (19%)
Other 70 26 (37%) 11(16%)
Cannabis/Cannabinoidsusebycancerpatientsbytumorsite
56
No. of activeusers
n=356(%)
Reasonfor Use
Anycancersymptom (combined) 70
Cancerrelated pain 46
Cancerrelated nausea 34
Other cancersymptoms 31
Anynon-cancerreason (combined) 56
ReasonsforCannabis/Cannabinoidsusebycancerpatientswithinthelast6months
Dr Marc Kerba TBCCJune12th2019
57
So what might we really know about
usefulness in cancer patients?-Two large well
conducted trials –Netherlands-Israel
58
Important aspects of this comprehensive study involving> 1700 cancer patients
• >60% achieved satisfactory pain reduction with cannabinoid therapy
• In relation to opioids
• 50% continued to take same dose
• 10% decreased dosing
• 36% ceased taking completely
• Other Improvements in: insomnia, restlessness, anxiety, depression, pruritus and headache.
• 30% of patients experienced one side effect,
• Commonest side effects were, dizziness, dry mouth, hyperphagia, sleepiness,psychoactive effect.
Conclusion: cannabis represents a safe well-tolerated palliation for the majority of cancer patients
59
60
Somepossibleclinicalrecommendations/concernsinCancerPatients
EVIDENCE FOR EFFCTS in CANCER PATIENTS
Cannabis can be a useful adjunct in treating cancer pain.
Cannabis is effective for nausea and vomiting.
Cannabis may be useful in some patients for stimulating appetite.
Cannabis may help treat anxiety, depression and insomnia.
There is moderate evidence that cannabinoids are effective for
seizures/spasticity.
There is no concrete evidence that cannabis cures cancer or
significantly alters tumor growth
There are a number of theoretical concerns regarding potential
interactions between cannabis/cannabinoids and various
cancer therapies or individual oncology drugs
61
Lets look at some study evidence
62
A systematic review identified 28 studies (27 placebo-controlled, 1 treatment-
controlled) of cannabis in a total of 2454 participants with chronic pain.
12 studies of neuropathic pain
6 trials of other types of pain
3 for cancer pain
Chronic Pain
3 for diabetic neuropathy
2 for fibromyalgia
2 for HIV-associated sensory neuropathy
Preparations tested included nabiximols, nabilone, inhaled cannabis, THC (oral or
oromucosal), and dronabinol.
Studies generally showed improvements in
pain measures with cannabis and cannabinoids.
63
Cannabis-Opioid Interactions
A study of 21patients with chronic pain treated with
sustained-release morphine or oxycodone found that
adding inhaled cannabis for 5 days
 Significantly decreased pain by 27% (95% CI 9-46)
 Had no significant effect on plasma opioid levels.
OPIOID
Co-administration of cannabis or cannabinoids withopioids
is safe and may allow for use of lower doses of opioids.
CANNABIS
A systematic review identified 28 RCTs (8 placebo-controlled,
20 treatment-controlled) with 1772 participants that examined
the effects of cannabinoids on CINV.
14studies tested nabilone (which mimics THC)
9 studies tested dronabinol (THC)
4 studies tested levonantradol (no longer used inmedicine)
1study tested nabiximols (THC and CBD)
Studies generally showed a benefit
of cannabinoids for CINV.
Chemotherapy-Induced
Nausea and Vomiting (CINV)
65
(Machado Rocha2008)
6 6
Summary:Chemotherapy-Induced
Nausea and Vomiting (CINV)
An RCT of 243 patients with CACS found no superiority of
cannabis extract or THC over placebo for affecting
appetite or quality of life.
A double-blind, RCT of 469 patients with CACS found that
megestrol acetate was more effective than dronabinol for
stimulating appetite and increasing weight gain.
 Combined treatment was no more effective than
megestrol acetate alone.
The effect of dronabinol on appetite and weight
gain are small; megestrol acetate is superior.
Summary:Appetite/Weight
Cancer-related Anorexia Cachexia Syndrome (CACS)
A randomized treatment-controlled crossover trial in 29
fibromyalgia patients with chronic insomnia found that
nabilone 0.5-1 mg/kg before bedtime was superior to
amitriptyline for improving sleep.
19 other studies that assessed sleep as a secondary outcome
measure found that cannabinoids (primarily nabiximols)
improved sleep quality.
A randomized controlled trial of 10 patients with
generalized Social Anxiety Disorder found that 4 0 0 mg
CBD significantly decreased anxiety.
Cannabinoids may help with some
measures of sleep quality/anxiety.
Sleep Disorders/Anxiety
What about cancer cure or changes in tumor
growth/progression
69
70
Current evidence – anti-tumour effects
NIH summary of laboratory/animal/preclinical studies
• Theoretically Cannabinoids mightcauseanti-tumour effects by variousmechanisms
• induction of cell death and inhibition of cell growth
• inhibition of tumour angiogenesis, invasion and metastasis
• Someevidenceof potential anti-tumour effects in cellcultures/xenografts
• glioma, hepatocellular carcinoma,non-small cell lung cancer and breast cancer
• CBDmayalso enhance uptake of cytotoxic drugs into certain malignantcells
• Thus far, shown in mouse models ofglioma
• Only 1 human study (Spanish,n=9)
• patients with glioblastoma multiforme(GBM)-non randomiseddesign
• THCdirectly infused into tumour daily by subcutaneouscatheter
• established safety but no conclusions reefficacy
• Guzmán et al, Br JCancer2006
71
Cannabis and Immunosuppression
• Possibly Good news: THC was found to induce cell death in different
types of cancer cells that have cannabinoid receptors.
• Possibly Bad news: it can lead to enhanced growth of tumors that
express low to undetectable levels of cannabinoid receptors by
specifically suppressing the antitumor immune response.
All these studies have been done in vitro and therefore little is known
about the immune effects of chronic low- dose exposure to cannabis.
72
Possible drug Interactions and other safety
concerns in oncology
73
74
The cytochrome system and drug metabolism
What potential interactions need we be mindful of?
Cannabis Pharmacokinetics
• Most of the potential cannabinoid cytochrome interactions concern
inhibition, rather than stimulation of transport or metabolism
• THC is metabolized by CYP3A4 and CYP2C9
• CBD is metabolized by CYP3A4 and 2CY2C19
• Both THC and CBD competitively inhibit CYP3A4, with CBD being far more
potent in this regard
• A number of anticancer medications are also metabolized by cytochromes
CYP3A4 and CYP2D6
Brigden and England Oncology Exchange 17, 3, 2018
75
Pharmacokinetic Interactions AndCannabis
Drugsthat maytheoretically increase/decrease cannabis/cannabinoidblood levels
1.CYP2C9 inhibitors may increase serum concentration of THC
Strong inhibitors: capecitabine, 5-fluorouracil
Moderate inhibitors: abiraone, sorafenib, omeprazole, Septra
2.CYP3A4 inhibitors may increase serum concentration of THC & CBD
Strong inhibitors: ketoconazole, clarithromycin, antiretrovirals,
idelalasib moderate: aprepitant, diltiazem, imatinib, nilotinib,
fluconazole, grapefruit
3.CYP3A4 inducers may reduce serum levels of THC and CBD
Strong inducers: carbamazepine, phenytoin, enzalutamide
76
Brigden and England Oncology Exchange 17, 3, 2018
Purity concerns-few Canadian studies
Despite legalization, quality control problems persist
• American study-After analyzing > 600 samples from certified growers /sellers,
a state licensed lab detected little THC/CBD and lots of contamination.
• The average CBD amount: just 0.1 %
• Several marijuana flowers were "crawling" with up to 1 million fungal spores.
• Some grower spray crops with dangerous pesticides-residues may pass into
cannabis smoke
• Any extraction process may leave behind residual solvents
• Standards for quality control and analytical testing need to be rigorously
enforced
77
Some Provincial and College Issues
78
• Listing
conditions for
which marijuana
can be obtained,
including other
conditions as
determined in
writing...”
Why Canadian regulatorybodies wereappropriately leery of
US style "Marijuana Pill Mills”
79
CMA, Canadian Family Physician, CMPA, Individual Provincial College’s Positions
• The Canadian Medical Association has consistently opposed Health
Canada’s approach which places physicians in the role of gatekeeper
in authorizing access to marijuana.
• Current Canadian Family Physician guidelines do not enthusiastically
endorse cannabinoids
• CMPA publications detailed individual physician’s responsibility and
informed decision-making- also emphasize no obligation on the part
of reluctant physicians to participate in prescribing
• All of the above-? Relevance after legalization
80
81
Some ethical and professional issues
82
If an individual decides to take the
endorsement plunge
83
First-Somequestionstopose…
Dr Marc Kerba TBCCJune 12th, 2019
84
Next: Be sure to satisfy any legal and documentation concerns
• Few absolute contraindications but if recommending should assess/council for
psychosis, bipolar disorder, significant cardiac disorder, lactation and pregnancy, prior
history of significant substance abuse, and documented cannabis allergies.
• Should document education:driving not recommended for 4 hours after inhaled, 6
hours after oral, or 8 hours if any “high” or euphoria experienced , as well as other risks
• Fortunately no longer necessary to arrange and document regular follow-ups as per
earlier pre-legalization individual provincial requirements
85
Some final considerations if one decides to recommend
POTENTIAL AREAS OF CAUTION
Cannabis is contraindicated with any history of psychosis; current or past
substance use disorder, cardiovascular or respiratory disease; pregnancy.
• Use caution in patients with active mood disorders, risk factors for
cardiovascular disease, users of high doses of alcohol or benzodiazepines
• Use caution in patients younger than 25.
• Do not suggest smoking dried product- suggest oral intake or
vaporization, which is likely safer in the long run.
• Recommend products with a balanced THC/CBD ratio (for example,
5%: 6% or 9%:9%).
• Once started and effects accessed , THC/CBD ratio can be further adjusted to
meet symptom needs
.
“Start low, go slow” 86
Trying to Summarize/Make Sense of a
Very Complex Topic
87
Some final conclusions-my take1
• "Love it or leave it"-medical marijuana/cannaboid use is now commonly
encountered in clinical practice in Canada, so it is critical for all health
care providers to understand both the scientific rationale and practical
implications of possible usage.
• Medical marijuana/cannabinoids are not a panacea- may have significant
health risks as well as many potential medical benefits.
• IF physicians decide to make recommendations/endorsement for medical
cannabis based on an individual's medical history/situation, appropriate
documentation and counselling are recommended
88
Some final conclusions-my take 2
Specific to oncology
• Marijuana/cannabinoids are particularly appealing for oncology
patients offering the possibility of a single medication to encompass a
variety of problems, such as pain, nausea, anorexia, sleep disorders ,
and anxiety
• More research is clearly needed in relations to indications, efficacy,
potential interactions with other oncology therapies, plus who is most
likely to benefit
89
As always-Potential therapeutic benefit and convenience
But never without a little Risk!
Some potential resources
University of California's Center
for Medicinal Cannabis Research
www.cmcr.ucsd.edu
The CanadianConsortium
for the Investigation of Cannabinoids
www.ccic.net
Patients Out of Time
9 1
www.medicalcannabis.com
Additional potential resources
9 2

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BR-KAM MED MARJ NOV 2022.pptx

  • 1. Medical Marijuana and Clinical Oncology in 2022 "The Good the Bad and the Potentially Ugly" 1
  • 3. Some disclaimers No financial or other intellectual conflicts of interest to report Slides/materials have been derived from the internet and various other educational resources-special thanks to Dr Kerba University of Calgary To paraphrase our current prime minister “Some may have smoked but of course they never inhaled!” 3
  • 4. What we hope to exploretoday • History • Biology, pharmacology, and neuropharmacology of cannabinoids • Individual products and their mechanism of effect • Some of the current evidence for use • Potential concerns : drug interactions, college and provincial recommendations, other possible issues • Some Considerations: If you do take the endorsement plunge 4
  • 6. History of cannabisasamedicine for cancer • First reported medical use>3000 yearsago • Siberian Ice Maiden: 5th century BC • Traditional Indian medicine http://siberiantimes.com • Analgesic, sedative, anxiolytic, appetite- Introduced into UKby O’Shaughnessyin 1842 • British physician working inIndia • Analgesic,anti-convulsant • Fell out of favour in1930s • Plant material too variable • Shelf-life short andunpredictable • Replacedby pure opiates and morereliable synthetic drugs • Removedfrom UK/USPharmacopeia1932 & ’41 • Prohibition 1930s related to bad publicity and “Reefer Madness” • Until recently-illegal in Canada since the 1970’s 6
  • 7. 7
  • 8. Some Terminology • Cannabis-is the botanical term for the plants Cannabis sativa or Cannabis indica • Marijuana -is a cultural term for the cannabis plant - refers to the dried leaves, flowers, stems, and seeds • Medical marijuana/cannabis-marijuana that is recommended/ endorsed by a medical professional for the treatment of a variety of medical conditions 8
  • 10. Cannabismaybeendogenous, synthetic or derived fromplants • Phytocannabinoids • derived from plants: Cannabissativa • dried leaves and flowering heads(marijuana) • also resin of upper leaves & flowering beds (hashish) • Synthetic cannabinoids • synthetic THC:dronabinol,nabilone • many other forms (someillicit) • Endogenous:Endocannabinoids - anandamide • alter intracellular signaling • ?function is to modulate painresponse and a variety of other physiological functions 10
  • 11. Cannabissativa Marijuana (dried leaves/ flowering heads) Isolated purecompounds Non-cannabinoids Cannabinoids Psychoactive Δ9- THC Δ8-THC cannabinol (CBN)(weak) Active, not psychoactive Cannabidiol (CBD) Inactive >60 compounds >400 chemical compounds >70 types of cannabinoids Most potent psychoactive ingredient Phytocannabinoids Kalant H. PainResManage2001;6:80-91 Dr Marc KerbaTBCCJune12th 2019 11
  • 12. Forms of phytocannabanoids (plant-derived cannabis) • Inhaled leaf (smoked or vaporized) • rapid onsetbut short duration(2-4 hrs) • Buccalspray: Nabiximols (Sativex) • 1:1 THC:CBD,TGAregistered forMS • Ingested forms • cannabisoil • oral drops • oral capsule(liposomalformulation) • onset30-90 mins, duration 4-12hrs • Concentration of THC,CBD,other constituents vary widely but customizable with commercial preparations ie THC/CBD ratio 12
  • 13. The synthetic products maybe less than ideal 13
  • 14. Who Currently Uses Marijuana/Cannabinoids 14
  • 15. Marijuana/Cannabinoids are commonly used In North America, marijuana/cannabinoids are the 3rd most commonly used substances after alcohol and tobacco: Probably 22 Million Users in the last 30 days (8% of people 12 years and older) 2014 National Survey of Drug Use and Health 15
  • 16. Some homegrown Canadian statistics- pun intentional • More than 200 types of medical cannabis are available from Canadian licensed producers • The highest % of THC studied is 9.4%, but many current products around 15%. • 43 % of adults reported prior lifetime usage- 12% within the past year. • Average user consumed cannabis 2 -3 x week - 40% actually consuming >14 grams / week. 16
  • 17. Why Do North Americans Use Marijuana/Cannabinoids? Among North Americans who used marijuana in the past year: 17 SOURCE: Pew Charitable Trust, 2013 (reference list). 47% 30% 23% For Fun For Medical Reasons For Fun and for Medical Reasons
  • 18. Why do North Americans Use Medical Marijuana/Cannabinoids? DISORDER THAT REQUIRES TREATMENT % CITING AS REASON FOR MJ USE Chronic Pain 58.2% Mental Health Disorders 22.9% Sleep Disorders 21.3% Neurological Disorders 16.6% HIV 1.6% Cancer 1.5% Glaucoma 1.3% 18 SOURCE: Reinarman et al., 2011 (reference list).
  • 19. Who Uses Marijuana/Cannabinoids-1 ? • Joe (23 years old) • First used at a party age 15, continued using through college • Now uses when he goes out or is playing video games with friends • Also uses when stressed out • On average, uses about 4-5 times/week 19
  • 20. Who Uses Marijuana/Cannabinoids-2 ? • Maria & Terry (46 & 48 years old) • Used in college; stopped when she got pregnant • Now smoke socially and when they go to concerts • Maria uses when work stresses her out • Terry uses for pain stemming from chronic neuropathy 20
  • 21. Who Uses Marijuana/Cannabinoids-3 ? • Elise (78 years old) • Never used marijuana until she turned 63 • First used to improve appetite during chemotherapy for breast cancer • Cancer has now metastasized to her spine. • Conventional painkillers don’t work well; now uses several times a day for pain relief 21
  • 22. Meanwhile in Colorado, Oregon , California and more northern climes 22
  • 23. Colorado – The impact- of some early aspects of legalization was actually studied 23
  • 24. Colorado – Some Initial Impacts (2014) • Traffic fatalities involving operators testing positive for marijuana increased 100% from 2007 to 2012 • Increase in youth current marijuana users in 2012, to 10.47% of youth from 7.55% -nationally. Colorado, now ranked 4th in the nation, 39% higher than the national average • School drug related suspensions/expulsions increased 32% from school years 2008/2009 through 2012/2013 • A 57% increase in marijuana-related emergency room visits from 2011 through 2013 • Hospitalizations related to marijuana increased 82% from 2008 to 2013 24
  • 25. Did US legalization produce increased compassionate care danda use of cannabinoids/marijuana? <5% ■ Less than 5% of users had cancer, HIV/AIDS, or life-threatening diseases ■ 90% are registered for ailments such as general pain or headaches 25
  • 26. US legalization-Increased compassionate care use versussimply increased access to marijuana? >80% ■ Most card holders in CA and CO are white men between the ages of 17 -35 ■ No true history of chronic illness ■Often history of Alcohol and Drug Use 26
  • 27. • Wearenow in alegalizedenvironment • Bill C45the “CannabisAct” receivedRoyalAssent June21st2018 (Thank-you Wilson-Raybould...) • Legalto purchase cannabis from retailors authorizedby provinces – Oils – Dry or freshleaves – Seeds – Plants – Edibles -pending • Legal to purchase from any federally licensed producer And What about Canada-1? Regulation-BillC-45 Dr Marc Kerba TBCCJune 12th 2019 27
  • 29. Canadian veterans' affairs-it was a marijuana growth powerhouse before funding was cut 29
  • 31. Phylogenetically the endocannabinoids system evolved long before the actual plants appeared • The endocannabinoid system appears to help regulate numerous aspects of normal physiologic function, including cognition, coordination, memory, appetite, pain perception, heart rate, gastrointestinal mobility, intraocular pressure and immune function 31
  • 32. CB1 and CB2 receptors • CB1 receptors are the most widely expressed, located mainly in the central and peripheral nervous systems, plus a few other locations including cardiovascular, visual and gastrointestinal systems. • CB2 receptors have a more limited distribution, being located primarily in the immune system, including lymphatic tissue, spleen, macrophages and the immune cells of the CNS • Psychotropic effects are largely due to activation of the CB1 receptors, while the CB2 receptors in the periphery affect immune cells and play a role in inflammation and the immune response 32
  • 33. 33
  • 34. Where THC acts in the brain 34
  • 35. WARNING if you are under age 25: Possible mis-wiring of the early brain: THC disrupts cortex development in fetus (Tortoriello et al., The EMBO J 2014) • THC reorganizes wires in the developing and adult nervous systems (Kano et al, 2009, Keimpema et al, 2010) • THC disrupts development and maintenance of connections critical for highly ordered executive and cognitive functions (Kittler et al, 2000). 35
  • 36. ? Explains the documented effects of cannabinoids on the brain of adolescents • The cerebellum plays a role in balance, psychomotor speed, language generation, rhythm production, inhibition, attention, and memory 36
  • 37. Adolescent Marijuana Users Have Enlarged Brain Cerebellum: Association with Poor Executive Function Source: Medina KL, Nagel BJ, Taper SF. Abnormal cerebellar morphometry in abstinent adolescent marijuana users. Psychiatry Research: Neuroimaging 182: 152-159, 2010. Following one month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are associated with poorer executive and cognitive functioning. . Chronic adolescent MJ users have shown significantly poorer sustained attention, cognitive inhibition, and abstract reasoning 37
  • 40. Some cannabinoid pharmacology •THC identified in 1964 •Smoking: o1 cigarette contains 0.5 to 1g of cannabis o20% absorbed by lungs oOnset 15 minutes, duration 3 to 4 hours Oral consumption: oProlonged but poor absorption-average 10-15% oOnset 3-4 hours, duration 6 to 8 hours •Converted to metabolites o11-hydroxy-THC o11-nor-carboxy-THC • Accumulates in fat stores oT1/2 = 20-30 hours • Removal from body: o1/3 excreted as urine o2/3 eliminated in feces 40
  • 41. Vaporization of medical cannabis • Cannabinoids vaporize at a temp lower than combustion • Increasingly popular • Lower % of noxious chemicals • Volcano unit costs around $450 http://www.volcanovaporizer.com/products-page/complete-sets/ Accessed 08/31/2012 41
  • 42. A reversal of potency problems- “It’s not your dad’s ‘pot’ anymore” • Marijuana growers have worked hard to make the drug as potent as possible. • In 1960s-70s average THC concentrations were 1-2%. Today, they are as high as 20% 42
  • 43. Cannabinoid Physiology and Psychological Effects 43
  • 44. Potential effects of cannabis • Low-dose • mild euphoria, relaxation, sociability, reduced anxiety • temporal slowing • High-dose • agitation, anxiety, depersonalisation • dry mouth and eyes • tachycardia • psychomotor function impairment • paranoia, hallucinations, psychosis • Long-term • possible impaired verbal reasoning, memory, attention • addictive potential (< opioids), mild withdrawal syndrome Longo NEJM 2014 44
  • 45. However adverse events in cancer patients appear tolerable and possibly transient for most patients 45 Practical Considerations in Medical Cannabis Administration And Dosing MacCalluma et al, European Journal of Internal Medicine 49 (2018) 12–19
  • 46. Cannabis and psychosis • There is reasonable evidence that heavy cannabis use, and perhaps acute use in sensitive individuals, can induce an acute psychosis (Paranoia) • Scientific literature documents that heavy marijuana use can precipitate schizophrenic episodes but it is unknown if usge can cause the underlying psychotic disorder • At a population level, assuming a causal relationship, elimination of cannabis might reduce the incidence of schizophrenia by approximately 8%, 46
  • 47. Marijuana and abuse/dependence • SUD falls on a continuum of alcohol and drug use 47 PROBLEMATIC SUBSTANCE USE Risky Substance Use Substance Abuse Substance Dependence SUBSTANCE USE DISORDERS (SUD)
  • 48. Marijuana abuse/dependence • Most individuals use marijuana without developing SUD. • However, because usage is so widespread, more people end up using marijuana problematically than other drugs. • In LA County, marijuana use accounted for more substance use disorders treatment admissions (23.3%) than any other drug, including alcohol (22%). SOURCES: Los Angeles County DPH, 2011; NIDA, 2012a (reference list). 48
  • 49. Cannabis use disorder-How might the addictive risk compare? DRUG LIFETIME RISK OF DEPENDENCE Nicotine 32% Heroin 23% Cocaine 17% Alcohol 15% Marijuana 9% 49 SOURCE: Bostwick, 2012 (reference list).
  • 50. Cannabis withdrawal syndrome • A true clinical entity noted in heavy users • 3 (or more) of the following signs and symptoms develop within approximately 1 week: • Irritability, anger, or aggression. • Nervousness or anxiety. • Sleep difficulty (e.g., insomnia, disturbing dreams). • Decreased appetite or weight loss. • Restlessness. • Depressed mood. • At least 1 of the following physical symptoms causing significant discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache. 50
  • 51. Cannabinoid hyperemesis syndrome Impressyourcolleagueswithyourdiagnosticacumen • First described in 2004 • Associated with chronic, heavy use of cannabis -presumably recreational or medical • Patient presents to emerg →complaint-recurrent episodes of severe nausea, retching and cyclical vomiting in the absence of other pathology • Pathgnomic history→temporary relief from hot showers/baths triggers compulsive showering! • Symptoms stop after cannabinoid cessation but may recur within weeks of resuming Schreck B., et al. Cannabinoid hyperemesis syndrome: review of the literature DrugAlcohol Depend. (2017) 182 27–32.
  • 53. Resurgencein interest in cannabisas treatmentforcancerover last 20 years • Non-legal use in community: anecdotes • Researchsince 1980s (esp. Israel) • Identified endogenous cannabinoids with influenceon neurologic, immune, gastro-intestinal systems • Synthetic THCdeveloped • FDAapproved: nauseaand vomiting due to chemotherapy • Dronabinol 1986 ,Nabilone2010) • Subsequently approved in various jurisdictions • Clinical trials launched in a variety of countries • Medical prescribing permitted in a number of countries including Europe, Canada, Australia, Israel etc 53
  • 54. Medline-indexedpublicationson cannabisor cannabinoids AND cancerhave increased dramatically since the 1970‘s 160 140 120 100 80 60 40 20 0 Number of papers Y ear 54
  • 55. Alberta’a own contributions-What’s That, Bud? Dr Marc Kerba TBCCJune 12th2019 55
  • 56. Dr Marc Kerba TBCCJune12th2019 Malignancy All respondents (n=1987) Anylifetime use (n=834) Usein last 6 months(n=356) Breast 428 166 (39%) 65 (15%) Lung 171 78 (46%) 43 (25%) Genitourinary 286 107 (37%) 43 (15%) Brain/H&N 240 105 (44%) 42 (18%) Gastrointestinal 345 152 (44%) 70 (20%) Hematologic 290 135 (47%) 55 (19%) Skin 28 13 (46%) 3 (11%) Gynecologic 129 52 (40%) 24 (19%) Other 70 26 (37%) 11(16%) Cannabis/Cannabinoidsusebycancerpatientsbytumorsite 56
  • 57. No. of activeusers n=356(%) Reasonfor Use Anycancersymptom (combined) 70 Cancerrelated pain 46 Cancerrelated nausea 34 Other cancersymptoms 31 Anynon-cancerreason (combined) 56 ReasonsforCannabis/Cannabinoidsusebycancerpatientswithinthelast6months Dr Marc Kerba TBCCJune12th2019 57
  • 58. So what might we really know about usefulness in cancer patients?-Two large well conducted trials –Netherlands-Israel 58
  • 59. Important aspects of this comprehensive study involving> 1700 cancer patients • >60% achieved satisfactory pain reduction with cannabinoid therapy • In relation to opioids • 50% continued to take same dose • 10% decreased dosing • 36% ceased taking completely • Other Improvements in: insomnia, restlessness, anxiety, depression, pruritus and headache. • 30% of patients experienced one side effect, • Commonest side effects were, dizziness, dry mouth, hyperphagia, sleepiness,psychoactive effect. Conclusion: cannabis represents a safe well-tolerated palliation for the majority of cancer patients 59
  • 60. 60
  • 61. Somepossibleclinicalrecommendations/concernsinCancerPatients EVIDENCE FOR EFFCTS in CANCER PATIENTS Cannabis can be a useful adjunct in treating cancer pain. Cannabis is effective for nausea and vomiting. Cannabis may be useful in some patients for stimulating appetite. Cannabis may help treat anxiety, depression and insomnia. There is moderate evidence that cannabinoids are effective for seizures/spasticity. There is no concrete evidence that cannabis cures cancer or significantly alters tumor growth There are a number of theoretical concerns regarding potential interactions between cannabis/cannabinoids and various cancer therapies or individual oncology drugs 61
  • 62. Lets look at some study evidence 62
  • 63. A systematic review identified 28 studies (27 placebo-controlled, 1 treatment- controlled) of cannabis in a total of 2454 participants with chronic pain. 12 studies of neuropathic pain 6 trials of other types of pain 3 for cancer pain Chronic Pain 3 for diabetic neuropathy 2 for fibromyalgia 2 for HIV-associated sensory neuropathy Preparations tested included nabiximols, nabilone, inhaled cannabis, THC (oral or oromucosal), and dronabinol. Studies generally showed improvements in pain measures with cannabis and cannabinoids. 63
  • 64. Cannabis-Opioid Interactions A study of 21patients with chronic pain treated with sustained-release morphine or oxycodone found that adding inhaled cannabis for 5 days  Significantly decreased pain by 27% (95% CI 9-46)  Had no significant effect on plasma opioid levels. OPIOID Co-administration of cannabis or cannabinoids withopioids is safe and may allow for use of lower doses of opioids. CANNABIS
  • 65. A systematic review identified 28 RCTs (8 placebo-controlled, 20 treatment-controlled) with 1772 participants that examined the effects of cannabinoids on CINV. 14studies tested nabilone (which mimics THC) 9 studies tested dronabinol (THC) 4 studies tested levonantradol (no longer used inmedicine) 1study tested nabiximols (THC and CBD) Studies generally showed a benefit of cannabinoids for CINV. Chemotherapy-Induced Nausea and Vomiting (CINV) 65
  • 67. An RCT of 243 patients with CACS found no superiority of cannabis extract or THC over placebo for affecting appetite or quality of life. A double-blind, RCT of 469 patients with CACS found that megestrol acetate was more effective than dronabinol for stimulating appetite and increasing weight gain.  Combined treatment was no more effective than megestrol acetate alone. The effect of dronabinol on appetite and weight gain are small; megestrol acetate is superior. Summary:Appetite/Weight Cancer-related Anorexia Cachexia Syndrome (CACS)
  • 68. A randomized treatment-controlled crossover trial in 29 fibromyalgia patients with chronic insomnia found that nabilone 0.5-1 mg/kg before bedtime was superior to amitriptyline for improving sleep. 19 other studies that assessed sleep as a secondary outcome measure found that cannabinoids (primarily nabiximols) improved sleep quality. A randomized controlled trial of 10 patients with generalized Social Anxiety Disorder found that 4 0 0 mg CBD significantly decreased anxiety. Cannabinoids may help with some measures of sleep quality/anxiety. Sleep Disorders/Anxiety
  • 69. What about cancer cure or changes in tumor growth/progression 69
  • 70. 70
  • 71. Current evidence – anti-tumour effects NIH summary of laboratory/animal/preclinical studies • Theoretically Cannabinoids mightcauseanti-tumour effects by variousmechanisms • induction of cell death and inhibition of cell growth • inhibition of tumour angiogenesis, invasion and metastasis • Someevidenceof potential anti-tumour effects in cellcultures/xenografts • glioma, hepatocellular carcinoma,non-small cell lung cancer and breast cancer • CBDmayalso enhance uptake of cytotoxic drugs into certain malignantcells • Thus far, shown in mouse models ofglioma • Only 1 human study (Spanish,n=9) • patients with glioblastoma multiforme(GBM)-non randomiseddesign • THCdirectly infused into tumour daily by subcutaneouscatheter • established safety but no conclusions reefficacy • Guzmán et al, Br JCancer2006 71
  • 72. Cannabis and Immunosuppression • Possibly Good news: THC was found to induce cell death in different types of cancer cells that have cannabinoid receptors. • Possibly Bad news: it can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response. All these studies have been done in vitro and therefore little is known about the immune effects of chronic low- dose exposure to cannabis. 72
  • 73. Possible drug Interactions and other safety concerns in oncology 73
  • 74. 74 The cytochrome system and drug metabolism
  • 75. What potential interactions need we be mindful of? Cannabis Pharmacokinetics • Most of the potential cannabinoid cytochrome interactions concern inhibition, rather than stimulation of transport or metabolism • THC is metabolized by CYP3A4 and CYP2C9 • CBD is metabolized by CYP3A4 and 2CY2C19 • Both THC and CBD competitively inhibit CYP3A4, with CBD being far more potent in this regard • A number of anticancer medications are also metabolized by cytochromes CYP3A4 and CYP2D6 Brigden and England Oncology Exchange 17, 3, 2018 75
  • 76. Pharmacokinetic Interactions AndCannabis Drugsthat maytheoretically increase/decrease cannabis/cannabinoidblood levels 1.CYP2C9 inhibitors may increase serum concentration of THC Strong inhibitors: capecitabine, 5-fluorouracil Moderate inhibitors: abiraone, sorafenib, omeprazole, Septra 2.CYP3A4 inhibitors may increase serum concentration of THC & CBD Strong inhibitors: ketoconazole, clarithromycin, antiretrovirals, idelalasib moderate: aprepitant, diltiazem, imatinib, nilotinib, fluconazole, grapefruit 3.CYP3A4 inducers may reduce serum levels of THC and CBD Strong inducers: carbamazepine, phenytoin, enzalutamide 76 Brigden and England Oncology Exchange 17, 3, 2018
  • 77. Purity concerns-few Canadian studies Despite legalization, quality control problems persist • American study-After analyzing > 600 samples from certified growers /sellers, a state licensed lab detected little THC/CBD and lots of contamination. • The average CBD amount: just 0.1 % • Several marijuana flowers were "crawling" with up to 1 million fungal spores. • Some grower spray crops with dangerous pesticides-residues may pass into cannabis smoke • Any extraction process may leave behind residual solvents • Standards for quality control and analytical testing need to be rigorously enforced 77
  • 78. Some Provincial and College Issues 78
  • 79. • Listing conditions for which marijuana can be obtained, including other conditions as determined in writing...” Why Canadian regulatorybodies wereappropriately leery of US style "Marijuana Pill Mills” 79
  • 80. CMA, Canadian Family Physician, CMPA, Individual Provincial College’s Positions • The Canadian Medical Association has consistently opposed Health Canada’s approach which places physicians in the role of gatekeeper in authorizing access to marijuana. • Current Canadian Family Physician guidelines do not enthusiastically endorse cannabinoids • CMPA publications detailed individual physician’s responsibility and informed decision-making- also emphasize no obligation on the part of reluctant physicians to participate in prescribing • All of the above-? Relevance after legalization 80
  • 81. 81
  • 82. Some ethical and professional issues 82
  • 83. If an individual decides to take the endorsement plunge 83
  • 85. Next: Be sure to satisfy any legal and documentation concerns • Few absolute contraindications but if recommending should assess/council for psychosis, bipolar disorder, significant cardiac disorder, lactation and pregnancy, prior history of significant substance abuse, and documented cannabis allergies. • Should document education:driving not recommended for 4 hours after inhaled, 6 hours after oral, or 8 hours if any “high” or euphoria experienced , as well as other risks • Fortunately no longer necessary to arrange and document regular follow-ups as per earlier pre-legalization individual provincial requirements 85
  • 86. Some final considerations if one decides to recommend POTENTIAL AREAS OF CAUTION Cannabis is contraindicated with any history of psychosis; current or past substance use disorder, cardiovascular or respiratory disease; pregnancy. • Use caution in patients with active mood disorders, risk factors for cardiovascular disease, users of high doses of alcohol or benzodiazepines • Use caution in patients younger than 25. • Do not suggest smoking dried product- suggest oral intake or vaporization, which is likely safer in the long run. • Recommend products with a balanced THC/CBD ratio (for example, 5%: 6% or 9%:9%). • Once started and effects accessed , THC/CBD ratio can be further adjusted to meet symptom needs . “Start low, go slow” 86
  • 87. Trying to Summarize/Make Sense of a Very Complex Topic 87
  • 88. Some final conclusions-my take1 • "Love it or leave it"-medical marijuana/cannaboid use is now commonly encountered in clinical practice in Canada, so it is critical for all health care providers to understand both the scientific rationale and practical implications of possible usage. • Medical marijuana/cannabinoids are not a panacea- may have significant health risks as well as many potential medical benefits. • IF physicians decide to make recommendations/endorsement for medical cannabis based on an individual's medical history/situation, appropriate documentation and counselling are recommended 88
  • 89. Some final conclusions-my take 2 Specific to oncology • Marijuana/cannabinoids are particularly appealing for oncology patients offering the possibility of a single medication to encompass a variety of problems, such as pain, nausea, anorexia, sleep disorders , and anxiety • More research is clearly needed in relations to indications, efficacy, potential interactions with other oncology therapies, plus who is most likely to benefit 89
  • 90. As always-Potential therapeutic benefit and convenience But never without a little Risk!
  • 91. Some potential resources University of California's Center for Medicinal Cannabis Research www.cmcr.ucsd.edu The CanadianConsortium for the Investigation of Cannabinoids www.ccic.net Patients Out of Time 9 1 www.medicalcannabis.com