medical marijuana: what physicians need to know · 2018. 4. 26. · anxiety, panic attacks ......
TRANSCRIPT
Medical Marijuana
What’s the Buzz?
THC vs CBD?
Alan Kaplan MD CCFP(EM) FCFP
Pain Consultant
• Faculty: Alan Kaplan MD CCFP(EM) FCFP
• Chair Family Physician Airways Group of Canada
• Past Chair of Special Interest Focused Practice, College
of Family Physicians in Respiratory Medicine
• Chronic Pain Consultant
• Relationships with commercial interests:
– Have given one talk for Cannimed in March 2018
Faculty/Presenter Disclosure
• This program has received no financial support .
• This program has received no in-kind support.
• Potential for conflict(s) of interest:
– A) there are no organizations supporting this program
– B) I have given one talk for Cannimed in March 2018
– C) EVERY DAY, I see patients admitted to hospital with the
untoward effects of THC
Disclosure of Commercial Support
My bias is that smoking is BAD and is the major cause of preventable deaths
I want to help patients manage their pain in a safe way
Mitigating Potential Bias
Objectives
a) Understand the pros and cons of
prescribing medical marijuana
b) Understand the difference between
CBD and THC
c) Understand where to place medical
marijuana in your pain management
strategies
History
History
Evidence from 3rd millenium BC
Shakespeare might have used cannabis
Queen Victoria- menstrual cramps
Criminalized in 1906 (USA-DC)
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CBD/THC Relationship
Over 80 different cannabinoids in the cannabis plant influences effects Cannabinol, terpenes, terpenoids, flavenoids
Main active ingredients are THC (tetrahydrocannabinol) and CBD (cannabidiol)
Provide different potency and therapeutic effects
React differently with each person’s biochemistry and therefore have different potential for adverse or undesired effects
Health Canada. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids
[Health Canada, 2013]. at http://www.hc-sc.gc.ca/dhp-mps/marihuana/med/infoprof-eng.php
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Natural Antagonism
CBD
no (or less) euphoria
anti-anxiety
anti-psychotic
Neuroprotective
Anti-inflammatory
bradycardia
Loss of antagonism may lead to
increased side effects and poor tolerability.
THC
euphoria
anxiety
psychosis
cognitive impairment
tachycardia
Cannabidiol (CBD)
• Non-psychoactive cannabinoid?
• Second most common cannabinoid after THC
• Present in hemp
• Has unusual ability to antagonize CB1 receptors at a low nM
levels in presence of THC, despite having little binding affinity
• Can potentially modulate the effects on THC associated
adverse events, such as memory impairment
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Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of
Pharmacology. 2011;163(7):1344-1364. doi:10.1111/j.1476-5381.2011.01238.x.
CBD for psychosis??
Maybe CBD does not cause as much psychosis?? Treatment strategy???
http://www.drugabuse.gov/publications/research-reports/marijuana/how-does-marijuana-produce-its-
effects
Effects of Drug Use on the
Hippocampus
Drugs of abuse are potent negative regulators of adult
neurogenesis in the hippocampus
Chronic administration of opiates, THC, ethanol or nicotine
decreases hippocampal function, decreasing ability of adult
brain to adapt to new information
Regional Brain Abnormalities Associated
with Long-term heavy Cannabis Use Arch
Gen Psychiatry 2008;65:694-701
15 long term (>10 years) and heavy (>5 joints daily) cannabis using men compared with 16 age matched non using controls by MRIs of brains
Cannabis users had bilaterally reduced hippocampal and amygdala volumes p=.001
Increase in positive symptoms (psychotic) p<.001
Significantly worse performance on measures of verbal learning p<.001
Are Cannabinoids Addicting?
Both heroin and cannabinoids increase dopamine levels
in the nucleus accumbens
This effect is blocked by naloxone
When chronic THC use is stopped, the secretion of
“stress” chemicals in the brain is similar to withdrawal
from alcohol, cocaine or opioids
Therefore THC behaves similar to other addicting drug
Gianluigi, et al. Science 1997; 276:2048-2050
Rodriguez de Fonseca, et al. Science 1997; 276: 2050-52
Le Bec et al. Encephale 2009; 35(4): 377-85
00
5050
100100
150150
200200
00 6060 120120 180180
Time (min)Time (min)
% o
f B
as
al D
A O
utp
ut
% o
f B
as
al D
A O
utp
ut
NAc shellNAc shell
EmptyEmpty
BoxBox FeedingFeeding
Source: Di Chiara et al.Source: Di Chiara et al.
FOODFOOD
100100
150150
200200
DA
Co
nc
en
tra
tio
n (
% B
as
eli
ne
)D
A C
on
ce
ntr
ati
on
(%
Ba
se
lin
e)
MountsMountsIntromissionsIntromissionsEjaculationsEjaculations
1515
00
55
1010
Co
pu
latio
n F
req
uen
cy
Co
pu
latio
n F
req
uen
cy
Sample
Number
Sample
Number
11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414 1515 1616 1717
ScrScrScrScr
BasBasFemale 1 PresentFemale 1 Present
ScrScrFemale 2 PresentFemale 2 Present
ScrScr
Source: Fiorino and PhillipsSource: Fiorino and Phillips
SEXSEX
Natural Rewards Elevate Dopamine LevelsNatural Rewards Elevate Dopamine Levels
00
100100
200200
300300
400400
500500
600600
700700
800800
900900
10001000
11001100
00 11 22 33 44 5 hr5 hr
Time After AmphetamineTime After Amphetamine
% o
f B
as
al R
ele
as
e%
of
Bas
al R
ele
as
e
DADADOPACDOPACHVAHVA
AccumbensAccumbens AMPHETAMINEAMPHETAMINE
00
100100
150150
200200
250250
00 11 22 3 hr3 hr
Time After NicotineTime After Nicotine
% o
f B
as
al R
ele
as
e%
of
Bas
al R
ele
as
e
AccumbensAccumbensCaudateCaudate
NICOTINENICOTINE
Source: Di Chiara and ImperatoSource: Di Chiara and Imperato
Effects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine Levels
THC/Marijuana
00
100100
150150
200200
250250
00 11 22 33 44 5hr5hrTime After MorphineTime After Morphine
% o
f B
as
al R
ele
as
e%
of
Bas
al R
ele
as
e
AccumbensAccumbens
0.50.51.01.02.52.51010
Dose (mg/kg)Dose (mg/kg)
MORPHINEMORPHINE
Cannabis Dependency
Percentage of people who
have ever used drug
Percentage of users
who became dependent
Tobacco
Alcohol
Cocaine
Heroin
46%
2%
16%
Marijuana(Cannabinoids)
Tranquilizers (and other
prescription drugs)
13%
92%
76% 32%
15%
9%
9%
17%
23%
Adverse Effects: Short-term anxiety, panic attacks
distorted perception, hallucinations
Cannabis use is associated with psychosis especially when started in the teenage years
This increased risk may be as much as 2 – 4 fold
increased heart rate and blood pressure
decreased memory & learning
difficulty thinking & problem solving
decreased coordination
visuomotor skills deficit
*Actual impairment persists past perceived impairment*
*Effects primarily associated with THC*
What about Driving?
Some evidence that marijuana use is associated with an
increased risk of motor vehicle accidents
It is illegal to drive in Ontario after smoking marijuana
No data exists regarding what is a safe dose of medical
marijuana to drive
This also may vary depending upon the strain
Effects of smoked marijuana last about 3 – 4 hours so
prudent not to drive for at least 4 hours after smoking
marijuana
POT CHECK!
immunosuppression
inhalation: increased risk cancer of head, neck, lungs, respiratory tract
increased risk testicular cancer
occlusion brain arteries, increased stroke
oculomotor control deficit
hyperemesis syndrome
testosterone suppression and possible impotence.
can increase prolactin in women leading to potential problems with ovulation and fertility
Adverse Effects: Long-term“associated with”
Adverse Effects: Long-term, cont.“associated with”
Neurological changes
sustained decreased IQ
adolescents: change in neuroanatomy?
altered memory, esp verbal
decreased cerebral blood flow
decreased neural efficiency
increased DA neurotransmission, psychosis, anxiety
disorder(s), schizophrenia
+ genetics mental illnessyounger age +
extent of use
Cannabinoid Hyperemesis Syndrome
chronic heavy users can develop severe nausea, emesis
and abdominal pain which resolves once stopping
marijuana
National Post September 1, 2017
Smoking is BAD!
No other medication uses smoke as a delivery system
Cannabis combustion produces hundreds of chemicals that are potentially toxic and carcinogenic
Worsens lung function and increases cancer risk
One joint = 8 cigarettes
Smoking, vaporizing cause rapid rise and decline in serum THC levels
Even 1-2 inhalations can cause cognitive impairment
This is unacceptable for a long-term medication
Rapid rise and fall sets up ideal addiction risk, as per Cigarette smokers
www.cfpc.ca/Dried_Cannabis_Prelim_Guidance
Cannabis and death rates Study from 1999-2010 compared 13 states with medical
cannabis laws vs. no medical cannabis laws
States with medical cannabis laws had a 24.8% lower mean
annual opioid overdose mortality rate (95% CI, -37.5% to -
9.5%; P = .003) compared with states without medical
cannabis laws1
In 2013 there were 0 deaths from marijuana2
Have to consume 1/3 your bodyweight -to 15,000 pounds of
cannabis all at once to reach the LD3
1.http://www.ncbi.nlm.nih.gov/pubmed/25154332
2. http://www.drugwarfacts.org/cms/Causes_of_Death#sthash.XRaCjZG6.dpbs
3. http://druglibrary.org/schaffer/library/mj_overdose.htm
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Prescription Cannabinoids
Pharmaceutical agents containing synthetic
cannabinoids are available in Canada
nabilone (Cesamet®) THC only (1mg $1.55)
CBD/THC 1:1 (Sativex®)(12.25/day)
These are not medical cannabis, and are
dispensed through pharmacies
http://www.cmcia.ca/insurance-and-provincial-drug-benefit-program-
coverage/
Nabilone
Synthetic THC
Available in Canada for a number of years
Useful for sleep, pain and nausea
Should be trialed first before medical marijuana
HOWEVER, many patients cannot tolerate because of
sedation
Starting dose is usually 0.5 – 1.0 mg at night
Health Canada
“Dried marijuana is not an approved drug or medicine
in Canada. The Government of Canada does not endorse
the use of marijuana, but the courts have required
reasonable access to a legal source of marijuana when
authorized by a physician.”
Health Canada Government of Canada. Medical Use of Marijuana - Drugs and Health Products - Health Canada.
http://www.hc-sc.gc.ca/dhp-mps/marihuana/index-eng.php.
Published June 13, 2005. Accessed December 13, 2014.
Legalization of Cannabis in
Canada
In April 2017, the government of Canada introduced the Cannabis Act to legalize and regulate recreational cannabis in Canada. The act is designed to decriminalize many aspects of cannabis use and distribution whilst reducing the legal burden of minor cannabis possession charges.
The goal is to have this enacted into Canadian law by no later than July 2018.12
The act states that the current medical cannabis program in Canada will remain unchanged. At this point, it is impossible to determine what impact these changes will have on the medical cannabis patient.
Positives could include lower cannabis cost as suppliers have a larger market for cannabis products and there can be easier access to cannabis through a wider number of retail settings.
Issues include taxation of cannabis purchased through non-medical routes and a focus of LP’s on the recreational market which could limit strains and products used by some medical users.
Assessment for Medical Marijuana
Complete history and physical
Addiction assessment including an ORT
Collateral information
Urine drug testing at time of assessment
Patient agreement
Contraindicated if current
alcohol/drug misuse
Patients who report using medical
marijuana, versus patients with
similar pain conditions: Are more likely to use opioids problematically
Are more likely to use cocaine
Have worse psychosocial function
Marijuana use worsens prognosis in substance users
Aharonovich 2005, Mojarrad 2013
Contraindications/precautions to
medical marijuana
Youth < 25
Current/past hx psychosis
Active substance use disorder
Cardiovascular or respiratory disease
Mood or anxiety disorder
Pregnant/breast feeding
Pregnancy & Lactation
*very lipophilic*
Pregnancy: “Unsafe”
Lower birth weight, shorter gestational period,
abnormal startle response, tremulousness,
smaller head size, premature labor, prolonged
or arrested deliveries
Lactation: “Likely Unsafe”
Poor attention, concentration, and judgment,
problem solving difficulties, ADHD
Cannabis Dependency
Be aware that cannabis dependency does exist
Remember the 4 C’s
Loss of Control
Compulsive Use
Cravings
Use Despite Consequences.
Screening
for risk?
Screening
for risk?
The Process
Pt = patient
HCP = healthcare provider
LP = licensed producer
Pt consults authorized
HCP
HCP provides medical
document
Pt registers with LP
and places order
LP sends medical
cannabis to pt
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Medical document
Patient and healthcare practitioner information,
Duration of the prescription (maximum of 12 months),
Daily quantity of cannabis in a number of grams, and
May include any specific product recommendations, such as limiting THC concentration or restricting to cannabis oil only (NOTE: the licensed producer may not comply with these specifications).
Dosing High CBD - up to 20: 1THC
High THC - up to 25: 0 CBD
Hybrids – anywhere in between
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Inhalation (vaporizing? YES) Oral (oils or edibles)
THC Plasma Levels
Absorption • >95% • 10–30% (up to 50%)
Onset of Action • within seconds • 30–90 min (up to 120 min)
Duration of Action • 2–3 (up to 4) hrs • 5–8 (up to 12) hrs
Adapted from Grotenhermen F. J Cannabis Ther 2003;3:3-51.
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Cannabinoids: Inhalation vs Oral Characteristics
Time during and after smoking (hours)
ng/mL
Time after oral ingestion (hours)
ng/mL
Note: For the purpose of image clarity, the y-axis of the Inhalation graph uses increments of 20 ng/mL and the y-axis of the Oral graph uses
increments of 5 ng/mL.
1.Abrams DI, et al. Clin Pharmacol Ther 2011;90:844-51.
2.Geffrey AL, et al. Epilepsia 2015;56:1246-51.
Drug-Drug Interactions
Pharmacokinetic
There are no clinically significant drug interactions
between cannabis and other medications
Pharmacodynamic
Noted interactions with drugs that cause similar side
effects (e.g., opioids, benzodiazepines, anticholinergic
medications, etc.)
There is potential for additive dizziness, drowsiness and
sedation
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But!
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And
What do I do?
Comprehensive pain assessment of pain in the patient
Pain effect, treatments, psychiatric history
Phq9, GAD 7, BPI, UDS, Substance use risk
Never a first line product for me
What do I do?
Cannabis oils, high in CBD for pain
Occasionally add in THC component for sleep at night
only!
Will use vaporizer rarely, in palliative care only, for
more rapid response to pain as the long term harms are
less relevant..
See q 1-3 months
Follow up
Conclusions
Medicinal marijuana has a number of properties that can be useful in pain management. Not all strains are the same!!
Like all treatments there is a risk benefit ratio
Are we with MM now as to opioids 25 y ago??
Proper assessment including addiction screening are essential
Apply the same goals and expectations with marijuana as you would with any other therapeutic agent
Medical marijuana is a reasonable option for some but not all chronic pain patients (especially the higher CBD ratio strains)
DO NO HARM!!
Who wants samples?
Discussion:
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