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Dazed and Confused
Peter Barish, PGY2
Disclosures
• I have no financial disclosures
• As far as other disclosures…
• There was one time in college…
• ….but I didn’t inhale!
Learning Objectives
Review trends in use and public perception of marijuana
Understand the connection between marijuana and psychiatric
illness
Address the affects of smoking marijuana on lung health
including cancer and COPD
Identify indications for and steps required to prescribe medical
marijuana
Recognize common misconceptions about the health benefits of
marijuana
Changing Perceptions – the 1930s
Federal Bureau of Narcotics PSA
Changing Perceptions
• 1970 – Controlled Substances Act
– MJ listed as Schedule 1 Drug
• 1985: dronabinol (synthetic THC) approved in the
US for treatment of intractable nausea
• 1996-2015: 23 states + PR medical marijuana, 4
states and D.C. legalize recreational use
• 2008-2010: IOM, ACP, AMA
– Petitioned DEA/FDA to reschedule marijuana to
schedule II
Washington Initiative 502
Kids these days…
Biehl et al. CHEST 2015
Is everybody doing it?
Is everybody doing it?
Lifetime
Past year
Past month
National survey of drug use and health, 2014
Marijuana use over the long run
Volkow et al. NEJM 2014
Just say no?
Use goes up
as perceived
risk goes
down
Volkow et al. NEJM 2014
Risk? What risk?
% seeing “great risk” in regular use
•8th graders
•10th graders
•12th graders
Year
Johnston et al. 2014
Case 1
Mr. W – smokes marijuana daily and has for 5
years
“Hey, Dr. Barish, man, I’m thinking about getting
serious about my acting career in 15-20 years.”
“Addiction? Man, it’s just a little weed. I am
not addicted, amigo.”
How do you counsel your
patient about addiction?
Name: David Wooderson
Age: 22 years old
Hobbies: Cruisin’, driving to get
Stones tickets.
Voted most likely to win an
Oscar
Marijuana is not physically addictive
FALSE!
(it definitely is)
Probability of developing substance use disorder
Probability of Transition to Dependence
Marijuana, Alcohol, Nicotine and Cocaine
Addiction to MJ:
9% of users overall
17% if use begins in
adolescence
20-25% if daily use in
adolescence
Lopez-Quintero, C. et al. Drug & Alcohol Dependence 2011
Marijuana and Addiction 111
• Symptoms after MJ cessation:
– Irritability, anger, or aggression
– Nervousness or anxiety
Marijuana is less addictive than
– Sleepnicotine,
difficultyalcohol
(eg, insomnia,
disturbing
dreams)
or cocaine but a
– Decreased
appetite
or weight
loss
real addiction
syndrome
exists
and
– Restlessness
DAILY users are at higher risk
– Depressed mood
– Physical symptoms: abdominal pain,
shakiness/tremors, sweating, fever, chills, or
headache
• Symptoms usually persist for 1-2 weeks
Case 2
• Mr. S presents for his annual physical.
• He smokes marijuana several times daily and
has since he was 15 years old
Slater’s mother is concerned about some
talk of aliens and government conspiracies.
“Woah Dr. B. you didn’t know the founding
fathers were into aliens, man?! Washington
Name: Ron Slater
and Jefferson, man, they talk to me all the
Age: 23 years old
time about that stuff.
They Could
warned
me about
that tracking
Slater’s
marijuana
use device
in my have
brain.caused
Don’t his
think
I don’t know about
concerning
that”
symptoms?
Hobbies: US History, Aliens,
Marijuana.
Thinks Martha Washington was
a hip, hip lady, man.
Smoking marijuana increases your risk of
developing a psychotic disorder
Maybe!
(probably)
Marijuana and Psychosis 1
• Many epidemiologic studies show an
association between marijuana use and
Schizophrenia, other psychosis
• 50,000 initial subjects
• Examined hospital discharges from 1970-1996 for diagnoses of
schizophrenia
Zammitt et al. BMJ 2002
Marijuana and Psychosis 1
Psychosis/S
CZ
Psychosis/
SCZ
Psychosis/
SCZ
Cannabis causes
psychosis
Only among genetically
vulnerable people
Cannabis precipitates
early psychosis
Psychosis/
SCZ
Psychosis/
SCZ
Self-medication
hypothesis
Marijuana and Psychosis 1
• TRAILS study – Cannabis use and psychosis
vulnerability in early adolescence
– >2000 young adolescents enrolled; longitudinal trial
– Assessed for MJ use and vulnerability for psychosis at
3 time points (13.6 yrs, 16.3 yrs, 19.1 yrs)
T1
T2
T3
Psych.
Vuln.
Psych.
Vuln.
Psych.
Vuln.
Cannabis use
Cannabis use
Cannabis use
Griffith-Lendering et al. 2012
Marijuana and Psychosis 1
• Genetic Vulnerability?
– Catechol-O-Methyltransferase (COMT) regulates
dopamine activity in synapse
– Valine allele found to be associated with psychosis
in MJ users
No MJ use
MJ use
Caspi et al. Biol Psych 2005
Recap Psych!
• Well-established correlation between MJ and
psychosis, schizophrenia
• Causality is difficult to establish – remains
controversial
• Some longitudinal data do suggest causality
• Genetic susceptibility may be playing a role
Case 3
You see a new patient in clinic, William, who is
concerned about lung disease
“I’ve used marijuana. But I never
inhaled.”
“I’m really asking for my friend,
Barry. He used to smoke a lot of
weed. Is he going to get
emphysema?
Are Bill and Barry at risk for
chronic lung disease?
Name: William Jefferson Clinton
Age: 45 years old
Hobbies: Being President, Jazz
Saxophone
Hopes to one day understand
what the definition of “is” is.
Smoking marijuana, like tobacco, may lead to
obstructive lung disease
Cough, cough
279 habitual heavy smokers of marijuana
“Recruited from the Los Angeles metropolitan area
using newspaper advertisements and radio
announcements”
Tashkin et al. 1986
Cough, cough
Percent of abnormal symptoms
Cough
Sputum
Acute
Bronchitis
episode
Wheeze
SOB
MJ + Toacco
23.1
25.6
14.1
34.8
4.4
MJ only
18.4
19.7
13.4
24.8
0.7
Tobacco
only
24.3
Non-smoker
1.1
Inhaling smoke into your
lungs
respiratory
25.7 causes10.0
37.1
symptoms
5.6
2.2
7.8
8.6
2.2
PFTs for the win
What is
marijuana
doing to my
PFTs?
http://mmdsboston.com/pulmonary-function-testing/
PFTs vary with DAILY smoking behavior
Episodes per mo (MJ) and episodes per d (T)
Pletcher, JAMA 2012
PFTs change with LIFETIME exposure
MJ does not cause a
reduction in lung function
measured by PFTs
Joint-years (MJ) and Pack-years (T)
Pletcher, JAMA 2012
Histopathologic changes with MJ use
Fligel et al. performed Bronchoscopy on 241 volunteers
Smokers of MJ, Cocaine and Tobacco
What’s in that cigarette?
• 15 men, habitual smokers of both
marijuana and tobacco
• Measured the dynamics of smoking MJ
and tobacco cigarettes
• Examined particulate matter delivered to
each smoker
Wu et al. NEJM 1988
What’s in that cigarette?
Marijuana, compared with tobacco:
• 3X more insoluble particulates
(tar)
• 4x higher “tar burden”
• 4x greater carboxyhemoglobin
sat
Wu et al. NEJM 1988
“But Doctor B
What about
the CANCER,
man?”
Marijuana and Lung Cancer
•6 case-control studies
•New Zealand study showed
increased risk for lung cancer
•Pooled analysis – no
association with MJ smoke
alone
Marijuana and Lung Cancer
•Case control study – compared cases of OSCC to matched controls
•No association found with “ever-used” marijuana
• Difficult to control for tobacco use
• Data remain controversial
• THC may have chemopreventive effects
Recap Lung!
• Marijuana causes respiratory symptoms
similar to tobacco
• MJ does NOT cause COPD – FVC increases for
reasons not entirely known
• MJ causes histopathologic changes in the
lungs similar to tobacco…but
• There is no good evidence linking MJ smoking
to lung cancer
The Wonders of Weed
Does Marijuana Cure Cancer?
From the Lab
Pre-clinical models suggest that Cannabinoids may inhibit tumor
growth in breast, lung cancer
• Similar results have been shown in NSCLC
• No evidence in humans
It remains to be seen if CBD can be
used therapeutically for cancer
On the clinic schedule
“I have night
blindness”
Not this guy (sorry, Seth)
Case 4
Marilyn is a 68 yo woman with
metastatic Breast ca
• Chemotherapy with doxorubicin
• She complains of low energy, minimal
appetite and substantial pain
• Taking Zofran and Compazine for nausea
with minimal success
Option 1: Prescribe
medical marijuana for
the relief of pain and
nausea
Option 2: Continue to
use conventional
medications
Marilyn lives in WA state and is interested in using
marijuana to treat her pain
As her primary care physician, how would you
advise her to treat her pain and nausea?
Data-driven uses for MJ
• Nausea
– THC effective for chemotherapy nausea
– Watch out for hyperemesis!
• AIDS-associated anorexia/wasting
– Some evidence but mostly for dronabinol
– May improve appetite and lead to weight gain, but the data are
not robust
• Chronic Pain
– Central CB1 receptors
– Both MJ and dronabinol have been effective
– Very patient specific
• Spasticity (MS or Paraplegia)
– Likely effective but no statistically sig results
Volkow et al. NEJM 2014
Whiting et al. JAMA 2015
You can do it! (except for VA)
• For-providers form on
WA DOH website
–
–
–
–
–
–
–
Cancer
HIV
Intractable Pain
PTSD
HCV
ESRD on HD
Glaucoma
• Must significantly
interfere with ADLs
Take-Home Points!
• Addiction to MJ exists
• There is likely a causative relationship between
MJ and psychosis in some patients
• Smoking MJ causes respiratory symptoms and
concerning path changes but…
• NO good data to support MJ causing lung cancer
at this time
• Medical Marijuana may be prescribed for a select
number of debilitating diseases
• It does not cure cancer…yet
Acknowledgements
• Thanks to Renata and the Clin Ed team for all
your help and critique
• Tyler Albert
• Jehan Budak
• Jenell Stewart