Download Medical Marihuana: Clearing the Air

Medical Marihuana: Clearing the
Air
Sara Feinauer, PharmD, BCPS
November 2014
Google: Smoke. http://campbellpropertymanagement.com/blog/2014/08/05/159-new-laws-go-smoke-quick-look-medical-marijuana-smoke-foul/
Disclosure
• No disclosures concerning a conflict of interest
with commercial entities that may be
referenced in this presentation.
Objectives
• 1. Describe how medical marihuana may
provide medicinal benefits
• 2. Compare and contrast the benefits versus
risks of using medical marihuana
• 3. List usages and restrictions as applicable to
the state of Michigan in regards to the use of
medical marihuana
Overview
Risks
Uses
Laws
Medical Marihuana
Marijuana vs. Marihuana1
• Per Initiated Law 1 of 2008 and administrative
rules:
– “Marihuana is one of two acceptable spellings in
the dictionary and is consistent with the spelling
in the Michigan Public Health Code, Act 368 of
1978, and Initiated Law 2008.”
Marihuana: A History2,3
• Prior to 1937, marihuana was commonly used
as a bronchodilator
– Used most often for asthma in the 1800s
• Dropped from the US pharmacopeia in 1941
• Most commonly used illicit substance
worldwide
– 3.9% of adult population (15-64 years old)
Marihuana: A Controversy2,3
• DEA states that there are legal products
available
• AMA supports rescheduling to schedule II
– “Known medicinal value, while acknowledging the
importance of proper medical supervision and
accepting that more research is necessary into the
side effects and possible dangers of medical
marijuana use”
Limitation to Uses2
• Relief of symptoms, not cure
• Evidence often anecdotal
• Route of use
• Amount for use
How does it work?2,4
• Tetrahydrocannabinol (THC) is a partial agonist
at cannabinoid receptors (CB1, CB2) in the
endocannabinoid system
– THC primary effect on CB1
How does it work?2,4
CB1
•Brain
•PNS
•ANS
•Psychoactive
CB2
•Neurons
•Immune cells
CB1 Effects2,4
Sedation
Analgesic
Anxiolytic
Psychiatric
Appetite
Stimulant
Appetite
Stimulant
Nausea
and
Vomiting
Glaucoma
Chronic
Pain
Uses
Multiple
Sclerosis
Medical Marijuana. Pharmacist’s Letter. January 2013.
Appetite Stimulant2
Cancer
HIV
• Dronabinol < megestrol
• Oral cannabis ≠ placebo
• Smoking stimulates appetite
• Dronabinol and THC (2% and
3.9%) > placebo
Chronic Pain5,6
• >45 studies
– Cancer, diabetes, fibromyalgia, MS, HIV,
rheumatoid arthritis, spinal injuries
– Majority show benefit
– Quarter of studies showed no improvement
• No benefit in acute pain
Chronic Pain4,6,7
• THC 10 mg was better than placebo
– Analgesically similar to 60mg codeine
• 3.56% THC cigarettes TID x 5 days decreased
pain intensity over placebo
– 3.56% and 7% studied
– 9 cumulative “puffs” (240 minutes) = ½ cigarette
– 19mg (3.56%) 34mg (7%) THC consumed
Multiple Sclerosis2,5
• Benefit shown from both oral intake and
smoking
– PO may reduce urge incontinence
• >24 studies
– Relax rigid muscles
– Decrease pain
Nausea and Vomiting2,7
• Modest anti-emetic
• Different mechanism than commercially
available products
• Possible adjunctive treatment
• Most studies available look at commercial
products vs. medical marihuana
• Smoking 8.4-16.9 mg THC had limited benefit
compared to 8 mg ondansetron
Glaucoma2,7
• Smoking marihuana reduces intraocular
pressure short-term
– 60-65% decrease for open angle glaucoma
– Decreases blood flow to optic nerve
– Linear relationship to amount smoked
– Benefit for 3-4 hours = 8-10 marihuana cigarettes
smoke/day for continual benefit
• Unknown benefit to visual function
Alzheimer’s
Disease
Schizophrenia
Autism
Possible
Benefit
Digestive
Disorders
Cancer
Epilepsy
Vaida B. Medical Marijuana: What the Research Shows. April 02, 2014.
http://www.medscape.com/viewarticle/822942
Alzheimer’s Disease5,8
• 1 trial from 1997 showed THC could ease
symptoms
• Participants showed less agitation and better
appetites
• Decrease amyloid beta at low concentrations
• Potential neuroprotective effect
– Memory impairment only seen at “abuse”
concentrations
Autism5
• 2 animal studies show possible symptom
benefit
• Study at University of California in progress
Cancer5
• Several human and animal studies
• Small study (9 participants) showed THC and
other cannabinoids may slow brain cancer
growth
• Lab studies of human cells show potential to
slow breast and leukemia cancer cells
Epilepsy5
• Anecdotal and animal studies show
cannabidiol (CBD) may help seizures in
children
• New York University to begin studying
marihuana benefit for epilepsy in children
Digestive Disorders5
• Anecdotal, early studies
– Smoking marihuana can help with: colitis, irritable
bowel syndrome, and Crohn’s disease
– Reduces bowel inflammation and decrease acid
reflux
– Some patients retained more nutrients
– Some had disease remission
Schizophrenia5
• 2 trials
• THC and cannabidiol could help psychotic and
other symptoms
• Possible link to causing schizophrenia in
adolescents who start
• National Institute of Health funding clinical trial
to study ease of symptoms
Other possibilities7
• Tourette’s
– Oral THC helped decrease tics after 6 weeks
compared to placebo
• Levodopa-induced dyskinesias in Parkinson’s
Disease
Question 1
• Which of the following properties is an
example of the possible beneficial aspects of
using medical marihuana?
a.
b.
c.
d.
Anxiolytic
Analgesic
Appetite stimulant
All of the above
Risks9
“What the data are showing is for the majority
of the population, cannabis is not associated
with severe, long-term adverse outcomes, but
there is a misconception that this means it is
safe for nearly everyone, which is not true.”
Limitations to Risks
• Recreational use is not the same as medicinal
use
• No consensus on definitions of low vs. heavy
use
• Most studies use oral commercial forms
Abuse9-11
• States with legalized marihuana have higher rates
of use/abuse/dependence
• Clinical and epidemiologic studies show link
between early cannabis use and increased
exposure to heavier drugs
– No true causal relationship – genetic and
environmental influences
– Screening processes
• Addiction potential 9-10%
– Highest when starting as a teenager
Irritability
Decreased
appetite
Anger
Withdrawal
Craving
Depression
Insomnia
Side Effects2
• Serious side effect risks low compared to
many other prescription drugs
Common Side Effects6
Dry mouth, red eyes
Nausea/Vomiting
Sedation
Dizziness
Altered sense of time
Decreased GI motility
Confusion
Increased heart rate and BP fluctuations
Increased well-being
Muscle relaxation
Increased appetite
Cough
Chronic Use6
Apathy
Impaired memory
Sexual dysfunction
Bullous emphysema
Increased risk of MI in middle age
Ischemic stroke
Unknown Risks2
• Lung cancer
• Testicular cancer
• Increased risk of psychosis
Other risks6,9
• “Motivational syndrome”
• Intoxicating doses impair reaction time, motor
coordination, and visual perceptions
– Driving may be impaired for up to 8 hours
• Dependency similar to other pain medications
Lung Disease3
• Marihuana smoke contains 70% more
carcinogenic ingredients than cigarette smoke
• Similar compounds to cigarette smoke
• Research with lung cancer is conflicting
• Combustive marihuana is a respiratory irritant
Lung Disease3
• Meta-analysis Tetrault et al.
– Consistent association between short-term use
and bronchodilation
• Increase FEV1, peak flow, and airway conductance
– Also found no consistent association with longterm smoking and airflow obstruction
– Benefit is non-linear, increase FEV1 with low levels
of exposure, but decrease FEV1 at high levels
Lung Disease3
• CARDIA (Coronary Artery Risk Development in
Young Adults)
– 20 year follow up with no airflow obstruction with
occasional or low cumulative marihuana smokers
• NHANES III (National Health and Nutrition
Examination Survey)
– Both marihuana and tobacco increase respiratory
symptoms
• Fligiel et al. suggests physical exam and
spirometry may not be sensitive enough in
asymptomatic smokers
Lung Disease3
• Associated with chronic bronchitis symptoms
and airway inflammation, however low
cumulative doses are not a risk factor for
COPD
• Apical bullous lung disease
– Linked to heavy smoking in young adults
– Deeper and longer inhalations
– Related to technique
– Very rare and possibly coincidental
Lung Cancer3
• Research is conflicting
– THC effects on cytokines suggest cancer cell
growth but cannabinoids seem to inhibit cell
proliferation in vitro
• Histopathologic and immunohistologic
evidence suggested molecular markers of
pretumor progression, Moir et al.
– Epidemiologic evidence linking is rare
Lung Cancer3
• Swedish study
– > 50,000 men, 18-20 years old
– Extended follow-up
– Heavy cannabis smoking = >50 uses
• Two-fold greater risk in developing lung cancer
• Article conclusion: “Any toxicity pales when
compared to the greatest legalized killer in the
world – tobacco.”
Study Flaws3
• Most people who smoke marihuana also
smoke tobacco
• Most studies lack power to associate
marihuana with COPD
• Under-reporting
• Wide variety of definitions for “heavy” use
Question 2
• True or False: Smoking marijuana has been
conclusively linked to lung cancer.
True
False
Pharmacist stuff…
Medical Marijuana. Google. saintpetersblog.com
Drug Interactions6
• CYP450 3A4 and 2C inhibitor
• Little evidence of clinically significant
interactions at medicinal doses
• Unclear if risk equivalent when smoking
(undergoes less hepatic first-pass metabolism)
• Use caution with anti-cholinergics and CNS
depressants (additive effects)
Contraindications/Precautions6
Contraindication
Precautions
• Abnormal sensitivity to
marihuana
• Severe personality
disorders/psychoses
• Pregnant/breastfeeding
• Children/adolescents
• Elderly
• Cardiovascular disease
• Addictive disorders
Pharmacokinetics6,7
• THC immediately in plasma following
inhalation
– Rapidly absorbed within seconds, peak
concentration 3-10 minutes
• Low oral bioavailability improved when in oilbased formulation
• Active metabolites higher after oral use than
smoking
Pharmacokinetics7
• Cannabidiol (CBD) has extensive first-pass
metabolism
– Oral: peak 30-120 minutes and detected for 180240 minutes after ingestion
• Rapid onset and predictable decay allow for
self-titration
• Overdose is rare
Medical Marihuana9,12
• “Not your parents’ pot”
– Current cannabis more potent
– Higher levels of THC
• 1960-1970’s: <5% THC
• Last 10 years: 15-20% THC
• Prescriptions should specify THC
concentrations not greater than 9%
Types of
Medical
Marihuana
Sativa
Indica
Leung L. Cannabis and its derivatives: Review of medical use. J Am Board Fam Med
2011;24:425-462.
Smoking
Topical
Vaporizing
Routes
Tincture
Eating
Drinking
Methods, Forms and Routes of Medical Marijuana Administration.
http://svphyto.org/wp-content/uploads/2013/06/Methods-Formsand-Routes-of-Medical-Marijuana-Administration.pdf
Smoking3,4,6,13
Pros
• Most immediate relief
• Refined control
• Self-titration
Cons
• Respiratory irritation
• Combustion creates additional byproducts
• Possible contaminants
• Amount delivered depends on individual techniques/lung
capacity
Smoking13
• Potentially greater benefit in:
– Tourette’s Syndrome
– Glaucoma
– Pain
– HIV-induced neuropathic pain
Smoking2,3
• No FDA approved drug is available
administered by smoking
– Most studied route for medical marihuana
• Despite lack of marihuana standardization,
smoking is an unpredictable route of
administration
– Dependent on user: time of inhale, method of
inhale, time of exhale
Vaporizing13
• Smokeless alternative
– Considered safest route
– Not the same as water pipes
– Heat cannabis below point of combustion
producing less byproducts but allowing essential
oils to volatize
Marijuana Vaporizer. Google. lelandkim.com
• Similar effects to smoking
Eating13
• Cannabinoids extracted into fats (butter/oils)
• Ingested via baked goods/candy-like products
• Active ingredients must be metabolized by liver
– Can take 30 minutes – 2 hours before effects
– Effects last 2-8 hours
• Side effects typically stronger than smoking
• More difficult to regulate doses
• Oral use potentially more beneficial in: MS
spasticity, peripheral/central neuropathic pain
Drinking13
• Tea
– Boil water and pour over cannabis
– Steep for 1.5 hours – not readily water soluble
– Effects similar to eating
Tinctures13
• Alcohol used to extract cannabinoids
• Effects similar to eating
• Faster onset and quicker offset than eating
– Effects in 5 minutes – 1 hour
– Last up to 4 hours
• May drop or spray into mouth and absorb
through mucous membranes
• Can drop in hot water to burn off alcohol
Topical13
• Can be absorbed through skin
• Ideal for ointments
Commercially Available2
• Dronabinol (Marinol®) – schedule III
• Nabilone (Cesamet®) – schedule II
– Use: nausea with chemotherapy agents
• Nabiximols (Sativex®)
– Buccal spray approved in Canada, currently studied in
US for neuropathic pain in adults with MS
• Epidiolex®
– FDA approved in 2013 for children’s epilepsy
– Highly restricted use
Commercially Available2,13
• Typically these agents are too psychoactive
– Narrow gap between therapeutic dose and
adverse effects
• Euphoria, cognitive clouding, drowsiness
• Only based off of THC (psychoactive
component)
• A combination of cannabinoids (cannabidiol
and THC) as found in medicinal marihuana can
have affect over benefit and side effect profile
Michigan Medical Marihuana Act9
• Department of Justice: Will not challenge
state laws that legalize marihuana
– Focus on:
•
•
•
•
Preventing distribution to minors
Stop drug trafficking by gangs/cartels
Prevent drugged driving
Prohibit public lands for growing
Michigan Medical Marihuana Act14
Debilitating
qualifying
medical
condition
Registered
with MMMP
MI Resident
Patient
“Usable” Marihuana14
Leaves
Flowers
Michigan Medical Marihuana Act14
Caregivers
Physicians
• Must meet state
requirements for
protection
• May care for up to
5 patients
• Must meet state
requirements for
protection
• Bona fide
physician – patient
relationship
MMMA: Updates14
Public Act
460
• Limit transportation
Public Act
512
• Define bona fide physician-patient relationship
• Further definitions: enclosed, locked facility,
primary caregiver
Public Act
514
• Proof of residency
• Further definitions
• Add confidentiality
Debilitating Medical Condition14
Cancer
Glaucoma
Positive HIV status
AIDS
Hepatitis C
Amyotrophic Lateral Sclerosis
Crohn’s disease
Agitation of Alzheimer’s disease
Nail patella syndrome
Debilitating Medical Condition14
Cachexia or wasting syndrome
Severe and chronic pain
Severe nausea
Seizures
Severe and persistent muscle spasms
Any other medical condition or its treatment approved by the department
Debilitating Medical Condition14
Approved
• Parkinson’s
Disease
• PTSD
Denied
• Asthma
• Autism
• Insomnia
• Bipolar disorder
Question 3
• Which of the following is NOT a valid use for
medical marihuana in Michigan?
a.
b.
c.
d.
Glaucoma
Crohn’s Disease
Nail patella
Schizophrenia
Updates15
• Dispensaries shutdown in February 2013 as
“public nuisance”
– House legislation to add new rules and limitations
for reopening
• Michigan Court of Appeals in July 2013 said
“pot brownies” are not “usable marihuana”
under the law, unless contain actual plant
material
– Legislation also to redefine to include edibles
Conclusions
• Marihuana has shown possible medicinal
benefit in multiple indications
• Marihuana use does not come without risks
• Further studies need to be done
Resources
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Michigan Medical Marihuana Program. LARA. http://www.michigan.gov
Medical Marijuana. Pharmacist’s Letter. January 2013.
Manish J et al. Marijuana and Lung Diseases. Curr Opin Pulm Med. 2014;20(2):173-197.
Leung L. Cannabis and its derivatives: Review of medical use. J Am Board Fam Med 2011;24:425-462.
Vaida B. Medical Marijuana: What the Research Shows. April 02, 2014.
http://www.medscape.com/viewarticle/822942
Zanni GR. Medical marijuana potential and pitfalls. http://www.pharmacytimes.com
Medical Marijuana. Clinical Pharmacology. 2014.
Harrison P. Marijuana Compound a Novel Treatment for Alzheimer’s? September 05, 2014.
http://www.medscape.com/viewarticle/831199
Melvil NA. Public in a haze about marijuana safety. September 04 2013.
http://www.medscape.com/viewarticle/810427
Alcohol and Drug Information. National Council on Alcoholism and Drug Dependence, Inc.
https://ncadd.org/for-the-media/alcohol-a-drug-information.
Nicotine Addiction: Past and Present. How Tobacco Smoke Causes Disease. 2010. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK53018/
Collier R. MediData: How potent is medical marijuana. CMAJ. Aug 26, 2014.
Methods, Forms and Routes of Medical Marijuana Administration. http://svphyto.org/wpcontent/uploads/2013/06/Methods-Forms-and-Routes-of-Medical-Marijuana-Administration.pdf
Michigan Medical Marihuana Program. LARA. http://www.michigan.gov
Oosting J. Michigan medical marihuana rule changes hit speed bump. October 01, 2014.
http://www.mlive.com/lansing-news/index.ssf/2014/10/michigan_medical_marijuana_rul.html
Questions?
Smoke. Google. http://textures8.com/smoke-abstract-background-sixty-five/