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Medical Marijuana Pros and Cons: What Doctors Need to Know


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Title: Medical Marijuana Pros and Cons: What Doctors Need to Know

Medical MarijuanaPros and ConsWhat Doctors
Need to Know
  • Colorado Physician Health Program

Speaker Disclosure
  • Nothing to report at this time
  • Speaker Bureau
  • Consultant
  • Grant/Research support
  • Stock Shareholder
  • Employee/Other

  • Statement of need  The use of prescription
    medical marijuana is legal in the state of
    Colorado without many provisions or forethought
    as to the possible problems and consequences
    such as  Is there a legitimate treatment option
    and for whom?  What is the potential impact on
    the medical community?
  • Program Goal Provide education based on the
    literature regarding the safety and effectiveness
    of marijuana used medicinally.  Present the
    potential problems inherent in this legislation
    and suggest the safeguards needed to protect
    those at risk for consequences.
  • Objectives
  • Identify the medical conditions which have been
    shown to benefit from medical
  • marijuana.
  • Clarify what is oral-pharmaceutical cannabinoids
    and what is smoked cannabis.
  • Describe the consequences of marijuana use
    physically, psychiatrically and cognitively.
  • Determine how this treatment is viewed currently
    by the FDA the DEA and their
  • ultimate relation to the prescribing
  • Determine what safeguards need to be in place to
    protect those who consequences
  • from the treatment would outweigh any
    potential benefit.

  • Complex alkaloid mixture of more than 400
    compounds derived from the Cannabis sativa plant
  • 60 different compounds described with activity on
    the cannabinergic system
  • Most abundant cannabinoids are
  • Delta-9 tetrahydrocannabinol (most psychoactive)
  • Cannabidiol
  • Cannabinol

Cannabinergic system
  • Two main cannabis receptors
  • CB1 present throughout CNS
  • Hippocampus
  • Cortex
  • Olfactory areas
  • Basal ganglia
  • Cerebellum
  • Spinal cord
  • CB2 located peripherally, linked with immune
  • Spleen
  • macrophages

History of Marijuana
  • 6000 BC Cannabis seeds used as food in China
  • 4000 BC Textiles made of hemp in China
  • 2727 BC first recorded medicinal use in Chinese
  • 1400 BC to AD trade moves product through
    India, Mediterranean countries, Europe numerous
    medicinal uses reported

History of Marijuana
  • 1378 Emir of the Ottoman Empire makes the first
    edict against eating hashish or smoking cannabis
    1st War on Drugs
  • 1798 Napoleon declared total prohibition on
    marijuana after realizing much of the Egyptian
    lower class were habitual smokers
  • 1868 Egypt 1st modern country to outlaw
    cannabis ingestion
  • 1890 Hashish made illegal in Turkey

History of Marijuana
  • Introduced to North America in 1600s by Puritans
    Hemp for ropes, sails, clothing cannabis a
    common ingredient in medicines, sold openly in
  • 1937 Marijuana Tax Act transfer of cannabis
    illegal throughout US except for medicinal and
    industrial use, expensive excise tax and detailed
    logs required
  • 1969 found to be unconstitutional since it
    violated 5th Amendment privilege against

(No Transcript)
History continued
  • 1970 Controlled Substance Act classified
    cannabis as having
  • High abuse potential
  • No medical use
  • Not safe to use under medical supervision
  • 1975 FDA establishes Compassionate Use Program
    for Medical Marijuana Glaucoma, Multiple
    Sclerosis, Cancer
  • 1986 Dronabinol placed into Schedule II by DEA
  • 2003 Canada 1st country in world to offer
    medical marijuana to patients

Compassionate Use not based on any research
  • Glaucoma - 1 cause of blindness
  • 1992 American Academy of Ophthalmologys
    Committee on Drugs no scientific verifiable
    evidence that the use of marijuana is safe and
    effective in the treatment of glaucoma
  • 1997 NEI no studies have demonstrated that
    marijuana can safely and effectively lower IOP
    any more than a variety of drugs on the market

  • 1999 Institute of Medicine although IOP can
    be reduced by using cannabinoids and marijuana,
    the effect is too short lived and requires too
    high doses.
  • There are too many side effects to recommend
    lifelong use in the treatment of glaucoma
  • Would have to smoke 10-12 joints per 24 hours to
    maintain low IOP through out the day

  • Four cannabinoid products available
  • Herbal cannabis extract, Sativex, delta-9-THC
    and cannabidiol in oromucosal spray
  • Dronabinol synthetic delta-9-THC, Marinol
  • Nabilone synthetic derivative of delta-9-THC,
  • Herbal form of cannabis medical marijuana

  • Dronabinol (Marinol) and nabilone (Cesamet)
    indicated for chemotherapy-induced nausea and
  • Dronabinol (Marinol) approved for HIV-associated
  • Sativex (oromucosal spray) conditionally approved
    for neuropathic pain in multiple sclerosis and
    cancer pain
  • Herbal smoked marijuana found to be safe and
    effective for HIV-associated disorders

Most of the Research to Date
  • Most studies done with oral preparations, not
    smoked cannabis
  • Most studies short term 2 weeks average (few
    hours to one year max)
  • Most studies exclude anyone with a history of
    major psychiatric disorder other than depression
    and history of substance abuse

Studies of Effects on Pain
  • Lit review of cannabinoids given by any route for
    treatment of pain Campbell et al. BMJ
  • 9 RCTs, 222 patients, 5 trials cancer pain 2
    chronic non-malignant pain 2 post-operative
    pain none evaluated cannabis
  • Cannabinoids are no more effective than codeine
    in controlling pain and have depressant effects
    on the CNS that limit their use. In acute
    postoperative pain they should not be used.
    Before cannabinoids can be considered for
    treating spasticity and neuropathic pain, further
    valid randomized controlled studies are needed.

Side Effects of Cannabis
  • Most of our knowledge about the negative effects
    of marijuana come from recreational use
  • Literature review of safety studies of medical
    cannabinoids over past 40 years 23 RCTs (median
    exposure to cannabinoids 2 weeks, range 8 hrs to
    12 months) Wang et al. CMAJ 2008171669-1678

Side Effects
  • 4779 adverse events reported in those assigned to
    the intervention
  • 96.6 were not serious
  • 164 serious events no different from controls
    (RR) 1.04
  • Rate of nonserious events higher among those
    assigned medical cannabinoids than controls
    (RR)1.86 dizziness most common event

Studies with Smoked Cannabis
  • Double-blind, placebo controlled, crossover trial
    of smoked cannabis for the short term treatment
    of neuropathic pain associated with HIV five
    study phases over 7 weeks five days of active
    or placebo smoking with washout periods
  • Participants had documented HIV, neuropathic pain
    refractory to a least two previous analgesics, 5
    or higher on pain scale (Ellis et al.
    Neuropyschopharmacology 200934672-680)

Studies of Smoked Cannabis
  • Four smoking sessions per day, titrating dose
    (1-8 THC) to achieve maximum tolerable dose
  • Exclusion criteria
  • Current substance use disorder
  • Lifetime history of dependence on cannabis
  • Concurrent use of medication with cannabinoids
  • Previous psychosis with or intolerance to

  • significantly reduced neuropathic pain intensity
    compared to placebo
  • 46 with cannabis reported a 30 reduction in
    pain versus 18 with placebo
  • Another study with almost identical outcomes
    52 vs 24, gt30 reduction in pain with 3 smoking
    sessions/day (Abrams et al. Neurology
  • All patients were required to have prior
    experience smoking marijuana so they would know
    how to inhale and what neuropsychological effects
    to expect

Dose-dependent effects of smoked cannabis on
Capsaicin-induced pain and hyperalgesia in
healthy volunteers (Wallace et al.
Anesthesiology. 2007107785-796)
  • Randomized, double-blinded, placebo-controlled,
    crossover design
  • High dose training session, 15 subjects
  • 100 mg capsaicin injected intradermally ventral
    forearm spontaneous pain
  • Stroking and von Frey hair stimulation elicited
  • Low dose 2 THC, medium dose 4THC, high dose 8

  • Capsaicin injections induced spontaneous and
    elicited pain in all subjects
  • No difference in pain perception between any of
    the cannabis doses and placebo during early
    (right arm) course
  • Low dose did not differ from placebo at any time
  • During late course (left arm) medium dose
    subjects reported decreased pain sensation, high
    dose subjects reported increased perception of
    pain consistent with other reports that chronic
    delivery of cannabinoids can cause thermal

So To Review
  • Marijuana (smoked/oral) used as a therapeutic,
    not recreational agent, is a drug as defined by
    the FDA
  • All new drugs must be scientifically evaluated
    before they may be allowed to enter the stream of
    interstate commerce
  • The drug does not have to be proven superior to
    already approved drugs, its benefits must
    outweigh the risks when used for the purpose for
    which it has been approved

The fact that it is a botanical does not preclude
scientific investigation
  • Digitalis purpurea fox glove - CHF
  • Papaver somniferum opium poppy
  • Atropa belladonna nightshade -IBS
  • Ephedra sinica ephedrine - hypotension
  • Salix alba willow tree - ASA
  • Taxis brevifolia Pacific Yew tree breast

DEA Scheduling Drugs depends on
  • Does the drug have a currently accepted medical
    use in the United States?
  • What is the drugs safety under medical
  • What is its addiction liability?
  • Is there a potential for significant diversion
    for illegal use?
  • Are individuals using it on their own initiative
    or only on physicians prescription?
  • Is the drug similar in its pharmacology to other
    controlled drugs?

(No Transcript)
So in spite of all this
  • In the November 2000 general election,
    Coloradoans passed Amendment 20 and the Colorado
    Department of Public Health and Environment was
    tasked with implementing and administrating the
    Medical Marijuana Registry program
  • March 2001 - Colorado Board of Health approved
    the Rules and Regulations
  • June 2001 - Registry began accepting applications
    for Registry Identification cards

As of September 30, 2009
  • 19,691 new patient applications received
  • 24 denied, 21 cards revoked, 236 died, 2,054
    cards expired total of 17,356 current patients
    (increase of 2,979 patients in one month
    compared with stats from 8/31/09)
  • 73 male, average age 40, 8 minors lt18
  • 57 in the Denver/metro area
  • 67 have designated primary care-giver
  • Over 800 different physicians have signed for
    patients in Colorado

  • Cachexia 414 2
  • Cancer 492 3
  • Glaucoma 188 1
  • HIV/AIDS 193 1
  • Muscle spasms 5,273 30
  • Seizures 482 3
  • Severe pain 15,654 90
  • Severe nausea 3,612 21

Rules and Regulations
  • Patient will be deemed to have established an
    affirmative defense to such allegation
    (possession of marijuana) where
  • Patient was previously diagnosed by a physician
    as having a debilitating medical condition
  • Patient was advised by his or her physician, in
    the context of a bona fide physician-patient
    relationship, that the patient might benefit from
    the medical use of marijuana in connection with a
    debilitating medical condition

Conditions considered debilitating
  • Cachexia
  • Severe Pain
  • Severe Nausea
  • Seizures
  • Persistent Muscle Spasms
  • Any other medical condition approved by the state
    health agency

Rules and Regulations
  • Patient may engage in the medical use of
    marijuana with no more marijuana than is
    medically necessary to address a debilitating
    medical condition
  • No more than 2 ounces and no more than six
    plants, 3 or fewer being mature
  • No patient shall engage in medical use of
    marijuana in plain view of, or in a place open
    to, the general public

So what can we expect?
  • Since the vast majority of these patients most
    likely dont have debilitating illnesses that
    will result in death anytime in the near future
    they will be exposed to long term effects of
    cannabis rather than short term as in all the
  • Therefore their risks may be the same as for
    recreational users

Therefore Physicians Recommending Medical
  • Will need to get a thorough history - medically,
    psychiatrically and substance abuse keep a
    chart and have a patient/physician relationship
  • Will need to attempt to decide what level of
    marijuana use is most appropriate
  • Will need to recommend patients not drive etc.
    when under the influence
  • Will need to follow patients closely for side
    effects and unintended consequences

Marijuana use and Cancer risk
  • Marijuana smoke contains several of the same
    carcinogens and co-carcinogens as tobacco smoke
  • Benzoapyrene, a procarcinogenic polycyclic
    aromatic hydrocarbon, is present in marijuana tar
    at higher concentrations than in tobacco tar
  • Marijuana smoking involves inhalation of 3 times
    the amount of tar as tobacco smoke

Cancer Studies involving Marijuana
  • Studies are small in number and are retrospective
    in nature
  • Confounded by concomitant use of tobacco
  • Confounded by underreporting of marijuana use
    because such use is often illegal

Cannabis use and risk of Lung Cancer Aldington et
al. Eur Respir J. 200831280-286
  • Case-controlled study of lung cancer in adults lt
    55yrs of age in New Zealand
  • 79 cases of lung cancer and 324 controls
  • Risk of lung cancer increased 8 for each
    joint-yr (1 joint/day for one year) of cannabis
    smoking after adjustment for confounding
    variables including tobacco
  • Risk increased 7 for each pack-yr tobacco
  • Long-term cannabis use increases risk of lung
    cancer in young adults

Head and Neck Cancers
  • Retrospective, case-controlled study, 173 proven
    cases of head and neck cancer and 176 controls
    matched with respect to age, sex, race,
    education, tobacco, alcohol use
  • Risk of cancer 2.6 fold greater in cannabis users
    than non-users
  • 3-fold greater increase in those lt 55 yrs
  • Zhang et al. Cancer Epidemiol Biomark Prev

Other Cancers
  • In a cohort study among non-tobacco smokers,
    ever-marijuana smokers had increased risk for
    prostate cancer - RR3.1, and cervical cancer -
    RR1.4 Sidney et al. Cancer Causes Control
  • Another cohort study found an increased risk of
    malignant primary adult-onset glioma for
    ever-marijuana smokers RR1.9 Efird et al. J
    Neurooncol 20046857-69

Metabolism of Marijuana
  • Massive first pass metabolism via the oral route
    only 10-20 reaches systemic circulation
    unchanged takes 30 60 minutes to achieve an
    effect key side effect on CNS can be dysphoria
    rather than euphoria
  • Via the lungs onset of action within seconds
    high experienced with serum concentration of 3
    ng/ml, produced by as little as 2-3 mg D9THC,
    average joint contains 0.5 1.0 g of cannabis

Routes of Administration
  • Where theres smoke, theres harm, There is no
    future in smoking marijuana as a conventional
    medicine Janet Joy PhD
  • Until there is an alternative, for a small
    segment of the population there is a modest
    clinical benefit of smoked marijuana
  • Sound theoretical reasons for intrathecal or
    epidural cannabinoids may produce spinal cord
    analgesia without effects on cerebral receptors
    that are associated with psychotropic effects

Marijuana and Cognitive Impairment
  • Use of 4 joints or more per week resulted in a
    decrement in mental test performance, subjects
    who smoked regularly for a decade or more did the
    worst Messinis et al. Neurology 200666737
  • Long-term marijuana users were impaired 70 of
    the time on a decision making test, compared to
    55 for short-term users and 8 for non-users

Marijuana and Cognitive Impairment
  • Heavy marijuana use (daily for at least one
    month) is associated with residual
    neuropsychological effects even after a day of
    supervised abstinence from the drug Harrison et
    al. JAMA 1996275521
  • Unknown whether this is due to residue of drug in
    the brain, withdrawal effects or frank neurotoxic
    effect of the drug

Regional Brain Abnormalities Associated with
Long-term heavy Cannabis Use Arch Gen Psychiatry
  • 15 long term (gt10 years) and heavy (gt5 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) plt.001
  • Significantly worse performance on measures of
    verbal learning plt.001

Multiple Sclerosis and Cannabis A cognitive and
psychiatric study
  • 10 subjects with MS and current cannabis users
    compared with 40 subjects with MS who did not use
  • psychiatric diagnosis higher in cannabis users
  • Slower mean performance time on SDMT (index of
    information processing speed, working memory and
    sustained attention) in the cannabis users
  • Neurology 200871164-169

Marijuana and Driving
  • Laboratory tests and driving studies show that
    cannabis may acutely impair several
    driving-related skills in a dose related fashion
  • Effects between individuals vary more than for
    alcohol because of tolerance, differences in
    smoking technique, and different absorptions of
    THC Sewell et al. Am J Addictions
  • More pronounced with highly automatic driving
    functions less with complex tasks that require
    conscious control opposite from that seen with

Effects of Marijuana Intoxication and Pilot
Performance Am J Psychiatry 19851421325-1329
  • Ten experienced licensed private pilots trained
    for 8 hours on a flight stimulator landing task
  • Each smoked a THC cigarette (19 mg)
  • 24 hours later their mean performance on the
    flight task showed trends toward impairment in
    all variables, some tasks showed significant
  • Despite the deficits, the pilots reported no
    awareness of impaired performance

Marijuana and Mental Illness
  • Study in Australia tracked 1600 girls for 7 years
    Arseneault et al. BMJ 20023251212
  • Those who used marijuana every day were 5 times
    more likely to suffer from depression and anxiety
    than non-users
  • Teenage girls who used the drug a least once a
    week were twice as likely to develop depression
    than those who did not use
  • Cannabis use increased the risk of developing
    schizophrenia symptoms specific to cannabis and
    early onset prior to age 15

Risk of Psychosis
  • Increased by 40 in people who have used cannabis
    Cohen et al. Australian New Zealand J Psychiatry
  • Dose-response effect leading to an increased risk
    of 50-200 in the most frequent users
  • Approximately 14 of psychotic outcomes in young
    people would not have occurred if cannabis had
    not been consumed

Early Cannabis use associated with psychosis
related outcomes in young adults Arch Gen Psych
  • Sibling pair analysis within a prospective birth
    cohort in Australia
  • 3801 young adults cannabis use and 3
    psychosis-related outcomes (nonaffective
    psychosis, hallucinations, and Delusional
    Inventory score)
  • Early cannabis use is associated with
    psychosis-related outcomes in young adults

Marijuana and Schizophreniadouble-edged sword
  • Low doses may improve frontal lobe functioning by
    acutely increasing blood flow to cortices
    concerned with cognition, mood and perception
    increasing availability and utilization of
  • Continued use depresses cerebral flow and high
    doses augment mesolimbic dopamine release,
    opposing therapeutic effects of antipsychotic
    drugs and exacerbating psychosis
  • It also suppresses PFC dopamine utilization
    resulting in cognitive dysfunction

Marijuana and Addiction
  • Approximately 10 of regular marijuana users
    become addicted to it
  • Compared with 15 for alcohol, 32 for nicotine
    and 26 for opiates

Pros and Cons of Marijuana
  • Not associated with death
  • Not as addicting as other drugs
  • Modest benefit demonstrated for small segment of
    the population in short term use
  • Marked negative cognitive effects
  • Very dangerous to adolescent brain development
    and occurrence of mental illness
  • Cancer risk
  • Driving impairment

Whats the going rate?
  • One joint weighs _at_ 0.9 grams with 3.56 THC
    (Abrams study)
  • 0.9 g 0.03 oz
  • ¼ oz 7.1 g
  • 1 oz 28 g
  • 1 oz 31 joints at 3 joints per day need 3 oz
    per month
  • 900/month

Case Vignette Denver Post December 2009
  • 44-year-old female, grandmother and advocate for
    medical marijuana used the drug for chronic
    back pain most of her life
  • Gave her 3-year-old grandson a peanut butter
    cookie made with cannabis butter
  • The next day she had trouble rousing the boy and
    called an ambulance
  • Police seized the jar of cannabis butter and the
    boy had the drug in his system
  • A week later the grandmother took her own life