Medical Marijuana: Pros and Cons A

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Medical Marijuana Pros and ConsA Prescription
for Trouble?

• Elizabeth Libby Stuyt, MD
• University of Colorado, Department of Psychiatry
• Medical Director, Circle Program
• Colorado Mental Health Institute at Pueblo
• 2012 Colorado Behavioral Healthcare Council
• Annual Training Conference, Sept 28, 2012

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Conflicts

• The Circle Program is now funded in part by
  Medical Marijuana Tax proceeds

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Cannabis

• 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

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Cannabinergic system

• Two main cannabis receptors
• CB1present throughout CNS
• Hippocampus
• Cortex
• Olfactory areas
• Basal ganglia
• Cerebellum
• Spinal cord
• CB2 located peripherally,
• linked with immune system
• Spleen
• macrophages

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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
  Pharmacopoeia
• 1400 BC to AD trade moves product through
  India, Mediterranean countries, Europe numerous
  medicinal uses reported

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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

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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
  pharmacies
• 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
  self-recrimination

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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

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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

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Glaucoma

• 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

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Indications

• Dronabinol (Marinol) and nabilone (Cesamet)
  indicated for chemotherapy-induced nausea and
  vomiting
• Dronabinol (Marinol) approved for HIV-associated
  anorexia
• 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

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Canada

• 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,
  Cesamet
• Herbal form of cannabis medical marijuana

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Research Issues

• MJ is a Schedule I drug a barrier to conducting
  prospective RCTs, DB w/ placebo
• Studies are short - two weeks average, ranging
  from a few hours to one year
• Most studies conducted with oral TCH preps rather
  than smoked cannabis
• Most studies exclude anyone with a history of
  major psychiatric disorder other than depression
  and/or history of substance abuse
• Most studies done to date
• Short in length (average two weeks)
• Small N (lacking power)
• Retrospective in nature
• Confounded by uncontrolled variables
• Concomitant tobacco use
• Comorbid illnesses

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Studies of Effects on Pain

• Lit review of cannabinoids given by any route for
  treatment of pain Campbell et al. BMJ
  20013231-6
• 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.

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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

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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

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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)

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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
  cannabinoids

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Results

• 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
  200768515-521)
• All patients were required to have prior
  experience smoking marijuana so they would know
  how to inhale and what neuropsychological effects
  to expect

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More Studies of Smoked Cannabis

• Ware et al. CMAJ. 2010E694-E701.
• N21
• Inclusion Criteria
• Outpatients with gt 3 month hx neuropathic pain
• Pain caused by physical trauma or surgery
• Pain intensity gt 4 (0 to 10 scale)
• Randomized, double-blind, placebo-controlled,
  four-period crossover design
• THC concentration 0, 2.5, 6 or 9.4
• Three daily dosages x 5 days
• 9 day washout period.
• Participants advised not to drive a vehicle or
  operate heavy machinery while on study drug

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Ware et al. CMAJ. 2010E694-E701(cont)

• Average daily pain intensity
• 5.4 on 9.4 THC cannabis
• 6.1 on Placebo(0 THC)
• (p0.023difference 0.7, 95 CI 0.02-1.4)
• No difference observed between 2.5, 6, 0
• The reduction is modest when compared with that
  from other drugs for neuropathic pain such as
  gabapentin or pregabalin
• A joint with a 9.4 THC content would impair
  the majority of us

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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
  pain
• Low dose 2 THC, medium dose 4THC, high dose 8
  THC

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Results

• 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
  point
• 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
  hyperalgesia

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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

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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
  cancer

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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
  supervision?
• 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?

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Rocky Mountain HighColorado

• November 2000
• Coloradoans passed Amendment 20
• 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 rules and
  regulations
• June 2001
• MMJ Registry began accepting applications
  for Registry Identification Cards.

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The Flood Gates Opened

• February 2009
• Obama administration indicated that Medical
  Marijuana prosecution would have low priority
• October 2009
• Obama administration will not seek to arrest
  medical marijuana users and suppliers as long as
  they conform to state laws
• Applications increased dramatically
• September 2009 3,523 applications
  received/month
• December 2009 10,585 applications received/month

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The Passage of Amendment 20

• Storefront Medical Marijuana dispensaries
  sprouted like weeds!

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MMJ A Recession Proof Industry

• Marijuana Growers
• Caregivers
• Legal
• Doctors making recommendations ()
• Grow Lights
• Vaporizers
• Pipes
• Edibles
• Advertising (Westword has gone green)
• Festivals
• Delivery Services

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There are more medical marijuana dispensaries in
Denver than Starbucks and liquor stores
combinedThe Denver Post
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September 30, 2009 June 30, 2012

• 19,691 new patient applications received
• 17,356 patients with valid ID cards
• 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

• 184,002 new patient applications received
• 99,960 patients with Valid ID cards
• 68 male, average age 42, 47 minors lt18
• 56 in the Denver/metro area
• 54 have designated primary care-giver
• Over 900 different physicians have signed for
  patients in Colorado

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Conditions (as of June 2012)
Condition of Patients Percentage
Cachexia 1,215 1
Cancer 2,583 3
Glaucoma 1,021 1
HIV/AIDS 632 1
Muscle Spasms 17,286 17
Seizures 1,708 2
Severe Pain 93,679 94
Severe Nausea 11,567 12
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Either our state is experiencing an epidemic of
severe pain in youthful males or..Amendment
20 is being exploited by recreational users
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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

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Conditions considered debilitating

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

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Lobbying for New Conditionsunsuccessful so far

• Opioid Dependence
• PTSD
• Bipolar Disorder
• Anxiety Disorders
• Depression
• Tourettes Disorder

• Asthma
• Atherosclerosis
• Crohns Disease
• Diabetes Mellitus
• Hepatitis C
• Hypertension
• MRSA
• Rheumatoid Arthritis

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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

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Problems with the physicians

• In the fall of 2009 _at_ 900 doctors had written
  approval letters (7 of licensed MDs)
• 15 doctors 72 of forms
• 5 doctors 50 of forms
• One doctor signed 3,500 in a two day period

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SB 109 - 2010

• Defines a bona fide relationship
• Physician must have an unrestricted medical and
  DEA license
• Addresses physician conflict of interest
  physician can not be employed by the dispensary
• Allows CMB to examine care of providers
• Two physicians need to independently examine
  those lt 21.

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Implications

• The vast majority of these patients dont have
  debilitating illnesses
• The majority of the patients are young males who
  will be exposed to the long term effects of
  cannabis exposure
• Studies conducted are all short term
• Therefore their risks may be the same as for
  recreational users and/or addicts

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Therefore Physicians Recommending Medical
Marijuana

• 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

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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

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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

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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

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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
  199981071-1078.

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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
  19978722-728.
• 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

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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

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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

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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

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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

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How Drugs of Abuse affect the Learning and Memory
part of the Brain
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Natural Rewards Elevate Dopamine Levels
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Effects of Drugs on Dopamine Levels
Source Di Chiara and Imperato
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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

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Regional Brain Abnormalities Associated with
Long-term heavy Cannabis Use Arch Gen Psychiatry
200865694-701

• 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

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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
  cannabis
• psychiatric diagnosis higher in cannabis users
  p0.04
• Slower mean performance time on SDMT (index of
  information processing speed, working memory and
  sustained attention) in the cannabis users
  p0.006
• Neurology 200871164-169

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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
  200918185-193.
• More pronounced with highly automatic driving
  functions less with complex tasks that require
  conscious control opposite from that seen with
  alcohol

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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
  impairment
• Despite the deficits, the pilots reported no
  awareness of impaired performance

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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

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Risk of Psychosis

• Increased by 40 in people who have used cannabis
  Cohen et al. Australian New Zealand J Psychiatry
  200842357-368.
• 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

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Early Cannabis use associated with psychosis
related outcomes in young adults Arch Gen Psych
201067

• 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

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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
  dopamine
• 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

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Spice

• Synthetic cannabinoids AM694 and HU210 found in
  Spice products are 500 to 600 times more potent
  than the THC found in traditional marijuana
• The THC in high potency marijuana and Spice
  products are potentially harmful to embryonic
  development as early as 2 weeks after conception
• Utero exposure to THC linked to anencephaly,
  ADHD, Depression, Aggression

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Rats exposed to nicotine as adolescents
self-administer more nicotine than rats exposed
as adults Levin ED et al. Psychopharm
2000169141-149
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Rats First Exposed to Nicotine in Adolescence
Show Greater Sensitization to Cocaine Than Rats
First Exposed as Adults
Activity level after cocaine administration was
measured by counting the number of times in 10
minutes each rat crossed light beams projected in
a grid across its cage.
Sources Collins et al, 2004, Levin et al, 2003,
NIDA Notes v19.2
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Marijuana and Addiction

• Approximately 10 of regular marijuana users
  become addicted to it
• But this is old data, based on marijuana with
  less THC concentrations
• Some medicinal marijuana blends, ie Connie
  Chung strain contain 20 times more THC than
  marijuana found 40 years ago
• Compared with 15 for alcohol, 32 for nicotine
  and 26 for opiates

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The number of adults with substance use disorders
is trending upward and expected to double by the
year 2020
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Colorado ranks 5th in the nation for adolescent
marijuana use.
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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

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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

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The Hippocratic Oath

• First.do no harm
• The practice of medicine is a privilege. not a
  right!

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Malignant versus Non-malignant

• There is definitely a place for Medical Marijuana
  when people are suffering with terminal
  conditions
• Cachexia appetite stimulant
• Nausea secondary to chemotherapy
• Pain mild improvement
• Neither opioid medications nor medical marijuana
  is the answer for chronic, non-malignant pain

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Physician Motives

• Financial incentives and/or personal political
  views should not influence treatment
  recommendations
• Conflicts of interest ethically/legally
  proscribed
• Investment in dispensaries
• kickbacks for referrals

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Societal Costs

• Public Safety
• Cognitive impairment in safety sensitive
  positions
• Workplace accidents
• Driving and Accidents
• National Transportation Safety Board
• Studied 182 fatal truck accidents in 1999
• Just as many accidents were caused by drivers
  impaired by MJ as by drivers impaired by Etoh
• Increased criminal activity?
• A large percentage of those arrested for crimes
  test positive for MJ
• Nationwide 40 of adult males tested positive for
  MJ at the time of their arrest

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Societal Costs

• Sending the wrong message to children?
• Soda pot
• Edibles (colorful cookies, cupcakes, candy)
• Its organic, green, natural
• Wellness ads (promoting MJ)
• Case Example Peanut Butter spiced with MJ

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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

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In the End Prevention is Key