disposablepotpipes_cannabis_3
TRANSCRIPT
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Medical Marijuana: Pros Medical Marijuana: Pros and Consand Cons
A “Prescription” for Trouble?A “Prescription” for Trouble?
Elizabeth ‘Libby’ Stuyt, MDElizabeth ‘Libby’ Stuyt, MDUniversity of Colorado, Department of PsychiatryUniversity of Colorado, Department of Psychiatry
Medical Director, Circle ProgramMedical Director, Circle Program Colorado Mental Health Institute at PuebloColorado Mental Health Institute at Pueblo
2012 Colorado Behavioral Healthcare Council 2012 Colorado Behavioral Healthcare Council Annual Training Conference, Sept 28, 2012Annual Training Conference, Sept 28, 2012
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ConflictsConflicts The Circle Program is now funded in The Circle Program is now funded in
part by Medical Marijuana Tax part by Medical Marijuana Tax proceedsproceeds
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CannabisCannabis Complex alkaloid mixture of more than Complex alkaloid mixture of more than
400 compounds derived from the 400 compounds derived from the Cannabis sativa plantCannabis sativa plant
60 different compounds described with 60 different compounds described with activity on the cannabinergic systemactivity on the cannabinergic system
Most abundant cannabinoids are Most abundant cannabinoids are Delta-9 tetrahydrocannabinol (most psychoactive)Delta-9 tetrahydrocannabinol (most psychoactive) CannabidiolCannabidiol Cannabinol Cannabinol
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Cannabinergic systemCannabinergic system Two main cannabis receptorsTwo main cannabis receptors CB1–present throughout CNSCB1–present throughout CNS
HippocampusHippocampus CortexCortex Olfactory areas Olfactory areas Basal gangliaBasal ganglia CerebellumCerebellum Spinal cordSpinal cord
CB2 – located peripherally, CB2 – located peripherally, linked with immune systemlinked with immune system
SpleenSpleen macrophagesmacrophages
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History of MarijuanaHistory of Marijuana 6000 BC – Cannabis seeds used as food 6000 BC – Cannabis seeds used as food
in Chinain China 4000 BC – Textiles made of hemp in 4000 BC – Textiles made of hemp in
ChinaChina 2727 BC – first recorded medicinal use 2727 BC – first recorded medicinal use
in Chinese Pharmacopoeia in Chinese Pharmacopoeia 1400 BC to AD – trade moves product 1400 BC to AD – trade moves product
through India, Mediterranean countries, through India, Mediterranean countries, Europe – numerous medicinal uses Europe – numerous medicinal uses reported reported
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History of MarijuanaHistory of Marijuana 1378 – Emir of the Ottoman Empire 1378 – Emir of the Ottoman Empire
makes the first edict against eating makes the first edict against eating hashish or smoking cannabis – 1hashish or smoking cannabis – 1stst “War “War on Drugs”on Drugs”
1798 – Napoleon declared total 1798 – Napoleon declared total prohibition on marijuana after realizing prohibition on marijuana after realizing much of the Egyptian lower class were much of the Egyptian lower class were habitual smokershabitual smokers
1868 – Egypt – 11868 – Egypt – 1stst modern country to modern country to outlaw cannabis ingestionoutlaw cannabis ingestion
1890 – Hashish made illegal in Turkey1890 – Hashish made illegal in Turkey
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History of MarijuanaHistory of Marijuana Introduced to North America in 1600s by Introduced to North America in 1600s by
Puritans – Hemp for ropes, sails, clothing; Puritans – Hemp for ropes, sails, clothing; cannabis a common ingredient in cannabis a common ingredient in medicines, sold openly in pharmaciesmedicines, sold openly in pharmacies
1937 – Marijuana Tax Act – transfer of 1937 – Marijuana Tax Act – transfer of cannabis illegal throughout US except for cannabis illegal throughout US except for medicinal and industrial use, expensive medicinal and industrial use, expensive excise tax and detailed logs required excise tax and detailed logs required
1969 – found to be unconstitutional since 1969 – found to be unconstitutional since it violated 5it violated 5thth Amendment privilege against Amendment privilege against self-recriminationself-recrimination
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History continuedHistory continued 1970 – Controlled Substance Act – 1970 – Controlled Substance Act –
classified cannabis as having:classified cannabis as having: High abuse potentialHigh abuse potential No medical useNo medical use Not safe to use under medical supervisionNot safe to use under medical supervision
1975 – FDA establishes Compassionate 1975 – FDA establishes Compassionate Use Program for Medical Marijuana – Use Program for Medical Marijuana – Glaucoma, Multiple Sclerosis, CancerGlaucoma, Multiple Sclerosis, Cancer
1986 – Dronabinol placed into Schedule II 1986 – Dronabinol placed into Schedule II by DEAby DEA
2003 – Canada – 12003 – Canada – 1stst country in world to country in world to offer medical marijuana to patientsoffer medical marijuana to patients
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Compassionate Use – not based Compassionate Use – not based on any research on any research
Glaucoma - #1 cause of blindnessGlaucoma - #1 cause of blindness 1992 – American Academy of 1992 – American Academy of
Ophthalmology’s Committee on Drugs Ophthalmology’s Committee on Drugs – no scientific verifiable evidence that – no scientific verifiable evidence that the use of marijuana is safe and the use of marijuana is safe and effective in the treatment of glaucomaeffective in the treatment of glaucoma
1997 – NEI – no studies have 1997 – NEI – no studies have demonstrated that marijuana can demonstrated that marijuana can safely and effectively lower IOP any safely and effectively lower IOP any more than a variety of drugs on the more than a variety of drugs on the marketmarket
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GlaucomaGlaucoma 1999 – Institute of Medicine – although 1999 – Institute of Medicine – although
IOP can be reduced by using IOP can be reduced by using cannabinoids and marijuana, the effect cannabinoids and marijuana, the effect is too short lived and requires too high is too short lived and requires too high doses.doses.
There are too many side effects to There are too many side effects to recommend lifelong use in the recommend lifelong use in the treatment of glaucomatreatment of glaucoma
Would have to smoke 10-12 joints per Would have to smoke 10-12 joints per 24 hours to maintain low IOP through 24 hours to maintain low IOP through out the dayout the day
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IndicationsIndications Dronabinol (Marinol) and nabilone Dronabinol (Marinol) and nabilone
(Cesamet) indicated for chemotherapy-(Cesamet) indicated for chemotherapy-induced nausea and vomitinginduced nausea and vomiting
Dronabinol (Marinol) approved for HIV-Dronabinol (Marinol) approved for HIV-associated anorexiaassociated anorexia
Sativex (oromucosal spray) conditionally Sativex (oromucosal spray) conditionally approved for neuropathic pain in multiple approved for neuropathic pain in multiple sclerosis and cancer painsclerosis and cancer pain
Herbal smoked marijuana – found to be Herbal smoked marijuana – found to be safe and effective for HIV-associated safe and effective for HIV-associated disordersdisorders
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CanadaCanada Four cannabinoid products availableFour cannabinoid products available
Herbal cannabis extract, “Sativex”, delta-Herbal cannabis extract, “Sativex”, delta-9-THC and cannabidiol in oromucosal spray9-THC and cannabidiol in oromucosal spray
Dronabinol synthetic delta-9-THC, Dronabinol synthetic delta-9-THC, “Marinol”“Marinol”
Nabilone synthetic derivative of delta-9-Nabilone synthetic derivative of delta-9-THC, “Cesamet”THC, “Cesamet”
Herbal form of cannabis – “medical Herbal form of cannabis – “medical marijuana” marijuana”
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Research IssuesResearch Issues MJ is a Schedule I drug – a barrier to conducting prospective MJ is a Schedule I drug – a barrier to conducting prospective
RCTs, DB w/ placeboRCTs, DB w/ placebo Studies are short - two weeks average, ranging from a few Studies are short - two weeks average, ranging from a few
hours to one yearhours to one year Most studies conducted with oral TCH preps rather than Most studies conducted with oral TCH preps rather than
smoked cannabissmoked cannabis Most studies exclude anyone with a history of major Most studies exclude anyone with a history of major
psychiatric disorder other than depression and/or history of psychiatric disorder other than depression and/or history of substance abusesubstance abuse
Most studies done to date:Most studies done to date: Short in length (average two weeks)Short in length (average two weeks) Small N (lacking power)Small N (lacking power) Retrospective in natureRetrospective in nature Confounded by uncontrolled variablesConfounded by uncontrolled variables
Concomitant tobacco useConcomitant tobacco use Comorbid illnessesComorbid illnesses
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Studies of Effects on PainStudies of Effects on Pain Lit review of cannabinoids given by any route Lit review of cannabinoids given by any route
for treatment of painfor treatment of pain Campbell et al. BMJ 2001;323:1-6Campbell et al. BMJ 2001;323:1-6 9 RCTs, 222 patients, 5 trials cancer pain; 2 9 RCTs, 222 patients, 5 trials cancer pain; 2
chronic non-malignant pain; 2 post-operative chronic non-malignant pain; 2 post-operative pain; none evaluated cannabispain; none evaluated cannabis
““Cannabinoids are no more effective than Cannabinoids are no more effective than codeine in controlling pain and have codeine in controlling pain and have depressant effects on the CNS that limit their depressant effects on the CNS that limit their use. In acute postoperative pain they should use. In acute postoperative pain they should not be used. Before cannabinoids can be not be used. Before cannabinoids can be considered for treating spasticity and considered for treating spasticity and neuropathic pain, further valid randomized neuropathic pain, further valid randomized controlled studies are needed.”controlled studies are needed.”
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Side Effects of CannabisSide Effects of Cannabis Most of our knowledge about the Most of our knowledge about the
negative effects of marijuana come negative effects of marijuana come from recreational usefrom recreational use
Literature review of safety studies of Literature review of safety studies of medical cannabinoids over past 40 medical cannabinoids over past 40 years – 23 RCTs (median exposure to years – 23 RCTs (median exposure to cannabinoids 2 weeks, range 8 hrs to cannabinoids 2 weeks, range 8 hrs to 12 months) Wang et al. CMAJ 12 months) Wang et al. CMAJ 2008;17:1669-16782008;17:1669-1678
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Side EffectsSide Effects 4779 adverse events reported in 4779 adverse events reported in
those assigned to the interventionthose assigned to the intervention 96.6% were not serious96.6% were not serious 164 serious events – no different 164 serious events – no different
from controls (RR) 1.04from controls (RR) 1.04 Rate of nonserious events higher Rate of nonserious events higher
among those assigned medical among those assigned medical cannabinoids than controls (RR)1.86 cannabinoids than controls (RR)1.86 – dizziness most common event– dizziness most common event
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Studies with Smoked CannabisStudies with Smoked Cannabis Double-blind, placebo controlled, Double-blind, placebo controlled,
crossover trial of smoked cannabis for crossover trial of smoked cannabis for the short term treatment of the short term treatment of neuropathic pain associated with HIV neuropathic pain associated with HIV – five study phases over 7 weeks – – five study phases over 7 weeks – five days of active or placebo smoking five days of active or placebo smoking with washout periodswith washout periods
Participants had documented HIV, Participants had documented HIV, neuropathic pain refractory to a least neuropathic pain refractory to a least two previous analgesics, 5 or higher two previous analgesics, 5 or higher on pain scale on pain scale (Ellis et al. (Ellis et al. Neuropyschopharmacology 2009;34:672-680)Neuropyschopharmacology 2009;34:672-680)
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Studies of Smoked CannabisStudies of Smoked Cannabis Four smoking sessions per day, titrating dose Four smoking sessions per day, titrating dose
(1-8% THC) to achieve maximum tolerable (1-8% THC) to achieve maximum tolerable dosedose
Exclusion criteriaExclusion criteria Current substance use disorderCurrent substance use disorder Lifetime history of dependence on cannabisLifetime history of dependence on cannabis Concurrent use of medication with Concurrent use of medication with
cannabinoidscannabinoids Previous psychosis with or intolerance to Previous psychosis with or intolerance to
cannabinoids cannabinoids
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ResultsResults ““significantly reduced neuropathic pain significantly reduced neuropathic pain
intensity compared to placebo”intensity compared to placebo” 46% with cannabis reported a 46% with cannabis reported a ≥≥ 30% 30%
reduction in pain versus 18% with placeboreduction in pain versus 18% with placebo Another study with almost identical Another study with almost identical
outcomes – 52% vs 24%, >30% reduction outcomes – 52% vs 24%, >30% reduction in pain with 3 smoking sessions/dayin pain with 3 smoking sessions/day (Abrams et al. Neurology 2007:68:515-521)(Abrams et al. Neurology 2007:68:515-521)
““All patients were required to have prior All patients were required to have prior experience smoking marijuana so they experience smoking marijuana so they would know how to inhale and what would know how to inhale and what neuropsychological effects to expect”neuropsychological effects to expect”
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More Studies of Smoked CannabisMore Studies of Smoked Cannabis Ware et al. CMAJ. 2010;E694-E701.Ware et al. CMAJ. 2010;E694-E701.
N=21N=21 Inclusion CriteriaInclusion Criteria
Outpatients with > 3 month hx neuropathic painOutpatients with > 3 month hx neuropathic pain Pain caused by physical trauma or surgeryPain caused by physical trauma or surgery Pain intensity > 4 (0 to 10 scale)Pain intensity > 4 (0 to 10 scale)
Randomized, double-blind, placebo-controlled, Randomized, double-blind, placebo-controlled, four-period crossover design four-period crossover design
THC concentration = 0, 2.5%, 6% or 9.4% THC concentration = 0, 2.5%, 6% or 9.4% Three daily dosages x 5 daysThree daily dosages x 5 days 9 day washout period.9 day washout period.
Participants Participants advisedadvised not to drive a vehicle or operate not to drive a vehicle or operate heavy machinery while on study drugheavy machinery while on study drug
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Ware et al. CMAJ. 2010;E694-E701(cont)Ware et al. CMAJ. 2010;E694-E701(cont)
Average daily pain intensity:Average daily pain intensity: 5.4 on 9.4% THC cannabis 5.4 on 9.4% THC cannabis 6.1 on Placebo(0% THC)6.1 on Placebo(0% THC) (p=0.023;difference = 0.7, 95% CI 0.02-1.4)(p=0.023;difference = 0.7, 95% CI 0.02-1.4)
No difference observed between 2.5%, 6%, 0%No difference observed between 2.5%, 6%, 0% The reduction is modest when compared with The reduction is modest when compared with
that from other drugs for neuropathic pain that from other drugs for neuropathic pain such as gabapentin or pregabalinsuch as gabapentin or pregabalin
A “joint” with a 9.4% THC content would impair A “joint” with a 9.4% THC content would impair the majority of usthe majority of us
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Dose-dependent effects of smoked cannabis on Capsaicin-Dose-dependent effects of smoked cannabis on Capsaicin-induced pain and hyperalgesia in healthy volunteersinduced pain and hyperalgesia in healthy volunteers
(Wallace et al. Anesthesiology. 2007;107:785-796)(Wallace et al. Anesthesiology. 2007;107:785-796)
Randomized, double-blinded, placebo-Randomized, double-blinded, placebo-controlled, crossover designcontrolled, crossover design
High dose training session, 15 subjectsHigh dose training session, 15 subjects 100 mg capsaicin injected intradermally 100 mg capsaicin injected intradermally
ventral forearm – spontaneous painventral forearm – spontaneous pain Stroking and von Frey hair stimulation – Stroking and von Frey hair stimulation –
elicited painelicited pain Low dose 2% THC, medium dose Low dose 2% THC, medium dose
4%THC, high dose 8% THC4%THC, high dose 8% THC
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ResultsResults Capsaicin injections induced spontaneous Capsaicin injections induced spontaneous
and elicited pain in all subjectsand elicited pain in all subjects No difference in pain perception between No difference in pain perception between
any of the cannabis doses and placebo any of the cannabis doses and placebo during early (right arm) courseduring early (right arm) course
Low dose did not differ from placebo at any Low dose did not differ from placebo at any time pointtime point
During late course (left arm) medium dose During late course (left arm) medium dose subjects reported decreased pain subjects reported decreased pain sensation, high dose subjects reported sensation, high dose subjects reported increased perception of pain – consistent increased perception of pain – consistent with other reports that chronic delivery of with other reports that chronic delivery of cannabinoids can cause thermal cannabinoids can cause thermal hyperalgesiahyperalgesia
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So To ReviewSo To Review Marijuana (smoked/oral) used as a Marijuana (smoked/oral) used as a
therapeutic, not recreational agent, is a therapeutic, not recreational agent, is a drugdrug as defined by the FDA as defined by the FDA
All new drugs must be scientifically All new drugs must be scientifically evaluated before they may be allowed to evaluated before they may be allowed to enter the stream of interstate commerceenter the stream of interstate commerce
The drug does not have to be proven The drug does not have to be proven superior to already approved drugs, its superior to already approved drugs, its benefits must outweigh the risks when used benefits must outweigh the risks when used for the purpose for which it has been for the purpose for which it has been approvedapproved
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The fact that it is a botanical does The fact that it is a botanical does not preclude scientific investigationnot preclude scientific investigation
Digitalis purpurea – fox glove - CHFDigitalis purpurea – fox glove - CHF Papaver somniferum – opium poppyPapaver somniferum – opium poppy Atropa belladonna – nightshade -IBSAtropa belladonna – nightshade -IBS Ephedra sinica – ephedrine - Ephedra sinica – ephedrine -
hypotensionhypotension Salix alba – willow tree - ASASalix alba – willow tree - ASA Taxis brevifolia – Pacific Yew tree – Taxis brevifolia – Pacific Yew tree –
breast cancerbreast cancer
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DEA – Scheduling Drugs depends on:DEA – Scheduling Drugs depends on: Does the drug have a currently accepted Does the drug have a currently accepted
medical use in the United States?medical use in the United States? What is the drug’s safety under medical What is the drug’s safety under medical
supervision?supervision? What is its addiction liability?What is its addiction liability? Is there a potential for significant diversion Is there a potential for significant diversion
for illegal use?for illegal use? Are individuals using it on their own initiative Are individuals using it on their own initiative
or only on physician’s prescription?or only on physician’s prescription? Is the drug similar in its pharmacology to Is the drug similar in its pharmacology to
other controlled drugs?other controlled drugs?
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““Rocky Mountain High”Rocky Mountain High”ColoradoColorado
November 2000 November 2000 Coloradoans passed Amendment 20 Coloradoans passed Amendment 20 Colorado Department of Public Health and Colorado Department of Public Health and
Environment was tasked with implementing Environment was tasked with implementing and administrating the Medical Marijuana and administrating the Medical Marijuana Registry program Registry program
March 2001 March 2001 Colorado Board of Health approved rules and Colorado Board of Health approved rules and
regulations regulationsJune 2001June 2001 MMJ Registry began accepting applications for MMJ Registry began accepting applications for
Registry Identification Cards. Registry Identification Cards.
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The Flood Gates OpenedThe Flood Gates Opened February 2009 February 2009
Obama administration indicated that Medical Obama administration indicated that Medical Marijuana prosecution would have low priorityMarijuana prosecution would have low priority
October 2009 October 2009 Obama administration will not seek to arrest Obama administration will not seek to arrest
medical marijuana users and suppliers as long medical marijuana users and suppliers as long as they conform to state laws as they conform to state laws
Applications increased dramaticallyApplications increased dramatically September 2009 – 3,523 applications September 2009 – 3,523 applications
received/monthreceived/month December 2009 – 10,585 applications December 2009 – 10,585 applications
received/monthreceived/month
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Storefront “Medical” Marijuana Storefront “Medical” Marijuana dispensaries sprouted like weeds! dispensaries sprouted like weeds!
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Marijuana GrowersMarijuana Growers CaregiversCaregivers Legal Legal Doctors making recommendations ($$$$)Doctors making recommendations ($$$$) Grow LightsGrow Lights VaporizersVaporizers PipesPipes EdiblesEdibles Advertising (Westword has gone “green”)Advertising (Westword has gone “green”) FestivalsFestivals Delivery ServicesDelivery Services
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September 30, 2009 June 30, 2012 19,691 new patient 19,691 new patient
applications receivedapplications received 17,356 patients with valid 17,356 patients with valid
ID cardsID cards 73% male, average age 73% male, average age
40, 8 minors <1840, 8 minors <18 57% in the Denver/metro 57% in the Denver/metro
areaarea 67% have designated 67% have designated
primary care-giverprimary care-giver Over Over 800800 different different
physiciansphysicians have signed for have signed for patients in Coloradopatients in Colorado
184,002 new patient 184,002 new patient applications receivedapplications received
99,960 patients with Valid 99,960 patients with Valid ID cardsID cards
68% male, average age 68% male, average age 42, 47 minors <1842, 47 minors <18
56% in the Denver/metro 56% in the Denver/metro areaarea
54% have designated 54% have designated primary care-giverprimary care-giver
Over Over 900900 different different physiciansphysicians have signed for have signed for patients in Coloradopatients in Colorado
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Conditions (as of June 2012)Condition # of Patients PercentageCachexia 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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Rules and RegulationsRules and Regulations ““Patient will be deemed to have established an Patient will be deemed to have established an
affirmative defense to such allegation” affirmative defense to such allegation” (possession of marijuana) where:(possession of marijuana) where:
Patient was previously diagnosed by a Patient was previously diagnosed by a physician as having a debilitating medical physician as having a debilitating medical conditioncondition
Patient was advised by his or her physician, in Patient was advised by his or her physician, in the context of a bona fide physician-patient the context of a bona fide physician-patient relationship, that the patient might benefit from relationship, that the patient might benefit from the medical use of marijuana in connection with the medical use of marijuana in connection with a debilitating medical conditiona debilitating medical condition
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Conditions considered debilitatingConditions considered debilitating
CachexiaCachexia Severe PainSevere Pain Severe NauseaSevere Nausea SeizuresSeizures Persistent Muscle SpasmsPersistent Muscle Spasms Any other medical condition Any other medical condition
approved by the state health agencyapproved by the state health agency
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Lobbying for New ConditionsLobbying for New Conditionsunsuccessful so far:unsuccessful so far:
AsthmaAsthma AtherosclerosisAtherosclerosis Crohn’s DiseaseCrohn’s Disease Diabetes MellitusDiabetes Mellitus Hepatitis CHepatitis C Hypertension Hypertension
MRSAMRSA Rheumatoid Rheumatoid
ArthritisArthritis
Opioid DependenceOpioid Dependence PTSDPTSD Bipolar DisorderBipolar Disorder Anxiety DisordersAnxiety Disorders DepressionDepression Tourette’s DisorderTourette’s Disorder
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Rules and RegulationsRules and Regulations Patient may engage in the medical use Patient may engage in the medical use
of marijuana with no more marijuana of marijuana with no more marijuana than is medically necessary to address a than is medically necessary to address a debilitating medical conditiondebilitating medical condition
No more than 2 ounces and no more No more than 2 ounces and no more than six plants, 3 or fewer being maturethan six plants, 3 or fewer being mature
No patient shall engage in medical use No patient shall engage in medical use of marijuana in plain view of, or in a of marijuana in plain view of, or in a place open to, the general publicplace open to, the general public
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Problems with the physiciansProblems with the physicians In the fall of 2009 @ 900 doctors had In the fall of 2009 @ 900 doctors had
written approval letters (7% of written approval letters (7% of licensed MDs)licensed MDs)
15 doctors – 72% of forms15 doctors – 72% of forms 5 doctors – 50 % of forms5 doctors – 50 % of forms One doctor signed 3,500 in a two day One doctor signed 3,500 in a two day
periodperiod
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SB 109 - 2010SB 109 - 2010 Defines a bona fide relationshipDefines a bona fide relationship Physician must have an unrestricted Physician must have an unrestricted
medical and DEA licensemedical and DEA license Addresses physician conflict of interest – Addresses physician conflict of interest –
physician can not be employed by the physician can not be employed by the dispensarydispensary
Allows CMB to examine care of providersAllows CMB to examine care of providers Two physicians need to independently Two physicians need to independently
examine those < 21.examine those < 21.
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ImplicationsImplications The vast majority of these patients The vast majority of these patients
don’t have debilitating illnesses don’t have debilitating illnesses The majority of the patients are young The majority of the patients are young
males who will be exposed to the long males who will be exposed to the long term effects of cannabis exposureterm effects of cannabis exposure
Studies conducted are all short termStudies conducted are all short term Therefore their risks may be the same as Therefore their risks may be the same as
for recreational users and/or addictsfor recreational users and/or addicts
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Therefore Physicians Therefore Physicians Recommending Medical MarijuanaRecommending Medical Marijuana
Will need to get a thorough history - Will need to get a thorough history - medically, psychiatrically and substance medically, psychiatrically and substance abuse – keep a chart and have a abuse – keep a chart and have a patient/physician relationshippatient/physician relationship
Will need to attempt to decide what level of Will need to attempt to decide what level of marijuana use is most appropriatemarijuana use is most appropriate
Will need to recommend patients not drive Will need to recommend patients not drive etc. when under the influenceetc. when under the influence
Will need to follow patients closely for side Will need to follow patients closely for side effects and unintended consequenceseffects and unintended consequences
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Marijuana use and Cancer riskMarijuana use and Cancer risk Marijuana smoke contains several of Marijuana smoke contains several of
the same carcinogens and co-the same carcinogens and co-carcinogens as tobacco smokecarcinogens as tobacco smoke
Benzo[Benzo[αα]pyrene, a procarcinogenic ]pyrene, a procarcinogenic polycyclic aromatic hydrocarbon, is polycyclic aromatic hydrocarbon, is present in marijuana tar at higher present in marijuana tar at higher concentrations than in tobacco tarconcentrations than in tobacco tar
Marijuana smoking involves inhalation Marijuana smoking involves inhalation of 3 times the amount of tar as of 3 times the amount of tar as tobacco smoketobacco smoke
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Cancer Studies involving MarijuanaCancer Studies involving Marijuana
Studies are small in number and are Studies are small in number and are retrospective in natureretrospective in nature
Confounded by concomitant use of Confounded by concomitant use of tobaccotobacco
Confounded by underreporting of Confounded by underreporting of marijuana use because such use is marijuana use because such use is often illegaloften illegal
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Cannabis use and risk of Lung Cannabis use and risk of Lung Cancer Cancer Aldington et al. Eur Respir J. 2008;31:280-286Aldington et al. Eur Respir J. 2008;31:280-286
Case-controlled study of lung cancer in Case-controlled study of lung cancer in adults adults << 55yrs of age in New Zealand 55yrs of age in New Zealand
79 cases of lung cancer and 324 controls79 cases of lung cancer and 324 controls Risk of lung cancer increased 8% for each Risk of lung cancer increased 8% for each
joint-yr (1 joint/day for one year) of joint-yr (1 joint/day for one year) of cannabis smoking after adjustment for cannabis smoking after adjustment for confounding variables including tobaccoconfounding variables including tobacco
Risk increased 7% for each pack-yr tobacco Risk increased 7% for each pack-yr tobacco ““Long-term cannabis use increases risk of Long-term cannabis use increases risk of
lung cancer in young adults”lung cancer in young adults”
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Head and Neck CancersHead and Neck Cancers Retrospective, case-controlled study, Retrospective, case-controlled study,
173 proven cases of head and neck 173 proven cases of head and neck cancer and 176 controls matched with cancer and 176 controls matched with respect to age, sex, race, education, respect to age, sex, race, education, tobacco, alcohol usetobacco, alcohol use
Risk of cancer 2.6 fold greater in Risk of cancer 2.6 fold greater in cannabis users than non-userscannabis users than non-users
3-fold greater increase in those 3-fold greater increase in those << 55 yrs 55 yrs Zhang et al. Cancer Epidemiol Biomark Zhang et al. Cancer Epidemiol Biomark
Prev 1999;8:1071-1078.Prev 1999;8:1071-1078.
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Other CancersOther Cancers In a cohort study – among non-tobacco In a cohort study – among non-tobacco
smokers, ever-marijuana smokers had smokers, ever-marijuana smokers had increased risk for prostate cancer - increased risk for prostate cancer - RR=3.1, and cervical cancer - RR=1.4 RR=3.1, and cervical cancer - RR=1.4 Sidney et al. Cancer Causes Control 1997;8:722-728.Sidney et al. Cancer Causes Control 1997;8:722-728.
Another cohort study found an increased Another cohort study found an increased risk of malignant primary adult-onset risk of malignant primary adult-onset glioma for ever-marijuana smokers – glioma for ever-marijuana smokers – RR=1.9 RR=1.9 Efird et al. J Neurooncol 2004;68:57-69Efird et al. J Neurooncol 2004;68:57-69
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Metabolism of MarijuanaMetabolism of Marijuana Massive first pass metabolism via the oral Massive first pass metabolism via the oral
route – only 10-20% reaches systemic route – only 10-20% reaches systemic circulation unchanged – takes 30 – 60 circulation unchanged – takes 30 – 60 minutes to achieve an effect – key side minutes to achieve an effect – key side effect on CNS can be dysphoria rather effect on CNS can be dysphoria rather than euphoriathan euphoria
Via the lungs – onset of action within Via the lungs – onset of action within seconds – “high” experienced with serum seconds – “high” experienced with serum concentration of 3 ng/ml, produced by as concentration of 3 ng/ml, produced by as little as 2-3 mg D9THC, average “joint” little as 2-3 mg D9THC, average “joint” contains 0.5 – 1.0 g of cannabiscontains 0.5 – 1.0 g of cannabis
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Routes of AdministrationRoutes of Administration ““Where there’s smoke, there’s harm”, Where there’s smoke, there’s harm”,
“There is no future in smoking marijuana as “There is no future in smoking marijuana as a conventional medicine” Janet Joy PhDa conventional medicine” Janet Joy PhD
Until there is an alternative, for a small Until there is an alternative, for a small segment of the population – there is a segment of the population – there is a modestmodest clinical benefit of smoked marijuana clinical benefit of smoked marijuana
Sound theoretical reasons for intrathecal or Sound theoretical reasons for intrathecal or epidural cannabinoids – may produce spinal epidural cannabinoids – may produce spinal cord analgesia without effects on cerebral cord analgesia without effects on cerebral receptors that are associated with receptors that are associated with psychotropic effectspsychotropic effects
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Marijuana and Cognitive ImpairmentMarijuana and Cognitive Impairment
Use of 4 joints or more per week Use of 4 joints or more per week resulted in a decrement in mental test resulted in a decrement in mental test performance, subjects who smoked performance, subjects who smoked regularly for a decade or more did the regularly for a decade or more did the worst worst Messinis et al. Neurology 2006;66:737Messinis et al. Neurology 2006;66:737
Long-term marijuana users were Long-term marijuana users were impaired 70% of the time on a decision impaired 70% of the time on a decision making test, compared to 55% for making test, compared to 55% for short-term users and 8% for non-usersshort-term users and 8% for non-users
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Marijuana and Cognitive ImpairmentMarijuana and Cognitive Impairment
Heavy marijuana use (daily for at least Heavy marijuana use (daily for at least one month) is associated with residual one month) is associated with residual neuropsychological effects even after a neuropsychological effects even after a day of supervised abstinence from the day of supervised abstinence from the drugdrug Harrison et al. JAMA 1996;275:521 Harrison et al. JAMA 1996;275:521
Unknown whether this is due to residue Unknown whether this is due to residue of drug in the brain, withdrawal effects of drug in the brain, withdrawal effects or frank neurotoxic effect of the drugor 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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0
50
100
150
200
0 60 120 180Time (min)
% o
f Bas
al D
A O
utpu
t
NAc shell
EmptyBox Feeding
Source: Di Chiara et al.
FOOD
100
150
200
DA
Con
cent
ratio
n (%
Bas
elin
e)
MountsIntromissionsEjaculations
15
0
5
10
Copulation Frequency
SampleNumber
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
ScrScrBasFemale 1 Present
ScrFemale 2 Present
Scr
Source: Fiorino and Phillips
SEX
Natural Rewards Elevate Dopamine LevelsNatural Rewards Elevate Dopamine Levels
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0100200300400500600700800900
10001100
0 1 2 3 4 5 hrTime After Amphetamine
% o
f Bas
al R
elea
se
DADOPACHVA
Accumbens AMPHETAMINE
0
100
150
200
250
0 1 2 3 hrTime After Nicotine
% o
f Bas
al R
elea
se
AccumbensCaudate
NICOTINE
Source: Di Chiara and Imperato
Effects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine Levels
THC/Marijuana
0
100
150
200
250
0 1 2 3 4 5hrTime After Morphine
% o
f Bas
al R
elea
se
Accumbens
0.51.02.510
Dose (mg/kg)
MORPHINE
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Effects of Drug Use on the Effects of Drug Use on the HippocampusHippocampus
Drugs of abuse are potent negative Drugs of abuse are potent negative regulators of adult neurogenesis in regulators of adult neurogenesis in the hippocampusthe hippocampus
Chronic administration of opiates, Chronic administration of opiates, THC, ethanol or nicotine decreases THC, ethanol or nicotine decreases hippocampal function, decreasing hippocampal function, decreasing ability of adult brain to adapt to new ability of adult brain to adapt to new informationinformation
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Regional Brain Abnormalities Associated Regional Brain Abnormalities Associated with Long-term heavy Cannabis Usewith Long-term heavy Cannabis Use Arch Gen Arch Gen
Psychiatry 2008;65:694-701Psychiatry 2008;65:694-701 15 long term (>10 years) and heavy (>5 15 long term (>10 years) and heavy (>5
joints daily) cannabis using men compared joints daily) cannabis using men compared with 16 age matched non using controls by with 16 age matched non using controls by MRIs of brainsMRIs of brains
Cannabis users had bilaterally reduced Cannabis users had bilaterally reduced hippocampal and amygdala volumes p=.001hippocampal and amygdala volumes p=.001
Increase in positive symptoms (psychotic) Increase in positive symptoms (psychotic) p<.001p<.001
Significantly worse performance on Significantly worse performance on measures of verbal learning p<.001measures of verbal learning p<.001
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Multiple Sclerosis and Cannabis: A Multiple Sclerosis and Cannabis: A cognitive and psychiatric studycognitive and psychiatric study
10 subjects with MS and current 10 subjects with MS and current cannabis users compared with 40 cannabis users compared with 40 subjects with MS who did not use subjects with MS who did not use cannabiscannabis
psychiatric diagnosis higher in cannabis psychiatric diagnosis higher in cannabis users p=0.04users p=0.04
Slower mean performance time on SDMT Slower mean performance time on SDMT (index of information processing speed, (index of information processing speed, working memory and sustained working memory and sustained attention) in the cannabis users p=0.006attention) in the cannabis users p=0.006
Neurology 2008;71:164-169Neurology 2008;71:164-169
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Marijuana and DrivingMarijuana and Driving Laboratory tests and driving studies show that Laboratory tests and driving studies show that
cannabis may acutely impair several driving-cannabis may acutely impair several driving-related skills in a dose related fashionrelated skills in a dose related fashion
Effects between individuals vary more than Effects between individuals vary more than for alcohol because of tolerance, differences for alcohol because of tolerance, differences in smoking technique, and different in smoking technique, and different absorptions of THCabsorptions of THC Sewell et al. Am J Addictions Sewell et al. Am J Addictions 2009;18:185-193.2009;18:185-193.
More pronounced with highly automatic More pronounced with highly automatic driving functions; less with complex tasks that driving functions; less with complex tasks that require conscious control – opposite from that require conscious control – opposite from that seen with alcoholseen with alcohol
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Effects of Marijuana Intoxication and Effects of Marijuana Intoxication and Pilot PerformancePilot Performance Am J Psychiatry 1985;142:1325-1329Am J Psychiatry 1985;142:1325-1329
Ten experienced licensed private pilots Ten experienced licensed private pilots trained for 8 hours on a flight trained for 8 hours on a flight stimulator landing taskstimulator landing task
Each smoked a THC cigarette (19 mg)Each smoked a THC cigarette (19 mg) 24 hours later their mean performance 24 hours later their mean performance
on the flight task showed trends toward on the flight task showed trends toward impairment in all variables, some tasks impairment in all variables, some tasks showed significant impairmentshowed significant impairment
Despite the deficits, the pilots reported Despite the deficits, the pilots reported no awareness of impaired performanceno awareness of impaired performance
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Marijuana and Mental IllnessMarijuana and Mental Illness Study in Australia tracked 1600 girls for 7 Study in Australia tracked 1600 girls for 7
yearsyears Arseneault et al. BMJ 2002;325:1212 Arseneault et al. BMJ 2002;325:1212 Those who used marijuana every day were 5 Those who used marijuana every day were 5
times more likely to suffer from depression times more likely to suffer from depression and anxiety than non-usersand anxiety than non-users
Teenage girls who used the drug a least once Teenage girls who used the drug a least once a week were twice as likely to develop a week were twice as likely to develop depression than those who did not usedepression than those who did not use
Cannabis use increased the risk of developing Cannabis use increased the risk of developing schizophrenia symptoms – specific to schizophrenia symptoms – specific to cannabis and early onset – prior to age 15cannabis and early onset – prior to age 15
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Risk of PsychosisRisk of Psychosis Increased by 40% in people who have Increased by 40% in people who have
used cannabisused cannabis Cohen et al. Australian New Cohen et al. Australian New Zealand J Psychiatry 2008;42:357-368.Zealand J Psychiatry 2008;42:357-368.
Dose-response effect leading to an Dose-response effect leading to an increased risk of 50-200% in the most increased risk of 50-200% in the most frequent usersfrequent users
Approximately 14% of psychotic Approximately 14% of psychotic outcomes in young people would not outcomes in young people would not have occurred if cannabis had not have occurred if cannabis had not been consumedbeen consumed
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Early Cannabis use associated with Early Cannabis use associated with psychosis related outcomes in young psychosis related outcomes in young
adults adults Arch Gen Psych 2010;67Arch Gen Psych 2010;67
Sibling pair analysis within a Sibling pair analysis within a prospective birth cohort in Australiaprospective birth cohort in Australia
3801 young adults – cannabis use and 3801 young adults – cannabis use and 3 psychosis-related outcomes 3 psychosis-related outcomes (nonaffective psychosis, hallucinations, (nonaffective psychosis, hallucinations, and Delusional Inventory score)and Delusional Inventory score)
Early cannabis use is associated with Early cannabis use is associated with psychosis-related outcomes in young psychosis-related outcomes in young adultsadults
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Marijuana and SchizophreniaMarijuana and Schizophreniadouble-edged sworddouble-edged sword
Low doses may improve frontal lobe Low doses may improve frontal lobe functioning by acutely increasing blood flow to functioning by acutely increasing blood flow to cortices concerned with cognition, mood and cortices concerned with cognition, mood and perception – increasing availability and perception – increasing availability and utilization of dopamineutilization of dopamine
Continued use depresses cerebral flow and Continued use depresses cerebral flow and high doses augment mesolimbic dopamine high doses augment mesolimbic dopamine release, opposing therapeutic effects of release, opposing therapeutic effects of antipsychotic drugs and exacerbating antipsychotic drugs and exacerbating psychosis psychosis
It also suppresses PFC dopamine utilization It also suppresses PFC dopamine utilization resulting in cognitive dysfunctionresulting in cognitive dysfunction
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SpiceSpice Synthetic cannabinoids AM694 and HU210 Synthetic cannabinoids AM694 and HU210
found in Spice products are 500 to 600 times found in Spice products are 500 to 600 times more potent than the THC found in more potent than the THC found in traditional marijuanatraditional marijuana
The THC in high potency marijuana and Spice The THC in high potency marijuana and Spice products are potentially harmful to products are potentially harmful to embryonic development as early as 2 weeks embryonic development as early as 2 weeks after conceptionafter conception
Utero exposure to THC linked to Utero exposure to THC linked to anencephaly, ADHD, Depression, Aggressionanencephaly, ADHD, Depression, Aggression
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Rats exposed to nicotine as adolescents self-Rats exposed to nicotine as adolescents self-administer more nicotine than rats exposed as administer more nicotine than rats exposed as
adults adults Levin ED et al. Psychopharm 2000;169:141-149Levin ED et al. Psychopharm 2000;169:141-149
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Rats First Exposed to Nicotine in Adolescence Rats First Exposed to Nicotine in Adolescence Show Greater Sensitization to Cocaine Than Show Greater Sensitization to Cocaine Than
Rats First Exposed as AdultsRats First Exposed as Adults
Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2
*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.
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Marijuana and AddictionMarijuana and Addiction Approximately 10% of regular marijuana Approximately 10% of regular marijuana
users become addicted to itusers become addicted to it But this is old data, based on marijuana with But this is old data, based on marijuana with
less THC concentrationsless THC concentrations Some medicinal marijuana blends, ie Some medicinal marijuana blends, ie
“Connie Chung” strain contain 20 times “Connie Chung” strain contain 20 times more THC than marijuana found 40 years more THC than marijuana found 40 years agoago
Compared with 15% for alcohol, 32% for Compared with 15% for alcohol, 32% for nicotine and 26% for opiatesnicotine and 26% for opiates
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The number of adults with The number of adults with substance use disorders is substance use disorders is
trending upward and expected trending upward and expected to double by the year 2020to double by the year 2020
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Colorado ranks 5Colorado ranks 5thth in the nation in the nation for adolescent marijuana use.for adolescent marijuana use.
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Pros and Cons of MarijuanaPros and Cons of Marijuana Not associated with Not associated with
deathdeath Not as addicting as Not as addicting as
other drugsother drugs ModestModest benefit benefit
demonstrated for demonstrated for smallsmall segment of segment of the population in the population in short term useshort term use
Marked negative Marked negative cognitive effectscognitive effects
Very dangerous to Very dangerous to adolescent brain adolescent brain development and development and occurrence of occurrence of mental illnessmental illness
Cancer riskCancer risk Driving impairmentDriving impairment
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What’s the going rate?What’s the going rate? One joint weighs @ One joint weighs @
0.9 grams with 0.9 grams with 3.56% THC (Abrams 3.56% THC (Abrams study)study)
0.9 g = 0.03 oz0.9 g = 0.03 oz ¼ oz = 7.1 g¼ oz = 7.1 g 1 oz = 28 g1 oz = 28 g 1 oz = 31 joints; at 3 1 oz = 31 joints; at 3
joints per day – need joints per day – need 3 oz per month3 oz per month
$900/month$900/month
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The Hippocratic OathThe Hippocratic Oath
First……….do no harmFirst……….do no harm
The practice of medicine is a The practice of medicine is a privilegeprivilege……. not a right!……. not a right!
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Malignant versus Non-malignantMalignant versus Non-malignant There is definitely a place for Medical There is definitely a place for Medical
Marijuana when people are suffering Marijuana when people are suffering with terminal conditionswith terminal conditions Cachexia – appetite stimulantCachexia – appetite stimulant Nausea – secondary to chemotherapyNausea – secondary to chemotherapy Pain – mild improvement Pain – mild improvement
Neither opioid medications nor Neither opioid medications nor medical marijuana is the answer for medical marijuana is the answer for chronic, non-malignant painchronic, non-malignant pain
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Physician MotivesPhysician Motives Financial incentives and/or personal Financial incentives and/or personal
political views should not influence political views should not influence treatment recommendationstreatment recommendations
Conflicts of interest – ethically/legally Conflicts of interest – ethically/legally proscribedproscribed Investment in dispensariesInvestment in dispensaries ““kickbacks for referrals”kickbacks for referrals”
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Societal CostsSocietal Costs Public SafetyPublic Safety
Cognitive impairment in safety sensitive positionsCognitive impairment in safety sensitive positions Workplace accidentsWorkplace accidents Driving and AccidentsDriving and Accidents
National Transportation Safety BoardNational Transportation Safety Board Studied 182 fatal truck accidents in 1999Studied 182 fatal truck accidents in 1999 Just as many accidents were caused by drivers Just as many accidents were caused by drivers
impaired by MJ as by drivers impaired by Etohimpaired by MJ as by drivers impaired by Etoh Increased criminal activity?Increased criminal activity?
A large percentage of those arrested for crimes A large percentage of those arrested for crimes test positive for MJtest positive for MJ
Nationwide 40% of adult males tested positive for Nationwide 40% of adult males tested positive for MJ at the time of their arrestMJ at the time of their arrest
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Societal CostsSocietal Costs Sending the wrong message to children?Sending the wrong message to children?
Soda “pot”Soda “pot” Edibles (colorful cookies, cupcakes, Edibles (colorful cookies, cupcakes,
candy)candy) ““It’s organic, green, natural”It’s organic, green, natural” Wellness ads (promoting MJ)Wellness ads (promoting MJ) Case Example: Peanut Butter “spiced” Case Example: Peanut Butter “spiced”
with MJwith MJ
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Case Vignette Case Vignette Denver Post – December 2009Denver Post – December 2009
44-year-old female, grandmother and 44-year-old female, grandmother and advocate for medical marijuana – used the advocate for medical marijuana – used the drug for chronic back pain most of her lifedrug for chronic back pain most of her life
Gave her 3-year-old grandson a peanut Gave her 3-year-old grandson a peanut butter cookie made with cannabis butterbutter cookie made with cannabis butter
The next day she had trouble rousing the The next day she had trouble rousing the boy and called an ambulanceboy and called an ambulance
Police seized the jar of cannabis butter and Police seized the jar of cannabis butter and the boy had the drug in his systemthe boy had the drug in his system
A week later the grandmother took her own A week later the grandmother took her own lifelife
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In the End – Prevention is KeyIn the End – Prevention is Key