Medical Marijuana Pros and Cons A Prescription for

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Medical Marijuana: Pros and Cons A “Prescription” for Trouble? Elizabeth ‘Libby’ Stuyt, MD University

Medical Marijuana: Pros and Cons A “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

Conflicts n The Circle Program is now funded in part by Medical Marijuana Tax

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

Cannabis n n n Complex alkaloid mixture of more than 400 compounds derived from

Cannabis n n n 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 n n n Delta-9 tetrahydrocannabinol (most psychoactive) Cannabidiol Cannabinol

Cannabinergic system n n Two main cannabis receptors CB 1–present throughout CNS n n

Cannabinergic system n n Two main cannabis receptors CB 1–present throughout CNS n n n n Hippocampus Cortex Olfactory areas Basal ganglia Cerebellum Spinal cord CB 2 – located peripherally, linked with immune system n n Spleen macrophages

History of Marijuana n n 6000 BC – Cannabis seeds used as food in

History of Marijuana n n 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

History of Marijuana n n 1378 – Emir of the Ottoman Empire makes the

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

History of Marijuana n n n Introduced to North America in 1600 s by

History of Marijuana n n n Introduced to North America in 1600 s 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 5 th Amendment privilege against selfrecrimination

History continued n 1970 – Controlled Substance Act – classified cannabis as having: n

History continued n 1970 – Controlled Substance Act – classified cannabis as having: n n n 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 – 1 st country in world to offer medical marijuana to patients

Compassionate Use – not based on any research n n n Glaucoma - #1

Compassionate Use – not based on any research n n n Glaucoma - #1 cause of blindness 1992 – American Academy of Ophthalmology’s 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

Glaucoma n n n 1999 – Institute of Medicine – although IOP can be

Glaucoma n n n 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

Indications n n Dronabinol (Marinol) and nabilone (Cesamet) indicated for chemotherapy-induced nausea and vomiting

Indications n n Dronabinol (Marinol) and nabilone (Cesamet) indicated for chemotherapy-induced nausea and vomiting Dronabinol (Marinol) approved for HIVassociated 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

Canada n Four cannabinoid products available Herbal cannabis extract, “Sativex”, delta-9 THC and cannabidiol

Canada n Four cannabinoid products available Herbal cannabis extract, “Sativex”, delta-9 THC and cannabidiol in oromucosal spray n Dronabinol synthetic delta-9 -THC, “Marinol” n Nabilone synthetic derivative of delta-9 -THC, “Cesamet” n Herbal form of cannabis – “medical marijuana” n

Research Issues n n n MJ is a Schedule I drug – a barrier

Research Issues n n n 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: n Short in length (average two weeks) n Small N (lacking power) n Retrospective in nature n Confounded by uncontrolled variables n Concomitant tobacco use n Comorbid illnesses

Studies of Effects on Pain n Lit review of cannabinoids given by any route

Studies of Effects on Pain n Lit review of cannabinoids given by any route for treatment of pain Campbell et al. BMJ 2001; 323: 1 -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. ”

Side Effects of Cannabis n n Most of our knowledge about the negative effects

Side Effects of Cannabis n n 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 2008; 17: 16691678

Side Effects n n 4779 adverse events reported in those assigned to the intervention

Side Effects n n 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 n n Double-blind, placebo controlled, crossover trial of smoked cannabis

Studies with Smoked Cannabis n n 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 2009; 34: 672 -680)

Studies of Smoked Cannabis n n Four smoking sessions per day, titrating dose (18%

Studies of Smoked Cannabis n n Four smoking sessions per day, titrating dose (18% THC) to achieve maximum tolerable dose Exclusion criteria n Current substance use disorder n Lifetime history of dependence on cannabis n Concurrent use of medication with cannabinoids n Previous psychosis with or intolerance to cannabinoids

Results n n n “significantly reduced neuropathic pain intensity compared to placebo” 46% with

Results n n n “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%, >30% reduction in pain with 3 smoking sessions/day (Abrams et al. Neurology 2007: 68: 515 -521) n “All patients were required to have prior experience smoking marijuana so they would know how to inhale and what neuropsychological effects to expect”

More Studies of Smoked Cannabis n n Ware et al. CMAJ. 2010; E 694

More Studies of Smoked Cannabis n n Ware et al. CMAJ. 2010; E 694 -E 701. n N=21 n Inclusion Criteria n Outpatients with > 3 month hx neuropathic pain n Pain caused by physical trauma or surgery n Pain intensity > 4 (0 to 10 scale) n Randomized, double-blind, placebo-controlled, fourperiod crossover design n THC concentration = 0, 2. 5%, 6% or 9. 4% n Three daily dosages x 5 days n 9 day washout period. Participants advised not to drive a vehicle or operate heavy machinery while on study drug

Ware et al. CMAJ. 2010; E 694 -E 701(cont) n n Average daily pain

Ware et al. CMAJ. 2010; E 694 -E 701(cont) n n Average daily pain intensity: n 5. 4 on 9. 4% THC cannabis n 6. 1 on Placebo(0% THC) n (p=0. 023; difference = 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

Dose-dependent effects of smoked cannabis on Capsaicininduced pain and hyperalgesia in healthy volunteers (Wallace

Dose-dependent effects of smoked cannabis on Capsaicininduced pain and hyperalgesia in healthy volunteers (Wallace et al. Anesthesiology. 2007; 107: 785 -796) n n n Randomized, double-blinded, placebocontrolled, 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 4%THC, high dose 8% THC

Results n n Capsaicin injections induced spontaneous and elicited pain in all subjects No

Results n n 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

So To Review n n n Marijuana (smoked/oral) used as a therapeutic, not recreational

So To Review n n n 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 n n

The fact that it is a botanical does not preclude scientific investigation n n n 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

DEA – Scheduling Drugs depends on: n n n Does the drug have a

DEA – Scheduling Drugs depends on: n n n Does the drug have a currently accepted medical use in the United States? What is the drug’s 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 physician’s prescription? Is the drug similar in its pharmacology to other controlled drugs?

“Rocky Mountain High” Colorado November 2000 Coloradoans passed Amendment 20 Colorado Department of Public

“Rocky Mountain High” Colorado 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.

The Flood Gates Opened n n n February 2009 n Obama administration indicated that

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

The Passage of Amendment 20 Storefront “Medical” Marijuana dispensaries sprouted like weeds!

The Passage of Amendment 20 Storefront “Medical” Marijuana dispensaries sprouted like weeds!

MMJ – A Recession Proof Industry n n n Marijuana Growers Caregivers Legal Doctors

MMJ – A Recession Proof Industry n n n Marijuana Growers Caregivers Legal Doctors making recommendations ($$$$) Grow Lights Vaporizers Pipes Edibles Advertising (Westword has gone “green”) Festivals Delivery Services

“There are more medical marijuana dispensaries in Denver than Starbucks and liquor stores combined”

“There are more medical marijuana dispensaries in Denver than Starbucks and liquor stores combined” The Denver Post

September 30, 2009 n n n 19, 691 new patient applications received 17, 356

September 30, 2009 n n n 19, 691 new patient applications received 17, 356 patients with valid ID cards 73% male, average 40, 8 minors <18 57% in the Denver/metro area 67% have designated primary care-giver Over 800 different physicians have signed for patients in Colorado June 30, 2012 n n n 184, 002 new patient applications received 99, 960 patients with Valid ID cards 68% male, average 42, 47 minors <18 56% in the Denver/metro area 54% have designated primary care-giver Over 900 different physicians have signed for patients in Colorado

Conditions (as of June 2012) Condition # of Patients Percentage Cachexia 1, 215 1%

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% 17, 286 17% 1, 708 2% Severe Pain 93, 679 94% Severe Nausea 11, 567 12% Muscle Spasms Seizures

Either our state is experiencing an epidemic of severe pain in youthful males or…….

Either our state is experiencing an epidemic of severe pain in youthful males or……. . Amendment 20 is being exploited by recreational users

Rules and Regulations n n n “Patient will be deemed to have established an

Rules and Regulations n n n “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 n n n Cachexia Severe Pain Severe Nausea Seizures Persistent Muscle

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

Lobbying for New Conditions unsuccessful so far: n n n n Asthma Atherosclerosis Crohn’s

Lobbying for New Conditions unsuccessful so far: n n n n Asthma Atherosclerosis Crohn’s Disease Diabetes Mellitus Hepatitis C Hypertension MRSA Rheumatoid Arthritis n n n Opioid Dependence PTSD Bipolar Disorder Anxiety Disorders Depression Tourette’s Disorder

Rules and Regulations n n n Patient may engage in the medical use of

Rules and Regulations n n n 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

Problems with the physicians n n In the fall of 2009 @ 900 doctors

Problems with the physicians n n In the fall of 2009 @ 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

SB 109 - 2010 n n n Defines a bona fide relationship Physician must

SB 109 - 2010 n n n 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 < 21.

Implications n n The vast majority of these patients don’t have debilitating illnesses The

Implications n n The vast majority of these patients don’t 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

Therefore Physicians Recommending Medical Marijuana n n Will need to get a thorough history

Therefore Physicians Recommending Medical Marijuana n n 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 n n n Marijuana smoke contains several of the

Marijuana use and Cancer risk n n n Marijuana smoke contains several of the same carcinogens and co-carcinogens as tobacco smoke Benzo[α]pyrene, 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 n n n Studies are small in number and are

Cancer Studies involving Marijuana n n n 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. 2008;

Cannabis use and risk of Lung Cancer Aldington et al. Eur Respir J. 2008; 31: 280 -286 n n n Case-controlled study of lung cancer in adults < 55 yrs of age in New Zealand 79 cases of lung cancer and 324 controls Risk of lung cancer increased 8% for each jointyr (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 n n Retrospective, case-controlled study, 173 proven cases of head

Head and Neck Cancers n n 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 < 55 yrs Zhang et al. Cancer Epidemiol Biomark Prev 1999; 8: 1071 -1078.

Other Cancers n In a cohort study – among non-tobacco smokers, ever-marijuana smokers had

Other Cancers n In a cohort study – among non-tobacco smokers, ever-marijuana smokers had increased risk for prostate cancer RR=3. 1, and cervical cancer - RR=1. 4 Sidney et al. Cancer Causes Control 1997; 8: 722 -728. n Another cohort study found an increased risk of malignant primary adult-onset glioma for ever-marijuana smokers – RR=1. 9 Efird et al. J Neurooncol 2004; 68: 57 -69

Metabolism of Marijuana n n Massive first pass metabolism via the oral route –

Metabolism of Marijuana n n 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 D 9 THC, average “joint” contains 0. 5 – 1. 0 g of cannabis

Routes of Administration n “Where there’s smoke, there’s harm”, “There is no future in

Routes of Administration n “Where there’s smoke, there’s harm”, “There is no future in smoking marijuana as a conventional medicine” Janet Joy Ph. D 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 n n Use of 4 joints or more per week

Marijuana and Cognitive Impairment n n 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 2006; 66: 737 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 n n Heavy marijuana use (daily for at least one

Marijuana and Cognitive Impairment n n 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 1996; 275: 521 Unknown whether this is due to residue of drug in the brain, withdrawal effects or frank neurotoxic effect of the drug

How Drugs of Abuse affect the Learning and Memory part of the Brain

How Drugs of Abuse affect the Learning and Memory part of the Brain

Natural Rewards Elevate Dopamine Levels 200 % of Basal DA Output NAc shell 150

Natural Rewards Elevate Dopamine Levels 200 % of Basal DA Output NAc shell 150 100 50 Empty Box Feeding SEX 200 150 100 15 10 5 0 0 0 60 120 Time (min) Source: Di Chiara et al. 180 Scr Bas. Female 1 Present Sample 1 2 3 4 5 6 7 8 Number Scr Female 2 Present 9 10 11 12 13 14 15 16 17 Mounts Intromissions Ejaculations Source: Fiorino and Phillips Copulation Frequency DA Concentration (% Baseline) FOOD

Accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 %

Accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 % of Basal Release AMPHETAMINE Accumbens MORPHINE Dose (mg/kg) DA DOPAC HVA 0 1 2 3 4 Time After Amphetamine 5 hr 250 NICOTINE 200 Accumbens Caudate 150 100 0 250 0 1 2 3 hr Time After Nicotine Source: Di Chiara and Imperato % of Basal Release Effects of Drugs on Dopamine Levels 0. 5 1. 0 2. 5 10 200 150 100 0 0 1 2 3 4 Time After Morphine 5 hr THC/Marijuana

Effects of Drug Use on the Hippocampus n n Drugs of abuse are potent

Effects of Drug Use on the Hippocampus n n 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

Regional Brain Abnormalities Associated with Long-term heavy Cannabis Use Arch Gen Psychiatry 2008; 65:

Regional Brain Abnormalities Associated with Long-term heavy Cannabis Use Arch Gen Psychiatry 2008; 65: 694 -701 n n 15 long term (>10 years) and heavy (>5 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) p<. 001 Significantly worse performance on measures of verbal learning p<. 001

Multiple Sclerosis and Cannabis: A cognitive and psychiatric study n n 10 subjects with

Multiple Sclerosis and Cannabis: A cognitive and psychiatric study n n 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 p=0. 04 Slower mean performance time on SDMT (index of information processing speed, working memory and sustained attention) in the cannabis users p=0. 006 Neurology 2008; 71: 164 -169

Marijuana and Driving n n n Laboratory tests and driving studies show that cannabis

Marijuana and Driving n n n Laboratory tests and driving studies show that cannabis may acutely impair several drivingrelated 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 2009; 18: 185 -193. More pronounced with highly automatic driving functions; less with complex tasks that require conscious control – opposite from that seen with alcohol

Effects of Marijuana Intoxication and Pilot Performance Am J Psychiatry 1985; 142: 1325 -1329

Effects of Marijuana Intoxication and Pilot Performance Am J Psychiatry 1985; 142: 1325 -1329 n n 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

Marijuana and Mental Illness n n Study in Australia tracked 1600 girls for 7

Marijuana and Mental Illness n n Study in Australia tracked 1600 girls for 7 years Arseneault et al. BMJ 2002; 325: 1212 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 n Increased by 40% in people who have used cannabis Cohen

Risk of Psychosis n Increased by 40% in people who have used cannabis Cohen et al. Australian New Zealand J Psychiatry 2008; 42: 357 -368. n n 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

Early Cannabis use associated with psychosis related outcomes in young adults Arch Gen Psych 2010; 67 n n n 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 Schizophrenia double-edged sword n n n Low doses may improve frontal lobe

Marijuana and Schizophrenia double-edged sword n n n 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

Spice n n n Synthetic cannabinoids AM 694 and HU 210 found in Spice

Spice n n n Synthetic cannabinoids AM 694 and HU 210 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

Rats exposed to nicotine as adolescents selfadminister more nicotine than rats exposed as adults

Rats exposed to nicotine as adolescents selfadminister more nicotine than rats exposed as adults Levin ED et al. Psychopharm 2000; 169: 141 -149

Rats First Exposed to Nicotine in Adolescence Show Greater Sensitization to Cocaine Than Rats

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 v 19. 2

Marijuana and Addiction n Approximately 10% of regular marijuana users become addicted to it

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

The number of adults with substance use disorders is trending upward and expected to

The number of adults with substance use disorders is trending upward and expected to double by the year 2020

Colorado ranks 5 th in the nation for adolescent marijuana use.

Colorado ranks 5 th in the nation for adolescent marijuana use.

Pros and Cons of Marijuana n n n Not associated with death Not as

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

What’s the going rate? n n n One joint weighs @ 0. 9 grams

What’s the going rate? n n n One joint weighs @ 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

The Hippocratic Oath n n First………. do no harm The practice of medicine is

The Hippocratic Oath n n First………. do no harm The practice of medicine is a privilege……. not a right!

Malignant versus Non-malignant n There is definitely a place for Medical Marijuana when people

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

Physician Motives n n Financial incentives and/or personal political views should not influence treatment

Physician Motives n n Financial incentives and/or personal political views should not influence treatment recommendations Conflicts of interest – ethically/legally proscribed Investment in dispensaries n “kickbacks for referrals” n

Societal Costs n Public Safety n Cognitive impairment in safety sensitive positions n Workplace

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

Societal Costs n Sending the wrong message to children? n Soda “pot” n Edibles

Societal Costs n Sending the wrong message to children? n Soda “pot” n Edibles (colorful cookies, cupcakes, candy) n “It’s organic, green, natural” n Wellness ads (promoting MJ) n Case Example: Peanut Butter “spiced” with MJ

Case Vignette Denver Post – December 2009 n n n 44 -year-old female, grandmother

Case Vignette Denver Post – December 2009 n n n 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

In the End – Prevention is Key

In the End – Prevention is Key