Cutting Through the Haze Magdalena Casagrande, PGY-5 Psychiatry - - PowerPoint PPT Presentation

Cutting Through the Haze

Magdalena Casagrande, PGY-5 Psychiatry Resident Island Schizophrenia Conference November 18, 2016

 Presenter: Magdalena Casagrande  Relationships with commercial interests:

 Grants / Research Supports: None  Speakers Bureau / Honoraria: None  Consulting Fees: None  Other: Employee of Vancouver Island Health Authority

 This program has received financial support from

Otsuka / Lundbeck, Janssen and Mylan in the form

• f unrestricted educational grants.

 This program has received in-kind support from

Lundbeck Inc, BMS in the form of logistical support.

 Potential for conflict(s) of interest:

 I have no actual or potential conflict of interest in

relation to this presentation

 There has been no influence from the funders on the

content of my presentation

 I will present information that is evidence-based

rather than reporting on personal clinical experiences

 I will be using generic names when discussing

medications

 New cannabis regulations in Canada

 “Health Canada today announced the Access to Cannabis for

Medical Purposes Regulations. Under the ACMPR, Canadians […] will be able to produce a limited amount of cannabis for their own medical purposes, or designate someone to produce it for them. They will also have the option of purchasing [...] cannabis from one of the 34 producers licensed by Health Canada.”

 Statement from Health Canada concerning access to cannabis for

medical purposes, August 11th 2016

 Emotionally-charged topic fueled by a myriad of political,

legal & philosophical interests & opinions

 Recognize the ubiquity of marijuana use  Review the psychobiology of cannabis  Consider the medical uses of marijuana  Explore the link between mental illness & marijuana  Have a joint discussion on the medical implications of

changing social policy

 Cannabis is the most commonly used illegal drug in

Canada

 Younger Canadians are the biggest consumers

CADUMS 2008 – 2012, CTADS 2013

McCreary Centre Society, BC Adolescent Health Survey 2013

9% of South Vancouver Island youth used marijuana the previous Saturday

>60% of South Vancouver Island youth tried marijuana for the first time at 14 years or younger

McCreary Centre Society, BC Adolescent Health Survey 2013

 Mixture of dried flowers, leaves & stems from the

common hemp plant

 Contains > 100 cannabinoids, chemically related

compounds that mimic effects of endocannabinoids

 Principal cannabinoids in marijuana

 Δ9-tetrahydrocannabinol (THC) – psychoactive

ingredient

 Cannabidiol (CBD) – virtually no psychoactive effects,

may have beneficial medical properties

National Institute on Drug Abuse, www.drugabuse.gov, updated Mar 2016

Mehmedic Z et al. J Forensic Sci 2010 National Institute on Drug Abuse, Potency Monitoring Program 2014

% THC / CBD content

 Ancient & recently discovered lipid signaling system

implicated in regulatory processes aimed at maintaining body homeostasis

 Metabolism, sleep / wake cycle, immune function,

neural development, memory, emotinal state...

 Composed of:

 Lipids called endocannabinoids - anandamide & 2-AG*  CB1 & CB2 receptors, metabolic enzymes

 There is much research interest in the role of the

endocannabinoid system in neurological, psychiatric & inflammatory diseases

Health Canada, Information for Health Care Professionals: Cannabis and the Cannabinoids, 2013 * 2-arachidonoyl-glycerol

 Physiological

 Increased HR / BP / RR, conjunctival injection,

increased appetite, dry mouth, slowed reaction time

 Psychological

 Sense of well-being, euphoria, relaxation, altered

perception of time, impaired short-term memory, anxiety, paranoia, frank psychosis

 When ingested, psychoactive effects are often delayed

 Inadvertent consumption of more THC than intended,

leading to increased risk of adverse effects like psychosis & panic

National Institute on Drug Abuse, www.drugabuse.gov, updated Mar 2016

 THC & CBD are the primary cannabinoids found in

marijuana

 The potency of marijuana has significantly increased

• ver the last few decades

 Endocannabinoids mediate a variety of bodily

functions in a manner that is not yet fully understood

 THC & CBD interact in a complex manner with the

endocannabinoid system to produce psychotropic & potentially therapeutic effects, respectively

 Since landmark court decision R. v. Parker (2000), Health

Canada has regulated access to cannabis for medical purposes

 Under MMPR* program, people were not able to grow their

• wn marijuana, relying on federally licensed producers

 Allard et al. v. Canada (Feb 2016)  ‘Allard decision’

 MMPR* regulations were deemed to violate charter rights to

reasonable access

 Today, Health Canada regulates production & distribution

• f marijuana for medical purposes through ACMPR*

 Eligible clients can now access cannabis by registering with

licensed producers, growing their own or designating someone else to grow it for them

* Marihuana for Medical Purposes Regulations Health Canada Understanding the New ACMPR Aug 2016 * Access to Cannabis for Medical Purposes Regulations

 Completed by a

physician or nurse practitioner

 No need to cite a

specific indication

 No requirement to

monitor outcome

Health Canada, www.hc-sc.gc.ca/dhp-mps/marihuana/info/med-eng.php, updated Aug 2016

 College of Physicians & Surgeons of BC (July 2015)

 ‘Physicians are advised that they should not prescribe any

substance for their patients without knowing the risks, benefits, potential complications and drug interactions associated with the use of that agent.’

 ‘Physicians may be the subject of […] liability if the use of

marijuana produces unforeseen or unidentified negative effects.’

 Outlines for whom cannabis would not be appropriate

 Under the age of 25, personal / family hx psychosis, substance use

disorder, cardiovascular / respiratory disease, pregnant  Recommends steps that physicians, who chooses to prescribe

marijuana, should abide by

 College of Family Physicians of Canada (Feb 2013)

 ‘Physicians cannot be expected to prescribe a drug

without the safeguards in place as for other medications – solid evidence supporting the effectiveness and safety of the medication, and a clear set of indications, dosing guidelines and precautions.’

 ‘The CFPC recommends the “declaration” approach in

lieu of “prescribing”. A “declaration” […] states only that the patient meets Health Canada criteria allowing access to marijuana for medical use. […] a declaration does not give doses or directions, and does not imply that the physician recommends or advises the patient to smoke or ingest marijuana.’

 8 federally licensed producers in BC, 4 of which are on

Vancouver Island

 Dried marijuana & oils are shipped directly to clients

 35 dispensaries in Victoria (all illegal)

 Dried marijuana, oils, edibles, marijuana paraphernalia  City of Victoria regulations require each dispensary to

submit a rezoning application & to obtain an annual business license fee

 Sept 2016: 82,000 Canadians registered with licensed

producers

 Registration is not condition-specific so no available

data on this

Cleverley B Times Columnist Jul 23, 2016 City of Victoria Medical Cannabis Businesses www.victoria.ca/medicalcannabis Sept 23, 2016 Health Canada news.gc.ca/web/article-en.do?nid=1127659 Sept 21, 2016

 Recent meta-analysis found:

 Moderate-quality evidence to support use of

cannabinoids for treatment of spasticity & pain related to cancer or neuropathy

 Low-quality evidence suggesting that cannabinoids were

associated with improvements in nausea & vomiting due to chemotherapy, weight gain in HIV, & sleep disorders

 Other: Epilepsy, cancer, glaucoma, neurodegenerative

diseases, arthritis, inflammatory bowel disease, ALS...

Whiting P et al. JAMA 2015 Alexander SPH et al. Prog Neuropsychopharmacol Biol Psychiatry 2016 Reddy DS et al. J Pharm Exp Ther 2016

 Prescription cannabinoids approved by Health Canada

 Nabilone – synthetic derivative of THC in pill form  Nabiximols – oral sprary containing equal proportions

• f THC & CBD

Health Canada, Information for Health Care Professionals: Cannabis and the Cannabinoids 2013

Medical Marijuana Prescription Cannabinoids Plant species Pharmaceutical product Regulated by ACMPR* Program Regulated by Health Canada Patient pays Government pays Individual has a ‘medical need’ Specific indications Recommendation by physician Standard prescribing procedures

* Access to Cannabis for Medical Purposes Regulations

 Medical marijuana has been legal in Canada since 2001;

however, there is a lack of standardized, evidence-based guidelines for prescribing & monitoring practices

 Prescription cannabinoids are regulated as pharmaceutical

agents by Health Canada while medical marijuana is regulated by the ACMPR* Program

 Research provides evidence for potential therapeutic effects

• f cannabinoids

 There are many local dispensaries in Victoria offering easy

access to a variety of illegal marijuana products

* Access to Cannabis for Medical Purposes Regulations

 Preliminary research supports further exploration of

the use of cannabinoids, in particular cannabidiol, for the following disorders:

 Post-traumatic stress disorder  Generalized anxiety disorder  Social anxiety disorder  Panic disorder  Obsessive compulsive disorder  Psychosis  Tourette’s disorder

Blessing EM et al. Neurotherapeutics 2015 Iseger TA et al. Schizophr Res 2015 Korem N et al. J Basic Clin Physiol Pharmacol 2015 Whiting P et al. JAMA 2015

 Marijuana use is associated with increased risk of:

 Depression (OR 1.17 – 1.62)  Anxiety (OR 1.06 – 1.68)  Psychosis (OR 1.4 – 2.09)

 What is less clear is the direction of causality

 Individuals with mental illness are 7x more likely to use

marijuana weekly than people without a mental illness

 Influenced by:

 Genetic vulnerability  Amount & potency of drug use  Age of first use

 Marijuana may also exacerbate course of illness in people

with schizophrenia

Moore TH et al. Lancet 2007 Kedzior KK et al. BMC Psychiatry 2014 Lev-Ran S et al. Psychol Med 2014 Lev-Ran S et al. Compr Psychiatry 2013

 Prospective 15-year study of Swedish conscripts

(N=45,570)

Andreasson S et al. Lancet 1987

5 10 15 20 25 30 1 - 10 11 - 50 > 50 Cases of schizophrenia per 1000 Cannabis consumption at conscription (# times)

 Risk of first-episode psychosis increases with use of

high-potency cannabis (skunk), but not with use of low-potency cannabis (hash)

Di Forti M et al. Lancet Psychiatry 2015

1 0.49 0.62 0.91 1.9 2.7 5.4 1 2 3 4 5 6 Never used cannabis Hash less than weekly Hash on weekends Hash daily Skunk less than weekly Skunk on weekends Skunk daily Risk of first-episode psychosis (OR)

 Endocannabinoid system

is involved in processes critical to adolescent brain development

 Synaptic pruning  White matter

development

 These processes are

susceptible to cannabis exposure, making the adolescent brain vulnerable to the effects

• f cannabis

Lubman DI et al. Pharmacol Ther 2015

1 1.2 1.4

1 - 10 11 - 50 > 50

Relative risk of receiving social assistance in the future

Cannabis exposure during adolescence (number of times)

Danielsson AK et al. Addiction 2015

0.2 0.4 0.6 0.8 1

High school completion Degree attainment Less than monthly Monthly or more Weekly or more Daily Adjusted Odds Ratio Compared with non-users

Adolescent cannabis use before age 17 & adverse outcomes at age 30

Silins E et al. Lancet 2014 Arseneault L et al. BMJ 2002

5 10

Cannabis use at age 15 Cannabis use at age 18

Risk of schizophrenia symptoms at age 26

Regression Coefficient

5 10 15 20

Suicide attempt Cannabis dependence Other drug use Adjusted Odds Ratio Compared with non-users

Age

0.0% 0.2% 0.4% 0.6% 0.8% 1.0% 1.2% 1.4% 1.6% 1.8%

5 10 15 21 25 30 35 40 45 50 55 60 65

Percentage in each age group who develop first-time dependence THC ALCOHOL TOBACCO

NIAAA, National Epidemiologic Survey on Alcohol and Related Conditions 2003

Adolescence is a critical time for preventing substance use disorders

Volkow N, Marijuana: The Highs & Lows 2015

 Adolescent Brain Cognitive Development (ABCD)

National Longitudinal Study in the United States

 10 year study of 10,000 children from age 10  20 years

to assess effects of drugs on individual brain development trajectories

National Institute on Drug Abuse, www.drugabuse.gov

 There is preliminary evidence that cannabinoids, in

particular cannabidiol, may ameliorate symptoms of various mental health disorders

 While an association between marijuana use & mental

illness exists, it is inherently difficult to prove causality

 Potency of cannabis may play an important role in the risk

for developing psychosis

 Due to ongoing neurodevelopment, the adolescent brain is

particularly vulnerable to the effects of cannabis

 Addiction is a developmental disorder, highlighting the

importance of intervening during the adolescent period to prevent the development of substance use disorders

 IPSOS poll August 2015

 65% Canadians support

decriminalization of marijuana

 British Columbians are

most in favour (74%)

IPSOS, www.ipsos-na.com, updated 2016

10 20 30 40 50 60 70 1987 1997 2004 2012 2015

 Men (72%) are more likely than women (59%) to support

decriminalization

 Those aged 18 – 34 years are most supportive of its

decriminalization (70%)

Percent

University of Michigan, Monitoring the Future Study 2014

 Substance misuse is preventable

 Youth past month marijuana use increased 20%

in 2013-14 compared to 2011-12

2 4 6 8 10 12 14 National Average Colorado Average

 The prevalence of

marijuana use in Colorado is higher, and is increasing faster, than the national average across all age groups

Percent

Youth ages 12 – 17 years Past month marijuana use

Rocky Mountain High Intensity Drug Trafficking Area, The Legalization of Marijuana in Colorado: The Impact 2016

Commercialization Legalization

Trends in past- year cannabis use among 15 – 34 year-olds pre and post legal change in Europe

European Monitoring Centre for Drugs & Drug Addiction, The State of the Drug Problem in Europe 2011

 Cannabis appears to carry significant health risks,

especially for people who use it frequently or begin to use it at an early age

Zhang MW et al. J Addict 2015 Volkow ND et al. NEJM 2014 National Institute on Drug Abuse, www.drugabuse.gov, updated Mar 2016

 Vascular &

respiratory effects

 Mixed results on

risk of lung & esophageal cancer

 Reproductive

effects

 ‘Drugged driving’ - Recent cannabis use is associated

with dose-dependent risk of motor vehicle accidents

 Risk is even higher if cannabis is combined with alcohol

 Data from Colorado, before & after marijuana

restrictions were eased, revealed an increase in cannabis-related emergency department visits:

 Increased prevalence of severe burns from attempted

THC extraction from marijuana plant

 Cannabis hyperemesis syndrome caused by ingestion of

high-THC content product

 Unintentional ingestion of edible products by young

children

United Nations Office on Drugs & Crime, World Drug Report 2015 Wang GS, JAMA Pediatric 2013 Hartman RL et al. Clin Chem 2013

 In August, CMA submitted recommendations to the

Task Force on Marijuana Legalization & Regulation:

 Minimum age for purchase & consumption = 21 years  Restricted access to cannabis until age 25 years  Set legal age for cannabis consumption nationally  Public education campaigns  Prohibit marketing & advertising of cannabis  Ban high potency cannabis with restrictions on potency

• f edibles

 Do not permit public smoking of cannabis  Discourage cannabis that is too cheap or too expensive

Canadian Medical Association, Legalization, Regulation and Restriction of Access to Marijuana Aug 29, 2016

 Cannabis use is prevalent in Canada, particularly among adolescents

 Majority of South Vancouver Island youth who tried cannabis did so by

the age of 14

 The potency of cannabis has increased dramatically, the health

implications of which are, as of yet, unclear

 Medical marijuana is legally prescribed in Canada to eligible people

under the new ACMPR* program

 There is a lack of standardized, evidence-based prescribing and

monitoring guidelines

 There is evidence that cannabinoids, in particular cannabidiol, may

positively influence the trajectory of various mental health disorders

 At the same time, there appears to be an association between

marijuana use & mental illness, although it is inherently difficult to prove causality

* Access to Cannabis for Medical Purposes Regulations

 Due to ongoing neurodevelopment, the adolescent brain appears to be

particularly vulnerable to the effects of cannabis

 Cannabis use, especially during adolescence, can lead to addiction

 Importance of intervening during the adolescent period to prevent the

development of substance use disorders

 Cannabis use can lead to to potential long-term health risks & public

health consequences

 Particularly for those who use high potency cannabis frequently or

begin using it at an early age

 Perceived risk of marijuana is declining

 Changing attitudes towards cannabis use have been variably shown to

precede changes in reported use

 Marijuana research faces many challenges & is desperately needed to

provide the public, health-care providers & policy-makers with quality, evidence-based information



Alexander SPH: Therapeutic potential of cannabis-related drugs. Prog Neuropsychopharmacol Biol Psychiatry 2016; 64:157-166.



Andreasson S et al: Cannabis and schizophrenia: A longitudinal study of Swedish conscripts. Lancet 1987; 330:1483-86.



Arseneault L et al: Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002; 325:1212-13.



Blessing EM et al: Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics 2015; 12:825-36.



Canadian Medical Association: CMA Submission: Legalization, Regulation and Restriction of Access to Marijuana Aug 29, 2016.



City of Victoria: Medical Cannabis Businesses, Sept 23, 2016. Available at: www.victoria.ca/medicalcannabis



Cleverley B: Victoria council drafting rules for marijuana shops. Times Columnist July 23, 2016. Available at: http://www.timescolonist.com/news/local/victoria-council-drafting-rules-for-marijuana-shops-1.2308687



College of Family Physicians of Canada: Statement on Health Canada’s proposed changes to medical marijuana regulations. Position Statement Feb 2013.



College of Physicians & Surgeons of BC: Professional standards and guidelines: Marijuana for medical purposes. Position Statement July 2015.



Danielsson AK et al: Cannabis use among Swedish men in adolescence and the risk of adverse life course outcomes: Results from a 20 year- follow-up study. Addiction 2015; 110:1794-1802.



Di Forti M et al: Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case- control study. Lancet Psychiatry 2015; 2:233-38.



ElSohly MA: Potency monitoring program quarterly report number 124. National Institute on Drug Abuse, 2014.



European Monitoring Centre for Drugs & Drug Addiction: The State of the Drug Problem in Europe. Annual report 2011.



Hartman RL, Huestis MA: Cannabis effects on driving skills. Clin Chem 2013; 59(3):478-92.



Health Canada: Canadian alcohol and drug use monitoring survey (CADUMS). 2008 – 2012. Available at: http://www.hc-sc.gc.ca/hc-ps/drugs- drogues/cadums-esccad-eng.php



Health Canada: Information for Health Care Professionals: Cannabis and the Cannabinoids, 2013. Available at: http://www.hc-sc.gc.ca/dhp- mps/marihuana/index-eng.php



IPSOS: Support for decriminalization of marijuana in small amounts holding steady at two in three Canadians, 2015. Available at: www.ipsos- na.com



Iseger TA et al: A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res 2015; 162:153-61.



Johnston LD et al: Key findings on adolescent drug use. Monitoring the Future Study, 2014. Available at: http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2014.pdf



Kedzior KK, Laeber LT: A positive association between anxiety disorders and cannabis use or cannabis use disorders in the general population – a meta-analysis of 31 studies. BMC Psychiatry 2014; 14:136-158.



Korem N et al: Targeting the endocannabinoid system to treat anxiety-related disorders. J Basic Clin Physiol Pharmacol 2015; doi: 10.1515/jbcpp-2015-0058.



Lev-Ran S et al: Cannabis use and cannabis use disorders among individuals with mental illness. Compr Psychiatry 2013; 54:589-98.



Lev-Ran S et al: The association between cannabis use and depression: A systematic review and meta-analysis of longitudinal studies. Psychol Med 2014; 44:797-810.



Lubman DI et al: Cannabis and adolescent brain development. Pharmacol Ther 2015; 148:1-16.



McCreary Centre Society: Results of the 2013 BC Adolescent Health Survey – South Vancouver Island. BC Adolescent Health Survey 2013.



Mehmedic Z et al: Potency trends of delta-9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci 2010; 55(5):1209-17.



Moore TH et al: Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370:319-28.



National Institute on Drug Abuse: Marijuana, 2016. Available at: http://www.drugabuse.gov/drugs-abuse/marijuana



National Institute on Alcohol Abuse and Alcoholism: National Epidemiologic Survey on Alcohol and Related Conditions, 2003.



Reddy DS, Golub V: The pharmacological basis of cannabis therapy for epilepsy. J Pharm Exp Ther 2016; doi: 10.1124/jpet.115.23015.



Rocky Mountain High Intensity Drug Trafficking Area: The Legalization of Marijuana in Colorado: The Impact, 2016. Available at: http://www.mpisdcounty.net/2016/01/13/the-legalization-of-marijuana-in-colorado-2016-the-impact/



Silins E et al: Young adult sequelae of adolescent cannabis use: an integrative analysis. Lancet 2014; 1:286-93.



Statistics Canada: Canadian tobacco, alcohol and drugs survey (CTADS). 2013. Available at: http://healthycanadians.gc.ca/science-research- sciences-recherches/data-donnees/ctads-ectad/index-eng.php



United Nations Office on Drugs & Crime: World Drug Report. UNODC Research, 2015.



Volkow ND: Marijuana: The Highs & Lows. NIH presentation, 2015.



Volkow ND et al: Adverse health effects of marijuana use. NEJM 2014; 370:2219-27.



Wang GS et al: Pediatric marijuana exposure in a medical marijuana state. JAMA Pediatrics 2013; 167(7):630-33.



Whiting P et al: Cannabinoids for medical use: A systematic review and meta-analysis. JAMA 2015; 313(24):2456-73.



Zhang MW, Ho RCM: The cannabis dilemma: A review of its associated risks and clinical efficacy. J Addict 2015; Article ID 707596.