28/01/2021 1 Cannabis Myths and Facts

28/01/2021

Cannabis Myths and Facts

Professor Mary Cannon Department of Psychiatry RCSI University of Medicine and Health Sciences Ireland

A developmental approach to mental health

the services

Early Child & Adult Intervention Adolescent Psychiatry Psychiatry

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Early Origins of “Adult” Mental Disorder

Dunedin Multidisciplinary Health and Development Study Children born in 1972‐73 (N=1037)

Poulton R, Caspi A, Moffitt TE, Cannon M, Murray R, Harrington H‐L. (2000) Children’s self‐reported psychotic symptoms predict adult schizophreniform disorders: a 15‐year longitudinal study. Archives of General Psychiatry 57:1053‐1058 4

Childhood Disorders Adult Disorders

75% before age 18

3 5 7 9 11 13 15 18 26

Early Intervention & Prevention

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Lessons from oncology: Don’t try to cure it –just prevent it!

Wired magazine, 2007 7

MODELS OF PREVENTION

Tertiary Secondary Risk Intervention Intervention Primary (In/Out patient Prevention (Early interventions treatment of those (School based services for with disorder) interventions for psychosis) bullying).

Opportunity 1. Opportunity 2. Opportunity 3.

Age

Overview see ‐ Arango et al. (2018). Cost effectiveness ‐ see Campion & Knapp, (2018)

Prevention

Tertiary prevention

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Prevention

Secondary prevention

Prevention

Primary prevention

The first major study: Sweden, 1987 (CANNABIS AND SCHIZOPHRENIA: A longitudinal study of Swedish conscripts, Sven Andreasson et al, pg. 1483, The Lancet, Dec. 26, 1987)

Relative risk of schizophrenia, based on uses at time of conscription (~ age 18)

0 Risk of schizophrenia

Never used 1‐10 times 11‐50 times > 50 times

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Early Origins of “Adult” Mental Disorder

Dunedin Multidisciplinary Health and Development Study Children born in 1972‐73 (N=1037)

Increased Risk with early cannabis use (Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study, Louise Arseneault, Mary Cannon et al, pg. 325, BMJ, Nov. 23, 2002

Proportion of Cannabis Users who developed a psychotic disorder by age 26

Users by age 18 4.7%

Schizophreniform disorder

10.3% Users by age 15

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Authors N F-up Adjusted risk (years) O R (95% CI) Swedish Andréasson et 45,570 15 2.3 (1.0-5.3) conscript al., 1987 cohort Zammit et al., 50,053 27 3.1 (1.7-5.5) 2002

NEMESIS van Os et al., 4,848 3 2.7 (1.2-6.5) 2002

Dunedin Arseneault et 759 11 4.5 (1.1-18.2) Study al., 2002

Arseneault, Cannon, Witton and Murray, Br J Psychiatry 2004:184, 110-7

Authors N Pooled OR

Arseneault et al., 2004 M -A 2.3 (1.7-3.0)

McLeod et al., 2004 Sys -

Smit et al 2004 Sys -

Semple et al, 2005 M-A 2.9 (2.4-3.6)

Henquet et al. 2005 M-A 2.1 (1.7-2.5)

The role of Cannabis - Public Health Warnings

The National Academy of Sciences, Engineering, and Medicine, 2017:

Cannabis use is likely to increase the risk of developing schizophrenia and other psychoses; the higher the use the greater the risk.

The United States Surgeon General, 2019:

Higher doses of THC are more likely to produce anxiety, agitation, paranoia, and psychosis…

Marijuana use is also linked to risk for and early onset of psychotic disorders, such as schizophrenia.

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Potency is increasing

Incidence of First Episode Psychosis across Europe

Cambridge Amsterdam +Leiden region London

Paris + Clermont Ferrant Verona

Bologna Barcelona, Madrid +3

Palermo

Incidence of first episode psychosis across Europe

70 61.64 60 London

47.44 50 44.71 Amsterdam Paris 40

30 24.83 22.08 21.95 19.68 18.53 20 17.17 15.9 17.7 12.66 11.2 10 6.3

0 London Amsterdam Madrid Santiago Oviedo Clermont Verona Cambridge Leiden Barcelona Valencia Paris FerrandBologna Palermo

Jongsma et al. JAMA Psychiatry 2018

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What is the explanation for the low rates in Italy/Spain?

• Any of the factors we have discussed? Yes ‐ Migration

• Mediterranean Diet?

• Vitamin D?

• Families v social isolation?

• High Potency Cannabis

The effect of daily use of high-potency cannabis on the odds for psychotic was particularly visible in London and Amsterdam

*Adjusted for age, gender, ethnicity, level of Ed, employment status and other drugs (tobacco, alcohol, stimulants, Ketamine, Legal highs, Hallucinogenics).

Di Forti et al, Lancet Psych, On Line March 23 2019

Relationship between the frequency of cannabis use and the rate of psychosis

Prevalence of daily cannabis use in population controls (%) Adjusted psychosis incidence (rate per 100,000) 20 60 Adjusted psychosis incidence 50 (%)

15 (rate per 100,000) 40

10 30

20 5

in population controls controls population in 10

Prevalence of daily cannabis use daily of Prevalence r=0.8, p=0.0109 0 0 London Amsterdam Madrid Paris Palermo Cambridge Gouda Barcelona Bologna & Voorhout

Di Forti et al, Lancet Psych, On Line March 23 2019

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Population Attributable Fraction

• If nobody smoked high potency cannabis, 12% of all cases of first episode psychosis across Europe would be prevented, rising to 32% in London and 50% in Amsterdam

Incidence of schizophrenia in Camberwell, South London

Crude incidence SZ

1965‐1968 1969‐1972 1973‐1977 1977‐ 1982 1983‐1987 1988‐1992 1993‐1997 2011‐2012

Boydell J et al 2001, 2006; Quattrone D In preparation 26

Changes in Incidence of psychosis over time

1. The incidence of cannabis‐induced psychosis more than doubled in Denmark between 2006 and 2016 ‐ Hjorthøj et al, 2019

2. Cannabis was decriminalized in Portugal in 2001. From 2002 till 2015, the proportion of psychosis patients diagnosed as cannabis dependent rose from less than 1% to over 10%

Robin Murray & Wayne Hall JAMA Psychiatry. On‐line April 8th 2020

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Environmental Risk Factors for First Episode Psychosis*

• Obstetric Events (Cannon, 2002) OR 1.9 • Childhood adversity (Varese 2012) OR 2.8 • Migration (Bourque, 2011) OR 2.1 • Urbanicity (Vassos, 2012) OR 2.4 • Heavy cannabis use (Marconi 2016) OR 3.9 • Recent life events (Beards 2013) OR 3.2

* From meta‐analyses by Evangelos Vassos

Finding the balance

Substance use

Parent‐child conflict Parental Support

Childhood adversity Self‐concept

McMahon et al, Psychological Medicine (in press); Healy et al (2019) JCCP; Coughlan et al 2019 EIP 29

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Myth or Fact? Cannabis is a Medicine

Myth or Fact? Cannabis is a “medicine”

72 Systematic Reviews (Review of Reviews)

This report found inconsistent results in systematic reviews of cannabis‐based medicines compared to placebo for chronic neuropathic pain, pain management in rheumatic diseases and painful spasms in MS. The authors also concluded that cannabis was not superior to placebo in reducing cancer pain. Results from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis‐based medicines may outweigh benefits.

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Cannabidiol in Epilepsy • CBD shown to be effective in controlled clinical studies in:

• Dravet syndrome (a genetic condition also know as severe myoclonic epilepsy of infancy) • Reduces tonic-clonic, tonic, clonic and atonic seizures

• Lennox-Gastaut syndrome • Reduces drop seizures

• Other studies in other epilepsies ongoing

• No formal clinical studies of THC in epilepsy

Cannabis for Medical Use ‐ A Scientific Review

February 2017 www.hpra.ie/publications

In summary, the HPRA considers that there is some scientific evidence to support the use of cannabis or cannabinoids as a medical treatment in patients who have failed available treatments, for the following medical conditions:

• Spasticity associated with multiple sclerosis; • Intractable nausea and vomiting associated with the use of chemotherapy; • Severe, refractory (treatment‐resistant) epilepsy.

The scientific evidence is currently insufficient to recommend use in other medical conditions.

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Myth 3: Cannabis is not addictive

Side Effects of THC

Psychosis Depression Anxiety Suicidal thoughts Suicide attempts Dependence Cognitive Impairment 38

Myth: There is a public health benefit in legalizing cannabis

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Myth of Fact?

Cannabis is safe

“No‐one ever died of cannabis –right?”

Cannabis in Colorado

Key dates in Colorado

• 2000 –no medical marijuana and no commercialization • 2001–2009 ‐ medical marijuana legalized but not commercialized • 2010–2013 ‐ medical marijuana commercialization • 2014‐ date ‐ era of retail commercialization

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Cannabis related hospitalization by era of legalization

Full legalization

Commercialised Medical Cannabis

Medical Cannabis

Fatal crashes involving cannabis impaired drivers

Cannabis poisonings over time, by age‐group

Full legalization

Commercialised Medical Cannabis

Medical Cannabis

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Number of cannabis poisonings in Children aged 0‐8 yrs in Colorado

Full legalization 70

50 Commercialised Medical Cannabis 40 Medical 30 Cannabis 20

0 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17

Cannabis related ED visits

Full legalization Commercialised Medical Cannabis

Cannabis and Suicide

25 Commercialised Full legalization Medical Medical Cannabis Cannabis 20

crude rate suicide 5 % cannabis present

0 06 07 08 09 10 11 12 13 14 15 16

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Cannabis and Child Maltreatment statistics

Myth or Fact? Cannabis legalization advances social justice goals

• Eliminates the black market • More revenue for public services • Reduces racial inequity in arrests and imprisonment

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Drug overdose deaths Colorado 2000‐2019

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The “Playbook”

Inventing Conflicts of Interest: A History of Tobacco Industry Tactics Allan M. Brandt, PhD

January 2012, Vol 102, No. 1 | American Journal of Public Health Brandt

“The SAB had been hand‐picked by Hill & Knowlton, which was always on the lookout for skeptics (and, even better, skeptics who smoked).”

"Doubt is our product," Michaels quotes a cigarette executive as saying, "since it is the best means of competing with the 'body of fact' that exists in the minds of the general public. It is also the means of establishing a controversy." Michaels argues that, for decades, cigarette manufacturers knew that their product was hazardous to people's health, but hired mercenary scientists who "manufactured uncertainty by questioning every study, dissecting every method, and disputing every conclusion". In doing so the tobacco industry waged a campaign that "successfully delayed regulation and victim compensation for decades".

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Barnes, Michael P and Jennifer C Barnes. The Evidence For Medical Use. 2016. Web. 10 Nov. 2016.

Myth or Fact? We are losing the “War on Drugs”

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Smyth et al (2019) Irish Medical Journal

Abraham Lincoln ‘…public sentiment is everything. With it, nothing can fail; against it, nothing can succeed.’

Myth or Fact?

Cannabis is not a Gateway drug…

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Twin Studies show that cannabis is a gateway drug

Lynskey et al (2003) JAMA In an Australian sample of same sex twin ‐ Twin who used cannabis by age 17 had odds of other drug use that were 2‐5 times higher than the co‐twin who did not use cannabis by age 17

Myth or Fact? States / countries that legalize cannabis see reduced youth use

Teen Use Post Recreational Marijuana Legalisation

• Coley et al (2020) , Anderson et al (2019) Youth Risk Behaviour Survey. (1999‐2017) No increase in past month adolescent use post RML But did not include Oregon or Washington and of 6 states included 5 had RML in 2016 or 2017

• Cerda (2020) National Survey of Drug Use and Health (2008‐2016) Colorado, Oregon, Alaska and Washington Increase in Cannabis Use Disorder (25% increase) 12‐17 year olds post RML

“ “The study’s findings suggest that although marijuana legalization advanced social justice goals, the small post‐RML increase in risk for CUD among respondents aged 12 to 17 years and increased frequent use and CUD among adults 26 years or older in this study are a potential public health concern” The seriousness of the long‐term consequences of CUD in adolescents suggests the need for additional study…..”

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Teen Use Post Recreational Marijuana Legalisation

• Cerda (2020) National Survey of Drug Use and Health (2008‐2016) Colorado, Oregon, Alaska and Washington Increase in Cannabis Use Disorder (25% increase) 12‐17 year olds post RML

Teen Use Post Recreational Marijuana Legalisation

• Cerda (2020) National Survey of Drug Use and Health (2008‐2016) Colorado, Oregon, Alaska and Washington Increase in Cannabis Use Disorder (25% increase) 12‐17 year olds post RML

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Myth or Fact? Alcohol is more harmful to young people than cannabis

Myth: Alcohol is more harmful to young people than cannabis

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A natural experiment…

High” Achievers? Cannabis Access and Academic Performance Marie and Zolitz (2017)

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In Press, Psychological Medicine

Systematic review of 7 longitudinal studies with baseline measure of IQ in adolescence prior to cannabis use

Frequent/ Dependent cannabis use in adolescence was associated with on average a 2 point decline in IQ compared to not using cannabis

This may be driven by declines in verbal IQ

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Persistent cannabis users show neuropsychological decline from childhood to midlife Meier et al PNAS 2012

From: Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood: A Systematic Review and Meta-analysis JAMA Psychiatry. 2019;76(4):426-434. doi:10.1001/jamapsychiatry.2018.4500

Gabriella Gobbi et al

Forest Plot Showing Adjusted Odds Ratio (OR) and 95% CIs for Depression and Anxiety in Young Adulthood According to Cannabis Use in Individual Studies Date of download: 10/2/2019 Copyright 2019 American Medical Association. All Rights Reserved. 84

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Cannabis is a young person’s drug

Median age of onset of use 18‐19, half of young people who use cannabis start use as children.

Incidence of use growing in young people

Degenhardt, L., Chiu, W. T., Sampson, N., Kessler, R. C., Anthony, J. C., Angermeyer, M., ... & Karam, A. (2008). Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys. PLoS medicine, 5(7), e141.

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Warnings from US Surgeon General NO AMOUNT OF CANNABIS IS SAFE FOR THE DEVELOPING BRAIN

Jerome Adams (2019)

Professor Sir Robin Murray

Kings College London

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“[I was] addicted to weed, a massive comfort eater, I never left my house, I just watched loads of Gilmore Girls while cutting my hair at 4 o’clock in the morning and gluing it to my walls, telling myself ‘This is who I am!’ I didn’t do anything to help myself for a full year.”

On top of her extra‐curricular activities, nothing was happening when it came to music. What she did, she says, wasn’t good, because of the identity crisis she was undergoing. https://www.goldenplec.com/featured/cmat‐plec‐picks‐2021/ 91

Stormzy “If you’ve got mental health problems, stop smoking weed. It’s not good for your mental health. “I have suffered with mental health problems for the past few years. “When I used to feel depressed, I would lock myself away and smoke weed and I would just get worse and worse and worse. “It does not help your situation. It will f**k you up. It feels good for, like, 20 minutes and then after that … we all know, us weed smokers, we know how it goes.” https://www.capitalfm.com/artists/stormzy/mental‐health‐depression‐quit‐weed/ 92

Cannabis Tobacco Alcohol

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Thank you for listening.

Any questions ?