David Nutt Public Lecture Cfar Auckland2013

Welcome: Professor David Nutt, Imperial College London

Drugs without the hot air:

A proper assessment of drug harms and their relative dangers

David Nutt FMedSci

Edmond J Safra Prof of

Neuropsychopharmacology

Imperial College London

[email protected]

Hon Consultant psychiatrist CNWL

Chair Independent Scientific Committee on Drugs (ISCD)

drugscience.org.uk

[email protected]

Drugs without the hot air Auckland 2013

What killed Amy Winehouse?

1. drug overdose

2 alcohol overdose

3 both the above

Amy Winehouse's death due to acute

alcohol poisoning

Blood alcohol 450mg/%

= 5.5 x legal driving limit

Why not use this

to inform people

of the harms of

alcohol?

Despite being

in recovery

What is a drug?

And who says?

Back to the science .

The drinks industry?

What is a drug?

something a politician once used but now regrets

Jaqui Smith (Home Sec)

I smoked cannabis but didnt enjoy

David Cameron (Prime Minister)

I did things when young that I I shouldnt have we all did

etc etc

Release

What I say

a drug is

a chemical which when taken produces physiological changes

Which in relation to controlled drugs relates to

pleasurable/desirable effects in the brain

Or damaging ones..

Death from drugs?

Gavin Britton Leah Betts

alcohol poisoning water poisoning following

MDMA use

(drinking game after Exeter

University golf match)

Note in newspaper Billboards all over the UK

Drug related deaths - UK

10

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000

Tobacco Alcohol Opiates

0

200

400

600

800

1,000

1,200

1,400

Source: Smoking and drinking among adults, 2009. Office for National Statistics

Drug Misuse Declared: Findings from the 2010/11 British Crime Survey England and

Wales. Home Office

Estimates of the Prevalence of Opiate Use and/or Crack Cocaine Use, 2009/10:

Sweep 6 report. The Centre for Drug Misuse Research

Deaths for people under

age 65 from major diseases

compared with 1970 - UK

Nick Sheron Southampton

Liver disease

The inexorable rise of liver deaths

80% due to

alcohol

20% viral

Note in this period alcohol consumption

increased about 60%

14

0

500

1,000

1,500

2,000

2,500

16-24 25-34 35-44 45-54 55-64 65-74 75+Age group

Num

ber o

f dea

ths

0%

5%

10%

15%

20%

25%

30%

% o

f all de

aths

by a

ge g

roup

Wholly attributable conditions Partially attributable chronic conditions

Partially attributable acute consequences % of all deaths by age group

Figure 1. Number (% of all deaths in each age group) of male deaths attributable to alcohol consumption by

age and type of condition (2005)

0

100

200

300

400

500

600

700

800

900

1,000

16-24 25-34 35-44 45-54 55-64 65-74 75+

Age group

Num

ber o

f dea

ths

0%

2%

4%

6%

8%

10%

12%

14%

16%

% o

f all de

aths

by a

ge g

roup

Wholly attributable conditions Partially attributable chronic conditions

Partially attributable acute consequences % of all deaths by age group

Figure 2. Number (% of all deaths in each age group) of female deaths attributable to alcohol consumption by

age and type of condition (2005)

Male deaths from alcohol

http://www.nwph.net/nwpho/publications/alcoholattributablefractions.pdf

Alcohol the most common reason for death in men under 50

Alcohol is the most destructive drug to the brain

Normal

Alcohol addiction

12.20 12.20

5,49

4.39

6.66 8

The more you drink the more comorbid diseases you get cause-specific relative risk by alcohol consumption

White et al. BMJ 2002;325(7357):191

0 10 20 30 40 50 60 70 80

Alcohol (units/week)

0 10 20 30 40 50 60 70 80

Alcohol (units/week)

0 10 20 30 40 50 60 70 80

Alcohol (units/week)

0 10 20 30 40 50 60 70 80

Alcohol (units/week)

0 10 20 30 40 50 60 70 80

Alcohol (units/week)

5.0

4.0

3.0

2.0

1.0

0.0

Re

lati

ve

ris

k

5.0

4.0

3.0

2.0

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Lip, pharynx, and oral cancer

Oesophageal cancer Colon cancer Rectal cancer Ischaemic heart disease

Liver cancer Laryngeal cancer Breast cancer Essential hypertension Injuries

Ischaemic stroke Haemorrhagic stroke Cirrhosis Non-cirrhotic chronic liver disease

Chronic pancreatitis

Men and women

Men

Women

UK government

refused to act

on alcohol

because of this

minor beneficial

effect!

Wide impact of alcohol on human diseases

What about cannabis?

Rise in incidence and prevalence of cannabis use since 1970 in England and Wales (Hickman et al 2007, Addiction 102, 597-606)

Ever use

Period prevalence

Incident

Cannabis < 18

20x increase in cannabis users over last 40 years

Self-reported cannabis use and prevalence/incidence rates of schizophrenia and

psychoses in England, 1996 to 2005/06

0

5

10

15

20

25

1996

1998

2000

2001

/200

2

2002

/200

3

2003

/200

4

2004

/200

5

2005

/200

6

Annual prevalence rates ofschizophrenia and psychosesper 10,000 PYE

Annual prevalence rate ofschizophrenia per 10,000 PYE

Annual incidence rates ofschizophrenia and psychosesper 10,000 PYE

Annual incidence rates ofschizophrenia per 10,000 PYE

If anything schizophrenia is declining

Frisher et al (2009) Weissenborn and (Nutt 2011)

Self-reported cannabis use and prevalence/incidence rates of schizophrenia and

psychoses in England, 1996 to 2005/06

0

5

10

15

20

25

1996

1998

2000

2001

/200

2

2002

/200

3

2003

/200

4

2004

/200

5

2005

/200

6

Annual prevalence rates ofschizophrenia and psychosesper 10,000 PYE

Annual prevalence rate ofschizophrenia per 10,000 PYE

Annual incidence rates ofschizophrenia and psychosesper 10,000 PYE

Annual incidence rates ofschizophrenia per 10,000 PYE

If anything schizophrenia is declining

To prevent one case of schizophrenia one would

have to prevent 5000 young men from ever

smoking cannabis

ACMD 3rd cannabis report 2009

Therefore no need to reclassify from Class C

The MCDA 16 criteria of drug harm Multi Criteria Decision Analysis approach

Harm to self

Harm to others

Drugs ranked according to total harm

UK experts MCDA approach

Nutt King & Phillips Lancet Nov 2010

Alcohol

Cannabis

Tobacco

New European data 2013

ISCD European study FP7 2013 20 European countries

No correlation of UK Drugs Act

classification with MCDA results

22

0

1

2

3

4

5

0 20 40 60 80

UK

Dru

gs

Act

cla

ssif

icat

ion

ISCD results

A

C

B

U

linear r = 0.04

No correlation of UK Drugs Act

classification with ISCD results

23

0

1

2

3

4

5

0 20 40 60 80

UK

Dru

gs

Act

cla

ssif

icat

ion

ISCD results

A

C

B

U So the law is incorrect .. and therefore unjust (and ineffective)

May add to harms

And .impedes research and treatment developments

How the media distort drug knowledge

Police complicity: The Scunthorpe two (17/03/10)

Two young men found dead

Officers believe both lads had M-CAT (mephedrone) and also had access to heroin substitute methadone which they

used to bring them down from the high of mephedrone

- they had also been drinking heavily until 2am

Nick's dad wept as he urged youngsters to avoid the drug "I don't want him to be labelled a druggie because he wasn't.

He was just on a night out with friends enjoying himself, a

normal, caring, hard-working lad. (The Sun, 17/03/10)

Media clamor to get the drug banned

26

0

50

100

150

200

250

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Mephedrone becomes

available online

Source: Deaths related to drug poisoning in England and Wales, 2010,

Office for National Statistics

An unexpected benefit of mephedrone

Mephedrone

appears to have

reduced cocaine

deaths

Perverse effect of banning mephedrone

replacement with more toxic analogues

0

20

40

60

80

100

120

140

Time for Enlightenment? Many banned drugs have potential as treatments

Cannabis pain spasticity nausea weight loss insomnia

MDMA to assist trauma therapy PTSD

Psilocybin for depression, cluster headaches, OCD

LSD for terminal illnesses

Ketamine depression and pain

Mephedrone & Naphyrone for treatment of depression and addiction

Time for Enlightenment? Many banned drugs have potential as

treatments

Cannabis pain spasticity nausea weight loss insomnia

MDMA to assist trauma therapy PTSD

Psilocybin for depression, cluster headaches, OCD

LSD for terminal illnesses

Ketamine depression and pain

Mephedrone & Naphyrone for treatment of depression and addiction

The worst censorship

of research since ..

The banning of the Heliocentric

theory of the universe

1616 The papal Congregation of the Index banned all

books advocating the Copernican system of explaining

planetary motion - Not revoked until 1758

Galileo

Galilei

1564-1642 Giordano Bruno

1548-1600

Nicolaus

Copernicus

1473-1543

To read more about this Nature Reviews Neuroscience June 2013

www.nature.com/nrn/journal/vaop/ncurrent/abs/nrn3530.html

http://drugscience.org.uk/blog/2013/06/11/lets-get-war-drugs-out-our-hospitals-and-

laboratories/

Two Nobel prize winners who used LSD

Francis Crick Kary Mullis (PCR)

Double Helix Polymerase Chain Reaction

Before it was banned

No problem can be solved from the same level of consciousness that created it Albert Einstein

Clinical Interest in LSD in the

1950s and 1960s

Hundreds of psychiatrists worldwide

1000 clinical papers

40,000 patients

40 books

6 International conferences

Results were overwhelmingly positive, describing safe and effective treatments.

(Masters and Houston, 1971)

One example

LSD in alcoholism

Effect size >= all current therapies

Since the banning NO clinical trials only one neuroscience study

LSD

Mescaline

Affinity for 5-HT2A

Potency in man

Glennon et al. 1984. Human dose data from Shulgin 1978

Resurrecting psychedelic research with psilocybin All these drugs stimulate 5HT2A receptors

Psilocybin magic mushrooms Short acting if used iv = 30 min effect

PET image

[11C]Cimbi-36

5HT2A receptor

agonist

Copenhagen

5HT2A receptors most densely expressed cortex)

Note = agonist / high affinity state of the receptor as

[11C]Cimbi-36 an agonist

The 5-HT2A receptor in humans revealed by PET

Our first Psilocybin Studies

unexpected decrease in rCBF

Carhart-Harris et al. 2012. PNAS

Psilocybin attenuates activity in the brain

region that causes depression

Carhart-Harris

and Nutt PNAS 2012

fMRI BOLD image

A number of effective treatments for depression suppress mPFC activity:

SSRIs Kennedy et al. 01 CBT Goldapple et al. 04 Sleep deprivation Gillin et al. 01 ECT Bonne et al. 96 Placebo Mayberg et al. 02 Deep brain stimulation Mayberg et al. 05 Ketamine Deakin et al. 08

Clinical trial funded by MRC with Profs

Curran and Piling UCL will start this year

IF UK drug regulations can be overcome

C4: Drugs Live

The ecstasy trial Probably first ever funding of serious scientific study by TV company

MDMA research only possible through independent funding

Opportunity to demonstrate scientific process and get vital harm reduction info to public

John Snow

5% of British soldiers returning from

combat in Iraq met the criteria for

PTSD

In US soldiers the incidence of PTSD

is as high as 18%.

More returning

soldiers from Iraq

and Afghanistan

have committed

suicide from

untreated PTSD than

ever died in the

conflict out there.

PTSD

Mithoefer 2009 44

0

10

20

30

40

50

60

70

80

90

100

Placebo MDMA

% w

ith

PT

SD

MDMA-v- placebo for treatment resistant PTSD % meeting PTSD diagnosis pre/post

Mithoefer et al Journal of Psychopharmacology 2010

80% of

MDMA

treated

group go

into

remission

Mithoefer 2009 45

0

10

20

30

40

50

60

70

80

90

100

Placebo MDMA

% w

ith

PT

SD

MDMA-v- placebo for treatment resistant PTSD % meeting PTSD diagnosis pre/post

Mithoefer et al Journal of Psychopharmacology 2010

80% of

MDMA

treated

group go

into

remission

Almost almost all responders

stay well when followed up

one year later

How does MDMA

work?

Reduces brain

blood flow

particularly in sub-

cortical regions

Carhart-Harris et al

Int J of

Neuropsychopharmacology

In press

Memory

responses

MDMA v- placebo

Enhanced

positive ratings

of good and

reduced

negative ratings

of bad

memories

Carhart-Harris et al Int J of Neuropsychopharmacology In press

MDMA effects: memory and fMRI

May explain

therapeutic potential

in PTSD Carhart-Harris et al Int J of Neuropsychopharmacology

In press

How illegal status distorts reason

Jan 2011 after BBC reported our psilocybin fMRI study

study Jim Dobbin MP demanded of the Drugs Minister

why was Professor Nutt allowed to use an illegal drug in a scientific study

2012 after the MDMA program on Nov 19th another PQ

what licences were held from her Department for the drugs used in the recent Channel 4 documentary on

MDMA; what is the process for revoking such

licenses and how this process would be initiated

Sensible ways forward

Fully endorse harm reduction approaches at all levels

Improve understanding of relative harm

Take politics out of decision making independent experts decide

Accept that young people like to experiment protect from harm of all sorts at this stage - Including from criminalisation

Provide accurate and credible information

Remove penalties for possession for personal use

Gather evidence on the impact of drug classification

Introduce a class D category for new drugs

Ease the restrictive holding regulations for the study of illegal drugs encourage research e.g. on MDMA and psychedelic psychotherapy

Putting science in charge 1 MCDA on Nicotine products

Nutt et al submitted

Putting science in charge 2

A safe alcohol

A synthetic alcohol now within the scope of modern neuroscience

+ antidote

New Scientist 2006

The Scientist Jan 2011

Should have the same health benefits as snus

and ecigarettes have for cigarettes

Thanks and questions?

Read more about it

All proceeds to the

Independent

Scientific Committee

on Drugs = ISCD

www.drugscience.org.uk