Welcome:

Professor David Nutt, Imperial College London

Drugs without the hot air:

A proper assessment of drug harms and
their relative dangers
 Drugs without the hot air
Auckland 2013

David Nutt FMedSci

Edmond J Safra Prof of
Neuropsychopharmacology
Imperial College London
d.nutt@imperial.ac.uk
Hon Consultant psychiatrist CNWL
Chair Independent Scientific Committee
on Drugs (ISCD)
drugscience.org.uk

profdavidnutt@twitter.com
What killed Amy Winehouse?

1. drug overdose

2 alcohol overdose

3 both the above

 Amy Winehouse's death due to acute
alcohol poisoning

Despite being
in recovery

Why not use this

to inform people
of the harms of
alcohol? Blood alcohol 450mg/%
= 5.5 x legal driving limit
Back to the science .

What is a drug?

And who says?

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?
Note in newspaper Billboards all over the UK

Gavin Britton Leah Betts

alcohol poisoning water poisoning following
MDMA use
(drinking game after Exeter
University golf match)
 Drug related deaths - UK

90,000 1,400
80,000 1,200
70,000 1,000
60,000 800
50,000 600
40,000 400
30,000 200

20,000 0

10,000
0
Tobacco Alcohol Opiates

Source: Smoking and drinking among adults, 2009. Office for National Statistics
Drug Misuse Declared: Findings from the 2010/11 British Crime Survey England and 10
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
The inexorable rise of liver deaths

80% due to
alcohol Liver disease
20% viral

Deaths for people under

age 65 from major diseases
compared with 1970 - UK

Note in this period

alcohol consumption
increased about 60%

Nick Sheron Southampton

 Male deaths from alcohol

2,500 30%

25%
2,000

20%
Number of deaths

1,500

% of all deaths
by age group
15%

1,000

10%

500
5%

0 0%
16-24 25-34 35-44 45-54 55-64 65-74 75+
Age group
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)

Alcohol the most common reason for death in men under 50

1,000 16%

900
14%

http://www.nwph.net/nwpho/publications/alcoholattributablefractions.pdf
800
12%
700
 Alcohol is the most destructive drug to the brain
Normal

Alcohol addiction
12.20 12.2
Wide impact
The more you drink of
thealcohol
more comorbidon human
diseases you get diseases
cause-specific relative risk by alcohol consumption

39 UK government
Lip, pharynx, and Oesophageal cancer Colon cancer Rectal cancer Ischaemic heart
oral cancer disease
5.0 refused to act
4.0
on alcohol
Relative risk

3.0
2.0
because of this
1.0 minor beneficial
0.0
effect!
Liver cancer Laryngeal cancer Breast cancer Essential hypertension Injuries
5.0
Men and women
4.0
Relative risk

Men
3.0
Women
2.0
1.0
0.0

Ischaemic stroke Haemorrhagic stroke Cirrhosis Non-cirrhotic chronic Chronic pancreatitis

liver disease
5.0
4.0
Relative risk

3.0
2.0
1.0
0.0
0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80
49 Alcohol (units/week) Alcohol (units/week) Alcohol (units/week) Alcohol (units/week) Alcohol (units/week)
White et al. BMJ 2002;325(7357):191
8
66
What about cannabis?
20x increase in cannabis users over last 40 years

Ever use

Period prevalence
Incident

Cannabis < 18

Rise in incidence and prevalence of cannabis use since 1970 in England and Wales
(Hickman et al 2007, Addiction 102, 597-606)
If anything schizophrenia is declining
Self-reported cannabis use and prevalence/incidence rates of schizophrenia and
psychoses in England, 1996 to 2005/06
25
Annual prevalence rates of
schizophrenia and psychoses
20 per 10,000 PYE

15 Annual prevalence rate of

schizophrenia per 10,000 PYE

10

Annual incidence rates of

5 schizophrenia and psychoses
per 10,000 PYE

0
Annual incidence rates of
2

6
96

98

00

00

00

00

00

00

schizophrenia per 10,000 PYE

19

19

20

/2

/2

/2

/2

/2
01

02

03

04

05
20

20

20

20

20

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

If anything schizophrenia is declining
Self-reported cannabis use and prevalence/incidence rates of schizophrenia and
psychoses in England, 1996 to 2005/06
25 To prevent one case of schizophrenia one would
have to prevent 5000 young men from ever
Annual prevalence rates of
schizophrenia and psychoses
20 smoking cannabis per 10,000 PYE

15 Annual prevalence rate of

ACMD 3rd cannabis report 2009 schizophrenia per 10,000 PYE

10
Therefore no need to reclassify from Class C rates of
Annual incidence
5 schizophrenia and psychoses
per 10,000 PYE

0
Annual incidence rates of
2

6
96

98

00

00

00

00

00

00

schizophrenia per 10,000 PYE

19

19

20

/2

/2

/2

/2

/2
01

02

03

04

05
20

20

20

20

20
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
Alcohol

Tobacco

Cannabis

Nutt King & Phillips Lancet Nov 2010

New European data 2013

ISCD European study FP7 2013 20 European countries

 22

No correlation of UK Drugs Act

classification with MCDA results
5
UK Drugs Act classification
4U

3C linear r = 0.04

2B

1A

0
0 20 40 60 80
ISCD results
 23

No correlation of UK Drugs Act

classification with ISCD results
5

So the law is incorrect ..

UK Drugs Act classification
4U
and therefore unjust (and ineffective)
3C

May add to harms

2B

And .impedes
1A research and treatment
developments
0
0 20 40 60 80
ISCD results
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

An unexpected benefit of mephedrone
Mephedrone becomes
available online
250

Mephedrone
200
appears to have
reduced cocaine
150 deaths

100

50

0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Source: Deaths related to drug poisoning in England and Wales, 2010, 26

Office for National Statistics
 Perverse effect of banning mephedrone
replacement with more toxic analogues

140
120
100
80
60
40
20
0
 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

The worst censorship
MDMA to assist trauma therapy PTSD

of research since ..
Psilocybin for depression, cluster headaches, OCD

LSD for terminal illnesses

Ketamine depression and pain

Mephedrone & Naphyrone for treatment of depression

and addiction
 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
Giordano Bruno Nicolaus Galilei
1548-1600 Copernicus 1564-1642
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

Before it was banned

Francis Crick Kary Mullis (PCR)

Double Helix Polymerase Chain Reaction
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
Resurrecting psychedelic research with psilocybin
All these drugs stimulate 5HT2A receptors
Affinity for
5-HT2A
LSD

Psilocybin magic mushrooms

Short acting if used iv = 30 min effect

Mescaline

Potency in man

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

 The 5-HT2A receptor in humans
revealed by PET

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
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
 PTSD
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.
MDMA-v- placebo for treatment resistant
PTSD % meeting PTSD diagnosis pre/post
100

90

80

70
% with PTSD

60 80% of
MDMA
50
treated
40
group go
into
30 remission
20

10

Placebo MDMA
Mithoefer et al Journal of Psychopharmacology 2010 Mithoefer 2009 44
MDMA-v- placebo for treatment resistant
PTSD % meeting PTSD diagnosis pre/post
100

90

80

70

Almost almost all responders

% with PTSD

60 80% of
MDMA
stay well when followed uptreated
50

group go
one year later 40

30
into
remission
20

10

Placebo MDMA
Mithoefer et al Journal of Psychopharmacology 2010 Mithoefer 2009 45
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
Carhart-Harris et al Int J of Neuropsychopharmacology therapeutic potential
In press in PTSD
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