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
d.nutt@imperial.ac.uk
Hon Consultant psychiatrist CNWL
Chair Independent Scientific Committee
on Drugs (ISCD)
drugscience.org.uk

profdavidnutt@twitter.com
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
N
u
m
b
e
r

o
f

d
e
a
t
h
s
0%
5%
10%
15%
20%
25%
30%
%

o
f

a
l
l
d
e
a
t
h
s

b
y

a
g
e

g
r
o
u
p
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
N
u
m
b
e
r

o
f

d
e
a
t
h
s
0%
2%
4%
6%
8%
10%
12%
14%
16%
%

o
f

a
ll
d
e
a
t
h
s

b
y

a
g
e

g
r
o
u
p
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
R
e
l
a
t
i
v
e

r
i
s
k

5.0
4.0
3.0
2.0
1.0
0.0
R
e
l
a
t
i
v
e

r
i
s
k

5.0
4.0
3.0
2.0
1.0
0.0
R
e
l
a
t
i
v
e

r
i
s
k

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
1
9
9
6
1
9
9
8
2
0
0
0
2
0
0
1
/
2
0
0
2
2
0
0
2
/
2
0
0
3
2
0
0
3
/
2
0
0
4
2
0
0
4
/
2
0
0
5
2
0
0
5
/
2
0
0
6
Annual prevalence rates of
schizophrenia and psychoses
per 10,000 PYE
Annual prevalence rate of
schizophrenia per 10,000 PYE
Annual incidence rates of
schizophrenia and psychoses
per 10,000 PYE
Annual incidence rates of
schizophrenia 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
1
9
9
6
1
9
9
8
2
0
0
0
2
0
0
1
/
2
0
0
2
2
0
0
2
/
2
0
0
3
2
0
0
3
/
2
0
0
4
2
0
0
4
/
2
0
0
5
2
0
0
5
/
2
0
0
6
Annual prevalence rates of
schizophrenia and psychoses
per 10,000 PYE
Annual prevalence rate of
schizophrenia per 10,000 PYE
Annual incidence rates of
schizophrenia and psychoses
per 10,000 PYE
Annual incidence rates of
schizophrenia 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 3
rd
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
U
K

D
r
u
g
s

A
c
t

c
l
a
s
s
i
f
i
c
a
t
i
o
n

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
U
K

D
r
u
g
s

A
c
t

c
l
a
s
s
i
f
i
c
a
t
i
o
n

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
i
t
h

P
T
S
D

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
i
t
h

P
T
S
D

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 19
th
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 J an 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