Health Policy

Development of a rational scale to assess the harm of drugsof potential misuse
David Nutt, Leslie A King, William Saulsbury, Colin Blakemore

Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classiﬁcation systems that
purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classiﬁcation
systems are generally neither speciﬁed nor transparent, which reduces conﬁdence in their accuracy and undermines
health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, withan expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included
ﬁve legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classiﬁed(ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harmwhen used by two separate groups of experts. The ranking of drugs produced by our assessment of harm diﬀered fromthose used by current regulatory systems. Our methodology oﬀers a systematic framework and process that could be
used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.

Introduction
Drug misuse is one of the major social, legal, andpublic-health challenges in the modern world. In the UK,
the total burden of drug misuse, in terms of health,social, and crime-related costs, has been estimated to be
between £10 billion and £16 billion per year,1 with theglobal burden being proportionately enormous.2,3Current approaches to counter drug misuse areinterdiction of supply (via policing and customs control),education, and treatment. All three demand clarity interms of the relative risks and harms that drugs engender.
At present, in the UK, attitudes to policing and thepunishments for possession and supply of drugs are
scaled according to their classiﬁcation under the Misuse
of Drugs Act of 1971,4 while education and health-careprovision are nominally tailored to the known actions
and harms of speciﬁc drugs. Most other countries andinternational agencies—eg, the UN and WHO—havedrug classiﬁcation systems that purport to be structured
according to the relative risks and dangers of illicit drugs.
However, the process by which harms are determined isoften undisclosed, and when made public can be
ill-deﬁned, opaque, and seemingly arbitrary. In part, thislack of clarity is due to the great range and complexity offactors that have to be taken into account in estimation ofharm and the fact that scientiﬁc evidence is not only
limited in many of the relevant areas but also evolves
progressively and in unpredictable ways.
These qualiﬁcations apply to the evidence base of thecurrent UK Misuse of Drugs Act, in which drugs aresegregated into three classes—A, B, and C—that are
intended to indicate the dangers of each drug, class A
being the most harmful and class C the least. The
classiﬁcation of a drug has several consequences, inparticular determining the legal penalties for importation,
supply, and possession, as well as the degree of police
eﬀort targeted at restricting its use. The current
classiﬁcation system has evolved in an unsystematic way
from somewhat arbitrary foundations with seemingly
little scientiﬁc basis.
www.thelancet.com Vol 369 March 24, 2007

Here, we suggest a new system for assessing thepotential harms of individual drugs on the basis of fact
and scientiﬁc knowledge. This system is able to respondto evolving evidence about the potential harm of current
drugs and to rank the threat presented by any new street
drug.

Lancet 2007; 369: 1047–53
See Comment page 972
Psychopharmacology Unit,
University of Bristol, Bristol,
UK (Prof D Nutt FMedSci);
Forensic Science Service,
London, UK (L A King PhD);
Police Foundation, London(W Saulsbury MA); Medical
Research Council, London(Prof C Blakemore FRS); andDepartment of Physiology,
Anatomy and Genetics, Oxford,
UK (Prof C Blakemore)
Correspondence to:Prof David Nutt,
Psychopharmacology Unit,
University of Bristol, Bristol
BS1 3NY, UK
david.j.nutt@bristol.ac.uk

Categories of harm
There are three main factors that together determine theharm associated with any drug of potential abuse: thephysical harm to the individual user caused by the drug;
the tendency of the drug to induce dependence; and theeﬀect of drug use on families, communities, andsociety.5–8

PhysicalAssessment of the propensity of a drug to cause physicalharm—ie, damage to organs or systems—involves asystematic consideration of the safety margin of the
drug in terms of its acute toxicity, as well as its likelihood
to produce health problems in the long term. The eﬀectof a drug on physiological functions—eg, respiratory
and cardiac—is a major determinant of physical harm.
The route of administration is also relevant to theassessment of harm. Drugs that can be taken
intravenously—eg, heroin—carry a high risk of causingsudden death from respiratory depression, and therefore
score highly on any metric of acute harm. Tobacco andalcohol have a high propensity to cause illness and death
as a result of chronic use. Recently published evidenceshows that long-term cigarette smoking reduces life
expectancy, on average, by 10 years.9 Tobacco and alcohol
together account for about 90% of all drug-related deathsin the UK.
The UK Medicines and Healthcare Regulatory
Authority, in common with similar bodies in Europe, theUSA, and elsewhere, has well-established methods toassess the safety of medicinal drugs, which can be usedas the basis of this element of risk appraisal. Indeed
several drugs of abuse have licensed indications in
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Health Policy

medicine and will therefore have had such appraisals,
albeit, in most cases, many years ago.
Three separate facets of physical harm can be identiﬁed.
First, acute physical harm—ie, the immediate eﬀects (eg,
respiratory depression with opioids, acute cardiac crises
with cocaine, and fatal poisonings). The acute toxicity ofdrugs is often measured by assessing the ratio of lethal
dose to usual or therapeutic dose. Such data are available
for many of the drugs we assess here.5–7 Second, chronic
physical harm—ie, the health consequences of repeateduse (eg, psychosis with stimulants, possible lung disease
with cannabis). Finally, there are speciﬁc problems
associated with intravenous drug use.
The route of administration is relevant not only to acutetoxicity but also to so-called secondary harms. For
instance, administration of drugs by the intravenous
route can lead to the spread of blood-borne viruses suchas hepatitis viruses and HIV, which have huge health
implications for the individual and society. The potential
for intravenous use is currently taken into account in the
Misuse of Drugs Act classiﬁcation and was treated as aseparate parameter in our exercise.

DependenceThis dimension of harm involves interdependent
elements—the pleasurable eﬀects of the drug and its
propensity to produce dependent behaviour. Highly
pleasurable drugs such as opioids and cocaine arecommonly abused, and the street value of drugs is
generally determined by their pleasurable potential.
Drug-induced pleasure has two components—the initial,
rapid eﬀect (colloquially known as the rush) and theeuphoria that follows this, often extending over several
hours (the high). The faster the drug enters the brain thestronger the rush, which is why there is a drive toformulate street drugs in ways that allow them to be
injected intravenously or smoked: in both cases, eﬀects
on the brain can occur within 30 seconds. Heroin, crack
cocaine, tobacco (nicotine), and cannabis (tetrahydrocannabinol) are all taken by one or other of these rapid
routes. Absorption through the nasal mucosa, as withpowdered cocaine, is also surprisingly rapid. Taking thesame drugs by mouth, so that they are only slowly
absorbed into the body, generally has a less powerfulpleasurable eﬀect, although it can be longer lasting.
An essential feature of drugs of abuse is that theyencourage repeated use. This tendency is driven byvarious factors and mechanisms. The special nature of
drug experiences certainly has a role. Indeed, in the caseof hallucinogens (eg, lysergic acid diethylamide [LSD],
mescaline, etc) it might be the only factor that drives
regular use, and such drugs are mostly used infrequently.
At the other extreme are drugs such as crack cocaine andnicotine, which, for most users, induce powerfuldependence. Physical dependence or addiction involves
increasing tolerance (ie, progressively higher doses being
needed for the same eﬀect), intense craving, and1048

withdrawal reactions—eg, tremors, diarrhoea, sweating,and sleeplessness—when drug use is stopped. Theseeﬀects indicate that adaptive changes occur as a result ofdrug use. Addictive drugs are generally used repeatedly
and frequently, partly because of the power of the craving
and partly to avoid withdrawal.
Psychological dependence is also characterised byrepeated use of a drug, but without tolerance or physicalsymptoms directly related to drug withdrawal. Some drugs
can lead to habitual use that seems to rest more on craving
than physical withdrawal symptoms. For instance,cannabis use can lead to measurable withdrawal symptoms,
but only several days after stopping long-standing use.
Some drugs—eg, the benzodiazepines—can induce
psychological dependence without tolerance, and physicalwithdrawal symptoms occur through fear of stopping. This
form of dependence is less well studied and understoodthan is addiction but it is a genuine experience, in thesense that withdrawal symptoms can be induced simply by
persuading a drug user that the drug dose is being
progressively reduced although it is, in fact, being
maintained at a constant level.10
The features of drugs that lead to dependence andwithdrawal reactions have been reasonably wellcharacterised. The half-life of the drug has aneﬀect—those drugs that are cleared rapidly from the bodytend to provoke more extreme reactions. The
pharmacodynamic eﬃcacy of the drug also has a role; themore eﬃcacious it is, the greater the dependence. Finally,
the degree of tolerance that develops on repeated use isalso a factor: the greater the tolerance, the greater the
dependence and withdrawal.
For many drugs there is a good correlation between
events that occur in human beings and those observed instudies on animals. Also, drugs that share molecularspeciﬁcity (ie, that bind with or interact with the sametarget molecules in the brain) tend to have similar
pharmacological eﬀects. Hence, some sensible
predictions can be made about new compounds before
they are used by human beings. Experimental studies ofthe dependence potential of old and new drugs are
possible only in individuals who are already using drugs,
so more population-based estimates of addictiveness (ie,capture rates) have been developed for the morecommonly used drugs.11 These estimates suggest thatsmoked tobacco is the most addictive commonly used
drug, with heroin and alcohol somewhat less so;
psychedelics have a low addictive propensity.

SocialDrugs harm society in several ways—eg, through thevarious eﬀects of intoxication, through damaging family
and social life, and through the costs to systems of healthcare, social care, and police. Drugs that lead to intense
intoxication are associated with huge costs in terms ofaccidental damage to the user, to others, and to property.
Alcohol intoxication, for instance, often leads to violent
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Health Policy

behaviour and is a common cause of car and otheraccidents. Many drugs cause major damage to the family,
either because of the eﬀect of intoxication or because
they distort the motivations of users, taking them awayfrom their families and into drug-related activities,
including crime.
Societal damage also occurs through the immense
health-care costs of some drugs. Tobacco is estimated tocause up to 40% of all hospital illness and 60% of
drug-related fatalities. Alcohol is involved in over half ofall visits to accident and emergency departments andorthopaedic admissions.12 However, these drugs also
generate tax revenue that can oﬀset their health costs tosome extent. Intravenous drug delivery brings particular
problems in terms of blood-borne virus infections,especially HIV and hepatitis, leading to the infection ofsexual partners as well as needle sharers. For drugs thathave only recently become popular—eg, 3,4-methylenedioxy-N-methylamphetamine, better known as ecstasy
or MDMA—the longer-term health and social
consequences can be estimated only from animal
toxicology at present. Of course, the overall use of a drug
has a substantial bearing on the extent of social harm.

Assessment of harm
Table 1 shows the assessment matrix that we designed,
which includes all nine parameters of risk, created by
dividing each of the three major categories of harm into
three subgroups, as described above. Participants wereasked to score each substance for each of these nineparameters, using a four-point scale, with 0 being no risk,
1 some, 2 moderate, and 3 extreme risk. For some analyses,
the scores for the three parameters for each category wereaveraged to give a mean score for that category. For thesake of discussion, an overall harm rating was obtained bytaking the mean of all nine scores.
The scoring procedure was piloted by members of thepanel of the Independent Inquiry into the Misuse ofDrugs Act.13 Once reﬁned through this piloting, anassessment questionnaire based on table 1, with additional
guidance notes, was used. Two independent groups ofexperts were asked to do the ratings. The ﬁrst was thenational group of consultant psychiatrists who were on
the Royal College of Psychiatrists’ register as specialists in
addiction. Replies were received and analysed from 29 of
the 77 registered doctors who were asked to assess
14 compounds—heroin, cocaine, alcohol, barbiturates,
amphetamine, methadone, benzodiazepines, solvents,
buprenorphine, tobacco, ecstasy, cannabis, LSD, andsteroids. Tobacco and alcohol were included because theirextensive use has provided reliable data on their risks andharms, providing familiar benchmarks against which theabsolute harms of other drugs can be judged. However,direct comparison of the scores for tobacco and alcoholwith those of the other drugs is not possible since the factthat they are legal could aﬀect their harms in various
ways, especially through easier availability.
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Parameter
Physical harm

Dependence

Social harms

One

Acute

Two

Chronic

Three

Intravenous harm

Four

Intensity of pleasure

Five

Psychological dependenceSixPhysical dependence

Seven

Intoxication

Eight

Other social harms

Nine

Health-care costs

Table 1: Assessment parameters

Having established that this nine-parameter matrix
worked well, we convened meetings of a second groupof experts with a wider spread of expertise. Theseexperts had experience in one of the many areas of
addiction, ranging from chemistry, pharmacology, andforensic science, through psychiatry and other medical
specialties, including epidemiology, as well as the legal
and police services. The second set of assessments wasdone in a series of meetings run along delphic
principles, a new approach that is being used widely to
optimise knowledge in areas where issues and eﬀects
are very broad and not amenable to precise
measurements or experimental testing,14 and which is
becoming the standard method by which to develop
consensus in medical matters. Since delphic analysis
incorporates the best knowledge of experts in diverse
disciplines, it is ideally applicable to a complex variable
Class in Misuse Commentsof Drugs Act
EcstasyA

Essentially 3,4-methylenedioxy-N-methylamphetamine (MDMA)

4-MTA

A

4-methylthioamphetamine

LSD

A

Lysergic acid diethylamide

CocaineA

Includes crack cocaine

HeroinA

Crude diamorphine

Street methadone

A

Diverted prescribed methadone

Amphetamine

B..

Methylphenidate

Beg, Ritalin (methylphenidate)

Barbiturates

B..

BuprenorphineCeg, Temgesic, Subutex

BenzodiazepinesCeg, Valium (diazepam), Librium (chlordiazepoxide)

GHB

C

Gamma 4-hydroxybutyric acid

Anabolic steroids

C..

CannabisC..

Alcohol..

Not controlled if over 18 years in UK

Alkyl nitrites..

Not controlled

Ketamine..

Not controlled at the time of assessment; controlled as class C since
January, 2007

Khat

..

Not controlled

Solvents..

Not controlled; sales restrictedTobacco..

Not controlled if over 16 years in UK

Table 2: The 20 substances assessed, showing their current status under the Misuse of Drugs Act

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Health Policy

3·0
Class
A
B
C
No class

Mean score (from independent experts)

2·5

2·0

1·5

1·0

0·5

rb
it e
m urat
et es
ha
do
n
Al e
co
h
Be Ket ol
nz am
od
i in
Am aze eph pineet samin
Bu To epr bacen coorphCa ine
nn
ab
So is
lve
nt
4- s
M
TA
M
et
hy
An lph LSD
ab enol idaic
ste te
ro
id
s
GH
B
E
Al cstakyl n sy
itr
at
es
Kh
at

in

St

re

Ba

et

ro
He

Co

ca

in

0·0

Figure 1: Mean harm scores for 20 substancesClassiﬁcation under the Misuse of Drugs Act, where appropriate, is shown by the colour of each bar.

such as drug misuse and addiction. Initial scoring wasdone independently by each participant, and the scoresfor each individual parameter were then presented to
the whole group for discussion, with a particularemphasis on elucidating the reasoning behind outlierscores. Individuals were then invited to revise theirscores, if they wished, on any of the parameters, in thelight of this discussion, after which a ﬁnal mean score
was calculated. The complexity of the process meansthat only a few drugs can be assessed in a single
meeting, and four meetings were needed to complete
the process. The number of members taking part in thescoring varied from eight to 16. However, the full rangeof expertise was maintained in each assessment.
This second set of assessments covered the
14 substances considered by the psychiatrists plus, forcompleteness, six other compounds (khat, 4-methylthioamphetamine [4-MTA], gamma 4-hydroxybutyric acid
[GHB], ketamine, methylphenidate, and alkyl nitrites),some of which are not illegal, but for each of which there
have been reports of abuse (table 2). Participants were toldin advance which drugs were being covered at eachmeeting to allow them to update their knowledge andconsider their opinion. Recent review articles5,6,7,15–18 were
provided.
Occasionally, individual experts were unable to give ascore for a particular parameter for a particular drug andthese missing values were ignored in the analysis—ie,
they were neither treated as zero nor given someinterpolated value. Data were analysed with the statistical
functions in Microsoft Excel and S-plus.

Results3·0

35
Psychiatrists

1

2

2·5
4

6

2·0

7
9
10

8
1·5

11

13 12

14

1·0

0·5

0·0
0·0

0·5

1·0

1·5

2·0

2·5

3·0

Independent experts

Figure 2: Correlation between mean scores from the independent experts
and the specialist addiction psychiatrists
1=heroin. 2=cocaine. 3=alcohol. 4=barbiturates. 5=amphetamine.
6=methadone. 7=benzodiazepines. 8=solvents. 9=buprenorphine. 10=tobacco.
11=ecstasy. 12=cannabis. 13=LSD. 14=steroids.

1050

Use of this risk assessment system proved straightforward
and practicable, both by questionnaire and in open delphic
discussion. Figure 1 shows the overall mean scores of the
independent expert group, averaged across all scorers,
plotted in rank order for all 20 substances. The classiﬁcationof each substance under the Misuse of Drugs Act is also
shown. Although the two substances with the highest
harm ratings (heroin and cocaine) are class A drugs, overall
there was a surprisingly poor correlation between drugs’
class according to the Misuse of Drugs Act and harm score.
Of both the eight substances that scored highest and theeight that scored lowest, three were class A and two were
unclassiﬁed. Alcohol, ketamine, tobacco, and solvents (allunclassiﬁed at the time of assessment) were ranked as
more harmful than LSD, ecstasy, and its variant 4-MTA (allclass A drugs). Indeed, the correlation between classiﬁcationby the Misuse of Drugs Act and harm rating was not
signiﬁcant (Kendall’s rank correlation –0·18; p=0·25;
Spearman’s rank correlation –0·26, p=0·26). Of theunclassiﬁed drugs, alcohol and ketamine were given
especially high ratings. Interestingly, a very recent
recommendation from the Advisory Council on the Misuse
of Drugs that ketamine should be added to the Misuse ofDrugs Act (as a class C drug) has just been accepted.19
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Health Policy

We compared the overall mean scores (averaged acrossall nine parameters) for the psychiatrists with those of
the independent group for the 14 substances that wereranked by both groups (ﬁgure 2). The ﬁgure suggeststhat the scores have some validity and that the process isrobust, in that it generates similar results in the hands ofrather diﬀerent sets of experts.
Table 3 lists the independent group results for each of
the three subcategories of harm. The scores in eachcategory were averaged across all scorers and thesubstances are listed in rank order of harm, based on
their overall score. Many of the drugs were consistent intheir ranking across the three categories. Heroin, cocaine,barbiturates, and street methadone were in the top ﬁveplaces for all categories of harm, whereas khat, alkyl
nitrites, and ecstasy were in the bottom ﬁve places for all.
Some drugs diﬀered substantially in their harm ratings
across the three categories. For instance, cannabis was
ranked low for physical harm but somewhat higher for
dependence and harm to family and community.
Anabolic steroids were ranked high for physical harm
but low for dependence. Tobacco was high for dependence
but distinctly lower for social harms, because it scoredlow on intoxication. Tobacco’s mean score for physicalharm was also modest, since the ratings for acute harmand potential for intravenous use were low, although thevalue for chronic harm was, unsurprisingly, very high.
Drugs that can be administered by the intravenous
route were generally ranked high, not solely because they
were assigned exceptionally high scores for parameterPhysical harm
Mean

Acute

three (ie, the propensity for intravenous use) and nine(health-care costs). Even if the scores for these twoparameters were excluded from the analysis, the highranking for such drugs persisted. Thus, drugs that can beadministered intravenously were also judged to be very
harmful in many other respects.

Discussion
The results of this study do not provide justiﬁcation forthe sharp A, B, or C divisions of the current classiﬁcationsin the UK Misuse of Drugs Act. Distinct categorisationis, of course, convenient for setting of priorities forpolicing, education, and social support, as well as todetermine sentencing for possession or dealing. But
neither the rank ordering of drugs nor their segregation
into groups in the Misuse of Drugs Act classiﬁcation is
supported by the more complete assessment of harm
described here. Sharply deﬁned categories in any ranking
system are essentially arbitrary unless there are obvious
discontinuities in the full set of scores. Figure 1 shows
only a hint of such a transition in the spectrum of harm,in the small step in the very middle of the distribution,
between buprenorphine and cannabis. Interestingly,
alcohol and tobacco are both in the top ten, higher-harmgroup. There is a rapidly accelerating harm value fromalcohol upwards. So, if a three-category classiﬁcation
were to be retained, one possible interpretation of our
ﬁndings is that drugs with harm scores equal to that ofalcohol and above might be class A, cannabis and thosebelow might be class C, and drugs in between might be
Dependence

Chronic

Intravenous

Mean

Social harm
Pleasure

Psychological Physicaldependence dependence

Mean

Intoxication

Socialharm

Health-carecosts

Heroin

2·78

2·8

2·5

3·0

3·00

3·0

3·0

3·0

2·54

1·6

3·0

3·0

Cocaine

2·33

2·0

2·0

3·0

2·39

3·0

2·8

1·3

2·17

1·8

2·5

2·3

Barbiturates

2·23

2·3

1·9

2·5

2·01

2·0

2·2

1·8

2·00

2·4

1·9

1·7

Street methadone

1·86

2·5

1·7

1·4

2·08

1·8

2·3

2·3

1·87

1·6

1·9

2·0

Alcohol

1·40

1·9

2·4

NA

1·93

2·3

1·9

1·6

2·21

2·2

2·4

2·1

Ketamine

2·00

2·1

1·7

2·1

1·54

1·9

1·7

1·0

1·69

2·0

1·5

1·5

Benzodiazepines

1·63

1·5

1·7

1·8

1·83

1·7

2·1

1·8

1·65

2·0

1·5

1·5

Amphetamine

1·81

1·3

1·8

2·4

1·67

2·0

1·9

1·1

1·50

1·4

1·5

1·6

Tobacco

1·24

0·9

2·9

0

2·21

2·3

2·6

1·8

1·42

0·8

1·1

2·4

Buprenorphine

1·60

1·2

1·3

2·3

1·64

2·0

1·5

1·5

1·49

1·6

1·5

1·4

Cannabis

0·99

0·9

2·1

0

1·51

1·9

1·7

0·8

1·50

1·7

1·3

1·5

Solvents

1·28

2·1

1·7

0

1·01

1·7

1·2

0·1

1·52

1·9

1·5

1·2

4-MTA

1·44

2·2

2·1

0

1·30

1·0

1·7

0·8

1·06

1·2

1·0

1·0

LSD

1·13

1·7

1·4

0·3

1·23

2·2

1·1

0·3

1·32

1·6

1·3

1·1

Methylphenidate

1·32

1·2

1·3

1·6

1·25

1·4

1·3

1·0

0·97

1·1

0·8

1·1

Anabolic steroids

1·45

0·8

2·0

1·7

0·88

1·1

0·8

0·8

1·13

1·3

0·8

1·3

GHB

0·86

1·4

1·2

0

1·19

1·4

1·1

1·1

1·30

1·4

1·3

1·2

Ecstasy

1·05

1·6

1·6

0

1·13

1·5

1·2

0·7

1·09

1·2

1·0

1·1

Alkyl nitrites

0·93

1·6

0·9

0·3

0·87

1·6

0·7

0·3

0·97

0·8

0·7

1·4

Khat

0·50

0·3

1·2

0

1·04

1·6

1·2

0·3

0·85

0·7

1·1

0·8

Table 3: Mean independent group scores in each of the three categories of harm, for 20 substances, ranked by their overall score, and mean scores for each of the three subscales

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Health Policy

class B. In that case, it is salutary to see that alcohol andtobacco—the most widely used unclassiﬁed substances—would have harm ratings comparable withclass A and B illegal drugs, respectively.
Participants were asked to assess the harm of drugs
administered in the form that they are normally used. Ina few cases, the harms caused by a particular drug could
not be completely isolated from interfering factors
associated with the particular style of use. For example,
cannabis is commonly smoked as a mixture with tobacco,
which might have raised its scores for physical harm anddependence, among other factors. There is a further
degree of uncertainty resulting from polydrug use,
especially in the so-called recreational group of drugs
that includes GHB, ketamine, ecstasy, and alcohol, forwhich adverse eﬀects could be attributed mainly to oneof the components of commonly used mixtures. Crackcocaine is generally deemed to be more dangerous thanpowdered cocaine, but they were not consideredseparately in this study. Similarly, the scores for the
benzodiazepines might have been biased in the directionof the most abused drugs, especially temazepam.
Individual scoring for particular benzodiazepines and forthe various forms in which other drugs are used would
be more appropriate should this or any other system ofharm classiﬁcation be used in a formal setting.
In view of the small numbers of independent scores,
we did not think that estimation of correlations between
the nine parameters was legitimate. There is quite likely
to be some redundancy—ie, the nine parameters might
not represent nine independent measures of risk. In
much the same way, the principal components of theparameters were not extracted, partly because we thoughtthat there were insuﬃcient data and partly because
reduction of the number of parameters to a core group
might not be appropriate, at least until further assessment
panels have independently validated the entire system.
Our analysis gave equal weight to each parameter ofharm, and individual scores have simply been averaged.
Such a procedure would not give a valid indication ofharm for a drug that has extreme acute toxicity, such as
the designer drug contaminant MPTP (1-methyl 4-phenyl
1,2,3,6-tetrahydropyridine), a single dose of which candamage the substantia nigra of the basal ganglia soseverely that it induces an extreme form of Parkinson’s
disease. Indeed, this simple method of integrating scores
might not deal adequately with any substance that isextremely harmful in only one respect. Take tobacco, forinstance. Smoking tobacco beyond the age of 30 years
reduces life expectancy by an average of up to 10 years,9and it is the commonest cause of drug-related deaths,
placing a huge burden on health services. However,tobacco’s short-term consequences and social eﬀects areunexceptional. Of course, the weighting of individual
parameters could be varied to emphasise one facet ofrisk or another, depending on the importance attachedto each. Other procedural mechanisms, such as those of1052

multi-criteria decision analysis,20 could be used to takeaccount of variation of ranking across diﬀerent
parameters of harm. Despite these reservations about
the interpretation of integrated scores and the need forfurther consideration of the weighting of parameters ofharm, we were greatly encouraged by the generalconsistency of scores across scorers and acrossparameters of harm for most drugs.
Our ﬁndings raise questions about the validity of thecurrent Misuse of Drugs Act classiﬁcation, despite thefact that it is nominally based on an assessment of risk tousers and society. The discrepancies between our ﬁndings
and current classiﬁcations are especially striking in
relation to psychedelic-type drugs. Our results alsoemphasise that the exclusion of alcohol and tobacco from
the Misuse of Drugs Act is, from a scientiﬁc perspective,
arbitrary. We saw no clear distinction between sociallyacceptable and illicit substances. The fact that the twomost widely used legal drugs lie in the upper half of the
ranking of harm is surely important information thatshould be taken into account in public debate on illegal
drug use. Discussions based on a formal assessment ofharm rather than on prejudice and assumptions might
help society to engage in a more rational debate about therelative risks and harms of drugs.
We believe that a system of classiﬁcation like ours, basedon the scoring of harms by experts, on the basis of scientiﬁc
evidence, has much to commend it. Our approach provides
a comprehensive and transparent process for assessmentof the danger of drugs, and builds on the approach to thisissue developed in earlier publications5–8,11,12,21,22 but covers
more parameters of harm and more drugs, as well as using
the delphic approach, with a range of experts. The system
is rigorous and transparent, and involves a formal,
quantitative assessment of several aspects of harm. It caneasily be reapplied as knowledge advances. We note that anumerical system has also been described by MacDonald
and colleagues23 to assess the population harm of drug use,
an approach that is complementary to the scheme
described here, but as yet has not been applied to speciﬁc
drugs. Other organisations (eg, the European Monitoring
Centre for Drugs and Drug Addiction24 and the CAM
committee of the Dutch government25) are currently
exploring other risk assessment systems, some of which
are also numerically based. Other systems use delphic
methodology, although none uses such a comprehensive
set of risk parameters and no other has reported on such awide range of drugs as our method. We believe that oursystem could be developed to aid in decision-making byregulatory bodies—eg, the UK’s Advisory Council on the
Misuse of Drugs and the European Medicines Evaluation
Agency—to provide an evidence-based approach to drugclassiﬁcation.
Contributors
All authors contributed to the study design, analysis, and writing of themanuscript. All authors saw and approved the ﬁnal version of themanuscript.

www.thelancet.com Vol 369 March 24, 2007

Health Policy

Conﬂict of interest statement
We declare that we have no conﬂict of interest.
Acknowledgments
Some of the ideas developed in this paper arose out of discussion atworkshops organised by the Beckley Foundation, to whom we are
grateful. We thank David Spiegelhalter of the MRC Biostatistics Unit for
advice on statistics. An early version of this paper was requested by theHouse of Commons Select Committee on Science and Technology toassist in their review on the evidence base of the drug laws, andappeared unacknowledged as Appendix 10 of their report.26
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