Health Policy

DEVELOPMENT OF A RATIONAL SCALE TO ASSESS THE HARM OF DRUGS OF
POTENTIAL MISUSE

Summary

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, with an
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 harm when used by two separate groups of experts.
The ranking of drugs produced by our assessment of harm differed from
those 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, and public-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 UKP10 billion and UKP16 billion per year,1
with the global burden being proportionately enormous.[2,3]

Current approaches to counter drug misuse are interdiction of supply
(via policing and customs control), education, and treatment. All
three demand clarity in terms of the relative risks and harms that
drugs engender. At present, in the UK, attitudes to policing and the
punishments 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-care provision are nominally tailored to the
known actions and harms of specific drugs. Most other countries and
international agencies-eg, the UN and WHO-have drug 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 is often undisclosed, and when made public can be
ill-defined, opaque, and seemingly arbitrary. In part, this lack of
clarity is due to the great range and complexity of factors that have
to be taken into account in estimation of harm 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 the current UK
Misuse of Drugs Act, in which drugs are segregated 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, in particular
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.

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

Categories of Harm

There are three main factors that together determine the harm
associated with any drug of potential abuse: the physical harm to the
individual user caused by the drug; the tendency of the drug to
induce dependence; and the effect of drug use on families,
communities, and society.[5-8]

Physical

Assessment of the propensity of a drug to cause physical harm-ie,
damage to organs or systems-involves a systematic 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
effect of a drug on physiological functions-eg, respiratory and
cardiac-is a major determinant of physical harm. The route of
administration is also relevant to the assessment of harm. Drugs that
can be taken intravenously-eg, heroin-carry a high risk of causing
sudden death from respiratory depression, and therefore score highly
on any metric of acute harm. Tobacco and alcohol have a high
propensity to cause illness and death as a result of chronic use.
Recently published evidence shows 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 deaths in the UK.

The UK Medicines and Healthcare Regulatory Authority, in common with
similar bodies in Europe, the USA, and elsewhere, has
well-established methods to assess the safety of medicinal drugs,
which can be used as the basis of this element of risk appraisal.
Indeed several drugs of abuse have licensed indications in 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 of drugs 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 repeated use
(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 acute toxicity
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 such as 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 a separate
parameter in our exercise.

Dependence

This 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 are commonly 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 the euphoria that follows this, often
extending over several hours (the high). The faster the drug enters
the brain the stronger the rush, which is why there is a drive to
formulate 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 with
powdered cocaine, is also surprisingly rapid. Taking the same drugs
by mouth, so that they are only slowly absorbed into the body,
generally has a less powerful pleasurable effect, although it can be
longer lasting.

An essential feature of drugs of abuse is that they encourage
repeated use. This tendency is driven by various factors and
mechanisms. The special nature of drug experiences certainly has a
role. Indeed, in the case of 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 and nicotine,
which, for most users, induce powerful dependence. Physical
dependence or addiction involves increasing tolerance (ie,
progressively higher doses being needed for the same effect), intense
craving, and withdrawal reactions-eg, tremors, diarrhoea, sweating,
and sleeplessness-when drug use is stopped. These effects indicate
that adaptive changes occur as a result of drug 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 by repeated use of a
drug, but without tolerance or physical symptoms 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 physical withdrawal symptoms occur through fear of
stopping. This form of dependence is less well studied and understood
than is addiction but it is a genuine experience, in the sense 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 and withdrawal
reactions have been reasonably well characterised. The half-life of
the drug has an effect-those drugs that are cleared rapidly from the
body tend to provoke more extreme reactions. The pharmacodynamic
efficacy of the drug also has a role; the more efficacious it is, the
greater the dependence. Finally, the degree of tolerance that
develops on repeated use is also 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 in studies on animals. Also, drugs
that share molecular specificity (ie, that bind with or interact with
the same target 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 of the 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 more commonly used drugs.[11] These estimates
suggest that smoked tobacco is the most addictive commonly used drug,
with heroin and alcohol somewhat less so; psychedelics have a low
addictive propensity.

Social

Drugs harm society in several ways-eg, through the various effects of
intoxication, through damaging family and social life, and through
the costs to systems of health care, social care, and police. Drugs
that lead to intense intoxication are associated with huge costs in
terms of accidental damage to the user, to others, and to property.
Alcohol intoxication, for instance, often leads to violent behaviour
and is a common cause of car and other accidents. 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 away from 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 to cause up to 40% of all hospital
illness and 60% of drug-related fatalities. Alcohol is involved in
over half of all visits to accident and emergency departments and
orthopaedic admissions.[12] However, these drugs also generate tax
revenue that can offset their health costs to some extent.
Intravenous drug delivery brings particular problems in terms of
blood-borne virus infections, especially HIV and hepatitis, leading
to the infection of sexual partners as well as needle sharers. For
drugs that have 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 were asked to score each substance for each of these
nine parameters, 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 were averaged to give a
mean score for that category. For the sake of discussion, an overall
harm rating was obtained by taking the mean of all nine scores.

Click to view table http://www.mapinc.org/images/LancetTable1.gif

Table 1. Assessment parameters

The scoring procedure was piloted by members of the panel of the
Independent Inquiry into the Misuse of Drugs Act.13 Once refined
through this piloting, an assessment questionnaire based on table 1,
with additional guidance notes, was used. Two independent groups of
experts were asked to do the ratings. The first was the national
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, and steroids. Tobacco and alcohol
were included because their extensive use has provided reliable data
on their risks and harms, providing familiar benchmarks against which
the absolute harms of other drugs can be judged. However, direct
comparison of the scores for tobacco and alcohol with those of the
other drugs is not possible since the fact that they are legal could
affect their harms in various ways, especially through easier availability.

Having established that this nine-parameter matrix worked well, we
convened meetings of a second group of experts with a wider spread of
expertise. These experts had experience in one of the many areas of
addiction, ranging from chemistry, pharmacology, and forensic
science, through psychiatry and other medical specialties, including
epidemiology, as well as the legal and police services. The second
set of assessments was done 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 such as drug misuse and addiction. Initial
scoring was done independently by each participant, and the scores
for each individual parameter were then presented to the whole group
for discussion, with a particular emphasis on elucidating the
reasoning behind outlier scores. Individuals were then invited to
revise their scores, if they wished, on any of the parameters, in the
light of this discussion, after which a final mean score was
calculated. The complexity of the process means that 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 the
scoring varied from eight to 16. However, the full range of expertise
was maintained in each assessment.

This second set of assessments covered the 14 substances considered
by the psychiatrists plus, for completeness, 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 told in advance which drugs were
being covered at each meeting to allow them to update their knowledge
and consider their opinion. Recent review articles [5,6,7,15-18] were provided.

Click to view table http://www.mapinc.org/images/LancetTable2.gif

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

Occasionally, individual experts were unable to give a score for a
particular parameter for a particular drug and these missing values
were ignored in the analysis-ie, they were neither treated as zero
nor given some interpolated value. Data were analysed with the
statistical functions in Microsoft Excel and S-plus.

Results

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 classification of 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 the eight that scored lowest, three were
class A and two were unclassified. Alcohol, ketamine, tobacco, and
solvents (all unclassified at the time of assessment) were ranked as
more harmful than LSD, ecstasy, and its variant 4-MTA (all class A
drugs). Indeed, the correlation between classification by 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 the unclassified 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 of Drugs Act (as a class C drug) has just been accepted.[19]

Click to enlarge image http://www.mapinc.org/images/LancetFigure1.gif

Figure 1. Mean harm scores for 20 substances

Classification under the Misuse of Drugs Act, where appropriate, is
shown by the colour of each bar.

We compared the overall mean scores (averaged across all nine
parameters) for the psychiatrists with those of the independent group
for the 14 substances that were ranked by both groups (figure 2). The
figure suggests that the scores have some validity and that the
process is robust, in that it generates similar results in the hands
of rather different sets of experts.

Click to enlarge image http://www.mapinc.org/images/LancetFigure2.gif

Figure 2. Correlation between mean scores from the independent
experts and the specialist addiction psychiatrists

1=heroin. 2=cocaine. 3=alcohol. 4 rbiturates. 5=amphetamine.
6=methadone. 7 nzodiazepines. 8=solvents. 9=buprenorphine.
10=tobacco. 11istasy. 12Ennabis. 13=LSD. 14=steroids.

Table 3 lists the independent group results for each of the three
subcategories of harm. The scores in each category were averaged
across all scorers and the substances are listed in rank order of
harm, based on their overall score. Many of the drugs were consistent
in their ranking across the three categories. Heroin, cocaine,
barbiturates, and street methadone were in the top five places 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 scored low on intoxication. Tobacco's mean score
for physical harm was also modest, since the ratings for acute harm
and potential for intravenous use were low, although the value for
chronic harm was, unsurprisingly, very high.

Click to view table http://www.mapinc.org/images/LancetTable3.gif

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

Drugs that can be administered by the intravenous route were
generally ranked high, not solely because they were assigned
exceptionally high scores for parameter three (ie, the propensity for
intravenous use) and nine (health-care costs). Even if the scores for
these two parameters were excluded from the analysis, the high
ranking for such drugs persisted. Thus, drugs that can be
administered intravenously were also judged to be very harmful in
many other respects.

Discussion

The results of this study do not provide justification for the sharp
A, B, or C divisions of the current classifications in the UK Misuse
of Drugs Act. Distinct categorisation is, of course, convenient for
setting of priorities for policing, education, and social support, as
well as to determine 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-harm group. There is a rapidly
accelerating harm value from alcohol 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 of alcohol
and above might be class A, cannabis and those below might be class
C, and drugs in between might be class B. In that case, it is
salutary to see that alcohol and tobacco-the most widely used
unclassified substances-would have harm ratings comparable with class
A and B illegal drugs, respectively.

Participants were asked to assess the harm of drugs administered in
the form that they are normally used. In a 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 and dependence, 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, for which
adverse effects could be attributed mainly to one of the components
of commonly used mixtures. Crack cocaine is generally deemed to be
more dangerous than powdered cocaine, but they were not considered
separately in this study. Similarly, the scores for the
benzodiazepines might have been biased in the direction of the most
abused drugs, especially temazepam. Individual scoring for particular
benzodiazepines and for the various forms in which other drugs are
used would be more appropriate should this or any other system of
harm 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 the parameters were
not extracted, partly because we thought that 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 of harm, and
individual scores have simply been averaged. Such a procedure would
not give a valid indication of harm 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 can
damage the substantia nigra of the basal ganglia so severely 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 is extremely harmful in only one respect. Take
tobacco, for instance. Smoking tobacco beyond the age of 30 years
reduces life expectancy by an average of up to 10 years,[9] and 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 are unexceptional. Of course, the weighting of
individual parameters could be varied to emphasise one facet of risk
or another, depending on the importance attached to each. Other
procedural mechanisms, such as those of multi-criteria decision
analysis,[20] could be used to take account of variation of ranking
across different parameters of harm. Despite these reservations about
the interpretation of integrated scores and the need for further
consideration of the weighting of parameters of harm, we were greatly
encouraged by the general consistency of scores across scorers and
across parameters of harm for most drugs.

Our findings raise questions about the validity of the current Misuse
of Drugs Act classification, despite the fact that it is nominally
based on an assessment of risk to users and society. The
discrepancies between our findings and current classifications are
especially striking in relation to psychedelic-type drugs. Our
results also emphasise 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 socially acceptable and illicit
substances. The fact that the two most widely used legal drugs lie in
the upper half of the ranking of harm is surely important information
that should be taken into account in public debate on illegal drug
use. Discussions based on a formal assessment of harm rather than on
prejudice and assumptions might help society to engage in a more
rational debate about the relative risks and harms of drugs.

We believe that a system of classification like ours, based on 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 assessment of the danger of drugs, and builds
on the approach to this issue developed in earlier publications
[5-8,11,12,21,22] 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 can easily be
reapplied as knowledge advances. We note that a numerical system has
also been described by MacDonald and colleagues [23] 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 Addiction[24] 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 a wide range of drugs as
our method. We believe that our system could be developed to aid in
decision-making by regulatory 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 drug classification.

Contributors

All authors contributed to the study design, analysis, and writing of
the manuscript. All authors saw and approved the final version of the
manuscript.

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 at
workshops 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 the House of Commons Select Committee on Science and
Technology to assist in their review on the evidence base of the drug
laws, and appeared unacknowledged as Appendix 10 of their report.26

References

1. Foresight. Brain science, addiction and drugs, 2005
http://www.foresight.gov.uk/Previous_Projects/Brain_Science_Addiction_and_Drugs/index.html
(accessed March 11, 2007)

2. Lopez AD, Murray CJL. The global burden of disease. Nat Med 1998;
6: 1241-1243.
http://www.thelancet.com/journals/lancet/medline/record/MDLN.11062535

3. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJthe
Comparative Risk Assessment Collaborating Group. Selected major risk
factors and global and regional burden of disease. Lancet 2002; 360:
1347-1360.
http://www.thelancet.com/journals/lancet/article/PIIS0140673602114036/abstract
Abstract |
http://www.thelancet.com/journals/lancet/article/PIIS0140673602114036/fulltext
Full Text |
http://download.thelancet.com/pdfs/journals/0140-6736/PIIS0140673602114036.pdf?clusterid=thelancet&mis=.pdf
Full-Text PDF (199 KB)

4. UK Home Office. Misuse of Drugs Act
http://www.drugs.gov.uk/drugs-laws/misuse-of-drugs-act/ (accessed
March 11, 2007)

5. King LA, Moffat AC. A possible index of fatal drug toxicity in
humans. Med Sci Law 1983; 23: 193-197.
http://www.thelancet.com/journals/lancet/medline/record/MDLN.6633207 MEDLINE

6. Gable RS. Toward a comparative overview of dependence potential
and acute toxicity of psychoactive substances used nonmedically. Am J
Drug Alcohol Abuse 1993; 19: 263-281.
http://www.thelancet.com/journals/lancet/medline/record/MDLN.8213692 MEDLINE

7. Gable RS. Comparison of acute lethal toxicity of commonly abused
psychoactive substances. Addiction 2004; 99: 686-696.
http://www.thelancet.com/journals/lancet/medline/record/MDLN.15139867 MEDLINE

8. Goldstein A, Kalant H. Drug policy: striking the right balance.
Science 1990; 249: 1513-1521.
http://www.thelancet.com/journals/lancet/medline/record/MDLN.2218493 MEDLINE

9. Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to
smoking: 50 years' observations on male British doctors. BMJ 2004;
328: 1519-1528.

10. Tyrer P, Owen R, Dawling S. Gradual withdrawal of diazepam after
long-term therapy. Lancet 1983; 1: 1402-1406.
http://www.thelancet.com/journals/lancet/medline/record/MDLN.14031860 MEDLINE

11. Anthony JC, Warner L, Kessler R. Comparative epidemiology of
dependence on tobacco, alcohol, controlled substances and inhalants:
basic findings from the National Comorbidity Survey. Exp Clin
Psychopharmacol 1994; 2: 244-268.

12. Academy of Medical Sciences. Calling time: the nation's drinking
as a major health issue. London: Academy of Medical Sciences, 2004

13. Drugs and the Law. Report of the Independent Inquiry into the
Misuse of Drugs Act 1971. London: The Police Foundation, 2000

14. Turoff M. The design of a policy delphi. Technological
Forecasting and Social Change 1970; 2: 149-171.

15. Corkery JM. Drug seizures and offender statistics. UK 2000.
London: Home Office Statistical Bulletin, 2002:.

16. Griffiths C, Brock A, Mickleburgh M. Deaths relating to drug
poisoning: results for England and Wales 1993-2000. Health Statistics
Quarterly 2002; 13: 76-82.

17. Nutt DJ, Nash J. Cannabis-an update. London: Home Office, 2002

18. Gonzalez A, Nutt DJ. Gammahydoxybutyrate abuse and dependency. J
Psychopharm 2005; 19: 195-204.

19. UK Home Office. Proposed changes to Misuse of Drugs
legislation
http://www.homeoffice.gov.uk/documents/2005-cons-ketamine/?version=1
(accessed Feb 28, 2007)

20. Figuera J, Greco S, Ehrgott M. Multiple criteria decision
analysis: state of the art. Boston, Dordrecht, London: Springer Verlag, 2005

21. Hall W, Room R, Bondy S. Comparing the health and psychological
risks of alcohol, cannabis, nicotine and opiate use In: Kalant H,
Corrigal W, Hall W, Smart R, eds. The health effects of cannabis.
Toronto: Addiction Research Foundation, 1999

22. MacCoun R, Reuter P. Drug war heresies: learning from other
vices, times and places. Cambridge: Cambridge University Press, 2001

23. MacDonald Z, Tinsley L, Collingwood J, Jamieson P, Pudney S.
Measuring the harm from illegal drugs using the Drug Harm Index
http://www.homeoffice.gov.uk/rds/notes/rdsolr2405.html (accessed Feb 28, 2007).

24. EMCDDA. Guidelines for the risk assessment of new synthetic
drugs. Luxembourg: EMCDDA, Office for Official Publications of the
European Communities, 1999

25. van Amsterdam JDC, Best W, Opperhuizen A, de Wolff FA. Evaluation
of a procedure to assess the adverse effects of illicit drugs. Regul
Pharmacol Toxicol 2004; 39: 1-4.

26. House of Commons Science and Technology Committee. Drug
classification: making a hash of it? Fifth Report of Session 2005-06,
2006
http://www.publications.parliament.uk/pa/cm200506/cmselect/cmsctech/1031/103102.htm
(accessed Feb 28, 2007)

Affiliations

a. Psychopharmacology Unit, University of Bristol, Bristol, UK

b. Forensic Science Service, London, UK

c. Police Foundation, London

d. Medical Research Council, London

e. Department of Physiology, Anatomy and Genetics, Oxford, UK

Correspondence to: Prof David Nutt, Psychopharmacology Unit,
University of Bristol, Bristol BS1 3NY, UK