[Vision2020] Lancet Medical Journal: Rational Scale to Assess Harm of Drugs

[Ted Moffett]

After the post from Tim Lohrmann on law enforcement conduct discussed in the
video below, it seemed appropriate to objectively assess the medical and
social facts regarding the harm to society from various drugs, and how these
facts are rationally, or not, reflected in drug laws,
enforcement, access, and regulation:

http://video.google.com/videoplay?docid=4838183480791433140&ei=FSGeSKajNam0qAP68NDQCg&q=maryland+mayor+drug+raid&vt=lf&hl=en

http://mailman.fsr.com/pipermail/vision2020/2008-August/055344.html
--------------------
Access to this "Lancet" medical journal study is restricted,
though registration for the full text of this article if offered for free.
I offer the text in full below.  The charts and tables do not show, so the
simple 1-20 ratings of the relative harm of various drugs is at the top.

Note alcohol is rated fifth most harmful, tobacco rated ninth, just below
number eight amphetamine.  I don't agree with the relative rating of the
drugs in all cases (Cannabis at 11 and LSD at 14?), but the method used is
based on a wide sampling of relevant professional opinion.  Perhaps the
ratings in part express how widespread the use of each drug is, rather than
the danger of use per "dosage" per person.

Why do we allow any advertising, and sale of tobacco and alcohol at grocery
or convenience stores, given the harm of promotion of these drugs?  I am not
advocating making use of tobacco or alcohol more criminalized.

Harsh criminalization of drug use (I am not suggesting total unregulated
legalization of drugs...even alcohol and tobacco are illegal for those
underage) is a failed policy that creates a class of well paid profit
seeking business people, always finding clever ways to elude detection, who
often use mules, also well paid, for the risky aspects of the business,
insulating the "upper management " from law enforcement, turns casual users
and low level sellers into criminals by the millions (the cost of arresting,
prosecuting and jailing all these offenders is incredible), and undermines
civil rights, as the video under discussion amply demonstrates.

Drug abuse can be mitigated by solving other social problems that are
associated with this destructive behavior, such as poverty and low paying
jobs that are a joke compared to the profits to be made in the drug
trade, domestic violence, family dysfunction, and lack of education, among
other problems... Widespread drug abuse is a symptom of
social/economic/political/spiritual dysfunction.  The causes of this
dysfunction should be addressed.  If drug abuse was lessened, the market
would be reduced.  As long as there is a strong demand, someone will supply,
given the profits.

Amazing that those who promote the virtues of free market capitalism
advocate massive government interference and draconian criminalization in
the free market for a product consumers clearly demand and freely chose to
use.  The success of the illegal drug trade, given the billions government
ostensibly spends to stop this business and the number jailed, is a
demonstration of the power of supply and demand in the marketplace.  It
seems the example of illegal drugs poses a serious theoretical problem for
the advocates of free markets who impose their morality to restrict the
market in this case.  At least the late Milton Friedman, famous free market
advocate and Noble Prize winning economist, was consistent on this issue,
calling the "war on drugs" a "socialist enterprise."

http://www.druglibrary.org/special/friedman/socialist.htm
---------------
I don't think the problem of drug abuse can be solved completely, just as
stopping murder or war totally seems impossible.  Some people will abuse
drugs no matter how perfect our world, just as some will eat themselves into
obesity and heart disease, at great cost to society (should we criminalize
Haagen Dazs ice cream and McDonalds double cheeseburgers?).  The government
should not be everyones nanny...

The legal drugs alcohol and tobacco (odd how they are usually called
"legal," yet they are not legal for those underage, a not trivial segment of
the population, who have very easy access, making a mockery of the underage
laws), of considerable power and harm to society, should not be dispensed in
check out lines to families along with eggs, milk and bread (what message
does this send to impressionable minds?), nor should multimillion dollar
advertising campaigns be allowed.  Maybe keep alcohol and tobacco in liquor
stores, and ban all advertising for them.

Does anyone doubt that the fact that wine, beer and tobacco are available in
grocery stores, and are still legally promoted by advertising, is due to the
huge profits generated by widespread convenient access to these dangerous
addictive substances, and the lobbying by the alcohol and tobacco industries
to block more restrictive regulation?

Ted Moffett
--------------------------------
Most dangerous drugs

Research recently published in the medical journal The Lancet rates the most
dangerous drugs (starting with the worst) as follows:
 *1. *Heroin
*2. *Cocaine
*3. *Barbiturates
*4. *Street methadone
*5. *Alcohol
*6. *Ketamine
*7. *Benzodiazepines
*8. *Amphetamine
*9. *Tobacco
*10. *Buprenorphine
*11. *Cannabis
*12. *Solvents
*13. *4-MTA
*14. *LSD
*15. *Methylphenidate
*16. *Anabolic steroids
*17. *GHB
*18. *Ecstasy
*19. *Alkyl nitrates
*20. *Khat
--------------------------
http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/abstract

The Lancet 2007; 369:1047-1053
DOI:10.1016/S0140-6736(07)60464-4

*Health Policy*

Development of a rational scale to assess the harm of drugs of potential
misuse

Prof David Nutt<http://www.thelancet.com/search/results?search_mode=cluster&search_area=cluster&search_cluster=thelancet&search_sort=date&restrictname_author=author&restricttype_author=author&restrictterm_author=nutt0d&restrictdesc_author=David+Nutt>FMedSci
 [image: email address] <david.j.nutt at bristol.ac.uk>
a<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#aff1>
 [image: Corresponding Author
Information]<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#cor1>,
  Leslie A King<http://www.thelancet.com/search/results?search_mode=cluster&search_area=cluster&search_cluster=thelancet&search_sort=date&restrictname_author=author&restricttype_author=author&restrictterm_author=king0la&restrictdesc_author=Leslie+A+King>PhD
 b<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#aff2>,
  William Saulsbury<http://www.thelancet.com/search/results?search_mode=cluster&search_area=cluster&search_cluster=thelancet&search_sort=date&restrictname_author=author&restricttype_author=author&restrictterm_author=saulsbury0w&restrictdesc_author=William+Saulsbury>MA
 c<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#aff3>
 and
Prof Colin Blakemore<http://www.thelancet.com/search/results?search_mode=cluster&search_area=cluster&search_cluster=thelancet&search_sort=date&restrictname_author=author&restricttype_author=author&restrictterm_author=blakemore0c&restrictdesc_author=Colin+Blakemore>FRS
 d<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#aff4>
 e<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#aff5>

 See Comment<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604711/fulltext>
 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.
Back to top<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#article-outline>

  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
£10 billion and £16 billion per
year,1<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib1>with
the global burden being proportionately enormous.
2,3<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib2>

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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib4>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib5>
 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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib9>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib5>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib10>

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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib11>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib12>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#tbl1>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.
  [image: Table Thumbnail Icon]

Click to view table
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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib13>Once
refined through this piloting, an assessment questionnaire based on
table
1<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#tbl1>,
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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib14>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#tbl2>).
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 articles5,6,7,15–18<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib5>were
provided.
  [image: Table Thumbnail Icon]

Click to view table
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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#fig1>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib19>
  [image: Mean harm scores for 20 substances]
Click to enlarge image
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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#fig2>).
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.
  [image: Correlation between mean scores from the independent experts and
the specialist addiction psychiatrists]
Click to enlarge image
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.

Table 3<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#tbl3>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.
  [image: Table Thumbnail Icon]

Click to view table
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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#fig1>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib9>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib20>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
publications5–8,11,12,21,22<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib5>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib23>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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib24>and
the CAM committee of the Dutch government
25<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib25>)
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<http://www.thelancet.com/journals/lancet/article/PIIS0140673607604644/fulltext#bib26>
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