APPENDIX 14
Supplementary memoranda from the Advisory
Council on the Misuse of Drugs (ACMD)
A RATIONAL SCALE FOR ASSESSING THE RISKS
OF DRUGS OF POTENTIAL MISUSE
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 recently been estimated to be somewhere between £10
billion and £16 billion per year (Ref 1).
The main current approaches to drug misuse are
interdiction of supply (via policing and customs control), education
and treatments. All three demand clarity in terms of the relative
risks and harms that drugs engender. At present, attitudes to
policing and the punishments for possession and supply of drugs
are scaled according to their classification under the Misuse
of Drugs Act (MDAct), while education and health care provision
are nominally tailored to the known actions and harms of specific
drugs.
In the current MDAct, the three Classes—A,
B or C— are intended to reflect the dangers of the drug,
Class A being the most harmful and C the least. The classification
of a drug determines several factors, in particular the legal
penalties for importation, supply and possession, as well as the
degree of police effort targeted at limiting its use. As well
as being given a Class, all drugs are also placed in one of five
Schedules depending on whether they have clinical utility and,
if so, their safe-keeping and prescribing requirements. Drugs
with no present clinical use are in Schedule 1 (eg MDMA, LSD),
the most abusable clinically useful drugs (eg diamorphine [heroin],
morphine) are in Schedule 2 and the less risky drugs are in lower
Schedules. The current classification system has evolved in an
unsystematic way from somewhat arbitrary foundations with seemingly
little scientific basis. In this paper we suggest a new system
for evaluating the risks of individual drugs that is based as
far as possible on facts and scientific knowledge. We suggest
it could form the basis of a new classification system for the
MDAct. It provides a rational means to rank the relative threat
from any new street drug, as well as to respond to evolving evidence
about the potential harm of current drugs.
Beginning from first principles, we suggest
that there are three main factors that together determine the
harm associated with any drug of potential abuse. These are:
— The physical harm to the individual
user caused by the drug;
— The tendency of the drug to
induce dependence;
— The impact of drug use on families,
communities and society.
The MDAct classification refers only to drugs
that are currently illegal in the UK. The system we propose is
intended to be of more general value. We intend this to be flexible
and of broad utility. It is applicable to different cultures and
traditions, and to changing social attitudes. It applies to all
drugs, legal or illegal, when used for other than medicinal purposes.
CATEGORIES OF
HARM
Physical harm
Assessing the propensity of a drug to cause
physical harm, ie damage to organs, 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 impact of a drug on physiological functions, such as
respiration and the heart, are major determinants of physical
harm. The route of administration is relevant to the assessment
of harm. Drugs such as heroin, especially taken intravenously,
carry a high risk of causing sudden death from respiratory depression,
and they therefore score highly on acute harm. Tobacco and alcohol
have a high propensity to cause illness and death on chronic administration.
Recently published evidence shows that long-term cigarette smoking
reduces life expectancy, on average, by 10 years (Ref 2). Tobacco
and alcohol together account for about 90% of all drug-related
deaths in the UK.
The Medicines and Healthcare Regulatory Authority
[MHRA], through the Committee on the Safety of Medicines (CSM),
has well-established methods of assessing the safety of medicinal
drugs that can be used as the basis of this aspect of risk appraisal.
Indeed a number of drugs of abuse have licensed indications in
medicine and will therefore have had such appraisals, albeit,
in most cases, determined many years ago. Three separate aspects
of physical harm can be identified:
— Acute—meaning the immediate
effects, eg respiratory depression with opiates, acute cardiac
crises with cocaine, and fatal poisonings;
— Chronic—referring to the
health consequences of repeated use, eg psychosis with stimulants,
possible lung disease with cannabis;
— The specific aspect of intravenous
(iv) use.
The route of administration is relevant not
only to acute toxicity but also to "secondary" harms.
For instance, administration of drugs by the iv route can lead
to the spread of blood-borne viruses such as hepatitis and HIV,
which have huge health implications for the individual and society.
The potential for iv use is currently taken into account in the
MDAct classification and was treated as a separate parameter in
our exercise.
Dependence
This dimension of harm involves interdependent
elements—the pleasurable effects the drug produces and its
propensity to produce dependent behaviour. Highly pleasurable
drugs such as opiates and cocaine are frequently 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 drugs in ways that allow them to be injected intravenously
or smoked: in both cases, effects on the brain can occur within
30 sec. 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 a variety
of factors and mechanisms. The special nature of drug experiences
certainly plays a part. Indeed, in the case of hallucinogens (LSD,
mescaline, etc) it might be the only factor that drives regular
use, and such drugs are usually rather infrequently used. 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 (progressively higher
doses being needed for the same effect), intense craving, and
withdrawal reactions, such as tremors, diarrhoea, sweating and
sleeplessness, when drug use is stopped. These indicate that adaptive
changes occur as a result of drug use. Addictive drugs are repeatedly
used, 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
and without physical symptoms directly related to drug withdrawal.
Some drugs, such as cannabis, can lead to habitual use that seems
to rest only on craving without obvious physical withdrawal symptoms.
But some other drugs, such as the benzodiazepines, can induce
psychological dependence without tolerance, in which physical
withdrawal symptoms occur through fear of stopping. This form
of dependence is less well studied and understood than addiction
but is a robust phenomenon, in the sense that withdrawal symptoms
can be induced simply by persuading a drug user that the drug
dose is being progressively reduced while it is, in fact, being
maintained constant (Ref 3).
The features of drugs that lead to dependence
and withdrawal reactions have been reasonably well characterised
and include:
— The drug half life (those that
are cleared rapidly from the body tend to provoke more extreme
reactions).
— The pharmacodynamic efficacy
of the drug (more efficacy = more dependence).
— The degree of tolerance that
develops on repeated use (more tolerance = more dependence and
withdrawal).
For many drugs there is a good correlation between
the phenomena seen in humans and those observed in studies on
animals. Also, drugs that share molecular specificity (having
similar tendencies to 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 humans.
Social harms
Drugs harm society in a number of ways. The
main ones are through the various effects of intoxication, through
damaging family and social life, and through the costs to the
healthcare, social care and policing systems. 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 frequent cause of car and other accidents. Many drugs cause
major damage to the family, either because of the impact 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
healthcare 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 A&E visits and orthopaedic
admissions (REF 4). 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.
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
sub-groups described above.
Table 1
ASSESSMENT PARAMETERS
| Category of harm
| Parameter | |
| Physical Harm | 1 |
Acute |
| 2 | Chronic
|
| 3 | IV harm
|
| Dependence | 4 | Intensity of pleasure
|
| 5 | Psychological dependence
|
| 6 | Physical dependence
|
| Social Harms | 7 | Intoxication
|
| 8 | Other social harms
|
| 9 | Healthcare costs
|
| |
|
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
[eg Table 3], the scores for the three parameters for each category
were averaged to give a mean score for that category. An overall
harm rating was obtained by taking the mean of all nine scores.
The scoring procedure was piloted by members of the panel
of the Independent Inquiry into the MDAct (the Runciman Committee
2000; Ref 5). Once refined through this piloting, an assessment
form based on Table 1, with additional guidance notes, was used.
Two independent groups of experts were asked to perform 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 canvassed on 14 compounds (those listed
in legend to fig 2). Tobacco (cigarettes) and alcohol were also
included because their extensive use has provided reliable data
on their risks and harms: hence, they provide familiar benchmarks
against which the absolute harms of other drugs can be judged.
Following this assessment a second group was convened that
also assessed these 14 substances and for completeness an additional
six abused compounds (khat, 4MTA, GHB, ketamine, methylphenidate,
alky nitrites (Table 2)). This group was made up of individuals
with a wide range of expertise in addiction—ranging from
the forensic science service through to general practitioners
and epidemiologists and included law enforcement officers. Scoring
was done independently and individual scores were then presented
to the whole group for a "Delphic" type discussion.
Individuals were allowed to revise their score on any of the parameters
in the light of this discussion, after which a final mean score
was calculated. The number of members taking part in the scoring
varied from eight to 16 over the course of several meetings.
Table 2
THE 20 SUBSTANCES ASSESSED SHOWING THEIR CURRENT STATUS
UNDER THE MDACT AND THE MISUSE OF DRUGS REGULATIONS
| Substance | Class in Act
| Schedule in Regulations | Comments
|
| Ecstasy | A | 1
| Essentially MDMA |
| 4-MTA | A | 1
| 4-methythioamphetamine |
| LSD | A | 1
| Lysergide |
| Cocaine | A | 2
| includes crack cocaine |
| Heroin | A | 2
| Crude diamorphine |
| Street Methadone | A | 2
| |
| Amphetamine | B | 2
| |
| Methylphenidate | B | 2
| eg "Ritalin" |
| Barbiturates | B | most in 3
| |
| Buprenorphine | C | 3
| Pending move to Class B |
| Benzodiazepines | C | most in 4(1)
| |
| GHB | C | 4(1)
| 4-hydroxybutyric acid |
| Anabolic Steroids | C | 4(2)
| |
| Cannabis | C | 1
| |
| Alcohol | - | -
| Not controlled |
| Alkyl Nitrites | - | -
| Not controlled |
| Ketamine | - | -
| Not controlled, but moving to class C in 2006
|
| Khat | - | -
| Not controlled |
| Solvents | - | -
| Not controlled |
| Tobacco | - | -
| Not controlled |
| |
| |
RESULTS AND
DISCUSSION
Use of this risk assessment system proved straightforward
and practicable. The overall mean scores by the independent group
averaged across all scorers, are plotted in rank order for all
20 substances in Figure 1. The classification of each substance
under the MDAct is also shown by the shading of the bars of the
histogram. Although the two substances with the highest harm ratings
(heroin and cocaine) are Class A drugs, overall there is a surprisingly
poor correlation between MDAct Class and harm score. Of both the
8 highest and the 8 lowest substances in the ranking of harm,
three are Class A and two are unclassified. Alcohol, ketamine,
tobacco and solvents (all unclassified) were ranked as more harmful
than LSD, ecstasy and its variant 4-MTA (all Class A). Indeed,
the correlation between MDAct classification and harm rating was
not statistically significant (Kendall's rank-correlation = -0.18;
2P = 0.25. Spearman's rank-correlation = -0.26; 2P = 0.26). Interestingly,
of the unclassified drugs, alcohol and ketamine were rated particularly
high, and the Advisory Council on the Misuse of Drugs has recently
recommended that ketamine should be added to the MDAct (as Class
C) [Ref 5A] .
Figure 2 compares 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 (see
legend to Fig.2). The average scores for the two groups were remarkably
well correlated (r = 0.892; t = 6.8; P <
0.001) which suggests the scores and process
have validity.
Figure 1
The mean scores for 20 substances (all
parameters; independent experts)
The respective classification, where appropriate,
under the Misuse of Drugs Act is shown above each bar. Class A
drugs are indicated by black bars, B by dark grey, and C by light
grey. Unclassified substances are shown as unfilled bars.
Table 3 lists the independent group results
for each of the three sub-categories 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. On the other hand, some drugs differed considerably in
their harm rating 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) and physical harm (since the ratings
for acute harm and potential for iv use were low). There was also
good agreement between the independent group and the psychiatrists
in their scores for the individual categories of harm.
Table 3
THE MEAN INDEPENDENT GROUP SCORES IN EACH
OF THE THREE CATEGORIES OF HARM, FOR 20 SUBSTANCES, RANKED BY
THEIR OVERALL SCORE, AS SHOWN IN FIGURE 1
| Substance | Group 1 Physical harm
| Group 2 Dependence | Group 3 Social harms
|
| Heroin | 2.78 | 3.00
| 2.54 |
| Cocaine | 2.33 | 2.39
| 2.17 |
| Barbiturates | 2.23 | 2.01
| 2.00 |
| Street Methadone | 1.86 |
2.08 | 1.87 |
| Alcohol | 1.40 | 1.93
| 2.21 |
| Ketamine | 2.00 | 1.54
| 1.69 |
| Benzodiazepines | 1.63 |
1.83 | 1.65 |
| Amphetamine | 1.81 | 1.67
| 1.50 |
| Tobacco | 1.24 | 2.21
| 1.42 |
| Buprenorphine | 1.60 | 1.64
| 1.49 |
| Cannabis | 0.99 | 1.51
| 1.50 |
| Solvents | 1.28 | 1.01
| 1.52 |
| 4-MTA | 1.44 | 1.30
| 1.06 |
| LSD | 1.13 | 1.23
| 1.32 |
| Methylphenidate | 1.32 |
1.25 | 0.97 |
| Anabolic Steroids | 1.45 |
0.88 | 1.13 |
| GHB | 0.86 | 1.19
| 1.30 |
| Ecstasy | 1.05 | 1.13
| 1.09 |
| Alkyl Nitrites | 0.93 | 0.87
| 0.97 |
| Khat | 0.50 | 1.04
| 0.85 |
| |
| |
Drugs that can be administered by the iv route were ranked
relatively high, and this was not caused solely by exceptionally
high scores for parameter three (propensity for iv use) and nine
(healthcare costs). Even if the scores for these two parameters
were excluded from the analysis, the high ranking for such drugs
persisted. In other words, drugs that can be administered intravenously
were also judged to be substantially harmful in many other respects.
Figure 2
Correlation between mean scores from the independent experts
and from the psychiatrists. one = heroin; two = cocaine; three
= alcohol; four = barbiturates; five = amphetamine; six = methadone;
seven = benzodiazepines; eight = solvents; nine = buprenorphine;
10 = tobacco; 11 = ecstasy; 12 = cannabis; 13 = LSD; 14 = steroids.
The correlation coefficient is r = 0.892 (P <
0.001). The straight line shows the least
squares fit.
Independent Experts
The results of this study do not provide justification
for the sharp A/B/C divisions of the MDAct classification. Distinct
categorisation is, of course, convenient for setting the priorities
for policing, education and social support, as well as for determining
sentencing for possession or dealing. But, first, the rank ordering
of drugs in the MDAct classification is not confirmed by the more
complete assessment of harm described here. Second, sharp divisions
in any ranking system are essentially arbitrary unless there are
obvious discontinuities in the set of scores. There is only a
hint of a discontinuity in the spectrum of harm in Figure 1 is
the small step in the very middle of the distribution, between
buprenorphine and cannabis. Interestingly, alcohol and tobacco
both appear in the top 10, higher-harm group. There is a rapidly
accelerating harm value for drugs higher than alcohol. So, one
possible interpretation of our findings is that drugs more dangerous
than alcohol might be Class A, cannabis and those below might
be Class C, and drugs in between might be B. In that case, it
is salutary to see that alcohol and tobacco—the most widely
used unclassified substances—would have harm ratings comparable
to Class B illegal drugs.
The participants in this study were asked to
assess the harm of drugs in the form that they are normally used.
In a few cases, it was clear that 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 mixed with tobacco, which might have elevated
its scores for physical harm, dependence, etc. There is a further
level of uncertainty resulting from polydrug use, particularly
in the so-called recreational group of drugs including GHB, ketamine,
ecstasy and alcohol, where adverse effects may be attributed mainly
to one of the components of common mixtures. Crack cocaine is
generally considered to be more dangerous than powdered cocaine,
but here they were considered together. Similarly the scores for
the benzodiazepines might have been biased in the direction of
the most abused drugs, especially temazepam. Individual scoring
of particular benzodiazepines and of other drugs that can be used
in different forms might be more appropriate.
With such relatively small numbers of independent
scores, we did not think that it was legitimate to estimates correlations
between the nine parameters. It is quite likely that there is
some redundancy: that is to say, they might not represent nine
independent measures of risk. Similarly, the principal components
of the parameters were not extracted, partly because it was felt
that there were insufficient data and partly because it might
not be appropriate to reduce the number of parameters to a core
group", at least until further assessment panels have independently
validated the entire system.
Our analysis gave equal weight to each parameter
of harm: 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, a single dose of which damages the substantia
nigra of the basal ganglia and induces an extreme form
of Parkinson's disease. Indeed, this simple form of the system
of scoring 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 reduces life expectancy by
an average of up to 10 years (A1) (Ref 2). It is the commonest
cause of drug-related deaths, and it is a huge burden on the Health
Service. But its short-term consequences and social effects are
modest. Of course, the weighting of individual parameters could
easily be changed, to emphasize one aspect of risk or another,
depending on the importance attached to each. And other procedural
mechanisms could be introduced to take account of extremely high
values for single parameters of harm.
Despite these qualifications, we were impressed
by the consistency of the scores between different groups of scorers
and the correlation between scores across the categories of harm,
for most drugs. Our findings raise questions about the validity
of the current MDAct classification, despite the fact that this
is nominally based on an assessment of risk to users and society.
This is especially true in relation to psychedelic type drugs.
They also emphasise that the exclusion of alcohol and tobacco
from the MDAct is, from a scientific perspective, arbitrary. The
fact that these two legal and widely used drugs lie in the upper
half of the ranking of harm is surely important information to
be taken into account in public debate on the impact of illegal
drug use.
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. It is rigorous, and
involves a formal, quantitative evaluation of several aspects
of harm. And it can easily be reapplied, as knowledge advances.
We note that a numerical system has also been described by MacDonald
et al. (Ref 6) for assessing the overall harm of drug use:
an approach that is complementary to the scheme described here.
CONCLUSIONS
The approach to harm estimation that we propose
provides a comprehensive and transparent process for the evaluation
of the danger of drugs. It could be developed to aid in decision-making
by regulatory bodies such as the UK's Advisory Council on the
Misuse of Drugs and the European Medicines Evaluation Agency.
Moreover, our findings reveal no clear distinction between socially
accepted and illicit substances. We note that other organisations
[eg the European Monitoring Centre for Drugs and Drug Addiction
(EMCDDA) (REF 7) and the CAM committee of the Dutch government
[REF 8] are currently exploring other risk assessment systems,
some of which are also numerically based. Such approaches might
help society to engage in a more rational debate about the relative
risks and harms of drugs, by basing discussion on a formal assessment
of harm rather than on prejudice and assumptions.
ACKNOWLEDGEMENTS
Some of the ideas developed in this paper arose
out of discussion at workshops organised by the Beckley Foundation
(Beckley Park, Oxford OX3 9SY), to whom we are grateful. We thank
Dr David Spiegelhalter of the MRC Biostatistics Unit for advice
on statistics.
June 2006
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