The health and psychological consequences of cannabis use chapter 3

National Drug Strategy
Monograph Series No. 25

3. Evidential principles 



3.1 Issues in appraising health hazards

The evaluation of the health hazards of any drug is difficult for a
variety of scientific and sociopolitical reasons. First, causal
inferences about the effects of drugs on human health are not easy to
make (ARF/WHO, 1981). Even inferences about the relatively direct and
transient effects of acute drug use may be complicated by individual
variability in response to a standard dose of a drug, and by the fact
that serious adverse effects are relatively rare. Inference becomes
more difficult the longer the interval between use and alleged ill
effects: it takes time for such effects to develop, and it may take
considerably longer for the research technology to be developed that
enables these effects to be identified and confidently attributed to
the drug use rather than some other factor (Institute of Medicine,
1982). In the case of chronic tobacco use, for example, it has taken
over three hundred years to discover that it increases premature
mortality from cancer, and heart disease. Moreover, new health hazards
of tobacco use, such as passive smoking, continue to be discovered. 

Second, in making causal inferences about drug use and its
consequences there is a tension between the rigour and relevance of
the evidence. The most rigorous evidence is provided by laboratory
investigations using experimental animals, or in vitro preparations of
animal cells and micro-organisms in which well controlled drug doses
are related to precisely measured biological outcomes. The relevance
of such research to human disease, however, is often problematic. A
great many inferences have to be made in linking the occurrence of
specific biological effects in laboratory animals or cell cultures to
the likely effects of the drug under existing patterns of human use. 

Epidemiological studies of relationships between drug use and human
disease have manifestly greater relevance to the appraisal of the
health risks of human drug use, but this is purchased at the price of
reduced rigour. Doses of drugs over periods of years are difficult to
quantify in the best of circumstances. The vagaries of human memory
which make quantification of consumption difficult in the case of
tobacco and alcohol are magnified in the case of illicit drugs by the
non-standard doses and contaminants in blackmarket drugs, and the
reluctance of users to report illicit drug use. The fact that
different patterns of drug use and other life-style factors are often
correlated (e.g. alcohol and tobacco), makes attribution of
ill-effects to particular drugs even more difficult (Task Force on
Health Risk Assessment, 1986).

Third, appraisals of the hazards of recreational drug use are
unavoidably affected by the societal approval or disapproval of the
drug in question. As Room (1984) has observed, when evaluating the
impact of alcohol on non-industrialised societies, anthropologists
have often engaged in problem deflation in response to the problem
inflation of missionaries and colonial authorities. In our own
culture, the economic interests of tobacco and alcohol industries
provide a potent reason for problem deflation with these drugs. Such
problem deflationists often discount the adverse effects of alcohol
use, either by contesting the evidence for adverse effects, or by
denying that there is a causal connection between alcohol use and
particular adverse health effects.

Similar processes have been at work in the appraisal of the health
effects of recreational cannabis use. The countercultural symbolism of
cannabis use in the late 1960s has introduced a strong sociopolitical
dimension to the debate about the adverse health effects of cannabis.
Politically conservative opponents of cannabis use, for example,
justify its continued prohibition by citing evidence of the personal
and social harms of its use. When the evidence is uncertain, as it is
with many of the alleged effects of chronic use, they resolve the
uncertainty by assuming that the cannabis is unsafe until proven safe.
Complementary behaviour is exhibited by some proponents of
decriminalisation. Evidence of harm is discounted or discredited, and
uncertainties about the ill-effects of chronic cannabis use are
resolved by demanding more and better evidence, arguing that until
this uncertainty is resolved individuals should be allowed to exercise
their free choice about whether or not they use the drug. 

Such approaches to the appraisal of evidence have not always been
consistently applied. Both sides of the debate would reject the
application of their own approaches to the appraisal of cannabis to
the appraisal of the health hazards of alcohol, pesticides,
herbicides, or chemical residues in food. While we do not claim to be
unaffected by these processes, we will be as explicit as possible
about the evidential standards that we have used, and as even-handed
as we can in their application.



3.2 Evidential desiderata

The following issues must be addressed in specifying what we have
taken to be the evidential desiderata in our appraisal of the health
risk of cannabis use: the burden of proof; standard of proof; criteria
for causal inference; preference for relevance or rigour; approaches
to estimating the magnitude of risk; and the desirability of a
comparative appraisal of the risks.

The burden of proof concerns who bears the responsibility for making a
case; those who make a claim of adverse health effects, or those who
doubt it (see Rescher, 1977, chapter XII). Who bears the burden of
proof determines the way in which an issue is decided in the face of
uncertainty: if the burden falls on those who claim that the drug is
safe, uncertainty will be resolved by assuming that it is unsafe until
proved otherwise; conversely, if the burden falls on those who claim
that the drug is unsafe, then it will be assumed to be safe until
proven otherwise.

It is by no means agreed who bears the burden of proof in the debate
about the health effects of cannabis use. Proponents of continued
prohibition appeal to established practice (Whately, 1846), arguing
that since the drug is illegal, the burden of proof falls upon those
who want to legalise it. Some proponents of its legalisation counter
that this begs the question, since there was no evidence, they argue,
that cannabis was harmful when its use was first made a criminal
offence. Others argue that the burden of proof falls upon those who
wish to use the criminal law to prevent adults from freely choosing to
use a drug (e.g. Husak, 1992).

We will vary the burden of proof on the basis of the state of the
evidence and argument. Once a prima facie case of harm has been made,
positive evidence of safety will be required rather than the simple
absence of any evidence of ill effect. We will assume that a prima
facie case has been made either when there is direct evidence that the
drug has ill effects in animals or humans (e.g. from a case-control
study), or when there is some compelling argument that it could, e.g.
the inference that since tobacco smoking causes lung cancer and
cannabis and tobacco smoke are similar in their constituents, it is
probable that heavy cannabis smoking also causes lung cancer. 

The standard of proof reflects the degree of confidence required in an
inference that there is a causal connection between drug use and harm.
In courts of law, the standard of proof demanded depends upon the
seriousness of the offence at issue and the consequences of a verdict,
with a higher standard of proof, "beyond reasonable doubt", being
demanded in criminal cases, while the "balance of probabilities" is
acceptable in civil cases. Although these legal standards are not
directly translatable into scientific practice, scientists generally
require something closer to the standard of "beyond reasonable doubt"
than the balance of probabilities before drawing confident conclusions
that a drug causes harm. 

If we were to demand that such a standard be met for the health
effects of cannabis, this review would be exceedingly brief.
Consequently, we will relax the criteria and indicate when the
evidence permits a causal inference to be made on the balance of
probabilities. We will take this standard to be exemplified in the
consensus of informed scientific opinion that sufficient evidence has
been provided to infer a probable causal connection between drug use
and a harm (e.g. Fehr and Kalant, 1983; Institute of Medicine, 1982). 

In the trade-off between relevance and rigour, our preference will be
for human evidence, both experimental and epidemiological, rather than
animal and in vitro studies. In the absence of human evidence, in
vitro and animal experiments will be taken as raising a suspicion that
drug use has an adverse effects on human health. The degree of
suspicion raised will be in proportion to the number of such animal
studies, the consistency of their results across different species and
experimental preparations (Task Force on Health Risk Assessment,
1986), and the degree of expert consensus that the inferences from
effects in vitro and in vivo to adverse effects under existing
patterns of human use are valid. The degree of consensus on the latter
point will be indicated by the views expressed in authoritative
reviews in peer reviewed journals or contributions to international
consensus conferences (e.g. Fehr and Kalant, 1983; Institute of
Medicine, 1982).

The criteria for causal inference that we will use are standard ones
(see Hall, 1987), namely:

1.	Evidence that there is a relationship between drug use and a
	health outcome provided by one of the accepted types of
	epidemiological research design (namely, case-control,
	cross-sectional, cohort, or experiment).

2.	Evidence (usually provided by a statistical significance test or
	the construction of a confidence interval) that the relationship is
	unlikely to be due to chance.

3.	Good evidence that drug use precedes the adverse effect (e.g. a
	cohort study).

4.	Evidence either from experiment, or statistical or other form of
	control, which makes it unlikely that the relationship is due to some
	other variable which is related to both drug use and the adverse
	effect. 

In appraising a body of literature as a whole we determine the extent
to which the evidence meets the criteria outlined by Hill (1977). 

Ideally, once a strong case has been made for a causal connection
between drug use and an adverse health effect, the magnitude of risk
needs to be estimated so the seriousness of the risk can be
quantified. For example, the consumption of large amounts of water
over a short period of time can kill human beings, but this is not a
good reason for counselling people against drinking water. The
quantities required to produce intoxication and death are so large
(e.g. 30 or more litres) that only diseased or psychotic individuals
consume them.

The standard epidemiological measures of risk magnitude are relative
risk and population attributable risk. The relative risk is the
increase in the odds of experiencing an adverse health outcome among
those who use the drug compared to those who do not (that is, the
number of times greater the risk of experiencing an effect is among
those who use the drug compared with those who do not). The population
attributable risk represents that proportion of cases with an adverse
outcome which is attributable to drug use. The two measures of risk
magnitude have different uses and implications. Relative risk is of
greatest relevance to individuals attempting to estimate the increase
in their risk of experiencing an adverse outcome if they use a drug.
Attributable risk is of most relevance to a societal appraisal of the
harms of drug use. 

The importance of the two measures of risk magnitude depends upon the
prevalence of drug use and the base rate of the adverse outcome. An
exposure with a low relative risk may have a large public health
impact if a large proportion of the population is exposed (e.g.
cigarette smoking and heart disease). Conversely, an exposure with a
high relative risk may have little public health importance because
very few people are exposed to it. Accordingly, an appraisal of the
public health importance of illicit drug use must take some account
not only of the relative risk of harm, but also the prevalence of use
and the base rate of the adverse effect. As will become apparent in
the course of this review, it is very difficult to estimate either
relative or attributable risk of any probable adverse health effects
of cannabis use because few epidemiological studies have been
conducted.

A different way of assessing the health risk posed by cannabis use has
had to be used: a comparative qualitative appraisal of its risks with
those of other widely used recreational drugs such as alcohol and
tobacco (ARF/WHO, 1981). The motive for such comparisons is that they
reduce the operation of double-standards in the health appraisal of
drug use by reminding us that the drugs we currently tolerate pose
major health risks. They also help to put the risk of newer drugs into
perspective, so that we can use a common standard when making societal
decisions about whether or not to tolerate such drug use. The task of
comparison, however, is more difficult than it seems at first. 

First, we know much more about the quantitative risks of acute and
chronic tobacco and alcohol use than we know about the health risks of
currently illicit drugs. This is largely because the legal drugs have
been consumed by substantial proportions of the population, over
centuries in the case of tobacco, and millennia in the case of
alcohol, and there have been more than 40 years of scientific studies
of the health consequences of their use. The contemporary illicit
drugs, by contrast, have been much less widely used in Western
society, and for a shorter period, primarily by healthy young adults;
there have also been few studies of their adverse health effects, and
there have been even fewer attempts to quantify the risks of their
use.

Second, the prevalence of use of currently legal and illegal drugs is
so different that any comparison based upon existing patterns of use
will disadvantage the legal drugs (Peterson, 1980). In principle, this
problem could be addressed by estimating what the health risks of
cannabis use might be if its prevalence was to approach that of
alcohol and tobacco. This approach has not been adopted here because
in the absence of good data on the quantitative risks of cannabis use,
a large number of contestable assumptions would have to be made to
permit such estimates to be made. 

These obstacles provide strong reasons for cautiously interpreting
comparisons of the health hazards of cannabis with those of alcohol
and tobacco. They do not, however, provide insurmountable objections
to such comparisons. We will accordingly make some qualitative
comparisons with the health risks of alcohol and tobacco after we have
considered the evidence on the adverse health effects of cannabis. 



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