Chronic
(long-term) toxicity
4.13 Cannabis can have
untoward long-term effects on cognitive performance, i.e. the
performance of the brain, particularly in heavy users. These have
been reviewed for us by the Royal College of Psychiatrists and
the Royal Society. While users may show little or no impairment
in simple tests of short-term memory, they show significant impairments
in tasks that require more complex manipulation of learned material
(so-called "executive" brain functions) (Edwards Q 21).
There is some evidence that some impairment in complex cognitive
function may persist even after cannabis use is discontinued[10];
but such residual deficits if present are small, and their presence
controversial (van Amsterdam Q 494, Hall Q 741). Dr Jan
van Amsterdam of the Netherlands National Institute of Public
Health and the Environment, who has reviewed the literature on
long-term cognitive effects of prolonged heavy use and kindly
came to Westminster to tell us his findings, pointed out the practical
difficulties of assessing possible residual effects (Q 487). These
include the impossibility of obtaining predrug baseline
values (i.e. measures of the cognitive functioning of the subject
before their first use of cannabis), the difficulty of estimating
the drug dose taken, the need for a lengthy "washout"
period after termination of use to allow for the slow elimination
of residual cannabis from the body, and the possibility of confusing
long-term deficits with withdrawal effects. He felt that many
of the published reports on this subject had not taken adequate
account of these problems.
4.14 The occurrence
of an "amotivational syndrome" in long-term heavy cannabis
users, with loss of energy and the will to work, has been postulated.
However it is now generally discounted (van Amsterdam Q 503);
it is thought to represent nothing more than ongoing intoxication
in frequent users of the drug (RCPsych p 283).
4.15 Animal experiments
have shown that cannabinoids cause alterations in both male and
female sexual hormones; but there is no evidence that cannabis
adversely affects human fertility, or that it causes chromosomal
or genetic damage (WHO report ch.7). The consumption of cannabis
by pregnant women may, however, lead to significantly shorter
gestation and lower birth-weight babies in mothers smoking cannabis
six or more times a week (WHO report ch.8; DH p 47). These
effects may be due to the inhalation of carbon monoxide in cannabis
smoke, which lowers the ability of the blood to carry oxygen to
the foetus, rather to any direct effect of cannabinoids. If so,
they are comparable with the effects of smoking tobacco.
4.16 The NHS National
Teratology [i.e. foetal abnormality] Information Service advise,
"There are a few case reports of malformations following
marijuana use in pregnancy. However, there is no conclusive evidence
to suggest either an increase in the overall malformation rate
or any specific pattern of malformations". Nevertheless,
they warn: "We would not recommend the legalisation of cannabis
because of the potential fetotoxicity that may occur if it is
used in pregnancy" (p 280).
4.17 Most of our witnesses
regard the consequences of smoking cannabis as the most important
long-term risk associated with cannabis use[11].
Cannabis smoke contains all of the toxic chemicals present in
tobacco smoke (apart from nicotine), with greater concentrations
of carcinogenic benzanthracenes and benzpyrenes It has been estimated
(BMA p 11) that smoking a cannabis cigarette (containing
only herbal cannabis) results in approximately a fivefold
greater increase in carboxyhaemoglobin concentration[12],
a threefold greater increase in the amount of tar inhaled,
and a retention in the respiratory tract of one third more tar,
than smoking a tobacco cigarette. Cannabis resin, the most commonly
used form of cannabis in the United Kingdom, is often smoked mixed
with tobacco, thus adding the well-documented risks of exposure
to tobacco smoke, while complicating the picture for the researcher.
4.18 Regular cannabis
smokers suffer from an increased incidence of respiratory disorders,
including cough, bronchitis and asthma. Microscopic examination
of the cells lining the airways of cannabis smokers has revealed
the presence of an inflammatory response and some evidence for
what may be pre-cancerous changes. There is as yet no epidemiological
evidence for an increased risk of lung cancer (DH p 46, Q 205);
but, by analogy with tobacco smoking, such a link may take 25-30 years
or more before it becomes evident, and the widespread use of smoked
cannabis in Western societies dates only from the 1970s. There
are some reports of an increased incidence of cancers of the mouth
and throat in young cannabis users[13],
but so far these involve only small numbers and no cause and effect
relationship has been established. Nevertheless, Professor Hall
considers it a "pretty reasonable bet" that heavy users
incur a risk of cancer (Q 741); and the risk is considered by
some of our witnesses to be sufficiently serious to rule out any
approval of long-term medical use of smoked cannabis, and to justify
the present prohibition on recreational use.
Tolerance
to cannabis
4.19 Tolerance is the
phenomenon whereby a regular user of a drug requires more each
time to achieve the same effect. It is not an adverse effect in
itself; but it may make medical use more difficult, and recreational
use more damaging as the user's demand for the drug increases.
4.20 Dr Pertwee
told us that both animal and human data show that tolerance can
develop on repeated administration of high doses of cannabinoids;
tolerance may develop more readily to some effects in animals
(e.g. lowering of body temperature) than to others (Q 304). However
Clare Hodges[14],
a sufferer from MS, said that she had not experienced tolerance
to the palliative effects of low doses of cannabis, and had been
taking the same dose (9g of herbal cannabis per week, costing
about £30 per week, usually smoked) for six years; neither
had other medical users reported tolerance in their experience
(QQ 117-119; cp LMMSG p 269).
4.21 Whether tolerance
develops may therefore depend on how much drug is consumed, and
how often. Neil Montgomery, a research journalist currently
studying cannabis users through the Department of Social Anthropology
at the University of Edinburgh, said that his observations of
heavy cannabis users (using more than 28g of cannabis resin per
week) suggested that they needed as much as eight times higher
doses to achieve the same psychoactive effects as regular users
consuming smaller doses of the drug (Q 570). Clear evidence
of tolerance has also been reported in volunteers given large
doses of THC under laboratory conditions (Pertwee Q 304).
4.22 This conforms
with the evidence of Professor Wall, who compared the experience
with morphine and related opiate pain-relieving agents during
the past 20-30 years, pioneered by Dame Cicely Saunders and
the Hospice movement. This has shown that tolerance (and addiction—see
below) are not major problems in the medical use of these drugs,
although in recreational use they may pose severe problems (Q 120).
Dependence
on cannabis
4.23 The repeated use
of cannabis or cannabinoids does not result in severe physical
withdrawal symptoms when the drug is withdrawn; so many have argued
that these drugs are not capable of inducing dependence. Dr Pertwee,
and Dr David Kendall of the University of Nottingham (p 267),
however, described new evidence from animal studies showing marked
signs of withdrawal in animals treated repeatedly with large doses
of cannabinoids and then challenged with a newly developed cannabinoid
CB1 receptor antagonist (see Box 1) called SR141716A. This has
provided the first real evidence for physical dependence and withdrawal
symptoms in animals (QQ 308-310).
4.24 The BMA report
says that withdrawal symptoms from cannabis in man are mild and
shortlived; but in the light of the newer definitions of
dependence noted in Box 2 this evidence is inconclusive. Professor
Ashton indicated that she felt cannabis to be potentially addictive,
and compared the withdrawal symptoms—tremor, restlessness
and insomnia—to those experienced by users of alcohol, sleeping
pills or tranquillisers. She had talked to students with quite
severe cannabis withdrawal problems (Q 73).
