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Select Committee on Science and Technology Report (The text of the report
on medical marijuana commissioned by the House of Lords says the Government
should allow doctors to prescribe cannabis for medical use. "Far from being
a step towards general legalisation, our recommendation would make the ban
on recreational use easier to enforce.")
Date: Wed, 11 Nov 1998 14:50:02 -0800
From: owner-mapnews@mapinc.org (MAPNews)
To: mapnews@mapinc.org
Subject: MN: UK: Press Release: House of Lords Cannabis Report
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Pubdate: Wed, 11 Nov 1998
Source: The House of Lords, Science and Technology Committee (UK)
Contact: Fax: +0171-219 6715 or 0171-219 4931
Mail: Science and Technology Committee, House of Lords, London, SW1A 0PW
Website: http://www.parliament.the-stationery-office.co.uk/pa/ld/ldhome.htm
Note: Thanks to a tip from Stuart Kocher that led us to this important
document. It is being posted by chapters, but first, the press release:
Select Committee on Science and Technology Report
***
H O U S E of L O R D S
P R E S S I N F O R M A T I O N
EMBARGO 0001 HOURS
WEDNESDAY 11th NOVEMBER 1998
***
LORDS SAY, LEGALISE CANNABIS FOR MEDICAL USE
The Government should allow doctors to prescribe cannabis for medical
use: this is the conclusion of a report by the House of Lords Science
and Technology Committee, published today.
Lord Perry of Walton, chairman of the inquiry said: "We have seen enough
evidence to convince us that a doctor might legitimately want to
prescribe cannabis to relieve pain, or the symptoms of multiple
sclerosis (MS), and that the criminal law ought not to stand in the way.
Far from being a step towards general legalisation, our recommendation
would make the ban on recreational use easier to enforce. Above all, it
would show compassion to patients who currently risk prosecution to get
help."
MEDICAL USE
Cannabis is a "Schedule 1" drug, and cannot be used at all in medicine,
except for research under special Home Office licence. The Lords
recommend that it should be moved to "Schedule 2". This would allow
doctors to prescribe it, subject to certain special regulations, and it
would allow doctors and pharmacists to supply it in accordance with a
prescription.
The report sets out evidence that cannabis can be effective in some
patients to relieve the symptoms of MS, and against certain forms of
pain. The Lords say, this evidence is enough to justify a change in the
law. They are less convinced about its effectiveness in other
conditions, including epilepsy, glaucoma and asthma.
The Lords welcome the fact that clinical trials of cannabis are
currently being launched, by the Royal Pharmaceutical Society, and by Dr
Geoffrey Guy of GW Pharmaceuticals, with a view to the eventual
licensing of cannabis as a medicine. The Lords say, however, that
cannabis should be rescheduled now, rather than waiting several years
for the results of these trials.
If cannabis ever becomes a licensed medicine, the Lords do not envisage
it being licensed for smoking; they call for research into alternative
delivery systems.
At present, people who use cannabis for medical reasons risk
prosecution; and juries sometimes refuse to convict such people, which
brings the law into disrepute. If prescription were legalised, then
someone using cannabis for medical reasons who was accused of
recreational use could clear himself at once by producing the
prescription. [More]
RECREATIONAL USE
The Lords find enough evidence of toxic effects of cannabis to justify
maintaining the present ban on recreational use. Besides being
intoxicating, they report that:
- regular heavy use can lead to psychological dependence, and even in
some cases to physical dependence, involving withdrawal symptoms;
- cannabis can pose a risk to people with a heart condition;
- cannabis can exacerbate pre-existing mental illness;
- smoking cannabis is as bad for the lungs as smoking tobacco, and may
cause cancer.
NOTES FOR EDITORS
1. The report follows an inquiry which began in April, and included 12
public hearings. A list of the Lords who took part in the study is
attached :
2. The report is published by The Stationery Office: Cannabis, HL
Paper 151, ISBN 0 10 4151986, £9.50.
3. The evidence taken by the Committee is published separately as HL
Paper 151-I, ISBN 0 10 4792981, £22.60.
4. The full text will be on the Internet on publication, accessible
via the UK Parliament home page at www.parliament.uk
4. The Government are required to respond in writing to the report;
and the report will be debated in the House of Lords.
Further information from Elaine Morgan/Tessa Perfect
House of Lords Committee Office
'Phone 0171-219 6075; Fax 0171-219 4931 [Ends]
CHAIRMAN
Lord Perry of Walton FRS (Lib Dem): former Professor of Pharmacology;
founding Vice-Chancellor of the Open University 1969-81.
MEMBERS
Lord Butterfield (Cons): Vice-Chancellor of Nottingham University
1970-75; Regius Professor of Physic (ie medicine), Cambridge, 1975-87;
Vice-Chancellor of Cambridge University 1983-85.
Lord Butterworth (Cons): Vice-Chancellor of the University of Warwick
1963-85.
Lord Carmichael of Kelvingrove (Lab): MP 1962-83; former junior Minister
in various departments.
Lord Dixon-Smith (Cons): former Chairman, Association of County
Councils.
Lord Kirkwood (Lib Dem): metallurgist; former lecturer, Sheffield
University.
Lord Nathan (cross-bench): solicitor; former member of Royal Commission
on Environmental Pollution.
Lord Porter of Luddenham (cross-bench): Nobel Prize for Chemistry 1967;
President of the Royal Society 1985-90.
Lord Rea (Lab): former GP.
Lord Soulsby of Swaffham Prior (Cons): Emeritus Professor of Animal
Pathology, Cambridge; President of the Royal Society of Medicine.
Lord Walton of Detchant (cross-bench): former professor of Neurology and
Dean of Medicine, Newcastle University; former President of the General
Medical Council, the British Medical Association, and the World
Federation of Neurology.
Lord Winston (Lab): Dean of the Institute of Obstetrics and Gynaecology.
***
Select Committee on Science and Technology Ninth Report
***
CANNABIS:
THE SCIENTIFIC AND MEDICAL EVIDENCE
CHAPTER 1 INTRODUCTION
1.1 Cannabis has been used medically for thousands of years in
oriental and Middle Eastern countries and as an intoxicant for many
hundreds of years in India and in the Middle East; and it was employed
in Western medicine for at least two millennia. The medical use of
cannabis in Europe and North America, however, declined in this century
because of the lack of any standardised preparations of the plant
product and its unreliable absorption when given by mouth, and because
of the development of more potent and reliable drugs for the conditions
for which cannabis was then being used.
1.2 During the 1960s and 1970s there was a large increase in the
use of smoked cannabis as an intoxicant in the USA and in Europe, where
it had been largely unknown previously as a drug of abuse. The
recreational use of cannabis has continued to increase in recent years,
particularly among the young. Medical use in the United Kingdom was
prohibited in 1973; but cannabis is now the most widely used of all
illegal intoxicants.
1.3 During the 1980s and 1990s there has been renewed interest in
the potential medical uses of cannabis and its derivatives. Substantial
numbers of patients with various conditions are illegally
selfmedicating with cannabis and are convinced that they derive medical
benefit-although scientific evidence for or against such a conclusion is
largely lacking. This has led to calls for cannabis again to be made
available for medical applications.
1.4 In Britain this debate has led a number of expert bodies to
review the medical and scientific evidence for and against such
proposals. The British Medical Association published a report on the
topic in 1997[1]. The Department of Health recently commissioned three
literature reviews on cannabis, at the request of the Advisory Council
on the Misuse of Drugs (ACMD); we have seen these (they were placed in
the Library of the House on 9 June), and the authors have all given
evidence to this inquiry[2]. Reports were also published last year by
the US National Institutes of Health and the American Medical
Association[3].
1.5 In the light of this heightened interest in cannabis, and
particularly the report by the BMA, we decided to examine the scientific
and medical evidence to determine whether there was a case for relaxing
some of the current restrictions on the medical uses of cannabis. We
have also considered whether the continued prohibition of recreational
use is justified on the basis of the scientific evidence of adverse
effects. Recreational use raises other issues besides the adverse
effects of the drug; these are outside our remit "to consider science
and technology", belonging instead to the realms of law, sociology and
even philosophy, and we have not considered them. Neither have we
considered whether cannabis is a stepping stone or gateway to other more
dangerous drugs; we have confined our considerations solely to cannabis.
1.6 Chapters 2 and 3 of this Report are introductory, giving brief
accounts of the history of cannabis and its pharmacology. In Chapters
4-7 we review the evidence which we have received on the four key
issues: the adverse effects of taking cannabis; current and proposed
medical uses; recreational use; and the implications of possible changes
to the law. Our conclusions and recommendations are set out in Chapter
8.
1.7 This report was prepared by Sub-Committee I, whose members are
listed in Appendix 1. They received evidence from the persons and
organisations listed in Appendix 2, to all of whom we are grateful for
their help. We are particularly grateful to the Sub-Committee's
Specialist Adviser, Professor Leslie Iversen FRS, Visiting Professor of
Pharmacology at the University of Oxford. Professor Iversen attended two
international conferences on the Sub-Committee's behalf; his accounts of
these appear in Appendices 3 and 4. Abbreviations are listed in Appendix
5.
1.8 We also acknowledge the assistance of the Parliamentary Office
of Science and Technology (POST). POST's report Common Illegal Drugs and
their Effects (May 1996), and POST note 113 Cannabis Update (March
1998), have been particularly helpful.
***
1 Therapeutic uses of cannabis, BMA/Harwood Academic Publishers, 1997,
ISBN 90-5702-318-0. Back
2 Cannabis: clinical and pharmacological aspects, by Prof C H Ashton;
Psychiatric aspects of cannabis use, by Dr A Johns; Therapeutic aspects
of cannabis and cannabinoids, by Dr P Robson. Back
3 NIH Report on the medical uses of marijuana, August 1997; AMA
Medical Marijuana, December 1997. Back
***
Select Committee on Science and Technology Ninth Report
***
CHAPTER 2 HISTORY OF THE USE OF CANNABIS
2.1 The earliest known reference to cannabis is in Assyrian
tablets of the seventh century BC. It has thus been in use for at least
2600 years. Like very many other herbs, it has been used medically for a
wide variety of ailments, especially throughout Asia and the Middle
East. The mild euphoria that it induces led to its use as an intoxicant,
perhaps most notably in countries where Islam prohibited the use of
alcohol.
2.2 In Western medicine, it appeared in the Herbal (i.e.
pharmacopoeia) of Dioscorides of about 60 AD, and in all subsequent
herbals. The 16th century saw a detailed interest in cannabis, with
reports of it and its usages being sent back by many travellers to the
East, and the number of possible uses given in the herbals doubled. In
England, the Herbal of John Gerard (1597) recommended it as it
"consumeth wind and drieth up seed [i.e. semen]", and quoted Dioscorides
as recommending it for easing the pain of earache and for the treatment
of jaundice. Nicholas Culpeper, in his Herbal (1653), gave the same
indications for the use of cannabis seeds, and also recommended the
decoction of the roots, as this "allayeth inflammations, easeth the pain
of gout, tumours or knots of joints, pain of hips...".
2.3 In these and other early Herbals, each medicine was said to
have multiple uses, often without justification. More critical views
ultimately prevailed, but only slowly. Thus by 1788 the New Edinburgh
Dispensatory still included three quarters of the entries of
Dioscorides, but excluded most animal products. Such exotic remedies as
"scrapings of an elephant's tooth", "dust from the walls of a wrestling
school" and, remarkably, as a cure for quartan malaria, "seven bed bugs
in meat and beans", had been eliminated. The loss of the animal products
and most of the minerals left the 1788 New Dispensatory consisting
mainly of herbal remedies. There was little change for 150 years, and
the British Pharmacopoeia of 1914 included most of the contents of the
volume of 1788. But the situation was about to change radically, with
the rise of synthetic pharmaceutical chemistry.
2.4 Meanwhile, in 1833 Samuel Carey in his Supplement to the
Pharmacopoeia and Treatise on Pharmacology advised that cannabis could
be used to make "an agreeable intoxicating drink". This is the only
British reference to cannabis as an intoxicant known to us from this
period.
2.5 Cannabis was reintroduced into British medicine in 1842 by Dr
W O'Shaughnessy, an army surgeon who had served in India. In Victorian
times it was widely used for a variety of ailments, including muscle
spasms, menstrual cramps, rheumatism, and the convulsions of tetanus,
rabies and epilepsy; it was also used to promote uterine contractions in
childbirth, and as a sedative to induce sleep. It is said to have been
used by Queen Victoria against period pains: there is no actual proof of
this at all, but Sir Robert Russell, for many years her personal
physician, wrote extensively on cannabis, recommending it for use in
dysmenorrhoea. It was administered by mouth, not by smoking, but usually
in the form of a tincture (an extract in alcohol). Cannabis extracts
were also incorporated in many different proprietary medicines.
2.6 "People were well aware at that stage that [cannabis] was an
unpredictable drug" (Edwards Q 26). The advent of a host of new and
better synthetic drugs led to the abandonment of many ancient herbal
remedies, including cannabis. Thus in the British Pharmacopoeia of 1932
no fewer than 400 herbal remedies were omitted, among them cannabis,
extract of cannabis and tincture of cannabis-though all three remained
in the British Pharmaceutical Codex of 1949[4].
2.7 Until 1968, the only control of medicines in the United
Kingdom (other than those regarded as dangerous) was provided by the
pharmacopoeias, which set quality standards for the preparation of
drugs. The Medicines Act 1968 was enacted following the thalidomide
tragedy: it gave the Government power to license pharmaceutical
companies, and individual products and clinical trials. It also
established the Medicines Commission and the Committee on the Safety of
Medicines, to advise the Government on the exercise of their new powers.
Existing drugs received "licences of right". The licensing powers are
now exercised through the Medicines Control Agency (MCA). Doctors may
prescribe an unlicensed drug, or a licensed drug for an unlicensed
indication ("off-label"); but they do so at their own risk, and without
the benefit of the surveillance for adverse effects which is conducted
in respect of licensed medicines through the "yellow card" system.
2.8 Drug abuse has been the subject of international conventions
since 1912. In 1961 these were consolidated and brought up to date by
the UN Single Convention on Narcotic Drugs. Cannabis and cannabis resin
were listed in Schedule IV, which entitled (but did not oblige) parties
to adopt "special measures of control", and to ban them altogether
"except for amounts which may be necessary for medical and scientific
research only, including clinical trials..." (Article 2.5). According to
the Home Office (p 150), this reflected "WHO's view that the drug was
widely abused, had no therapeutic value and was obsolete in medical
practice". Under the Dangerous Drugs Act 1964 (shortly consolidated by
the Dangerous Drugs Act 1965), which implemented the Convention in the
United Kingdom, cannabis was still able to be prescribed, though subject
to certain controls. The tincture received a "licence of right" under
the Medicines Act 1968; doctors were therefore still able to prescribe
it.
2.9 The scale of drug abuse increased dramatically during the
1960s. In 1971 the UN adopted a further Convention on Psychotropic
Substances; and the United Kingdom enacted the Misuse of Drugs Act 1971,
which repealed the Act of 1965 and other enactments, replacing them with
a more comprehensive and flexible regime. Cannabinol and its derivatives
including THC (the chemical which gives cannabis its psychoactive
properties-see Chapter 3) appeared in Schedule I to the Convention, and
parties were therefore obliged to ban them "except for scientific and
very limited medical purposes by duly authorized persons" (Article
7(a)). In 1973 the licences of right granted in 1968 were reviewed, and
the original Misuse of Drugs Regulations (SI 1973 No. 797) were made
under the 1971 Act. Cannabis's licence of right was not renewed, and the
Regulations listed cannabis, cannabis resin and cannabinol and its
derivatives in Schedule 4-which is now Schedule 1 to the Misuse of Drugs
Regulations 1985 (No. 2066)-thereby prohibiting medical use altogether.
2.10 According to the MCA, by 1973 there was "insufficient
evidence" to support medical use of the tincture (Q 174), and it was
rarely prescribed except to patients who were already drug misusers. The
Parliamentary Under-Secretary of State for Health told the Commons on 14
January 1998 (col. 320), "It was rarely used and, when it was, it was
used mainly for its sedative qualities. Advice at the time from the
World Health Organization was that cannabis was no more effective than
any other available drug in treating the conditions for which it was
used, so its use was stopped." According to the Department of Health,
there was also a problem of diversion to recreational use through bogus
prescriptions (Q 174).
***
4 The British Pharmaceutical Codex, produced by the Royal
Pharmaceutical Society of Great Britain, was a source of officially
recognised standards for pharmaceutical preparations until 1979. Since
then it has been in the process of being superseded by the British and
European Pharmacopoeias. Back
***
CHAPTER 3 PHARMACOLOGY OF CANNABIS AND THE CANNABINOIDS
3.1 The plant Cannabis sativa is also known as hemp; it is related
to the nettle and the hop. It grows readily in a warm climate, and may
be grown in more temperate regions. As a drug of abuse, it usually takes
the form of herbal cannabis (marijuana), consisting of the dried leaves
and female flower heads, or cannabis resin (hashish), the resin secreted
by the leaves and flower heads, which may be compressed into blocks.
3.2 The family of chemically related 21carbon alkaloids found
uniquely in the cannabis plant are known as cannabinoids. There are more
than 60 different cannabinoids; one of these, D9tetrahydrocannabinol
(THC), is the most abundant and accounts for the intoxicating properties
of cannabis. Other cannabinoids which occur in some abundance (e.g.
cannabidiol and cannabinol) are not psychoactive, but it is thought that
they may modify the effects of THC. The amounts and proportions of the
various cannabinoids in each plant vary from strain to strain, and can
be adjusted by breeding. By coincidence, the chemistry and pharmacology
of cannabis were among the principal interests of the late Lord Todd,
when he worked at Manchester University in the 1930s; he went on to
become, among other things, the first Chairman of the House of Lords
Select Committee on Science and Technology on its establishment in 1979.
3.3 THC and other cannabinoids dissolve readily in fat but not in
water. This limits the possible formulations of cannabis and cannabinoid
preparations, and slows down their absorption from the gut. On the other
hand, when cannabis is smoked (in a "joint" or "reefer", or in a pipe),
THC is absorbed very quickly into the bloodstream, through the large
surface area of the pharynx and the lungs. After smoking, the
psychoactive effects of THC are perceptible within seconds, and peak
effects are achieved within minutes. When cannabis or cannabinoids are
taken by mouth, peak effects may not occur for several hours, but they
last longer. After smoking or oral ingestion, the drug persists in the
brain longer than in the blood; so the psychological effects persist for
some time after the level of THC in the blood has begun to decline.
3.4 Smoking delivers 30 per cent or more of the total THC in a
cannabis cigarette to the blood stream. The proportion of THC absorbed
after taking cannabis by mouth is 2-3 times less, because after
absorption in the gut the drug is largely degraded by metabolism in the
liver before it reaches the general circulation. Preliminary reports
indicate that absorption into the circulation can be increased if THC is
administered by rectal suppository, as this route delivers the drug
directly into the circulation, avoiding the liver.
3.5 Once THC has entered the bloodstream, it is widely distributed
in the body, especially in fatty tissues. The slow release of THC from
these tissues produces low levels of drug in the blood for several days
after a single dose, but there is little evidence that any significant
pharmacological effects persist for more than 4-6 hours after smoking or
6-8 after oral ingestion. The persistence of the drug in the body, and
the continuous excretion of degradation products in the urine, can
however give rise to cannabispositive forensic tests days or even weeks
after the most recent dose. (The implications of this for roadside
testing of drivers are considered below, at paragraph 4.9.)
3.6 According to Professor Trevor Robbins, speaking for the
Medical Research Council (MRC), "Cannabinoid pharmacology has exploded
in the last decade1/4, opening up1/4all sorts of exciting possibilities" (Q
628). These advances are reviewed in evidence to this Committee by the
Royal Society and by Dr Roger Pertwee of the University of Aberdeen[5].
It is now recognised that THC interacts with a naturally occurring
system in the body, known as the cannabinoid system. THC takes effect by
acting upon cannabinoid receptors (see Box 1). Two types of cannabinoid
receptor have been identified: the CB1 receptor and the CB2 receptor.
CB1 receptors are present on nerve cells in the brain and spinal cord as
well as in some peripheral tissues (i.e. tissues outside the brain); CB2
receptors are found mainly on cells of the immune system and are not
present in the brain.
3.7 The roles played by CB1 and CB2 receptors in determining the
various effects of cannabis in the whole organism remain to be
established. Among the effects of cannabinoids known from animal
experiments to be mediated by CB1 receptors are pain relief, impairments
in memory and in the control of movements, lowering of body temperature
and reductions in the activity of the gut. As CB1 receptors are the only
ones known to exist in the brain, it is assumed that they mediate the
intoxicant effects of THC. Little is known about the physiological role
of the more recently discovered CB2 receptor, but it seems to be
involved in the modulation of the function of the immune system.
BOX 1: CANNABIS PHARMACOLOGY-TERMINOLOGY
In common with many other drugs, the effects of THC result from its
ability to activate special proteins known as receptors found on the
surface of certain cells. The drug binds specifically to these proteins
and activates a series of processes within the cells, leading to
alterations in the cell's activity. Drugs, such as THC, that are able to
"switch on" a receptor are known as agonists at that receptor. Other
substances, however, bind to the receptor and, rather than activating
it, prevent its activation by agonists; such substances are known as
receptor antagonists. The term cannabinoid was originally used to
describe the family of naturally occurring chemicals found in cannabis,
of which THC is the principal member. It is now also taken to encompass
all those substances capable of activating cannabinoid receptors. These
include the naturally occurring plant cannabinoids, certain synthetic
substances (e.g. nabilone-see Box 4 below), and the recently discovered
endogenous cannabinoids (see paragraph 3.8 below).
3.8 Another important recent discovery has been that the body
contains naturally occurring ("endogenous") compounds that can activate
cannabinoid receptors. The most important of these "endogenous
cannabinoids" are the fatlike materials arichidonylethanolamide
("anandamide") and 2arichidonylglycerol (2AG).
3.9 These discoveries have transformed the character of scientific
research on cannabis, from an attempt to understand the mode of action
of a psychoactive drug to the investigation of a hitherto unrecognised
physiological control system in the brain and other organs. Although the
physiological significance of this system is still largely unknown, one
of the principal actions of THC and the endogenous cannabinoids seems to
be to regulate the amounts of chemical messenger substances released
from nerves in the brain, thus modulating neural activity.
3.10 The discovery of the endogenous cannabinoid system has
significant implications for future pharmaceutical research in this
area. Drugs that selectively activate CB1 or CB2 receptors (agonists),
or selectively block one or other of these receptor types (antagonists),
have already been developed by some pharmaceutical companies (Lambert p
109 and Q 438; Pertwee Q 285). Agonists to the CB2 receptor may have
beneficial effects in modulating immune responses, and would not be
expected to possess any psychoactive properties as the CB2 receptor is
not found in the brain. Antagonists to the CB1 receptor are also being
investigated, as novel therapeutic agents with the potential of reducing
memory deficits associated with ageing or neurological disease, as novel
treatments for schizophrenia or other psychoses, and as appetite
suppressants.
3.11 It seems likely that most of the putative medical indications
proposed for cannabis involve actions of the drug on CB1 receptors in
the central nervous system. Extensive attempts were made by academic and
pharmaceutical industry researchers during the 1970s to develop new
chemically modified cannabinoid molecules that separated the desired
therapeutic effects from the psychoactive properties of these
substances; but so far no such compound has been discovered.
3.12 Research continues apace. Professor Patrick Wall of St
Thomas' Hospital[6] reports "intense activity in universities and
pharmaceutical companies" in this field; "Large numbers of cannabinoids
are being synthesised and investigated particularly by US companies" (p
31); "It is an exciting period" (Q 101, cp Q 125, Pertwee QQ 281-298 and
Notcutt Q 411). According to Dr Lambert, "The pharmaceutical industry
has now provided the researcher with a wide range of tools to probe the
cannabinoid system"[7].
3.13 Recent data from animal studies reveal that, in common with
various drugs of addiction (heroin, cocaine, nicotine and amphetamines),
THC activates the release of the chemical messenger dopamine in some
regions of the brain of rats (Pertwee Q 311, Wall Q 126). This is
considered important as this pattern of dopamine release is thought to
be associated with the rewarding properties of these drugs and hence may
be related to their ability to cause dependence.
3.14 Other recent scientific findings indicate a relationship
between the cannabinoid system in the brain and the naturally occurring
opioid system[8]. The ability of THC to trigger dopamine release in the
rat brain is blocked by prior administration of naloxone, a drug that
selectively blocks the actions of opiates in the brain. This suggests
that some of the psychoactive effects of THC and other cannabinoids may
be mediated indirectly through an ability to activate the opioid system
(Pertwee Q 311). Recent studies have also shown that the administration
of THC to animals enhances the pain-relieving effects of morphine and
related opiates. Furthermore, administration of naloxone (the
opiate-blocker) to animals previously treated repeatedly with a
cannabinoid produced some physical withdrawal signs; conversely,
administration of a cannabinoid antagonist to animals previously
dependent on heroin elicited some (but not all) of the signs of opiate
withdrawal (see Appendix 4, paragraph 8). On the other hand, although
some of the actions of THC may involve activation of the opioid system,
THC does not mimic morphine or heroin either in its effects on animals
or in the subjective experience of human users.
3.15 This new information may or may not be relevant to the debate
as to whether cannabis induces physical dependence. We discuss the
degree to which cannabis may induce dependence in man below, in Chapter
4.
***
5 Dr Pertwee is a world expert on the cannabinoids, and current
President of the International Cannabinoid Research Society. At the
University of Aberdeen, he heads a research team of eight scientists
engaged in research in this area. He was a contributing author to the
BMA report. Back
6 Professor Wall is editor-in-chief of the medical journal Pain; he
was a contributing author to the BMA report, and appeared before us on
behalf of the ACT. Back
7 Hirst R A, Lambert D G and Notcutt W G, Pharmacology and potential
therapeutic uses of cannabis. Br. J. Anaesthesia, July 1998. Back
8 The opioid system consists of receptors normally activated by the
enkephalins and endorphins, normally released in response to pain and
stress. They are also activated by morphine, heroin and other opiates.
Back
***
Select Committee on Science and Technology Ninth Report
***
CHAPTER 4 TOXIC EFFECTS OF CANNABIS AND CANNABINOIDS: REVIEW OF THE
EVIDENCE
4.1 The prohibition of the recreational use of cannabis, and some
of the doubts about medical use, are based on the presumption that
cannabis is harmful to individual and public health. We have tested the
strength of that presumption, and this Chapter records what we have
found. New research on this subject is constantly coming forward, so
this cannot be said to be the last word on it. Although cannabis is not
in the premier league of dangerous substances, new research tends to
suggest that it may be more hazardous to health than might have been
thought only a few years ago (Edwards QQ 21, 27).
4.2 In assessing the adverse effects associated with cannabis use,
we have been assisted by a number of detailed recent reviews, including
the recent WHO report Cannabis: a health perspective and research agenda
(WHO/MSA/PSA/97.4); the Australian National Drug Strategy report The
health and psychological consequences of cannabis use (1994) and other
documents[9] submitted by Professor Wayne Hall, Executive Director of
the Australian National Drug and Alcohol Research Centre in Sydney, and
his colleagues; and the recent reviews noted above commissioned by the
Department of Health. The evidence submitted to us by the Royal Society
and the Royal College of Psychiatrists is also particularly relevant.
Acute (short-term) effects of cannabis
4.3 The acute toxicity of cannabis and the cannabinoids is very
low; no-one has ever died as a direct and immediate consequence of
recreational or medical use (DH QQ 219223). Official statistics record
two deaths involving cannabis (and no other drug) in 1993, two in 1994
and one in 1995 (HC WA 533, 21 January 1998); but these were due to
inhalation of vomit. Animal studies have shown a very large separation
(by a factor of more than 10,000) between pharmacologically effective
and lethal doses.
4.4 One minor toxic side-effect of taking cannabis which merits
attention is the short-term effect on the heart and vascular system.
This can lead to significant increases in heart rate and a lowering of
the blood pressure (Pertwee Q 299). For this reason patients with a
history of angina or other cardiovascular disease could be at risk and
should probably be excluded from any clinical trials of cannabis-based
medicines.
4.5 The most familiar short-term effect of cannabis is to give a
"high" - a state of euphoric intoxication. This is, of course, precisely
the effect sought by the recreational user, analogous to the effect of
alcohol and sought for similar reasons. We have been told, however, that
people who use cannabis for medical purposes regard it as an unwelcome
side-effect (Hodges Q 97).
4.6 Intoxication with cannabis leads to a slight impairment of
psychomotor and cognitive function, which is important for those driving
a vehicle, flying an aircraft or operating machinery (DH Q 197). The
Department of Health rate this as "the major concern from a public
health perspective" raised by recreational use (p 46), and Professor
Hall considers it the most serious possible short-term consequence of
cannabis use, both for the user and for the public (p 222).
4.7 There is some disagreement about how long such impairments
persist after taking cannabis: most assume that they last for only a few
hours (e.g. Kendall p 266); but Professor Heather Ashton of the
University of Newcastle-upon-Tyne, principal author of the BMA report,
suggested that subtle cognitive impairments could persist for 24 or even
48 hours or more (Q 72), whereas the DETR say "probably .... 24 hours at
most" (Press Notice 94/Transport, 11 February 1998). On the other hand
the impairment in driving skills does not appear to be severe, even
immediately after taking cannabis, when subjects are tested in a driving
simulator. This may be because people intoxicated by cannabis appear to
compensate for their impairment by taking fewer risks and driving more
slowly, whereas alcohol tends to encourage people to take greater risks
and drive more aggressively (POST note 113; cp DH p 240).
4.8 Analysis of blood samples from road traffic fatalities in
1996-97 (the results of the first 15 months of a three year DETR
study-Press Notice 94/Transport, 11 February 1998) showed that 8 per
cent of the victims were positive for cannabis, including 10 per cent of
the victims who were driving. However, it is not clear what figures
would have been obtained from a random sample of road users not involved
in accidents (DH Q 211); and some of those who tested positive may have
taken the cannabis as much as 30 days before, so that the effects would
have worn off long since (DH p 240). The interpretation of traffic
accident data is further confounded by the fact that 22 per cent of the
drivers found to be cannabispositive also had evidence of alcohol
intake; proportions of alcoholpositives among cannabispositive drivers
as high as 75 per cent have been reported in other countries in similar
studies. Professor Hall considers cannabis's contribution to danger on
the roads to be very small; in his view the major effect of cannabis use
on driving may be in amplifying the impairments caused by alcohol (cp
Keen Q 42). According to a survey of 1,333 regular cannabis users by the
Independent Drug Monitoring Unit (IDMU) in 1994, users who drove
reported a level of accidents no higher than the general population;
those with the highest accident rates were more likely to be heavier
poly-drug users.
4.9 It is difficult to see how cannabis intoxication could be
monitored, if its use were permitted. There could be no equivalent of
the breathalyser for alcohol, since small amounts of cannabis continue
to be released from fat into the blood long after any short-term
impairment has worn off (see paragraph 3.5 above).
4.10 A single dose of cannabis for an inexperienced user, or an
overdose for an habitual user, can sometimes induce a variety of
intensely unpleasant psychic effects including anxiety, panic, paranoia
and feelings of impending doom (BMA p 9, RCPsych p 282). These adverse
reactions are sometimes referred to as a "whitey" as the subject may
become unusually pallid (Montgomery Q 577). These effects usually
persist for only a few hours.
4.11 In some instances cannabis use may lead to a longer-lasting
toxic psychosis involving delusions and hallucinations that can be
misdiagnosed as schizophrenic illness (Strang Q 239, van der Laan Q
512). This is transient and clears up within a few days on termination
of drug use; but the habitual user risks developing a more persistent
psychosis, and potentially serious consequences (such as action under
the Mental Health Acts and complications resulting from the
administration of powerful neuroleptic drugs) may follow if an erroneous
diagnosis of schizophrenia is made. It is also well established that
cannabis can exacerbate the symptoms of those already suffering from
schizophrenic illness (Q 239) and may worsen the course of the illness;
but there is little evidence that cannabis use can precipitate
schizophrenia or other mental illness in those not already predisposed
to it (RCPsych p 283).
4.12 These relatively rare adverse psychological effects of
cannabis are not considered to represent a serious limitation on the
potential medical use of the drug (Strang Q 244), save that patients
suffering from schizophrenic illness or other psychoses should be
excluded. However they do constitute an issue for public health.
According to the Department of Health, cannabis contributes to the extra
cost of acute psychiatric services imposed by drug misuse, though this
cannot be separately costed (p 46; cp RCPsych p 282). The Royal College
of Psychiatrists (p 284) believe that the proportion of users who
experience acute adverse mental effects is "significant".
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).
BOX 2: DEFINITIONS OF DEPENDENCE
The consumption of any psychoactive drug, legal or illegal, can be
thought of as comprising three stages: use, abuse, and addiction. Each
stage is marked by higher levels of drug use and increasingly serious
consequences. Abuse and addiction have been defined and redefined by
various organisations over the years. The most influential current
system of diagnosis is that published by the American Psychiatric
Association (DSM-IV, 1994). This uses the term substance dependence
instead of addiction, and defines this as a cluster of symptoms
indicating that the individual continues to use the substance despite
significant substance-related problems. The symptoms may include
tolerance (the need to take larger and larger doses of the substance to
achieve the desired effect), and physical dependence (an altered
physical state induced by the substance which produces physical
withdrawal symptoms, such as nausea, vomiting, seizures and headache,
when substance use is terminated); but neither of these is necessary or
sufficient for the diagnosis of substance dependence. Using DSM-IV,
dependence can be defined in some instances entirely in terms of
psychological dependence; this differs from earlier thinking on these
concepts, which tended to equate addiction with physical dependence. The
DSM-IV system also defines substance abuse as a less severe diagnosis,
involving a pattern of repeated drug use with adverse consequences but
falling short of the criteria for substance dependence.
4.25 Professor Griffith Edwards, a member of the Advisory Council
on the Misuse of Drugs[15] (Q 27), said that, using internationally
agreed criteria (DSM-IV-see Box 2), there seemed no doubt that some
regular cannabis users become dependent, and that they suffer withdrawal
symptoms on terminating drug use. According to the WHO report, cannabis
dependence is characterised by a loss of control over drug use,
cognitive and motivational impairments that interfere with work
performance, lowered self-esteem and often depression. Professor Hall
wrote, "By popular repute, cannabis is not a drug of dependence because
it does not have a clearly defined withdrawal syndrome. There is,
however, little doubt that some users who want to stop or cut down their
cannabis use find it very difficult to do so, and continue to use
cannabis despite the adverse effects that it has on their lives." In
oral evidence he added that users who sought treatment for cannabis
dependence had typically taken large amounts of cannabis every day for
perhaps 15 years or more (Q 745).
4.26 The Institute for the Study of Drug Dependence likewise
conclude that, while physical dependence is rare, "Regular users can
come to feel a psychological need for the drug or may rely on it as a
"social lubricant": it is not unknown for people to use cannabis so
frequently that they are almost constantly under the influence" (p 263).
4.27 One measure of the significance of cannabis dependence is the
proportion of users who become dependent. Since cannabis dependence is
poorly defined, and the total number of users is unknown, this figure is
elusive. Data from a recent study of 200 regular users in Australia[16]
suggest that more than 50 per cent of such users may be classified as
dependent, although many of these do not consider themselves as
dependent. This corresponds with the finding of an American study of
1991, cited by the WHO report, that "about half of those who use
cannabis daily will become dependent". According to Professor Hall,
"Epidemiological studies suggest that cannabis dependence in the sense
of impaired control over use is the most common form of drug dependence
after tobacco and alcohol, affecting as many as one in ten of those who
ever use the drug" (p 221).
4.28 Neil Montgomery estimates that approximately 5 per cent of
regular cannabis users are heavy users, consuming as much as 28g of
cannabis resin per week. "These are people who have become dependent on
cannabis; they are psychologically addicted to the almost constant
consumption of cannabis...Becoming stoned and remaining stoned
throughout the day is their prime directive" (Q 554).
4.29 Another measure of the extent of cannabis dependence is the
number of people who seek treatment for it. Department of Health figures
(1996) show that in 6 per cent of all contacts with regional drug
clinics cannabis was the main drug of misuse (Q 27). A similar figure,
that cannabis users constitute 7 per cent of all new admissions to drug
treatment centres in Australia, was reported recently. Dr Philip
Robson[17], who runs a Regional Drug Dependence Unit in Oxford, said
that 4.9 per cent of those admitted to his unit cited cannabis as their
main drug (Q 462). However he did not regard cannabis as an important
drug of addiction: "The drug falls well below the threshold of what
would be expected for a dependencyproducing drug which has clinical
significance...I do not meet people who are prepared to knock over old
ladies in the street or burglarise houses or commit other crimes to
obtain cannabis". Professor Robbins estimated that at least 2 per cent
of regular cannabis users (whom he defined as those using cannabis more
than once a week) in the USA are dependent, on the basis of an estimate
of 5m users and an official figure of 100,000 on specific treatment for
cannabis dependency syndrome (Q 623).
4.30 It has been suggested that US figures may be inflated by
people on compulsory treatment, for instance after testing positive at
work, who may not in fact be dependent. According to Professor Hall,
however, "In Australia ... drug testing is uncommon and there is no
cannabis treatment industry. Yet treatment services...have seen an
increase in the number of persons seeking help for cannabis" (p 221). He
even suggests that the figures may be kept down by the widespread belief
that it is not possible to be dependent on cannabis (Q 748).
4.31 Giving up cannabis is widely believed to be relatively easy:
according to the Department of Health, "studies report that of those who
had ever been daily users only 15 per cent persisted with daily use in
their late twenties" (p 45). Most epidemiological studies in Britain and
the United States have shown that the illicit use of cannabis mainly
involves people in their late teens and twenties, with relatively few
users over the age of 30.
4.32 It has been assumed that young cannabis users give up the
habit when they enter their thirties; IDMU (p 236), however, suggest
that this pattern may be changing. The British Crime Survey (1996) shows
that although the prevalence of cannabis use falls after the age of 30,
the greatest proportional increases in the period 1991-1996 were in
older age groups, with incidence of past use doubling in the 40-44 age
group (from 15 per cent to 30 per cent) and trebling in the 45-59 age
group (from 3 per cent to 10 per cent). IDMU conclude that the current
relatively low levels of cannabis use in the over-30 age group may
reflect a generational and cultural divide, rather than substantial
numbers of users giving up.
4.33 It is therefore clear that cannabis causes psychological
dependence in some users, and may cause physical dependence in a few.
The Department of Health sum up the position thus (p 45, cp Edwards Q
28): "Cannabis is a weakly addictive drug but does induce dependence in
a significant minority of regular cannabis users."
***
9 Including Hall W, Room R and Bondy S, A comparison of the health
effects of alcohol, cannabis, tobacco and opiates, in Kallant H,
Corrigal W, Hall W and Smart R eds The Health Effects of Cannabis,
Addiction Research Foundation, Toronto, 1998; and articles awaiting
publication in Addiction (Respiratory risks of cannabis smoking, 1998,
93, 1461), Drug and Alcohol Review, and the Lancet Seminar series (14
November 1998). Back
10 N Solowij, Cannabis and Cognitive Functioning, Cambridge University
Press, 1998. Back
11 See in particular DH p 46; papers kindly supplied by Professor
Donald Tashkin, University of California Los Angeles School of Medicine,
and Professor Hall; and Appendix 3, paragraph 8. Back
12 Carboxy-haemoglobin is formed by the action of carbon monoxide on
haemoglobin in the blood. It interferes with the transport of oxygen
around the body. Back
13 E.g. Taylor FM III, Marijuana as a potential respiratory
carcinogen: a retrospective analysis of a community hospital population,
South. Med. J. 1988, 81, 1213. Back
14 Miss Hodges is the founder-Director of the UK Alliance for Cannabis
Therapeutics (ACT). "Clare Hodges" is a nom de guerre. Back
15 Professor Edwards is Professor Emeritus of Addiction Behaviour at
the Institute of Psychiatry, University of London; past Chairman of the
National Addiction Centre; and editor-in-chief of the journal Addiction.
The ACMD is established under the Misuse of Drugs Act 1971, to advise
the Government. Back
16 By Dr Wendy Swift, Australian National Drug and Alcohol Research
Centre. Back
17 Consultant psychiatrist, Warneford Hospital; senior clinical
lecturer, University of Oxford; author of one of the reviews for the
Department of Health referred to in paragraph 1.4. Back
***
Select Committee on Science and Technology Ninth Report
***
CHAPTER 5 MEDICAL USE OF CANNABIS AND CANNABINOIDS: REVIEW OF THE
EVIDENCE
5.1 The main reason for our inquiry is that there are now calls
for the law to be changed to permit wider medical use of cannabinoids,
and to permit the medical use of cannabis itself. This Chapter reviews
the evidence which we have received about current and proposed medical
uses for cannabis and the cannabinoids. It is important to distinguish
the different substances and preparations; for instance, cannabis leaf
must be distinguished from cannabis extract, and whole cannabis from
THC. It is also important, though not always easy, to distinguish the
various possible routes of administration, e.g. by smoking and by mouth.
Current medical use of cannabis
5.2 Today in the United Kingdom, medical use of cannabis itself is
illegal (see Box 3) but quite widespread. According to the BMA report,
"many normally law-abiding citizens-probably many thousands in the
developed world" use cannabis illegally for therapy. Most such users
smoke their cannabis, but some take it by mouth. The UK Alliance for
Cannabis Therapeutics (ACT) know of 200 people in the United Kingdom who
have used cannabis for MS (p 29); 53 took part in a recent study of
perceived effects of smoked cannabis[18] (Q 262). Clare Hodges writes,
"It is impossible to know how many people with MS use cannabis...My
impression is that most people with MS do not". A Multiple Sclerosis
Society survey produced a figure of one per cent; but the Society
believe the true figure to be higher (Q 341).
BOX 3: CURRENT LEGAL CONTROLS
The regulation of cannabis in the United Kingdom under the Misuse of
Drugs Act 1971 is complicated. Schedule 2 to the Act classifies cannabis
itself, and cannabis resin, as Class B controlled drugs, and the
cannabinoid cannabinol and its derivatives (defined as THC and 3-alkyl
homologues thereof) as Class A controlled drugs. Offences involving
Class A drugs attract stiffer penalties. Under the Act it is an offence
to import, export, produce, supply or possess controlled drugs (though
it is not an offence to use them); it is also an offence to cultivate
cannabis plants, or to permit premises to be used for smoking cannabis.
Reference is often made in this context to "Schedule 1 and Schedule 2".
These are Schedules not to the Act itself, but to the Misuse of Drugs
Regulations 1985 (No. 2066) made under the Act. Schedules 2-5 list drugs
to which various exemptions from the Act apply; in particular, drugs in
Schedule 2 may be administered by, or on the instructions of, a doctor
or dentist (Regulation 7), may be produced by a practitioner or
pharmacist (Reg. 8), may be supplied (Reg. 8) and possessed (Reg. 10) by
various classes of person, including practitioners, pharmacists and
heads of laboratories, and may be possessed by patients (Reg. 10).
Schedule 1 lists drugs to which the exemptions do not apply; cannabis,
cannabis resin, and cannabinol and its derivatives (other than
dronabinol-see Box 5) appear in Schedule 1. The 1985 Regulations also
empower the Secretary of State to license anyone to produce, possess or
supply any controlled drug, including a Schedule 1 drug (Reg. 5); to
license cultivation of cannabis plants (Reg. 12); and to approve
premises for smoking cannabis for research purposes (Reg. 13). The
position in practice is therefore that cannabis and most of its
derivatives may not be used in medicine, and may be possessed for
research only under Home Office licence. There are two psychoactive
cannabinoids, nabilone and dronabinol, which may be used for medicine:
see Boxes 4 and 5. Two non-psychoactive cannabinoids, cannabidiol and
cannabichromene, are not controlled drugs, and could in theory be
prescribed as unlicensed medicines, but no-one is currently doing so.
This UK regime is one of the most restrictive in the world. Places with
a more liberal regime include the Netherlands, Italy, Spain, Canada, and
some states of Germany, Australia and the USA.
5.3 The ACT also know of 50 users with spinal injury, and 20 with
other conditions. A survey conducted by the newspaper Disability Now in
1997 among its disabled readers revealed, among 200 respondents, 40
people taking cannabis for MS, 40 for spinal injury, 35 for back pain,
27 for arthritis and 64 for other conditions. IDMU's surveys of 2,794
regular cannabis users have revealed 78 whose main reason for using it
is medical (p 244).
5.4 We have received written evidence (not included in the volume
of printed evidence) from four patients suffering from MS (besides Miss
Hodges) who report that cannabis has a beneficial effect on their
symptoms and call for a change in the law to permit the prescription of
cannabis. Dr Fred Schon, a consultant neurologist, described the
apparently dramatic improvement obtained by selfmedication with smoked
cannabis resin by an MS patient who had developed a severe and disabling
abnormality of eye movements (p 303). We have also heard from people who
have used cannabis against epilepsy, ME and pain, and as an anti-emetic
after chemotherapy. Further anecdotal evidence was provided by the
Alliance for Cannabis Therapeutics and the London Medical Marijuana
Support Group.
5.5 According to Neil Montgomery, some users of cannabis for
medical purposes are also, or have been, recreational users, and their
medical use is to some extent conditioned by their recreational
experience (p 132). Three of the nine such users who have given us
evidence are in this category. An increasing number are growing their
own cannabis, "primarily to avoid problems of impurity", or buying in
bulk to ensure consistency of dose; either course exposes them to
stiffer sentences, if caught, than the frequent purchase of small
quantities (cp IDMU p 261). Medical users typically take cannabis as
frequently as, but in smaller quantities than, recreational users (Q
567).
5.6 Use of cannabis for medical purposes is sometimes connived at
by the medical professions. Clare Hodges took medical advice before
trying cannabis for her MS, and was not dissuaded (p 27). "Over 50
patients have told the ACT that their doctors have recommended that they
try cannabis for symptomatic relief" (p 29); and 50 of the 200
respondents to the Disability Now survey said their doctor knew and
approved. 100 doctors are associated with the ACT (Q 96). Most medical
users tell the Multiple Sclerosis Society that their doctors are "mildly
supportive" (Q 341). One user's doctor knows that she uses cannabis for
pain relief and is unconcerned. Another took to cannabis for his
epilepsy on a doctor's recommendation. On the other hand, a third user's
consultant would not support his letter to us, "due to the advances in
anti-emetic drugs". According to Dr William Notcutt, a consultant
anaesthetist[19], self-medication with cannabis for pain is now common,
and "Advising on its use can be part of the pharmacological management
of pain nowadays" (p 101, Q 434). Finally, the BMA report on medical use
was itself prompted by a resolution in favour of medical use of "certain
additional cannabinoids", passed by the BMA's Annual Representative
Meeting in 1997.
5.7 The Government consider that the burden of proof rests on the
proponents of medical use of herbal cannabis. As recently as 1 March
1994, the then Home Office Minister referred in a Commons answer to
"long-standing advice that cannabis has no recognised medical use" (HC
WA 632). Since then, the Government line appears to have softened a
little: on 2 July 1997, Tessa Jowell MP, the Minister of State for
Health, said that officials were keeping available research under
review. "At present the evidence is inconclusive. The key point is that
a cannabis-based medicine has not been scientifically demonstrated to be
safe, efficacious and of suitable quality" (HC WA 174). On 27 October
1997, Paul Flynn MP put it to George Howarth MP, Under-Secretary of
State at the Home Office, that cannabis was already widely used,
illegally, by sufferers from MS, cerebral palsy and glaucoma; the
Minister replied, "All drugs used for medical purposes have to be
scientifically tested. If cannabis succeeds in those tests...the
Secretary of State for Health...would be willing to consider allowing
medicinal use of it. Unfortunately, as of now, there is no such
evidence" (col. 580; see also HL 20 April 1998, WA 192, and HC 5 May
1998, WA 351).
5.8 The Department of Health say the same in written evidence:
"There is insufficient evidence to demonstrate the effectiveness of
cannabis as a therapeutic agent at this stage" (p 48). In oral evidence
they went a little further: "We very much recognise the importance of
research in this area and its potential value, particularly when
addressed to the needs of patients for whom we have relatively little
else to offer" (Q 167). But MS is not the only condition where
conventional treatments are relatively limited in their effects, and the
Department warned against allowing the "added frisson" of cannabis to
distort the perspective (Q 225).
Advice to medical users
5.9 Given that use of cannabis for medical purposes is clearly
going on in spite of the law, we asked some of our witnesses what advice
they would give to people conducting or contemplating medical use, and
to their doctors. The Department of Health suggest that doctors should
advise users as to the legal position, and as to the "limited evidence"
of efficacy. However, "one has also to recognise that people may choose
to do things that their doctors advise against, and there would be a
necessity for the doctor subsequently to continue to work to support
that individual" (Q 172). One official went so far as to say, off the
cuff but not off the record, "Other people's decisions have to be other
people's decisions" (Q 224).
5.10 The BMA advise users of cannabis for medical purposes to be
aware of the risks, to enrol for clinical trials, and to talk to their
doctors about new alternative treatments; but they do not advise them to
stop (Q 55). The Multiple Sclerosis Society "does not actually condone
or encourage individuals in breaking the law" (Q 341).
Current medical uses of cannabinoids
5.11 Although cannabis itself is illegal, certain cannabinoids are
in current use in UK medicine, within the law. Cannabinoids have
antinausea effects, and have been used clinically to suppress the
nausea and vomiting associated with chemotherapy in cancer patients.
This is the only medical indication for which adequate data from
controlled clinical trials exist, mostly from studies in the 1970s with
pure THC and the synthetic cannabinoid nabilone, an analogue of THC,
which were found to be as effective as prochlorperazine and other
antinausea agents available at the time. On the basis of this evidence
nabilone was licensed and is available as a prescription medicine in the
United Kingdom for this indication (see Box 4). However, according to
Professor Malcolm Lader of the Institute of Psychiatry, University of
London[20] (Q 7), it has been little used. He believes that this is
largely due to the fact that more powerful antinausea medicines were
introduced in the 1980s-the serotonin antagonists ondansetron (Zofran),
granisetron (Kytril) and tropisetron (Navoban), which are now widely
used in conjunction with cancer chemotherapy (cp Hall p 221 and Appendix
3 paragraph 13). They have the advantage over the waterinsoluble
cannabinoids that they can be delivered intravenously as well as by
mouth, and they are effective in up to 90 per cent of patients. There
have been no clinical trials to compare the effectiveness of
cannabinoids with the serotonin antagonists (RPharmSoc p 287).
Box 4: NABILONE
Nabilone is an analogue of D9-THC. It was licensed in 1982 for
prescription-only hospital-only use against nausea arising from
chemotherapy and unresponsive to other treatment. It is manufactured
synthetically by Eli Lilly & Co. Ltd and sold in the United Kingdom by
Cambridge Selfcare Diagnostics Ltd; a pack of 20 1mg capsules (to be
taken by mouth) costs £102. 5,400 packs were sold in 1997-98. It is not
a controlled drug. According to Dr Kendall of the University of
Nottingham, nabilone is not widely used to treat nausea (p 268).
Nabilone is used "very infrequently" in MS-probably less than cannabis
itself (MSSoc Q 353). However Dr Notcutt is using it for pain control at
James Paget Hospital in Great Yarmouth-see paragraph 5.14.
5.12 This means that cannabis and cannabinoids are likely to be of
benefit as anti-emetics only to the small proportion of patients who do
not respond to existing treatments, or possibly in the treatment of the
delayed stages of emesis which can occur for some days following cancer
chemotherapy, and which do not respond well to the serotonin
antagonists. Nevertheless, cannabinoids are undoubtedly effective as
antiemetics and more research in this field might explore their use in
combination with the serotonin antagonists, help to determine for which
patients they are most appropriate, and examine the potential of the
allegedly less psychoactive cannabinoid D8THC, for which there have
been encouraging preliminary clinical results (Q 74).
5.13 THC itself (dronabinol-see Box 5) is licensed as an
anti-emetic in the USA, but not in this country. The BMA report
recommends that it should be licensed here. This would depend on the
manufacturer applying for a licence; in the mean time, doctors may
prescribe it on an unlicensed basis at their own risk.
BOX 5: DRONABINOL
Dronabinol is THC. It is marketed as Marinol, synthetic D9-THC in sesame
oil, supplied in soft gelatine capsules (to be taken by mouth)
containing 2.5, 5 or 10mg of THC. It is licensed in the USA as an
anti-emetic, and also to stimulate the appetite of AIDS patients.
Marinol is manufactured by Unimed Pharmaceuticals Inc. in the USA; it is
significantly more expensive than nabilone (Notcutt Q 427). It is not
licensed as an anti-emetic here; but in 1995, on WHO advice, it was
moved from Schedule 1 to Schedule 2 of the 1985 Regulations (by the
Misuse of Drugs (Amendment) Regulations 1995, No. 2048), and may
therefore be prescribed on the named-patient basis defined in the 1985
Regulations (see Box 6). In a 1997 survey in the USA, only 6 per cent of
1,500 oncologists said they had prescribed dronabinol in the previous
year (Brett p 204, cp Hall p 222). According to the BMA, take-up in the
United Kingdom is low, because of the administrative obstacles and the
availability of good alternatives (Q 83). According to Dr Notcutt of
James Paget Hospital, Great Yarmouth (Q 422), it is not in practice
available in the United Kingdom at present.
5.14 Dr Notcutt is currently treating patients suffering from
intractable pain with nabilone, on an unlicensed basis. He has treated a
total of 60 patients with a variety of chronic pain conditions,
including MS, cancer, peripheral nerve damage and spinal lesions. As
many as 50 per cent have derived some pain relief from nabilone, but a
significant number of patients are unable to tolerate the side effects
of the drug (unpleasant psychoactive effects and drowsiness) (Q 400) and
the overall success rate is about 30 per cent (p 104).
5.15 Cannabis has been advocated to treat anorexia, but the
scientific basis of this remains unclear. In normal subjects cannabis
intake is followed about three hours later by an increased appetite
("the munchies"), particularly for sweet foods (Pertwee Q 256). Regular
users of cannabis, however, become tolerant to this effect and appetite
may even be depressed. According to the BMA report clinical trials have
failed to establish any beneficial effect of THC on appetite in patients
with anorexia nervosa. However, in controlled clinical trials in
patients with advanced AIDSrelated illnesses, dronabinol significantly
reduced nausea, prevented further weight loss and improved patients'
mood. On the basis of such data the US Food and Drug Administration have
licensed dronabinol for the treatment of anorexia associated with AIDS;
Dr Robson sees this as "the most compelling indication" for
cannabis-based medicines (Q 458).
5.16 There is a concern with regard to the use of cannabinoids in
AIDS because of the possible immunosuppressive effects of these drugs
(BMA QQ 79, 80, Hall Q 742). Such effects could be damaging in patients
whose immune system is already compromised, although there is no
evidence of any relationship between cannabis use and the rate of
progression to AIDS in HIVpositive men (Robson Q 460).
5.17 The BMA report recommends that the licensed indications for
nabilone be extended to preventing weight loss and treating anorexia in
patients with cancer or AIDS, and that dronabinol should be licensed in
this country for this indication. As noted already, this would depend on
application by the manufacturers; in the mean time, doctors may
prescribe "off-label" at their own risk. Dronabinol is a controlled
drug, listed in Schedule 2 to the Misuse of Drugs Regulations (see Box
2); so prescription would have to be on the "named-patient" basis
defined in the Regulations (see Box 6).
BOX 6: PRESCRIPTION ON THE NAMED-PATIENT BASIS
Under Regulation 15 of the Misuse of Drugs Regulations 1985, any
prescription for a drug listed in Schedule 2 (or Schedule 3) to the
Regulations shall: "(a) be in ink or otherwise so as to be indelible
and be signed by the person issuing it with his usual signature and
dated by him; (b) insofar as it specifies the information required by
sub-paragraphs (e) and (f) below to be specified, be written by the
person issuing it in his own handwriting; (c) except in the case of a
health prescription, specify the address of the person issuing it; (d)
have written thereon, if issued by a dentist, the words "for dental
treatment only" and, if issued by a veterinary surgeon or a veterinary
practitioner, a declaration that the controlled drug is prescribed for
an animal or herd under his care; (e) specify the name and address of
the person for whose treatment it is issued or, if it is issued by a
veterinary surgeon or veterinary practitioner, of the person to whom the
controlled drug prescribed is to be delivered; (f) specify the dose to
be taken and- (i) in the case of a prescription containing a controlled
drug which is a preparation, the form and, where appropriate, the
strength of the preparation, and either the total quantity (in both
words and figures) of the preparation or the number (in both words and
figures) of dosage units, as appropriate, to be supplied; (ii) in any
other case, the total quantity (in both words and figures) of the
controlled drug to be supplied; (g) in the case of a prescription for a
total quantity intended to be supplied by instalments, contain a
direction specifying the amount of the instalments of the total amount
which may be supplied and the intervals to be observed when supplying."
Proposed new indications for cannabis-based medicines
5.18 Besides those conditions noted above for which cannabinoids
are already used within the law, the conditions most often cited are MS
and pain. Claims are also made in connection with epilepsy, glaucoma and
asthma. We review the evidence on each of these conditions below.
Multiple sclerosis
5.19 The Multiple Sclerosis Society has in its membership 35,000
of the total of 85,000 patients suffering from this disease in the
United Kingdom. The Society estimate that more than 1 per cent of these
patients, and possibly as many as 3-4 per cent, are illegally using
cannabis for relief of symptoms (Q 341). Representatives of the Society
described for us the commonest symptoms of the disease. Fatigue is the
most frequent in 95 per cent of patients, followed by balance problems
(84 per cent), muscle weakness (81 per cent), incontinence (76 per
cent), muscle spasms (66 per cent), pain (61 per cent) and tremor (35
per cent) (Q 334). Although the interferons (alpha and beta) are proving
to be of some value in relapsing-remitting and progressive cases of the
disease, these symptoms are still poorly controlled by existing
treatments, and no cure has been found.
5.20 Dr Lorna Layward of the Multiple Sclerosis Society, and Dr
Pertwee, reviewed for us the six published clinical trials of cannabis
or cannabinoids in MS. These have involved small numbers of patients (a
total of 41 subjects worldwide), but some positive results have been
reported, especially for spasticity, pain associated with spasticity,
tremor and urinary bladder control (QQ 262, 372). Dr Pertwee took part
in the study of perceived effects of cannabis on MS noted above: in a
postal survey of 112 MS patients selfmedicating with cannabis in the
United Kingdom and the USA, more than 90 per cent reported a beneficial
effect on spasticity, and many also reported pain relief and improved
urinary control (Q 262).
5.21 Dr Layward and Dr Pertwee referred to experimental results in
animals which offer a scientific basis for the use of cannabis and
cannabinoids in the treatment of MS. In an MSlike disease in mice
(experimental autoimmune encephalomyelitis), low doses of cannabinoids
alleviate the muscle tremor seen in such animals. Cannabinoids also
suppress spinal cord reflexes in animals (QQ 262, 356).
5.22 It is natural to wonder whether the beneficial effects of
cannabis reported by MS patients might simply be related to the feeling
of well-being caused by the intoxicant properties of the drug. Clare
Hodges said that cannabis greatly helped her physical symptoms,
specifically the relief of discomfort in bladder and spine, and relief
from nausea and tremors (Q 98). "Cannabis helps my body relax. I
function and move much easier. The physical effects are very clear. It
is not just a vague feeling of well-being". She positively prefers to
avoid intoxication, and feels able to control the dose of cannabis to
obtain physical relief without getting high (p 27, Q 98; cp LMMSG p
270). Professor Wall likened this to the experience of patients using
selfadministered morphine or related narcotics for pain control, who
control the dose to achieve a bearable level of pain without muddled
thinking (Q 98).
5.23 The BMA report concluded, "It is somewhat paradoxical that
cannabinoids are reported to be of therapeutic value in neurological
disorders...since very similar symptoms can be caused by cannabis
itself...it is not clear how much of the reputed effects of cannabis in
motor disorders are due to psychoactive or analgesic effects".
Nevertheless, it recommended that "A high priority should be given to
carefully controlled trials of cannabinoids in patients with chronic
spastic disorders which have not responded to other drugs". This view is
shared by many of our witnesses.
5.24 The BMA report calls for the extension of the licensed
indications for nabilone, and for the licensing of dronabinol, for use
in MS and other chronic spastic disorders unresponsive to standard
drugs. The wording of the report is ambiguous: on p 9 it says,
"Depending on the results of...trials there may be a case for
considering extension of the indications..."; on p 80 it says, "There is
a case for the extension of the indications" for such use pending
trials. The latter is repeated in the BMA's written evidence to us (p
10). According to Professor Ashton the ambiguity is inadvertent; and a
letter from Professor Nathanson of the BMA (p 206) confirms that the BMA
does indeed support licensing pending further research.
5.25 The National Drug Prevention Alliance suggest that this
ambiguity reflects disagreement between Professor Ashton, the main
author, and editors at the BMA. They would regard licensing in advance
of trials as "an extraordinary aberration" (p 279). The Christian
Institute say it would set "a very bad precedent" (p 208). In any case,
the MCA are not prepared to allow anecdotal evidence as a substitute for
clinical trials (QQ 168, 178, 189); and no application to extend the
licence for nabilone has in fact been made (Q 191).
***
18 Consroe P, Musty R, Rein J, Tillery W and Pertwee R, The perceived
effects of smoked cannabis on patients with MS, Eur. Neurol. 1997, 38,
44. Back
19 Dr Notcutt is a consultant in anaesthesia and pain management at
James Paget Hospital, Great Yarmouth, and a senior lecturer at the
University of East Anglia. He has extensive experience of the clinical
use of nabilone (see Box 4) for the unlicensed indication of pain
control. Back
20 Chairman of the Technical Sub-Committee of the ACMD. Back
***
Select Committee on Science and Technology Ninth Report
CHAPTER 6 RECREATIONAL USE OF CANNABIS
Prevalence
6.1 Cannabis is by far the most widely used illicit drug in the
United Kingdom, as in most other Western countries; and almost all of
this use is for recreational rather than medical purposes. According to
the Department of Health, "Cannabis is now the third most commonly
consumed drug after alcohol and tobacco" (p 47).
6.2 Cannabis dominates the drug crime statistics, and the figures
are rising. Figures for the whole United Kingdom for 1996 (Home Office
Statistical Bulletin 10/98) show that 72,745 drug offenders (77 per cent
of the total) committed offences involving cannabis (alone or with other
drugs). There were 91,432 seizures of cannabis in 1996 (75 per cent of
the total for all drugs) and this involved record quantities of cannabis
resin (66,921 kg), herbal cannabis (34,373.6 kg) and cannabis plants
(116,119 plants). These figures, which are the most recent available,
represent more than a threefold increase over 1990, with a particularly
sharp increase in the number of offences related to the cultivation of
cannabis plants and the numbers of plants seized.
6.3 It is difficult to put a figure on the prevalence of cannabis
use in the United Kingdom. The Parliamentary Office of Science and
Technology, in their Cannabis Update of March 1998, gave figures from
the British Crime Survey 1994 which indicate that in the adult
population (16-59) 1 in 5 had "ever tried" cannabis (1 in 20 within the
previous month) and in the 1629 age group just over 1 in 3 had "ever
tried" cannabis (1 in 20 within the previous month). These figures are
not dissimilar to those in the WHO report for other countries in
Europe[23], with somewhat higher figures for the USA, Canada and
Australia. They suggest that as many as 7.5m people aged 16-59 in the
United Kingdom have used cannabis at least once, and that between 1.5m
and 2m take the drug at least once a month (cp Montgomery Q 559). The
Royal College of Physicians have established a Joint Working Party with
the Royal College of Psychiatrists which among other matters will review
the epidemiology of illicit drug use in the United Kingdom.
Pattern of use
6.4 The pattern of cannabis consumption in the United Kingdom
varies according to geography, socioeconomic conditions and the age of
the user. Professor Edwards observed that cannabis is and has been used
in very different ways in different times and places; for instance,
there are people in south London who smoke 20 joints a day (Q 26). Dr
Robson cautions that much of the use of cannabis in the community does
not come to the attention of the health services or the police, and
therefore little is known about it (Q 456).
6.5 The Independent Drug Monitoring Unit conducted a survey of
1,333 regular cannabis users who attended a major pop festival in
Britain in the summer of 1994 (p 231). The majority were daily cannabis
users with an average consumption of about 24.8g of cannabis resin per
month. Respondents gave highly positive subjective ratings to cannabis
(as opposed to negative subjective ratings to solvents, cocaine and
heroin). More than 60 per cent believed that cannabis had been of
benefit to their physical or mental health. They would prefer that the
law was more liberal, but a majority (70 per cent) did not think that
they would use more if it was.
6.6 Dr James Robertson, a GP working in Edinburgh, has reported
the results of a survey (funded by the Royal College of General
Practitioners) of 328 consecutive patients attending his surgery
(average age 33.7 years)[24]. 200 patients (61 per cent) said that they
had used cannabis at least once, and more detailed interviews of 101 of
these revealed that 90 were regular users, with 67 using cannabis on a
daily basis. Most spent £25 or less per week on cannabis, but a small
number of individuals spent £100 or more per week.
6.7 Neil Montgomery described for us various ways to take cannabis
recreationally (QQ 544-554). He divides recreational users into three
groups:
· Casual Irregular use, in amounts up to 1g of resin at a
time, to an annual total of no more than 28g (Q 545);
· Regular Regular use, typically of 0.5g of resin a day
(equivalent to 3 or 4 smokes of a joint or pipe), adding up to about
3.5g per week (Q 548);
· Heavy More or less permanently stoned, using more than 3.5g
of resin per day and 28g or more per week (Q 554). The smallest group,
around 5 per cent. "The extent to which a heavy user can consume
cannabis is largely unappreciated."
Herbal cannabis appears to be consumed at twice the rate of cannabis
resin, presumably because of its lower content of THC. Comparable data
are provided by IDMU (pp 231-3).
6.8 According to POST's Cannabis Update, 9 per cent of ever-users
use cannabis daily, and 14 per cent several times a week, making it of
all illegal drugs the one most likely to be used regularly. According to
Professor John Strang, Director of the National Addiction Centre, few
users end up in hospital with acute psychiatric problems, and most
regular users are not nowadays advised by their doctor to change their
habits (Q 244). For the risk of dependence, see Chapter 4.
6.9 Many cannabis users also consume a variety of other
psychoactive agents. As the commonest method of using cannabis in the
United Kingdom is to smoke cannabis resin mixed with tobacco, nicotine
use is very high among cannabis users. Among other things, this makes it
difficult to assess the respiratory risks of smoked cannabis as they are
confused with the well-established risks of smoked tobacco. Alcohol use
is also common, but regular cannabis users may consume less than
non-cannabis users. Drug treatment clinics often see poly-drug users,
who are consuming a variety of illicit substances, of which cannabis is
commonly one (QQ 42, 216, 487, 515, 562; DH p 47).
6.10 According to the Department of Health, most cannabis users
have discontinued by their mid to late 20s (p 46); and of those who have
ever been daily users, only 15 per cent persist with daily use in their
late 20s (p 45). Neil Montgomery has identified a group of regular users
who stop in their 30s and start again in their 50s (Q 575).
Content of cannabis consumed in the United Kingdom
6.11 Some of our witnesses expressed concern that the preparations
of illicit cannabis used in the United Kingdom today are more potent
than previously, exposing users to a greater risk of acute intoxication
and long-term adverse effects. Professor Ashton (p 12) suggested that "a
typical 1970s `reefer' contained about 10mg of THC..., while a typical
`joint' today may contain 60-150mg or more of THC. This increase in
potency results from sophisticated plant breeding and cultivation
methods leading to highly potent varieties of cannabis, such as
Skunkweed". Other witnesses made similar assertions (e.g. Q 33).
6.12 However, the Home Office Forensic Science Service, who have
data on the THC content of seized cannabis samples, do not support the
view that most users in the United Kingdom are exposed to material
containing ten times as much THC as in the 1960s and 1970s. They say,
"Cannabis resin...has a mean THC content of 4-5 per cent, although the
range is from less than 1 per cent to around 10 per cent. This pattern
has remained unchanged for many years" (p 218). Cannabis resin, imported
most commonly from Morocco, Afghanistan or Pakistan (IDMU p 230), is the
form of cannabis most widely used in the United Kingdom, and accounted
for two thirds by weight of all seized material in 1996 (Home Office
Statistical Bulletin 10/98). One of our witnesses, a user and convicted
dealer, claimed that most modern cannabis is in fact weaker than
material from the 1960s.
6.13 On the other hand, there appears to have been an increase in
the THC content of herbal cannabis-probably because of the use of new
strains of cannabis plant and improved growing conditions. In the United
States, the University of Mississippi have analysed the THC content of
seized cannabis on behalf of the US government since 1980 (see Appendix
4, paragraph 13). They report an increase in the THC content of herbal
cannabis from around 2 per cent in 1980-81 to more than 4 per cent in
1997. The Forensic Science Service report that herbal cannabis in the
United Kingdom currently also contains an average of 4-5 per cent THC.
They also report that cannabis grown in the home, using improved growing
techniques and improved plant varieties, now produces herbal cannabis
with a considerably higher THC content, with an average close to 10 per
cent THC and a range extending to over 20 per cent (p 218). Use of
"hydroponic" cannabis (grown in a nutrient solution rather than in soil)
appears to be increasing rapidly, with plant seizures in the United
Kingdom up from 11,839 plants in 1992 to 116,119 in 1996.
6.14 Professor Hall suggested, "More potent forms of cannabis need
not inevitably have more adverse effects on users' health than less
potent forms. Indeed, it is conceivable that increased potency may have
little or no adverse effect if users are able to titrate their dose to
achieve the desired state of intoxication. If users do titrate their
dose, the use of more potent cannabis products would reduce the amounts
of cannabis material that was smoked, thereby marginally reducing the
respiratory risks of cannabis smoking" (p 221; cp IDMU p 235).
6.15 The overall quality of imported cannabis resin appears to
have fallen in recent years; many users perceive cannabis resin as
adulterated and forensic analysis frequently confirms that this is the
case, with the addition of caryophyllene, a constituent of cloves, being
particularly common (IDMU p 230; Montgomery p 132 and QQ 577, 589). Yet
Professor Hall considers that concern about herbicide contamination is
unfounded, and that case history evidence of health problems from
microbial contamination is limited. Neil Montgomery calls for research
in this area.
The state of the law
6.16 This Government show no sign of taking a softer line against
recreational use of cannabis than their predecessors. According to the
White Paper Tackling Drugs (Cm 3945) of April 1998, "The more evidence
that becomes available about the risks of, for example, cannabis...the
more discredited the notion that any of the substances currently
controlled under the 1971 Act are harmless". This echoes the view of
Professor Edwards of the ACMD: "We are in a rapidly changing field of
knowledge"; and new knowledge is making cannabis look more dangerous,
not less (QQ 21, 27).
6.17 Most of our professional witnesses agree that the adverse
effects of cannabis fully justify prohibition (e.g. Henry/RCPath p 224).
The only argument on the other side is that cannabis is arguably less
dangerous than alcohol or tobacco (e.g. RCGP p 281, Kendall p 268).
Professor Hall acknowledged this, but noted "the difficulty in
predicting the effect that relaxation of cannabis prohibition would have
on current patterns of cannabis use and the harms caused by that use" (p
222).
6.18 The Under-Secretary of State at the Home Office, George
Howarth MP, told us confidently that legalising recreational use would
cause such use to increase (Q 674). Professor Edwards, writing for the
Royal Society, is less sure: "We would expect weakening of controls over
cannabis to result in increased use levels, but this is an empirical
question on which research at present is not conclusive...Removal of
prohibition on cannabis would have to be described as a voyage into the
unknown. Some added harm and some added costs would undoubtedly result"
(p 303). There is international experience which might throw light on
this question, but we have not explored it in detail.
6.19 We have not considered the wider range of social and
criminological issues which would be raised by any proposal to change
the law on recreational cannabis use. These include enforcement, the
impact on use of other illegal drugs, and the international context and
the danger of "drug tourism"; as well as ethical, philosophical and
religious questions about the freedom of the individual, the nature of
society and the morality of mind-altering drugs. As we said when we
began this enquiry, these matters fall outside our remit as a Science
and Technology Committee. An Independent Inquiry into the Misuse of
Drugs Act, chaired by Lady Runciman of Doxford and supported by the
Police Foundation, is currently considering the matter in its wider
context; they expect to report next year.
***
23 See also the Annual Report on the State of the Drugs Problem in the
EU 1997, by the European Monitoring Centre for Drugs and Drug Addiction.
Back
24 Br. J. Gen. Pract. 1996, 46, 671. Back
CHAPTER 7 CHANGING THE LAW ON MEDICAL USE AND RESEARCH: REVIEW OF THE
EVIDENCE
7.1 In law, it would be possible to make cannabis and/or
additional cannabinoids prescribable by moving them from Schedule 1 to
Schedule 2 to the Misuse of Drugs Regulations, in advance of any
cannabis-based medicine being licensed and reaching the market. However,
the Government are not willing to reschedule cannabis in advance of
licensing. Licensing depends on research and clinical trials: the
Government are satisfied with the arrangements for allowing research and
trials, but some of our witnesses are not. In the mean time, medical use
remains illegal.
Prosecution for use of cannabis for medical purposes
7.2 It is not known what proportion of prosecutions for possession
of cannabis arise from medical use. The ACT drew our attention to 15
reported cases of people charged with cultivation, possession and/or
supply in medical situations since 1996: of the 12 cases where the
outcome was known, one resulted in a sentence of 50 hours' community
service; in the other 11, either the prosecution was abandoned, the
defendant was acquitted, or the sentence was no greater than a
conditional discharge. IDMU offer further figures (p 258); they comment
that, although outcomes in such cases are highly variable, juries seem
more likely to acquit "where there is convincing medical evidence, given
similar circumstances concerning paraphernalia".
7.3 People who use cannabis for medical purposes face prosecution
if caught cultivating or possessing cannabis; but, according to Austin
Mitchell MP, "It is bringing the law into a certain amount of difficulty
and disrepute because either the police are cautioning or the courts are
giving very lenient sentences" (Q 132). Dr Pertwee considers it
unsatisfactory that such people are sometimes prosecuted, unsatisfactory
that law-breaking is sometimes tolerated, and unsatisfactory that the
position is inconsistent around the country (Q 313).
7.4 The BMA report recommends, "While research is under way,
police, the courts and other prosecuting authorities should be aware of
the medicinal reasons for the unlawful use of cannabis by those
suffering from certain medical conditions for whom other drugs have
proved ineffective" (cp Q 55). Similarly the Multiple Sclerosis Society
want the law to treat people caught using cannabis for medical reasons
in an "appropriately compassionate fashion" (p 90). They report that
most people convicted in such circumstances receive a suspended
sentence; but they are concerned about the way the system treats people
as much as about the verdict (Q 341; cp IDMU p 261).
7.5 Mr Howarth, the Under-Secretary of State, declined to comment
on how the Crown Prosecution Service and the courts treat such cases (QQ
668-673), beyond observing that in some cases the plea-in-mitigation of
medical use might be trumped-up (Q 674). The Home Office added that
official statistics do not distinguish between cases with a medical
aspect and cases without; but that, on the anecdotal evidence, outcomes
in medical cases were not obviously out of line with outcomes in purely
recreational cases (Q 675). (The proportion of persons in the United
Kingdom dealt with for possession of cannabis who are cautioned rather
than prosecuted rose from 35 per cent in 1986 to 62 per cent in
1995-Home Office Statistical Bulletin 10/98.)
Possible transfer from Schedule 1 to Schedule 2
7.6 According to the Home Office (p 150), cannabis could be
transferred from Schedule 1 to Schedule 2 by statutory instrument,
subject to negative resolution in Parliament. The ACMD would have to be
consulted first. According to the Minister (Q 676), under the 1961 UN
Convention, rescheduling cannabis itself and cannabis resin would not
require international agreement; but, under the 1971 Convention,
rescheduling cannabinol and its derivatives other than dronabinol would
require prior amendment of the Schedules to the Convention through the
WHO and the UN Commission on Narcotic Drugs, as happened in the case of
dronabinol in 1995.
7.7 Rescheduling would allow doctors to prescribe; but the Home
Office say, "Our understanding is that the ability of doctors to
prescribe cannabis would be hampered in practice if a cannabis-based
medicine had not been granted a marketing authorisation by the MCA". The
Minister said that there were "compelling policy reasons" for requiring
an MCA licence first (Q 676). When asked to explain the practical
difficulties, he referred to the extra burden of responsibility which a
doctor takes on by prescribing an unlicensed medicine (Q 679); he
queried the wisdom of permitting prescription without proof of safety
and quality (Q 680); and he noted that the ACMD had not called for
change (Q 688).
7.8 Rescheduling would also allow doctors and pharmacists to
manufacture and supply (Q 680); anyone else, including a pharmaceutical
company, would require a Home Office licence. It would not in itself
disapply section 8 of the Misuse of Drugs Act, which makes it an offence
to allow cannabis to be smoked on premises; but this could be done by
secondary legislation (Q 684).
7.9 So the Government could reschedule cannabis; the next question
is, whether they should. Dr Lambert says, "Many patients are already
illegally using cannabis...Their needs must be addressed whilst formal
studies are undertaken"[25]. IDMU finds the present position "inhumane",
and "unjustifiable both on moral and on public health grounds" (p 229).
Dr Pertwee says (p 68), "A strong case can be made on the grounds of
common sense and compassion for allowing doctors to prescribe...(oral)
cannabis now for serious symptoms including muscle spasms"; but he
admits that it will take better evidence to persuade the Department of
Health (Q 263; see also paragraph 7.15 below).
7.10 Dr Robson described the present position as an "affront to
humanity" (Q 460). He called for "compassionate reefers" for AIDS and
cancer patients (p 118), and possibly for patients with non-terminal
conditions who might feel that the increased risk of cancer was worth
taking (Q 469). He suggested that patients might be made to confirm in
writing that the doctor had explained the risks; and that, if it were
felt necessary, the number of doctors entitled to prescribe cannabis
could be limited, as in the case of diamorphine (heroin) or cocaine
prescribed for addicts under the Misuse of Drugs (Supply to Addicts)
Regulations 1997 (Q 471). He added that research into synthetic
cannabinoids might soon make herbal cannabis obsolete; but, in the mean
time, "it just is not a dangerous enough drug for me to want to ban it"
(Q 472).
7.11 The ACT want "medical preparations of natural cannabis...to
be made available on a doctor's prescription while research is going
ahead" (p 28), by moving cannabis from Schedule 1 to Schedule 2 (Q 133).
They argue that "we know now that cannabis can be effective and is safe
enough to be prescribed by a doctor...and there are people who need
treatment now". Similarly, six of our witnesses, all users of cannabis
for medical purposes themselves, want cannabis to be prescribable or
otherwise legalised for medical use. 195 out of 200 respondents to the
Disability Now survey, of whom 192 were disabled and 134 had taken
cannabis for medical purposes, wanted such use to be legalised.
7.12 The London Medical Marijuana Support Group (p 271) consider
the issue to be one of patients' rights: "Please do not continue to make
sick people criminals". They call for either rescheduling, or a new
system involving registration of patients. They would solve the problem
of supply by allowing patients to grow their own, or by setting up
co-operatives, or by permitting commercial cultivation. They argue that
different users get benefit from different preparations; so they do not
want a standardised preparation-though this would be better than
nothing.
7.13 If the law cannot be changed, it could in theory be applied
with flexibility. IDMU suggest "directives to the CPS on criteria to use
when deciding whether a prosecution of a medical cannabis user is in the
public interest" (p 225). According to the Home Office, however,
systematic non-enforcement would be "quite unacceptable" (Q 671).
7.14 Though some witnesses to this Committee favour immediate
transfer from Schedule 1 to Schedule 2, others are against it. Professor
Radda insisted that anecdotal evidence, however large in volume, was not
sufficient reason for rescheduling (Q 657). Sir William Asscher
considers that immediate rescheduling would actually threaten proper
trials, such as those proposed by his working party (see Chapter 5), by
encouraging patients to use cannabis in an uncontrolled way rather than
enrolling for the trial and risking receiving a placebo (Q 808).
7.15 The Multiple Sclerosis Society want sufferers to be able to
make "informed choice about therapeutic agents"; therefore they would
not support prescription of cannabis for MS in advance of proper trials
(p 90, Q 368). The Royal Society say that, pending proper trials, "There
is no persuasive case for the non-experimental medical use of cannabis";
and they are against smoking (p 295). The Royal Pharmaceutical Society
take the same line (p 289); so does Professor Strang, who would be
worried if cannabis were given "some easy track" (Q 249); so does Edward
Jurith, on sabbatical in Manchester from the post of General Counsel to
the White House Office of National Drug Control Policy (p 265). The
Christian Institute agree: "The rules must remain the same for all
substances...Rescheduling cannabis would declare that cannabis is
suitable for medical use. The studies have not been done to demonstrate
this" (p 207). They add that permitting cannabis to be smoked "would
profoundly damage current health promotion attempts to dissuade
smoking". They suggest that other steps might be taken to help MS
sufferers who are resorting to cannabis. Dr Pertwee considers that
permitting prescription of cannabis could not be justified until both
nabilone and dronabinol had been tried and failed (Q 314).
7.16 The BMA report recommends, "The WHO should advise the UN
Commission on Narcotic Drugs to reschedule certain cannabinoids under
the UN Convention on Psychotropic Substances, as in the case of
dronabinol [which was rescheduled in 1995]. In response the Home Office
should alter the Misuse of Drugs Act accordingly." Alternatively, "The
Government should consider changing the Misuse of Drugs Act to allow the
prescription of cannabinoids to patients with particular medical
conditions that are not adequately controlled by existing treatments".
On the other hand, David Nutt, Professor of Psychopharmacology at the
University of Bristol[26], considers that the availability of nabilone,
which may be prescribed on an unlicensed basis for any of the conditions
identified by the BMA, makes it unnecessary to change the law (p 280).
7.17 The Royal Pharmaceutical Society caution that, if unlicensed
use of cannabinoids becomes more common (as the BMA think it might,
following their report-Q 83), there should be "full consultation between
the medical and pharmacy professions" (p 290). They urge the Government
to consider moving all cannabinoids from Schedule 1 to Schedule 2.
Research
7.18 As noted in Chapter 3, cannabinoid pharmacology is currently
a lively field of research. However, until Dr Guy's initiative, no new
cannabis-based medicines were in commercial clinical development (Wall Q
134). As to why this should be so, most of our witnesses point to the
"stigma" of working with a "disreputable" substance and a Schedule 1
controlled drug (e.g. Austin Mitchell MP Q 132, Pertwee Q 317, Robson Q
482). Others point to the likelihood that a non-synthetic cannabis-based
medicine would be cheap and therefore unprofitable, and the markets for
it small (RPharmSoc p 289; Lader QQ 7, 17)-though Professor Ashton and
the BMA believe that the global market is potentially large (Q 57). Dr
Pertwee believes that drug companies are very interested in the
possibility of cannabinoids which avoid psychotropic effects by acting
only on the CB2 receptor (Q 281); they are "dying to get in there, but
they do not know what to do" (Q 295).
7.19 Dr Notcutt believes that what puts companies off research
involving a Schedule 1 drug is not the stigma, but the "sheer
difficulty" (Q 414). The principal additional difficulty is the
requirement to obtain a licence from the Home Office (see Box 8). If
cannabis were moved to Schedule 2 to the Regulations, research licences
would no longer be required (Q 677).
BOX 8: CANNABIS RESEARCH LICENCES
Licences to possess any Schedule 1 drug for research may be granted by
the Home Office under section 7 of the Misuse of Drugs Act and
Regulation 5 of the Misuse of Drugs Regulations. The Under-Secretary of
State at the Home Office, George Howarth MP, explained to us the
conditions under which licences are granted (Q 662). There must be a
legitimate reason for the research; details of method and timetable;
ethical approval; and safeguards including safe custody and
record-keeping. The research would normally be expected to be conducted
at a university hospital or pharmaceutical company; and the method of
administration must allow for control of dosage. According to the Home
Office, there have been a total of 27 applications for cannabis research
licences, of which 25 have been approved and two agreed in principle; no
application for a licence has been refused (HC WA 255, 18 Dec. 1997).
The Home Office supplied us with a list of 22 current licences. All are
granted to named researchers, 20 at universities and two in hospitals.
Most are for teaching or testing purposes; only three appear to be for
research. Four of the licences were issued this year, compared with 22
over the previous 24 years; the Home Office attribute the increase to a
Royal Pharmaceutical Society symposium on medical uses of cannabis in
July 1997 (Q 666). There are 80 current research licences for Schedule 1
substances other than cannabis (Q 665). Among our witnesses, cannabis
research licences are or have been held by Dr Pertwee, Dr Schon (see p
303 and Q 664), Dr Holdcroft (see paragraph 5.29), and Dr Guy (see
paragraph 5.44); and Jo Barnes has a licence "in principle" for the
Exeter pilot study (see paragraph 5.47).
7.20 In addition to the lack of commercial development work, there
is little clinical research in this area. Professor Wall comments, "It
is a paradox that a subject of such intense scientific interest should
receive so little clinical attention. One reason...[is] the daunting and
excessive bureaucratic control which artificially separates studies of
cannabis from drugs such as narcotics. The other reason is the general
social atmosphere which labels cannabis with every possible negative
attitude" (p 31, cp Q 143). He compares the attitude to medical use of
narcotics before the work of Dame Cicely Saunders (Q 127). Similarly Dr
Lambert says, "The Schedule 1 status of cannabis has made modern
clinical research almost impossible, primarily because of the legal,
ethical and bureaucratic difficulties in conducting trials with
patients. In addition, the general attitude towards cannabis...has not
helped"[27]. This is regrettable, since there is "a wide range of
possibilities and a massive opportunity for research". The Royal
Pharmaceutical Society blame the "disappointing" lack of evidence on the
"stigma" attached to cannabis, and the burden of licensing (p 288).
7.21 Professor Hall also believes that research has been chilled
by the link with recreational use. He regards this link as "spurious".
He observes, "The recent discovery of the cannabinoid receptor may help
to overcome some of the resistance...by holding out the prospect that
the psychoactive effects...can be disengaged from [the] other
therapeutically desirable effects" (p 222). The Multiple Sclerosis
Society believe that the stigma attached to cannabis as a medicine can
be countered by "raising awareness" and taking the issue seriously,
which to some extent has already happened (Q 372); and they know of
numerous volunteers for trials (Q 389).
7.22 Dr Holdcroft notes two further difficulties: the lack of
standardised preparations (she produced her own capsules), and the
medicolegal problems of working with cannabis-naive subjects[28]. Dr
Notcutt blames the licensing system, and the problem of supply (Q 413);
he is optimistic that Dr Guy's initiative may surmount both obstacles.
Austin Mitchell MP believes that ethical committees "run a mile" from
sanctioning clinical research using a Schedule 1 drug (Q 132). Professor
Edwards likewise points to ethical problems (Q 19); he recommends,
before blind trials, "a small series of open clinical investigations
with repeat and careful observations on the individual patient". The
National Drug Prevention Alliance, noting that the prospective markets
may be too small to warrant the commercial cost of trials, suggest that
trials might be grant-aided from public funds (p 279-they regard this as
preferable to licensing without trials).
7.23 The Department of Health say, "Both the Home Office and MCA
have always indicated that they are prepared to look sympathetically at
well-founded research proposals in this area" (p 48, cp Q 167). However
Dr Kendall calls for "relaxation of the level of control" over trials (p
268). Dr Robson, in his review for the Department, says, "Research will
only be possible if the regulations imposed under the Misuse of Drugs
Act are made more flexible". IDMU say (p 229), "The present licensing
system and policy has severely limited research opportunities and should
be reviewed"; given the rise in research activity noted above, the
United Kingdom academic community and pharmaceutical industry may miss
opportunities if the research licensing regime is not relaxed.
7.24 Yet the Multiple Sclerosis Society believe that the present
system obstructs research more by its effect on attitudes than by
practicalities (Q 388); and it is the impression of Austin Mitchell MP
(Q 132) and Clare Hodges (Q 136) that the Home Office are already more
flexible than they used to be. Professor Radda believes that a good
research proposal will receive a licence without difficulty, and that
scientists today are well used to regulation of this kind (Q 630). Dr
Guy says that, although consultation was lengthy (from application to
grant took 4 months-Q 663), the Home Office have been "most helpful" (p
162).
7.25 The BMA report said, "The regulation of cannabis and
cannabinoids should be sufficiently flexible to allow such compounds to
be researched without a Misuse of Drugs Act licence issued by the Home
Office". In evidence, the BMA reported "very positive feedback" from the
Department of Health and the Home Office on the pace of the licensing
process (Q 82); but they said that at present there was serious delay (Q
92). The Home Office responded, saying, "Applications for research
licences are dealt with as expeditiously as the circumstances allow" (p
149); the Minister gave the time from application to grant in the last
six cases, which averaged seven weeks (Q 663). The BMA hope that
guidelines for trials would help to accelerate the process (Q 92).
7.26 The Committee put to the BMA the idea of a meeting between
the Home Office and researchers, and they welcomed it (Q 93). The Home
Office say that they would be happy to hold such a meeting, jointly with
the Department of Health: "It would provide a useful opportunity to
highlight some of the complex issues involved such as the supply of
standardised cannabis, and the adoption of sound methodologies". Work is
now in hand to set up such a meeting (Q 686).
Medical use and recreational use
7.27 "Without pressing the panic button", Professor Edwards points
out that cannabis or preparations of cannabis supplied for medical use
might be diverted to recreational use (Q 20). Professor Hall warns that,
if doctors were allowed to prescribe cannabis, some might be tempted to
profit from bogus prescriptions (Q 761). New Department of Health
guidelines on clinical management of drug abuse are to cover "leakage"
of prescribable controlled drugs (such as methadone) onto the black
market; the Department comment that leakage of nabilone is "highly
unlikely", since it is dispensed only by hospital pharmacies in small
amounts (p 217). The BMA report says, "It would be prudent to develop a
labelling system that does not identify prescribed drugs as
cannabinoids, and to warn patients that such drugs should be kept in a
place inaccessible to others". Professor Nathanson added that, ideally,
cannabis-based medicines would be developed which had minimal
psychoactive effects (Q 76).
7.28 On 23 January 1997, the then Under-Secretary of State, Home
Office, told the House of Commons, "Many of those calling for the
medical use of cannabis are using it as a stalking horse to promote the
campaign for its legalisation" (HC col. 1060). David Copestake, a
Methodist Minister who has researched and written in this field, takes
this view; he observes that medical uses were once touted for tobacco (p
213). The NDPA say the same, claiming that the BMA has been "hi-jacked"
and that the ACT are "very familiar" with lobbyists for legalisation (p
278). The Christian Institute agree (p 208).
7.29 The ACT insist that they are not calling for general
legalisation (p 28). They point out that heroin (diamorphine) may be
prescribed (it is a Class A drug under the Misuse of Drugs Act, yet in
Schedule 2 to the 1985 Regulations). Dr Notcutt observes that there is
no evidence that heroin abuse is thereby encouraged, and lists several
other drugs of potential abuse which are used unlicensed in chronic pain
(p 105). The MRC make the same point, and say (as do several other
witnesses), "The question of potential medical uses for cannabis and its
derivatives must be considered quite separately from the question of
prohibition of recreational use" (p 144). According to Professor Hall,
there is a stalking-horse element to the debate on medical use; but this
should not be allowed to influence the argument either way (p 222).
7.30 The Department of Health still detect an element of the
stalking-horse. However they acknowledge and support "the genuine
concern of some people to find medicinal products for intractable
conditions" (Q 176).
***
25 Hirst R A, Lambert D G and Notcutt W G, op. cit. Back
26 A member of the Independent Inquiry into the Misuse of Drugs
Act-see paragraph 6.19. Back
27 Hirst R A, Lambert D G and Notcutt W G, op. cit. Back
28 Holdcroft A et al, op. cit. Back
***
Select Committee on Science and Technology Ninth Report
***
CHAPTER 8 OPINION OF THE COMMITTEE
Medical use of cannabis: recommendations
8.1 We recognise that, in all the evidence we have received, there
is not enough rigorous scientific evidence to prove conclusively that
cannabis itself has, or indeed has not, medical value of any kind.
8.2 Nevertheless we have received enough anecdotal evidence (see
above, paragraphs 5.4, 20-22, 27-30) to convince us that cannabis almost
certainly does have genuine medical applications, especially in treating
the painful muscular spasms and other symptoms of MS and in the control
of other forms of pain.
8.3 We therefore recommend that clinical trials of cannabis for
the treatment of MS and chronic pain should be mounted as a matter of
urgency. We warmly welcome the fact that, in the course of our inquiry,
both Dr Geoffrey Guy of GW Pharmaceuticals, and the Royal Pharmaceutical
Society's working group under Sir William Asscher, have set off down
this route (paragraphs 5.44-48). We welcome the Asscher group's
intention to compare the effects of a standardised preparation of
natural cannabis with those of the one synthetic cannabinoid already
available, dronabinol, on the basis of the same dose level of THC.
8.4 Although neither Dr Guy nor the Asscher group contemplate
trials of smoked cannabis, we agree with the Chief Executive of the MRC
that such a trial should not be ruled out (paragraph 5.57). However we
recognise the dangers of smoking, and we do not envisage smoking being
used to administer any medicine eventually licensed. For this reason we
recommend that research be promoted into alternative modes of
administration (e.g. inhalation, sub-lingual, rectal) which would retain
the benefit of rapid absorption offered by smoking, without the adverse
effects.
8.5 The Government have said repeatedly that, if sufficient
evidence in favour of cannabis as a medicine were produced for the MCA
to be prepared to license it, they would amend the Misuse of Drugs
Regulations so as to permit it to be prescribed. The problem with this
policy is that it will take several years at least for this to happen.
The Asscher group's trials are not expected to be complete before
mid-2001, and will lead only to "proof of principle", leaving others to
proceed with any pharmaceutical development. Dr Guy does not expect to
receive a product licence in under five years. In the mean time, 85,000
people in this country will continue to suffer the very unpleasant
symptoms of MS. Only a small proportion of these are known to have tried
cannabis illegally; but of these, significant numbers report great
relief of their symptoms. We do not believe that this position is
satisfactory.
8.6 We therefore recommend that the Government should take steps
to transfer cannabis and cannabis resin from Schedule 1 to the Misuse of
Drugs Regulations to Schedule 2 (see Box 3), so as to allow doctors to
prescribe an appropriate preparation of cannabis, albeit as an
unlicensed medicine and on the named-patient basis (see Box 6), and to
allow doctors and pharmacists to supply the drug prescribed. This would
also, incidentally, allow research without a special licence from the
Home Office (see Box 8).
8.7 It is argued in some quarters that some of those who campaign
for medical use see it as a stalking-horse for the legalisation of
recreational use (paragraphs 7.28-30). We do not see this as a reason to
resist medical use if, as we believe, it is justified by the evidence.
We prefer the argument recently advanced by Austin Mitchell MP in the
House of Commons (14 January 1998, col. 317): at present, people who use
cannabis for medical reasons are caught in the front line of the war
against drug abuse. This makes criminals of people whose intentions are
innocent, it adds to the burden on enforcement agencies, and it brings
the law into disrepute. Legalising medical use on prescription, in the
way that we recommend, would create a clear separation between medical
and recreational use, under control of the health care professions. We
believe it would in fact make the line against recreational use easier
to hold.
8.8 Before moving cannabis out of Schedule 1, the Government are
required by law to consult the Advisory Council on the Misuse of Drugs.
We recommend that they do so at once, and respond to this report only
after receiving and considering the advice of the Council. We recognise
that this may take longer than the time normally allowed for such
responses.
Medical use of cannabinoids: recommendations
8.9 Unlike cannabis itself, the cannabinoid THC (dronabinol) and
its analogue nabilone are already accepted by the Government as having
medical value (paragraphs 5.11-17)-producing the anomaly that, while
cannabis itself is banned as a psychoactive drug, THC, the principal
substance which makes it psychoactive, is in legitimate medical use.
Some of our witnesses are prepared (paragraph 5.50) to contemplate wider
medical use of the cannabinoids, but not of cannabis itself. We
disagree, since some users of both find cannabis itself more effective
(paragraph 5.51). We do, however, welcome the inclusion of THC in the
trials proposed by the Asscher group, in like-for-like comparison with
cannabis itself.
8.10 Dronabinol (THC), though not licensed in this country, has
already been moved to Schedule 2 to the Misuse of Drugs Regulations, and
nabilone is a licensed medicine and not a controlled drug; so no
Government action is required in either case to permit clinical trials
or indeed prescription. All cannabinoids other than THC remain in
Schedule 1, and transferring them would require agreement through the
WHO under the 1971 Convention. We do not regard this as a priority,
since we are not persuaded that any other cannabinoid has a convincing
medical use; but we recommend that the Government should raise the
matter of rescheduling the remaining cannabinoids with the WHO in due
course, in order to facilitate research.
Why change the law?
8.11 Our principal reason for recommending that the law be
changed, to make legal the use of cannabis for medical purposes, is
compassionate. Illegal medical use of cannabis is quite widespread
(paragraphs 5.2-3); it is sometimes connived at and even in some cases
encouraged by health professionals (paragraph 5.6); and yet at present
it exposes patients and in some cases their carers to all the distress
of criminal proceedings, with the possibility of serious penalties. We
acknowledge that, if our recommendation were implemented, the United
Kingdom would be moving out of step with many other countries; we
consider that the Government should not be afraid to give a lead in this
matter in a responsible way.
8.12 As a secondary reason, we would observe that the law in this
area appears to be being enforced inconsistently, and in some cases with
a very light hand (paragraphs 7.2-5). Some cases are not brought to
court; where users of cannabis for medical purposes have been
prosecuted, the sentence has sometimes been light; and there have even
been cases where juries have refused to convict. The Minister told us
that he was content to leave this as a matter for the discretion of the
prosecuting authorities and the courts (QQ 668-673). That is a
constitutionally proper position for a Minister; but it is not the right
position for Parliament. If statute law is not enforced, Parliament is
brought into disrepute; either enforcement must be tightened up, or the
law must be changed. In this case, we recommend the latter.
8.13 A further subsidiary advantage of transfer from Schedule 1 to
Schedule 2 would be the encouragement which this would give to research
(paragraphs 7.18-26). There are exciting research opportunities in this
field (see Chapter 3), which (on the basis of the number of grants by
the MRC and the Wellcome Trust, and the number of Home Office research
licences-paragraph 5.39 and Box 8) are not being fully taken up in this
country, despite the excellence of British biomedical science. We are
satisfied that the Home Office are not being deliberately obstructive;
and we are glad that they have already taken up our proposal for a
meeting between the research community and those responsible for the
research licensing regime (paragraph 7.26). But, now that research in
this field has taken off, and the existence of important medical
applications is (in our view) well established, it is not appropriate
for research to continue to be subject to this extra layer of
administration. Transfer to Schedule 2 would also go some way to
removing the stigma which many of our witnesses believe hangs over
research in this field, deterring researchers, funding bodies,
pharmaceutical companies and local ethics committees alike from
involvement in research which might turn out to be of great importance.
8.14 As the Minister pointed out to us, a doctor who prescribed
cannabis on these terms, in the absence of a product licensed by the MCA
for the relevant indication, would take on himself full responsibility
for the consequences (Q 679). This is true. However we have received
evidence from doctors who are currently prescribing nabilone on an
unlicensed basis (Notcutt Q 405). We believe that the overwhelming
majority of members of the medical profession can be trusted not to be
reckless in this matter, and that the professional regulatory bodies
will deal effectively with any who are.
8.15 The Minister also observed that, in some cases, someone
charged with a cannabis offence may claim medical use as a bogus defence
or plea in mitigation (Q 674). We do not doubt that this happens at
present; and, in the case of some people, it may be hard to tell where
recreational use stops and medical use begins (paragraph 5.5).
Rescheduling so as to permit prescription would in fact make this
problem easier to deal with: rather than having to investigate
individual medical histories, as at present, the authorities would
simply ask to see the prescription.
8.16 As with any medicine, there are some groups of patients for
whom cannabis-based medicines will not be appropriate. On the evidence
before us, cannabis-based medicines should not be prescribed for persons
with, or predisposed towards, schizophrenic illness (paragraph 4.12) or
cardiovascular conditions (paragraph 4.4); nor, pending further
research, should they be prescribed for pregnant women (paragraphs
4.15-16). As with many medicines, users should be warned of possible
effects on driving ability (paragraphs 4.6-9) and cognitive function
(paragraph 4.13). As with any potentially addictive medicine, the risk
of addiction (paragraphs 4.23-33) should be weighed up when deciding
whether to prescribe, and the user should be warned. Therefore, if
doctors are permitted to prescribe cannabis on an unlicensed basis, the
medical professional bodies should provide firm guidance on how to do so
responsibly (paragraph 7.17).
8.17 As with any medicine which is open to abuse, safeguards must
be put in place by the professional regulatory bodies to prevent
diversion to improper purposes (paragraph 7.27). These might include a
system of declarations to be signed by the doctor and the patient.
Recreational use
8.18 It is believed in some quarters that the current absolute
prohibition on the recreational use of cannabis and its derivatives is
not justified by the adverse consequences for the user and the public.
On the evidence before us, we disagree. On the contrary, we endorse the
Government's statement in Tackling Drugs: "The more evidence becomes
available about the risks of...cannabis,...the more discredited the
notion that [it is] harmless" (paragraph 6.16).
8.19 The harms must not be overstated: cannabis is neither
poisonous (paragraph 4.3), nor highly addictive, and we do not believe
that it can cause schizophrenia in a previously well user with no
predisposition to develop the disease. However, we are satisfied that:
- It is intoxicating, enough to impair the ability to carry out
safety-critical tasks (such as flying, driving or operating machinery)
for several hours after taking (paragraphs 4.6-9);
- It can have adverse psychic effects ranging from temporary
distress, through transient psychosis, to the exacerbation of
pre-existing mental illness (paragraphs 4.10-12);
- Regular use can lead to psychological dependence (paragraphs
4.23-33); and, in some dependent individuals (perhaps 5-10 per cent of
regular users), regular heavy use can produce a state of near continuous
intoxication, making normal life impossible;
- Withdrawal may occasionally involve unpleasant symptoms
(paragraphs 4.23-25);
- Cannabis impairs cognitive function during use (paragraph 4.6);
- It increases the heart rate and lowers the blood pressure,
carrying risks to people with cardiovascular conditions, especially
first-time users who have not developed tolerance to this effect
(paragraph 4.4).
8.20 Moreover, it is possible, though not proved, that the effects
of cannabis on driving etc. may last longer than a few hours after
taking (paragraph 4.7); that the damage to cognitive function may endure
after withdrawal (paragraph 4.13); and that cannabis has adverse effects
on the immune system (paragraph 5.16) and on fertility and reproduction
(paragraphs 4.15-16).
8.21 In addition, smoking cannabis carries similar risks of
respiratory disorders to smoking tobacco. It is also possible, though
not proved, that exposure to cannabis smoke increases the risk of
cancers of the mouth, throat and lung (paragraphs 4.17-18).
8.22 Therefore, on the basis of the scientific evidence which we
have collected, we recommend that cannabis and its derivatives should
continue to be controlled drugs.
Summary of recommendations
8.23
(i) Clinical trials of cannabis for the treatment of MS and
chronic pain should be mounted as a matter of urgency (paragraph 8.3).
(ii) Research should be promoted into alternative modes of
administration (e.g. inhalation, sub-lingual, rectal) which would retain
the benefit of rapid absorption offered by smoking, without the adverse
effects (paragraph 8.4).
(iii) The Government should take steps to transfer cannabis and
cannabis resin from Schedule 1 to the Misuse of Drugs Regulations to
Schedule 2, so as to allow doctors to prescribe an appropriate
preparation of cannabis, albeit as an unlicensed medicine and on the
named-patient basis, and to allow doctors and pharmacists to supply the
drug prescribed (paragraph 8.6).
(iv) The Government should consult the Advisory Council on the
Misuse of Drugs on this matter at once, and respond to this report only
after receiving and considering their advice (paragraph 8.8).
(v) The Government should raise the question of rescheduling the
remaining cannabinoids with the WHO in due course (paragraph 8.10).
(vi) If doctors are permitted to prescribe cannabis on an
unlicensed basis, the medical professional bodies should provide firm
guidance on how to do so responsibly (paragraph 8.16); and safeguards
must be put in place by the professional regulatory bodies to prevent
diversion to improper purposes (paragraph 8.17).
(vii) Cannabis and its derivatives should continue to be
controlled drugs (paragraph 8.22).
***
Select Committee on Science and Technology Ninth Report
***
APPENDIX 1
Members of the Sub-Committee which conducted the enquiry
* Lord Butterfield
* Lord Butterworth
* Lord Carmichael of Kelvingrove
* Lord Dixon-Smith
* Lord Kirkwood
* Lord Nathan
* Lord Perry of Walton (Chairman)
* Lord Porter of Luddenham
* Lord Rea
* Lord Soulsby of Swaffham Prior
* Lord Walton of Detchant
* Lord Winston
* Co-opted members
The Sub-Committee appointed as its Specialist Adviser:
Professor Leslie Iversen FRS, Visiting Professor of Pharmacology,
University of Oxford
APPENDIX 2
Witnesses
The following witnesses gave evidence. Those marked * gave oral
evidence. Those marked ** gave written evidence which is not printed,
but is available for inspection at the House of Lords Record Office
(0171-219 5316):
** Academy of Medical Sciences (with Royal Society)
** Advisory Council on Misuse of Drugs
** Alliance for Cannabis Therapeutics
** Anonymous
** Professor Heather Ashton
** Association of Chief Police Officers
** Dr Anthony Blowers, Surrey's Drug Action Team
** Mary Brett, Dr Challoner's Grammar School (Boys), Amersham
** British Medical Association
** J Brown
** Christian Institute
** S Cooke
** David Copestake
** Dr Angela Coutts, University of Aberdeen
** Department of Complementary Medicine, University of Exeter
** R Creasey
** P Davidson
** M Davies
** S Day
** Department of Health
** Dutch National Institute of Public Health and the Environment
** Evangelical Coalition on Drugs Executive Committee
** C Fell
** Forensic Science Service
** L Gibson
** Professor Keith Green, Medical College of Georgia, USA
** Dr Geoffrey Guy
** Professor Wayne Hall, Executive Director, National Drug and Alcohol
Research Centre, Australia
** Professor John Henry, Imperial College School of Medicine (on behalf
of Royal College of Pathologists)
** Dr Anita Holdcroft, Imperial College School of Medicine
** Home Office
** M Humphreys
** Independent Drug Monitoring Unit
** Institute for the Study of Drug Dependence
** International Drug Strategy Institute
** Edward H Jurith
** Dr David Kendall, University of Nottingham Medical School
** Dr David Lambert
** D Lewis
** London Medical Marijuana Support Group
** Medical Research Council
** Medicines Control Agency
** Dr Tod H Mikuriya
** Austin Mitchell MP
** Mr Neil Montgomery
** Multiple Sclerosis Society
** National Addiction Centre
** National Drug Prevention Alliance
** NHS National Teratology Information Service
** Dr William Notcutt
** Professor David Nutt, University of Bristol
** Dr Roger Pertwee
** A Phillipson
** P Rigby
** Dr Philip Robson
** E Rorison
** Royal College of General Practitioners
** Royal College of Pathologists
** Royal College of Psychiatrists
** Royal Pharmaceutical Society of Great Britain
** Royal Society
** J Sayers
** Dr Fred Schon, Mayday Hospital Croydon and St George's Hospital
** Dr P Shaw
** Councillor C Simpson, Aberystwyth
** L Standen
** Dr Colin Stewart, Dundee Limb Fitting Centre
** G Vincent
** Young Christian Democrats
***
APPENDIX 3
Notes on Conference "Marihuana and Medicine" at New York University
Medical Center, New York, 20-21 March 1998
by Professor Leslie Iversen FRS, Specialist Adviser
1. The conference, organised by Professor G. Nahas and colleagues, gave
an overview of the current position in the USA. A topical issue there is
whether smoked marijuana should be permitted for medical use, since oral
formulations of tetrahydrocannabinol (THC) and nabilone are already
available medically.
2. M. Huestis (National Institute on Drug Abuse) reviewed new
information on the disposition and metabolism of cannabis in human
subjects, using sensitive analytical techniques to measure THC and some
of the major metabolites. Because a substantial proportion of the
absorbed THC is sequestered in fat tissues, the half life of the drug in
blood is > 4 days and the half life of the major urinary metabolite
11carboxylic acid THC is > 30 hours. By measuring the ratio of
unchanged THC to this metabolite in samples of blood or urine it may be
possible to calculate when the last dose of THC was taken-information
that could be of importance forensically. An unexpected finding was the
large variability between subjects in the amount of THC absorbed by
smoking a standard marijuana cigarette under laboratory conditions; even
though the number and frequency of puffs was controlled there was a
3fold range. For the same subject tested on different occasions there
was also a considerable variability in the amount of THC absorbed (17
per cent on average).
3. M. El Sohly (University of Mississippi) described the development of
a rectal suppository formulation for delivery of THC in the form of a
"prodrug" (the hemisuccinate ester) dissolved in a lipid base.
Absorption of THC increased in a dosedependent manner and was prolonged
(THC was measurable in blood for up to 8 hours). Because this route of
absorption avoids first pass metabolism in the liver, the amount of THC
absorbed into circulation was more than twice as great as after oral
dosage. Unfortunately there was a high variability between subjects in
the amount of THC absorbed (about 3fold). The advantages of this route
of administration seem clear, but it was thought unlikely to be popular
in the United States where suppository formulations have never been
widely accepted.
4. B. Thomas (Research Triangle Institute) reviewed the operation of
his laboratory which supplies standard marijuana cigarettes to the 8
individual glaucoma patients licensed in the US to receive this
medication, and to research groups in the US and elsewhere. By using
standard growing conditions (at the University of Mississippi) and
different strains of cannabis plant they are able to generate marijuana
cigarettes of consistent quality and standard THC content (standard =
1.8 per cent THC; strong = 4.0 per cent THC) free of microbial or insect
contamination. Placebo cigarettes are prepared using leaf material
extracted with alcohol to remove THC.
5. Roger Pertwee (University of Aberdeen) reviewed current knowledge of
the two cannabinoid receptors CB1 (found in the brain and some
peripheral organs) and CB2 (peripheral only). The presence of CB2
receptors on cells in the immune system has prompted some pharmaceutical
companies to become interested in this as a possible target for the
discovery of novel immunesuppressant or antiinflammatory drugs. The
French company Sanofi and the Canadian company MerckFrosst have
reported novel synthetic antagonists/agonists acting selectively at
these sites. The availability of novel synthetic antagonists acting at
the CB1 receptors (eg SR141716A (Sanofi), LY 320135 (Eli Lilly)) has
provided valuable new research tools. New drugs are also being designed
based on the structure of the endogenous cannabinoid anandamide.
6. R. Mechoulam (Hebrew University, Israel) described his
identification of Ä9THC as the principal psychoactive compound in
cannabis extracts, and his subsequent discovery of anandamide as the
naturally occurring cannabislike compound in the brain. Other naturally
occurring fatty acid derivatives also interact with cannabis receptors,
and one of these, 2arachidonylglycerol, may act selectively at CB2
receptors.
7. E. Gardner (Albert Einstein College of Medicine, New York) described
studies of the interaction of THC with reward pathways in rat brain. He
confirmed earlier work from an Italian laboratory (Tanda et al, 1997,
Science, 276:20482050) that administration of THC (0.5mg/kg) to rats
caused an increase in dopamine release in the nucleus accumbens region
of the brain and, furthermore, that this release could be blocked by
coadministration of the drug naloxone, which blocks opiate receptors in
the brain. He also found that THC sensitised rats to the rewarding
effects of intracranial selfstimulation and that this effect was also
blocked by naloxone. These results are potentially important as they
indicate that THC stimulates dopamine pathways in the brain known to be
activated by various addictive drugs-nicotine, amphetamine, heroin and
cocaine. The blocking effects of naloxone suggest that THC may exert at
least part of its rewarding effects indirectly by promoting a release of
opiatelike chemicals in the brain.
8. D. Tashkin (University of California Los Angeles) surveyed the
effects on the lung of long-term marijuana use. He conducted large scale
studies in the 1980s in heavy marijuana smokers and compared them with
subjects who smoked tobacco. Marijuana smokers showed some bronchial
symptoms (cough, wheeze and bronchitis), but there was no evidence for
any significant reduction in overall respiratory function. When data
were collected annually for a further 8 years, the marijuana smokers did
not show the agerelated decline in respiratory function seen in tobacco
smokers. Nevertheless, there was concern about the longer-term effects
of marijuana smoking. Examination of the lining of the airways revealed
inflammatory changes in chronic marijuana smokers, with an increase in
the number of mucussecreting cells and sometimes what appeared to be
precancerous alterations in cells lining the lungs. Examination of lung
biopsy specimens showed an increased expression of certain genes that
are markers of lung tumours. In addition the immune defence system
appears to be depressed in the lungs of marijuana smokers. The defending
white cells (macrophages), although present in increased numbers, had a
decreased ability to kill bacteria or fungi and produced reduced amounts
of nitric oxide and cytokines, the normal defence chemicals. Suppression
of immune system function may be related to a direct effect of cannabis
on receptors on the macrophages and other immune system cells. Although
there was no evidence for increases in lung cancers in marijuana
smokers, there were some reports of increases in cancers of mouth and
throat. The reduction in immune system function could make marijuana
smokers especially vulnerable to lung infections.
9. K. Coe (formerly at Pfizer Research) and L. Lemberger (formerly at
Eli Lilly Research) gave historical reviews of the development of novel
drugs for the treatment of pain and prevention of nausea based on
cannabinoid chemical structures. A project at Pfizer in the 1970s led to
the discovery of the synthetic compound levonantradol and the related
compound CP55,940. These compounds had a much greater water solubility
than THC and proved to be up to 100 times more potent than morphine in
some animal tests of pain. Levonantrodol entered pilot scale clinical
trials and was effective in suppressing postoperative pain and in
preventing nausea and vomiting associated with cancer chemotherapy. It
was evident, however, that the drug did not separate the beneficial
clinical effects from intoxicant effects, and the company abandoned the
project in 1980. CP55,940 proved valuable, however, in radioactively
labelled form as a probe which led to the identification of the cannabis
CB1 receptor in the brain.
10. At Eli Lilly during the same period there was also a hope that the
beneficial effects of cannabinoids could be separated from unwanted
psychoactivity, and this led to the discovery and development of
nabilone. Clinical trials established the effectiveness of this drug in
the treatment of the nausea and vomiting associated with cancer
chemotherapy. Although some patients complained of the druginduced
"high", this appeared milder than that associated with THC. However,
although nabilone was approved for medical use by the Food and Drug
Administration, the US Drug Enforcement Agency insisted that it be given
a "Schedule II" classification [i.e. a compound with some medical use
but a high abuse potential, so doctors using it have to keep detailed
records]. This led to the company withdrawing from the project and also
failing to give any substantial marketing support to the compound.
Postmarketing surveillance reports in the UK, where the compound has
some limited use, have not shown any danger of abuse.
11. W. Notcutt (Great Yarmouth), a consultant in a pain clinic,
reported on the positive effects of nabilone in the relief of pain in
some of his patients who were suffering from chronic pain and not
responding to other medications. In a total of 55 patients he observed
beneficial effects of nabilone (improved sleep, reduced pain) in about
one third.
12. K. Green (Medical College of Georgia) and M. Forbes (Columbia
University College, NY) discussed the possible use of cannabis in the
treatment of glaucoma. There are more than 2 million glaucoma patients
in the USA alone, and glaucoma is a major cause of blindness. THC or
smoked marijuana does cause a marked fall in intraocular pressure in
both normal subjects and patients with glaucoma (up to 45 per cent
reduction), but the effect is transient and returns to baseline within
34 hours. It is difficult to achieve longer-term control of intraocular
pressure as this would require frequent repeat dosing. THC cannot be
delivered topically to the eye (the preferred route for antiglaucoma
medications) because of its low water solubility. It is possible that an
improved topical delivery formulation, or topical use of a more water
soluble synthetic cannabinoid, could be developed in the future. In the
USA a small group of patients (8) have individual permission to use
smoked marijuana to treat their glaucoma.
13. R. Graller (New Orleans) reviewed the use of cannabis in the
treatment of nausea and vomiting. Although there have been several
controlled clinical trials showing the effectiveness of orally
administered THC and nabilone in patients receiving cancer chemotherapy,
there are few data on smoked marijuana. In recent years a new class of
antinausea drugs, the 5HT3 antagonists (e.g. ondansetron, granisetron)
have radically improved the treatment of nausea and vomiting in cancer
patients. He found that a combination of granisetron and the steroid
dexamethasone controlled the symptoms in more than 90 per cent of
patients. Unlike THC which cannot be given intravenously, granisetron
can be given by this route as well as by mouth.
14. G. Francis (McGill University, Montreal) discussed the use of
cannabis in the treatment of multiple sclerosis. There are few effective
treatments for this disease, and more than 250,000 patients in the USA.
Some symptoms are particularly poorly controlled by existing medicines,
notably tremor, pain and spasticity. There are many anecdotal reports
that these symptoms are eased by smoked marijuana, but so far there have
been few controlled clinical trials. A currently ongoing study with 600
subjects aims to compare smoked marijuana with a placebo (cigarettes
with THC removed). Results available so far suggest that the subjective
reports of improvement by patients are not always accompanied by
improvement in objective measures of performance.
APPENDIX 4
Notes on the International Cannabinoid Research Society 1998 Symposium
on Cannabinoids, La Grande Motte, France, 23-25 July 1998
by Professor Leslie Iversen FRS, Specialist Adviser
1. The annual meeting of this group of research scientists was held for
the first time outside North America and was attended by about 150
scientists, largely from academia. Of the 135 papers presented 73
originated from the United States and 50 from Europe (including 12 from
Britain, 5 of which were from Dr Pertwee's group in Aberdeen).
Endogenous cannabinoids
2. A substantial number of papers focused on the naturally occurring
cannabinoids in the brain and in peripheral tissues. At least two lipid
derivatives are now recognised: anandamide (arichidonylethanolamide)
and an arichidonic acid ester, 2arachidonylglycerol (2AG). The latter
substance is as potent as anandamide and is present in much larger
quantities than anandamide in the brain. Several papers focused on the
biochemical mechanisms involved in the synthesis and degradation of
these lipids in the brain, and progress has been made in defining the
biochemical mechanisms involved. Attention has also focused on the
development of metabolically more stable chemical analogues of
anandamide and 2AG with improved activity in whole animal studies: the
naturally occurring compounds are rapidly degraded and are thus not very
active in vivo. Another lipid, palmitoylethanolamide, may represent the
natural activator of CB2 receptors, although there was some disagreement
about its pharmacological activity and selectivity.
Cannabinoid receptors
3. Several groups are studying the detailed molecular architecture of
the CB1 and CB2 receptors and beginning to identify the precise sites at
which the cannabinoids bind to these proteins. Studies of the receptors
in in vitro model systems have revealed some interesting differences
between the effectiveness of various cannabinoids in activating the
receptors. In particular Ä9THC appears to act as only a partial agonist
at the CB1 receptor (i.e. it cannot elicit a maximum response).
Cannabidiol, one of the most abundant plant alkaloids, on the other hand
appears to act as an antagonist at the CB1 receptor.
4. The CB1selective antagonist drug SR141716A and the related
CB2selective antagonist SR144528 from the French pharmaceutical company
Sanofi were the subject of many papers, and these compounds have proved
to be important new research tools for probing cannabinoid functions.
Scientists from Sanofi revealed that they are developing SR141716A for
clinical trials, with schizophrenia as their first target (on the
rationale that high doses of THC can cause a schizophrenialike
psychosis). A novel CB1 antagonist CP272871 from Pfizer was described
for the first time; it has properties similar to those of SR141716A.
5. The CB2 receptor, located principally on cells in the immune system,
has attracted attention from a number of major pharmaceutical companies
as a potential target for discovering novel antiinflammatory or
immuno-suppressant drugs. There has been progress in identifying
CB2selective drugs (by Merck Frosst, GlaxoWellcome, and Smith Kline
Beecham) but so far there is little confidence that this target will
prove useful. Dr Nancy Buckley (US National Institutes of Health)
described the "CB2 knockout mouse" in which as a result of genetic
engineering the CB2 receptor is no longer expressed. These mice seem
remarkably normal in their immune cell population and in immune function
and have not so far assisted in understanding the role normally played
by the CB2 receptors.
Adverse effects
6. D. Tashkin (UCLA) reported that treatment of mice with THC (5 mg/kg
four times a week) led to more rapid growth of implanted lung cancer
cells and decreased survival. He suggests that THC may suppress
immunemediated eradication of tumour cells.
7. A session sponsored by the US National Institute on Drug Abuse
focused on the effects of long-term cannabis use on frontal lobe
function in man. A series of studies using imaging, cerebral blood flow
and electroencephalographic measurements indicated depressed frontal
lobe function in long-term cannabis users, and there were accompanying
subtle deficits in sensory and cognitive processing, the so-called
"executive functions" of the brain. There was little evidence that any
of these effects persisted after cessation of drug intake.
8. Billy Martin et al (Virginia, USA) described an animal model of
cannabis dependence. When dogs were treated with high doses of THC for
714 days and then challenged with the CB1 antagonist SR141716A clear
physical signs of withdrawal became apparent; these included trembling,
shaking, restlessness, vomiting and diarrhoea. By using the antagonist
challenge model it has become much clearer that physical dependence and
withdrawal can occur with THC, at least in animals. Furthermore, de
Fonseca et al (Madrid) reported that the administration of SR141716A to
morphinedependent animals elicited a behavioural and endocrine syndrome
similar to that seen in opiate withdrawal, although considerably milder.
Conversely some withdrawal signs could be elicited in
cannabinoid-dependent animals when challenged with the opiate receptor
antagonist naloxone, suggesting an interaction between the opioid and
cannabinoid systems in the brain.
Possible applications of cannabinoids
9. The interaction of opiate and cannabinoid mechanisms was also
highlighted by Sandra Welch (Medical College of Virginia, USA) who
reported that low doses of THC significantly potentiated the
painrelieving effects of morphine and other opiates in a mouse model of
arthritislike pain. Higher doses of THC were also by themselves fully
effective in causing analgesia in this model. She is planning a clinical
trial (with the approval of the US Food & Drug Administration) of low
doses of THC (dronabinol) in conjunction with selfadministered morphine
in patients suffering from cancer pain, in the hope that the drug
combination may make morphine more effective in such patients.
10. D. Piomelli ( San Diego, USA) described powerful analgesic effects
of anandamide when injected directly into the rat paw in an inflamed paw
model of inflammatory pain. The mechanism appeared to involve both CB1
and CB2 receptors located on sensory nerve fibres in the skin, and when
a combination of CB1selective and CB2selective compounds was injected
there was synergy between them. Experiments using radiolabelled
anandamide showed that >90 per cent of the injected dose remained in the
paw, and very little entered the brain or spinal cord. These results are
highly original and suggest the possibility that cannabinoids can exert
painrelieving actions without having to penetrate into the central
nervous system.
11. P. Consroe and R. Musty (University of Arizona, USA) described the
results of an anonymous survey of 106 patients with spinal cord injuries
who were selfmedicating with smoked marijuana. Patients smoked an
average of 4 joints a day, 6 days a week and had been doing so for >10
years. More than 90 per cent reported that cannabis helped improve
symptoms of muscle spasms of arms or legs, and improved urinary control
and function. Around 70 per cent reported pain relief. The results of
this survey and a similar one conducted with R. Pertwee in MS patients
may help to pinpoint the relevant symptoms to focus on as outcome
measures in future clinical trials of cannabis or cannabinoids.
12. D. Pate (University of Kuopio, Finland) described promising results
in the reduction of intraocular pressure when a metabolically stable
anandamide analogue was applied topically to normal rabbit eye. This
effect appeared to involve a local CB1 receptor mechanism as it could be
blocked by pretreating the animals with the antagonist SR141716A. In
order to deliver the waterinsoluble lipid derivative to the eye it was
dispersed in an aqueous solution containing a betacyclodextrin carrier.
Miscellaneous
13. M. El Sohly (University of Mississippi, USA) summarised results
obtained from the analysis of confiscated marijuana samples, a service
which has been running since 1980 and which involves the analysis of
samples from all regions of the United States. Data from 35,312 samples
were available. The potency of marijuana leaf samples (the commonest in
US seizures) rose from around 1.5 per cent THC content in 1980 to around
3 per cent in the 1980s and most recently to 3.87 per cent in 1996 and
4.15 per cent in 1997. The THC content of sinsemilla (the female plant
flower head) rose from around 6.5 per cent in 1980 to 9.22 per cent
(1996) and 11.53 per cent (1997). The increases are thought to be due to
improved culture conditions rather than to any genetic improvements.
Analysis of samples of cannabis resin or oil revealed few discernible
trends, with figures ranging from 3 per cent to 19 per cent THC content.
14. J. Khodabaks and O. Engelsma (Maripharm, Netherlands) described
their development of "The standardised medical grade marihuana plant".
Until recently this group has been supplying Dutch pharmacists with
medical grade marijuana, but its legal status has recently been
questioned. The laboratory cultivates standard cannabis plants selected
for a high yield of THC and low content of other cannabinoids; these are
cloned by propagating (by cuttings) from female plants. The plants are
grown under standard conditions and the female flower heads harvested
and vacuum-sealed for storage and then gammairradiated to sterilise the
preparations. Samples are routinely checked for THC and other
cannabinoids and to ensure that they are free of pesticides. The THC
content in different batches was highly consistent at 10.7 ± 0.1 per
cent (standard deviation). Interestingly, in the light of discussions
about the relevance of other cannabinoids in herbal cannabis,
cannabidiol and cannabinol were present in only minor amounts (<0.1 per
cent) in these samples.
APPENDIX 5
Abbreviations
ACMD
ACT
AMA
BMA
CMO
CPS
DETR
DH
HC
HL
FSS
IDMU
ISDD
LMMSG
MCA
MRC
MS
MSSoc
NDPA
NHS
NTIS
POST
RCGP
RCPath
RCPsych
RPharmSoc
THC
WA
WHO
UNAdvisory Council on the Misuse of Drugs
UK Alliance for Cannabis Therapeutics
American Medical Association
British Medical Association
Chief Medical Officer
Crown Prosecution Service
Department of the Environment, Transport and the Regions
Department of Health
House of Commons (Hansard)
House of Lords (Hansard)
Forensic Science Service
Independent Drug Monitoring Unit
Institute for the Study of Drug Dependence
London Medical Marijuana Support Group
Medicines Control Agency
Medical Research Council
Multiple sclerosis
Multiple Sclerosis Society
National Drug Prevention Alliance
National Health Service
NHS National Teratology Information Service
Parliamentary Office of Science and Technology
Royal College of General Practitioners
Royal College of Pathologists
Royal College of Psychiatrists
Royal Pharmaceutical Society of Great Britain
Tetrahydrocannabinol (Ä9tetrahydrocannabinol unless otherwise
specified)
Written Answer (in Hansard)
World Health Organization
United Nations
to the 1998 Daily News index for November 5-11