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Title:
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House of Lords (UK) Report on Cannabis for Medical Purposes | ||
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Author:
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Sub-committee |
Date:
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Nov. 4, 1998 |
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Summary:
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November 1998 report of Science and Technology Committee Comprehensive, with eye-opening recommendations | ||
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Download:
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N/A [get adobe acrobat (PDF) reader] | ||
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Html:
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TOC | Ch. 1 | Ch. 2 | Ch. 3 | Ch. 4 | Ch. 5 | Ch. 6 | Ch. 7 | Ch. 8 | App | ||
CHAPTER 5 - Part a
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).
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| 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).
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).
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| 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.
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| 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).
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| 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.
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
TOC | Ch. 1 | Ch. 2 | Ch. 3 | Ch. 4 | Ch. 5 | Ch. 6 | Ch. 7 | Ch. 8 | App