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British Medical Journal 1998 ( 4 April )
Cannabis as medicine: time for the phoenix to rise?
The evidence suggests so.
Since 1971 British doctors have been barred from prescribing cannabis under
the Misuse of Drugs Act. Many otherwise law abiding people have subsequently
thought it worthwhile to expose themselves to the risk, inconvenience, and
expense of obtaining illegally a drug they believe can ease symptoms
inadequately controlled by conventional medicines. Patients have told me
how effective cannabis can be in relieving aches and pains, numbing the
symptoms of opiate withdrawal, improving sleep, reducing anxiety, and
alleviating the vomiting, anorexia, and depression associated with AIDS
related disorders. Anecdotes such as these are all very well, but is there
any scientific evidence that cannabis has real therapeutic value?
The British Medical Association (BMA) has addressed this question with an
excellent report, which begins by reviewing the pharmacology.
(1) Only a few of the 60 or so chemicals unique to Cannabis sativa
(cannabinoids) have so far been studied, the best known of which is the main
psychoactive ingredient, delta -9-tetrahydrocannabinol (THC). Specific
cannabinoid receptors in the brain and in spleen macrophages, and naturally
occurring substances which bind to these (anandamides), have been identified
in recent years. These findings open the door to developing novel agents for
therapeutic use or exploring the physiological role of the anandamide system
which may be concerned with mood, memory and cognition, perception,
movement, coordination, sleep, thermoregulation, appetite, and immune
response (2) The report evaluates the scientific literature on cannabis and
cannabinoids in relation to the strengths and shortcomings of existing
medicines and proposes directions for research. The strongest evidence
relates to the effectiveness of delta-9-tetrahydrocannabinol and the
synthetic cannabinoid nabilone in relieving nausea and vomiting secondary to
cancer chemotherapy. Nabilone is licensed for this use in Britain, but
delta-9-tetrahydrocannabinol (as dronabinol) is not.
A pilot study suggests that the non-psychotropic : delta
-8-tetrahydrocannabinol has promise as an antiemetic in children.(3)
Proposals for research contained in this section are applicable to most of
the others: exploration of optimal regimens and the relative usefulness of
different cannabinoids; controlled comparisons with newer medicines alone
and as adjunctive therapy; specification of patient categories; and a focus
on other conditions producing similar symptoms.
Many anecdotal accounts indicate that cannabis and some cannabinoids can
relieve symptoms related to muscle spasticity, but the few controlled
studies offer only modest support for this. Good evidence exists from basic
research that several cannabinoids have analgesic and anti-inflammatory
properties, but eight small scale human studies listed here give equivocal
results. Again animal studies suggest that cannabidiol has possibilities as
an anticonvulsant, but the human data are lacking.
Delta-9-Tetrahydrocannabinol definitely reduces intraocular pressure and
produces bronchodilatation but its potential in glaucoma and asthma is not
compelling on current evidence.
Relief of symptoms in AIDS related disorders is one of the most interesting
possibilities. The appetite stimulating effect of oral dronabinol in
patients with AIDS (4) was convincing enough to win approval from the
American Food and Drug Administration for this indication. This attribute,
combined with antiemetic and possible analgesic, anxiolytic,(5) hypnotic,(6)
and antidepressant(7) properties, suggests a profile uniquely relevant to
this condition and a compelling reason for research.
Adverse effects relevant to clinical use are discussed. No deaths have been
attributed to cannabis toxicity alone. Common acute effects include
sedation; psychological symptoms (euphoria, anxiety, paranoia, impaired
memory); and physical symptoms such as dry mouth, ataxia, blurred vision,
weakness and incoordination, and tachycardia. Impaired psychomotor
performance may persist as long as 24 hours after a single dose.
Interactions with central nervous system depressants are possible, as is
aggravation or precipitation of psychosis in vulnerable individuals.
Physical and psychological dependence can occur, but withdrawal symptoms
are usually mild. Inconsistent effects on sex hormones and
immunosuppression in animals have been reported. Cannabis smoke is as rich
in toxic gases and particulates as tobacco smoke, so regular heavy smokers
probably face an increased risk of cardiovascular and respiratory diseases.
The report concludes that individual cannabinoids have a therapeutic
potential in several conditions in which other treatments are not fully
adequate and that they are safe drugs with a side effect profile better than
that of many drugs used for the same indications. The BMA recommends that
the government should amend the Misuse of Drugs Act to allow cannabinoids to
be prescribed in a range of medical conditions, calls for the setting up of
controlled clinical trials, and suggests that pharmaceutical companies
should search for novel analogues to open up new
therapeutic possibilities.
The BMA is not alone in arguing for enhanced access to cannabinoids in
clinical practice. Others include the Royal Pharmaceutical Society,(8) the
previous president of the Royal College of Physicians (L Turnberg, personal
communication), and many British doctors.(9) The role of cannabinoids in
modern therapeutics remains uncertain, but the evidence in this report shows
that it would be irrational not to explore it. The active components of a
plant which has been prized as a medicine for thousands of years should not
be discarded lightly, and certainly not through political expediency or as a
casualty of the war on drugs.
Philip Robson, Senior clinical lecturer.
Warneford Hospital, Oxford OX3 7JX
References:
- British Medical Association. Therapeutic uses of cannabis. Amsterdam:
Harwood Academic , 1997.
- Pertwee RG. Pharmacological, physiological and clinical implications of
the discovery of cannabinoid receptors: an overview. In: Pertwee R, ed.
Cannabinoid receptors. London: Harcourt Brace , 1995.
- Abrahamov A, Abrahamov A, Mechoulam R. An efficient new cannabinoid
antiemetic in pediatric oncology. Life Sciences 1995; 56:
2097-2102[Medline].
- Beal JE, Olson R, Lauberstein L, Morales JO, Bellman P, Yangco B, et al.
Dronabinol as a treatment for anorexia associated with weight loss in
patients with AIDS. Journal of Pain and Symptom Management 1995; 10:
89-97[Medline].
- Fabre LF, McLendon D. The efficacy and safety of nabilone (a synthetic
cannabinoid) in the treatment of anxiety. J Clin Pharmacol 1981; 21:
377-382S.
- Carlini EA, Cunha JM. Hypnotic and anti-epileptic effects of
cannabidiol. J Clin Pharmacol 1981; 21: 417-427.
- Regelson W, Butler JR, Schulz J, Kirk T, Peel L, Gleem ML, et al.
Delta-9-THC as an effective antidepressant and appetite-stimulating agent
in advanced cancer patients. In: Braude MC, Szara S, eds. The pharmacology
of marihuana. New York: Raven Press , 1976.
- Gray C. Cannabis: the therapeutic potential. Pharmaceutical J 1995;
254: 771-773.
- Meek C. Doctors want cannabis prescriptions allowed. BMA News Review
1994;Feb:15.
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