Editorial

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 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,
|gd-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 |gd-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
|gd-9-tetrahydrocannabinol (as dronabinol) is not. A pilot study suggests
that the non-psychotropic |gd-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.
|gd-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

1 British Medical Association. Therapeutic uses of cannabis. Amsterdam:
Harwood Academic, 1997.

2 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.

3 Abrahamov A, Abrahamov A, Mechoulam R. An efficient new cannabinoid
antiemetic in pediatric oncology. Life Sciences 1995;56:2097-102.

4 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.

5 Fabre LF, McLendon D. The efficacy and safety of nabilone (a synthetic
cannabinoid) in the treatment of anxiety. J Clin Pharmacol 1981;21:377-82S.

6 Carlini EA, Cunha JM. Hypnotic and anti-epileptic effects of cannabidiol.
J Clin Pharmacol 1981;21:417-27.

7 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.

8 Gray C. Cannabis: the therapeutic potential. Pharmaceutical J 1995;254:771-3.

9 Meek C. Doctors want cannabis prescriptions allowed. BMA News Review
1994;Feb:15.