Subj: Cannabis as medicine: time for the phoenix to rise?

Date: Apr 4, 1998

Source: British Medical Journal

BMJ No 7137 Volume 316

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.