are in Research / Therapeutic aspects
British Journal of Psychiatry
2001 The Royal College of Psychiatrists
178 February 2001
aspects of cannabis and cannabinoids[Substance
PHILIP ROBSON, FRCPsych, Consultant Psychiatrist and Senior Clinical
Lecturer, Warneford Hospital, Oxford OX3 7JX
editorial, p. 98, this issue.
(First received 22 July 1999,
final revision 14 March 2000, accepted 15 March 2000)
Background: Review commissioned in 1996 by the Department of Health (DOH).
therapeutic profile of cannabis and cannabinoids.
Method: Medline search, references supplied by DOH and others, and personal communications.
Conclusions: Cannabis and some cannabinoids are effective antiemetics and analgesics
and reduce intraocular pressure. There is evidence of symptom relief and improved
well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids
may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification.
Other properties identified by basic research await evaluation. Standard treatments
for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but
often produces unwanted effects, typically sedation, intoxication, clumsiness,
dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery
of specific receptors and natural ligands may lead to drug developments. Research
is needed to optimise dose and route of administration, quantify therapeutic and
adverse effects, and examine interactions.
Declaration of interest: Funding from DOH. Between writing this paper and its
acceptance for publication, P.R. was appointed Medical Director of GW Pharmaceuticals.
In 1996 I was commissioned by the Department of Health (DOH) to review the scientific
literature regarding the potential therapeutic utility of cannabis and its derivatives.
The review was based upon primary sources (identified from a Medline literature
search, reference lists supplied by the DOH and the Institute for the Study of
Drug Dependence, and personal communications with relevant academics and clinicians).
This paper is a greatly shortened version of the review. The 4 years which have
elapsed have seen little in the way of new clinical results but considerable advances
in cannabinoid basic science (Institute of Medicine, 1999).
Government licences have recently been granted for several controlled trials of
both synthetic and plant-derived cannabinoids in multiple sclerosis and chronic
pain. In January 2000, I was appointed Medical Director of GW Pharmaceuticals,
a company established to derive medicinal extracts from standardised cannabis
HISTORY OF THERAPEUTIC USE
The first formal report of cannabis as a medicine appeared in China nearly 5000
years ago when it was recommended for malaria, constipation, rheumatic pains and
childbirth and, mixed with wine, as a surgical analgesic (Mechoulam,
1986). There are subsequent records of its use throughout Asia, the Middle
East, Southern Africa and South America. Accounts by Pliny, Dioscorides and Galen
remained influential in European medicine for 16 centuries.
It was not until the 19th century that cannabis became a mainstream medicine in
Britain. W. B. O'Shaughnessy, an Irish scientist and physician, observed its use
in India as an analgesic, anticonvulsant, antispasmodic, anti-emetic and hypnotic.
After toxicity experiments on goats and dogs, he gave it to patients and was impressed
with its muscle-relaxant, anticonvulsant and analgesic properties, and recorded
its usefulness as an anti-emetic.
After these observations were published in 1842, medicinal use of cannabis expanded
rapidly. It soon became available 'over the counter' in pharmacies and by 1854
it had found its way into the United States Dispensatory. The American market
became flooded with dozens of cannabis-containing home remedies.
Queen Victoria's personal physician wrote (Reynolds, 1890),
on the basis of more than 30 years' experience, that "Indian hemp, when pure and
administered carefully, is one of the most valuable medicines we possess". He
found it incomparable for "senile insomnia", "night restlessness" and "temper
disease" in both children and adults, but not helpful in melancholia, "very uncertain"
in alcoholic delirium, and "worse than useless" in mania. It was very effective
in neuralgia, period pains, migraine, "lightning pain of the ataxic patient" and
gout, but useless in sciatica and "hysteric pains". He found it impressive in
clonic spasms and certain epileptiform convulsions related to brain damage, but
no good at all in petit mal or "chronic epilepsy", tetanus, chorea or paralysis
agitans. It effectively relieved nocturnal cramps, asthma and dysmenorrhoea.
was writing at a time when the zenith of cannabis as prescribed medicine and home
remedy was already past. Although Sir William Osler was still recommending it
for migraine sufferers in 1913, it was by then in steep decline because of variable
potency of herbal preparations, poor storage stability, unpredictable response
to oral administration, increasing enthusiasm for parenteral medicines and availability
of potent synthetic alternatives, commercial pressures and American concern about
recreational use. Cannabis was outlawed in 1928 by ratification of the 1925 Geneva
Convention on the manufacture, sale and movement of dangerous drugs. Prescription
remained possible until final prohibition under the 1971 Misuse of Drugs Act,
against the advice of the Advisory Committee on Drug Dependence.
In the USA, medical use was effectively ruled out by the Marijuana Tax Act 1937.
This ruling has been under almost constant legal challenge and many special dispensations
were made between 1976 and 1992 for individuals to receive 'compassionate reefers'.
Although this loophole has been closed, a 1996 California state law permits cultivation
or consumption of cannabis for medical purposes, if a doctor provides a written
endorsement. Similar arrangements apply in Italy and Canberra, Australia.
PHARMACOLOGY RELEVANT TO THERAPEUTICS
Cannabinol was isolated in 1895 and cannabidiol in 1934, but the most significant
discovery was that of [DELTA]9-tetrahydrocannabinol (THC) in 1964.
Chromatographic and spectroscopic methods subsequently uncovered many closely
Capsules of synthetic THC (dronabinol) have been available for restricted medical
use in the USA since 1985. Nabilone, a synthetic THC analogue, was marketed in
1983 and is the only cannabinoid licensed for prescription in the UK, restricted
to treatment of nausea and vomiting caused by cytotoxic chemotherapy unresponsive
to conventional anti-emetics. Use in other indications is only possible on a 'named
patient' basis if the drug is supplied by a hospital pharmacy.
In 1988, a specific protein receptor (known as CB1) for THC was discovered
in mouse nerve cells. This mediates most of the central nervous system (CNS) responses
to cannabinoids, and is abundant in basal ganglia, hippocampus and cerebellum,
globus pallidus, substantia nigra and cerebral cortex. An endogenous ligand was
identified in 1992 and labelled anandamide (ananda: 'bliss' in Sanskrit).
Anandamide has analgesic and tranquillising effects in animals, is involved in
muscle coordination and affects the secretion and function of certain hormones.
Other endogenous agonists almost certainly exist.
In 1993, a second receptor (CB2) was identified in rat spleen macrophages,
and this occurs only outside the CNS. There is scope for chemical manipulation
of cannabinoids to maximise selectivity for CB2 and so avoid psychoactive
effects. It is thought this receptor has relevance for anti-inflammatory and immunosuppressive
Pertwee (1995) has suggested that the anandamide system might
be concerned with mood, memory and cognition, perception, movement, coordination,
posture and skeletal muscle tone, sleep, thermoregulation, appetite and immune
Nausea and vomiting
Many cytotoxic drugs are powerful emetics, and this is the major limiting factor
in patients' acceptance of cancer chemotherapy (see Table 1
Table 1 Human randomised controlled trials (RCTs): anti-emetic effects
smokers receiving cancer chemotherapy have told their doctors that cannabis relieved
their nausea (Grinspoon & Bakalar, 1993). Sallan
et al's (1975) randomised control trial (RCT) compared oral THC and placebo
in 22 cancer patients who had proved resistant to conventional anti-emetics. Comparisons
using patients' self-reports of nausea and vomiting demonstrated that THC was
statistically superior to placebo. THC (10 mg/m2) produced euphoria
in the majority of patients, and one-third experienced sedation.
Subsequent RCTs (listed in Table 1) confirmed that natural
and synthetic THC is invariably superior to placebo. Comparisons with anti-emetics
available in the 1970s and 1980s suggest that THC is either equivalent in effect
or better. A combination of prochlorperazine and THC was superior to either drug
alone, and nabilone combined with prochlorperazine was better than dexamethazone
plus metoclopramide. Although THC and nabilone produced more unwanted effects
than comparison drugs, patients generally preferred them.
Children seem to respond well to nabilone and are tolerant of side-effects, but
larger studies are required. [DELTA]8-THC performed well in a pilot
study (Abrahamov et al, 1995) involving eight children aged
3-13 years with various blood cancers receiving chemotherapy, 60% of whom had
experienced distressing vomiting despite treatment with metoclopramide. [DELTA]8-THC
was given orally 2 hours before cytotoxics and repeated 6-hourly. No vomiting
was recorded during this treatment and over the following 2 days. Two children
were "slightly irritable" and one also showed "slight euphoria".
In a review of 12 studies involving 600 patients (Penta et al,
1981), THC was "effective" in 8/9 and nabilone in 3/3. The most common side-effects
were somnolence (33%), dry mouth (9%), ataxia (8%), dizziness (6%), dysphoria
(6%), and orthostatic hypotension (4%). A further review (Levitt,
1986) incorporating 55 studies, of which 32 were RCTs, showed that low-dose
preventive treatment gives better results than targeting established vomiting.
Younger patients may respond better than older ones.
Meta-analysis (Plasse et al, 1991) suggested that an optimal
balance of efficacy and unwanted effects was achieved with relatively modest doses
(7 mg/m2 or less). Sedation and psychotropic symptoms are commonly
reported, but are usually mild to moderate in intensity and resolve rapidly on
discontinuation. No "persistent or fatal" adverse effects have been reported.
Many American oncologists encourage nauseous patients to try cannabis and would
prescribe it if it were legal (Doblin & Kleiman, 1991).
Mode of action remains uncertain.
Multiple sclerosis and other neurological conditions
Drug therapy of muscle spasticity is generally only moderately effective and is
limited by adverse effects (see Appendix). Spasticity is a central
feature of multiple sclerosis (MS), cerebral palsy and spinal cord injury. Tremor,
ataxia and incontinence also contribute to the high incidence of anxiety and depression
in these conditions. Cannabis was often used to treat pain, muscle spasm, cramps
and ataxia in the 19th century, and many modern sufferers have reported benefits
(Grinspoon & Bakalar, 1993).
Most respondents to a questionnaire sent to British and American MS patients reported
problems with symptom control (Consroe et al, 1997). Those
who smoked cannabis claimed improvements in night-time spasticity and muscle pain
(91-98%); night leg pain, depression, tremor, anxiety, spasms on walking, paraesthesiae
(80-89%); leg weakness, trunk numbness, facial pain (71-74%); impaired balance
(57%); constipation (33%); memory loss (31%).
In a small single-blind comparison with placebo (Clifford, 1983),
THC improved tremor and ataxia in most patients. All experienced a 'high' at the
top dose (15 mg), and two reported dysphoria. Dose-related improvements in dystonia
were noted in five patients given cannabidiol 100-600 mg daily for 6 weeks. Hypotension,
dry mouth, sedation and light-headedness occurred but were described as mild.
Parkinsonian symptoms were aggravated in two subjects.
An RCT by Petro & Ellenberger (1981) compared the effects
of placebo and THC in doses of 5 or 10 mg on muscle tone, reflexes and muscle
power in nine MS patients. Both doses of THC reduced spasticity (P <
0.005). One patient receiving THC 10 mg and one patient receiving placebo felt
'high' but no other side-effects were recorded. In a small RCT (Ungerleider
et al, 1987) with 5-day treatment periods, THC 7.5 mg significantly improved
spasticity in comparison with placebo. Nabilone 1 mg on alternate days was compared
with placebo in a double-blind randomised crossover trial with 4-week treatment
periods in a single MS patient. Nocturia, muscle spasm and general well-being
showed striking improvement during each active treatment period. Mild sedation
was noted on active medication.
Cannabidiol had no beneficial effects in 15 patients with Huntington's disease
(Consroe et al, 1991). Posture and balance were impaired by
a single dose of smoked THC in 10 MS patients and 10 non-MS volunteers (Greenberg
et al, 1994), but there was no active control to determine the effects of
standard anti-spastic medication in this model.
Possible sites of action of cannabinoids in dystonia include basal ganglia, cerebellum,
spinal motor neurons, somatic nerves and neuromuscular junction.
Loss of appetite and weight in cancer and AIDS
Several studies have investigated effect on appetite and weight (Table
2). The appetite-stimulating effect of cannabis was confirmed in fasting and
non-fasting volunteers in an RCT of oral THC with alcohol, amphetamine and placebo
(Hollister, 1971). A standardised THC smoking regime over 25
days in a residential laboratory was associated with significant increases in
calorie intake and frequency of eating occasions in comparison with placebo.
Table 2 Human randomised controlled trials (RCTs): appetite and weight
in cancer patients also showed appetite improvements and slowing of weight loss.
Regelson et al's (1976) RCT explored the effect on appetite
(and mood) of oral THC in 54 cancer patients over a 2-week period. There were
nine with-drawals due to side-effects (six in THC period - dizziness, disassociation,
confused thinking, panic, "feelings of disturbance"; three in the placebo period
- anxiety, fits, dizziness, lethargy, weakness). Patients receiving THC in the
first period gained weight (P<0.05), and those receiving placebo first
showed reduced weight loss on transfer to THC (P<0.05). Depression,
tranquillity and "forthrightness" scores all improved on THC. In a quarter of
the patients, somnolence, dizziness and disassociation were severe enough to negate
Many people with AIDS have claimed that smoking marijuana inhibits nausea, improves
appetite, reduces anxiety, relieves aches and pains, improves sleep and inhibits
oral candidiasis. A small pilot study supported the hypothesis that dronabinol
might reduce weight loss or even promote weight gain (Plasse et
Beal et al (1995) conducted an RCT over 42 days of treatment
with dronabinol 5 mg daily in 139 AIDS patients who had lost at least 2.3 kg.
Six receiving dronabinol and three receiving placebo withdrew because of "perceived
drug toxicity". Dronabinol boosted appetite in comparison to placebo (P<0.015)
and nausea was reduced (P=0.05). Improvement in mood was a strong trend
(P=0.06) and there was a tendency toward weight gain (P=0.1). Dronabinol
produced more adverse effects than placebo (P<0.001), but 75% of these
were mild or moderate. Most frequent were euphoria (9), dizziness (5), thinking
abnormalities (5) and sedation (4).
Further investigation is amply justified. Careful monitoring of possible effects
upon the immune system is needed, although a prospective multi-centre study (Kaslow
et al, 1989), which followed nearly 5000 HIV-positive men for 18 months, showed
no link between use of psychoactive substances and mean T-cell counts or progression
Cannabinoids are effective analgesics in animal models with non-opiate mechanisms
predominating. There are many anecdotal reports (Grinspoon &
Bakalar, 1993) of benefits in bone and joint pain, migraine, cancer pain,
menstrual cramps and labour.
Five small RCTs (Table 3) show that THC is significantly superior
to placebo and produces dose-related analgesia peaking at around 5 hours, comparable
to but out-lasting that of codeine. Side-effects were also dose-related, and consisted
of slurred speech, sedation and mental clouding, blurred vision, dizziness and
ataxia. Levonantradol was also superior to placebo and notably long-acting, but
almost half the patients reported sedation. Cannabinoids may have considerable
potential in neuropathic pain (Institute of Medicine, 1999).
Table 3 Human randomised controlled trials (RCTs): pain
Raised intra-ocular pressure
Glaucoma due to obstructed outflow of aqueous humour or anatomical eye defects
is the most common cause of blindness in the Western world. Some RCTs investigating
this area are given in Table 4.
Table 4 Human randomised controlled trials (RCTs): raised intra-ocular pressure
There have been many anecdotal reports that street marijuana can relieve glaucoma
symptoms and individuals have successfully argued in the USA for legal access
to the drug (Grinspoon & Bakalar, 1993). A pilot study
of smoked marijuana and oral THC (15 mg) in 11 glaucoma patients found an average
intra-ocular pressure (IOP) reduction of 30% in seven subjects and no response
in four (Hepler et al, 1976).
Randomised controlled trials in volunteers confirmed that oral, injected or smoked
cannabinoids produce dose-related reductions of IOP (Hepler et
al, 1976; Perez-Reyes et al, 1976). Conjunctival engorgement and tear reduction
were often noted. THC, [DELTA]8-THC and 11-hydroxy-THC are more effective
than cannabinol, while cannabidiol was without effect. Tolerance may develop on
An RCT in patients showed IOP reductions of similar magnitude following smoked
THC along with "alterations in mental status" and tachycardia (Merritt
et al, 1980). THC eyedrops produced dose-related IOP reduction with minimal
side-effects though parallel reductions in the untreated eye (also seen in animal
models) suggested a systemic rather than local mode of action.
Insomnia, anxiety and depression
Randomised controlled trials investigating insomnia, anxiety and depression are
given in Table 5.
Table 5 Human randomised controled trials (RCTs): insomnia, anxiety, depression
Nabilone (1 mg three times daily) produced "dramatic improvements" on the Hamilton
Anxiety Scale in 20 anxious patients in comparison to placebo (P<0.001),
which were mirrored by other measures (Fabre & McLendon, 1981).
Seven days into the study, nabilone patients' anxiety scores were halved, and
this persisted unchanged throughout treatment. Side-effects included dry mouth,
dry eyes and drowsiness. The authors concluded that nabilone is a "very effective
anxiolytic deserving of further study". In a cross-over comparison of nabilone
(1-2.5 mg twice daily) and placebo in 11 anxious patients (Ilaria
et al, 1981), significant improvements in anxiety scores (P<0.05)
were again noted. The only clinically significant adverse effect was postural
hypotension with related dizziness, light-headedness or weakness. This was dose-related,
experienced by most patients, and tended to tolerate out over time.
data suggest that cannabidiol (160 mg) may be an effective hypnotic, and that
THC (0.1 mg/kg) may have antidepressant properties in cancer patients and others
(Grinspoon & Bakalar, 1993).
Epilepsy afflicts 1% of the world's population. Conventional anticonvulsants provide
unsatisfactory control for up to 30% of patients, and all can produce disabling
or even life-threatening adverse effects.
The effect of cannabinoids on seizure activity in laboratory animals is complicated.
Cannabidiol is a powerful anti-convulsant free of tolerance, but its profile varies
between species. THC can produce seizures in big doses or when genetically seizure-sensitive
animals are used, yet it is also robustly anticonvulsant in certain seizure models.
A lack of stereospecificity suggests that the mechanism may not be related to
a single receptor interaction. Serotonin, [gamma]-aminobutyric acid, acetylcholine
or prostaglandin systems may be involved.
There are many anecdotal reports of beneficial effects in humans with epilepsy
(Grinspoon & Bakalar, 1993) but research data are virtually
non-existent. Two single-case reports (Keeler & Reifler, 1967;
Consroe et al, 1975) give confounding information. A young man suffered seizures
on his regular medication and began smoking several cannabis cigarettes nightly
alongside this. No further seizures occurred while this combination was maintained.
In contrast, a man with grand mal epilepsy stopped taking anticonvulsants and
suffered no fits for 6 months. He then smoked cannabis on seven occasions over
a 3-week period and suffered three fits during this time, although not coincident
with actual intoxication.
Only one RCT (Cunha et al, 1980) exists. Fifteen poorly controlled
patients with secondary generalised epilepsy continued with their regular therapy
but were also given either cannabidiol or placebo daily for up to 4.5 months while
undergoing regular clinical and electroencephalogram evaluation. Half the patients
on cannabidiol remained "almost free" of fits throughout the experiment, and all
but one of the others showed "partial improvement". All but one of the placebo
patients remained entirely unchanged. Somnolence occurred in four patients receiving
Small-scale controlled studies in volunteers with asthma show that oral, smoked
and aerosolised THC has comparable bronchodilatory activity to salbutamol, although
onset is quicker with the latter. Dose-related tachycardia occurred in some individuals,
and subjective intoxication with higher doses. A THC aerosol was free of systemic
unwanted effects, but was irritant to the lungs (Tashkin et al,
1977). Nabilone does not produce bronchodilation. Since THC-induced bronchodilation
is not mediated through the sympathetic nervous system, synergistic combinations
with [beta]2-adrenoceptor stimulants might be possible.
Basic research indicates that THC and analogues inhibit opioid withdrawal (Chesher
& Jackson, 1985). Anecdotal reports from patients also point to beneficial
effects beyond those which could be accounted for by sedative or hypnotic activity.
Cannabinoids inhibit primary tumour growth and increase survival in animal tumour
models (Harris et al, 1976) by an unknown mechanism. They also
show antipyretic and anti-inflammatory activity (Formukong et al,
1989). Mechoulam (1986) has drawn attention to the lack
of modern research directed at possible antihelmintic, antimigraine and oxytocic
Therapeutic profile on existing evidence
Tetrahydrocannabinol and nabilone are effective anti-emetics but there are no
comparisons with 5-HT3 antagonists, so a role in modern anti-emetic
regimes remains to be determined. Currently, only nabilone is licensed in the
UK and available for prescription and research. THC (as dronabinol) has recently
been rescheduled to permit prescription but remains unlicensed and must be specially
imported on a named-patient basis. Delta-8-THC looks worthy of further investigation,
particularly in children, and is much simpler to synthesise than THC.
with MS have claimed a benefit from cannabis and small controlled trials support
this, although effect upon posture and balance requires clarification. THC is
an effective analgesic at the expense of sedation with larger doses and may have
special merit in neuropathic pain. No conclusions are possible as yet about anticonvulsant
potential. Some cannabinoids reduce IOP, though side-effects of products currently
available limit application and effects of tolerance are uncertain. The mechanism
for bronchodilation probably differs from that of [beta]2-stimulants,
so synergistic combinations may be possible.
Cannabis and THC are effective appetitc stimulants. Alongside anti-emetic, analgesic,
anxiolytic, hypnotic and antipyretic properties this suggests a unique role in
alleviating symptoms in selected patients with cancer or AIDS. This is a compelling
area for future research, although possible effects upon immune function require
Optimal doses and routes of delivery have not been established. Absorption by
the oral route is unreliable. Smoking the drug is generally not a viable option
since advantages such as rapid onset, accurate titration of effects and reliability
in patients who are vomiting have to be set against the likelihood of lung irritation
or damage, and it would in any case be unacceptable to most patients. However,
pending availability of more satisfactory preparations, I believe that the existing
profile of efficacy and toxicity justifies the provision of a legal supply of
standardised herbal material ('compassionate reefers') to patients with terminal
conditions who currently obtain relief with street cannabis. Sublingual sprays
or tablets, nebulisers and aerosols look promising for the future, and THC is
effective by the rectal route. Many potentially active cannabinoids have yet to
be investigated and the recent identification of a peripheral receptor may lead
to new drugs devoid of central nervous system effects.
Cannabis arouses passion in those who support or condemn it, and few people approach
the clinical literature with dispassionate objectivity. Poorly controlled research
produces ambiguous results which are then interpreted according to the prejudices
of the reader. Anecdotes seem to be more readily accepted when they point to adverse
rather than positive effects (Hall et al, 1994). Yet the known
adverse effects of oral cannabinoids are rarely intolerable or life-threatening,
in contrast to those associated with some standard therapies. A British Medical
Association survey indicated that many UK doctors believe that cannabis should
once again be available on prescription (Meek, 1994).
The way forward
Select Committee of the House of Lords recently examined the scientific information
concerning medical cannabis and took verbal and written evidence from a wide range
of witnesses. Their conclusion (House of Lords, 1998) published in November 1998,
was that, although cannabis should remain a controlled drug, the law should be
changed to allow doctors to prescribe "an appropriate preparation of cannabis
if they saw fit". The government rejected this recommendation on the day of publication.
auspices of the Royal Pharmaceutical Society, large-scale multi-centre trials
are under way to explore further the efficacy of cannabinoids in relieving spasticity
and postoperative pain. A pharmaceutical company has obtained a licence to cultivate
medicinal cannabis on a large scale in the UK. By selecting a specific genotype
then carefully controlling all other relevant variables such as soil conditions,
temperature and humidity, it is possible to obtain levels of purity in plant extracts
equal or superior to those of 'pure' synthetic cannabinoids. Most of the 60 or
so naturally occurring cannabinoids are present in tiny amounts, and synthetic
cannabinoids such as nabilone themselves contain up to 5% impurities, some of
which are of unknown identity. Whether obtained by synthetic means or by plant
extraction, it is essential that cannabinoids for prescription and research in
the future should demonstrate excellent purity, stability and bioavailability.
properties of cannabis are still mainly delineated by the anecdotal reports of
those who believe their symptoms are relieved by its use, and these accounts are
often dismissed as wishful thinking or even mischievous. Since the conventional
treatments for many of these disorders are both toxic and relatively ineffectual,
a more constructive response would be to expose such claims to careful scientific
examination and, in the meantime, search for a way to avoid criminalising those
who seek only to assuage their own suffering.
* Cannabis and its derivatives show
promise of beneficial effects in a number of medical conditions for which standard
treatment is less than satisfactory, and further controlled research is fully
* Cannabis is very safe in overdose, but often
produces unwanted effects which are better tolerated by patients with some conditions
(e.g. multiple sclerosis, chronic pain, AIDS, cancer) than others (e.g. glaucoma).
* Optimal for mutations, doses and routes of delivery have not
yet been established.
* Because of imposed time constraints, the review is not fully
comprehensive, although all accessed sources were incorporated.
* Much of the evidence is anecdotal, and many of the research studies cited have
serious methodological shortcomings.
* Few researchers (or
reviewers) approach the subject of cannabinoid therapeutics in a spirit of dispassionate
This review was originally commissioned and funded by the Department of Health.
The author thanks Dr Anthony Thorley for his support and encouragement. The views
expressed in the paper are those of the author and not necessarily of the Department
Phenothiazzines and butyrophenones can cause sedation, movement
disorders which may be irreversible, neuroleptic malignant syndrome, dry mouth,
blurred vision, urinary retention, hypotension, allergic reactions, jaundice,
hypothermia, hormonal disturbances, irreversible eye damage and, rarely, life-threatening
anaemias. Domperidone has a more benign profile but is not recommended
for long-term use. Metoclopramide produces movement disorders (1% of patients),
dizziness and drowsiness. Selective 5-HT3 antagonists (ondansetron,
granisetron) are newer and more expensive. Side-effects include constipation,
headache, flushing, liver enzyme changes, allergic reactions, visual disturbances,
chest pain and dysrhythmias.
Existing neurological treatments
Baclofen alleviates spasticity, but may accentuate muscle weakness. It
produces dose-related nausea and vomiting, drowsiness, vertigo, confusion, fatigue
and hypotonia. Less commonly, fits, psychiatric disorder and hypotension occur.
Sudden withdrawal can cause hallucinations. Diazepam is useful but can
worsen weakness or incoordination and cause drowsiness; ataxia, depression, disinhibition
and dependence. Dantrolene may cause weakness, hypotonia, drowsiness, dizziness,
vertigo and anxiety. Rarely, it damages the liver, and is not recommended in those
with co-existing heart or lung disease.
Existing glaucoma treatments
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