| The transformation of Cannabis sativa from illicit drug to medicinal
product continues, albeit slowly. In recent years the evidence base to
support its use has grown and the prospect of a licensed cannabis-based
product is now real.
However, the first large-scale randomised trial to assess cannabis use
in multiple sclerosis (MS) has produced mixed results, failing to show
objectively that cannabinoids can improve spasticity (Lancet 2003;362:1517).
Has too much been expected of cannabis? Or will this drug prove to be
as useful as some patients claim?
The CAMS trial (see Panel) was led by Dr John Zajicek, consultant neurologist
at Plymouth Hospitals NHS Trust. He emphasises the importance of the
trial, pointing out that many patients with MS use cannabis, despite
there being hardly any scientific evidence for its effects. “It
is already used illegally so there was quite a political will and patient
drive to find out if these drugs actually work.”
The CAMS study: main findings
The CAMS trial (cannabinoids for treatment
of spasticity and other symptoms related to multiple sclerosis)
involved 630 patients with
stable MS and muscle spasticity. In addition to standard MS medication,
the patients were randomly assigned to receive whole cannabis extract,
a synthetic version of tetrahydrocannabinol (THC) or placebo. All
trial medicines were given orally. The trial lasted 15 weeks, the
first five of which were spent establishing the best tolerated
dose for each patient. Trained assessors used a tool known as the
Ashworth score to rate spasticity before treatment started and
at intervals during the trial. Secondary outcomes such as mobility,
general wellbeing and patients’ subjective assessment of
the impact of treatment were also measured. The main findings were:
• Neither cannabis treatment had a significant effect on muscle
spasticity as measured by the Ashworth score
• There was evidence of a treatment effect on patient-reported
spasticity and pain. Improvement in spasticity was reported by
61 per cent, 60 per cent and 46 per cent of subjects taking cannabis
extract, THC and placebo, respectively
• More patients taking active treatment than placebo reported improvement
in spasms and sleep quality
• There was no evidence that cannabis had any impact on neurological
disability, coping with daily living, or wellbeing and mood
• Mobility, as measured by walking time, was improved with active
treatment
• Trial medicines were generally well tolerated |
Dr Zajicek believes the study has revealed the complexity of cannabis’s
value in MS. “Although we based the study around spasticity, we
also wanted to capture any treatment effects among the other important
symptoms described by people with MS. When patients were asked to describe
how they felt their symptoms, including spasticity, had been affected,
the picture was very different. They felt some of the impact of their
painful and distressing symptoms had been eased.”
The fact that patients did not report improvements in some symptoms,
such as tremor and depression, indicate that cannabis’s effects
were not due to the drug’s ability to make patients feel better
psychologically, Dr Zajicek explains.
Writing in an accompanying commentary in The Lancet (ibid, p1513), Dr
Luanne Metz and Dr Stacey Page from the University of Calgary, Canada,
conclude: “We now have as much evidence to support the use of these
oral cannabinoids for spasticity in ambulatory people with multiple sclerosis
as we do for many standard therapies for spasticity, including baclofen.
However, because we do not know how these cannabinoids compare to other
anti-spasticity treatments, they should generally only be considered
when other therapy has failed.”
They add that data to compare the risks and benefits of smoked cannabis
is still lacking. “Hopefully, this study will stimulate further
research to develop and evaluate safe, effective formulations of cannabis,
and will inform debate over the social and legal restrictions that limit
its use.”
Data from the CAMS study will now be handed over to the manufacturers
who supplied the trial medicines — Cannador (Institute for Clinical
Research, IKF, Berlin) and Marinol (Solvay Pharmaceuticals) — for
use in their discussions with appropriate regulatory authorities.
GW Pharmaceuticals is another company with an interest in cannabis-based
medicines, although it was not involved in the CAMS study. Over recent
years, it has completed a number of separate phase II and phase III trials
on Sativex, an oro-mucosal spray containing standardised cannabis extract,
in patients with MS. The company says the studies have provided positive
results and is waiting to hear the outcome of its licence application
for Sativex, which it submitted to the Medicines and Healthcare products
Regulatory Agency in March.
Professor Tony Moffat, chief scientist, Royal Pharmaceutical Society,
was on the steering committee of the CAMS study. He had hoped that the
trial would show greater benefits for patients. However, he is still
confident that cannabis will prove to be a useful medicinal product.
Professor Moffat agrees that, as an oro-mucosal spray, Sativex is a neat
device. He suspects that it could offer greater dosing flexibility to
patients than the oral medicines used in the CAMS study. However, he
points out that only part of the dose would be absorbed sublingually,
the rest being delivered orally.
He says that he would like to see more research done on transdermal and
pulmonary delivery of cannabinoids. “Patches would be useful for
people in chronic pain and pulmonary sprays may provide more immediate
relief for people who experience spasms.”
In the United Kingdom, possession and supply of cannabis remains an offence.
Indeed, it will only be possible to license a cannabis-based product
if cannabis is reclassified as a Schedule 2 drug. The Department of Health
is not likely to amend the misuse of drugs controls in a hurry. “It
would be premature to take such a step before the quality, safety and
efficacy of cannabis have been fully established,” a spokeswoman
said.
So when will this be? As well as the MHRA, the National Institute for
Clinical Excellence is looking at cannabinoid products in MS and is expected
to issue guidance in June 2004.
So the wait goes on to resolve whether or not reclassification of cannabis
will occur and whether MS patients using it will find themselves on the
right side of the law. |
