Statement on Sativex
Sativex is the trade name of a cannabis-based extract made by GW Pharmaceuticals,
a British company, with shares traded on the London Stock Exchange. Sativex
is a combination of the two major cannabinoids (chemical compounds) found
within cannabis, namely delta-9-THC and cannabidiol (CBD). Sativex is manufactured
by mixing these compounds and dissolving them in alcohol, the resulting preparation
being administered via an aerosol spray under the tongue.
Cannabis-based medicines are still subject to schedule 1 of the Misuse
of Drugs Act 1971, although they are in Class C, meaning that they probably
cause least harm amongst drugs with potential medicinal use. This means
that use of these drugs is illegal unless the Home Office gives approval
for medical use, so anyone using medicinal cannabis-based products, even
in the context of clinical trials, needs to have Home Office approval
and registration.
Sativex has been tested in a variety of conditions for the relief of pain and spasticity, most notably in people with multiple sclerosis (MS). In order for a drug to receive a licence for a particular indication in the UK, the manufacturers need to provide evidence to the licensing authorities (in the UK this is the Committee on Safety of Medicines (CSM) and the Medicines and Healthcare products Regulatory Agency – MHRA), to show that the drug does what the manufacturers claim it does, and that it is safe. Sativex has been refused a licence on the basis of the information submitted by GW Pharmaceuticals. This means that doctors cannot routinely prescribe Sativex in the UK, and the company are not permitted to advertise it. GW Pharmaceuticals are now conducting further trials to try and provide further evidence for the MHRA.
Sativex does have a licence for treating MS-related neuropathic pain in Canada, which was granted in April 2005. Clearly, Canadian interpretation of the evidence was different from that in the UK and it has therefore been possible for Canadian doctors to prescribe Sativex for MS-related pain.
Recently GW Pharmaceuticals announced that it had been informed by the Home Office that Sativex could be imported from Canada and be prescribed on a “named patient basis” in UK. This means in theory that doctors can write prescriptions for Sativex for people who they believe may benefit from the drug. This type of prescribing is only used when a drug does not have a licence for a particular indication. Individual doctors then assume responsibility for any side effects or problems that may arise from use of the drug. Because Sativex is a schedule 1 drug according to the Misuse of Drugs Act, the Home Office will need to develop a system of registration for anyone being prescribed Sativex in this way. This system has not yet been produced. In addition, individual doctors and health providers need to establish who is going to pay for drugs prescribed in this way. When there is already significant debate over the funding of licensed and well-proven therapies in the UK, it is unlikely that health providers will be swayed by the evidence of efficacy currently available, especially if the Committee on Safety of Medicines were not persuaded by this evidence.
Much of this debate has been prompted by the strong message emerging from patient groups, providing anecdotal evidence that cannabis-derived drugs may be helpful for a number of chronic symptoms, especially in MS. This has led to the illegal use of cannabis in MS, often exposing people with MS to unacceptable levels of risk associated with trying to obtain illegal supplies of the drug. In order to test whether cannabis has any therapeutic benefit in MS, the Medical Research Council (MRC) funded the Cannabinoids in MS study (CAMS), across 33 UK centres, with 630 people with MS being treated either with THC, cannabis extract or placebo capsules. This study had nothing to do with GW Pharmaceuticals, and all medicines were given orally as capsules. The results of this study showed that investigators could not prove an effect on muscle stiffness in the short-term using the best measurement methods available at that time. However, as recently published, there was strong evidence for an effect from the patient perspective, and support for more long-term effects beyond the main 15-week study period.
The real problem in this area has been in convincing independent observers that these drugs have an effect, when we are dealing with symptoms experienced by study participants who may guess what treatment they are taking because of side effects of the drug. In scientific terms, this is termed bias from unmasking. We have been working hard to get round some of these problems, but there is still an urgent need for further clinical trials to establish as conclusively as possible whether these drugs are effective, and for whom. The MRC has now funded the CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study for people with progressive MS who are still walking, to see if THC can alter the course of MS over the long-term. In addition, other studies are also about to start, including the MUSEC (MUltiple Sclerosis and Extract of Cannabis) study of oral cannabis extract (Cannador) for MS symptoms. This study includes newer ways of measuring MS symptoms and spasticity.
Whilst the announcement that Sativex is to be made available on a named patient basis is welcome, in that it may help to reduce the risk to which people with MS are exposed in buying illegal drugs, we would urge both doctors and patients to take part in clinical trials if at all possible. Further information on these trials can be obtained from our website at CUPID Study or CAMS Study. Ultimately, we need to provide convincing evidence that these drugs are effective and safe, and the only way we can do this is by scientific testing rather than compassionate prescribing.
Professor John Zajicek,
Peninsula Medical School,
Plymouth, UK
November 2005