Sativex
Encyclopedia
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
(MS) patients, who can use it to alleviate neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
, spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
, overactive bladder
Overactive bladder
Overactive bladder is a urological condition defined by a set of symptoms: urgency, with or without urge incontinence, usually with frequency and nocturia. Frequency is usually defined as urinating more than 8 times a day. The International Continence Society is responsible for this definition...
, and other symptoms. Nabiximols is also being developed in Phase III trials as a potential treatment to alleviate pain due to cancer. It has also been researched in various models of peripheral and central neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
. Nabiximols is distinct from all other pharmaceutically produced cannabinoids currently available because it is derived from cannabis
Cannabis
Cannabis is a genus of flowering plants that includes three putative species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis. These three taxa are indigenous to Central Asia, and South Asia. Cannabis has long been used for fibre , for seed and seed oils, for medicinal purposes, and as a...
plants, rather than a solely synthetic process. The drug is a pharmaceutical product standardised in composition, formulation, and dose, although it is still effectively a tincture of the cannabis plant. Its principal active cannabinoid components are the cannabinoids: tetrahydrocannabinol
Tetrahydrocannabinol
Tetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...
(THC) and cannabidiol
Cannabidiol
Cannabidiol is a cannabinoid found in Cannabis. It is a major constituent of the plant, representing up to 40% in its extracts.It has displayed sedative effects in animal tests...
(CBD). The product is formulated as an oromucosal spray which is administered by spraying into the mouth. Each spray delivers a fixed dose of 2.7 mg THC and 2.5 mg CBD.
In April 2011, GW licensed to Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
the rights to commercialise nabiximols in Asia (excluding China and Japan), Africa and the Middle East (excluding Israel).
Availability
In June 2010, the Medicines and Healthcare products Regulatory AgencyMedicines and Healthcare products Regulatory Agency
The Medicines and Healthcare products Regulatory Agency is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe....
of the United Kingdom licensed nabiximols as a prescription-only medicine for the treatment of spasticity due to multiple sclerosis. This regulatory authorization represents the world's first full regulatory approval for the medicine. The spray is being marketed in the UK by Bayer Schering Pharma. Many MS patients cannot receive nabiximols due to local primary care trust resistance to its funding.
Nabiximols was also approved in Spain for MS spasticity in the second half of 2010 and was launched in that country in March 2011. It was approved in the Czech Republic in April 2011, in Germany in May 2011 and in Denmark in June 2011. It has also been recommended for approval in Italy, Sweden and Austria with formal approvals expected in these countries during 2011. In Spain and other European markets (excluding the UK), nabiximols will be marketed by Almirall.
In Canada, nabiximols has been approved by Health Canada
Health Canada
Health Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies:Health Canada...
for the treatment of MS spasticity. It has also received a licence with conditions (NOC/c) for two additional uses: as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis, and also for pain due to cancer.
Nabiximols is available in a number of countries as an unlicensed medicine, which enables doctors to prescribe the product to individual patients who they consider may benefit. The product has been exported from the UK to a total of 28 countries to date.
In February 2007, GW and Otsuka Pharmaceutical
Otsuka Pharmaceutical Co.
, abbreviated OPC, is a pharmaceutical company headquartered in Tokyo, Osaka and Naruto, Japan. The company was established August 10, 1964, and currently has approximately 27,000 employees worldwide. The company focuses on pharmaceuticals related to nutrition...
announced an exclusive agreement for Otsuka to develop and market the drug in the United States. The first large scale US Phase IIb trial, Spray Trial, for cancer patients reported positive results in March 2010. GW and Otsuka have now commenced the Phase III development of nabiximols in cancer pain
Cancer pain
Pain is a symptom frequently associated with cancer. Cancer can cause pain by irritating or damaging nerves, by stimulating nociceptors , or by releasing chemicals that make nociceptors respond to normally non-painful stimuli. Cancer pain may be caused by the tumor itself or by medical...
.
Effectiveness
Of the two preliminary Phase III studies investigating the treatment of MS patients, one showed a reduction of spasticity of 1.2 points on the 0–10 points rating scale (versus 0.6 points under placeboPlacebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
), the other showed a reduction of 1.0 versus 0.8 points. Only the first study reached statistical significance. The Phase III approval study consisted of a run-in phase where the response of individuals to the drug was determined. The responders (42% of patients) showed a significant effect in the second, placebo controlled, phase of the trial. A 2009 meta-analysis of six studies found large variations of effectiveness, with a trend towards a reduction of spasticity.
Side effects
In early clinical trials, nabiximols has generally been well tolerated. The most common adverse effects in Phase III trials were dizziness (25%), drowsiness (8.2%) and disorientation (4%). 12% of patients stopped taking the drug because of the side effects. No investigations regarding the potential for dependenceSubstance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
are available, but such a potential is unlikely considering the pharmacological properties of the two components.