A literature review focuses on a research issue, it is a process of reviewing current knowledge, analysing previous studies and it helps the author note similarities and differences in research results. It also evaluates the strengths and weaknesses and will identify any gaps in the literature (Timmins and McCabe 2005). A literature review will also promote evidence based revision and development of protocols and guidelines (Polit and Beck 2006).
The aim for this literature review is to use specific information on the use of cannabis and cannabis based products to reduce pain in the patients with multiple sclerosis (MS). The rationale for choosing this subject was that the author had experienced a patient in clinical practice who used cannabis to relieve symptoms associated with pain. It was also acknowledged in an article in the Nursing Times that a new cannabis based drug Sativex was licensed to treat patients with multiple sclerosis in the UK (Nursing times 2010), however availability of this drug is restricted (MS Society 2011). As Multiple sclerosis is one of the most common long term conditions that nurses will care for and pain is one of the most common symptoms it is important that this is managed and understood by the nurses who will deliver care and support people with Multiple sclerosis.
The literature review will give a brief background of multiple sclerosis and the role of cannabis in managing pain. It will discuss how the search was conducted and review the content of cannabis based products that are used in managing pain in people with multiple sclerosis. It will also look at benefits and barriers to cannabis and identify any issues nurses may face in the use of cannabis in MS and give recommendations for future practice.
Background
Multiple sclerosis(MS) 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 of the brain and spinal cord as well as a broad spectrum of signs and symptoms(MS Society 2011). It affects the ability of nerve cells in the brain and spinal cord to communicate with each other. Nerve cells communicate by sending electrical signals called ‘action potentials’ down long fibers called axons (MSID 2011), which are wrapped in an insulating substance called myelin. In MS, the body’s own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals. It affects more than 100,000 people in the UK (MS Society 2011) and one of the most common reported symptoms of multiple sclerosis is pain (Zajicek and Apostu 2011; Lienau et al 2007). It is an unpredictable disease of the nervous system and to date there is no known cure (Hornby and Sharma 2010). Research has indicated that patients with MS have tried and would continue to use cannabis in the belief that it improves their symptoms (Wilkins 2006). Lienau et al (2007) agree with this and their findings were that the use of cannabis improved patient’s quality of life.
Cannabis is from the plant cannabis sativa and has been used for many centuries in various parts of the world as a medicine (Wilkins 2006; Zajicek and Apostu 2011). However it has only been over the past two decades that researchers have understood cannabis as a medicine (Wilkins 2006; Rog 2009). The cannabis plant contains over 60 different compounds, termed cannaboids (Rog 2009). One of the main ingredients is tetrahydrocannabinol (THC) this is the primary compound responsible for the psychoactive effects of cannabis (Iskedjian et al 2007). The compound is a mild analgesic (Hosking and Zajicek 2008), and it is believed to interfere with parts of the brain normally controlled by the endogenous cannabinoid neurotransmitter, anandamide (Iskedjian et al 2007). Anandamide is believed to play a role in pain sensation (Rog 2010).
Cannabidiol (CBD) is another major ingredient of medical cannabis and has been shown to relieve convulsions, inflammation and anxiety(Rog 2010), because cannabidiol relieves the above mentioned symptoms, cannabis strains with a high amount of CBD may benefit people with multiple sclerosis(Hosking and Zajicek 2008). Cannabidiol(CBD) is a therapeutic cannabinoid found in Cannabis sativa. It increases some of the effects of tetrahydrocannabinol(THC) and decreases other effects of THC. High levels of THC and low levels of CBD contribute to a strong, clear headed, more energetic high(Hosking and Zajicek 2008).
Robson (2001) suggests that there is some scientific evidence to suggest it may be useful in a wide range of conditions. But the complex nature of the substances contained within the plant makes it difficult for medical research to establish clearly its safety or efficacy, so its effects are far from proven or well understood, however current evidence supports cannabis treatment of pain in MS (Hosking and Zajicek 2010).
Cannabis is illegal to possess, grow, distribute or sell in the UK without the appropriate licenses. It is a Class B drug (O’Connell 2008), with penalties for unlicensed dealing, unlicensed production and unlicensed trafficking of up 14 years in prison. The maximum penalty for unauthorised or sanctioned possession is five years in prison (Home Office 2011), however the Home Office suggests in the same document ‘Drugs and the law’ advises that anyone caught in possession of cannabis could be arrested, or alternatively police may issue a warning, or penalty notice (Home Office 2011). The above information highlights the complications surrounding the use of cannabis.
Search strategy
To review the literature a comprehensive search of databases on Dundee University online library were used using CINAHL, MEDLINE, BNI and SCOPUS, search terms were put in using keywords ‘Multiple Sclerosis’ and ‘Cannabis’. The results from using these keywords brought up 595 articles (Table 1) and as a result of the large volume of literature found, limits were set in place and further keywords were determined, such as ‘MS’, ‘ Marijuana’, ‘Pain’, and ‘Nursing'(Table 1). ‘Sativex’ and ‘Cannabinoids’ were searched at a later date, using CINAHL PLUS a new version of database (Table 1). Publication dates were set at 2001-2011 and the criteria was set to English language and peer reviewed journals. The use of ‘or’ and ‘and’ were also used between the keywords to ensure articles were not missed. Exclusions were made from duplicates and articles that were unable to view due to restricted access, other exclusions were made as the content of some articles were not related to multiple sclerosis. The author also used handpicked information to provide background information and other information was sourced from government agencies, such as Home Office, NMC and the NHS.
Pain in multiple sclerosis is mainly caused by neuropathic or central pain (Lienau et al 2009). However another symptom of multiple sclerosis is spasms which could be painful this pain is known as nocierceptive as the pain is caused by excessive activity (Peat 2010). Rog (2007) suggests that central neuropath pain occurs in around 28% of patients with ms, and that tools are imperative to get an understanding of pain levels on an objective level. Numerical Rating Scale is a tool that rates how intense or severe their pain has been during a specified time period on a 0-10 scale, where 0 = ‘no pain’ and 10 = ‘ extreme pain’.
Visual analogue scales have images that represent levels of pain in a straight, horizontal line with one end indicating ‘no pain’ and the other end indicating ‘worst pain’. Individuals are then asked to mark where on the line their pain falls. These tools are well established and validated tools for the measurement of pain (Farrar et al 2001). The two types of scale have a similar reliability however, the numerical rating scale is generally preferred the easier to use in patients (Pollman et al 2005).
The MS International Federation also suggests that nurses and other health care professionals should ask questions to achieve a greater understanding of what type of pain it is (MSIF 2011). Solaro (2007) suggests that literature on pain management is lacking in MS and discussed the ethical issues regarding the barriers of studies on pain to identify best treatment based on comparisons of medication versus a placebo. Current treatments for MS are of little benefit, expensive, and are reported to have high risks of side effects (Russo 2008).
Corticosteroids have been found to have some value, but symptoms are poorly-controlled by existing medications, and as no cure has been found many patients are unable to tolerate the side-effects of conventional medications (Russo 2008) and believe that cannabis relieves their pain (MS Society 2011). Clinical and anecdotal reports of cannabinoids ability to reduce symptoms such as pain is plentiful in the literature (Zajicek et al 2003; Wade 2004; Rog et al 2005 and Chong et al 2006).
Centoneze et al (2009) argue that their findings showed there was some subjective improvement in pain however effects were not so different from the placebo group. Hazekamp and Grotenhermen (2010) suggest that if pain is noted on a subjective level, this is still beneficial to a patient and if a patient’s quality of life is improved then this should be considered. Ware et al (2005) suggest that reports of effectiveness of cannabis from patients should not be discounted as anecdotal and recommend this could be used as a valid indicator to target symptoms.
The author noted that this paper was funded by GW pharmaceuticals in which bias may be present as this is the company who are the licensed owners of Sativex. Cannaboids have a remarkable safety record, particularly when compared to other therapeutically active substances (Ashton 2001). Most significantly, the consumption of cannabis regardless of quantity or potency cannot induce a fatal overdose (Ashton 2001). The World Health Organization agree suggesting that the toxicity of cannabis is low and there have never been any reports of deaths due to cannabis intoxication alone.
However they also acknowledge that cannabis use is associated with numerous negative health consequences as well (WHO 2011) and cannabis smokers experience the same health problems as tobacco smokers (Wilkins 2006). Immediate effects may include light-headedness and faintness. Other side effects include increased heart rate, dry mouth, red eyes, impaired motor co-ordination (Pertwee 2007) and evidence also suggest that anxiety, panic, depression and psychosis may occur after excessive consumption of the drug (Wilkins 2006).
Wang et al (2008) agreed that cannabis could be a risk factor in psychosis, nevertheless felt that their findings were focused on the recreational use of cannabis. Smoked cannabis is widely used for symptoms including pain in patients with multiple sclerosis (Peat 2010) and in Canada patients with conditions such as MS are authorised to use herbal cannabis for medical purposes under their law (Wang et al 2008).
Honarmand et al (2011) acknowledge that previous research and trials reported a benefit of inhaled cannabis on pain, however their findings suggest that cannabis use affected their cognitive skills, which alarmed them as 50% of MS patients already have problems with their cognitive function to begin with a randomized control study that researched what effects cannabis played in symptoms of people with MS, found that it did not demonstrate any deterioration of cognitive function (Wade et al 2004).
The effects on memory and cognitive function in smoking cannabis modestly may not lead to any significant effect (O’Brien 2008). In a randomized placebo clinical trial cannaboids have been shown to be effective in reducing pain (Rog 2005; Russo 2008). There was a small but significant effect in the reduction of a numeric pain score study of 222 treated patients with 76 taking placebo in which the use of cannaboids were used (Iskedijan et al 2007).
An evaluation study published between 1980 and 2009 indicated that Sativex which is formulated as a mouth (oromucosal) spray containing two chemical extracts derived from the cannabis plant: delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) worth considering as an adjunctive agent in the management of neuropathic pain in patients with multiple sclerosis (Nummaka et al 2009).
The use of Sativex showed improvements in the numeric pain scales compared to placebo in a randomized controlled trial with MS patients (Rog et al 2005). In another finding Sativex showed improvement in subjective pain over placebo (Zaijicek et al 2003), however findings in a sample of 20 MS patients over a 6 week period using the visual analogue scale scoring for pain showed that Sativex was unable to reduce pain in MS subjects, it was also acknowledged on this study that no placebo was present (Russo et al 2007).
Macedo et al 2003 discusses that placebos are crucially important for the evaluation of health care interventions and indicate that drugs cannot get licensed without placebo effects, where as Biller Andoro (2004) and O’Brien (2008) argues that placebo interventions are ethically and legally controversial. A more recent study concluded that Sativex treatment in patients who have never used cannabis- was not associated with cognitive impairment (Wade et al 2004).
However the study did raise the possibility that higher dosages could precipitate changes in psychological disposition, especially in those patients with a prior history of psychosis. Research to monitor the safety and efficacy of long-term use of Sativex medicine in patients with MS was conducted. A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms.
Patients reported 292 unwanted effects, of which included oral pain, dizziness and diarrhoea. After the study was over, only 22 people continued with the cannabis treatment it was recommended that larger and longer terms studies were needed to be continued to monitor the long term side effects (Wade et al 2006). A systematic review was carried out Wang et al (2008) and it was also suggested that further studies should be considered to detect any issues for long term use especially regarding the development of cognitive effect of medical cannaboids used.
The large multicentre randomized placebo-controlled CAMS (Cannabis in Multiple Sclerosis) study researching the effect of cannabinoids for the treatment of spasticity and other symptoms such as pain related to MS enrolled over 600 patients. . The CAMS study did not show any statistically significant improvement in spasticity in patients on oral cannabis. However, there was evidence of a treatment effect on patient-reported spasticity and pain compared to placebo (Zajicek et al 2003).
A long-term follow-up to the CAMS study showed evidence of a small treatment effect of oral cannabinoids on pain measured by objective methods (Zajicek et al 2005). However Olsen (2009) debated that the clinical significance of this change from the patient perspective remained uncertain (Olsen 2009). Numerous surveys and double-blind studies have reported improvement in patients treated with cannabinoids for symptoms including pain (Zajicek et al 2003; Wade et al 2006 ;Rog et al 2005; Wissel et al 2006; Conte et al 2009).
Evidence also suggests that the side effects associated with cannabis are typically mild (Russo 2008). Cannabinoids may impede cognitive and psychomotor performance, resulting in temporary impairment (Honermand et al 2011) and if smoking cannabis there are risks on respiratory system (Wilkins 2006). However current treatments for MS are of are reported to have high risks of side effects (Russo 2008). Implications and the role of the nurse In the UK, 43% of patients with MS reported having experimented with cannabis at some point and 68% of this population used it to alleviate the symptoms of MS (Zajicek et al 2007).
The MS society estimates that 1-4% of the MS population in the UK are illegally using cannabis for symptom relief such as pain (MS Society 2011). This raises questions on the nurse supporting a person with MS. There is scarce literature of the implications of how nurses approach the illegalities of cannabis. Nurses have a professional requirement of confidentiality which is stipulated in the NMC, therefore if someone disclosed using cannabis a nurse has a professional duty of confidence (Griffith 2004).
As using cannabis is against the law there is no duty for a nurse to report this crime to the police, unless it is a major risk to the public (Griffith 2004). It is important that nurses support the use of quantitative research to help identify the medicinal qualities in cannabis use (Green and Vries 2010) and also look at the qualitative research to gain information from patients who use cannabis (Ware et al 2004). This would ensure nurses had the most up to date evidence which is encouraged by the Nursing and Midwifery Council (NMC 2008). Conclusion
Review of the current literature suggests that there are few randomized clinical trials of treatments for multiple sclerosis and pain alone with the use of cannabis, further studies need to be conducted on subjects who are cannabis free and the use of Sativex to see if pain is controlled, compared to other medication advised by NICE guidelines. As Sativex, has been licensed and approved for the use on the NHS it has not been approved by NICE and without NICE approval, local health authorities have no legal obligation to provide access to the drug.
The Author noted that there are no Sign Guidelines for the Management of MS. The Scottish medicine consortium is due to undertake an assessment of Sativex as a treatment for MS, however as it has not been approved and Sativex is not recommend for use. This impacts on patients with MS who use cannabis illegally. As Sativex could provide pain relief in a legal way, it would also ensure nurses are not faced with legal or ethical dilemmas in their patients using cannabis, and can empower nurses to offer an alternative to smoked cannabis, which may reduce smoking related illnesses.
In contrast to this there should also be clinical trials on the use of smoked cannabis and Sativex to analyse the measurement of pain and long term side effects. If patients are not offered cannaboids such as Sativex, nurses need to know about the use of cannabis and recognize pharmalogical issues and perhaps suggest alternative routes of using cannabis. Another recommendation if evidence suggests that cannabis can help pain, the UK could offer the same law as Canada in which patients with a chronic illness may be exempt from the law.