23 April 2015

Cannabis and Chronic Pain

Chronic non-malignant pain is pain defined as an "unpleasant sensory and emotional experience associated with actual or potential tissue damage" lasting either 3 months or longer or longer than expected given a certain injury. It can result from trauma, a disease process or an unknown cause. By adding the word “neuropathic” to the disorder name, the definition includes that the cause of pain is a direct result of damage or compression of a nerve. In contrast to “non-malignant” pain, chronic malignant pain is associated with a severe/worsening known disease process, and is often experienced by patients with cancer.

Approximately 11% of individuals residing in the United States (US) experience chronic non-malignant pain and it is therefore the leading cause of disability. Uncontrolled chronic non-malignant neuropathic pain can be severely debilitating, and safe and effective management is essential for maintaining optimised quality of life for patients. Opioids are commonly prescribed for patients with chronic pain, and are a useful and effective therapy for many. However, opioid use can lead to severe side effects, addiction/dependence and death in cases of overdose (accidental or intentional). Although most patients with chronic non-malignant pain who are prescribed opioids do not develop addiction/dependence, many develop abnormal/unhealthy drug-related behaviours (although the likelihood of developing these behaviours is decreased if patients are pre-screened for past addiction/dependence and alcohol/illegal drug use, and decision of whether or not to prescribe is modified given this information). 

Cannabinoid therapies (including whole-plant) may be an effective treatment option for chronic pain, and have the potential to work as an add-on therapies to help reduce patients’ opioid dosages. In some anecdotal cases, whole-plant cannabis has been reported to be able to fully replace opioid use (although these results should not be expected).

In Australia, a large study of people suffering from chronic problems such as back pain, migraine and arthritis has discovered many are turning to cannabis to relieve their symptoms, despite already being prescribed heavy-duty opioid medications such as morphine and oxycodone. In a finding that is likely to further intensify the debate about medical cannabis use, the National Drug and Alcohol Research Centre (NDARC) researchers found people who used the illegal 'drug' (cannabis is an annual, herbal plant) said it was more helpful than the highly addictive and potentially dangerous opioid medications.

Experience of adjunctive cannabis use for chronic non-cancer pain: Findings from the Pain and Opioids IN Treatment (POINT) study;
•There is increasing debate about the use of cannabis for medical purposes, including chronic non-cancer pain (CNCP)
•In 1,514 people prescribed opioids for CNCP, 16% had used cannabis for pain.
•A quarter reported that if they had access to cannabis, they would use it for pain relief.
•Those using cannabis for pain were younger, with greater pain severity and interference.
•They had been prescribed opioids for longer and were on higher opioid doses.

Millions of Australians suffer from chronic pain - a problem set to increase as the population ages. Yet there are few effective and safe long-term treatments, and accidental overdose deaths from prescribed pain drugs are now more common than deaths from heroin. Study leader Louisa Degenhardt found nearly 13% of 1,500 chronic pain patients, who were mainly aged in their late 40's and early 50's, had used cannabis in the past year despite being prescribed opioids. This compared to only 4.7% of the rest of the population, she wrote in the journal Drug and Alcohol Dependence. "One in three said they found it very effective to relieve their pain, that's a score of ten out of ten," she said. "Now these are all subjective scores but it means there is definitely a group of people who think that taking it was very beneficial." Professor Degenhardt, from NDARC and the University of Melbourne said the study raised important questions about whether the benefits of cannabis for pain should be more seriously explored, but also about the negative effects of drugs, such as patient dependence. "The people who were also trying cannabis for pain, they were younger but they had also been living with pain for longer," she said. "Their pain was so severe it had been interfering with their lives."

A study published in October 2014 in JAMA Internal Medicine found that opioid-related deaths were 25% lower in US states where medical cannabis is legal. Although this study found an association, rather than a cause-effect relationship, given cannabis’ highly favourable safety profile (especially in comparison to opioids) the results warrant further research.

A systematic review of 13 studies on the topic of cannabinoid therapy use for chronic neuropathic pain, published in the Winter 2015 volume of Journal of Oral & Facial Pain and Headache, found that “evaluation of these studies suggests that cannabinoids may provide effective analgesia (i.e. pain relief) in chronic neuropathic pain conditions that are refractory (i.e. not fully responsive) to other treatments.” 

To gather a sample of papers to review, the researchers used several online databases, as well as print sources dating back to 1950. Termed used in the searches included: marijuana; marihuana; cannabis; cannabinoids (endogenous, phytocannabinoids found in cannabis, synthetic cannabinoids); nabilone (a synthetic cannabinoid that functions like delta-9-tetrahydrocannabinol (THC) currently Food & Drug Administration (FDA) approved for the treatment of chemotherapy-induced nausea and vomiting); dronabinol (synthetic THC, currently FDA-approved for the treatment of chemotherapy-induced nausea and vomiting); THC, a phytocannabinoid; cannabidiol (CBD) a phytocannabinoid; ajulemic acid (a synthetic cannabinoid that is a breakdown product of THC, has demonstrated an ability to provide pain and inflammation relief without producing psychoactive effects); pain; chronic disease; neuropathic. The researchers limited the search to randomised placebo-controlled trials (the gold standard for clinical trials, allows for an examination of cause-effect relationships) and reduction in pain intensity and harmful events were compared among the studies. While 24 studies using the terms noted above were found, 11 did not fit the criteria. The remaining 13 studies that were analysed were rated using the Jadad Scale, which is used to assess the quality of clinical trials and, as noted by the researchers, “to measure bias in pain research”.

The researchers found that, “cannabis-based medicinal extracts used in different populations of chronic non-malignant neuropathic pain patients may provide effective analgesia in conditions that are refractory [i.e. not fully responsive] to other treatments” and that “the vast majority of adverse events listed were considered minor in nature”. Overall, improvements in “sleep quality, appetite, nausea, and anxiety” were also noted.

This review, conducted on studies that have examined the use of cannabinoid therapies for chronic non-malignant neuropathic pain, provides important details for the consideration of the place for cannabinoid use in symptom/disease/disorder treatment. While unable to draw new cause-effect relationships from systematic reviews, these types of studies help to answer a broad question, while limiting bias that is often found in individual papers. Given that this review was conducted in accordance with appropriate scientific methodology, and that a benefit to the use of cannabinoid therapies was found (with minimal adverse side effects), this study adds to growing evidence that cannabinoid therapies (including phytocannabinoids and isolated/synthetic cannabinoids) may be safe and clinically useful therapies in the management of chronic non-malignant neuropathic pain.

According to the authors, increased research will help to determine optimal specific cannabinoids (e.g. phytocannabinoid, synthetic, endogenous modulation), delivery methods, and length of treatment.

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