chronic pain and using cannabis as a treatment

Cannabis and Chronic Pain

Pain can be a difficult symptom of an injury, disease process or drug side effect that can greatly hinder an individual’s quality of life. Pain as a symptom can be either acute or chronic in nature. Acute pain can be referred to as sudden pain that is not long lasting; for instance, pain caused by a broken arm that ceases after the arm has healed is acute pain. Chronic pain lasts for weeks, months and even years and is diagnosed after an individual has been suffering with pain for over 3-6 months. Chronic pain is often caused by nerve damage (neuropathic pain) or chronic diseases (arthritis, cancer, diabetes, fibromyalgia, multiple sclerosis, etc.). Medications that treat pain include opioid analgesics, anti-inflammatories, anti-epileptics, and anti-depressants. The goal of treating acute pain entails facilitating recovery from the underlying injury, surgery or disease while controlling and reducing pain to an acceptable level with treatments that promote minimal pharmacological side effects. It is also important with acute pain management to prevent the progression of pain into a chronic state. The goal of chronic pain treatment is to reduce pain, correct any secondary consequences of the pain, and assist in restoring individuals level of function and quality of life. Chronic pain can be difficult to treat and often patients dealing with chronic pain require multiple treatments to bring symptoms to a manageable level.

Effective Analgesic

Cannabis has long been expressed by users as an effective analgesic. The problem with cannabis is that although it has been shown to provide therapeutic benefits for a wide range of condition types its psychoactive effects make it an undesirable candidate as a treatment option for the various conditions that may benefit from it. Various studies have examined the analgesic effects of cannabis and often these studies have focused primarily on the phytocannabinoid, delta-9-tetrahydrocannabinol (THC). Studies examining cannabis’ benefits on pain have often highlighted the beneficial role it can play in chronic pain, while highlighting its inefficiency in acute pain. Its potential as a therapeutic agent in chronic pain is important to examine primarily because acute pain is easily treatable with conventional therapies whereas chronic pain is difficult to treat requiring the development of novel treatment options.

Cannabis’ therapeutic potential on chronic pain has been examined by scientist in various studies. Cox et al (2007), showed that THC can produce analgesic effects in arthritic rats by activating both CB1 and CB2 receptors, as well as nonarthritic rats by activating CB1 receptors only. A study examining THC’s ability to alleviate diabetic neuropathy (nerve pain) found that THC delivered at a dose of 50 mg/kg orally to diabetic mice provided a potent analgesic effect (Williams et al, 2008). Although THC often exemplifies potent analgesic effects the difficulty with using THC on a patient population is managing its psychotropic side effect profile. Various methods have been suggested to cope with this issue; for instance, research has shown that the addition of other phytocannabinoids (ie, Cannabidiol) may help to alleviate the psychotropic effects of THC while still providing therapeutic benefits.

The use of low-doses of THC that do not produce a significant psychoactive response in combination with analgesics is another option for remedying the psychotropic issue. Studies have exemplified that THC acts synergistically with opioids as an opioid-sparing agent and when taken in combination with opioids can provide more pain relief than if one of these substances were taken alone. Cichewicz and McCarthy (2003), showed in their research that the analgesic effects of both morphine and codeine acted synergistically with THC rather than an additive interaction. This same study further showed that morphine-tolerant mice were more sensitive to the acute analgesic effects of THC which suggested that there was no risk of cross-tolerance development (Cichewicz and McCarthy, 2003). The synergy between opioids and THC were also reflected in chronic pain models, specifically chronic inflammatory and neuropathic pain models (Cox et al, 2007). Studies examining THC’s ability to reduce pain have determined that significant relief of chronic pain is possible through activation of peripheral CB1 receptors; CB2 receptors contribute to chronic pain primarily due to their prominence on microglial cells within the spinal cord that play a role in pain.

CBD for Chronic Pain

Cannabidiol (CBD) has also been examined for it’s potential as an analgesic primarily due to the growing evidence suggesting it’s antioxidant, anti-inflammatory, and neuroprotective effects. CBD is a very interesting phytocannabinoid as it has low affinity to both CB1 and CB2 receptors and does not bind with these receptors. CBD’s mechanism of action may derive from it’s interaction with other receptors outside the endocannabinoid system. CBD has been shown to be ineffective against acute pain but effective against pathological pain. Costa et al (2004), showed that CBD had potent analgesic effects in inflammatory pain only 1 hour after single, low dose administration; however, it was shown that CBD had no effect on acute pain as it provided no analgesic relief during abdominal stretching which is a model of visceral (internal organ) pain (Costa et al, 2007). The mechanism by which CBD may induce analgesic effects is not clearly known although certain suggestions have been hypothesized. For instance, CBD may produce analgesic effects in chronic pain models by lowering levels of key proinflammatory cytokines. This was exemplified in a study which examined the effectiveness of CBD in reducing neuropathic pain caused by rats using the cancer drug, paclitaxel; in this study pain was reduced in rats and it was suggested that since paclitaxel increases proinflammatory cytokines that CBD may play a role in lowering these cytokines (Ward et al, 2011). A more recent study has shown evidence that suggests CBD may reduce neuropathic pain in rats by targeting a3 glycine receptors (Xiong et al, 2012). In this study it was found that rats that lacked the a3 glycine receptors had a reduction in pain relief when compared to rats that lacked CB1 and CB2 receptors. A3 glycine receptors have been proposed as a potential target for chronic pain treatment, however, no therapeutic drug exists on the market that targets these receptors. Phytocannabinoids could act as a potential target for these receptors.

Other phytocannabinoids have also been implicated as potential therapeutic options for chronic pain. For instance, tetrahydrocannabivarin (THCV) has been shown to be a CB2 receptor partial agonist; CB2 receptor agonists have further been shown to be effective against many types of pain models including inflammatory, neuropathic, postsurgical, and cancer (Atwood and Mackie, 2010). Cannabierol (CBG) has been shown to a potent a2-adrenoreceptor agonist (Cascio et al, 2010); A2-adrenoreceptor agonists, such as the drug clonidine, have been shown to display analgesic effects and CBG has demonstrated similar pain relief potential in animal models (Comelli et al, 2012).

More Research is Necessary

There is still much more research that needs to be conducted in order to understand cannabis’ potential role in pain management. The current evidence regarding cannabis as a treatment option in pain indicates positive and beneficial results for the treatment of chronic pain. With the plant containing over 100 different cannabinoids, research has shown that a few of these cannabinoids do have potential as an analgesic and much more research is still required on the other cannabinoids within the plant. Furthermore, evidence is mounting indicating the benefits of using a whole-plant cannabis extracts instead of a single pure cannabinoid when managing chronic pain. Studies have shown that extracts produced from the whole cannabis plant produce more effective therapeutic benefits than a pure cannabinoid compound. A 2006 study, showed that CBD potentiates the effects of THC in pain models; in this study CBD administered through IV at 30mg/kg potentiated (amplified) the analgesic effects of THC (Varvel et al, 2006). Another study in 2008, showed that extracts of whole cannabis containing large amounts of CBD and small amounts of THC, other minor cannabinoids, and noncannabinoid components (flavonoids and terpeonoids) provided more pain relief than a single pure cannabinoid (Comelli et al, 2008). In this study, treatment was initially provided with a whole plant extract at a certain dosage to gather baseline data. The treatment was then repeated with the same dosage, but using only a single pure cannabinoid. Treatment was more effective when using the whole-plant extract than a single cannabinoid. The treatment was then further repeated using an extract that contained both THC and CBD; this extract as well did not provide as adequate of pain relief as the whole-plant extract. All of this suggested that the various compounds in the cannabis plant are acting synergistically to provide a more profound effect then when taken alone; this effect is referred to as the entourage effect and exemplifies the importance of the herbal form of cannabis in pain management.

 

References:

Atwood, B.K. and Mackie, K. (2010). CB2: A cannabinoid receptor with an identity crisis. British Journal of Pharmacology, 160(3), 467-479.

Cascio, M.G., Gauson, L.A., Stevenson, L.A., Ross, R.A., and Pertwee, R.G. (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. British Journal of Pharmacology, 159(1), 129-141.

Cichewicz, D.L. and McCarthy, E.A. (2003). Antinociceptive synergy between delta-9-tetrahydrocannabinol and opioids after oral administration. Journal of Pharmacology and Experimental Therapeutics, 304(3), 1010-1015.

Comelli, F., Filippi, G., Papaleo, E., De Gioia, I., Pertwee, R.G., and Costa, B. (2012). Evidence that the phytocannabinoid cannabigerol can induce antinociception by activating a2-adrenoreceptors: A computational and pharmacological study. Proceedings 22nd Annual Symposium on the Cannabinoids. International Cannabinoid Research Society: Freiburg, Germany, p.44.

Comelli, F., Giagnon, G., Bettoni, I., Colleoni, M., and Costa, B. (2008). Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved. Phytotherapy Research, 22(8), 1017-1024.

Costa, B., Colleoni, M., Conti, S., et al. (2004). Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn-Schmiedeberg’s Archives of Pharmacology, 143(2), 247-250.

Costa, B., Trovato, A.E., Comelli, F., Giagnoni, G. and Colleoni, M. (2007). The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. European Journal of Pharmacology, 556(1-3), 75-83.

Cox, M.L., Haller, V.L., and Welch, S.P. (2007). The antinociceptive effect of delta-9-tetrahydrocannabinol in the arthritic rat involves the CB2 cannabinoid receptor. European Journal of Pharmacology, 570(1-3), 50-56.

Cox, M.L., Haller, V.L., and Welch, S.P. (2007). Synergy between delta-9-tetrahydrocannabinol and morphine in the arthritic rat. European Journal of Pharmacology, 567(1-2), 125-130.

Varvel, S.A., Wiley, J.L, Yang, R., et al. (2006). Interactions between THC and cannabidiol in mouse models of cannabinoid activity. Psychopharmacology (Berlin), 186(2), 226-634.

Ward, S.J., Ramirez, M.D., Neelakantan, H., and Walker, E.A. (2011). Cannabidiol prevents the development of cold and mechanical allodynia in paclitaxel-treated female C57B16 mice. Anesthesia and Analgesia, 113(4), 947-950.

Williams, J., Haller, V.L., Stevens, D.L. and Welch, S.P. (2008). Decreased basal endogenous opioid levels in diabetic rodents: Effects on morphine and delta-9-tetrahydrocannabinol-induced antinociception. European Journal of Pharmacology, 584(1), 78-86.

Xiong, W., Cui, T., Cheng, K., et al. (2012). Cannabinoids suppress inflammatory and neuropathic pain by targeting a3 glycine receptors. Journal of Experimental Medicine, 209(6), 1121-1134.

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