For centuries the cannabis plant has been used in traditional medicines as a pain reliever and analgesic. However, research has shown that cannabis only relieves pain in limited cases, and in some cases actually increases pain sensitivity. One of the reasons for the paradoxical nature of cannabis in the treatment of pain has been the lack of disambiguation between the action of individual cannabinoids. The ways in which cannabis works for pain are quite complex and there are major differences between the actions of the psychoactive compound Tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). In this article, we will explore the effectiveness and applications of using CBD to relieve pain.
What is CBD?
Cannabidiol, or CBD, is one of the more than one hundred cannabinoids so far discovered in the Cannabis sativa plant. CBD primarily affects the CB2 type receptors of the peripheral nervous system, immune system, and the organs. But, unlike THC, CBDs effect on the body is widespread. Not only does CBD interact with the endocananbiniod system through CB1/2 receptors, it has been shown to interact with more than 76 different receptors the body. CBD has been widely shown to have strong anti-inflammatory, antioxidant, and neuroprotective properties. Furthermore, CBD has been shown to reduce anxiety, and is currently being trialed for the treatment of addiction. Unlike THC, CBD is non-psychoactive and has reduced legal restrictions concerning its production, use, and research.
The science of CBD in pain relief is being pushed much faster than that of THC, and the cohorts for which it is being prescribed is also much greater, including children and animals. The FDA has even approved a CBD drug, called Epidiolex, for the treatment of epilepsy. Because CBD is most often derived from the hemp plant, containing less than 0.3% THC, there are fewer legal barriers, and even countries such as China are looking to quickly ramp up production. A large part or the increase in market demand for CBD has been its value in the treatment of chronic pain, but is the hype justified by evidence?
CBD in the treatment of pain
Chronic pain has been found to affect more than a hundred million Americans, and presumably billions of people around the globe. Unlike nociceptive pain associated with tissue damage or injury, chronic pain is exceedingly difficult to diagnose and treat. The most common analgesics given to treat chronic pain are not necessarily effective, and are also highly addictive and have severe negative side effects. Opioids were responsible for the death of more than 351,630 Americans between 1999 and 2016. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have severe side effects, including servere gastrointestinal issues and cardiovascular events. CBD is non-rewarding and shows no potential for addiction or dependence, furthermore it has no significant known short- or long-term side effects.
So, it is obvious why a safe and natural alternative to pain relieve is needed, but can CBD live up to the task? In several animal studies, CBD has been shown to reduce nociceptive pain (for more info on the type of pain see our article here). Other studies have even shown that daily CBD use can reduce the pain sensitizing effect of THC to tissue injury .
Evidence has shown that CBD is most effective in treating neuropathic and central nervous system pain, the two for which safe and effective medications are most needed.
CBD and Neuropathic pain
The two drugs with the most data for neuropathic pain are Epidiolex and Stivex, both made by GW Pharmaceuticals. Epidiolex is 99% CBD, and Sativex is a 1:1 THC to CBD ratio oromucosal spray. As mentioned above, Epidiolex has already been FDA approved for the treatment of epilepsy. And is currently the focus of more than 272 clinical trails just in the US alone. Regarding pain management, Epidiolex is being trialed for musculoskeletal pain, dental pain, back pain, Chemotherapy induced neuropathy, knee osteoarthritis, and many others. This sudden rush to investigate and provide evidence for new uses of the compound comes after many previous studies have shown promising results in the treatment of neuropathic pain in both human and animal trials.
Neuropathic pain can have many causes, but generally is derived from and injury or illness, or by the body’s own immune system. Inflammation is characterized by pro-inflammatory cytokines, neutrophiles, and T lymphocytes. The proinflammatory compounds continue to be released, causing pain and discomfort to the patient.
Studies have shown that giving CBD at the time of surgery can reduce post-surgery inflammation and pain. This was also found when patients were given morphine, but unlike morphine the CBD was non-additive and patients did not develop a tolerance to it. Other studies, using mouse models, have shown that CBD can reduce the pain, inflammation, and other deleterious effects of neuropathy caused due to type 1 diabetes.
A thorough review published just this year looked at many mouse model studies int the investigation for the use of CBD in pain management . The results showed varying levels of efficacy for several types of neuropathic pain types, including those caused by inflammation, arthritis, myofascial pain, and several others such as the pain associated with Parkinson’s disease. Collectively, these studies give major reason for human clinical trials.
That same review looked at 15 clinical studies in humans, covering more than 2,599 patients. Most of these were conducted using the drugs Sativex/Nabiximols, which contain THC, so it is hard to tease out the independent effects of CBD. In highlighting just a few studies, we can turn first to a 2020 one looking at 97 chronic pain suffers. The patients had been suffering for more than 3 years, and using opioids daily. After eight weeks of treatment with CBD, 53% had eliminated all opioid use and 94% had reported an improvement in quality of life.
Similar promising results were observed in another placebo-controlled study using topical CBD creams for peripheral neuropathy. In that study, it was found that the CBD cream reduced overall pain, itchiness, and cold sensations when compared with the placebo.
Discussion on CBD and Pain Management
While cannabis has been used for thousands of years to relieve pain, most studies in the 20th century had mixed and often contradictory conclusions. The seemingly paradoxical nature of cannabis’ effectiveness in pain management is starting to become more clear as the disambiguation between the cannabinoids in the plant is being made. Although many more studies are necessary, we are starting to understand the complex ways in which CBD can reduce pain through the modulation of inflammatory processes, reducing oxidative stress, working as an antispasmodic, and many other direct and indirect routes.
It is still quite difficult to elucidate or quantify the effectiveness of CBD, as most studies use THC containing drugs. However, the limited studies available do seem to back up years of anecdotal and animal trial evidence, and as more research comes out it tends to strengthen that conclusion and provide for more evidence for the various mechanisms of action.
It should be noted however that CBD is generally used primarily in the treatment of chronic pain rather than acute pain types. It is not uncommon to hear someone say they have tried CBD but it did not work for them. It is important to remember that unlike most analgesics on the market, CBD is non-rewarding and non-psychoactive. So you don’t actually ‘feel’ it. Furthermore, it is most effective when consumed regularly, and those studies that utilized long-term, daily use showed the most success in decreasing pain and increasing quality of life.
Although more data is required, it does appear from the clinical trial data thus far that a combination of 1:1 THC to CBD is most effective in pain management. However, it is not enough data to determine wither this is due to its pharmacological effects or a fossil of the fact that GW Pharmaceuticals was first to the market with Sativex, and is thus leading the world in funding these clinical trials. However, since THC is still illegal in most places in the world, it is important to investigate the effects of CBD independent of THC. Not only does this allow for more widespread use, but would also allow for use among a wider range of individuals who may be weary of the psychoactive effects of THC or be restricted due to legal or work-related reasons.
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