Given the complex and persistent nature of chronic pain in many illnesses, cannabis and its constituents are frequently utilized to treat chronic pain. One of the main phytocannabinoids, cannabidiol (CBD), has become quite popular since it lacks the intoxicating properties of tetrahydrocannabinol (THC), another important component of cannabis. There has been a significant change in perception of the therapeutic potential of these old compounds as a result of the recent rescheduling of CBD as Epidiolex for the treatment of Dravet and Lennox-Gastaut syndromes.
Preclinical and clinical research have suggested that using CBD to treat chronic pain linked to a variety of diseases may be beneficial. Inadvertent side effects from overuse, contamination with adulterants in preparation or harsh chemicals in plant cultivation, and its teratogenicity in users’ offspring present risks with increasing access to cannabis-derived products, especially CBD, which is partially due to their approval for recreational and medicinal use in the United States.
Benefits and drawbacks of using cannabis for chronic pain.
The prevalence of chronic pain in the US Between 50 and 116 million American adults suffer from chronic pain, a startling amount that outnumbers the number of people who suffer from diabetes, cancer, and heart disease combined. These studies also reach the conclusion that medical costs and lost productivity associated with chronic pain range between $560 and $635 billion yearly. Despite some recent therapeutic improvements, many patients with chronic pain become resistant to standard medical care or experience negative side effects from commonly prescribed drugs with a high risk for addiction, such as opiates or non-steroidal anti-inflammatory drugs. Formulations containing CBD have been tested in the clinic since 2003 to determine their effectiveness in decreasing pain when other treatment options have failed.
Reliability and Safety of Products with Cannabidiol Labels
Cannabis sativa L. has been used by humans for rituals and medicine for thousands of years, and it has recently made strides in the treatment of a wide range of illnesses. Hemp, a type of Cannabis sativa that does not significantly produce psychotropic compounds, also contains CBD, the main non-psychoactive component of cannabis. The United States (US) Drug Enforcement Administration still classifies cannabis-derived CBD as a Schedule I substance, with the exception of Epidiolex, a pharmaceutical CBD extract from the plant and a Schedule V preparation. The US Hemp Farming Act of 2018 allowed the cultivation and processing of hemp and its components, starting a trend of both legal and illicit CBD product mass marketing. There are initiatives to give dispensary staff the scientific knowledge they need to make recommendations that are supported by evidence in states where cannabis has been legalized for either recreational or medical use, but these efforts are insufficient and frequently eclipsed by anecdotal knowledge of CBD and other cannabinoids.
The market oversaturation of CBD-labeled goods for human consumption, including but not limited to inhalants, bath salts, pastries, ointments, and liquids, is extremely concerning. Numerous forms make claims about their potential medical usefulness without any supporting evidence. Only 26 out of the 84 products tested for cannabis content were found to be accurate, according to reports. In a more recent study, the safety of utilizing CBD products that are not regulated has been questioned because, of 20 popular CBD products evaluated by CannaSafe, a California-based cannabis testing business, just three contained the ingredients listed on the labels. Two of these products contained no CBD, and almost 50% of the CBD products contained less than the declared 20% of CBD. In some of these CBD products, hazardous fumes and solvents have also been reported. Therefore, these unlicensed CBD-branded products could pose a major risk to your health. To minimize unintended negative effects of undisclosed ingredients in goods marketed as CBD, there is an urgent need to regulate CBD products following reliable testing.
Clinical Results for Cannabidiol in Chronic Intractable Pain
Since the early 2000s, randomized, double-blinded, and placebo-controlled clinical trials employing CBD for the treatment of chronic pain have demonstrated outcomes ranging from highly beneficial to placebo-equivalent. CBD medication dramatically decreased pain on a visual analog scale in a mixed cohort of patients with intractable pain brought on by multiple sclerosis, spinal cord injury, brachial plexus injury, and limb amputation. These trials, however, were frequently constrained by their small cohort sizes, and the diverse illness states suggested that the therapeutic benefits of CBD are context-dependent. This was demonstrated in a research where therapy did not enhance outcomes in patients with Crohn’s disease.
Additionally, topical application of CBD to patients with peripheral neuropathy of the lower limbs appeared to be useful in treating the chronic pain related to kidney transplantation and other pain conditions. Additionally, compared to placebo, CBD treatment dramatically reduced pain in fibromyalgia patients by more than 30% in a significant number of individuals. CBD medication did not significantly reduce measures of pain in studies with generalized chronic pain, although patient-reported quality of life and sleep quality steadily improved. A New Zealand study on the safety of CBD treatment in 400 non-cancer chronic pain patients found that it was safe to use for an extended period of time and that improvements in pain and quality of life were also self-reported.
A 1:1 CBD:THC ratio was frequently used in clinical studies to treat intractable chronic pain, and it was frequently in the form of Sativex, a well-tolerated oromucosal spray. When administered together, the negative and psychoactive effects of THC alone were frequently lessened. The CBD: THC formulations reduced mean pain scores in multiple sclerosis patients with chronic pain, improved neurophysical measurements in response to noxious stimuli, decreased intractable chronic pain in advanced cancer, and reduced refractory/neuropathic pain after unsuccessful spinal cord surgery. According to studies in two independent cohorts, there is conflicting evidence that CBD:THC treatment does not always relieve chronic pain in patients with brachial plexus avulsion or advanced cancer, demonstrating the heterogeneity in disease contexts for which cannabinoids may be effective. Of note, patients in these studies reported an improved quality of life despite the fact that their pain was not significantly reduced. These results are encouraging, but it is also important to assess the efficacy of treatment in other disease states that cause chronic pain, such as diabetic neuropathy, rheumatic disorders, and sickle cell disease. There is a clear need to further understand the mechanism of action of CBD.
Mechanistic Understandings For Chronic Pain Cannabidiol Treatment
There haven’t been many preclinical investigations into the mechanism of analgesia for CBD treatment of chronic pain. The research that are now accessible rely on rodent and in vitro models, however they offer alternate methods for more efficacy or molecular pathways that might be exploited to improve CBD use in the clinic. In rats and mice, chronic constriction injury to the sciatic nerve results in chronic pain that is relieved by prolonged treatment (i.e., > 7 days) with CBD in a way that is cannabinoid receptor-independent. Treatment is also accompanied by decreased levels of intestinal P-glycoprotein and hepatic cytochrome p450, which may increase the amount of circulating CBD that is bioavailable. High dosages of CBD interact with and specifically activate 1- and 1ß-glycine receptors, according to in vitro experiments utilizing human embryonic kidney cells, however these findings have not yet been verified in live animals.
As an alternative, there is early evidence that CBD may interact with 3-glycine receptors to lessen inflammation and hyperalgesia after adult Sprague-Dawley rats were subjected to simulated neuropathic pain by ligating the L5 spinal nerve. Additionally, CBD reduces hyperalgesia in a mouse model of diabetic neuropathy, and research suggests that this is because it lowers the inflammatory milieu (Toth et al., 2010). Paclitaxel treatment was used to replicate chemotherapy-related discomfort in mice. CBD had analgesic and anti-inflammatory effects by interacting with the 5-HT(1A) receptors in the spinal cord. Additionally, CBD relieves pain in rats with streptozotocin-induced diabetic neuropathy in a way that is 5-HT(1A)-dependent. In mice models of neuropathy caused by the drug cisplatin, CBD alleviated hyperalgesia but did not completely avoid it, similar to human trials. Following traumatic brain damage in mice, myofascial pain in rats, and a mouse model of Parkinson’s disease caused by 6-hydroxydopamine, CBD administration reduced mechanical hyperalgesia; however, further research is needed to examine potential mechanisms of action in these investigations. Preclinical research to clarify the processes by which CBD supports analgesia in the treatment of chronic pain is thriving, but there is still more to be done to better understand the mechanisms at work in the context of chronic disease.
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