Rheumatic diseases are an important cause of chronic pain, usually difficult to treat with current analgesic treatments,and in the absence of a cure for the disease, the treatment of pain should be an important part of the integral management.Analgesic treatment consisting on NSAID, antidepressants and opioids are effective only in 10 to 25% of patients,and new treatment options are required. Endocannabinoids are present in synovial fluid of joints of people with inflammatory arthritis and osteoarthritis , but not in normal controls, suggesting that synthesis of receptors follows inflammation and tissue injury.Blake et al. studied the effect of cannabis-based medicine vs. placebo for pain on movement, pain at rest, morning stiffness and sleep quality in patients with rheumatoid arthritis .On this study, cannabis-based treatment improved significantly pain during movement, pain at rest and quality of sleep, however, it showed no effect on morning stiffness.There were no serious adverse effects in the active treatment group.Nabilone was studied for pain management and quality of life in 40 patients with fibromyalgia.Nabilone was used on doses titrated up from 0.5 mg daily to 1 mg BID over 4 weeks vs. placebo. Patients were evaluated at the 2nd and at the 4th week with visual analogue scale for pain as main outcome, and a number of tender points; Fibromyalgia Impact Questionnaire and average tender point pain threshold were secondary endpoints.
This study showed a decrease on VAS in patients treated with nabilone, as well as the FIQ,the rest of the endpoints did not show any significant differences.On another study with nabilone, patients with skeletal and locomotor system chronic pain were treated with nabilone and placebo in a 14-week cross-over period followed by a 16-week medication switch period with a free choice of the study drugs.On this study, the pain intensity ,mobile vertical rack decreased while using cannabinoids, and patients favored nabilone when they were asked to decide the drug they wanted to continue with.Despite these results, three systematic reviews concluded that there is insufficient evidence to recommend any cannabinoid preparation for the treatment of rheumatic pain,based on limitations of included studies, due to small sample size, short study duration, heterogeneous medical conditions, and the differences on the products studied.Even though cannabinoids are usually well tolerated, some side effects had been seen as dizziness, drowsiness, nausea and dry mouth.There is no high-quality evidence of the benefits of cannabis-based drugs in patients with rheumatic diseases with chronic pain. Nevertheless, it is advised that patients concerned by the use of cannabis as a drug should be informed about the role of the endocannabinoid system on human health and that there is ongoing research on this field. Around 10 million people are diagnosed with cancer around the world each year.Cancer causes pain through different mechanisms: the tumor itself, chemotherapy, side effects of medications, or postoperative pain.Patients are usually threated with the three-step analgesic ladder proposed by the World Health Organization making NSAIDs and opioids the most common treatment for people with cancer, achieving appropriate relief in 71—86% of patients.
Pain may be experienced in all the stages of cancer, but advanced stages show the highest prevalence.Pain is one of the greatest fears of patients with cancer, and is associated with decreased quality of life, inability to cope with the disease, sleep disruption, and emotional symptoms such as anxiety and depression.As the treatment of pain in some patients with cancer is still a challenge, there is an interest in studying new treatment options, as cannabis-based medications.One study compared the efficacy of THC:CBD extract, THC alone or placebo in patients with intractable cancer related pain during two weeks, and showed a significant change on the Numerical Rating Scale favoring THC:CBD while compared to placebo, but no change with THC alone.There was no change on the median dose of opioid medication or number of doses between the treatment groups, and there was worsening in nausea and vomiting with the THC:CBD group when compared to placebo.On an extension study, THC:CBD oralmucosal spray was used in patients who had participated in the previous three arm study, this time on a two-week randomized controlled trial.Patients were asked to self-titrate the THC:CBD spray or THC spray, showing that the scores for pain severity and worst pain decreased in patients with THC:CBD; additionally, patients showed improvement of insomnia, pain and fatigue.On trials with Nabiximols®, patients with poorlycontrolled chronic cancer pain received low dose , medium dose or high dose during 5 weeks.The number of patients reporting analgesia was greater for Nabiximols than placebo, especially for the low and medium dose group.On another study, Nabiximols as an oromucosal spray was used as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain.Patients were able to self-titrate Nabiximols or placebo, showing that Nabiximols was superior to placebo in two of the three quality of life instruments evaluated at week 3 and on all three instruments evaluated at week 5.Despite all these results, the meta-analysis suggests that there is no strong argument to recommend the use of cannabinoid based medicines as a single treatment for cancer pain, this conclusion is mainly based on sample size and other limitations of the clinical trials.
There is some evidence that cannabinoids are effective adjuvants,but there is an important gap of scientific knowledge, and further research should be encourage as the cannabinoid system could play a role in the treatment of chronic pain related to cancer, but clinicians should caution against its use as analgesics.Nonetheless, cannabis has been studied for other cancerrelated symptoms, such as cachexia, nausea, and vomiting. For cancer-related cachexia, two studies reported no differences between appetite and/or nausea between cannabis and placebo, whereas a third study observed that THC was superior to placebo by increasing appetite.Additionally, in terms of nausea and vomiting, a meta-analysis provides mixed evidence.Evidence on relevant outcomes of cannabis managing cachexia, apetite and nausea is missing.Headache is associated with a decreased quality of life, disability, and individual and societal costs.Tension type headache is the most common of all types , followed by migraine and chronic daily headache . Treatment of headaches includes NSAIDs, triptans, antidepressants, verapamil, or ergotamine, nevertheless, less than half of patients go through remission. Cannabis has been used for the treatment of headaches since ancient times, it appears on the Ayurvedic preparations and in ancient Greece, however, it has been ignored by the scientific community for the last decades.No clinical trials comparing cannabis to placebo on headache were found. Nonetheless, the effects of cannabis can be evaluated from other studies that point at some evidence about its efficacy. On one study, medical marijuana was prescribed for patients with migraine, finding that the frequency of the headache was decreased on the arm that used marijuana.There is a clinical case report in which the use of recreational marijuana use and subsequent use of dronabinol provided pain relief.Because of this case report, a trial was made in which 139 patients with cluster headache were asked about history of cannabis use, finding that even though cannabis use is frequent, efficacy might be limited and should be not recommended until controlled trials and strong evidence is provided.One trial compared nabilone to ibuprofen in patients with medication overuse headache.Patients were given the medication daily during 8 weeks, finding that nabilone was more effective than ibuprofen in reducing pain intensity and daily analgesic intake.
However, there is insufficient evidence to advocate in favor of the use of cannabis-based medicine for the treatment of headache and more research is needed in order to prove both its efficacy and its risks.The aberrant use of opioid medication is common in people who experience chronic pain, and has become a public health issue.There has been a rising trend in the prescription of opioids in the US, which has quadruplicated over the last 15 years.Despite beliefs, opioids are not an ideal pharmacotherapy for chronic pain as they present a gradual hyperalgesia effect, which is induced over time, which leads patients to increase the opioid dosage over the years.A synergism has been proposed between cannabinoids and opioids as the antinociceptive effects of morphine are mediated by the mu-opioid receptors and might be enhanced by the activation of the kappa and delta-opioid receptors by THC.Receptors for opioids and cannabinoids are binded to similar intracellular signaling mechanisms through G proteins which lead to a decrease of the cAMP production.Additionally, there is some evidence that cannabinoids can increase the release of endogenous opioids and vice versa.Because of this synergy, the role that cannabis could play in decreasing opioids consumption has been studied. One study evaluated pharmacokinetics and safety of the combination of these drugs by exposing 21 patients with chronic pain to a regime with morphine or oxycodone BID and vaporized cannabis in the evening on day 1 and then three times a day during days 2—4 and in the morning of day 5.Pain was decreased after the addition of vaporized cannabis, however there was no change in the area under the plasma concentration-time curves for morphine or oxycodone after the exposure to cannabis.Bachhuber et al. showed that medical cannabis regulation was associated with a reduction in opioid overdose mortality in California, Oregon, and Washington.Unfortunately, there is no strong evidence that could support a recommendation on the synergic activity between cannabis and opioids, despite some research suggests that this interaction might be of clinical and pharmacological interests.Given the potential of cannabis as a medical treatment, and due to the concerns generated by the recreational use of cannabis, data about security is a priority for the regulation of cannabis-based medications. The extrapolation of the risk of the recreational use of cannabis is not ideal, vertical grow rack but it might provide some insight when there are limited studies in clinical setting. The COMPASS study examined the safety of cannabis for medical purposes comparing patients with severe chronic pain using THC at 12.5% vs. patients who were not using it.This study showed there was no difference in serious adverse events between the groups, however the cannabis group showed an increased risk of non-serious adverse effects; the most common were somnolence, amnesia, cough, nausea,dizziness, euphoric mood, hyperhidrosis and paranoia.This corresponds to the results of a systematic review, which showed that most adverse effects were mild, such as dizziness and light-headedness.
Concerning the medical harms of cannabis use, it has been suggested that low levels of cannabis smoking does not affect lung function over about 20 years, but some evidence might suggest that for a longer period of time, some adverse pulmonary effects might arise,however there is insufficient evidence to link the use of cannabis with cardiovascular events or cancer. It is important to notice that elder people can be at a higher risk as they have a slower drug metabolism, comorbidities and concomitant medications.On the psychomotor domain, cannabis can impair gait and stability, which might predispose to falls. On the cognitive domain, cannabis can worse pre-existing cognitive impairment by adding impairment of short-term memory and of emotional processing.There is concern about cardiovascular risk, especially of an increased risk of myocardial infarction, arrhythmia and stroke, and about mental health, especially on the risk of psychotic episodes.In addition to this, addiction and dependence should be considered. Addiction and dependence to cannabis has been assumed to be comparatively lower than other substances.According to the National Household Survey on Drug Abuse, the prevalence of dependence declined strongly with increasing age and adolescents were much more vulnerable to addiction and dependence.The challenges in the use of cannabis, including misuse, addiction and dependence are associated with social and personal factors and should be taken in consideration when using it for medical purposes.Cannabis is the most frequently used drug globally, with nearly 4% using cannabis in the past year . Globally, about 13 million people are estimated to meet criteria for Cannabis Use Disorder accounting for a global burden of disease of two million disability adjusted life years . Cannabis contains at least 144 different cannabinoids, of which the main psychoactive component is Δ-9-tetrahydrocannabinol . THC produces its effects by acting on the endocannabinoid system, which includes cannabinoid receptors , endocannabinoids that bind to these receptors , and enzymes involved in their breakdown such as Fatty Acide Amide Hydrolase .