Since it contains phytocannabinoids, terpenes, and many different effective compounds, the idea that cannabis can be used in the treatment of many diseases has existed for a long time. Scientific studies on this subject have increased significantly, especially in the last 5 years. It is known that cannabis is especially good for painful diseases and direct pain. So, is cannabis, which is famous for its pain-relieving properties, also good for neuropathic pain?
As it is known, one of the first effects of cannabis discovered on human health is its analgesic activity. Medical cannabis users also use cannabis mostly because of this effect. Although it is effective in many types of pain such as migraine, bone and joint pain, menstrual cramps, etc., its effectiveness is much higher in pain types that do not respond to conventional treatments such as neuropathic pain and cancer pain, which are difficult to treat. For this purpose, standardized cannabis extract Nabiximols, containing THC and CBD, has been used in the clinic since 2010.
What Is Neuropathy?
People with peripheral neuropathy generally describe the pain as burning and stabbing. In most cases, the symptoms observed can improve if they are caused by treatable conditions. Medications prescribed by doctors can reduce pain. Neuropathic pain is pain associated with nerves in the body. It is characterized by nerve damage or irritation.
The peripheral nervous system sends information from the spinal cord to the brain (central nervous system) to the rest of the body. Peripheral neuropathy can be caused by infections, injuries, exposure to toxins, and hereditary causes. One of the most common causes of peripheral neuropathy is diabetes mellitus. Diabetes mellitus is a metabolic disease caused by high blood sugar. Neuropathic pain can be seen in every part of the body. In the peripheral system, each nerve has its own function. Therefore, the symptoms depend on the type of nerve that is affected. Symptoms of neuropathy include:
- Throbbing, chills, burning pains, and freezing sensation
- Tingling in the hands and feet that radiates upward into the arms and legs
- Severe sensitivity to touch
- Paralysis or muscle weakness due to the motor nerves being affected
- lack of coordination
- Heat intolerance or altered sweating with autonomic nerve involvement
- Digestive, bladder, or bowel problems
- Dizziness in people due to constant blood pressure changes
Neuropathic pains do not improve with drugs in the classical painkiller group. Normal painkillers are not used in the treatment of neuropathic pain. Generally, there are some drugs developed for epilepsy treatments in people with this type of pain, and these drugs are only used for neuropathic pain. These epilepsy drugs are used in trigeminal neuralgia, cancer-related pain, phantom pain, diabetes-related neuropathic pain. Among the painkillers used in neuropathic pain treatments, another group other than epilepsy drugs is antidepressant drugs.
Antidepressant drugs are used not only in those with psychological problems, that is, in those who are depressed, but also in people who experience neuropathic pain. Both antidepressant drugs and antiepileptic drugs have secondary analgesic effects. This means secondary pain relief. Such drugs have an important place in the treatment of chronic pain. If these pains caused by the nervous system are not treated, it will make people’s lives very difficult.
What Is Neuropathic Pain?
Neuropathic pain symptoms can be titled “spontaneous pain” and “evoked pain”. Spontaneous pain may manifest as a burning sensation, frostbite, tingling, stinging, itching, electric shock sensation, a feeling of cutting the skin, a sharp object pricking the skin, or just a stinging sensation. As one, more, or all of these different pains can be seen in the same person, it is not necessary for these symptoms to be seen at the same time. In the chronic process, the types of pain may differ over time, for example, pain in the form of electric shocks at first may later subside or be added to a continuous burning.
On the other hand, induced pain is hyperesthesia, that is, the skin feels more painful than a pain-inducing stimulus, and allodynia, that is, a stimulus that normally does not cause pain (like touching a cotton ball) causes pain. Some types of pain specifically refer to neuropathic pain. For example, the sensation of electric shock is quite typical for neuropathic pain. Likewise, the sensation of allodynia by touch (tactile) or pressure (mechanical) when there is no visible change (such as a wound) in the tissue is also very typical for neuropathic pain.
The most well-known example is that patients who develop skin pain after shingles do not touch the aching areas, or they cannot wear underwear, or clothing depending on the location of shingles. To suspect neuropathic pain, there must be a disease or sign of a disease, whether of the peripheral nerves or of the central nervous system, i.e. the brain or spinal cord, that can cause neuropathic pain, such as diabetes or a previous stroke or a spinal cord trauma. In addition, the pain symptoms thought to be neuropathic pain should have a distribution pointing to the nervous system.
For example, if polyneuropathy due to diabetes and neuropathic pain due to it is thought, these complaints should be most prominent in especially the feet and should be absent or less in arms or upper legs. Or if neuropathic pain due to cerebral palsy is considered, it should be on one side of the body on the side of the stroke. In addition, if the underlying disease is demonstrated by examination methods (for example, diagnosis of diabetes or multiple sclerosis disease) and evidence of the neuropathic pain region is also revealed by examination methods (for example, revealing diabetic neuropathy with EMG, imaging a lesion on an MRI in multiple sclerosis disease will explain neuropathic pain) can now be called a “definite” diagnosis of neuropathic pain, but without this evidence, neuropathic pain can be inferred from the symptoms.
How Cannabis Helps With Neuropathic Pain
In 1890, Queen Victoria’s physician, Sir John Russell Reynolds, reported that cannabis is “the most useful medicine for the treatment of painful diseases such as dysmenorrhea, migraine, neuralgia, and also for convulsions and insomnia”. Cannabis is used to relieve the pain of advanced cancer patients, neuropathic pain, and spasticity of MS patients. Medical cannabis may be an option for the treatment of certain conditions such as neuropathic pain, AIDS cachexia, and chemotherapy-induced nausea.
Cannabis has been used as a pain-relieving agent for thousands of years. Evidence suggests that cannabinoids may be beneficial in the modulation of pain by inhibiting neuronal transmission in pain pathways. This suggests that cannabis may work in the treatment of neuropathic pain. Cannabis oil has the ability to relieve chronic pain and inflammation, so cancer patients undergoing chemotherapy often turn to cannabis oil for relief. It can also be part of natural fibromyalgia treatment.
A 2010 study published in the Canadian Medical Association Journal suggests that cannabis may help patients with chronic pain. In this study, 23 adults with post-traumatic or post-surgical neuropathic pain were randomly selected to take cannabis for 14 days in a four-day period. Average daily pain intensity was measured using an 11-point numerical rating scale, and results showed that a single inhalation of tetrahydrocannabinol herbal cannabis three times daily for five days reduced pain intensity, improved sleep, and was well tolerated.
A Scientific Approach: Cannabis and Neuropathic Pain
Clinical studies show that the importance of Δ9-THC will increase in the relief of difficult-to-treat pain types such as cancer pain, neuropathic pain, etc. Current research suggests that Δ9-THC may also be beneficial in Tourette’s syndrome. In a study conducted by the researchers in 2018, it was determined that low dose Δ9-THC significantly triggered neurogenesis in the hippocampus of aged rats.
Δ9-THC has also been found to reduce intraneuronal β-amyloid accumulation and exert an anti-inflammatory effect. It is known that different preparations of cannabis have been used for a long time in many gastrointestinal diseases such as gastrointestinal pain, gastroenteritis, diarrhea, etc.
Today, drugs used in the treatment of multiple sclerosis symptoms such as muscle spasticity, neuropathic pain, tremor, ataxia, and neurogenic bladder are not fully therapeutic and their use may be limited due to their side effects. This is the reason why cannabis is being tried at increasing rates by multiple sclerosis patients all over the world. Nabiximols started to be used in the treatment of spasticity and pain due to multiple sclerosis that did not respond to conventional treatments in many countries, especially in Canada and most European countries, after 2010.
During these treatments, psychoactive side effects and resistance were reported at very low levels and the patients tolerated the treatment well. It has also been proven by studies that cannabis reduces nightmares related to post-traumatic stress disorder and improves sleep quality in patients with chronic pain.
Other Medicinal Uses of Cannabis
Cancer is one of the most common diseases that cause death as a result of the uncontrolled division and proliferation of cells under the influence of genetic and environmental factors. The spread of cancer from the place where it started to other regions is called metastasis. The mass formed by the accumulation of cancer cells is called a tumor. Tumors are divided into benign or malignant. Benign tumors are not cancerous and do not metastasize and can often be surgically removed. Benign tumors have a very low risk of recurrence after removal. Non-cancerous cells undergo genetically programmed cell death.
However, cancer cells mutate, escaping gene control, which prevents constant division and uncontrolled development. Millions of new cancer cases and deaths from cancer occur every year in the world. Breast cancer accounts for approximately 30% of newly diagnosed cancers each year. In the etiology of cancer, environmental factors such as chemicals, radiation, and infectious substances may also play an important role in hereditary mutations and genetic factors. There is a website that provides information about the use of cannabis in cancer treatment in most western countries, especially the USA.
About one-fifth of cancer deaths are due to tobacco use. However, it is thought that smoking cannabis is not as high in cancer-causing effects as tobacco. That’s because, according to experts, based on the statistical results of data collected from different studies, there is little evidence of an increased risk of lung cancer among long-term cannabis smokers. Experts say cannabis smoke can be carcinogenic, although it is difficult to definitively link cannabis use and epidemiological cancer development, it has been reported that cannabinoids may have anti-cancer effects.
Cannabinoids have been shown to inhibit tumor growth or proliferation in laboratory animals, cell cultures, and in some cases in humans. Brain cancer is a leading cause of cancer deaths; “Gliomas”, which include tumors arising from the adhesive or supporting tissue of the brain, constitute 30% of all brain tumors and 80% of all malignant tumors. Researchers have found that THC has an effect on the control of malignant gliomas. The positive effects of cannabinoids in gliomas have attracted great interest due to the possibility of using cannabinoids as a new chemotherapy agent for patients, however, the subject has progressed very slowly in the clinical field.
Another important use of cannabis in cancer patients today is to alleviate the side effects and symptoms of cancer treatments. Because the palliative effects of THC including loss of appetite, nausea, and vomiting due to chemotherapy or radiotherapy, pain relief in cancer patients, improvement of psychiatric symptoms, and relief from insomnia are well known. Cannabinoids offer significant advantages over existing antitumoral therapies. Although cannabinoids relieve some cancer symptoms, how effective are these compared to or combined with conventional treatments; Uncertainty remains as to whether cannabis, purified cannabinoids, or synthetic cannabinoids are more effective.
As a result, although the use of cannabinoids in cancer patients is allowed, especially due to their analgesic and antiemetic effects, the data showing that cannabinoids have anti-cancer properties are increasing day by day in preclinical studies. Cannabinoids exert their effects by modulating signaling pathways that are crucial in controlling cell proliferation and survival. In many in vitro and in vivo experiments, cannabinoids have been shown to inhibit the proliferation of cancer cells, stimulate autophagy and apoptosis, and also have the potential to inhibit angiogenesis and metastasis.
- Cardiovascular Diseases
Heart diseases cause the death of millions of people in the world every year. Major cardiovascular ailments; coronary heart disease, cerebrovascular disease, high blood pressure, peripheral arterial diseases, rheumatic heart disease, congenital heart disease, and heart failure. ECS, and especially CB1 receptors, have important effects on heart function and blood circulation. According to experts, activation of CB1 receptors in the brain causes increased oxygen consumption of the heart and decreased blood flow through the coronary arteries.
Modulation of ECS functions shows that it may have a therapeutic effect on cardiovascular diseases. In the study where Russo brought together the cardiovascular risks of synthetic and natural cannabinoids; concluded to date that ultra-low dose of THC and therapeutic phytocannabinoids is cardioprotective, but high doses, often used recreationally, pose cardiovascular risks and hyperCB1 stimulation by potent full agonists is dangerous to the heart.
Researchers noted that the development of myocardial infarction, risk of an acute coronary syndrome, decreased angina and increased mortality may be associated with cannabis use, and the mechanisms for how cannabis causes these adverse cardiovascular effects are not fully understood.
However, according to Benowitz, the negative cardiovascular effects of smoking marijuana; oxidant damage can be counted as inflammation, endothelial dysfunction, induction of a prothrombotic state, and decreased oxygen-carrying capacity of red blood cells. These toxic effects can transform into plaque rupture, acute thrombosis, and/or vasoconstriction with decreased coronary blood flow, resulting in an increased risk of an acute coronary syndrome, cerebrovascular events, and sudden cardiac death.
- Diabetes Mellitus and Obesity
Diabetes is a serious disease in which insulin production is insufficient or the body responds insufficiently to insulin, resulting in high blood sugar, which affects multiple organs and systems. Insulin is a hormone needed to convert sugars, starches, and other foods into energy. There are two types of diabetes; In type 1, the pancreas does not produce enough insulin. In type 2, the body shows resistance to the existing insulin and insulin becomes ineffective. Most diabetic complications are associated with pathological changes in the vascular wall.
The most common microvascular complications of diabetes are; atherosclerosis that increases the risk of myocardial infarction, stroke, and peripheral artery disease. Diabetes complications have serious physical, emotional, and economic effects, and the biggest effects are kidney failure, non-traumatic lower-extremity amputation, and blindness. Some published research has shown an association between marijuana use and insulin levels. It is known that cannabinoid receptors are located in the pancreas and function in the regulation of glucose and insulin.
However, according to Alshaarawy and Anthony, active cannabis use is inversely associated with Diabetes mellitus and the available evidence does not support the possible protective effect of cannabis suggested in previous research. Researchers have linked the harms and benefits of cannabis use for diabetic patients and stated that the potential risks and benefits for diabetic patients are currently poorly explained. Di Marzo reported that CB1 receptor activation impairs plasma glucose clearance, while CB2 receptor activation increases glucose clearance.
Researchers have observed lower fasting insulin levels in cannabis users. Although cannabinoids appear to affect their relationship with diabetes in biochemical ways, serious research is needed to say whether this will lead to new treatments. Several hundred million people worldwide have diabetes. Obesity is one of the most important risk factors for insulin resistance. Bad eating habits cause diabetes to increase worldwide.
Tetrahydrocannabivarin is a neutral antagonist of CB1 receptors that antagonizes the psychoactive component THC. Pure THCV, but not as a CBD-containing extract, has been reported to induce hypophagia and weight loss in mice at doses as low as 3 mg/kg. Many in vitro and in vivo studies have been reported to confirm the role of the CB2 receptor and Diabetes mellitus in the treatment of obesity, hyperlipidemia, and Diabetes mellitus.
A recent study examined the potential role of CB2 receptor activation in the management of diabetes and its complications; It has been revealed that the decrease in the response to CB2 receptor activity is a sign of inflammation and oxidative stress, and the relationship between the activation of CB2 receptors and the decrease in proinflammatory cytokinesis and proapoptotic factors. These results show that THCV shows promise in the treatment of diabetes and obesity. Therefore, it is expected that medical cannabis can be part of the solution to obesity and diabetes problems and will be safer than rimonabant.
- HIV and AIDS
HIV originated in west-central Africa in the late 19th and early 20th centuries. HIV infection impairs the immune system, leaving the body vulnerable to diseases. AIDS, acquired immunodeficiency syndrome, caused by the HIV virus, is the stage in which the immune system is vulnerable to infections and cancers. Not all HIV-positive people develop AIDS. However, after AIDS occurs, there is a serious increase in mortality. However, definitive treatment for this disease has not yet been determined.
HIV/AIDS has a huge impact on society, both as a source of disease and discrimination. Patients with this disease state that they smoke cannabis to combat nausea, anorexia, stomach upset, illness, and anxiety associated with antiretroviral therapy. Researchers have reported that the use of cannabis, its active ingredient, or synthetic forms such as dronabinol, is beneficial in HIV/AIDS patients to increase appetite, promote weight gain and boost morale.
Dronabinol has been indicated in some countries for the treatment of AIDS-related anorexia. However, its positive effects in patients with HIV/AIDS have been found to be limited. Although combined antiretroviral therapy has been proven to increase immunity and survival in HIV, it has not been shown to provide significant benefit in neuropathic pain and therefore cannabinoid therapy may be an effective option as a pain reliever in HIV patients with pain.
Historically, cannabis has played an important role in alleviating many of the symptoms experienced by people who were HIV-infected prior to ART, and for various reasons it still continues to be used by many people with HIV during ART. Today, ΔTHC and CBD are the phytocannabinoids that have received the most attention due to their medicinal properties in HIV treatment. According to researchers, their therapeutic potential as immunomodulators remains intensely studied because they can suppress lymphocyte proliferation and inflammatory cytokine production. CB2 receptor activation has been determined in vitro to reduce CD4 T-cell infection and HIV replication with CXCR4tropic HIV.
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