CBD and pain
Preliminary evidence suggests that CBD may be a safe and effective way to manage various types of pain. Although CBD has shown beneficial effects under experimental conditions, few human clinical trials have yet been conducted and its effectiveness in managing pain in humans is still not supported by evidence.
Two types of pain and potential effects of CBD
While pain can be described by its characteristics, such as sharp or dull, hot or cold, tingling, numbness, etc., for therapeutic purposes pain is usually divided into two categories according to its cause:
1. Inflammatory pain
Inflammation is the result of the immune system and is your body's initial response to irritation or damage to body tissues - for example, when the area around a scratch becomes red and swollen. The inflammatory process can occur in response to infection or physical damage (swelling, bruising, fractures) as well as metabolic, degenerative and autoimmune conditions. If you are suffering from an acute injury, such as an ankle sprain, inflammation is readily apparent. However, when inflammation occurs internally in chronic conditions such as irritable bowel syndrome, heart disease or diabetes, symptoms can go unnoticed and potentially lead to significant tissue damage.
There are two types of inflammatory pain:
A) Acute inflammatory pain
Acute inflammation is the first stage of inflammation. It comes on quickly and ideally should go away quickly once the tissue is healed. Inflammation lasting less than three weeks is considered acute. This type of inflammatory pain involves swelling, inflammation and the movement of white blood cells to the affected area. During this phase, pro-inflammatory molecules called cytokines are released that trigger a cascade of responses leading to swelling, redness and increased temperature in the injured area. These same cytokines also activate pain receptors that send pain signals to your brain.
B) Chronic inflammatory pain
This is how pain is referred to when the inflammation does not go away even after a few weeks. When this happens, the pain sensors often become hyper-reactive, leading to increased sensitivity to lower levels of pain - that is, the pain signal is triggered much earlier than it would normally be. Chronic inflammatory pain can result from autoimmune disorders, cardiovascular disease, type 2 diabetes, gastrointestinal disorders, and other diseases. Stopping chronic inflammation is an important step toward alleviating chronic pain and a major goal of pharmaceutical drug development. CBD has been shown to directly increase levels of anti-inflammatory cytokines and decrease levels of pro-inflammatory cytokines - thereby reducing inflammation.
2. Neuropathic pain
This type of pain occurs when peripheral nerves, i.e. nerves outside the spinal cord and brain, are damaged. Peripheral nerve damage can result in permanent impairment of nerve function even after the nerve has recovered from the original damage. Causes of nerve damage can include:
- Trauma or injury
- Exposure to neurotoxic substances
- Metabolic disorder (such as diabetes or cardiovascular disease)
- Autoimmune diseases (such as rheumatoid arthritis).
Like chronic inflammatory pain, neuropathic pain can cause hypersensitivity to pain signals. Although chronic inflammatory pain usually responds well to anti-inflammatory medications, this is not the case with neuropathic pain. Instead, opioid-type agents (Oxycontin, morphine), anticonvulsants, anesthetics, and antidepressants are often used to treat neuropathic pain. These drugs can have significant side effects that can be intolerable for some patients, including:
- Dizziness
- Sleepiness
- Impaired coordination
- Damaged vision
- Memory loss
- Impaired ability to speak
- Increased susceptibility to viral infections
CBD in the fight against neuropathic pain
The endocannabinoid system controls the transmission of neural pain at many different sites along the pain pathway.
A) Reduction of pain transmission
The control occurs in the sensory nerves responsible for transmitting the first pain signals from the damaged tissue and also in areas in the central nervous system that control the amount of pain signals that reach the brain. One of the ways CBD and other cannabinoids reduce pain transmission is by activating glycine receptors in the spinal cord - which has inhibitory effects on messages informing the system of pain. If fewer pain signals reach the brain, the patient experiences less pain.
B) Protection of nerve tissue from damage
CBD also provides nerve protective effects that can prevent or reduce nerve damage. This has been demonstrated in research examining the protective effects of CBD on chemotherapy-induced nerve damage.
C) Reduction of inflammation
Additionally, the anti-inflammatory effects of CBD can prevent inflammatory processes from causing nerve damage - again leading to reduced neuropathic pain.
D) Support of microglia in the spinal cord
CBD inhibits the activity of cells in the brain and spinal cord called microglia. These cells, derived from the immune system, are thought to protect and support nerve cells and are known to accumulate in neuropathic pain syndromes. By inhibiting microglia, CBD may prevent the escalation of neuropathic pain. Unlike some conventional painkillers, CBD does not cause the development of tolerance, a process in which the same dose becomes less effective over time, leading patients to gradually increase doses.
Pain and your brain - how pain is amplified by the central nervous system
When pain persists and becomes chronic, the interpretive mechanisms in the brain can deteriorate - leading to hypersensitivity, heightened pain perception and worsening of chronic pain symptoms. This process is referred to as maladaptive pathological change and can cause physical changes in the brain, as evidenced by neuroimaging studies (a method of structural and functional brain imaging) showing reduced connectivity between the areas of the brain and spinal cord where pain is processed. This basically means that the more pain you feel, the easier it is to feel pain again, i.e. the threshold is lowered, so small triggers can lead to incorrect reactions to pain.
Impaired nervous system communication reduces your body's ability to appropriately interpret and respond to pain, leading to increased activity in the inflammatory cascade. This shows up on lab tests in the form of increased levels of pro-inflammatory signaling molecules and decreased levels of pain-inhibiting molecules such as IL-10. These changes are most evident in neuropathic pain syndromes, but have also been found to occur in chronic inflammatory conditions. In these types of conditions, pain can persist even after inflammation is suppressed.
Pain and your emotional state: how anxiety and depression cause and trigger chronic pain
Pain, anxiety and depression are intricately linked and often occur together. While it is easy to see how chronic inflammatory or neuropathic pain can lead to anxiety and depression, the process can also go the other way. These negative emotional states can cause physiological changes in the brain and body that promote pain. This makes pain management much more complex because the emotional aspect needs to be considered as well.
Anxiety and pain: blowing out the flame
Chronic pain sufferers often fear their condition. Once anxiety kicks in, the stress response is activated, leading to increased levels of stress chemicals - particularly cortisol and pro-inflammatory cytokines. Studies show that these stress chemicals can cause the pain-processing areas of the brain and spinal cord to become hypersensitive to pain - a condition known as anxiety-induced hyperalgesia. This basically means that when we are stressed, we experience more inflammation and feel more pain.
Depression and pain: an endless cycle
Depression and chronic pain can be mutually reinforcing. Chronic pain can cause depression by inhibiting the secretion of dopamine, the neurotransmitter responsible for feelings of reward and achievement - for example, when you do well at school or work, or successfully complete a marathon. Conversely, depression, i.e. low levels of dopamine, has been found to suppress activity in certain areas of the brain that inhibit pain messages, leading to heightened pain perception. In simple terms, pain causes depression by lowering dopamine levels - and low dopamine levels cause pain by suppressing the areas of the brain responsible for pain control.
How CBD can help with anxiety and depression
There is promising evidence that CBD has benefits in the treatment of complex pain syndromes involving anxiety and depression. A large clinical study of patients with anxiety and sleep disorders found that within the first month of CBD supplementation, anxiety decreased and sleep quality improved significantly. In laboratory animal studies, CBD has been shown to reduce symptoms of depression. However, there is still much to learn about the complex cause and effect relationship between pain, anxiety and depression, and CBD may be very useful in this regard for some, but less so for others.
CBD and pain relief: benefits at all levels of pain response
CBD can work through mechanisms that address pain response at all levels of the peripheral and central nervous system. Through these effects, CBD may provide relief for acute and chronic inflammatory and neuropathic pain.
1. CBD at the site of injury
CBD has demonstrated potent anti-inflammatory effects that have been found in preclinical studies to inhibit pain and prevent further tissue destruction. In autoimmune disorders such as rheumatoid arthritis, type 1 diabetes and others, inflammation and associated tissue destruction occurs continuously and is one of the underlying causes of pain. The anti-inflammatory activity of CBD may play a key role in the treatment of pain in these cases and in degenerative metabolic and neurological diseases such as type 2 diabetes, atherosclerosis and Alzheimer's disease. The endocannabinoid system also plays an important role in maintaining balance in the gastrointestinal system. CBD may prove useful in the treatment of chronic gastrointestinal pain syndromes such as Crohn's disease, irritable bowel syndrome and ulcerative colitis.
2. CBD in the spinal cord on its way to the brain
CBD appears promising in early studies for its ability to influence the transmission of pain sensations at the spinal cord level. It interacts with receptors for glycine, a calming neurotransmitter that modulates pain transmission in the brain and spinal cord. This may suggest a potential role for CBD in the prevention or treatment of chronic pain conditions without causing the sedative effects typically found with other painkillers.
3. CBD in the brain
Endocannabinoid receptors (CB1 and CB2 receptors) work in the brain where pain perception is expressed. In particular, activation of CB2 receptors facilitates the release of dopamine, which suppresses pain. There is evidence that CBD works in areas of the brain where memories are stored to suppress harmful or downright scary anxiety-inducing memories. This could prevent the stress response to certain memories in conditions such as PTSD that contribute to the overall perception of pain.
CBD can relieve pain by increasing levels of serotonin - one of the body's calming neurotransmitters. There is evidence that serotonin may have anti-inflammatory and antioxidant effects that also help modulate pain. Drugs that increase serotonin levels, known as serotonin reuptake inhibitors (SSRIs), are often used to relieve depression and anxiety and are also frequently prescribed for the treatment of chronic pain [9].
SSRIs bring with them many side effects, which include:
- Blurred vision
- Disorders of the digestive system
- Insomnia
- Sexual dysfunction
- Gaining weight
Preliminary evidence also shows that CBD can affect inflammatory conditions by increasing the activity of adenosine, a neuromodulator in the brain that "suppresses" inflammation triggered by an overactive immune system.
4. CBD in the gastrointestinal tract
The endocannabinoid system plays an important role in maintaining balance in the gastrointestinal system. CBD may prove useful in the treatment of chronic gastrointestinal pain syndromes such as Crohn's disease, irritable bowel syndrome and ulcerative colitis.
What the studies show: CBD for specific pains
Human clinical trials are the gold standard for all medical therapies. However, most human research on cannabinoids has focused largely on preparations that contain higher levels of THC, often in a 1:1 ratio with CBD. However, CBD research is quickly catching up to this, where it is needed, in terms of uses and benefits in combating ailments such as pain and inflammation.
The following human clinical trials and promising animal studies show some of the proven benefits and promising potential of using CBD for specific ailments:
1. Chemotherapy-induced pain
In an animal study, it was found that CBD can prevent painful hypersensitivity of nerve receptors to temperature and pressure, a side effect of chemotherapy drugs. The study found that CBD relieved pain by binding directly to serotonin receptors in the brain.
2. Chronic pain induced by NSAIDs
NSAIDs are a class of common anti-inflammatory agents such as aspirin and ibuprofen. Many kidney transplant patients suffer from chronic pain due to the toxic effects of NSAIDs (which they must take after surgery) on the kidneys. In a small clinical trial, kidney transplant patients were given doses of 50 mg to 150 mg of CBD twice a day. Results showed partial to complete pain relief in most participants during the first 15 days of the three-week study.
3. Neuropathic pain
A small clinical study with patients suffering from neuropathic pain of different origins compared the effects of a sublingual THC spray, a CBD spray or a combination of the two for 12 weeks. Although the results showed that the THC and THC:CBD combination therapies were more effective in reducing pain than CBD alone, CBD produced fewer side effects such as drowsiness and dry mouth while providing moderate relief. The CBD used in the study was not a full-spectrum extract and therefore did not offer the synergistic benefits of the entourage effect - due to the presence of other components in cannabis (such as THC and other cannabinoids), the overall effects are amplified.
As a result, when using pure CBD isolate, higher doses than those used in this study may be needed to achieve comparable effects.
4.Children's muscle and joint pain
In clinical trials, children with painful congenital musculoskeletal disorders received either CBD oil, a 20:1 combination of CBD and THC, or a 6:1 combination of CBD and THC for 5 months. Results showed significant improvements in pain severity and reductions in pain frequency and duration in all 3 groups. In the 20:1 group, a questionnaire assessing overall quality of life, including pain levels, showed improved scores at an average CBD dose of 92 mg per day.
5. Fibromyalgia
Fibromyalgia, which is challenging to treat, involves chronic muscle and joint pain throughout the body, fatigue, sleep disturbances and cognitive impairment. In the clinical trial, participants were given one of three forms of medical cannabis, one of which contained a high CBD:THC ratio of nearly 20:1. Results showed that none of the cannabis varieties resulted in pain relief that was greater than placebo. A closer look at the study, however, raises some questions about the efficacy of its setting.
In this study, participants used cannabis with vaporisation in four treatment sessions at least two weeks apart. Because inhaled cannabinoids are rapidly absorbed but also rapidly eliminated from the bloodstream, the inhalation route yields high peak levels but lower overall bioavailability compared with other forms of administration. Therefore, could a different form of administration or more frequent administration, thereby increasing and maintaining blood and tissue levels of CBD, produce different outcomes for fibromyalgia patients? Further research may be needed to investigate this effect.
The best forms and dosage of CBD for pain relief
Dosage recommendations for CBD always vary widely. There are many factors to consider when determining the best dose, including:
- What condition is treated
- Severity of symptoms
- Individual reactions to CBD
- The form of CBD used (capsules, sprays, vaporizer, etc.)
- Presence of other medications
- Basic health status
- Weight and size of the person taking CBD
- Age and gender of the person taking CBD
In animal studies, doses range from 1 to 20 mg/kg body weight. In studies in seizure disorders in children, doses are reported to range from 0.5 to 300 mg/kg bw per day. This is therefore a very wide variance in doses. In order to determine the best dosage level for the patient's pain relief needs while avoiding unpleasant side effects, it is best to proceed with caution when dosing CBD, gradually increasing the dose over two or more weeks. The patient should keep a symptom diary to help monitor how he or she responds to a particular product or dose level.
1. Oral use of CBD
Forms for oral administration include CBD oils, capsules and edibles. CBD in food and beverages enters the system more slowly and stays in circulation longer than other forms. Oral use of CBD is often recommended as the primary method of use in the treatment of chronic pain, but it is poorly absorbed compared to other methods. To improve the bioavailability of CBD when taken orally, nanotechnology is used to convert CBD molecules with high fat solubility, which are difficult to absorb, into small nanoparticles that are more easily absorbed in the intestinal tract.
2. CBD vaporization
Fast-acting methods such as CBD vaporizing oils and vaporizing pens are useful for sudden or rapid onset of pain or flare-ups of chronic pain. However, vaporization can be counterproductive in some cases because it can irritate the lungs and increase inflammation in the body.
3. External uses of CBD
Opinions on CBD products with external uses vary. These products include ointments, creams and patches. Some experts say the best use of these products is for topical treatments for muscle or joint injuries, such as an ankle sprain or muscle strain. Others say CBD for external use, which is absorbed slowly into the bloodstream, can be used as a systemic boost. These experts suggest that CBD with external use may prove particularly effective for maintaining consistent blood levels of CBD in patients with chronic pain, especially those who cannot tolerate oral or other forms of CBD use due to digestive or other problems.
4. CBD suppositories
CBD suppositories are another option for patients for whom oral consumption is not recommended, such as patients with gastrointestinal conditions who may have difficulty absorbing oral CBD, or for the very young and elderly.
Summary: Using CBD for Pain
Pain is a complex process that involves finely coordinated communication between the body and the brain. Pain sensors are first activated in response to a trigger, such as tissue damage, and send messages that travel to the brain and spinal cord. Once the messages are in the brain, the pain signals are processed, making us feel what we think of as pain. From what we know about the mechanisms of pain and the role of the endocannabinoid system in pain management, CBD may play a significant role. In short, CBD acts on the endocannabinoid system, which functions primarily to maintain balance in the body and acts as one of the natural pain management systems. CBD acts at many levels within the pain processing processes, from the tissue level where pain is generated to the spinal cord and brain where pain is processed. Studies show that CBD can produce significant effects in alleviating pain for a wide range of syndromes. The dosage of CBD when dealing with pain is highly individualized. It is recommended to start with a low dose and slowly increase it to determine the optimal dose for specific needs. Although more research is needed to confirm the effects of CBD on different types of pain, the interim findings are very promising.
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