CBD for Inflammation
Table of contents
What is Inflammation
Inflammation is the body’s first response to an event or irritant, which includes pathogens like viruses , bacteria or fungi, but it can also be due to a foreign object, radiation, chemicals or injury. Long-term inflammation can also be caused by disease, often have a name ending in “-itis.” (e.g., dermatitis, arthritis, bronchitis and cystitis).
Inflammation starts immediately, and is characterised by swelling, heat, the area turning red pain as well as a loss of mobility in certain instances. When inflammation occurs, a variety of chemicals and immune cells, called inflammatory mediators, are released.
- The hormones histamine and bradykinin
- Plasma proteins called prostaglandins
- Immune cells including leucocytes and cytokines
When the damaged cells release these hormones and proteins, it causes the blood vessels to leak fluid into the tissues, causing the swelling, heat and pain associated with an inflammatory response. These chemicals also cause irritation to the nerves, and cause pain signals to be sent to the brain, playing a protective function by alerting the person to the injury.
However, the inflammatory mediators have yet another function: They cause the small blood vessels in the tissue to become wider (dilate), allowing more blood to reach the injured tissue. This increase in blood flow allows for a higher volume of immune cells and oxygen to reach the injured tissue, aiding with the healing process.
Types of Inflammation
Depending on the cause of the inflammation, it can either be classified as acute (short-lived) or chronic (long-lasting). Acute inflammation lasts anything from hours to days, while chronic inflammation cans last as long as months and years. Chronic inflammation is often characterised by continuing, even after the first trigger is gone.
Causes of Acute inflammation
As mentioned, the most common causes of acute inflammation include:
- Pathogens (germs) like bacteria, viruses or fungi
- External injuries like scrapes or damage through foreign objects (for example a thorn in your finger)
- Effects of chemicals or radiation
Causes of Chronic inflammation
Chronic inflammation can originally be caused by the same causes as acute inflammation, and then turn chronic. Collectively known as chronic inflammatory diseases, these can last for years or even a lifetime. Their severity and level of activity varies, and include:
- Psoriasis – a chronic skin disease
- Arthritic conditions like rheumatoid and psoriatic arthritis as well as other painful conditions of the joints and musculoskeletal system
- Autoimmune diseases such as Crohn’s disease, Multiple Sclerosis, and fibromyalgia
- Chronic Inflammatory Pain Syndrome
- Alzheimer’s disease
Symptoms of Inflammation
Symptoms vary from person to person depending on the origin, type and duration. However, the most common symptoms may include any or a combination of:
- A swollen joint that may be warm to the touch
- Joint pain
- Joint stiffness
- A joint that doesn’t work as well as it should
- Often, you’ll have only a few of these symptoms
Inflammation may also cause flu-like symptoms including:
- Fatigue/loss of energy
- Loss of appetite
- Muscle stiffness
However, because Inflammation can cause disabilities that can interfere with daily life, it can also take its toll on mental health. Factors such as lowered self-esteem can cause feelings of anger, depression, anxiety, and frustration along with other symptoms that can include:
- Feeling fatigued, tired or wiped out
- Loss of appetite
- Trouble sleeping
- Feeling weak and lacking energy
Inflammation Medications and Treatments
Treatment for inflammation and inflammatory diseases may include a combination of medications, rest, exercise, and surgery to correct joint damage. An individual’s treatment plan will depend on several things, including your type of inflammation, age, overall health, and how severe the symptoms are. Generally, the goals of treatment are to correct, control, or slow down the disease process while also easing pain and inflammation.
A variety of drugs can ease pain, swelling and inflammation, while also preventing or slowing the progression of the inflammatory disease. Doctors often prescribe more than one and include medications like non-steroidal anti-inflammatory drugs (NSAIDs, such as aspirin, ibuprofen, or naproxen), corticosteroids (such as prednisone) and antimalarial medications (such as hydroxychloroquine).
Disease-modifying antirheumatic drugs (DMARDs) may also be prescribed and include azathioprine, cyclophosphamide, leflunomide, methotrexate, and sulfasalazine. Similarly, biologic drugs such as abatacept, adalimumab, certolizumab, etanercept, infliximab, golimumab, rituximab, and tocilizumab can also help reduce inflammatory diseases and symptoms.
In certain cases, non-drug medical procedures can also provide relief from inflammatory symptoms and diseases. These range from simple lifestyle changes and alternative therapies, to surgery in more severe cases. Recommended lifestyle changes include quitting smoking, limiting alcohol, maintaining a healthy weight, managing stress, regular physical activity and taking herbal supplements such as white willow bark, curcumin, green tea, or capsaicin. Vitamins and minerals like magnesium and vitamins B6, C, D, and E as well as omega-3 fatty acids also have some anti-inflammatory effects.
Many health care practitioners also recommend eating an anti-inflammatory diet. This diet recommends eating plenty of certain foods, and avoiding others. Foods to include are tomatoes, olive oil, leafy greens, fatty fish and fruits. Foods to avoid are refined carbohydrates, fried foods and transfers, sugary drinks, processed meats and margarine.
Alternative therapies in conjunction with more traditional treatments are also helpful. These can include acupuncture, biofeedback and physical therapy. In addition, relaxation techniques and stress management techniques, such as meditation, visual imagery, or deep breathing are also known to help.
For many the final option is surgery and include:
- Arthroscopy in which the doctor makes a few small cuts around the affected joint, and insert thin instruments to fix tears, repair damaged tissue, or take out bits of cartilage or bone
- Osteotomy where doctor a part of the bone is removed near a damaged joint
- Synovectomy where all or part of the lining of the joint (called the synovium) is removed if it’s inflamed or has grown too much
- Arthrodesis during which pins or plates are used to permanently fuse bones together.
- Joint replacement which a damaged joint is replaced with an artificial one made of metal, plastic, or ceramic
CBD for Inflammation
Cannabidiol (CBD) for inflammation is on elf the more researched topics and its anti-inflammatory properties are relatively well documented in the scientific literature. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, indicate that CBD has several mechanisms with which it exerts its anti-inflammatory and anti antioxidative properties.
Antioxidative and Anti-Inflammatory Properties of Cannabidiol
A recent 2020 review published in the journal Antioxidants, reviewed the data from several studies to ascertain the main biological properties and effects of CBD with a particular focus on its antioxidant, and anti-inflammatory properties.
Oxidative Stress in Inflammation
The result of an imbalance between oxidants and antioxidants is oxidative stress (referred to a redox imbalance), something that often accompanies inflammatory responses. The consequences of this redox imbalance are oxidative modifications of lipids, nucleic acids, and proteins that result in changes in the structure of the these molecules.
These modifications in turn, result in a disruption in their associated molecular interactions and signal transduction pathways. However, arguably the most important consequence is the important role these modifications play in the functioning of redox-sensitive transcription factors in the regulation of pathological conditions such as cancer, inflammatory diseases, and neurodegenerative diseases, characterized by redox imbalances and inflammation.
CBD for Oxidative Stress
After reviewing the relevant literature, the investigators concluded that CBD has the ability to directly reduce several key elements of oxidative stress responses.
The primary antioxidative mechanism of CBD is its ability to reduce oxidative conditions by preventing the formation of superoxide radicals. These are mainly generated by xanthine oxidase (XO) and NADPH oxidase (NOX1 and NOX4), reactive oxygen species (ROS) production and the of dihydrorodamine oxidation (DHR). CBD has been shown to reduce ROS production while also preventing DHR, that results in the protection of non-enzymatic antioxidants that prevents their oxidation. In fact, the data indicates that CBD exhibits far more (30–50%) antioxidant activity than α-tocopherol or vitamin C.
In addition, because CBD’s antioxidant activity begins at the level of protein transcription by activating the redox-sensitive transcription factor (responsible for the transcription of cytoprotective genes, including antioxidant genes), it has the ability to modify the redox balance by changing the level and activity of antioxidants.
For instance, CBD was found to increase the mRNA level of superoxide dismutase (SOD) and the enzymatic activity of Cu, Zn- and Mn-SOD, which are responsible for the metabolism of superoxide radicals. Moreover, CBD has been found to inhibit tryptophan degradation through the reduction of indoleamine-2,3-dioxygenase activity. This supports the action of antioxidant enzymes by preventing a reduction in the levels of microelements (e.g., Zn or Sn), which are necessary for the biological activity of some proteins, especially enzymes such as superoxide dismutase or glutathione peroxidase that results in a decrease in the development of pathological conditions.
This could potentially explain the recent findings that CBD treatments exhibit an unusual protective effect on lipids and proteins which participates in cell signaling pathways, against oxidative damage by modulating the level of oxidative stress.
CBD and Receptors
The effects of CBD on a variety of receptors may also account for its antioxidative and anti-inflammatory effects.
For instance, data indicates that CBD can also affect redox balance and inflammation through the modulation of mammalian transient receptor potential (TRP) channels, of which there are six subfamilies involved with different functions. For instance, a relationship has been suggested that there is a relationship between molecular signaling of vanilloid receptors (TRPV), especially TRPV1, and oxidative stress since ROS and lipid peroxidation products can regulate the physiological activity of TRPV1. CBD has been shown to activate TRPV1 as well as TRPV2, both directly or indirectly via an increase in anandamide (AEA) that results in the lowering of the level of oxidative stress.
Another receptor intricately involved with both inflammation and the immune system are GPR55 receptors, and are strongly expressed in the nervous and immune systems as well as in other tissues. CBD is a GPR55 antagonist that can modulate neuronal Ca2+ levels that can indirectly affect inflammation and redox balance via these molecules. However, while high expression of GPR55 reduces ROS production and low expression produces high levels of anti-inflammatory interleukins, an organism’s response to CBD depends on whether direct or indirect effects dominate.
Similarly, 5-HT1A receptors (a serotonin receptor) can reduce physiological and behavioral responses to restrictive stress as it can act as a membrane antioxidant by capturing ROS. Since CBD has direct affinity for the human 5-HT1A receptors, CBD can counteract oxidation of phospholipids and thus participate in the protection of biomembranes against oxidative modifications.
Finally, CBD is also an agonist of adenosine A2A receptors which like TRPV receptors, are G-protein coupled receptors. They are expressed in various cell types, and also regulate inflammatory processes, with adenosine and its agonists exhibiting anti-inflammatory activity. When adenosine is released, it reduces TNF-α levels acting as an immunosuppressant during inflammation as well as controlling neuroinflammatory diseases such as multiple sclerosis (MS). In addition, it has been found that A2A receptor activation can alleviate oxidative stress in mitochondria which suggests that CBD can prevent oxidative stress by activating A2A receptors.
CBD and Inflammation
A key element in the immune system’s response to combatting pathogens and repair tissue, is the overproduction of ROS that results in oxidative stress. Therefore, the metabolic modifications resulting from this ROS overproduction result in a variety of negative effects that potentially lead to the development or exacerbation of inflammatory responses. Based on the above, CBD shows promise for use as a pharmacotherapy in inflammation primarily via its antioxidant effects.
However, CBD also has direct anti-inflammatory properties via its interaction with the ECS. From clinical data, it is believed that the ECS, which includes G-protein coupled receptors and their associated endogenous lipid ligands, is potentially responsible for the therapeutic modulation of oxidative stress. Research has shown that CB2 activation leads to a decrease in ROS and TNF-α levels, which reduces oxidative stress and inflammation.
CBD has been shown to interact with the ECS through a variety of mechanisms and receptors which is suggestive of CBD having the potential to directly improve anti-inflammatory effects. In addition, clinical studies have confirmed that CBD reduces the levels of pro-inflammatory cytokines, inhibits T cell proliferation, induces T cell apoptosis and reduces migration and adhesion of immune cells. CBD’s anti-inflammatory activity has also been shown to be antagonized by both a selective CB2 antagonist and AEA, an endogenous CB2 receptor agonist.
Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation
In addition to the mechanisms outlined in the above review paper, a 2019 in vitro study published in a Special Issue of Roles and Functions of ROS and RNS in Cellular Physiology and Pathology, researchers investigated and evaluated the effect of CBD on the regulatory mechanisms associated CBD’s cytoprotective in addition to its anti-inflammatory properties.
It is well known that ultraviolet (UV) radiation is known to cause a redox imbalance and inflammation in keratinocytes, a primary type of cell found in the outermost layer of the skin. They postulated that, since CBD is a well-known anti-inflammatory and antioxidant compound, it should provide cytoprotection of cells from harmful factors such as ultraviolet (UV) radiation.
Spectrophotometric results on UV irradiated keratinocytes cultures indicated that CBD significantly enhanced the activity of antioxidant enzymes such as superoxide dismutase and thioredoxin reductase. Moreover, the researchers also found that CBD increasing the expression of Nrf2 activators and stimulating the transcription activity of Nrf2, a type of protein that protects against oxidative damage triggered by injury and inflammation.
Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action
In another review paper from 2020 published in another Special Issue Cannabidiol: New Vistas of Its Molecular Mechanisms, Biological Effects and Therapeutic Application, the investigators collected data to research CBD’s analgesic potential in the context of the molecular mechanisms described above.
The primary purpose of their investigation, was to make a detailed description of:
- The analgesic and anti-inflammatory effects of CBD in various models, including neuropathic pain, inflammatory pain, osteoarthritis and others
- The dose and route of the administration-dependent effect of CBD, on the reduction in pain, hyperalgesia or allodynia
- The production of pro and anti-inflammatory cytokines, were described depending on the disease model.
They concluded that CBD is a well-tolerated and safe natural compound exerting analgesic effects in both animal models of pain, as well as clinical studies. The data also indicated a positive influence of CBD in treatment for various diseases, and demonstrated to exert analgesic effects, diminishing hyperalgesia and mechanical/thermal allodynia through various mechanisms and routes of administration.
In addition, especially important is CBD’s prolonged anti-inflammatory effects. The researchers found that chronic CBD treatment allows for long-term therapeutic effects to be achieved, which may better influence the direct cause of the pain development, and therefore provide long-lasting analgesic effect, and do so without significant side effects or tolerance development.
Anecdotal Evidence on using CBD for inflammation
CBD is popular for use in inflammatory diseases, with many people reporting that they use it successfully for a variety of symptoms associated with inflammation and inflammatory diseases. These include symptom such as abdominal bloating, pain, joint inflammation and muscle tension as well as a reduction in migraines, eczema and stress.
CBD as a Complementary Treatment
CBD can be also be helpful as a complimentary therapy for inflammation patients in a variety of ways. As mentioned, many patients have co-existing conditions like depression, anxiety, sleep difficulties and muscle stiffness with CBD having the potential to help relieve many of these. For example, CBD can help relieve gastrointestinal issues like irritable bowel syndrome, diarrhea and nausea. Likewise, CBD can reduce symptoms associated with depression and anxiety while its calming properties can help mediate insomnia and other types of sleep difficulties via its calming properties and promoting REM sleep.
Inflammation and oxidative stress are intricately interconnected due to inflammation and oxidative stress “feeding off” each other. Traditionally, this has proven to be therapeutically challenging, however, CBD would seem to be a promising starting point for further drug development given its combination of anti-oxidant and anti-inflammatory actions on immune cells. Moreover, CBD can also act as a powerful ally when used as a complementary therapy. However, speak to your treating physician before using CBD as it is contraindicated with use with certain medications. They can also monitor dosage, symptom severity and other clinical parameters, helping ensure that your CBD treatment is both safe and effective.