How CBD works to help reduce Chronic pain & inflammation
We’ve all experienced varying degrees of pain at some point in our lives. Pain is the body’s response to injury and, when this system work as it should, it is designed to alert us that something is wrong. But sometimes this pain response system can go haywire, causing pain to linger long after the injury or illness has resolved. Most people have to resort to a range of treatment options that often include a combination of pharmaceutical interventions and lifestyle changes.
For many people these treatment options become expensive, ineffective or even dangerous (especially in the case of opioid medications), causing them to seek out safer long-term options. It is therefore fair to say that many people first become interested in using cannabidiol (CBD) to help relieve symptoms of pain and inflammation.
Especially for people suffering from difficult-to-treat chronic pain that is the result of inflammation, neuropathic pain conditions, or secondary pain that results from an illness like cancer look to CBD for symptom relief. In fact, anecdotal evidence suggest that many people report that medical cannabis and CBD is often as effective as many pharmaceutical treatments for pain relief. However, CBD also comes with a much more favourable side-effect profile that can limit the need for medications that are often addictive or potentially harmful.
In this article we will explore the different types of pain, the interplay between pain and inflammation, how CBD works to help reduce pain and inflammation as well as how to use it for effective symptom relief.
Different types of Chronic pain
Pain can be typed into three main categories, based on the duration and origin thereof. For instance, nociceptive pain, or the pain experienced due to physical damage or potential damage to the body, tend to be short lived. In contrast, chronic pain often lasts for months or even years, despite attempts at diagnosing, treating and resolving it. Similarly, pain can be as a result of inflammation in response to direct trauma. Or, in the case of neuropathic pain, it can be as a result of pain signals being sent to the brain, completely unprompted and without any clear cause.
1. Chronic Neuropathic Pain
Chronic neuropathic pain is a condition that is usually caused by nerve damage, or a malfunction in pain signalling within the nervous system. The condition tends to get worse over time and can flare up at any time without an obvious pain-inducing event or factor.
Individuals suffering from chronic neuropathic pain can experience intermittent or constant symptoms ranging from shooting pains, burning sensations and throbbing, to tingling and numbness that lasts for at least 12 weeks or longer. The debilitating nature of chronic neuropathic pain can often leave the sufferer unable to perform day-to-day activities, impair sleep, and compromise in overall health, and mental well-being.
2. Chronic Inflammatory Pain
Inflammation is the body’s response to fighting off things like infections, injuries and toxins that intend to do harm. When the inflammatory response is triggered, a range of chemicals including antibodies, histamines, and prostaglandins. These chemicals trigger an immune system response that prompts the healing process to begin by increasing blood flow to the affected area, as well as the leaking of fluid into the tissues that causes swelling and sometimes pain.
Chronic inflammatory pain conditions develop when this response persists, leaving the body in a constant state of arousal. Over time, this has a negative impact on the body that can cause the development of other, more serious conditions like rheumatoid arthritis, ulcerative colitis, Crohn's disease and even cancer.
3. Chronic Secondary Pain
Chronic pain that results from an illness is often referred to as chronic secondary pain as it is considered secondary to an underlying disease such as cancer-related pain, neuropathic pain, post-traumatic, post-surgical, and/or musculoskeletal pain. For pain to be diagnosed as chronic, it needs to last at least 12 weeks and may be steady or intermittent, that comes and goes depending on a variety of factors and situations including disease symptomology and treatment protocols.
Chronic secondary pain is often difficult to treat as the treating physician faces unique difficulties in managing patients suffering from cancer-associated pain or pain associated with multiple sclerosis. This is because these types of chronic pain conditions are often inadequately treated with opiates, antidepressants and anticonvulsant drugs due to the inherent difficulties associated with multi-drug interventions (e.g., the potential for drug interactions, multiple side effects profiles and toxicity).
The Role of the Endocannabinoid System in Pain & Inflammation
The role of the endocannabinoid system (ECS) in pain control and symptom relief has been repeatedly demonstrated due to a certain level of independent control and mediation it exerts in the central nervous system and pain signalling system. Data from various animal studies and clinical trials have shown that the ECS and its primary ligands (a.k.a. endocannabinoids) play a role in pain and pain relief by mediating not only the CB1 and CB2 cannabinoid receptors but also other receptors involved with pain signalling.
The Endocannabinoid System, Endocannabinoids, Pain & Inflammation
Together with the cannabinoid receptors and metabolising enzymes, endocannabinoids comprise the ECS. The endocannabinoids act as retrograde signalling messengers as well as modulators of postsynaptic transmission that interact with other neurotransmitters. They have also been shown to be involved with neuronal, glial, and endothelial cell functioning, modulating neuronal activity (both inhibitory and excitatory), anti-inflammatory, and vasodilatory effects.
The two primary endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), have the ability to behave as analgesics in both acute and chronic inflammation and neuropathic pain conditions. These analgesic effects are mediated via cannabinoid receptors found in areas of the nervous system important for pain processing as well as in the immune cells responsible for regulating the neuro‐immune interactions that mediate inflammatory pain.
The Endocannabinoid System, Cannabinoid Receptors, Pain & Inflammation
For instance, CB1 receptors are found primarily in the CNS (although also to a lesser extent in certain peripheral tissues), including within the brain, but more significantly for our purposes, they are found at central and peripheral levels of pain signalling pathways. This means that, when presynaptic CB1 receptors or their primary afferent nerve fibres are activated in different regions of the brain, the release of neurotransmitters are inhibited that results in a decrease in the transmission of pain signals.
Similarly, CB2 receptors are primarily localised to cells of the immune system, tissues responsible for immune cell production and regulation as well as immune cells themselves implying a role in inflammatory responses and processes. More recently, CB2 receptors have also been found to be present in the brain, in the lumbar spinal cord and on sensory neurons suggesting they are also involved with pain signalling and processing.
The Endocannabinoid System, Peripheral Receptors, Pain & Inflammation
In addition to the cannabinoid receptors, several studies have also established that the role of the ECS in pain and pain relief may also involve peripheral receptors. The ECS has been shown to have the ability to parallel and interact at a variety of points with other major endogenous pain control systems, mediating a variety of receptor sites including the endogenous opioids (endorphin), vanilloid receptor 1 (TRPV1), as well as glycine receptors. In addition, the ECS and endocannabinoids also play a major role in the immune system and its functioning.
For instance, CB1 receptors found in the brain and mu opioid receptor type 1 (MOR1) co-localise in the same presynaptic nerve terminals, also signalling through common receptor-mediated G-protein pathways. This indicates a functional interaction between the ECS and opioid systems that implicates it in the mediation of the release of the endogenous opioids responsible for pain control.
Similarly, multiple studies testing the activity of endocannabinoids and the ECS on TRPV1 receptors showed that these mediate and activate TRPVl inter- and intracellular signalling. The reason why this is significant is that TRPV1 receptors have definitively been implicated in pain facilitation, transmission, and detection as well as pain-related behaviours. In addition, stimulation of TRPV1 receptors inhibits pain by either acting on the downstream neurons that mediate pain relief, or by desensitising the activity of other neurons involved in inducing pain.
α3 Glycine receptors (GlyRs) are involved in several physiological and pathological processes including neuromotor activity, antinociception and muscle relaxation mechanisms. Research has shown that endocannabinoids, especially AEA can regulate and modulate glycine production by binding to α3 GlyRs in such a way that it changes that receptor's response to a stimulus. In other words, because of the way that AEA interacts with α3 GlyRs, it significantly reduces the expression of chronic inflammatory and neuropathic pain via the suppression of α3 GlyRs receptors.
Moreover, there is increasing evidence showing that the ECS regulates the immune response at both the cellular and adaptive immune level. Research is showing that immune cells are not only able to be influenced by, but are also able to generate and secrete endocannabinoids themselves. This leads to changes in the way in which immune-cells behave and the production of other inflammatory responses that subsequently influence tissue inflammation, that results in anti-inflammatory and anti-oxidative effects.
When taken together, what all this means is that there is a delicate interplay between the ECS, and various pain signalling systems within the brain and body. The reason for this is that endocannabinoids and cannabinoid receptors are found at almost every level of the pain pathway - from peripheral sites such as peripheral nerves and immune cells, to primary sites including the spinal cord, and higher brain regions associated with the control of pain.
How CBD Works for Chronic Pain & Inflammation
Research has shown that the ECS can induce analgesia in preclinical models of both acute and chronic pain conditions. This is why so much work has been done to examine the role of ECS in pain processing and the potential of targeting it for pain control, and also why cannabinoid based medicines like CBD oil is so effective at managing pain.
As mentioned, endocannabinoids have the ability to suppress behavioural responses to painful stimuli as well as suppress pain processing through activation of cannabinoid CB1 and CB2 receptor subtypes. Think of it endocannabinoids as being similar to a type of synaptic “circuit breaker” that regulates a variety of physiological and pathological conditions including pain and inflammation.
Plant cannabinoids like CBD share this ability to regulate, modulate and control pain and inflammation because they share the same molecular targets with endocannabinoids. Researchers have identified several ways in which CBD targets a variety of receptor sites and systems, potentially explaining its powerful analgesic properties. For instance:
CBD’s Effects on the Endocannabinoid System (ECS)
We’ve already mentioned that peripheral cannabinoid receptors play an important role in the body’s ability to inhibit and control pain. CBD has been shown to suppress pain processing by activating the CB1 receptors that suppress pain signals. Similarly, CBD can also mediate the CB2 receptors that are responsible for stimulating endogenous opioid receptors.
Research has also shown that an imbalance of endocannabinoids, in particular AEA, can cause pain signals to increase. CBD has the ability to restore the balance of the endocannabinoids thought to play a role in blocking pain signals, in turn, reducing pain signals.
CBD’s Effects on Glycine Receptors, Inflammation & Oxidative Stress
Glycine receptors (GlyRs) have long been known to inhibit the neurotransmission of pain signals and targeting them as a therapeutic site for peripheral pain relief. This is because α3 GlyRs in particular are concentrated into regions of the spinal cord where pain receptors converge and stop. In addition, scientists have now also shown that inflammatory mediators inhibits α3 GlyRs that causes a heightened sensitivity to chronic inflammatory pain. CBD has been shown to suppress α3 GlyRs receptors that significantly reduces chronic inflammatory and neuropathic pain processing and perception.
Similarly, inflammation and oxidative stress are intimately involved in the genesis of a variety of chronic pain conditions. Prostaglandins are a type of lipid that are responsible for both sustaining homeostatic functions within the body and are also released every time the body is injured or under attack. This is because prostaglandins mediate and control processes such as inflammation, blood flow and the formation of blood clots at the injury site, as well as throughout the rest of the body. For prostaglandins to be synthesised, an enzyme called cyclooxygenase (COX) is needed, and these COX enzymes is also what is blocked by anti-inflammatory drugs (NSAIDs) like Ibuprofen and Naproxen.
CBD has been shown to decrease the activity of the COX enzyme, causing the inhibition of the biosynthesis and release of prostaglandins in a similar way to NSAIDs. Researchers have also shown that CBD exerts an immunosuppressive effect on the cells that play a role in inflammation, inhibiting and fighting inflammation and its associated oxidative stress. Scientists hypothesise that it is because of these multi-receptor and multi-site interactions of CBD that serves as the mechanisms that account for its ability to reduce the body’s inflammatory response as well as any associated pain.
Other ways CBD can help with pain & inflammation
CBD can also help people suffering from chronic neuropathic pain, inflammation or secondary pain in more indirect ways. Many people suffering from chronic pain conditions and inflammation suffer from comorbid conditions such as depression, anxiety, sleep difficulties and cognitive challenges such as brain fog and mental fatigue.
In addition to its primary analgesic and anti-inflammatory properties, CBD can also be used as an effective complimentary therapy to help reduce many of the comorbid symptoms that accompany chronic pain and inflammation. CBD has repeatedly been shown to reduce feelings of depression and anxiety. Similarly, CBD has the ability to mediate sleep difficulties by promoting REM sleep.
However, the most profound way in which CBD can benefit patients suffering from chronic pain and inflammation is to help reduce the amount of pain medications they need while also mediating certain side effects. Especially in the case of opioids, many pain patients become dependent on them, with the addiction often causing more discomfort than the original pain condition itself. So, in addition to reducing the amount of pain medications taken, CBD can simultaneously also aid with recovery from opioid addiction. One study in particular showed that the anxiolytic properties of CBD, coupled with its minimal adverse side effects, make it a viable treatment protocol for a variety of symptoms associated with opioid addiction.