The Wonders of Cannabidiol

Since CBD is currently rising in popularity, it is essential that people know why and how it works.

CBD and Oxidative Stress

CBD has been targeted as a therapeutic tool in man's battle against illness. Oxidative stress and the resulting inflammation have been linked to many human conditions that produce illness, hence the emphasis upon anti-oxidants in the diet. CBD has been shown to moderate both oxidation and inflammation.

Our body's immune system uses oxidative stress as a weapon to combat invading pathogens and to initiate tissue repair. Reactive molecules of oxygen are generated when they are given an extra electrical charge. These molecules attack invading organisms and stimulate the body to repair the damage that is inflicted upon tissue. When excessive or unresolved, these reactive oxygen molecules can also create damage to healthy organs and tissue in the body.

The complexity of this relationship has made the creation of a therapeutic tool difficult. The recent discovery of the endocannabinoid system and its involvement in oxidative stress has made it an area to be explored to combat autoimmune disease, as well as other disease states that have been linked to the immune system.

Microglia

Microglia are the primary immune cells of the central nervous system and are similar to peripheral macrophages. They act as the major inflammatory cell type in the brain and respond to pathogens and injury by becoming 'activated' - a process whereby they rapidly change their form and function, proliferate and migrate to the site of infection/injury, where they phagocytize and destroy pathogens, in addition to removing damaged cells.

As part of their response, microglia secrete cytokines and chemokines, as well as prostaglandins, nitric oxide and reactive oxygen species (ROS), all of which help to elevate and direct the immune response. Additionally, they are instrumental in the final resolution of the inflammatory response through the production of anti-inflammatory cytokines, such as Il-10.

While seeking out and destroying pathogens is an important and protective role, microglia have also been extensively studied for their harmful roles in neurodegenerative diseases such as Alzheimer's and Parkinson's or brain injuries such as ischemic and traumatic brain damage.

Neuropathic Pain and Cannabinoids

Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies; however, cannabinoids, drugs that share the same target as Δ9-tetrahydrocannabinol (Δ⁹-THC) have the potential to address this unmet need.

Neuropathic pain associated with nerve injury, diabetes, chemotherapeutic treatment, human immunodeficiency virus (HIV), multiple sclerosis and herpes zoster (shingles) have all been investigated as conditions amenable to treatment by Δ⁹-THC and cannabidiol (CBD). In animals, cannabinoids attenuate the neuropathic pain produced by traumatic nerve injury, disease and toxic insults. Effects of mixed cannabinoid CB1/CB2 agonists, CB2-selective agonists and modulators of the endocannabinoid system (i.e., inhibitors of its transport or degradation) have also been investigated in animal models and show promise for treatment of humans.

Effects of genetic disruption of cannabinoid receptors or enzymes controlling endocannabinoid degradation on neuropathic pain have been tested. In humans, effects of smoked marijuana, synthetic Δ⁹-THC analogs (e.g., Marinol) and medicinal Cannabis preparations containing both Δ₉-THC and CBD (e.g., Sativex) in reducing neuropathic pain states have been successful. Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment.

Neuroinflammation, Psychiatric Disorders and CBD

The etiology of psychiatric disorders such as depression and schizophrenia remains unclear while, in many aspects, the neuropathology of these disorders has recently been reported to be closely associated with neuroinflammation. Microglia, which are the major players of innate immunity in the central nervous system, respond rapidly to even minor pathological changes in the brain and may contribute directly to the neuroinflammation by producing various proinflammatory cytokines and free radicals.

Researchers have recently shown the inhibitory effects of some antidepressants and antipsychotics upon the release of inflammatory cytokines and free radicals from activated microglia, both of which have recently been known to cause the synaptic pathology, a decrease in neurogenesis and white matter abnormalities found in the brains of patients with psychiatric disorders. Microglial activation may not be the primary cause of psychiatric disorders, but it may be closely related to the pathology of the acute stage of psychiatric disorders. The neuroinflammation hypothesis of psychiatric disorders may shed new light upon the treatment potential of CBD regarding depression and schizophrenia.

Cannabinoids and Metabolic Disorders

Oxidative stress and inflammation play critical roles in the development of diabetes and its complications. Recent studies provide compelling evidence that the newly discovered endocannabinoid system may significantly influence ROS production, inflammation and subsequent tissue injury, in addition to its well-known metabolic effects and functions.

The possible modulation of the activity of this system holds tremendous therapeutic potential in the treatment of obesity and metabolic syndrome, in addition to diabetes and diabetic complications. Research focusing upon the role of the endocannabinoid system in primary diabetes and its impact on various diabetic complications (such as diabetic cardiovascular dysfunction, nephropathy, retinopathy and neuropathy) has been promising.

The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as CBD and Δ⁹-tetrahydrocannabivarin (THCV or THV) - which are devoid of psychotropic effects, yet possess potent anti-inflammatory and/or antioxidant properties for use in the treatment of diabetes and diabetic complications - has been explored and has been successful in animal models.

CBD does seem to be a wonderful starting point for further drug development, based not only upon its antioxidant properties, but also its anti-inflammatory actions on immune cells, such as macrophages and microglia. CBD also has the advantage of not having psychotropic side effects. Studies on models of human diseases support the idea that CBD attenuates inflammation far beyond its antioxidant properties, for example, by targeting inflammation-related intracellular signaling events that activate the inflammatory response. However, the details on how CBD targets inflammatory signaling remain to be defined.

The therapeutic utility of CBD is a relatively new area of investigation that portends future discoveries on the interplay between inflammation and oxidative stress, a relationship that underlies tissue and organ damage in many human diseases.