Cannabidiol (CBD) has pharmacological effects, including anti-inflammatory and antioxidant properties. It is an active compounds found in Cannabis sativa L. CBD is one of the main pharmacologically active phytocannabinoids (cannabinoids from the plant). It is non-psychoactive, meaning not producing an effect (such as changes in perception or behavior) on the mind or mental processes.
CBD as Antioxidant and Anti-inflammatory Agent
Atalay et al., 2019 reviewed the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD. CBD potential antioxidant properties because of its free cationic radicals exhibit several resonance structures in which unpaired electrons are distributed mainly on ether and alkyl moieties, as well as on the benzene ring. CBD antioxidant activity showed that it can regulate the state of redox directly by affecting the components of the redox system and indirectly by interacting with other molecular targets associated with redox system components.
Like other antioxidants, CBD interrupts free redical chain reactions, capturinfg free radicals or transforming them into less active forms. CBD reduces oxidative conditions by preventing the formation of superoxide radicals. It also promoted a reduction in NO levels in the liver of doxorubicin-treated mice and in the paw tissue of rats in a chronic inflammation model. CBD reduces reactive oxygen species (ROS) production and decreases beta amyloid formations in the neurons by reducing the concentration of transition metal ions. By lowering ROS level, CBD also protects non-enzymatic antioxidants, preventing their oxidations.
CBD in Cardiovascular Disease Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. Jadon et al., 2917 reported that a single dose of CBD reduces resting blood pressure and the blood pressure response to stress, particularly cold stress, and especially in the post-test periods. This may reflect the anxiolytic and analgesic effects of CBD, as well as any potential direct cardiovascular effects. CBD also affected cardiac parameters but without affecting cardiac output.
The vascular effects of cannabidiol were not affected by endothelial denudation, nitric oxide synthase inhibition, pertussis toxin, cannabinoid CB1 or cannabinoid CB2 receptor antagonism, or capsaicin pre-treatment. A study from O'Sullivan et al., 2009 showed that cannabidiol binds to and activates PPARgamma (Peroxisome proliferator-activated receptor gamma), member in the nuclear receptor superfamily which mediates part of the regulatory effects of dietary fatty acids on gene expression. As PPARgamma also coordinates adipocyte differentiation, it is an important component in storing the excess nutritional energy as fat.
CBD in Lungs
In lungs, CBD could play a role in enabling improvements in lung function, healthier oxygen levels, and repair of structural damage to the lungs. Salles et al., 2020 reported that apelin levels decrease with acute respiratory distress syndrome (ARDS); CBD appeared to aid in normalizing apelin levels in addition to improving lung function in laboratory models of ARDS. Apelin is a peptide with significant role in the central and peripheral regulation of immunity, CNS (Central Nervous System), metabolic and cardiovascular system. CBD treatment was able to reverse the symptoms of ARDS towards a normal level.
CBD in Cancer
In cancers, the redox balance is altered so that increased ROS production favors tumor progression and expansion while evading cell death. ROS damage DNA by oxidizing guanine and forming 8-hydroxyguanine and 8-nitroguanine. This could lead to deletions/insertions, mutations in base pairing, and strand breaks followed by mutagenic repair. Genome instability plays a key role in tumor progression through the accumulation of mutations that promote uncontrolled growth and evade cell death. CBD, alone or with other agents, has been shown to successfully induce cell death, inhibit cell migration and invasion in vitro, decrease tumor size, vascularization, growth, and weight, and increase survival and induce tumor regression in vivo. Co-treatment of CBD and antioxidants, including N-acetyl cysteine (NAC) and α-tocopherol (i.e., vitamin E), attenuated CBD’s killing effects. CBD exerts its anti-proliferative effects on breast cancer cells through a variety of mechanisms, including apoptosis, autophagy, and cell cycle arrest. CBD has also been shown to inhibit migration, invasion, and metastasis in aggressive breast cancer in vivo and in vitro. Primary tumor size has been shown to decrease along with the number of lung metastatic foci, volume, and vascularization in CBD-treated mice. CBD induced anti-proliferative effects and apoptosis-mediated cell death (via the intrinsic pathway) in prostate cancer cells.
CBD in GI
The activation of cannabinoid receptors in the gut, which does not only suppresses many of the IBD (Inflammatory Bowel Diseases)-related symptoms, such as diarrhea and visceral hypersensitivity, but also inhibits the inflammatory reaction. All components of the ECS, Endocannabinoid System, (CB1 and CB2 receptors, the endocannabinoids AEA and 2-AG, and proteins responsible for their synthesis and degradation) are widely distributed in the GI tract, and there is plenty of evidence that their expression is substantially altered during inflammation. There is a large body of evidence that cannabinoids exert immunomodulatory, mainly immunosuppressive effect. Both synthetic CB receptor agonists and endocannabinoids were shown to impair cellular and humoral immunity by reducing inflammatory cell recruitment, inducing T cell apoptosis and suppressing the production of numerous pro-inflammatory cytokines and chemokines.
CBD in RASF (rheumatoid arthritis synovial fibroblasts)
A study by Lowin et al., 2020 reported that CBD decreases cell viability, proliferation, and cytokine production but increases intracellular calcium and PoPo3 levels of RASF and all effects were enhanced by TNF pre-stimulation.
CBD binds to several receptor. CBD increases intracellular calcium levels, reduces cell viability and IL-6/IL-8/MMP-3 production of RASF. CBD possesses anti-arthritic activity and might ameliorate arthritis via targeting synovial fibroblasts under inflammatory conditions.
CBD in COVID-19
CBD inhibits SARS-CoV-2 replication and promotes the host innate immune response. It acts after cellular infection, inhibiting viral gene expression and up-regulates its antiviral signaling pathway. Further studies are needed in adding Ivermectin with CBD, as Ivermectin inhibits the viral docking to host receptors and also Ivermectin has anti-inflammatory effect.
This world need a balm of Gilead, a hope that heals. Natural remedies and cheap parasitic drug as Ivermectin, have given hopes in dealing with certain diseases. Perhaps the practise of risky drugs such as COVID-19 vaccines need to be ruled out, as we do not know the long term impact of those drugs.