cbd anti inflammatory

Cbd anti inflammatory

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Type of CBD

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This 2004 animal study found that CBD's observed anti-inflammatory effects could be attributed to this cannabinoid's stimulation of the TRPV1 receptor, one of the most essential TRP neuroreceptors. Most importantly, this study reported that the ability of CBD to reduce inflammatory pain was also mediated by TRPV1 activation.

Cbd anti inflammatory

Furthermore, hydrogenated CBD derivatives such as (+)-dihydrocannabidiol and (+)-tetrahydrocannabidiol have CB1 receptor affinity ( Table 2 ) and show anti-inflammatory effects on the peritoneal cells of C57BL/6 mice and a macrophage cell line. This behavior may suggest that the activation of pro-inflammatory mediators is not directly through the CB1 cannabinoid receptor [123]. Similarly, the (+)-8,9-dihydro-7-hydroxy-CBD derivative (HU-465), which has anti-inflammatory activity, especially at higher concentrations, binds to both CB1 and CB2 receptors, while its (−) enantiomer, (−)-8,9-dihydro-7-hydroxy-CBD (HU-446) has negligible affinity for both CB1 and CB2 receptors ( Table 2 ). However, both HU-465 and HU-446 have been found to exhibit anti-inflammatory activity by inhibiting the release of IL-17 in mouse encephalitogenic T cells (TMOG) [124].

PPARγ cooperates also with another transcription factor, Nrf2, which controls the expression of genes encoding cytoprotective proteins, particularly antioxidant proteins [28,88]. PPARγ may bind to specific elements in the promoter region of genes it regulates, including Nrf2, catalase (CAT), glutathione S-transferase (GST), heme-oxygenase-1 (HO-1), and manganese-dependent superoxide dismutase (Mn-SOD). In contrast, Nrf2 can regulate PPARγ expression by binding to the PPARγ promoter in the sequence of antioxidant response elements (ARE) that are located in the -784/-764 and -916 regions of the PPARγ promoter [89,90]. The reduction in PPARγ expression in Nrf2 knockout mice provides confirmation of this regulation [91].

This review summarizes the chemical and biological effects of CBD and its natural and synthetic derivatives. Particular attention was paid to the antioxidant and anti-inflammatory effects of CBD and its derivatives, bearing in mind the possibilities of using this phytocannabinoid to protect against oxidative stress and the consequences associated with oxidative modifications of proteins and lipids. Although CBD demonstrates safety and a good side effect profile in many clinical trials [4], all of the therapeutic options for CBD discussed in this review are limited in a concentration-dependent manner.

Important in CBD therapeutic applications is the lack of psychotropic effects. Furthermore, this phytocannabinoid is not teratogenic or mutagenic [133]. Until recently, CBD was thought to have only low toxicity to humans and other species [134], but recent studies indicate an increase in ALT and AST levels after CBD treatment, which disqualifies it as the drug of choice [135,136]. In addition, it has been found that CBD may interfere with the hepatic metabolism of some drugs by inactivating cytochrome P450 3A and P450 2C [137]. Such interactions should be considered when co-administering CBD with other drugs metabolized by above enzymes.

5.1. CB1/CB2 Receptors

Chemical structure of cannabidiol (CBD) [16].

Relatively recently, multidirectional biological effects have been demonstrated in various preclinical models, including the antioxidant and anti-inflammatory effects of cannabidiol [14,73]. In the context of the above data, CBD seems to be more preferred than other compounds from the phytocannabinoid group. Regardless of the beneficial pharmacological effects of CBD itself, if this compound is present in the Δ 9 -THC environment, the undesirable effects of 99-THC are reduced, which improves its safety profile [132].

Another natural phytocannabinoid is cannabimovone (1-[(1R, 2R, 3R, 4R)-3-(2,6-dihydroxy-4-pentylphenyl)-2-hydroxy-4-prop-1-en-2-ylcyclopentyl] ethanone), which has low affinity for the CB1 and CB2 receptors, but significant affinity for TRPV1 ( Table 2 ) [117].

3.8. 5-HT1A Receptor

Indirect antioxidant and anti-inflammatory effects of CBD (closed arrows indicate inhibition; opened arrows indicate activation.

Oxidative stress resulting from overproduction of ROS is a key element of the immune system’s response to combat pathogens and initiates tissue repair. However, metabolic modifications resulting from overproduction of ROS also have many negative aspects and lead to the development and/or exacerbation of many diseases. It is believed that the endocannabinoid system, which includes G-protein coupled receptors and their endogenous lipid ligands, may be responsible for the therapeutic modulation of oxidative stress in various diseases. In this context, the phytocannabinoid cannabidiol, which was identified several decades ago and may interact with the cannabinoid system, is a promising molecule for pharmacotherapy.