Cannabis sativa L. Bioactive Compounds and Their Protective Role in Oxidative Stress and Inflammation

Abstract

Cannabis (Cannabis sativa L.) plants from the family Cannabidaceae have been used since ancient times, to produce fibers, oil, and for medicinal purposes. Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) are the main pharmacologically active compounds of Cannabis sativa. These compounds have, for a long time, been under extensive investigation, and their potent antioxidant and inflammatory properties have been reported, although the detailed mechanisms of their actions have not been fully clarified. CB1 receptors are suggested to be responsible for the analgesic effect of THC, while CB2 receptors may account for its immunomodulatory properties. Unlike THC, CBD has a very low affinity for both CB1 and CB2 receptors, and behaves as their negative allosteric modulator. CBD activity, as a CB2 receptor inverse agonist, could be important for CBD anti-inflammatory properties. In this review, we discuss the chemical properties and bioavailability of THC and CBD, their main mechanisms of action, and their role in oxidative stress and inflammation.

Cannabinoids and Chronic Liver Diseases

“…Given that CB1R is highly expressed in the CNS, most of the popular effects exerted by THC include its psychotropic effects and impact on appetite stimulation [ 11 , 25 ]. THC also has anti-inflammatory properties by inhibiting the proinflammatory response and shifting the immune response toward an anti-inflammatory phenotype, inducing apoptosis, and suppressing cell proliferation, mainly through the activation of CB2R [ 26 ]. In addition to classical cannabinoid receptors, THC can also activate GPR55 and GPR18, isoforms of PPAR, as well as members of TRPV receptors [ 17 , 26 ].…”

“…Unlike THC, CBD is a non-psychoactive phytocannabinoid, and it possesses analgesic, neuroprotective, anticonvulsant, antiemetic, spasmolytic, and anti-inflammatory properties [ 11 , 26 ]. CBD has been proposed by some to act as a negative allosteric modulator of CB1R, and it has been shown to exert its anti-inflammatory properties through non-CBRs by inhibiting the activity of the NF-kappa B pathway, the activator protein-1 and nuclear factor of activated T-cell transcriptional activity, and leading to the suppression of proinflammatory cytokines (IL-2, TNF-α, INF-γ) and immune-cell activation and proliferation [ 26 , 27 , 28 ]. Moreover, CBD can induce the secretion of anti-inflammatory cytokines via the upregulation of STAT3 transcription factor, which governs the production of tumor growth factor beta (TGF-β), one of the main immunosuppressive cytokines [ 26 ].…”

“…CBD has been proposed by some to act as a negative allosteric modulator of CB1R, and it has been shown to exert its anti-inflammatory properties through non-CBRs by inhibiting the activity of the NF-kappa B pathway, the activator protein-1 and nuclear factor of activated T-cell transcriptional activity, and leading to the suppression of proinflammatory cytokines (IL-2, TNF-α, INF-γ) and immune-cell activation and proliferation [ 26 , 27 , 28 ]. Moreover, CBD can induce the secretion of anti-inflammatory cytokines via the upregulation of STAT3 transcription factor, which governs the production of tumor growth factor beta (TGF-β), one of the main immunosuppressive cytokines [ 26 ]. As for THC, CBD has also been found to modulate the activity of nonclassical cannabinoid receptors, including GPRs and TRP channels (namely TRPV1, TRPV2, and TRPA1, which are activated, and TRPM8, which is inhibited), as well as PPARs [ 25 ].…”

“…As for THC, CBD has also been found to modulate the activity of nonclassical cannabinoid receptors, including GPRs and TRP channels (namely TRPV1, TRPV2, and TRPA1, which are activated, and TRPM8, which is inhibited), as well as PPARs [ 25 ]. Both THC and CBD have also been found to exert antioxidant activity by scavenging free ROS and blocking ROS generation [ 26 ]. Finally, the cannabis plant contains other less abundant phytocannabinoids, including tetrahydrocannabivarin (THCV), delta-9-tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and tetrahydrocannabivarinic acid (THCVA), which have been found to exert diverse biological activities, similar to CBD ( Table 1 ) [ 25 ].…”

NMR Spectroscopy Applied to the Metabolic Analysis of Natural Extracts of Cannabis sativa

“…Indeed, the interest from the scientific community in the therapeutic potential of CBD oil is growing every day [ 18 ]. The reason is simple: it has already been used in various scientific studies for the treatment of numerous health problems, and is now recognized as one of the main elements of the so-called “therapeutic Cannabis ” [ 19 , 20 , 21 ]. Industrial hemp crops, with a low THC content, have always been exploited as food and as a source of textile fibers, but they disappeared in the 1970s due to their association with the type of plants rich in THC [ 22 ].…”