Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

Abstract

In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

“…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.…”

“…It has been shown that CBD can also affect redox balance and inflammation by modulating mammalian transient receptor potential (TRP) channels [72,73]. CBD activates vanilloid receptors (TRPV), directly or indirectly, by increasing the level of endogenous AEA, which is one of the endogenous TRPV1 agonists [64].…”

Nursing Students’ Knowledge and Attitudes Regarding Medical Marijuana: A Descriptive Cross-Sectional Study

“…Cannabinoids are constituents of cannabis, of which tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most studied so far [4]. While THC, due to its psychoactive properties, has given marijuana a bad name by encouraging its consumption for recreational purposes, CBD lacks such effects [5]. However both cannabinoids are currently commercialized as medicinal products (ex.…”

CBD Reverts the Mesenchymal Invasive Phenotype of Breast Cancer Cells Induced by the Inflammatory Cytokine IL-1β

“…inactivation by CBD, a crucial point for crosstalk in the IL-1β-and CBD-induced pathways, 6D cells could undergo reversion to an epithelial phenotype. The acidic precursor of CBD (cannabidiolic acid, CBDA) has been able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2), highlighting the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms [27]. Here, we demonstrated this association, for the first time, between CBD and the inflammatory IL-1β/IL-1R/β-catenin pathway through CB1 activation.…”