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Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that exists in the Cannabis sativa plant. CBD has been found to act on various receptors, including both cannabinoid and non-cannabinoid receptors. In addition, CBD has antioxidant effects that are independent of receptors. CBD has demonstrated modulatory effects at different organ systems, such as the central nervous system, immune system, and the gastrointestinal system. Due to its broad effects within the body and its safety profile, CBD has become a topic of therapeutic interest. This literature review summarizes previous research findings with regard to the effect of CBD on the gastrointestinal (GI) system, including its effects at the molecular, cellular, organ, and whole-body levels. Both pre-clinical animal studies and human clinical trials are reviewed. The results of the studies included in this literature review suggest that CBD has significant impact on intestinal permeability, the microbiome, immune cells and cytokines. As a result, CBD has been shown to have therapeutic potential for GI disorders such as inflammatory bowel disease (IBD). Furthermore, through interactions with the gut, CBD may also be helpful in the treatment of disorders outside the GI system, such as non-alcoholic liver disease, postmenopausal disorders, epilepsy, and multiple sclerosis. In the future, more mechanistic studies are warranted to elucidate the detailed mechanisms of action of CBD in the gut. In addition, more well-designed clinical trials are needed to explore the full therapeutic potential of CBD on and through the gut. [ABSTRACT FROM AUTHOR]

Retinal pigment epithelial (RPE) cells contribute to several clinical conditions resulting in retinal fibrotic scars. Myofibroblast trans -differentiation of RPE cells is a critical step in the process of retinal fibrosis. In this study, we investigated the effects of N-oleoyl dopamine (OLDA), a newer endocannabinoid with a structure distinct from classic endocannabinoids, on TGF-β2-induced myofibroblast trans -differentiation of porcine RPE cells. Using an in vitro collagen matrix contraction assay, OLDA was found to inhibit TGF-β2 induced contraction of collagen matrices by porcine RPE cells. This effect was concentration-dependent, with significant inhibition of contraction observed at 3 μM and 10 μM. OLDA did not affect the proliferation of porcine RPE cells. Immunocytochemistry showed that at 3 μM, OLDA decreased incorporation of α-SMA in the stress fibers of TGF-β2-treated RPE cells. In addition, western blot analysis showed that 3 μM OLDA significantly downregulated TGF-β2-induced α-SMA protein expression. Taken together these results demonstrate that OLDA inhibits TGF-β induced myofibroblast trans -differentiation of RPE cells. It has been established that classic endocannabinoid such as anandamide, by activating the CB1 cannabinoid receptor, promote fibrosis in multiple organ systems. In contrast, this study demonstrates that OLDA, an endocannabinoid with a chemical structure distinct from classic endocannabinoids, inhibits myofibroblast trans -differentiation, an important step in fibrosis. Unlike classic endocannabinoids, OLDA has weak affinity for the CB1 receptor. Instead, OLDA acts on non-classic cannabinoid receptors such as GPR119, GPR6, and TRPV1. Therefore, our study indicates that the newer endocannabinoid OLDA and its non-classic cannabinoid receptors could potentially be novel therapeutic targets for treating ocular diseases involving retinal fibrosis and fibrotic pathologies in other organ systems. • N-oleoyl dopamine (OLDA) is a newer endocannabinoid with a distinct structure. • Retinal pigment epithelium (RPE) converts to myofibroblast during retinal fibrosis. • OLDA inhibited myofibroblast trans -differentiation of RPE cells. • OLDA has the potential to be developed to a new treatment of retinal fibrosis. • The receptors for OLDA could be novel targets for treating fibrosis in general. [ABSTRACT FROM AUTHOR]

Highly variable patterns of seed production ('masting') have been hypothesized to be driven by internal dynamics of resource storage and depletion. This hypothesis predicts that if seed production is artificially reduced, then the availability of unused stored resources should result in subsequent enhancement of the seed crop. We tested this prediction in two oak species with contrasting patterns of annual seed production (highly variable and relatively constant) by means of controlled burns at various frequencies over a 17-year period. We found that controlled burns reduced acorn production by both species in the year of the burn. In the species with relatively constant productivity, acorn production returned to baseline levels in the year following a burn; however, in the species with highly variable productivity, acorn production significantly increased the year following a burn. These results support a key prediction of the stored resource hypothesis by means of a long-term experimental test in wild tree populations. Key words: masting, acorn production, resource allocation, fire, Quercus. Resume : On croit que la dynamique interne de l'emmagasinage et de l'epuisement des ressources serait responsable de la tres forte variation dans la production de graines (annee semenciere). Cette hypothese predit que si la production de graines est artificiellement reduite, la disponibilite des ressources inutilisees devrait se traduire par une augmentation subsequente de la production de graines. Nous avons verifie cette prediction chez deux especes de chene avec differents profils de production annuelle de graines, soit tres variable dans un cas et relativement constant dans l'autre cas, en effectuant des brulages diriges a differentes frequences sur une periode de 17 ans. Nous avons trouve que les brulages diriges ont reduit la production de glands chez les deux especes l'annee du brulage. Chez l'espece dont la productivite etait relativement constante, la production de glands est revenue au niveau de base l'annee qui a suivi un brulage. Par contre, chez l'espece dont la productivite etait tres variable, la production de glands a significativement augmente l'annee qui a suivi un brulage. Ces resultats supportent une prediction cle de l'hypothese de l'emmagasinage des ressources grace a un test experimental a long terme dans des populations naturelles d'arbres. [Traduit par la Redaction] Mots-cles: annee semenciere, production de glands, allocation des ressources, feu, Quercus., Introduction Many long-lived species of plants show highly variable patterns of seed production from year to year (Kelly and Sork 2002; Silvertown 1980). When intermittent episodes of intense reproduction are [...]