Cannabidiol improves metabolic dysfunction in middle-aged diabetic rats submitted to a chronic cerebral hypoperfusion

Zorzenon, Maria Rosa Trentin; Santiago, Amanda Nunes; Mori, Marco; Piovan, Silvano; Jansen, Cler Antônia; Padilha, Maria Eduarda Perina; Ciotta, Simone Rocha; Mathias, Paulo Cézar de Freitas; Guimarães, Francisco Silveira; Oliveira, Rúbia Maria Weffort de; Milani, Paula Gimenez; Mareze-Costa, Cecília Edna

doi:10.1016/j.cbi.2019.108819

Cited by 13 publications

(7 citation statements)

References 37 publications

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“…In this regard, cannabinoids such as HU-210 have been shown to attenuate neuronal damage and oxidative stress in diabetic mice and hyperglycemic pheochromocytoma PC12 cells through receptor independent mechanisms (Dagon et al, 2007). More recently, cannabidiol was shown to improve metabolic dysfunction in middle-aged streptozotocin-induce diabetes in rats submitted to chronic cerebral hypoperfusion, also probably involving antioxidant mechanisms (Zorzenon et al, 2019). To our knowledge, this study is the first to compare different cannabinoid agents in the context of hyperglycemia-induced injury in hippocampal neurons, thus providing novel and promising insight into the efficacy of these agents in reducing the toxic events underlying hyperglycemia, although the mechanisms involved in this protection require detailed characterization.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid-profiled agents improve cell survival via reduction of oxidative stress and inflammation, and Nrf2 activation in a toxic model combining hyperglycemia+Aβ1-42 peptide in rat hippocampal neurons

Elmazoğlu

Rangel-López

Medina-Campos

et al. 2020

Neurochemistry International

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Section: Discussionmentioning

confidence: 99%

Cannabinoid-profiled agents improve cell survival via reduction of oxidative stress and inflammation, and Nrf2 activation in a toxic model combining hyperglycemia+Aβ1-42 peptide in rat hippocampal neurons

Elmazoğlu

Rangel-López

Medina-Campos

et al. 2020

Neurochemistry International

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“…While a role of the endocannabinoid system in the regulation of glucose and blood lipids has been described [ 17 ], and CBD is thought to inhibit the actions of CBD receptors [ 20 , 21 ], data supporting a beneficial influence of CBD are mixed [ 16 ]. For example, in a variety of rat models, including high-fat diet and cerebral hypoperfusion, administration of CBD has been reported to both increase [ 52 ] and decrease [ 53 ] fasting insulin. In adult humans with type 2 diabetes, short-term (13-weeks) CBD administration (100 mg twice daily) had no effect on insulin [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function

et al. 2022

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Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ³ 25 kg/m2) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different CBD formulations were ingested (one per visit). On two additional occasions, CBD or placebo was ingested following a meal. CBD servings were standardized to 30 mg. Considerable pharmacokinetic variability existed between formulations; this pharmacokinetic variability transferred to several of the metabolites. CBD did not influence food induced thermogenesis but did favorably modify early insulin and triglyceride responses. Food appreciably altered the pharmacokinetics of CBD. Finally, CBD did not evoke physiologically relevant changes in markers of liver function. Collectively, these data suggest that consumers should be aware of the appreciable pharmacokinetic differences between commercial CBD formulations, CBD is unlikely to influence the caloric cost of eating but may prove to be of some benefit to initial metabolic responses, consuming CBD with food alters the dynamics of CBD metabolism and increases systemic availability, and low-dose CBD probably does not represent a risk to normal liver function.

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“…CBD was reported to reduce hyperphagia induced by 5-HT1A or CB 1 R agonists in animals [ 23 ]. Other similarities of EPM301 effects on DIO such as restoring liver function, lipid and glucose homeostasis, and hyperleptinemia are also common with CB 1 R negative allosteric modulators (e.g., CBD) or CB 1 R global or peripherally restricted antagonists (rimonabant or JD5037, respectively) [ 12 , 45 , 46 , 47 ]. These comparisons may explain the rationale to examine EPM301’s activity on CB 1 R as well.…”

Section: Discussionmentioning

confidence: 99%

The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity

Ben-Cnaan

Permyakova

Azar

et al. 2022

IJMS

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Obesity is a global medical problem; its common form is known as diet-induced obesity (DIO); however, there are several rare genetic disorders, such as Prader–Willi syndrome (PWS), that are also associated with obesity (genetic-induced obesity, GIO). The currently available therapeutics for treating DIO and GIO are very limited, and they result in only a partial improvement. Cannabidiolic acid (CBDA), a constituent of Cannabis sativa, gradually decarboxylates to cannabidiol (CBD). Whereas the anti-obesity properties of CBD have been reasonably identified, our knowledge of the pharmacology of CBDA is more limited due to its instability. To stabilize CBDA, a new derivative, CBDA-O-methyl ester (HU-580, EPM301), was synthesized. The therapeutic potential of EPM301 in appetite reduction, weight loss, and metabolic improvements in DIO and GIO was tested in vivo. EPM301 (40 mg/kg/d, i.p.) successfully resulted in weight loss, increased ambulation, as well as improved glycemic and lipid profiles in DIO mice. Additionally, EPM301 ameliorated DIO-induced hepatic dysfunction and steatosis. Importantly, EPM301 (20 and 40 mg/kg/d, i.p.) effectively reduced body weight and hyperphagia in a high-fat diet-fed Magel2null mouse model for PWS. In addition, when given to standard-diet-fed Magel2null mice as a preventive treatment, EPM301 completely inhibited weight gain and adiposity. Lastly, EPM301 increased the oxidation of different nutrients in each strain. All together, EPM301 ameliorated obesity and its metabolic abnormalities in both DIO and GIO. These results support the idea to further promote this synthetic CBDA derivative toward clinical evaluation in humans.

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Cannabidiol improves metabolic dysfunction in middle-aged diabetic rats submitted to a chronic cerebral hypoperfusion

Cited by 13 publications

References 37 publications

Cannabinoid-profiled agents improve cell survival via reduction of oxidative stress and inflammation, and Nrf2 activation in a toxic model combining hyperglycemia+Aβ1-42 peptide in rat hippocampal neurons

Cannabinoid-profiled agents improve cell survival via reduction of oxidative stress and inflammation, and Nrf2 activation in a toxic model combining hyperglycemia+Aβ1-42 peptide in rat hippocampal neurons

Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function

The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity

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