scholarly journals Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 71 ◽  
Author(s):  
Viviana di Giacomo ◽  
Annalisa Chiavaroli ◽  
Giustino Orlando ◽  
Amelia Cataldi ◽  
Monica Rapino ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Gene Expressions ◽  
Pomc Gene ◽  
Amide Hydrolase ◽  
Isolated Tissues ◽  
Antioxidant Effects ◽  
Da Release

Background: Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite although there are no studies elucidating their role in the hypothalamic appetite-regulating network. Consequently, the aim of the present research is to investigate the role of CBD and CBG in regulating hypothalamic neuromodulators. Comparative evaluations between oxidative stress and food intake-modulating mediators were also performed. Methods: Rat hypothalamic Hypo-E22 cells and isolated tissues were exposed to either CBD or CBG, and the gene expressions of neuropeptide (NP)Y, pro-opiomelanocortin (POMC) and fatty acid amide hydrolase were assessed. In parallel, the influence of CBD on the synthesis and release of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) was evaluated. The 3-hydroxykinurenine/kinurenic acid (3-HK/KA) ratio was also determined. Results: Both CBD and CBG inhibited NPY and POMC gene expression and decreased the 3-HK/KA ratio in the hypothalamus. The same compounds also reduced hypothalamic NE synthesis and DA release, whereas the sole CBD inhibited 5-HT synthesis. Conclusion: The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways.

scholarly journals Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

2021 ◽  
Vol 22 (3) ◽  
pp. 1047
Author(s):  
Dorsa Rafiei ◽  
Nathan J. Kolla
Keyword(s):  
Depressive Symptoms ◽  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Animal Models Of Depression ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

scholarly journals Suppression of acute and anticipatory nausea by peripherally restricted fatty acid amide hydrolase inhibitor in animal models: role of PPARα and CB1 receptors

2017 ◽  
Vol 174 (21) ◽  
pp. 3837-3847 ◽  
Author(s):  
Erin M Rock ◽  
Guillermo Moreno-Sanz ◽  
Cheryl L Limebeer ◽  
Gavin N Petrie ◽  
Roberto Angelini ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Cb1 Receptors ◽  
Anticipatory Nausea ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Role of the basolateral amygdala in mediating the effects of the fatty acid amide hydrolase inhibitor URB597 on HPA axis response to stress

2014 ◽  
Vol 24 (9) ◽  
pp. 1511-1523 ◽  
Author(s):  
Gaurav Bedse ◽  
Roberto Colangeli ◽  
Angelo M. Lavecchia ◽  
Adele Romano ◽  
Fabio Altieri ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hpa Axis ◽  
Basolateral Amygdala ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Response To Stress ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Role of Steroids on the Membrane Binding Ability of Fatty Acid Amide Hydrolase

2019 ◽  
Vol 4 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Annalaura Sabatucci ◽  
Monica Simonetti ◽  
Daniel Tortolani ◽  
Clotilde B. Angelucci ◽  
Enrico Dainese ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Membrane Binding ◽  
Acid Amide ◽  
Binding Ability ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Role of Fatty Acid Amide Hydrolase in the Transport of the Endogenous Cannabinoid Anandamide

2001 ◽  
Vol 59 (6) ◽  
pp. 1369-1375 ◽  
Author(s):  
Theresa A. Day ◽  
Fariborz Rakhshan ◽  
Dale G. Deutsch ◽  
Eric L. Barker
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Endogenous Cannabinoid ◽  
Fatty Acid Amide

scholarly journals The role of fatty acid amide hydrolase inhibition in nicotine reward and dependence

Life Sciences ◽  
2013 ◽  
Vol 92 (8-9) ◽  
pp. 458-462 ◽  
Author(s):  
Pretal P. Muldoon ◽  
Aron H. Lichtman ◽  
Loren H. Parsons ◽  
M. Imad Damaj
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer's disease

2021 ◽  
Author(s):  
Smita Jain ◽  
Akansha Bisht ◽  
Kanika Verma ◽  
Swarnima Negi ◽  
Sarvesh Paliwal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acid ◽  
Enzyme Inhibitors ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals N-Cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty acid amide hydrolase

2004 ◽  
Vol 379 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Kazuhito TSUBOI ◽  
Christine HILLIGSMANN ◽  
Séverine VANDEVOORDE ◽  
Didier M. LAMBERT ◽  
Natsuo UEDA
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Physiological Role ◽  
Ph Optimum ◽  
Ph Values ◽  
Amide Hydrolase ◽  
Derivatives Of ◽  
Fatty Acid Amide

Anandamide (N-arachidonoylethanolamine) and other bioactive N-acylethanolamines are degraded to their corresponding fatty acids and ethanolamine. This hydrolysis is mostly attributed to catalysis by FAAH (fatty acid amide hydrolase), which exhibits an alkaline pH optimum. In addition, we have identified another amidase which catalyses the same reaction exclusively at acidic pH values [Ueda, Yamanaka and Yamamoto (2001) J. Biol. Chem. 276, 35552–35557]. In attempts to find selective inhibitors of this acid amidase, we screened various derivatives of palmitic acid, 1-hexadecanol, and 1-pentadecylamine with N-palmitoylethanolamine as substrate. Here we show that N-cyclohexanecarbonylpentadecylamine inhibits the acid amidase from rat lung with an IC50 of 4.5 µM, without inhibiting FAAH at concentrations up to 100 µM. The inhibition was reversible and non-competitive. This compound also inhibited the acid amidase in intact alveolar macrophages. With the aid of this inhibitor, it was revealed that rat basophilic leukaemia cells possess the acid amidase as well as FAAH. Thus the inhibitor may be a useful tool to distinguish the acid amidase from FAAH in various tissues and cells and to elucidate the physiological role of the enzyme.

scholarly journals Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors

2021 ◽  
Vol 61 (1) ◽  
pp. 441-463
Author(s):  
Noëlle van Egmond ◽  
Verena M. Straub ◽  
Mario van der Stelt
Keyword(s):  
Cannabis Sativa ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Principal Component ◽  
Therapeutic Effects ◽  
Receptor Stimulation ◽  
Adverse Side Effects ◽  
Medicinal Properties ◽  
Amide Hydrolase

Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (−)- trans-Δ9-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB1 receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.

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