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Chemotherapy-induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol

CONCLUSIONS: Endocannabinoid-like lipoamines may have hitherto unrecognized roles in the metabolic side-effects associated with chemotherapy, with the N-acyl glycine subfamily in particular identified as a potential therapeutic target and/or biomarker of anabolic interventions. CBG-based treatments may represent a novel therapeutic option for chemotherapy-induced cachexia, warranting investigation in tumour-bearing cachexia models.

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Background: Muscle wasting, anorexia, and metabolic dysregulation are common side-effects of cytotoxic chemotherapy, having a dose-limiting effect on treatment efficacy, and compromising quality of life and mortality. Extracts of Cannabis sativa, and analogues of the major phytocannabinoid Δ9-tetrahydrocannabinol, have been used to ameliorate chemotherapy-induced appetite loss and nausea for decades. However, psychoactive side-effects limit their clinical utility, and they have little efficacy against weight loss. We recently established that the non-psychoactive phytocannabinoid cannabigerol (CBG) stimulates appetite in healthy rats, without neuromotor side-effects. The present study assessed whether CBG attenuates anorexia and/or other cachectic effects induced by the broad-spectrum chemotherapy agent cisplatin.

Methods: An acute cachectic phenotype was induced in adult male Lister-hooded rats by 6 mg/kg (i.p.) cisplatin. In total 66 rats were randomly allocated to groups receiving vehicle only, cisplatin only, or cisplatin and 60 or 120 mg/kg CBG (po, b.i.d.). Feeding behavior, bodyweight and locomotor activity were recorded for 72 hours, at which point rats were sacrificed for post-mortem analyses. Myofibre atrophy, protein synthesis and autophagy dysregulation were assessed in skeletal muscle, plasma metabolic profiles were obtained by untargeted 1H-NMR metabonomics, and levels of endocannabinoid-like lipoamines quantified in plasma and hypothalami by targeted HPLC-MS/MS lipidomics.

Results: CBG (120 mg/kg) modestly increased food intake, predominantly at 36-60hrs (p<0.05), and robustly attenuated cisplatin-induced weight loss from 6.3% to 2.6% at 72hrs (p<0.01). Cisplatin-induced skeletal muscle atrophy was associated with elevated plasma corticosterone (3.7 vs 13.1ng/ml, p<0.01), observed selectively in MHC type IIx (p<0.05) and IIb (p<0.0005) fibres, and was reversed by pharmacological rescue of dysregulated Akt/S6-mediated protein synthesis and autophagy processes. Plasma metabonomic analysis revealed cisplatin administration produced a wide-ranging aberrant metabolic phenotype (Q2Ŷ=0.5380, p=0.001), involving alterations to glucose, amino acid, choline and lipid metabolism, citrate cycle, gut microbiome function, and nephrotoxicity, which were partially normalized by CBG treatment (Q2Ŷ=0.2345, p=0.01). Lipidomic analysis of hypothalami and plasma revealed extensive cisplatin-induced dysregulation of central and peripheral lipoamines (29/79 and 11/26 screened, respectively), including reversible elevations in systemic N-acyl glycine concentrations which were negatively associated with the anti-cachectic effects of CBG treatment.

Conclusions: Endocannabinoid-like lipoamines may have hitherto unrecognized roles in the metabolic side-effects associated with chemotherapy, with the N-acyl glycine subfamily in particular identified as a potential therapeutic target and/or biomarker of anabolic interventions. CBG-based treatments may represent a novel therapeutic option for chemotherapy-induced cachexia, warranting investigation in tumour-bearing cachexia models.

Keywords: Cachexia; Cannabigerol; Cannabinoid; Chemotherapy; Cisplatin; Lipoamine.

Source: https://pubmed.ncbi.nlm.nih.gov/31035309/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=18gXB4q-CV5o0kQDSCt3HqwNcsXbn1PxqekJlWJaIbT8zAG16G&fc=20200804213200&ff=20200813151120&v=2.11.5

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Placed an order with Plain Jane, didn’t receive order confirmation email.

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Hey guys, just want to hear from some people who have ordered from them before and know if thats normal or not. This is my first time ordering from them, I took a screenshot when I checked out and it gave me my order number, I definitely put in the right email and stuff.

Usually most transactions online result in an instant email that notifies they got my order, I got nothing at all, just seems pretty weird and makes me a bit worried.

Is this normal?

Source: https://www.reddit.com/r/CBD/comments/ltugeb/placed_an_order_with_plain_jane_didnt_receive/

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I Tried Tommy Chong's Good Vibes Protocol CBD & It Changed Everything

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Oils, pills, even gummy bears — and it didn't do a thing for me. I wasn't the only one. I asked friends of mine, and most of us had tried CBD before and … Source:

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https://gayle-king-cbd-oil-review.medium.com/gayle-king-cbd-oil-real-reviews-and

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https://gayle-king-cbd-oil-review.medium.com/gayle-king-cbd-oil-real-reviews-and. Started by kaliertyiowe , Feb 27 2021 12:03 PM. Please log in to reply. Source:

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