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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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Newbie q: Is Broad Spectrum worth taking over Isolate?

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Does the extra substances in Broad spectrum really have any benefit without any THC?

I read the following but I dont know enough yet to agree or not: “You cannot get an entourage effect without THC. You cannot therefore completely extract the THC and call it anything but an isolate. You most certainly cannot claim it gives “the benefits of a full spectrum” because it literally cannot do so. There is no such thing as “broad spectrum.” It’s a nonsense term that companies selling isolates are using to trick you into buying their weakened products.”

What are the thoughts of people, esp. those who’ve tried broad and isolate?

Source: https://www.reddit.com/r/CBD/comments/jkz9ic/newbie_q_is_broad_spectrum_worth_taking_over/

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HOPE™ Products for Autism Launch in Australia After Earlier US Debuts in Pennsylvania and Louisiana

Zelira Therapeutics Ltd (ASX: ZLD, OTCQB: ZLDAF) just announced that its proprietary cannabinoid medicines, HOPE 1™ and HOPE 2™are now available by prescription to patients in Australia. The HOPE™ forumations, developed by Zelira and noted autism advocate Erica Daniels, first launched in 2019 in Pennsylvania and this fall in Louisiana.  “We have had great success […]

The post HOPE™ Products for Autism Launch in Australia After Earlier US Debuts in Pennsylvania and Louisiana appeared first on Green Market Report.

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Zelira Therapeutics Ltd (ASX: ZLD, OTCQB: ZLDAF) just announced that its proprietary cannabinoid medicines, HOPE 1 and HOPE 2are now available by prescription to patients in Australia. The HOPE™ forumations, developed by Zelira and noted autism advocate Erica Daniels, first launched in 2019 in Pennsylvania and this fall in Louisiana. 

“We have had great success with HOPE™ in the US and are thrilled to be able to offer it to patients as a treatment option through the Therapeutic Goods Administration’s (TGA) Special Access Scheme,” says Osagie Imosogie, Chairman of Zelira Therapuetics. “Zelira is proud of this latest achievement in our mission to bring cannabinoid medicine to patients around the world.”

The HOPE cannabinoid medicines were developed to support the needs of patients with Autism Spectrum Disorder (ASD) by Daniels and Zelira Therapeutics, which then licensed the proprietary formulas to Ilera Healthcare in Pennsylvania and Ilera Holistic Healthcare in Louisiana. HOPE has since established itself as one of the top selling formulated medicinal cannabis products in Ilera Healthcare’s portfolio. 

“Autism families are finally beginning to have access to a truly better alternative than the harsh pharmaceuticals of the past and I am so proud that HOPE is now available in Australia,” says Erica Daniels, founder of Hope Grows for Autism and co-creator of the HOPE forumalations. “What started off as a labor of love to find a way to treat my own son is now helping parents around the world.” 

HOPE is part of Zelira’s family of revenue generating medicinal cannabis formulations. The products consist of two pharmaceutical-grade proprietary formulations developed as pharmaceutical-grade products targeting Autism Spectrum Disorder (ASD) as a disease indication. 

“Following the success of the HOPE™ launches in Pennsylvania and Louisiana, we are excited to make these products available to patients and physicians in Australia,” says Dr. Richard Hopkins, Zelira’s global Managing Director. “This represents another key milestone in our commitment to bring the benefits of HOPE to patients in global markets.”


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Source: https://www.greenmarketreport.com/hope-products-for-autism-launch-in-australia-after-earlier-us-debuts-in-pennsylvania-and-louisiana/?utm_source=rss&utm_medium=rss&utm_campaign=hope-products-for-autism-launch-in-australia-after-earlier-us-debuts-in-pennsylvania-and-louisiana

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How long till I have a “normal” THC high again after vaping CBD?

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This week I started vaping CBD to try and cut back on my weed consumption during the week as it was starting to interfere with my college classes. The results have blown me out of the water so far, but I’ve also noticed how dampened my THC highs have become. I’m fine with it during the week as I don’t feel awful waking up after a late night sesh and can get my stuff done, but over the weekend I like to indulge a little more since I’ve cut back so much during the week. About how long does it typically take after pausing CBD consumption (I last vaped around 6 pm yesterday) to feel a full, normal high? I do appreciate the calm nature of the highs when you’re loaded up with CBD but it’s just not as satisfying for me in my free time. Any help appreciated 🙂

Source: https://www.reddit.com/r/CBD/comments/jky9co/how_long_till_i_have_a_normal_thc_high_again/

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