It is widely known though misunderstood that CBD will not get you high like marijuana and other products containing TCH. There is a link between CBD and another type of high.

Researchers have found a link between CBD and anandamide, the fatty acid neurotransmitter responsible for the famous feeling of “runners high”. Many people who run or perform high intensity cardio and other forms of intensity exercise report experiencing a feeling of a joyous “high”.

That high is caused by anandamide, or the “bliss molecule”. The name comes from the Sanskrit words for “bliss” and “joy”. This molecule interacts with your body’s natural endocannabinoid system, a system of cell-signaling that helps with multiple functions including sleep, mood, appetite, memory. The systems produce endocannabinoids that bind to receptors that are located in the central nervous system, called CB1 receptors, and CB2 receptors in the peripheral nervous system, and immune cells.

Anandamide reacts with the receptors in the central nervous system in the same way THC and CBD interact with these systems. Anandamide binding to the CB1 and CB2 receptors greatly impact the body’s functions tied to those receptors including mood, leading to the feel-good vibes after a tough cardio session. Those with higher levels of the “bliss molecule” were found to experience less fear and increased moods.

Anandamide is a type of endocannabinoid that reacts with CBD. When combined, CBD will increase levels of anandamide, which is why CBD can cause a relaxed and blissful feeling and can help with anxiety symptoms.

PMID: 

Antioxidants (Basel). 2019 Nov 22 ;8(12). Epub 2019 Nov 22. PMID: 31766676

Abstract Title: 

Oleuropein, a Bioactive Compound fromL., as a Potential Preventive and Therapeutic Agent in Non-Communicable Diseases.

Abstract: 

Growing scientific literature data suggest that the intake of natural bioactive compounds plays a critical role in preventing or reducing the occurrence of human chronic non-communicable diseases (NCDs). Oleuropein, the main phenolic component ofL., has attracted scientific attention for its several health beneficial properties such as antioxidant, anti-inflammatory, cardio- and neuro-protective, and anti-cancer. This article is a narrative review focused on the current literature concerning the effect of oleuropein in NCDs, such as neuro- and cardiovascular diseases, diabetes mellitus, chronic kidney diseases, and cancer, by its putative antioxidant and anti-inflammatory activity, but also for its other peculiar actions such as an autophagy inducer and amyloid fibril growth inhibitor and, finally, for its anti-cancer effect. Despite the increasing number of published studies, looking at the beneficial effects of oleuropein, there is limited clinical evidence focused on the benefits of this polyphenol as a nutraceutical product in humans, and many problems are still to be resolved about its bioavailability, bioaccessibility, and dosage. Thus, future clinical randomized trials are needed to establish the relation between the beneficial effects and the mechanisms of action occurring in the human body in response to the intake of oleuropein.

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PMID: 

J Biotechnol. 2019 Nov 30 ;308:82-86. Epub 2019 Nov 30. PMID: 31794783

Abstract Title: 

Molecular pathways involved in lymphedema: Hydroxytyrosol as a candidate natural compound for treating the effects of lymph accumulation.

Abstract: 

Lymphedema is a chronic accumulation of interstitial fluid due to inefficient lymph drainage. Major causes of lymphedema are malformations of lymphatic vessels, trauma, toxic damage and surgery. The swelling typically affects the limbs. Lymphedema may be primary, caused by genetic mutations and relatively rare, or secondary (acquired), due to external causes such as infections or surgery. Fluid accumulation induces pathological changes: activation of the inflammatory cascade, immune cell infiltration, tissue fibrosis, adipose accumulation. We focused on the inflammatory phenotype mediated by leukotriene B4, a lipid mediator of the inflammatory pathway, and the potential therapeutic effect of hydroxytyrosol. We conducted an electronic search in PubMed using"lymphedema","lymphedema pathway","hydroxytyrosol"as keywords. We found that lymphedema deregulates at least six molecular pathways and that hydroxytyrosol, a compound with antioxidant activity, can improve endothelial dysfunction, hemostatic and lipid profiles, and decrease oxidative stress and inflammation through inhibition of leukotriene B4 activity. This review is the first to highlight the possibility of using hydroxytyrosol to treat the secondary effects of lymphedema, especially inflammation. The possible effects of hydroxytyrosol on lymphedema should be tested in vitro and in vivo to find the best way to treat patients with lymphedema in order to improve their health status.

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PMID: 

Cell Tissue Res. 2019 Dec 14. Epub 2019 Dec 14. PMID: 31838605

Abstract Title: 

Therapeutic prospects of hydroxytyrosol on experimentally induced diabetic testicular damage: potential interplay with AMPK expression.

Abstract: 

Male reproductive dysfunction represents one of the overlooked consequences of diabetes that still deserve more scientific attention. We designed this study to explore the therapeutic potential of hydroxytyrosol (HT) on diabetic testicular damage and to investigate its relationship with adenosine monophosphate-activated protein kinase (AMPK) expression. In this context, 30 adult male Wistar rats were utilized and subdivided into control, diabetic and HT-treated diabetic groups. Testicular sections were prepared for histopathological examination and immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine, Sertoli cell vimentin, myoid cellα-SMA, androgen receptors and caspase-3. We also assessed oxidative enzymatic and lipid peroxidation biochemical profiles, sperm count, morphology and motility. Real-time PCR of AMPK expression in tissue homogenate was performed. We observed that HT restored testicular histopathological structure and significantly reduced oxidative DNA damage and the apoptotic index. The HT-treated group also exhibited significantly higher Sertoli cell vimentin, myoid cell α-SMA and androgen receptor immune expression than the diabetic group. A rescue of the oxidative enzymatic activity, lipid peroxidation profiles, sperm count, morphology and motility to control levels was also evident in the HT-treated group. Significant upregulation of AMPK mRNA expression in the HT-treated group clarified the role of AMPK as an underlying molecular interface of the ameliorative effects of HT. We concluded that HT exhibited tangible antioxidant and antiapoptotic impacts on the testicular cytomorphological and immunohistochemical effects of experimentally induced diabetes. Furthermore, AMPK has an impactful role in the molecular machinery of these effects.

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PMID: 

Molecules. 2019 Dec 10 ;24(24). Epub 2019 Dec 10. PMID: 31835609

Abstract Title: 

In Vitro Anti-Inflammatory Effects of Phenolic Compounds from Moraiolo Virgin Olive Oil (MVOO) in Brain Cells via Regulating the TLR4/NLRP3 Axis.

Abstract: 

Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, microglia cells are distributed throughout the brain and are constantly surveilling the central nervous system (CNS). In response to CNS injury, microglia quickly react by secreting a wide array of apoptotic molecules. Virgin olive oil (VOO) is universally recognized as a symbol of the Mediterranean diet. In the current study, using lipopolysaccharide (LPS)-stimulated BV2 microglia, the anti-inflammatory effects of VOO phenolic extracts from Moraiolo cultivar (MVOO-PE) were investigated. The results showed that low concentration of MVOO-PE prevented microglia cell death and attenuated the LPS-induced activation of toll-like receptor 4 (TLR4)/NOD-like receptor pyrin domain-containing-3 (NLRP3) signaling cascade. The levels of TLR4 and NF-kB were diminished, as well as NLRP3 inflammasome and interleukin-1β (IL-1β) production. Cyclooxygenase-2 (COX-2) isoenzyme and ionized calcium binding adaptor molecule 1 (Iba-1) inflammatory mediator were also reduced. By modulating the TLR4/NLRP3 axis, MVOO-PE pretreatment was able to significantly down-regulate the mRNA expression of inflammatory mediators andsuppress the cytokine secretion. Finally, we showed protective effect of MVOO-PE in a transwell neuron-microglia co-culture system. In conclusion, these results suggest that MVOO-PE could exerts anti-inflammatory activity on brain cells and become a promising candidate for preventing several neuroinflammatory diseases.

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PMID: 

J Nutr Biochem. 2018 05 ;55:113-123. Epub 2017 Dec 27. PMID: 29413486

Abstract Title: 

Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer's disease.

Abstract: 

Previous evidence suggested that extra-virgin olive oil (EVOO) is linked to attenuating amyloid-β (Aβ) pathology and improving cognitive function in Alzheimer's disease (AD) mouse models. In addition, we recently reported the beneficial effect of oleocanthal, a phenolic compound in EVOO, against AD pathology. Currently, medications available to target AD pathology are limited. Donepezil is an acetylcholine esterase inhibitor approved for use for all AD stages. Donepezil has been reported to have limited Aβ-targeting mechanisms beside its acetylcholine esterase inhibition. The aim of this study was to investigate the consumption of EVOO rich with oleocanthal (hereafter EVOO) as a medical food on enhancing the effect of donepezil on attenuating Aβ load and related toxicity in 5xFAD mouse model of AD. Our results showed that EVOO consumption in combination with donepezil significantly reduced Aβ load and related pathological changes. Reduced Aβ load could be explained, at leastin part, by enhancing Aβ clearance pathways including blood-brain barrier (BBB) clearance and enzymatic degradation, and shifting amyloid precursor protein processing toward the nonamyloidogenic pathway. Furthermore, EVOO combination with donepezil up-regulated synaptic proteins, enhanced BBB tightness and reduced neuroinflammation associated with Aβ pathology. In conclusion, EVOO consumption as a medical food combined with donepezil offers an effective therapeutic approach by enhancing the noncholinergic mechanisms of donepezil and by providing additional mechanisms to attenuate Aβ-relatedpathology in AD patients.

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PMID: 

Nutrients. 2019 Dec 7 ;11(12). Epub 2019 Dec 7. PMID: 31817919

Abstract Title: 

A Narrative Review on the Potential of Red Beetroot as an Adjuvant Strategy to Counter Fatigue in Children with Cancer.

Abstract: 

Cancer-related fatigue (CRF) is a debilitating adverse effect among children with cancer and a significant barrier to physical activity (PA) participation. PA interventions are effective at reducing fatigue and improving both quality of life (QOL) and functional outcomes in children with cancer. However, 50-70% of children with cancer do not meet PA guidelines. Thus, adjuvant methods are needed to increase PA participation. Given the growing interest in the use of beetroot juice to reduce exercise-induced fatigue, our narrative review evaluated the potential use of beetroot to improve PA participation to counter CRF and improve QOL. Our review of 249 articles showed a lack of published clinical trials of beetroot in children and adults with cancer. Trials of beetroot use had been conducted in a noncancer population (= 198), and anticancer studies were primarily in the preclinical phase (= 40). Although results are promising, with beetroot juice shown to counter exercise-induced fatigue in a variety of athletic and patient populations, its use to counter CRF in children with cancer is inconclusive. Pilot and feasibility studies are needed to examine the potential benefits of beetroot to counter CRF, increase PA participation, and improve QOL in children with cancer.

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PMID: 

Int J Mol Sci. 2018 Aug 8 ;19(8). Epub 2018 Aug 8. PMID: 30096819

Abstract Title: 

A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against Oxidative Stress.

Abstract: 

Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Cahomeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that can halt the progression of these age-associated neurodegenerative diseases. Numerous epidemiological studies indicate that long-term intake of a Mediterranean diet, characterized by a high consumption of extra virgin olive oil, correlates with better cognition in aged populations. Olive oil phenolic compounds have been demonstrated to have different biological activities like antioxidant, antithrombotic, and anti-inflammatory activities. Oleocanthal, a phenolic component of extra virgin olive oil, is getting more and more scientific attention due to its interesting biological activities. The aim of this research was to characterize the neuroprotective effects of oleocanthal against H₂O₂-induced oxidative stress in neuron-like SH-SY5Y cells. Moreover, protein expression profiling, combined with pathways analyses, was used to investigate the molecular events related to the protective effects. Oleocanthal was demonstrated to counteract oxidative stress, increasing cell viability, reducing reactive oxygen species (ROS) production, and increasing reduced glutathione (GSH) intracellular level. Proteomic analysis revealed that oleocanthal significantly modulates 19 proteins in the presence of H₂O₂. In particular, oleocanthal up-regulated proteins related to the proteasome, the chaperone heat shock protein 90, the glycolytic enzyme pyruvate kinase, and the antioxidant enzyme peroxiredoxin 1. Moreover, oleocanthal protection seems to be mediated by Akt activation. These data offer new insights into the molecular mechanisms behind oleocanthal protection against oxidative stress.

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PMID: 

Cell Physiol Biochem. 2018 ;49(6):2414-2426. Epub 2018 Sep 27. PMID: 30261513

Abstract Title: 

Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways.

Abstract: 

BACKGROUND/AIMS: Oleocanthal (OC), a phenolic compound present in extra virgin olive oil (EVOO), has attracted attention since its discovery for its relevant pharmacological properties in different pathogenic processes, including inflammation. Here, we investigated the involvement of OC in LPS-activated osteoarthritis (OA) human primary chondrocytes.METHODS: Human primary chondrocytes were harvested from articular cartilage samples obtained from OA patients. The effects of OC on the viability of chondrocytes were tested by MTT assay. Protein and mRNA expression of several catabolic and pro-inflammatory factors after OC treatment were measured by RT-qPCR and western blot respectively. Moreover, we analysed the NO production by Griess reaction. Finally, several pathways mediators were analysed by western blot.RESULTS: We demonstrated that OC did not have any cytotoxic effect. Oleocanthal inhibited NO production and strongly decreased NOS2 and COX-2 protein and mRNA expression in LPS-activated human primary OA chondrocytes. Interestingly, OC also inhibits MMP-13 and ADAMTS-5. In addition, OC downregulates several pro-inflammatory factors, such as IL-6, IL-8, CCL3, LCN2 and TNF-α induced by LPS in human primary OA chondrocytes. Finally, we demonstrated that OC exerts its effects through the MAPK/P38/NF-kB pathways.CONCLUSION: These data show that OC is able to block LPS-mediated inflammatory response and MMP-13 and ADAMTS-5 induction in human primary OA chondrocytes via MAPKs/NF-kB pathways, suggesting that OC may be a promising agent for the treatment of inflammation in cartilage and a potential molecule to prevent disease progression by inhibiting metalloproteases and aggrecanases.

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PMID: 

Biochim Biophys Acta Mol Cell Res. 2019 03 ;1866(3):474-485. Epub 2018 Oct 12. PMID: 30321616

Abstract Title: 

(-)‑Oleocanthal inhibits proliferation and migration by modulating Caentry through TRPC6 in breast cancer cells.

Abstract: 

Triple negative breast cancer is an aggressive type of cancer that does not respond to hormonal therapy and current therapeutic strategies are accompanied by side effects due to cytotoxic actions on normal tissues. Therefore, there is a need for the identification of anti-cancer compounds with negligible effects on non-tumoral cells. Here we show that (-)‑oleocanthal (OLCT), a phenolic compound isolated from olive oil, selectively impairs MDA-MB-231 cell proliferation and viability without affecting the ability of non-tumoral MCF10A cells to proliferate or their viability. Similarly, OLCT selectively impairs the ability of MDA-MB-231 cells to migrate while the ability of MCF10A to migrate was unaffected. The effect of OLCT was not exclusive for triple negative breast cancer cells as we found that OLCT also attenuate cell viability and proliferation of MCF7 cells. Our results indicate that OLCT is unable to induce Camobilization in non-tumoral cells. By contrast, OLCT induces Caentry in MCF7 and MDA-MB-231 cells, which is impaired by TRPC6 expression silencing. We have found that MDA-MB-231 and MCF7 cells overexpress the channel TRPC6 as compared to non-tumoral MCF10A and treatment with OLCT for 24-72 h downregulates TRPC6 expression in MDA-MB-231 cells. These findings indicate that OLCT impairs the ability of breast cancer cells to proliferate and migrate via downregulation of TRPC6 channel expression while having no effect on the biology of non-tumoral breast cells.

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