Identification of a sustainable two-plant diet that effectively prevents age-related metabolic syndrome and extends lifespan in aged mice.

The Journal of Nutritional Biochemistry

“The current system of food production is linked to both the increasing prevalence of chronic disease and the deterioration of the environment, and thereby calls for novel ways of producing nutritious foods in a sustainable manner.

In the “longevity village” of Bama, China, we have identified two plant foods, hemp seed and bitter vegetable (Sonchus oleraceus), that are commonly consumed by its residents and grow abundantly in unfarmed land without fertilizers or pesticides.

Here, we show that a diet composed of these two foods (the “HB diet”) provides a sufficient variety of nutrients and confers significant health benefits.

Aged mice allowed ad libitum access to the HB diet not only had longer life spans and improved cognitive function but were also protected against age-related metabolic syndrome, fatty liver, gut dysbiosis and chronic inflammation compared to aged mice fed a control Western diet.

Furthermore, longevity-related genes (including 5’adenosine monophosphate-activated protein kinase, sirtuin 1, nuclear respiratory factor 1 and forkhead box O3) were significantly up-regulated, while aging-related genes (including mammalian target of rapamycin and nuclear factor kappa B) were down-regulated.

These results demonstrate that the HB diet is capable of promoting health and longevity, and present a sustainable source of healthy foods that can help control the prevalence of chronic diseases and reduce agricultural impact on the environment.”

https://www.ncbi.nlm.nih.gov/pubmed/29080417

https://www.sciencedirect.com/science/article/pii/S0955286316303461?via%3Dihub

Plasma N-acylethanolamine and endocannabinoid levels in burning mouth syndrome: potential role in disease pathogenesis.

Journal of Oral Pathology & Medicine

“The objective was to measure endocannabinoid (eCB) ligands and non-cannabinoid N-acylethanolamine (NAE) molecules in plasma from individuals with burning mouth syndrome (BMS), and to determine if plasma eCB/NAE levels correlated with pain, inflammation and depressive symptomatology in this cohort.

RESULTS:

Plasma levels of PEA, but not OEA, AEA or 2-AG, were significantly elevated in patients with BMS, when compared to plasma from healthy individuals. Plasma PEA, OEA and AEA levels correlated with depressive symptomatology.

CONCLUSIONS:

This is the first evidence to indicate that circulating eCB/NAE levels are altered in BMS.”

https://www.ncbi.nlm.nih.gov/pubmed/29436743

http://onlinelibrary.wiley.com/doi/10.1111/jop.12692/abstract

The Association of Unfavorable Traffic Events and Cannabis Usage: A Meta-Analysis

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“In the last years were published many epidemiological articles aiming to link driving under the influence of cannabis (DUIC) with the risk of various unfavorable traffic events (UTEs), with sometimes contradictory results.

The primary objective of this study was to analyze whether there is a significant association between DUIC and UTEs.

Our analysis suggests that the overall effect size for DUIC on UTEs is not statistically significant, but there are significant differences obtained through subgroup analysis. This result might be caused by either methodological flaws (which are often encountered in articles on this topic), the indiscriminate employment of the term “cannabis use,” or an actual absence of an adverse effect.

A positive test for cannabis (i.e., blood) does not necessarily imply that drivers were impaired, as THC/metabolites might be detected in blood a long time after impairment, especially in chronic cannabis users, which could also induce an important bias in the analysis of the results.

When a driver is found, in traffic, with a positive reaction suggesting cannabis use, the result should be corroborated by either objective data regarding marijuana usage (like blood analyses, with clear cut-off values), or a clinical assessment of the impairment, before establishing his/her fitness to drive.”

https://www.frontiersin.org/articles/10.3389/fphar.2018.00099/full

Learning and Memory is Modulated by Cannabidiol When Administered During Trace Fear-Conditioning.

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“Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD).

Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD.

Therefore, we designed a study to investigate effects of CBD on fear learning and memory when administered to mice prior to administering a trace fear conditioning protocol which imposes cognitive demands on the learning and memory process.

Overall, the memory-modulating effects of a single pre-conditioning dose of CBD, which we show here, demonstrate the need to more fully characterize its basic effects on memory, suggest caution when using it clinically as an anxiolytic, and point to a need for more research into its potential as a therapeutic for treating memory-loss disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/29432803

https://www.sciencedirect.com/science/article/pii/S1074742718300224

Ultrasound-Assisted Extraction of Cannabinoids from Cannabis Sativa L. Optimized by Response Surface Methodology.

Journal of Food Science

“Ultrasonication was used to extract bioactive compounds from Cannabis sativa L. such as polyphenols, flavonoids, and cannabinoids.

On comparing the ultrasonic process with the control extraction, noticeably higher values were obtained for each of the responses.

Additionally, ultrasound considerably improved the extraction of cannabinoids present in Cannabis.

PRACTICAL APPLICATION:

Low frequency ultrasound was employed to extract bioactive compounds from the inflorescence part of Cannabis. The responses evaluated were-total phenols, flavonoids, ferric reducing assay and yield. The solvent composition and time significantly influenced the extraction process. Appreciably higher extraction of cannabinoids was achieved on sonication against control.”

https://www.ncbi.nlm.nih.gov/pubmed/29437231

http://onlinelibrary.wiley.com/doi/10.1111/1750-3841.14075/abstract

Cannabis use is associated with lower rates of initiation of injection drug use among street-involved youth: A longitudinal analysis.

Drug and Alcohol Review

“Street-involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so-called ‘gateway’ drugs, such as cannabis, on injection initiation is unknown.

The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street-involved youth in Vancouver, Canada.

In a multivariable analysis, ≥daily cannabis use was associated with slower rates of injection initiation (adjusted relative hazard 0.66, 95% confidence interval 0.45-0.98; P = 0.038). Sub-analyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids.

DISCUSSION AND CONCLUSIONS:

Given the expansion of cannabis legalisation throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29430806

http://onlinelibrary.wiley.com/doi/10.1111/dar.12667/abstract

Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis.

Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis.“Cannabinoids, acting through the CB1 cannabinoid receptor (CB1R), protect the brain against ischemia and related forms of injury.

This may involve inhibiting the neurotoxicity of endogenous excitatory amino acids and downstream effectors, such as nitric oxide (NO).

Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R.

Because NO has been implicated in neurogenesis, we investigated whether cannabinoid-induced neurogenesis, like cannabinoid neuroprotection, might be mediated through alterations in NO production.” https://aggregator.leafscience.org/role-for-neuronal-nitric-oxide-synthase-in-cannabinoid-induced-neurogenesis/

“Nitric oxide negatively regulates mammalian adult neurogenesis.”  http://www.pnas.org/content/100/16/9566.long

“Thus, cannabinoids appear to stimulate adult neurogenesis by opposing the antineurogenic effect of NO.” http://jpet.aspetjournals.org/content/jpet/319/1/150.full.pdf

Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.

Cover image

“Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important.

The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications.

Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes.

Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L. chemotypes with high content of cannabidiol (CBD)/cannabidiolic acid (CBDA) and cannabigerol (CBG)/cannabigerolic acid (CBGA), respectively, on human recombinant and pig kidney aldose reductase activity in vitro.

A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs. The extracts showed significant dose-dependent aldose reductase inhibitory activity (>70%) and higher than fractions.

The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors.

The extracts of Cannabis with high content of non-psychotropic cannabinoids CBD/CBDA or CBG/CBGA significantly inhibit aldose reductase activity.

These results may have some relevance for the possible use of C. sativa chemotypes based preparations as aldose reductase inhibitors.”

https://www.ncbi.nlm.nih.gov/pubmed/29427593

https://www.sciencedirect.com/science/article/pii/S0367326X17317598

“Dietary sources of aldose reductase inhibitors: prospects for alleviating diabetic complications.” https://www.ncbi.nlm.nih.gov/pubmed/19114390

“Edible vegetables as a source of aldose reductase differential inhibitors.”  https://www.ncbi.nlm.nih.gov/pubmed/28159579

Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

“Neurogenesis is one of the most important phenomenona affecting human life. This process consists of proliferation, migration and differentiation of neuroblasts and synaptic integrations of newborn neurons.
Proliferation of new cells continues into old age, also in humans, although the most extensive process of cell formation occurs during the prenatal period. It is possible to distinguish two regions in the brain responsible for neurogenesis: the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ). Hippocampal neurogenesis is very sensitive to various physiological and pathological stimuli.
The functional integration of the newly-born dentate granule cells into hippocampal circuitry, and their ability to mediate long-term potentiation in DG, has led to the hypothesis that neurogenesis in the adult brain may play a key role in learning and memory function, as well as cognitive dysfunction in some diseases.
Brain disorders, such as neurodegenerative diseases or traumatic brain injuries, significantly affect migration, proliferation and differentiation of neural cells. In searching for the best neurological drugs protecting neuronal cells, stimulating neurogenesis, while also developing no side-effects, endocannabinoids proved to be a strong group of substances having many beneficial properties.
Therefore, the latest data is reviewed of the various experimental studies concerning the analysis of the most commonly studied cannabinoids and their impact on neurogenesis.”

Acute ethanol inhibition of adult hippocampal neurogenesis involves CB1 cannabinoid receptor signaling.

Alcoholism: Clinical and Experimental Research

“Chronic ethanol exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. Together, these findings suggest that acute CB1R cannabinoid receptor activation and binge ethanol treatment reduce neurogenesis through mechanisms involving CB1R. ”   https://www.ncbi.nlm.nih.gov/pubmed/29417597  http://onlinelibrary.wiley.com/doi/10.1111/acer.13608/abstract

“Alcohol-induced neurodegeneration” http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A666727&dswid=174

“Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice.  Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain.”  http://molpharm.aspetjournals.org/content/66/2/204.full

“Activation of Type 1 Cannabinoid Receptor (CB1R) Promotes Neurogenesis in Murine Subventricular Zone Cell Cultures”   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660454/

“Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases”  https://www.ncbi.nlm.nih.gov/pubmed/27364363

“The endocannabinoid system and neurogenesis in health and disease.”   https://www.ncbi.nlm.nih.gov/pubmed/17404371

“The role of cannabinoids in adult neurogenesis. Pharmacological targeting of the cannabinoid system as a regulator of neurogenesis may prove a fruitful strategy in the prevention or treatment of mood or memory disorders.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543605/

“Regulation of Adult Neurogenesis by Cannabinoids”  https://www.researchgate.net/publication/264424221_Regulation_of_Adult_Neurogenesis_by_Cannabinoids

“Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats. Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.”  https://www.ncbi.nlm.nih.gov/pubmed/28933048

“Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement. CBD was observed to stimulate hippocampal neurogenesis.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

“Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Chronic administration of the major drugs of abuse including opiates, alcohol, nicotine, and cocaine has been reported to suppress hippocampal neurogenesis in adult rats. Plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis. Cannabinoids appear to be the only illicit drug whose capacity to produce increased hippocampal newborn neurons is positively correlated with its anxiolytic- and antidepressant-like effects. In summary, since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration.”  https://www.jci.org/articles/view/25509