Cannabinoid Receptor Type 1 Agonist ACEA Improves Cognitive Deficit on STZ-Induced Neurotoxicity Through Apoptosis Pathway and NO Modulation.

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“The cannabinoid system has the ability to modulate cellular and molecular mechanisms, including excitotoxicity, oxidative stress, apoptosis, and inflammation, acting as a neuroprotective agent, by its relationship with signaling pathways associated to the control of cell proliferation, differentiation, and survival. Recent reports have raised new perspectives on the possible role of cannabinoid system in neurodegenerative diseases like Alzheimer disease’s (AD).

Our study has demonstrated a participation of the cannabinoid system in cellular survival, involving the CB1 receptor, which occurs by positive regulation of the anti-apoptotic proteins, suggesting the participation of this system in neurodegenerative processes. Our data suggest that the cannabinoid system is an interesting therapeutic target for the treatment of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/30607903

https://link.springer.com/article/10.1007%2Fs12640-018-9991-2

Gender and the Politics of Marijuana

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“The objectives of this study were to understand why, even though women are more liberal than men on a broad range of issues, when it comes to the increasingly prominent issue of marijuana legalization, the direction of the gender gap is reversed, with women more conservative than men.

We find that women’s role as mothers cannot explain this gap, and that mothers are in fact no different from those without children in terms of their support for marijuana policy, as well as their reported use of marijuana. The greater religiosity of women does play a prominent role in the gender gap on marijuana policy, but does not account for the full difference of opinion between women and men. Our findings suggest that men’s greater propensity relative to women to use marijuana is a major driver behind the gender gap.

Conclusions

Not only are attitudes on marijuana legalization likely to continue to liberalize, but as marijuana legalization and marijuana use become normalized, rather than viewed as immoral and dangerous behavior, the existing gender gap should shrink.”

https://onlinelibrary.wiley.com/doi/abs/10.1111/ssqu.12558

“Drug use, religion explain ‘reverse gender gap’ on marijuana”  https://www.sciencedaily.com/releases/2018/11/181126134251.htm?fbclid=IwAR072Y-SGz0PElUfNtQCTe56kzRC5ZBDoBMmlW2oTagAOy-IOcT_8UxVCEI

Anti-inflammatory mechanisms of cannabinoids: an immunometabolic perspective.

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“A number of studies have implicated cannabinoids as potent anti-inflammatory mediators. However, the exact mechanism by which cannabinoids exert these effects remains to be fully explained.

The recent resurgence in interest regarding the metabolic adaptations undergone by activated immune cells has highlighted the intricate connection between metabolism and an inflammatory phenotype.

In this regard, evidence suggests that cannabinoids may alter cell metabolism by increasing AMPK activity. In turn, emerging evidence suggests that the activation of AMPK by cannabinoids may mediate an anti-inflammatory effect through a range of processes.

First, AMPK may promote oxidative metabolism, which have been shown to play a central role in immune cell polarisation towards a tolerogenic phenotype. AMPK activation may also attenuate anabolic processes which in turn may antagonise immune cell function. Furthermore, AMPK activity promotes the induction of autophagy, which in turn may promote anti-inflammatory effects through various well-described processes.

Taken together, these observations implicate cannabinoids to mediate part of their anti-inflammatory effects through alterations in immune cell metabolism and the induction of autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/30610735

https://link.springer.com/article/10.1007%2Fs10787-018-00560-7

Production, digestibility and allergenicity of hemp (Cannabis sativa L.) protein isolates.

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Food Research International

“Hemp (Cannabis sativa L.), traditionally cultivated for industrial use and harvested for fibers and seeds, has raised much interest as a sustainable crop in the last years.

Recently, hemp seeds and derived oil have started to be used in a variety of food products. Hemp-based food products are considered less allergenic than those from other edible seeds, although this statement has never been experimentally verified.

In this study high purity grade hemp flour (HF) and hemp protein isolate (HPI) were obtained through a fast and cheap process starting from defatted hemp cakes, a residue of hempseed oil extraction.

HPI resulted enriched at nearly 86% protein, mainly constituted by the storage protein edestin (accounting for 70% total protein). In vitro protein digestibility was determined using a static model of gastrointestinal digestion (GID), which included a final step with purified brush border membrane (BBM) enzyme preparations. HF and HPI showed a high degree of digestibility. The survival of potential bioactive and/or allergenic peptide sequences in digests was investigated by peptidomic analysis. Only a limited number of sequences survived GID. Among them, fragments from 12 seed proteins. These fragments were precursors of sequences with potential bioactive peptides, which might justify the bioactivity of HPI hydrolysates, reported in previous studies.

More importantly, all known hemp allergens, including the major thaumatin-like protein and LTP, were entirely eliminated by the HPI production process, neither fragments of the proteins were present after GID.

These data support the use of HPI as an ingredient for hypoallergenic foods.”

https://www.ncbi.nlm.nih.gov/pubmed/30599980

https://www.sciencedirect.com/science/article/pii/S0963996918307427?via%3Dihub

Cannabidiol.

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“Cannabidiol has not been studied in nursing women taking the pharmaceutical product.

Cannabidiol has been detected in the breastmilk of some mothers who used cannabis products recreationally.

If cannabidiol is required by the mother, it is not a reason to discontinue breastfeeding.

However, since no information is available on the use of cannabidiol during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.”

 https://www.ncbi.nlm.nih.gov/pubmed/30601607
https://www.ncbi.nlm.nih.gov/books/NBK535598/

Cannabinoid-mediated retinal rescue correlates with improved circadian parameters in retinal dystrophic rats.

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 Experimental Eye Research“Ocular pathologies and blindness have been linked to circadian disorders. In previous studies, our group has demonstrated that retinitis pigmentosa is associated with degenerative changes in the melanopsin system and weaker circadian patterns.

We have also shown that cannabinoids preserve retinal structure and function in dystrophic P23H rats.

This study is consequently aimed at examining whether the morphologic and functional rescue of retinal degeneration by cannabinoids is associated with amelioration of circadian parameters.

The synthetic cannabinoid HU210 (100 μg/kg, i.p.) or vehicle were administered to transgenic P23H rats three times per week, from postnatal day 24-90. Sprague-Dawley rats were used as a healthy control group. Locomotor activity and scotopic electroretinograms were recorded, and the retinal structure was analyzed at the end of the experiment. The ERG a- and b-wave amplitudes and photoreceptor cell number were more deteriorated in vehicle-administered P23H rats as compared to P23H rats treated with HU210. In cannabinoid-administered P23H rats, the locomotor activity circadian rhythms showed less disturbance than that observed in vehicle-administered P23H rats, the latter showing lower values for mesor, amplitude, acrophase, percentage of variance and non-parametric variables. A positive linear correlation was found between retinal values and circadian parameters of locomotor activity from P23H rats.

This study thus provides evidence of a positive correlation between cannabinoid-mediated rescue of retinal structure and function and improvement of circadian rhythmicity.”

https://www.ncbi.nlm.nih.gov/pubmed/30605663

https://www.sciencedirect.com/science/article/pii/S0014483518306511?via%3Dihub

Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.

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“Aversive learning and memory are essential to cope with dangerous and stressful stimuli present in an ever-changing environment. When this process is dysfunctional, however, it is associated with posttraumatic stress disorder (PTSD). The endocannabinoid (eCB) system has been implicated in synaptic plasticity associated with physiological and pathological aversive learning and memory.

OBJECTIVE AND METHODS:

The objective of this study was to review and discuss evidence on how and where in the brain genetic or pharmacological interventions targeting the eCB system would attenuate aversive/traumatic memories through extinction facilitation in laboratory animals and humans. The effect size of the experimental intervention under investigation was also calculated.

RESULTS:

Currently available data indicate that direct or indirect activation of cannabinoid type-1 (CB1) receptor facilitates the extinction of aversive/traumatic memories. Activating CB1 receptors around the formation of aversive/traumatic memories or their reminders can potentiate their subsequent extinction. In most cases, the effect size has been large (Cohen’s d ≥ 1.0). The brain areas responsible for the above mentioned effects include the medial prefrontal cortex, amygdala, and/or hippocampus. The potential role of cannabinoid type-2 (CB2) receptors in extinction learning is now under investigation.

CONCLUSION:

Drugs augmenting the brain eCB activity can temper the impact of aversive/traumatic experiences by diverse mechanisms depending on the moment of their administration. Considering the pivotal role the extinction process plays in PTSD, the therapeutic potential of these drugs is evident. The sparse number of clinical trials testing these compounds in stress-related disorders is a gap in the literature that needs to be addressed.”

https://www.ncbi.nlm.nih.gov/pubmed/30604182

https://link.springer.com/article/10.1007%2Fs00213-018-5127-x

Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues.

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“The endocannabinoid (eCB) system is widely expressed in many central and peripheral tissues, and is involved in a plethora of physiological processes. Among these, activity of the eCB system promotes energy intake and storage, which, however, under pathophysiological conditions, can favour the development of obesity and obesity-related disorders. It is proposed that eCB signalling is evolutionary beneficial for survival under periods of scarce food resources. Remarkably, eCB signalling is increased both in hunger and in overnutrition conditions, such as obesity and type-2 diabetes. This apparent paradox suggests a role of the eCB system both at initiation and at clinical endpoint of obesity. This review will focus on recent findings about the role of the eCB system controlling whole-body metabolism in mice that are genetically modified selectively in different cell types. The current data in fact support the notion that eCB signalling is not only engaged in the development but also in the maintenance of obesity, whereby specific cell types in central and peripheral tissues are key sites in regulating the entire body’s energy homeostasis.”

https://www.ncbi.nlm.nih.gov/pubmed/30599065

https://link.springer.com/article/10.1007%2Fs00018-018-2994-6

The Anti-Inflammatory Properties of Terpenoids from Cannabis.

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“Cannabinoids are well known to have anti-inflammatory effects in mammalians; however, the Cannabis plant also contains other compounds such as terpenoids, whose biological effects have not yet been characterized. The aim of this study was to compare the anti-inflammatory properties of terpenoids with those of cannabidiol (CBD).

Materials and Methods: Essential oils prepared from three monoecious nonpsychoactive chemotypes of Cannabis were analyzed for their terpenoid content and subsequently studied pharmacologically for their anti-inflammatory properties in vitro and in vivo.

Results: In vitro, the three essential oils rich in terpenoids partly inhibited reactive oxygen intermediate and nitric oxide radical (NO•) production in RAW 264.7 stimulated macrophages. The three terpenoid-rich oils exerted moderate anti-inflammatory activities in an in vivo anti-inflammatory model without affecting tumor necrosis factor alpha (TNFα) serum levels.

Conclusions: The different Cannabis chemotypes showed distinct compositions of terpenoids. The terpenoid-rich essential oils exert anti-inflammatory and antinociceptive activities in vitro and in vivo, which vary according to their composition. Their effects seem to act independent of TNFα. None of the essential oils was as effective as purified CBD. In contrast to CBD that exerts prolonged immunosuppression and might be used in chronic inflammation, the terpenoids showed only a transient immunosuppression and might thus be used to relieve acute inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30596146

https://www.liebertpub.com/doi/10.1089/can.2018.0014

Cannabidiol Affects Extracellular Vesicle Release, miR21 and miR126, and Reduces Prohibitin Protein in Glioblastoma Multiforme Cells.

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 Translational Oncology“Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant brain tumor in adults, with poor prognosis. Extracellular vesicles (EVs) are key-mediators for cellular communication through transfer of proteins and genetic material. Cancers, such as GBM, use EV release for drug-efflux, pro-oncogenic signaling, invasion and immunosuppression; thus the modulation of EV release and cargo is of considerable clinical relevance. As EV-inhibitors have been shown to increase sensitivity of cancer cells to chemotherapy, and we recently showed that cannabidiol (CBD) is such an EV-modulator, we investigated whether CBD affects EV profile in GBM cells in the presence and absence of temozolomide (TMZ). Compared to controls, CBD-treated cells released EVs containing lower levels of pro-oncogenic miR21 and increased levels of anti-oncogenic miR126; these effects were greater than with TMZ alone. In addition, prohibitin (PHB), a multifunctional protein with mitochondrial protective properties and chemoresistant functions, was reduced in GBM cells following 1 h CBD treatment. This data suggests that CBD may, via modulation of EVs and PHB, act as an adjunct to enhance treatment efficacy in GBM, supporting evidence for efficacy of cannabinoids in GBM.”

https://www.ncbi.nlm.nih.gov/pubmed/30597288

“Cannabidiol (CBD) is a phytocannabinoid derived from Cannabis sativa and known for its anti-neoplastic and chemo-preventive activities. Known anti-cancerous effects of cannabinoids include inhibition of tumor proliferation, angiogenesis and induction of tumor cell death, while in GBM, additional effects on inhibition of invasiveness and stem-cell like properties have been observed. CBD has also been shown to selectively inhibit GBM proliferation and to induce death of cultured human GBM cells, as well as being effective against other cancers.  We have recently shown that CBD is a novel modulator of EV release in several cancer cell lines and we and other groups have shown that EV-modulators, including CBD, can significantly increase sensitivity of various cancer cells to chemotherapy. This supports emerging evidence that CBD has anti-cancer effects and indicates that CBD can be used to lower anti-chemotherapeutic responses to TMZ as well as modifying EV cargo to an anti-oncogenic signature in GBM.”

https://www.sciencedirect.com/science/article/pii/S1936523318305990?via%3Dihub