Effect of an acute consumption of a moderate amount of ethanol on plasma endocannabinoid levels in humans.

“Animal experiments have shown that the endocannabinoid system (ECS) plays an important role in the regulation of ethanol intake. We investigated these effects in healthy volunteers who consumed a moderate amount of ethanol (red wine) and measured plasma levels of the endocannabinoids (ECs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) to test whether alcohol consumption influences the ECS in humans…

AEA, 2-AG and plasma glucose levels were significantly reduced after red wine consumption.

Water intake had no significant effect on AEA  but resulted in a gradual reduction in 2-AG concentrations…

The consumption of a moderate amount of red wine reduces plasma AEA and 2-AG concentrations, whereas the volume and caloric equivalent of the sugar containing, non-alcoholic liquid grape juice does not affect plasma ECs. Plain water has a differential effect on the ECS by reducing 2-AG concentrations without affecting AEA.”

http://www.ncbi.nlm.nih.gov/pubmed/22278319

Therapeutic Potential of Cannabinoids in Schizophrenia.

“Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia.

The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana’s psychoactive principle Δ9-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation.

…antipsychotic compounds which manipulate this system may provide a novel therapeutic target for the treatment of schizophrenia.

The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology.

Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/24605939

Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation.

“… the endocannabinoid system has been recognized as a major neuromodulatory system whose main functions are to exert and maintain the body homeostasis.

The coordinated neural, immune, behavioral and endocrine responses to inflammation are orchestrated to provide an important defense against infections and help homeostasis restoration in the body. These responses are executed and controlled mainly by the hypothalamic-pituitary adrenal axis. Also, the hypothalamic-neurohypophyseal system is essential for survival and plays a role recovering the homeostasis under a variety of stress conditions, including inflammation and infection.

Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions.

In the present review we focused on the endocannabinoids actions on the neuroendocrine response to inflammation and infection. We provide a detailed overview of the current understanding of the role of the endocannabinoid system in the recovering of homeostasis as well as potential pharmacological therapies based on the manipulation of endocannabinoid system components that could provide novel treatments for a wide range of disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24588819

The endocannabinoid signaling system in cancer.

Image result for trends in pharmacological sciences

“The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancerpathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23602129

Targeting the Endocannabinoid System for Neuroprotection: A 19F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.

“Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection…
The endocannabinoid system has been implicated as a therapeutic target for analgesia, anti-emesis, and neuroprotection… These findings provide a potential new therapeutic modality for neuroprotection through dual inhibition of FAAH and anandamide carrier proteins…”

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Intense exercise increases circulating endocannabinoid and BDNF levels in humans–possible implications for reward and depression.

“The endocannabinoid system is known to have positive effects on depression partly through its actions on neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF). As BDNF is also considered the major candidate molecule for exercise-induced brain plasticity, we hypothesized that the endocannabinoid system represents a crucial signaling system mediating the beneficial antidepressant effects of exercise…

These findings provide evidence in humans that acute exercise represents a physiological stressor able to increase peripheral levels of AEA and that BDNF might be a mechanism by which AEA influences the neuroplastic and antidepressant effects of exercise.”

http://www.ncbi.nlm.nih.gov/pubmed/22029953

“Neuroplasticity – exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Exercise is known to induce a cascade of molecular and cellular processes that support brain plasticity. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin that is also intimately connected with central and peripheral molecular processes of energy metabolism and homeostasis, and could play a crucial role in these induced mechanisms… We can only speculate which central regions and peripheral sources in particular circulating BDNF originates from,…” http://www.ncbi.nlm.nih.gov/pubmed/20726622

“Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans… cannabinoids modulate brain-derived neurotrophic factor (BDNF)… Delta(9)-THC increased serum BDNF levels…” http://www.ncbi.nlm.nih.gov/pubmed/18807247

“Antidepressant-like effects of Δ⁹-tetrahydrocannabinol…” http://www.ncbi.nlm.nih.gov/pubmed/22634064

“Antidepressant-like effects of cannabidiol… CBD treatment did not change hippocampal BDNF levels… CBD induces antidepressant-like effects…” http://www.ncbi.nlm.nih.gov/pubmed/20002102

Exercise-induced endocannabinoid signaling is modulated by intensity.

“Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward. Recent work shows that exercise activates the eCB system in humans and other mammals, suggesting eCBs are partly responsible for the reported improvements in mood and affect following aerobic exercise in humans.

However, exercise-induced psychological changes reported by runners are known to be dependent on exercise intensity, suggesting that any underlying molecular mechanism should also change with varying levels of exercise intensity.

Here, we examine circulating levels of eCBs following aerobic exercise (treadmill running) in recreationally fit human runners at four different intensities.

We show that eCB signaling is indeed intensity dependent, with significant changes in circulating eCBs observed following moderate intensities only (very high and very low intensity exercises do not significantly alter circulating eCB levels).

Our results are consistent with intensity-dependent psychological state changes with exercise and therefore support the hypothesis that eCB activity is related to neurobiological effects of exercise.

Thus, future studies examining the role of exercise-induced eCB signaling on neurobiology or physiology must take exercise intensity into account.”

http://www.ncbi.nlm.nih.gov/pubmed/22990628

Endocannabinoids and exercise.

“Exercise induces changes in mental status, particularly analgesia, sedation, anxiolysis, and a sense of wellbeing. The mechanisms underlying these changes remain unknown.

Recent findings show that exercise increases serum concentrations of endocannabinoids, suggesting a possible explanation for a number of these changes…

At first glance, it appears that the runner’s high phenomenon is, at present, not a scientific problem because it is built on circumstantial evidence and lacks a plausible mechanistic explanation. However, recent data in our laboratory showed that endurance exercise activates the endocannabinoid system, suggesting a new mechanism underlying exercise induced alterations of mental status.”

http://bjsm.bmj.com/content/38/5/536.long

Endocannabinoids as biomarkers of human reproduction.

“The search for suitable biomarkers of pregnancy outcome is a challenging issue in human reproduction, aimed at identifying molecules with predictive significance of the reproductive potential of male and female gametes.

Among the various candidates, endocannabinoids (eCBs), and in particular anandamide (AEA), represent potential biomarkers of human fertility disturbances…

Based on the available data, we suggest that the AEA tone has the potential to be exploited as a novel diagnostic biomarker of infertility,”

http://www.ncbi.nlm.nih.gov/pubmed/24516083

Updates in Reproduction Coming from the Endocannabinoid System.

“The endocannabinoid system (ECS) is an evolutionarily conserved master system deeply involved in the central and local control of reproductive functions in both sexes. The tone of these lipid mediators-deeply modulated by the activity of biosynthetic and hydrolyzing machineries-regulates reproductive functions from gonadotropin discharge and steroid biosynthesis to the formation of high quality gametes and successful pregnancy.

This review provides an overview on ECS and reproduction and focuses on the insights in the regulation of endocannabinoid production by steroids, in the regulation of male reproductive activity, and in placentation and parturition.

Taken all together, evidences emerge that the activity of the ECS is crucial for procreation and may represent a target for the therapeutic exploitation of infertility.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914453/