Tag Archives: endocannabinoid system

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

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“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.

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“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

Effects of exercise stress on the endocannabinoid system in humans under field conditions.

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“The effects of physical exercise stress on the endocannabinoid system in humans are almost unexplored. In this prospective study, we investigated in a crossover design and under field conditions at different altitudes the effects of physical exercise on the endocannabinoid system (ECS) in 12 trained healthy volunteers…

We conclude that the ECS is activated upon strenuous exercise whereas the combination with hypoxic stress further increases its activity.

In summary, physical exercise activates the endocannabinoid system, whereas the combination with high altitude enhances this activation.”

http://www.ncbi.nlm.nih.gov/pubmed/22101870

Endocannabinoids and exercise.

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“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

Exercise activates the endocannabinoid system.

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“Extensive documentation exists showing that exercise induces analgesia and sedation.

…we report here the first evidence that exercise of moderate intensity activates the endocannabinoid system, suggesting a new mechanism for exercise-induced analgesia and possibly other physiological and psychological adaptations to exercise.”

http://www.ncbi.nlm.nih.gov/pubmed/14625449

Physical activity and the endocannabinoid system: an overview.

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“Recognized as a “disease modifier”, physical activity (PA) is increasingly viewed as a more holistic, cost-saving method for prevention, treatment and management of human disease conditions.

The traditional view that PA engages the monoaminergic and endorphinergic systems has been challenged by the discovery of the endocannabinoid system (ECS), composed of endogenous lipids, their target receptors, and metabolic enzymes.

Indeed, direct and indirect evidence suggests that the ECS might mediate some of the PA-triggered effects throughout the body.

Moreover, it is now emerging that PA itself is able to modulate ECS in different ways.

Against this background, in the present review we shall discuss evidence of the cross-talk between PA and the ECS, ranging from brain to peripheral districts and highlighting how ECS must be tightly regulated during PA, in order to maintain its beneficial effects on cognition, mood, and nociception, while avoiding impaired energy metabolism, oxidative stress, and inflammatory processes.”

http://www.ncbi.nlm.nih.gov/pubmed/24526057

Updates in Reproduction Coming from the Endocannabinoid System.

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“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/

The endocannabinoid anandamide inhibits voltage-gated sodium channels nav1.2, nav1.6, nav1.7, and nav1.8 in Xenopus oocytes.

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“Anandamide is an endocannabinoid that regulates multiple physiological functions by pharmacological actions, in a manner similar to marijuana. Recently, much attention has been paid to the analgesic effect of endocannabinoids in terms of identifying new pharmacotherapies for refractory pain management, but the mechanisms of the analgesic effects of anandamide are still obscure…

Anandamide inhibited the function of α subunits in neuronal sodium channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8.

These results help clarify the mechanisms of the analgesic effects of anandamide.”

http://www.ncbi.nlm.nih.gov/pubmed/24557103

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors.

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“Human OX1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes…

In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations available for cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/24530395

Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor.

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“Here, we sought to ascertain whether different elements of the endocannabinoid system (ECS) were activated in human lipid-laden macrophages, and whether CB2R played any role in atherogenesis and inflammation of these cells…

CONCLUSIONS:

A fully active ECS is present in human macrophages and macrophage-derived foam cells. Selective activation of CB2R reduces CD36-dependent oxLDL accumulation and modulates production of inflammatory cytokines, thus representing a potential therapeutic strategy to combat atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/24529123