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Striking Similarities between Clinical and Biological Properties of Ketamine and Ethanol: Linking Antidepressant..

ethanol neuroprotective gene

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#1 Ruth

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Posted 08 August 2018 - 03:00 AM


Striking Similarities between Clinical and Biological Properties of Ketamine and Ethanol: Linking Antidepressant-After Effect and Burgeoning Addiction

Ketamine is an old drug of abuse showing currently a new wave in its spread. Also, ketamine`s therapeutic quality is currently under strong observation, especially in terms of its value in the treatment of depression and suicidality. It`s a potential revolution in understanding the mechanisms of antidepressant treatment that single and repeated therapeutic administrations of sub-anesthetic ketamine doses are associated with a rapid and robust but transient antidepressant after-effect (ADE) in patients with treatment resistant major depression. There is increasing evidence that this ADE might result primarily from ketamine`s feature of being a non-competitive antagonist of glutamatergic N-methyl-D-aspartate (NMDA)-receptors embedded in synaptic membranes of neuronal cortico-limbic networks promoting an extracellular glutamate surge, thereby mediating changes in synaptic and cellular plasticity via local glutamate non-NMDA-receptors. Here, we focus on a couple of striking clinical and biological overlaps with ketamine and ethanol being a non-competitive antagonist of NMDA-receptors, too. Among them, a good portion is currently assumed to be specifically involved in both, the mechanisms of ADE (in the case of ketamine) and the development of addiction (in the case of ethanol). These overlaps are mainly addressed here in more detail, what may draw the reader in terms of the treatment of mood disorders to both, the possibility of a progressing transfer from ADE to addiction when repeatedly using therapeutic ketamine pulses, and on the other hand, a hypothesized therapeutic `antidepressant window´ of modest and cautious ethanol use in depressives, who are (still?) not addicted to ethanol. Of course, more frequent and intense use of ethanol or ketamine would prepare the brain to tolerance and dependence possibly using the same pathways.

v) Activation of mTOR-signaling pathways [12,13,50,51]. vi) Synaptic adaptations, such as increasing number and size of dendritic spines in rodent hippocampal and prefrontal neurons [13,52,53]. vii) Repeated administration induced tolerance in euphoriant and stimulating actions [21,54] as well as in ADE [55-57], own unpublished observations]. viii) Repeated administration induced gene expression of specific NMDA receptor subunits in cortico-limbic brain regions [20,32,5860]. ix) Down-regulation of cerebellum following repeated drug administration [59]. x) Chronic or regular intake was associated with the development of addiction and neurotoxic effects that could lead to brain atrophy [32,34,54,61]. xi) Bioavailability of oral ketamine is low (20%) [34] and that of ethanol decreased from about 85% in young people down to 40% in the elderly [62].

#2 Ruth

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Posted 08 August 2018 - 03:06 AM

Low dose ethanol(wine?) plus magnesium https://onlinelibrar...1111/jphp.12880


During the last few decades, endocannabinoid system has emerged as a novel possible target for antidepressant treatment. Although the medical literature provides information on the mood‐changing effects of CB1 ligands, little is known about the possible interaction between the simultaneous activation or inhibition of the CB1 receptor and administration of other agents that possess antidepressant potential. The main goal of our study was to evaluate the influence of the CB1 cannabinoid receptor ligands (oleamide – an endogenous agonist and AM251 – an inverse agonist/antagonist) on the antidepressant‐like activity of biometals (i.e. magnesium and zinc).


Methods

The forced swim test and the tail suspension test in mice were used to determine the antidepressant‐like activity.


Key findings

Concomitant intraperitoneal administration of per se inactive doses of oleamide (5 mg/kg) or AM251 (0.25 mg/kg) and the tested biometals (i.e. magnesium, 10 mg/kg or zinc, 5 mg/kg) shortened the immobility time of animals in the forced swim test and the tail suspension test. The observed effect was not associated with an increase in spontaneous locomotor activity of mice.


Conclusions

The simultaneous modulation of the cannabinoid system and supplementation of magnesium or zinc produce at least additive antidepressant‐like effect
http://www.mdpi.com/...43/10/5/584/htm Given its neuromodulatory role in brain function [137,138,139], recent studies have investigated a relationship between selenium levels and depression. A rodent study found an association between selenium deficiency and decreased BDNF concentrations [140]. As a neurotrophic factor that has been extensively associated with the pathophysiology of major depressive disorder [141,142], it is plausible that BDNF concentrations could mediate the relationship between selenium deficiency and depression. In an intervention study performed on mice, Brüning et al. [143] showed that the administration of m-trifluoromethyl-diphenyl diselenide (m-CF3–PhSe)2, a multi-target selenium-based compound, reduced depressive symptoms as measured by immobility time in a forced swimming test (FST), in female mice, suggesting a potential antidepressant effect of selenium
http://www.jle.com/f...6/article.phtml Mots-clés : magnesium, memory, novel object recognition test, ACTH
DOI : 10.1684/mrh.2018.0435


Although a magnesium-mediated attenuation of memory deficits was reported in animal models of ageing and traumatic brain injury, a possible memory enhancement in healthy subjects has not been investigated yet. We used novel object recognition test (NORT) to examine the effects of acute (30 mg/kg) and chronic (50 mg/kg, 28 days) Mg-sulfate treatment on the long-term memory (LTM) in healthy adult male rats, and to test the sustainability of magnesium effects in the models of acute and chronic (21 days) ACTH administration (10 μg/animal), mimicking the stress- and depression-like conditions. A single dose of Mg-sulfate enhanced the LTM retrieval in the 24 h inter-trial NORT protocol, in healthy, as well as in rats acutely treated with ACTH. Memory enhancement was also detected after 4-week long Mg-sulfate intake, in both healthy and rats chronically treated with ACTH. While the present findings on procognitive effects of chronic Mg-sulfate treatment corroborate with those from studies on the therapeutic potential of Mg-threonate, the current study is the first to report on memory enhancement induced by a single dose of magnesium.

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#3 medievil

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Posted 08 August 2018 - 10:56 AM

Ketamine is a extremely effective and safe antidepressant given in clinical settings, it works for 10 days after one injection, compared to other antidepressants which are barely better then placebo (they do have an effect, as the placebo effect peters off so there might be a bigger difference long term). It increases neurogenesis and neurotrophic factors effectively targetting the root causes of depression compared to mostly blunting emotions.

 

It also is the only antidepressant that has been studied effectively for anhedonia in bipolar disorder. Some people take daily low doses but i dont think that would be as effective, its also a additive drug so do your research.

 

Alcohol is a toxin without any therapeutic potential and only has negative effects, and i havent heared about any anecdotes of people taking it daily in low doses for depression, but who knows i can research it.







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