• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
LongeCity .                       Advocacy & Research for Unlimited Lifespans

Photo
* * * * * 7 votes

Breakthroughs in depression!

depression

  • Please log in to reply
337 replies to this topic

#31 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 15 May 2014 - 12:30 AM

I suppose we would need to find out what the intended dose is of Ro 25-6981 for a person.  It looks like they are coming out with many new things and that is good.  I just wish there were something coming that is truly regenerative or actually a treatment for depression as opposed to just being habit forming.

 

Maybe there will be specifically rTMS or a new thing I found sTMS!



#32 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 15 May 2014 - 12:34 AM

sTMS

 

Penn Medicine is currently one of the first research sites in the country that is testing the effectiveness of another non-invasive, medication-free treatment called synchronized transcranial magnetic stimulation (sTMS). This is a new brain stimulation treatment that may also help alleviate symptoms of depression. The sTMS system uses low energy, synchronized transcranial magnetic stimulation synchronized to an individual’s natural brain rhythms as opposed to the stronger, high-frequency pulses utilized with traditional rTMS.  Penn is one of only 16 sites in the country testing this new technology.

 
“sTMS is an exciting new development in psychiatry since it offers the potential for an additional non-pharmacological treatment for the disabling symptoms of depression,” says Mahendra Bhati, MD, assistant professor of Clinical Psychiatry,  who, along with Michael Thase, MD, professor of Psychiatry and chief, Division of Mood and Anxiety Disorders Treatment & Research Program, is researching the new treatment at Penn. “Many patients can’t tolerate medications and TMS can be an effective treatment for these patients.  sTMS is unique when compared to all other treatments in psychiatry since sTMS uses physiological markers of brain activity to tailor treatment.  This offers the hope of individualized and potentially more effective treatment for the disabling and difficult to treat symptoms of depression.”
 
So how exactly does it work? Research has shown that the neuronal activity in the brains of people with depression shows abnormal brain rhythms in areas associated with depressive symptoms. sTMS therapy is based on the theory that the brain rhythms can be “tuned” to a normal resting rhythm using low energy magnetic fields synchronized to an individual’s brain activity. It is believed that this will restore normal brain rhythms leading to a reduction of depression symptoms and improved mood. Unlike conventional rTMS or medications, this type of magnetic stimulation is tailored to a patient's individual brain physiology.
 
More research is needed to determine the safety and efficacy of sTMS and the system is not yet FDA approved. Data from preliminary studies have shown that sTMS can improve depressive symptoms in a significant number of patients. The ongoing study at Penn and other sites seeks to confirm the findings from earlier studies and obtain FDA approval for sTMS when treating depression.
 
“They also have plans to make the device portable so it can be used at home where you can plug into the wall and listen to a built-in mp3 player.  It's painless, relaxing, and a physiologically tailored treatment for depression," says Dr. Bhati.  "If it works, it may be a treatment patients can administer to themselves in the convenience of their own home, unlike rTMS which requires five times a week visits to a doctor’s office.”
 
Researchers are hopeful that this kind of personalized approach to depression treatment will offer patients a greater variety of options to treat depression. Learn more about this trial and other depression research at Penn.
 
 
Great article on Botox, this actually sounds pretty promising
 
 
 
 


sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#33 Nattzor

  • Registered User
  • 549 posts
  • 102
  • Location:Sweden

Posted 15 May 2014 - 04:31 PM

TMS is quite far away from being available for the common man afaik, tDCS is more studied (I think) and way cheaper and easier to aquire.


Edited by Nattzor, 15 May 2014 - 04:31 PM.


#34 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 16 May 2014 - 01:00 AM

Org 26576

 

Ampakines live (!?) -- Merck published Org-26576 results in Depression (see below). 

 
Org-26576 was one of the low impacts from the Cortex-Organon partnership (along with Org-24448). As we know, Organon was running Org-24448 in Phase 2s in Schizo and Depression, but then switched over to the newer Org-26576 not long after the emergence of the CX-717 artifact (Org-24448 and CX-717 are 'sister' compounds in the benzofurazan family). 
 
Then Schering bought Organon in 2007, and Merck bought Schering, but it looks like Merck completed the Org-26576 Depression trial and the results were published in the Journal of Psychopharmacology (Dec 2012). Merck says the Depression results may show promise for future proof of concept trials. 
 
Also note that Schering also ran and completed an ADHD Phase 2 with Org-26576 (see next post), but I don't see these results published so far. But at least the Depression results were published in a prominent journal, and Merck says they "may show promise for future proof of concept trials". The original Organon-Cortex partnership included Org-26576, so (I think) Cortex could conceivably receive some milestones/royalties from Merck eventually down the road, assuming Cortex is still around. But at least this shows a glimmer of pharma interest out there for a Cortex developed Ampakine, and the AMPA approach generally. 
 
 
 
 
>>> J Psychopharmacol. 2012 Dec;26(12):1525-39. doi: 10.1177/0269881112458728. Epub 2012 Sep 6. 
 
Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial. 
Nations KR, Dogterom P, Bursi R, Schipper J, Greenwald S, Zraket D, Gertsik L, Johnstone J, Lee A, Pande Y, Ruigt G, Ereshefsky L. 
 
 
Source 
 
Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA. kari.nations@mail.utexas.edu 
 
 
Abstract 
 
 
Org 26576 acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. The aim of this Phase 1b study (N=54) was to explore safety, tolerability, pharmacokinetics, and pharmacodynamics of Org 26576 in depressed patients. Part I (N=24) evaluated the maximum tolerated dose (MTD) and optimal titration schedule in a multiple rising dose paradigm (range 100 mg BID to 600 mg BID); Part II (N=30) utilized a parallel groups design (100 mg BID, 400 mg BID, placebo) to examine all endpoints over a 28-day dosing period. Based on the number of moderate intensity adverse events reported at the 600 mg BID dose level, the MTD established in Part I was 450 mg BID. Symptomatic improvement as measured by the Montgomery-Asberg Depression Rating Scale was numerically greater in the Org 26576 groups than in the placebo group in both study parts. In Part II, the 400 mg BID dose was associated with improvements in executive functioning and speed of processing cognitive tests. Org 26576 was also associated with growth hormone increases and cortisol decreases at the end of treatment but did not influence prolactin or brain-derived neurotrophic factor. The quantitative electroencephalogram index Antidepressant Treatment Response at Week 1 was able to significantly predict symptomatic response at endpoint in the active treatment group, as was early improvement in social acuity. Overall, Org 26576 demonstrated good tolerability and pharmacokinetic properties in depressed patients, and pharmacodynamic endpoints suggested that it may show promise in future well-controlled, adequately powered proof of concept trials. 
 
 
D Cycloserine

26 adult out-patients with Recurrent Major Depressive Disorder, currently resistant to treatment (defined as 20 plus score on the 21-item Hamilton Depression Rating Scale, despite two or more adequate antidepressant medication trials) and been treated for at least 4 wk with a stable clinically determined dose of antidepressant medication, were randomised using a double-blind, placebo controlled parallel group design to receive increasing dose of DCS or placebo.The mean duration of the current episode was 13-14 months.

 
Results
 
DCS treatment led to significant improvement in depressive symptoms as measured by HAMD.Seven of 13 (54%) patients assigned to DCS qualified as responders (i.e. 50% HAMD total score reduction) vs. two of 13 (15%) assigned to placebo. Five of 13 (38 %) patients assigned to DCS were also considered remitters (i.e. HAMD total score below 7) vs. two of 13 (15%) assigned to placebo, although this difference was not statistically significant. More patients  ( 3 against one in placebo group) withdrew from experimental arm siting discomfort as reason.
 
Limitations: Small study. Remission rates were not statistically significant.
 
Conclusion: This study provides proof of concept evidence that antagonistic activity at the NMDAR-associated glycine site can induce antidepressant effects and reduce MDD severity. 54 % of DCS-treated subjects achieved treatment response. This is to be considered against the usually reported 60-65% response rate to the first antidepressant agent in depression.  Authors also measured  serum glycine levels and comment  that treatment targeting NMDAR glycine site may be particularly appropriate in those with high glycine levels.
 
 

 


TMS is quite far away from being available for the common man afaik, tDCS is more studied (I think) and way cheaper and easier to aquire.

 

I totally agree with that unfortunately, until it stats to be covered on most insurance plans! :( 


  • like x 1

#35 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 20 May 2014 - 01:47 AM

I am not sure I want to post this one because I can't find a study where it is being tested to treat depression or anything like that... however there is a ton of information about it on this board and it is available for purchase.

 

7,8-Dihydroxyflavone

 

 

Living a traumatic experience favours the persistence of fear associated with an aversive stimulus, known as fear conditioning and which, in mice, can be eased with a single dosis of 7,8-Dihydroxyflavone, a type of flavonoid which boosts the ability to acquire new emotional habits. These findings were published in the American Journal of Psychiatry in a study carried out by researchers at Emory University, USA, and UAB, who consider that the drug could be used in the effective treatment of post-traumatic stress, panic and phobia disorders in persons.

References

"Effect of 7,8-Dihydroxyflavone, a Small-Molecule TrkB Agonist, on Emotional Learning". Raul Andero, Scott A. Heldt, Keqiang Ye, Xia Liu, Antonio Armario, Kerry J. Ressler. Am J Psychiatry, December 1, 2010, doi: 10.1176/appi.ajp.2010.10030326.

 

Mice previously exposed to traumatic situations demonstrate a stronger ability to react to fear conditioning - acquired by associating a sonorous stimulus with an aversive stimulus - and lack the ability to inhibit this fear. This phenomenon is similar to that of people who suffer from Post-Traumatic Stress Disorder (PTSD), an anxiety disorder which appears after being exposed to highly traumatic situations, such as a violent attack, a natural disaster or physical abuse.

In the study researchers verified that the 7,8-Dihydroxyflavone dosis injected into mice who had undergone a traumatic experience made them eliminate fear conditioning quicker. The boost in this new behaviour is the result of 7,8-Dihydroxyflavone activating the TrkB receptors in the brain, probably those found in the amygdala, which are essential for emotional learning and memory.

7.8-Dihydroxyflavone is a type of flavonoid. These chemical compounds are present in our diets in elements such as red wine, citrus, cereals, tea and chocolate (at least 70% cocoa), etc. Chronic administration of foods rich in flavonoids in lab animals has demonstrated neuroprotective effects in long-living rodents, but the activation of TrkB receptors produced by these foods is surely low compared to the effects of 7,8-Dihydroxyflavone.

TrkB receptors in the brain are activated in mammals with the BDNF protein. There are different pathologies, such as depression or anxiety disorders, in which this protein shows alterations in its expression. Unfortunately, administration of the BDNF protein as a drug is limited given that a large part of the amount injected does not permeate the blood-brain barrier and cannot access the brain. Very recent studies have demonstrated that 7,8-Dihydroxyflavone is the first drug to imitate BDNF actions and enter the brain with much more efficacy than the same protein, thus revealing therapeutic actions in animal models suffering from Alzheimer's, strokes, Parkinson's and/or depression.

The results obtained in this study postulate that 7,8-Dihydroxyflavone as a drug could be useful as a treatment of disorders based on fear, such as PTSD, panic attacks and phobias. Researchers consider it convenient to study its effects combined with psychotherapy, administrating the drug in fear elimination therapy sessions for anxiety disorders or even shortly after a person experiences a traumatic situation.

Led by Dr Kerry Ressler of Emory University, Atlanta, the study was developed with the participation of Dr Antonio Armario, researcher at the Institute of Neuroscience of the UAB and professor of the Department of Cell Biology, Physiology and Immunology, and Dr Raul Andero, researcher at the Emory University. The article published in the American Journal of Psychiatry is part of Dr Andero's doctoral thesis.



#36 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 22 May 2014 - 01:42 AM

RG1578/RG7090

 

Link to PDF: http://www.researchg...antidepressants

 

This review focuses on the metabotropic glutamate (mGlu) receptors and their potential for drug targets for the treatment of depression. In particular, accumulating evidence has indicated the potential importance and usefulness of agents acting on mGlu2/3 and mGlu5 receptors. Preclinical and clinical evidence of mGlu2/3 receptor ligands and mGlu5 receptor antagonists are described. Moreover, their potential in clinic will be discussed in the context of neuronal mechanisms of ketamine, an agent recently demonstrated a robust effect for patients with treatment-resistant depression. This article is part of a Special Issue entitled 'mGluR'.

 

 

 

 

Ok so it is hard to find information on these but they do look very promising especially that they are a new class of drug!  I hope you have patience to read through that PDF.



#37 FeelsNumbMan

  • Registered User
  • 78 posts
  • 2
  • Location:United States

Posted 24 May 2014 - 04:40 AM

That's a whole lot of new stuff. I hope they'll all come out soon enough... Surely we shouldn't be suffering for the rest of our lives.



#38 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 27 May 2014 - 04:12 AM

That's a whole lot of new stuff. I hope they'll all come out soon enough... Surely we shouldn't be suffering for the rest of our lives.

 

I think some will and some won't but I do think in 5 to 10 years there will be a lot of options so I would remain hopeful!



#39 FeelsNumbMan

  • Registered User
  • 78 posts
  • 2
  • Location:United States

Posted 27 May 2014 - 06:06 AM

I thank you for taking your time to find all these things I had no idea even existed. I only hope that the fact these things aren't really known wouldn't hurt their development time. Is it even possible in getting something out quicker by just giving it more attention? Probably not huh.



#40 datrat

  • Registered User
  • 142 posts
  • 4
  • Location:san diego

Posted 28 May 2014 - 08:54 PM

I am not sure I want to post this one because I can't find a study where it is being tested to treat depression or anything like that... however there is a ton of information about it on this board and it is available for purchase.

 

7,8-Dihydroxyflavone

 

 

Living a traumatic experience favours the persistence of fear associated with an aversive stimulus, known as fear conditioning and which, in mice, can be eased with a single dosis of 7,8-Dihydroxyflavone, a type of flavonoid which boosts the ability to acquire new emotional habits. These findings were published in the American Journal of Psychiatry in a study carried out by researchers at Emory University, USA, and UAB, who consider that the drug could be used in the effective treatment of post-traumatic stress, panic and phobia disorders in persons.

References

"Effect of 7,8-Dihydroxyflavone, a Small-Molecule TrkB Agonist, on Emotional Learning". Raul Andero, Scott A. Heldt, Keqiang Ye, Xia Liu, Antonio Armario, Kerry J. Ressler. Am J Psychiatry, December 1, 2010, doi: 10.1176/appi.ajp.2010.10030326.

 

Mice previously exposed to traumatic situations demonstrate a stronger ability to react to fear conditioning - acquired by associating a sonorous stimulus with an aversive stimulus - and lack the ability to inhibit this fear. This phenomenon is similar to that of people who suffer from Post-Traumatic Stress Disorder (PTSD), an anxiety disorder which appears after being exposed to highly traumatic situations, such as a violent attack, a natural disaster or physical abuse.

In the study researchers verified that the 7,8-Dihydroxyflavone dosis injected into mice who had undergone a traumatic experience made them eliminate fear conditioning quicker. The boost in this new behaviour is the result of 7,8-Dihydroxyflavone activating the TrkB receptors in the brain, probably those found in the amygdala, which are essential for emotional learning and memory.

7.8-Dihydroxyflavone is a type of flavonoid. These chemical compounds are present in our diets in elements such as red wine, citrus, cereals, tea and chocolate (at least 70% cocoa), etc. Chronic administration of foods rich in flavonoids in lab animals has demonstrated neuroprotective effects in long-living rodents, but the activation of TrkB receptors produced by these foods is surely low compared to the effects of 7,8-Dihydroxyflavone.

TrkB receptors in the brain are activated in mammals with the BDNF protein. There are different pathologies, such as depression or anxiety disorders, in which this protein shows alterations in its expression. Unfortunately, administration of the BDNF protein as a drug is limited given that a large part of the amount injected does not permeate the blood-brain barrier and cannot access the brain. Very recent studies have demonstrated that 7,8-Dihydroxyflavone is the first drug to imitate BDNF actions and enter the brain with much more efficacy than the same protein, thus revealing therapeutic actions in animal models suffering from Alzheimer's, strokes, Parkinson's and/or depression.

The results obtained in this study postulate that 7,8-Dihydroxyflavone as a drug could be useful as a treatment of disorders based on fear, such as PTSD, panic attacks and phobias. Researchers consider it convenient to study its effects combined with psychotherapy, administrating the drug in fear elimination therapy sessions for anxiety disorders or even shortly after a person experiences a traumatic situation.

Led by Dr Kerry Ressler of Emory University, Atlanta, the study was developed with the participation of Dr Antonio Armario, researcher at the Institute of Neuroscience of the UAB and professor of the Department of Cell Biology, Physiology and Immunology, and Dr Raul Andero, researcher at the Emory University. The article published in the American Journal of Psychiatry is part of Dr Andero's doctoral thesis.

 

If you've been following the 7,8-DHF thread you'll already know about this, but if not there are at least two places to purchase this now; Transhuman Technologies and Indofine. The latter is a fully accredited chemical supplier. So far my personal experience with this has been extremely favorable. Definitely worth considering for depression.

 

edit; Sorry just learned that Indofine won't sell to individuals, shame too because it's a good price.
 


Edited by datrat, 28 May 2014 - 08:59 PM.


#41 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 31 May 2014 - 12:35 AM

This is very interesting the military will start on Jun 1st looking into a computer chip to fix depression, ptsd and anxiety!  It will be far off but that sounds like something that might really help!

 

http://www.13wmaz.co...n-ptsd/9677891/



#42 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 03 June 2014 - 12:42 AM

HTTLPR gene 

 

 

An analysis of 54 studies suggests that there really is a depression gene that can affect how people respond to stressful life events.

The new study, which appears in the Jan. 3 issue of the Archives of General Psychiatry, should help resolve controversy regarding the role of this gene.

People with a short variation of the serotonin transporter (5-HTTLPR) gene are more likely to become depressed when faced with certain stressful life events than their counterparts who have the longer variation, the new study showed.

What’s more, not all stressful life events are created equally when it comes to depression risk. For example, this gene raises risk of depression in people who have experienced stress related to childhood maltreatment and severe medical illness as opposed to other stressful events.

The “depression gene” was first put on the radar in 2003, and much hope was pinned on this gene. Its discovery was heralded as one of the greatest advances of the year. Things changed dramatically in 2009 after an analysis of 14 studies cast doubt on the gene’s effect on the relationship between stress and depression.

 

The new analysis included 54 studies published from 2001 and 2010 of more than 41,000 people. The results of the analysis show strong evidence that the short 5-HTTLPR gene does, in fact, affect an individual's ability to develop depression under stress.

“This is the final word,” says Srijan Sen, MD, PhD, an assistant professor in the department of psychiatry in Ann Arbor, Mich.

“A lot of resources and money have gone into looking at this one specific gene and whether it has an association with risk of depression, and now we can move as a field to look more broadly across the human genome to find other genes involved in depression,” he says. “This meta-analysis includes three or four times as many studies, and clearly there is an effect.”

Researchers still don’t know how this gene affects depression risk. “It seems like people who have the short genetic variant are more reactive to positive and negative events,” Sen says. “They react more emotionally in both ways.”

No one should go out and get tested for this gene given the small effect it has on depression risk, he says.

That said, discoveries like this one will help usher in the era of personalized medicine for the treatment of depression.

Depression still has a stigma associated with it, but “the more and more of the biology we figure out, the more we can at combat the stigma associated with depression,” Sen says.

 


  • like x 1

#43 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 03 June 2014 - 03:21 AM

New news on NSI-189!

 

 

http://seekingalpha....ntial-greatness

 

On June 17th we will see the results.



#44 Nattzor

  • Registered User
  • 549 posts
  • 102
  • Location:Sweden

Posted 03 June 2014 - 10:30 AM

New news on NSI-189!

 

 

http://seekingalpha....ntial-greatness

 

On June 17th we will see the results.

 

"New" ;)

 

Full data will be published on the 21st or 23rd.



#45 Nattzor

  • Registered User
  • 549 posts
  • 102
  • Location:Sweden

Posted 03 June 2014 - 01:27 PM

Dammit, I was wrong. It was the 24th the full data will be published (as your link said I noticed).



#46 Milkyway

  • Registered User
  • 132 posts
  • 9
  • Location:Tampa,FL
  • NO

Posted 03 June 2014 - 06:14 PM

That is good news about the NSI-189.  I don't think it negates the need for more innovative treatments like gene therapy and stem cell therapy to be used to treat depression.  It seems like it is initiative that should be assumed by the government though.  It seems that when these things are done by the private sector there is no accountability and the studies and results are not trustworthy.  I wonder if there would be a way to lobby the government to initiate these things.  I guess that is me just dreaming, though.



#47 Milkyway

  • Registered User
  • 132 posts
  • 9
  • Location:Tampa,FL
  • NO

Posted 03 June 2014 - 06:14 PM

That is good news about the NSI-189.  I don't think it negates the need for more innovative treatments like gene therapy and stem cell therapy to be used to treat depression.  It seems like it is initiative that should be assumed by the government though.  It seems that when these things are done by the private sector there is no accountability and the studies and results are not trustworthy.  I wonder if there would be a way to lobby the government to initiate these things.  I guess that is me just dreaming, though.



#48 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 04 June 2014 - 12:14 AM

That is good news about the NSI-189.  I don't think it negates the need for more innovative treatments like gene therapy and stem cell therapy to be used to treat depression.  It seems like it is initiative that should be assumed by the government though.  It seems that when these things are done by the private sector there is no accountability and the studies and results are not trustworthy.  I wonder if there would be a way to lobby the government to initiate these things.  I guess that is me just dreaming, though.

 

 

I agree with most of that... of course we all want the "real" cure but new treatments are always welcome.


BCM-95

 

I can't believe I didn't find this one earlier but this is the first time I have seen it!... The good news is you can get it right now and it has no known side effects!!  The bad news is, apparently it doesn't help you more if you are on a SSRI.

 

 

A highly absorbable form of curcumin (as BCM-95®,  distributed by Europharma) helped alleviate depression comparably to a couple of well-known antidepressant drugs in an animal study published in the journal Acta Poloniae Pharmaceutica (2011;68(5):769-75).

 

In the recent study, researchers compared BCM-95 to fluoxetine (active ingredient in Prozac®) and imipramine (active ingredient in Tofranil®) in an animal scientific model of depression.  They found the effect of the 100 mg/kg  curcumin was similar to that of the two drugs, but adding curcumin to the drugs had no amplified effects. They also found no adverse safety issues with the curcumin.

The researchers concluded curcumin's antidepressant- like activity could be due to an increase in brain levels of neurotransmitters including serotonin, norepinephrine and dopamine. "Curcumin can be a useful antidepressant especially in cases which respond to drugs having mixed effects on serotonin and catecholamines levels in the brain," they wrote.

BCM-95 is an extract of the spice turmeric, but only 2 to 5 percent of turmeric is curcumin. It was previously shown in human research to have 10-times the absorption of standard curcumin (Indian J Pharm Sci. 2008;70(4):445-449).

“It does not matter how much you take—it matters how much you absorb," said Benny Antony, lead author of the absorption trial. On the recent depression study, Antony reasoned the absorption improvements are influential on health benefits seen in recent studies. "BCM-95 curcumin is not only significantly better absorbed than standard curcumin; the curcuminoids are absorbed in the ratio in which they occur in nature," he said. "I personally feel this plays a role in BCM-95’s effectiveness, and I am glad to see more studies illuminating the health benefits of this extraordinary herb."



#49 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 06 June 2014 - 01:10 AM

This one seems pretty good as well it is available now, I would be interested to know if anyone has tried this?

 

 

L-acetylcarnitine

 

Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a well-tolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-ĸB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-ĸB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.


  • dislike x 1
  • like x 1

#50 Flex

  • Registered User
  • 1,629 posts
  • 137
  • Location:EU

Posted 12 June 2014 - 11:36 PM

I tried Valdoxan.

 

Its somehow anxiolytic, but rather weak. For comparsion: Mitrazepine is stronger

It unfortunaetly didnt helped me for my Sleep problems.

( I have problems falling asleep, so my treshold is somewhat too high)

 

Its a bit confusing. Some abstracts state that its a 5-ht2c antagonist as well,

But one said that its not active at those receptor.

 

Fell free to ask me about it if You want.

 

And thanks for those nice info´s

 

Btw:

(Afaik)

5-ht2a does interact with mGlu2/3 inversely.

i.e. activation of 5-ht2a inhibits mGlu2/3.

This effect could lead to haluzinations by Mushrooms or Lsd.


Edited by Flex, 12 June 2014 - 11:43 PM.


#51 adamh

  • Registered User
  • 679 posts
  • 57

Posted 13 June 2014 - 12:38 AM

Looking around I found the price of 7,8-Dihydroxyflavone to vary a huge amount from $5.70 per mg to a low of $82 for a whole gram. Has anyone tried this, I don't see any reports.

 

Edit: Nevermind, I see the group buy thread.


Edited by adamh, 13 June 2014 - 12:50 AM.


#52 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 13 June 2014 - 02:58 AM

I tried Valdoxan.

 

Its somehow anxiolytic, but rather weak. For comparsion: Mitrazepine is stronger

It unfortunaetly didnt helped me for my Sleep problems.

( I have problems falling asleep, so my treshold is somewhat too high)

 

Its a bit confusing. Some abstracts state that its a 5-ht2c antagonist as well,

But one said that its not active at those receptor.

 

Fell free to ask me about it if You want.

 

And thanks for those nice info´s

 

Btw:

(Afaik)

5-ht2a does interact with mGlu2/3 inversely.

i.e. activation of 5-ht2a inhibits mGlu2/3.

This effect could lead to haluzinations by Mushrooms or Lsd.

 

No problem, 5-ht2c I am a bit confused are you saying that activating that is what lsd and shrooms do?



#53 Flex

  • Registered User
  • 1,629 posts
  • 137
  • Location:EU

Posted 13 June 2014 - 09:19 AM

Shrooms and Lsd do activate 5-ht receptors, partially tough.

So therefore, a blockade or downregulation of mGlu is to be expected.


Edited by Flex, 13 June 2014 - 09:20 AM.


#54 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 14 June 2014 - 04:31 AM

Shrooms and Lsd do activate 5-ht receptors, partially tough.

So therefore, a blockade or downregulation of mGlu is to be expected.

 

That is interesting because I never was depressed until the first and only time I tried LSD and it screwed me up, perhaps that is my problem.  I mean I am not depressed now but it does happen now and then of course.



#55 Flex

  • Registered User
  • 1,629 posts
  • 137
  • Location:EU

Posted 14 June 2014 - 02:11 PM

Different causes could lead to depression.

Like a 5-ht2a/c imbalance, i.e. too much or something else.

 

5-ht2a as example increases the dopamine output in the subcortical areas but decreases it in the cortical areas.

Or Dopamine d2 receptors and 5-ht2a increase GSK3beta which impairs axonal egeneration,

However 5-ht1a and Lithium do counter this effect.

http://www.ncbi.nlm....pubmed/15039769

http://www.ncbi.nlm....les/PMC3055312/

 

But keep in mind, those Informations could never replace a Doctor !!

It could turn out e.g. that this is not for any reason siginficant.

 

I for myself had something like a migraine or cluster headaches due stress, hard to explain.

Maybe cannabis abuse has contributed to this too, dont know.

Anyhow Garlic has increase it, but Aspirine or cannabis releived it temporaly.

Curiously one single dose of LSD had healed me. Since then,in 2006, I have never experienced those headaches again.

 

You could take a look at pubmed.

But this can turn in a neverending story of trial and error, get perhaps dangerous or just costy for the various supplements.

 

Btw: Afaik Acetyl Carnitine does also increase the epigenetic expression of mGlu2


Edited by Flex, 14 June 2014 - 02:23 PM.


#56 Nemo888

  • Registered User
  • 214 posts
  • 70
  • Location:Ottawa

Posted 14 June 2014 - 04:06 PM

I'm not sure neurotransmitter dysfunction is a major cause of depression. The correlations are loose and easily confounded and in 40 years they have never been proved causative. Peptides to reduce inflammation and support neuronal regeneration seem much more effective. In a few cases it may be a neurotransmitter problem in a few cases, but clearly the vast majority are not. Even in those few cases neurotransmitters are not causative of the condition.


http://www.mediadesk...greifen_en.html Good article on using polypeptide antibodies to virtually cure stroke in rats. Posting from my phone so sorry if it is a bit of a mess.

__-------------------------------------------------------------

INFLAMMATION AND INSULIN RESISTANCE: IMPLICATIONS FOR PATHOPHYSIOLOGY AND TREATMENT
David Kemp

UT Southwestern
Recent research has identified a link between cardio metabolic illnesses and mood symptoms. Insulin resistance and other cardio metabolic risk factors predict increased risk of depression and decreased response to antidepressant and mood stabilizer treatments. This panel symposium will present new findings implicating inflammation, adipocytokines, and oxidative stress to the pathophysiology of mood states and discuss the role of anti-inflammatory and insulin-sensitizingagents as potential treatments for mood disorders. Results will be presented from an open-label proof-of-concept study evaluating the effects of pioglitazone, a peroxisome proliferator-activatedreceptor-gammaagonist with insulin sensitizing properties, on bipolar depression symptomseverity. This study found significant improvement to occur in depression severity with pioglitazone treatment. Moreover, a positive correlation was identified between reduction in depression severity and decreases in levels of interleukin 6 and adiponectin. Data on the relationship between cytokines and damage associated molecular patterns (DAMPs) by mood state will also be presented from two separate samples of patients and controls. These immunogenic markers were identified to become silent during interepisode periods and represent proxies of peripheral toxicity and illness activity. Specifically, higher levels of ccf DNA (nuclear(n)DNA (p < 0.0001) and mitochondrial (mt)DNA ( p= 0.032), as well as HSP70 (p = 0.02) were found in drug free bipolar patients compared to healthy controls . After pharmacological treatment, ccf nDNA (p = 0.013) and HSPs levels (p = 0.025) decreased in those patients that achieved clinical remission. Inaddition to bipolar disorder, recent findings relating inflammation to brain structure and function will be presented from a population with major depressive disorder (MDD). It was recently discovered that the ratios of kynurenic acid (KA) to 3-hydroxykynurenine (3HK)and KA/quinolinic acid (QA), putative neuroprotective indices, were lower in an unmedicated MDD group relative to a healthy control group, and that within the MDD group, the ratio of KA/QA was inversely correlated with the concentration of IL1RA, a proxy measure of IL1ß. Further, in the MDD group, the KA/QA ratio was positively correlated with total hippocampal volume and total amygdala volume. These results raise the possibility that immune dysregulation predisposes to mood disorders via its effect on glutamatergic signaling such that abnormal NMDA receptor signaling may be the unifying mechanism underlying the glutamate and inflammation hypotheses of depression.

In summary, the panel will focus on inflammatory cytokines and indicators of cell death or apoptosis that may represent useful biomarkers for assessing burden of disease in patients with mood disorders as well as targets for novel antidepressant treatments.
Learning Objectives:

To appreciate the role of inflammation and insulin resistance in the pathophysiology of mood disorders.

To understand the implications of inflammatory and cardiometabolic biomarkers on illness activity in bipolar disorder and recognize potential novel neurobiological targets for treating depression

________________________________________________________________________________________________________________________________

INDIVIDUAL ABSTRACT:
ASSOCIATION BETWEEN KYNURENINE PATHWAY METABOLITES AND GRAY MATTER VOLUMES OF THE HIPPOCAMPUS AND AMYGDALA IN PATIENTS WITH MOOD DISORDERS
Jonathan Savitz
Laureate Institute for Brain Research
Major Depressive Disorder (MDD) has been associated with reductions in hippocampal and amygdalar volume that are thought to reflect dendritic atrophy and/or decreases in neurogenesis.Some patients with mood disorders display elevated levels of pro-inflammatory cytokines such as IL1ß and TNF which increase the formation of kynurenine (KYN) pathway metabolites, including kynurenic acid (KA), a potentially neuroprotective antagonist of NMDA receptors, 3-hydroxykynurenine (3HK), a free radical generator, and quinolinic acid (QA), an NMDA agonist and potential neurotoxin. Whereas an association between molecular markers of inflammation and brain structu re and/or function has been found in animal models of depression, the relationship between the peripheral concentrations of kynurenine-pathway metabolites and morphometric MRI abnormalities in mood disorders remains unclear. Here I will present data showing that the ratios of KA/3HK and KA/QA, putative neuroprotective indices, were lower in an unmedicated MDD group relative to a healthy control group, and that within the MDD group, KA/QA was inversely correlated with the concentration of IL1RA, a proxy measure of IL1ß. Further, in the MDD group, the KA/QA ratio was positively correlated with total hippocampal volume and total amygdala volume. Secondly, I will present data from an independent sample of unmedicated subjects with MDD, medicated subjects with MDD, and healthy controls both to replicate the original finding and to examine the effects of medication on the relationship between neuromorphometric abnormalities and peripheral immune markers. Since both KA and QA affect glutamate release, our results raise the possibility that immune dysregulation predisposes to mood disorders via its effect on glutamatergic signaling such that abnormal NMDA receptor signaling may be the unifying mechanism underlying the glutamate and inflammation hypotheses of depression.
Learning Objectives:
?
The kynurenine theory of depression.
  • like x 1

#57 Flex

  • Registered User
  • 1,629 posts
  • 137
  • Location:EU

Posted 14 June 2014 - 08:16 PM

Thx for the Infos.

Sry I forgot that the monoamine hypotesis is somewhat outdated.

 

Btw: kynurenic-acid a metabolite of Serotonine, has maybe a potential to treat Cannabis addiction

http://www.livescien...renic-acid.html

 

But the elevation of Kynurenic acid impairs also cognition

Manipulating kynurenic acid levels in the brain - on the edge between neuroprotection and cognitive dysfunction

http://www.ncbi.nlm....pubmed/23030614

Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine

http://www.ncbi.nlm....pubmed/22038535

 

Found those further links if someone is interrested:

Ferulic acid-induced anti-depression and prokinetics similar to Chaihu-Shugan-San via polypharmacology

...FA induced anti-depression and prokinetics similar to CSS via inhibiting serotonin, norepinephrine and dopamine reuptakes, regulating HPA axis, increasing ghrelin and stimulating jejunal contraction simultaneously...

http://www.ncbi.nlm....pubmed/21791239

Antidepressant-like action of the bark ethanolic extract from Tabebuia avellanedae in the olfactory bulbectomized mice

...EET per se increased both CREB (Ser(133)) and GSK-3β (Ser(9)) phosphorylation (at doses of 10-30 and 30mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser(473)) and ERK2 phosphorylation levels were not altered in any group...

http://www.ncbi.nlm....pubmed/23237932

 

Serum hepatocyte growth factor levels and the effects of antidepressants in panic disorder

http://www.ncbi.nlm....pubmed/20483455

 

C-met the (or one of the) tagets of HGF, is activated by Dihexa,

but those pathways are implicated in cancer:

http://www.ncbi.nlm....?term=hgf c-met

Olive Phenolics as c-Met Inhibitors: (-)-Oleocanthal Attenuates Cell Proliferation, Invasiveness, and Tumor Growth in Breast Cancer Models

http://www.ncbi.nlm....pubmed/24849787


Edited by Flex, 14 June 2014 - 08:22 PM.


#58 ILIkeBeer

  • Topic Starter
  • Registered User
  • 135 posts
  • 9
  • Location:Earth

Posted 19 June 2014 - 01:24 AM

hydroxynoketamine

 

There may be a new compound to treat depression. Scientists have found that hydroxynoketamine (HNK) may treat symptoms of depression just as effectively and rapidly as ketamine without the unwanted side effects associated with the psychoactive drug.

"The clinical use of ketamine therapy for depression is limited because the drug is administered intravenously and may produce adverse effects such as hallucinations and sedation to the point of anesthesia," said Irving Wainer, one of the researchers, in a news release. "We found that the HNK compound significantly contributes to the anti-depressive effects of ketamine in animals, but doesn't produce the sedation or anesthesia, which makes HNK an attractive alternative as an antidepressant in humans."
HNK is actually one of several different compounds that are produced when ketamine is broken down in the body. The scientists tested HNK in rats to see if it alone could produce the same beneficial effects of ketamine without the unwanted side effects. The researchers gave the rats intravenous doses of ketamine, HNK and another compound produced by ketamine, called norketamine. The researchers analyzed the effect each had on stimulating certain cellular pathways in the rats' brains after 20, 30 and 60 minutes.
So what did they find? It turns out that the compound HNK, like ketamine, produced rapid antidepressant effects. Not only that, but HNK also stimulated neuro-regenerative pathways and initiated regrowth of neurons. It's also 1,000 times more potent than ketamine, doesn't act as an anesthetic agent and can even be taken by mouth.
"HNK's unique properties increase the possibility of the development of a self-administered, daily treatment that works quickly and can be taken at home for a variety of central nervous system diseases," said Wainer in a news release. "This is a very exciting discovery and we hope that the results of this study will enable future investigations into this potentially therapeutic and important compound."


#59 Milkyway

  • Registered User
  • 132 posts
  • 9
  • Location:Tampa,FL
  • NO

Posted 19 June 2014 - 02:10 AM

That's good to know.  Is there any chance it is not a scheduled substance so that we could have it synthesized.  Also, could you please convince my psychiatrist to prescribe it?  Anyway, hopeful.  Will look into it more.



sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#60 Nemo888

  • Registered User
  • 214 posts
  • 70
  • Location:Ottawa

Posted 20 June 2014 - 11:40 PM

miR135 Could Help Diagnose and Treat Mental Disorders http://wis-wander.we...rs#.U6S6fbGoq6L

The existing anti-depressants are not good enough: Some 60-70% of patients get no relief from them. For the other 30-40%, that relief is often incomplete, and they must take the drugs for a long period before feeling any effects. In addition, there are many side effects associated with the drugs. New and better drugs are clearly needed, an undertaking that requires, first and foremost, a better understanding of the processes and causes underlying the disorders.

 

The Weizmann Institute’s Prof. Alon Chen, together with his then PhD student Dr. Orna Issler, investigated the molecular mechanisms of the brain’s serotonin system, which, when misregulated, is involved in depression and anxiety disorders. Chen and his colleagues researched the role of microRNA molecules (small, non-coding RNA molecules that regulate various cellular activities) in the nerve cells that produce serotonin. They succeeded in identifying, for the first time, the unique “fingerprints” of a microRNA molecule that acts on the serotonin-producing nerve cells. Combining bioinformatics methods with experiments, the researchers found a connection between this particular microRNA, (miR135), and two proteins that play a key role in serotonin production and the regulation of its activities. The findings appeared today in Neuron.







Also tagged with one or more of these keywords: depression

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users