Yale Team Describes Secrets of ‘Magic’ Anti-Depressant

[faustus]

http://opa.yale.edu/...le.aspx?id=7693

this is kinda funny, cos for a long time there was talk of K causing NMDA receptor neurotoxicity. maybe it's dose dependent.

**********

Yale Team Describes Secrets of 'Magic' Anti-Depressant

Published: August 19, 2010

The bottom slide shows regeneration of synaptic connections in group receiving ketamine, compared to control group.

New Haven, Conn. — Yale researchers have discovered how a novel anti-depressant can take effect in hours, rather than the weeks or months usually required for most drugs currently on the market. The findings, described in the August 20 issue of the journal Science, should speed development of a safe and easy-to-administer form of the anti-depressant ketamine, which has already proven remarkably effective in treating severely depressed patients.

The Yale scientists found that, in rats, ketamine not only quickly improves depression-like behaviors but actually restores connections between brain cells damaged by chronic stress.

"It's like a magic drug—one dose can work rapidly and last for seven to 10 days," said Ronald Duman, professor of psychiatry and pharmacology at Yale and senior author of the study.

Ketamine traditionally has been used as a general anesthetic for children, but a decade ago researchers at the Connecticut Mental Health Center found that, in lower doses, the drug seemed to give patients relief from depression, Duman said. In these initial clinical studies, which have been replicated at the National Institute of Mental Health, almost 70 percent of patients who are resistant to treatment with all other forms of antidepressants were found to improve within hours after receiving ketamine. However, its clinical use has been limited because it has to be delivered intravenously under medical supervision and in some cases can cause short-term psychotic symptoms. It has also been used as a recreational drug, known as "Special K" or sometimes just "K."

So Duman, colleague George Aghajanian and the Yale team set out to map the molecular action of the drug in the prefrontal cortex of rats that could lead to potential targets for a safer and more easily used drugs. The team discovered that ketamine acts on a pathway that rapidly forms new synaptic connections between neurons—a process called "synaptogenesis."

"The pathway is the story. Understanding the mechanism underlying the antidepressant effect of ketamine will allow us to attack the problem at a variety of possible sites within that pathway," Aghajanian said.

The team identified a critical point in the pathway, the enzyme mTOR, which controls protein synthesis required for new synaptic connections. There are already promising leads on ways to sustain the initial rapid effect of ketamine by intervening at specific downstream targets.

An estimated 40 percent of people suffering depression do not respond to medication. And many others only respond after many months or years of trying different treatments. The authors note that ketamine also has been tested as a means to rapidly treat people with suicidal thoughts, a benefit usually not seen until weeks of treatment with traditional antidepressants.

Other Yale authors of the paper are Nanxin Li, Boyoung Lee, Rong-Jian Liu, Mounira Banasr, Jason M. Dwyer, Masaaki Iwata and Xiao-Yuan Li.

National Institute of Mental Health, the Connecticut Mental Health Center and Yale University School of Medicine funded the work.

PRESS CONTACT: Bill Hathaway 203-432-1322

[naja naja]

SO thats why I'm so happy

[Tripitaka]

IME helps with breaking op8 addiction cycles as well. $2 for 10 x 100ml doses in Nepal

Edited August 25, 2010 by Tripitaka

[vual]

interesting special k being used as a anti depressant... 1 does makes you artificially happy for 10days... sign me up.

[indigo264nm]

There's an interesting article I scrolled through a few months back reviewing studies of ketamine and NMDA antagonists as potential treatments for major depressive disorder, and I'm pretty sure that it's available as full text unless I'm still logged on through my uni library page.

Here's the abstract anyway...

Ketamine and the next generation of antidepressants with a rapid onset of action

Think there is some mention of the use of ketamine infusion for ECT procedures as well.

Edited August 25, 2010 by -=IndigoSunrise=-

[santiago]

if need be i would rather take ketamine than anything else to treat depression if the situation ever arose, not for the trippy related nonsense i just feel the long term effects have been studied better on the body and mind in relation to something like paroxetine, does ketamine theoretically increase or decrease weight gain, im leaning towards decreasing which in itself may be a better long result for cardiovascular disease. Doesnt traditional anti-depressant medication increase weight gain?

[Slybacon]

So do they make the rat depressed first or do they choose the most depressed from a bunch of sad rats and go from there?

[Rabaelthazar]

^^^ LOL

[Chiral]

Pity about the long /even short term psychical side-effects it's usage has on vital organs like the bladder.

[naja naja]

wat does it do to the bladder? Mine isn't wat it used tyo be.

[Alchemica]

Lower urinary tract problems have been reported...

A study in Bristol reported in the British Medical Journal on 3 May 2008 linked urinary tract disease with ketamine use. Symptoms reported by users include an increased need to urinate, passing blood in urine, leakage of urine and pain on urination. These symptoms are associated with the scarification of the bladder lining, which leads to a shrunken bladder, erythema, and contact bleeding, and can then move to the ureters and damage the kidneys.

In a study of 9 daily ketamine users, Shahani et al. found "marked thickening of the bladder wall, a small capacity, and perivesicular stranding, consistent with severe inflammation. At cystoscopy, all patients had severe ulcerative cystitis. Biopsies in 4 patients revealed epithelial denudation and inflammation with a mild eosinophilic infiltrate. Cessation of ketamine use, with the addition of pentosan polysulfate, appeared to provide some symptomatic relief."

 

http://en.wikipedia.org/wiki/Ketamine

It might be possible to fix it by moving from the "magic" antidepressant to the normal variety:

Duloxetine treatment of long-term ketamine abuse-related lower urinary tract symptoms: a case report

http://dx.doi.org/10...ych.2010.06.009

---

Does a less selective and specific uncompetitive NMDA antagonist, like DXM, have rapid antidepressant effects? Any Robo-chuggers feel great after a session?

HCN1 ion channels seem to play a role in synaptic plasticity - is HCN1 inhibitory activity lacking in DXM/DXO and likely to prevent it from showing antidepressant effects?

Edited August 28, 2010 by Alchemica