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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 42. This is the beginning of the thread.
Posted by saturn on November 26, 2006, at 13:30:40
A thread regarding ketamine for depression was brought up not too long ago.From what I've researched I believe it is or is expected to be undergoing FDA trials.
Has anyone heard anything more on this?
Is this likely hype--I believe it's hypothesized therapeutic mechanism is via NMDA-antagonism (same as Namenda--which hasn't panned out for depression)?
Posted by Quintal on November 26, 2006, at 14:30:49
In reply to Ketamine, posted by saturn on November 26, 2006, at 13:30:40
Well it certainly seems to be effective according to this study: http://www.biopsychiatry.com/ketaminedep.htm.
You can apply to enter a clinical trial of ketamine with this link (under 'Rapid Antidepressant Effects of Ketamine) here: http://patientinfo.nimh.nih.gov/DepressionAdult.aspx#137
Q
Posted by Quintal on November 26, 2006, at 14:42:57
In reply to Ketamine, posted by saturn on November 26, 2006, at 13:30:40
P.S: Assuming the clinical trial is still active of course.
>Is this likely hype--I believe it's hypothesized therapeutic mechanism is via NMDA-antagonism (same as Namenda--which hasn't panned out for depression)?
Would this make it similar to lamotrigine?
Q
Posted by zmg on November 26, 2006, at 15:47:39
In reply to Re: Ketamine » saturn, posted by Quintal on November 26, 2006, at 14:30:49
Quintal, I like biopsychiatry (.com) a lot, but its hardly unbiased and quite likely out of date. Nice find on the trial.
Posted by Tom Twilight on November 26, 2006, at 16:15:53
In reply to Re: Ketamine » Quintal, posted by zmg on November 26, 2006, at 15:47:39
Apparently Ketamine can help with Anxiety to
I'd like to try it
Posted by yxibow on November 27, 2006, at 4:29:22
In reply to Ketamine, posted by saturn on November 26, 2006, at 13:30:40
>
> A thread regarding ketamine for depression was brought up not too long ago.
>
> From what I've researched I believe it is or is expected to be undergoing FDA trials.
>
> Has anyone heard anything more on this?
>
> Is this likely hype--I believe it's hypothesized therapeutic mechanism is via NMDA-antagonism (same as Namenda--which hasn't panned out for depression)?
If this is true it would probably be under the same lockdown as Xyrem considering its street value. Its a dissociative anaesthetic not unlike PCP which is used legally in veterinary anaesthesia and mostly (human) pediatric procedures. In diverted doses it can make someone enter a "K-Hole" and forget who they are and all sorts of nasty things. Though it is schedule III for managed care, I highly doubt it would barely reach schedule II for depression purposes.-- Jay
Posted by Quintal on November 27, 2006, at 9:17:16
In reply to Re: Ketamine » Quintal, posted by zmg on November 26, 2006, at 15:47:39
> Quintal, I like biopsychiatry (.com) a lot, but its hardly unbiased and quite likely out of date.
?
Q
Posted by linkadge on November 27, 2006, at 12:16:59
In reply to Re: Ketamine » zmg, posted by Quintal on November 27, 2006, at 9:17:16
Supposedly the doses needed to achieve relief of depression symptoms is much less than needed to get high?
Though, I agree, nothing that really works will make it to the public.
Linkadge
Posted by Quintal on November 27, 2006, at 13:32:09
In reply to Re: Ketamine, posted by linkadge on November 27, 2006, at 12:16:59
I recall there being talk of introducing a ketamine inhaler for people who suffer from severe phantom pain refractory to opiates here in the UK. This was quite a while ago, but I don't know if it ever came out. I suspect not, but it has been tested for use on the battle field: http://www.defensetech.org/archives/001247.html
Q
Posted by zmg on November 28, 2006, at 1:39:12
In reply to Re: Ketamine » zmg, posted by Quintal on November 27, 2006, at 9:17:16
Honestly I just find the biopsychiatry site a little out-dated. I've tried following the off-shoot (abolitionist) but I find myself moving around a lot for information on alternative modalities.
Biopsychiatry is David Pearce (The Hedonistic Imperative) right? He'd done a whole slew of interesting sites quite a while ago, but all with a particular bend.
Posted by Quintal on November 28, 2006, at 8:47:32
In reply to Re: Ketamine » Quintal, posted by zmg on November 28, 2006, at 1:39:12
Well I don't use the hedonistic imperative website particularly. It was a study I found interesting that happened to be on that site when I used Google. I find the whole concept of gene therapy to engineer a state of mental wellbeing for everybody a fascinating concept though.
Q
Posted by zmg on November 28, 2006, at 11:33:40
In reply to Re: Ketamine » zmg, posted by Quintal on November 28, 2006, at 8:47:32
I do tend to agree. He's collected a great deal of interesting literature, I just wish it was still being updated.
Posted by madeline on November 28, 2006, at 12:55:31
In reply to Ketamine, posted by saturn on November 26, 2006, at 13:30:40
Also, please nobody print this out and sell it. I copied the article because I knew a lot of you wouldn't be able to access the journal online.
News Feature
Nature 443, 629-631 (12 October 2006) | doi:10.1038/443629a; Published online 11 October 2006Depression: Comfortably numb
Erika Check1Erika Check is a reporter for Nature in San Francisco.
Ketamine started life as an anaesthetic, then became a psychedelic club drug. Now researchers think ketamine could hold the key to understanding and treating depression, says Erika Check.
B held my hand and we started our roller coaster out... I can't feel my body anymore except this overriding general fuzziness. The lines on the ceiling become a tunnel and I am flying down it faster than sound... Then the room does a somersault and I with it... I'm scared... this is a thrill ride and the car is the dimensions of existence.Such are the wonders of the drug ketamine, according to U.S. 9, who described this experience with the drug on an online forum called the Erowid Experience Vaults1. Many others around the world use ketamine illegally, going "down the K-hole" to abandon reality and alter their consciousness. Now neuroscientists are getting in on the act. They are finding that although ketamine makes some lose their minds, it might help others to find their sanity.
Ketamine was invented in the 1960s by chemists at the drug company Parke-Davis in Detroit. The drug was a powerful anaesthetic, but also caused 'dissociative' effects, such as the feeling of leaving one's body and entering other planes of existence. Although popular with recreational drug users, ketamine is only used medically as an anaesthetic in animals and children, who are less prone to its psychedelic side effects.
But back in the 1960s, a handful of scientists used these side effects to explore human consciousness (see 'Exploring the dark'). Today, scientists are using ketamine as a tool to study mental illness, and perhaps even treat it. Clinical trials suggest that the drug might help patients with severe depression. And these experiments are changing the way scientists think about the nature of the disease and how it might be treated.
The World Health Organization estimates that depression is the world's leading cause of disability. But doctors and scientists are still mystified by what the disease actually is. The label 'depression' is a catch-all term for a condition with a huge array of possible symptoms and causes. Some depressed people feel sad, guilty or tired; others cycle into hyperexcited mania, or feel worried and anxious. Genes, stress and negative thought patterns have all been linked to depression. But it is not clear what chain of events causes a particular set of symptoms in an individual.
It's surprising. If anything, I would have expected these patients to crash and burn.
Nuri Farber
Scientists also aren't quite sure why modern antidepressant drugs succeed or fail to cure depression in different patients. The drugs act on neurotransmitters, the chemicals that brain cells use to communicate. Most of today's drugs target a particular class of neurotransmitter called the biogenic amines. These include serotonin, which is targeted by selective serotonin reuptake inhibitors, or SSRIs. Fluoxetine and sertraline, sold in the United States as Prozac and Zoloft, are members of this enormously popular category of drugs.But the drugs that act on biogenic amines take weeks to work, and fail to help at least 40% of depressed patients2. So neuroscientists suspect that these drugs don't hit depression at its source and are searching for other approaches.
The search took a dramatic turn in August this year, when a team led by Husseini Manji, at the National Institute of Mental Health in Bethesda, Maryland, published a study3 looking at the effects of ketamine on 18 severely depressed patients, all of whom had failed to respond to standard treatments.
In the double-blind trial, doctors gave the patients intravenous ketamine or placebo saline drips, and then scored the responses. After taking ketamine, 12 of the patients improved by at least 50% on a depression rating scale. Patients felt better as little as two hours after treatment. And one-third of the patients still felt better a week later.
T. EVANS/SPLIn the frame: ketamine may ease the effects of stress on brain cells.
Although unexpected, Manji's results are not the first to hint that ketamine has unexpected benefits. In 2000, John Krystal at Yale University and his colleagues published the results of a similar trial on eight severely depressed patients who didn't respond to standard medications4. This too suggested that ketamine might work as an antidepressant. Four of the patients felt much better after the ketamine treatments — their depression scores dropped by more than half, by one rating scale. And it worked fast. The patients felt better just three days after their treatment.Special forces
At the time, these results astonished other psychiatrists. "Ten years ago, I would have said there's no way in hell this drug would work as an antidepressant," says Nuri Farber, a psychiatrist at Washington University in St Louis. Many remained sceptical, and were wary about the whole idea of treating mentally unstable people with a psychoactive drug. Psychiatrists have on occasion used ketamine to deliberately destabilize normal subjects: by giving it to stable people, psychiatrists can induce a schizophrenia-like state and study the brain chemistry that may underlie the disease5. So psychiatrists didn't exactly rush to try ketamine in their own clinics. "It was such a small study, and nobody else was following this path. It was sort of a novelty," Krystal says. "People didn't take it as seriously as they might have."
T. DAGRADIJohn Krystal published one of the first studies to use ketamine as an antidepressant.
The findings languished in the literature until one of Krystal's colleagues, Dennis Charney, left Connecticut to work at the National Institute of Mental Health. There, he began working with Manji, who had been studying chemical relatives of ketamine in mice. Manji, Charney and a psychiatrist named Carlos Zarate decided to find out whether the ketamine study was more than a fluke.When they took ketamine, Zarate's patients did experience trippy side effects such as dizziness and euphoria. But most of these effects wore off after 80 minutes3 — before the drug's antidepressant effects kicked in. That is surprising: usually, drugs that trigger highs, such as cocaine or ecstasy, are followed by a depressive low. "It's not what I would have expected," says Farber. "If anything, I would have expected these patients to crash and burn."
One possible explanation for this is that ketamine uses different pathways to trigger its psychedelic and antidepressant effects. Another possibility is that patients have to go out of their minds before they can get back to normal. "What ketamine does is briefly make people crazy," says Eric Nestler, a neuroscientist and psychiatrist at the University of Texas Southwestern in Dallas. "The question becomes: is that disruption in cognitive function what's creating this improvement in mood?"
Right now, it is impossible to answer that question. But Zarate, Krystal and other researchers who have studied ketamine's link to depression have one idea about what's going on. Their hypothesis has to do with the way ketamine works in the brain.
Ketamine hinders the activity of a complex molecular machine called the N-methyl-D-aspartate receptor, the NMDA receptor for short. It is one of the receptors for a neurotransmitter called glutamate. That activity could relate to one theory of depression: that the disease occurs when brain cells are just too stressed to thrive. This link is based on two facts and one highly controversial idea.
What ketamine does is briefly make people crazy. Is that what's creating this improvement in mood?
Eric Nestler
First, scientists know that the NMDA receptor can control brain-cell growth and survival. Second, they know that excessive levels of glutamate kill brain cells in some conditions, such as stroke and Alzheimer's disease6. Here's the controversial part: there is some evidence supporting the idea that depression is caused by brain-cell death.So, by jamming the NMDA receptor, could ketamine be correcting a toxic glut of glutamate that is harming brain cells and causing depression? It is already known that stress floods the brain with glutamate, says Zarate. "It might be that these neurons are struggling to regulate glutamate, and if you stress them over and over, they become injured."
This hypothesis is still very new7. There is some evidence linking glutamate, and the NMDA receptor, to depression. Twenty-five years ago, for instance, scientists at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, showed that chemicals that target the NMDA receptor have antidepressant effects in animals8. Scientists have since found that deceased depressed human patients, such as suicide victims, have abnormal numbers of NMDA receptors. And brain-imaging studies have found that depressed people have much higher levels of glutamate in one region of their brains than healthy people9.
But Nestler and other psychiatrists caution that it is impossible to know yet whether ketamine affects brain-cell survival. Glutamate is the most common neurotransmitter in the brain, used by perhaps half of all brain cells. And the NMDA receptor is involved in a huge array of different processes, such as learning and memory, as well as cell growth and survival. So it is difficult to pin down the precise reason why tweaking glutamate through the NMDA receptor would influence human happiness. And although it is true that the NMDA receptor is involved in cell survival, this takes a long time, whereas ketamine's antidepressant effects seem to kick in within hours.
Until the mechanism can be clarified, psychiatrists say, Zarate's and Krystal's studies are important for one major reason: they provide evidence that biogenic amines such as serotonin don't tell the whole story about depression. "We've had a preoccupation over so many years with biogenic amines," says John Olney, a psychiatrist at Washington University who has been studying neurotransmitters for 35 years. "The idea that glutamate might be involved in depression has evolved very slowly. We're still trying to understand it."
What's the use?
Nestler agrees. "All our available drugs act on the serotonin and noradrenaline systems, and this drug clearly does not," he says. "It's very important as a proof of principle that a drug acting on a different neurotransmitter system can have a mood-elevating effect."Even if ketamine works, it's not an ideal drug. Clinical trials have studied the drug in only 26 patients, and no one has investigated how long its beneficial effects might last; there are also those psychedelic side effects. So neuroscientists are continuing to look into whether other drugs that hit the glutamate system could help mentally ill patients. A trial of one NMDA blocker — memantine, used to treat Alzheimer's patients — found the drug didn't cure depression10. But the study's authors think that is because memantine does not bind as tightly to the NMDA receptor as ketamine does.
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Another candidate, riluzole — already used in patients with Lou Gehrig's disease — seems more promising. It works by preventing brain cells from making excess glutamate and dumping it into surrounding brain tissue. Patients taking the drug have reported some improvement, but riluzole has yet to undergo large clinical trials for depression. Other drugs are entering tests.Whether or not these trials prove successful, at least the fresh take on depression is finally helping neuroscientists climb out of the serotonin rut. And maybe an ageing drug with a tarnished reputation will help them find their way.
Posted by rovers95 on November 28, 2006, at 20:13:39
In reply to Write up in NATURE about ketamine - LONG, posted by madeline on November 28, 2006, at 12:55:31
Apparently ketamine also raises magnesium, unlike memantine ketamine resets the HPA axis and increases dopamine, the only things that have similar eefects on the NMDA system are magnesium itself and possibly l-theanine?!
Contrary to what is archived on here lamictal is not an NMDA receptor antagonist......although it does inhibit glutamate by other actions.
But the big question is...will anything come of this ketamine study and how long will it take for someone to invent a drug structurally similar?!
Also what are these "other drugs" currently being trialled that are spoken of in the above trial??!!
I tried ketamine once earlier this year it worked 100% for about 5-6 days, hard to get hold of "good" stuff though and might not be safe in long run!!
I would try ritulek.......but im not a millionare!!
mark
Posted by madeline on November 29, 2006, at 3:25:30
In reply to Ketamine study - is anything gona come of this??!!, posted by rovers95 on November 28, 2006, at 20:13:39
my guess (and that's all it is) is that ketamine will be used in an inpatient setting only because of its mind altering (blowing?) properties.
Personally, I think it would be a hard sell in the US to launch a phase 2 or 3 clinical trial of ketamine for that same reason.
As far as similar compounds that could take years.
Posted by rovers95 on November 29, 2006, at 8:50:52
In reply to Re: Ketamine study - is anything gona come of this??!! » rovers95, posted by madeline on November 29, 2006, at 3:25:30
> my guess (and that's all it is) is that ketamine will be used in an inpatient setting only because of its mind altering (blowing?) properties.
>
> Personally, I think it would be a hard sell in the US to launch a phase 2 or 3 clinical trial of ketamine for that same reason.
>
> As far as similar compounds that could take years.
>
>I must admit i know very little about the pharmaceutical industry, but surely it would be in their best interests to take these studies into account and develop a similar product ASAP!!
It doesn't "blow your mind" at low doses!! think the hallucenegenic effects and the Ad effects are way apart!!!
mark
Posted by yxibow on November 29, 2006, at 17:50:14
In reply to Re: Ketamine study - is anything gona come of this??!!, posted by rovers95 on November 29, 2006, at 8:50:52
> > my guess (and that's all it is) is that ketamine will be used in an inpatient setting only because of its mind altering (blowing?) properties.
> >
> > Personally, I think it would be a hard sell in the US to launch a phase 2 or 3 clinical trial of ketamine for that same reason.
> >
> > As far as similar compounds that could take years.
> >
> >
>
> I must admit i know very little about the pharmaceutical industry, but surely it would be in their best interests to take these studies into account and develop a similar product ASAP!!
>
> It doesn't "blow your mind" at low doses!! think the hallucenegenic effects and the Ad effects are way apart!!!
Having seen the results of someone who took too much Ketamine and had to go in hospital, I think it is among the most vile of diverted medications. The possibility of going into a "K-Hole" is very real. It is a dissociative anaesthetic and one can really forget who they are. Its not candy and should never be treated as such. But, I also am not a proponent of demonizing the drug user as opposed to the pusher -- still, I don't think its particularly fair for tax dollars to be spent on heroic procedures in hospitals to save people who have taken an overdose of a street drug, as it is both legally and ethically required to treat every patient. I'd still vouch for treating the patient but with follow up conditions that they see outpatient (hard) drug counseling.
This will never see the light of day unless it is, as mentioned before, strictly controlled like Xyrem and amphetamine C-II derivatives are.
Posted by Quintal on November 29, 2006, at 18:03:52
In reply to Re: Ketamine study - is anything gona come of this » rovers95, posted by yxibow on November 29, 2006, at 17:50:14
Maybe people could have inpatient treatment like with ECT? I'm reading a book called 'DMT The Spirit Molecule' which is about a doctor's study into the mind altering effects of the hallucinogen DMT. The doctor discovered it had profound effects on a person's sense of wellbeing when administered in a contrlled hospital setting. Similar to what they are doing with ketamine in those clinical trials I imagine.
Q
Posted by zmg on November 29, 2006, at 18:18:13
In reply to Re: Ketamine study - is anything gona come of this » yxibow, posted by Quintal on November 29, 2006, at 18:03:52
Great book!
Posted by Quintal on November 29, 2006, at 18:25:59
In reply to Re: Ketamine study - is anything gona come of this » Quintal, posted by zmg on November 29, 2006, at 18:18:13
You have read it zmg?
Posted by zmg on November 29, 2006, at 18:33:33
In reply to Re: Ketamine study - is anything gona come of this » zmg, posted by Quintal on November 29, 2006, at 18:25:59
A couple of years ago. I've always found psychopharmacology interesting. I wish there were more books like it.
- Zach
Posted by Quintal on November 29, 2006, at 18:44:24
In reply to Re: Ketamine study - is anything gona come of this » Quintal, posted by zmg on November 29, 2006, at 18:33:33
Oh there are plenty where that came from Zach. I did a search of Amazon last week and I've just ordered a whole load.
Have you read 'Intoxication' by Roland K. Siegel Ph.D?
Jon
Posted by zmg on November 29, 2006, at 20:52:58
In reply to Re: Ketamine study - is anything gona come of this » zmg, posted by Quintal on November 29, 2006, at 18:44:24
I hadn't, but now that I've read the summary and some reviews I'll have to order it. Thanks.
You have a list in the book-section or something? I'd love to see more.
Posted by Quintal on November 29, 2006, at 22:30:18
In reply to Re: Ketamine study - is anything gona come of this » Quintal, posted by zmg on November 29, 2006, at 20:52:58
No I don't have a book list, but I can make one. What do I have to do, just write a list and post it under the Books section or is there a protocol?
Q
Posted by zmg on November 29, 2006, at 23:54:11
In reply to Re: Ketamine study - is anything gona come of this » zmg, posted by Quintal on November 29, 2006, at 22:30:18
That would work. I'm just trying not to hijack the topic here.
- Zach
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