14 ms·

Yale scientists explain how ketamine vanquishes depression within hours

216 points by 001sky 14y ago

001sky 14y ago
Orignal is http://www.sciencemag.org/content/338/6103/68 http://www.sciencemag.org/content/338/6103/68 (paywall) _________________ Abstract Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to months. A notable recent discovery shows that ketamine, a N-methyl-d-aspartate receptor antagonist, produces rapid (within hours) antidepressant responses in patients who are resistant to typical antidepressants. Basic studies show that ketamine rapidly induces synaptogenesis and reverses the synaptic deficits caused by chronic stress. These findings highlight the central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response.
- shrivats 14y ago
  For greater context, note that this is a Review article (that is to say, not an article describing new research, but rather an article synthesizing many recently published results and hypothesizing a theory that could unite them). It's part of a special issue that Science is doing this week that focuses on depression. See http://www.sciencemag.org/content/338/6103/67.full http://www.sciencemag.org/content/338/6103/67.full (not pay-walled) for a discussion of the various depression-centric papers that are in this issue.
  - samstave 14y ago
    With great context comes great information!
tokenadult 14y ago
From the press release submitted here: "In large doses, ketamine can cause short-term symptoms of psychosis and is abused as the party drug 'Special K.'" This is a general problem with drugs for mood disorders--the human mood regulatory system is very complicated, and it is possible for patients to engage in behavior that is dangerous to self and to others when they have low mood (are in a depressive episode) or when they have high mood (are in a manic episode). That's why a careful physician always asks about a patient's personal history when beginning treatment of someone seeking treatment for depression, to avoid starting out with treatments likely to trigger mania. Some human beings only get depressed, and never manic, but some can go awry in either direction. I heard a National Public Radio story with interviews of researchers on the same issue as the press release submitted here while on a drive this afternoon. What most excites researchers about the ketamine studies is not a prospect of using ketamine itself as a frequent first-line drug for treating depression, but rather as a model for understanding brain function better and eventually developing new drugs that are even longer-lasting for treating depression and even less likely to trigger mania. Human mood disorders are very diverse--there are probably hundreds of rare genetic variants that increase the risk of mood system disruption under varying kinds of environmental stress--so there surely will not be just one drug that will successfully treat all patients, but rather a gradually growing toolkit of better and better drugs to treat more and more patients with less risk and fewer side-effects. AFTER EDIT: User shrivats just kindly pointed, in a subcomment, to the overall summary of the Science special issue on depression, in which the ketamine research and related research is discussed. A paragraph describing another article in that issue is especially helpful for HN participants: "However, not all is bleak. There are individuals who overcome difficult situations and show astonishing resilience in the face of adverse circumstances and other forms of acute or chronic traumatic stress. Studying them might provide us with clues about what can go right. Southwick and Charney (p. 79) provide an overview of current ideas about why some people are more protected against stress and depression than others and how this knowledge may help us develop better treatments and successful prevention strategies." Several HN participants regularly write about strategies of building resilience to face the stress that many hackers face. Further research on that issue will also be part of the package in future improved treatments for mood disorders.
- im3w1l 14y ago
anigbrowl 14y ago
Interesting news, but the potential for abuse is worrisome. Recreational ketamine produces dissociative states similar to heavy drunkenness in the short term, and frequent repeat use is known to damage a part of the brain called Broca's region through cellular overheating, seriously impacting speech formation.
- joeyo 14y ago
  Interesting. Do you have a citation for the Brock's region damage?
  - anigbrowl 14y ago
    Here's a current one, but there are a great many more papers on the subject if you hit Google Scholar or suchlike: http://schizophreniabulletin.oxfordjournals.org/content/early/2011/11/22/schbul.sbr144.short http://schizophreniabulletin.oxfordjournals.org/content/earl... However, the specific condition I was thinking of is 'Olney's lesions' (overview: http://www.camtriplehelix.com/journal/issue/3/breathing-in-the-problem-a-link-between-inhalant-anaesthetics-and-alzheimers/pdf http://www.camtriplehelix.com/journal/issue/3/breathing-in-t...). It should be noted that some critical research has been withdrawn in this area, which I had missed, so that raises questions about the accuracy of my original remarks: http://www.erowid.org/chemicals/dxm/dxm_health1.shtml http://www.erowid.org/chemicals/dxm/dxm_health1.shtml
- Homunculiheaded 14y ago
  When looking at pharmaceutical drugs that also have a recreation use I think the number one thing to be concerned with is how addictive they are. From what I can find there really isn't any evidence to support the claim that ketamine is very addictive. Also depression is in and of itself dangerous. Even avoiding the entire topic of suicide, depression can lead to a variety of self destructive behaviors and poor decisions. Additionally plenty of people suffering from depression will naturally 'self medicate' with drugs that don't actually address the underlying neurological issues that ketamine might, and certainly can cause physical harm. I think it's somewhat odd that in the 21st century we still aren't comfortable seeing physical and mental illness on the same level. People committing suicide die of an illness in no different a way than people dying of cancer. Yet there is very little in the way of public support of combating suicide the way there is for cancer. There is little debate that opiates (dramatically more risk for abuse) should be used to treat physical pain, and yet people get very nervous about the potential for misuse in a much less risky drug which could provide similar relief to mental anguish.
chunkyslink 14y ago
I used to take quite a few drugs recreationally and I can quite honestly say that Ketamine gave me 'God like' experiences unlike anything else I have ever experienced. Repeatedly (and reproducibly) I could 'see' everything in the universe from the smallest particle to the planets and solar system in one go. I could comprehend nature, science and space and observe everything working as a system, from a point way above it all (it is dissociative after all). It made me euphoric and happy and when coming down from the experience I could (and still can) remember that feeling and how powerful it was / is. Of course to an observer I was basically asleep in a chair. This news doesn't surprise me at all.
- alwaysinshade 14y ago
  I had a somewhat different experience. I thought that I had stopped breathing and that my heart had ceased (in actual fact my body was numb - I couldn't feel a pulse) so I stood in front of a mirror completely naked for the next 20 minutes staring at my chest. Thankfully reason stepped in and I managed to compute that if my pulse or breathing had ceased, I'd be in a heap on the floor rather than obsessing in front of a mirror. Suddenly I felt calm and proceeded to throw out some cool graphics in Photoshop and made an excellent puff pastry quiche. Again, without clothes. My lesson was that drugs should be experimented with in the company of a friend or partner.
  - andersbreivik 14y ago
    * Take Ketamine * Make Quiche Wat.
  - deleted 14y ago
    [deleted]
  - ktizo 14y ago
    Sounds like quite a risky quiche. Did it come with extra crunchy bits?
    - 001sky 14y ago
      http://en.wikipedia.org/wiki/K-hole http://en.wikipedia.org/wiki/K-hole
soup10 14y ago
Recreational drugs temporarily make people happier? No way... I'm glad the fine minds at Yale are studying such important, ground breaking stuff. I can't wait until this research leads to new antidepressants that turn more people into zombies.
- hack_edu 14y ago
  The only difference between recreational drugs and prescribed medicine is your doctor's prescription.
  - waterlesscloud 14y ago
    And quality control.
    - robbiep 14y ago
      and set and setting
    - D3 14y ago
      But alcohol manufacturing processes have plenty of quality control applied to them. Not to mention that prescription medicines have a high incidence of being used recreationally. This point is moot.
- navs 14y ago
  I'd rather be a zombie than continue on as I do today
  - nitrogen 14y ago
    If you are depressed, until you can find a solution, please use all your intellectual might to fight against the emotional bondage of depression and hold on to the rational knowledge that there remains a better existence out there, and that one day you will find it.
  - OldSchool 14y ago
deleted 14y ago
[deleted]
scotty79 14y ago
Was the antidepressant effects of ketamine observed at normal anesthetic dosages (1-2mg/kg)?
- sneak 14y ago
  The antidepressant effects are found at even half of that.
siganakis 14y ago
Also of interest is the observation that Ketamine (and PCP) are associated with NMDA Antagonist Neurotoxicity (Olney's Lesions), a form of brain damage. Not really something you should want to self medicate with at this point until more research is done. http://www.dextroverse.org/txt/olney.txt http://www.dextroverse.org/txt/olney.txt http://en.wikipedia.org/wiki/Olneys_lesions http://en.wikipedia.org/wiki/Olneys_lesions
- civilian 14y ago
  I originally majored in biochemistry, so this stuff is a nerdy enjoyment. The levels of ketamine required to form Olney's Lesions are 40mg/kg (given olney.txt), whereas the typical dose to reach a k-hole (the highest recreational level) is 1mg/kg. http://www.erowid.org/chemicals/ketamine/ketamine_dose.shtml http://www.erowid.org/chemicals/ketamine/ketamine_dose.shtml Also: http://en.wikipedia.org/wiki/Olneys_lesions#Controversy http://en.wikipedia.org/wiki/Olneys_lesions#Controversy In addition, the dosage levels of recreational ketamine are lower than the anesthetic dosages of ketamine. Repeated use of ketamine would probably still cause problems though, though the problems would be more along the lines of general drug dependency and not being able to think straight. > Not really something you should want to self medicate with at this point until more research is done. I dunno. Depression can be really dangerous & costly too-- both from suicide and just generally not being happy in life.
  - dtf 14y ago
    Ketamine has been known to be "psychologically dependent" with heavy use - I guess the real world might seem a bit dull for some after all the crazy things that happen in the K-hole. But very heavy users can also experience extreme bladder damage, as their tolerance and dosage rise. It's fascinating to see these demonised recreational drugs being researched finally for their beneficial side-effects, sometimes in very small doses. Another one that comes to mind is the reported use of sub-psychoactive doses of LSD to combat the horror of cluster headaches.
    - civilian 14y ago
starpilot 14y ago
> In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. Research at Yale has shown that damage of these synaptic connections caused by chronic stress is rapidly reversed by a single dose of ketamine. There's burgeoning evidence that depression is tied to a lack of neurogenesis (creation of new brain cells), which may also be tied to serotonin levels. Some believe that the reason SSRIs take weeks to have antidepressive effects, even though serotonin levels are restored almost immediately, is that it takes a while for that to stimulate new brain cells. It's far from certain though that serotonin has anything to do with depression or neurogenesis. The atypical antidepressant tianeptine (currently unapproved in the US, but widely used in western europe) apparently reduces serotonin levels while boosting neurogenesis, the study of which is summarized well by Stanford neuroscientist Robert Sapolsky [1]: > … tianeptine prevented many of these stress-induced changes. These included the spectroscopic alterations, the inhibition of cell proliferation, and a significant increase in hippocampal volume (as compared with stress + vehicle animals). Of significance (see below), tianeptine did not prevent the stress-induced rise in cortisol levels. The restoration of hippocampal volume is important because it's been shown that low hippocampal volumes correlate with emotional abuse in adolescents [2] (also by Yale researchers). This was breathtaking for me - bad parenting literally causes brain damage. Special K and tianeptine aren't the only efforts at curing depression through neurogenesis. Neuralstem [3] is testing a drug in humans to treat major depressive disorder by restoring hippocampal volume, with a controlled study to complete early next year. That is the only new drug I'm aware of. Regardless, the serotonin model of depression, the one which produced Prozac etc. isn't the last word, and it's looking more likely that a dearth of new synapses may be the culprit in clinical depression. [1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ [2] http://www.medpagetoday.com/Pediatrics/DomesticViolence/30029 http://www.medpagetoday.com/Pediatrics/DomesticViolence/3002... [3] http://www.neuralstem.com/pharmaceuticals-for-depression http://www.neuralstem.com/pharmaceuticals-for-depression
- robbiep 14y ago
  On the point of neurogenesis this is also the theorised mechanism of Electroconvulsive therapy for Treatment-resistant depression - it's been interesting watching the evidence for the mechanisms of the 2 different treatments slowly grow
fluxon 14y ago
Yale scientists excitedly, repeatedly explain to anyone in the quad how ketamine vanquishes depression within hours, in, you know, a million million ways (yale.edu) I've read too many Onion headlines to ever read headlines like this again.
kevinalexbrown 14y ago
Here's my shot at "the most revealing job interview question" (not looking for a job, I do neuroscience in a separate area): The review explains why the rapid action of ketamine excites so many researchers: The discovery that ketamine rapidly increases the number and function of synaptic connections has focused attention on synaptogenesis as a fundamental process for the treatment of depressive symptoms and also suggests that disruption of synaptogenesis and loss of connections underlies the pathophysiology of depression. This excites researchers not because ketamine itself would be used to combat depression, but because depression is still extremely symptomatically defined, making it difficult to design treatments for. That's roughly how it's diagnosed in the diagnostic manual used by most psychiatrists: check off a list of symptoms, if you have enough, you're depressed. It's like going to the doctor and explaining that your stomach hurts and they say "well, looks like you have abdominal pain, here's some Advil." Treating the symptoms would be great if only there were a happiness dial in the brain. Indeed, the effect of most anti-depressants is often demonstrated prior to a mechanistic understanding of why they make many patients feel better. Recently there has been substantial evidence of "synaptogenesis" - the formation of new potential connections between neurons - from multiple treatments, including ketamine. So now we have this new picture emerging: depressed patients tend to have atrophied and "less-connected" neurons in some brain areas, and some drugs can reverse it, in particular ketamine can reverse it quite rapidly, and it works in rodents as well as humans. That makes it very amenable to study. The way this often works in the lab is the following. Take some rodents, subject them to unpredictable stress to get them depressed, then give some ketamine. It makes them better. Euthanize the rodents, slice the brains, and note that the non-ketamine ones have less dendritic spines in certain areas ("potential input points to a neuron"), but remarkably, the ketamine ones have more in those areas. The most important step comes next, where you try to find out what ketamine is actually doing, since, again, there's no happiness dial in the brain. Create strains of "knock-out" rodents, where you block the production of certain chemicals or proteins you think ketamine might affect by altering their genetic composition. This step is crucial, because it allows you to find out which effect of ketamine is providing the benefit, because there are many. You can do this both by observing both behavior (does the ketamine not improve mood in the genetically altered rodents?) and in physiology (does the ketamine still increase synaptogenesis in the altered rodents?). In the end you can kind of work out a map of sorts: ketamine does X things to the brain and Y in X are the ones that are important, sometimes in certain combinations. Then you can start creating intelligent drugs that pinpoint those important processes, to avoid the unfortunate side effects of drugs like ketamine. Moreover, you now have a better physiological understanding of depression, instead of just a symptomatic one. To put it in machine-learning language, it's like going from ideal observer analysis like mutual information, to an actual parametric model where you understand the distributions themselves.
agpen 14y ago
If you're going to take ketamine, please be careful, it's a very dangerous drug because studies show repeated exposure puts you at high risk of accidentally liking dubstep.
lutusp 14y ago
> Yale scientists explain how ketamine vanquishes depression within hours Translation: "Yale scientists speculate about how ketamine vanquishes depression within hours" And until there's a strictly designed study with a control group, we'll be no closer to a definitive answer. But considering the drug and its role and target, a control group would be unethical.
- lifeisstillgood 14y ago
  Err why is a non lethal, not particularly damaging drug going to be an unethical drug trial?
  - lutusp 14y ago
    > Err why is a non lethal, not particularly damaging drug going to be an unethical drug trial? Antidepression drugs, indeed all psychoactive drugs, are always a potential ethics issue. Consider the brouhaha that erupted when it was discovered that some antidepression drugs caused people to commit suicide or have suicidal thoughts: http://www.medicinenet.com/script/main/art.asp?articlekey=31649 http://www.medicinenet.com/script/main/art.asp?articlekey=31... A quote: "The FDA has warned that children and adults taking antidepressants can become suicidal in the first weeks of therapy and that physicians should watch patients closely when first giving the drugs or changing dosages. The FDA is asking drug manufacturers to place explicit warnings about the drugs' side effects, including the risk of suicide, on their labels." Any human-administered drug is a potential ethical issue, from vitamins upward. Imagine a study in which an experimental group is given a daily vitamin, and a control group is given a placebo but told they're receiving a vitamin. Several years go by and the relative health of the study participants is closely monitored. Can you not see the ethical issue here? Can you not imagine the lawsuits that would result from the parents of those in the control group who perhaps didn't thrive as expected, or for some completely imaginary consequence having nothing to do with the vitamin study, but sufficient to sue for civil damages? And finally, depression drugs are hardly "non lethal, not particularly damaging". They are a source of great controversy and have been the focus of a number of conflicts over the years.
    - 14y ago
pella 14y ago
Ketamine & autism "Drug Reverses Abnormal Brain Function in Rett Syndrome Mice" http://www.sciencedaily.com/releases/2012/10/121003132418.htm http://www.sciencedaily.com/releases/2012/10/121003132418.ht... "ScienceDaily (Oct. 3, 2012) — A promising study out October 3 in the Journal of Neuroscience showed that in a mouse model of Rett syndrome, researchers were able to reverse abnormalities in brain activity and improve neurological function by treating the animals with an FDA-approved anesthesia drug, ketamine. Rett syndrome is among the most severe autism-related disorders, affecting about one in 10,000 female births per year, with no effective treatments available."
DanBC 14y ago
Hacker News has a few readers who self-experiment with a variety of substances. I'm not trying to stop them, but there are reports of Ketamine abuse being damaging to the bladder. Some people have had their bladders removed. (http://www.bbc.co.uk/news/health-17411492 http://www.bbc.co.uk/news/health-17411492) (http://www.bbc.co.uk/news/uk-17344089 http://www.bbc.co.uk/news/uk-17344089) I have no idea on the dosing needed for harmful effects - is several large doses enough? Would very many small doses be harmful? Some people taking anti-depressants do so for a long time. Most are recommended to take them for at least two years to prevent relapse, but some medications (especially venlafaxine) can be hard to come off. (I've been told that I'll probably be taking venlafaxine for the rest of my life.) So, this news is exciting because better understanding of mental health problems is really important, and better treatments would be fantastic. But please be careful when self-experimenting with possible nootropics.
- ktizo 14y ago
  My understanding is that ketamine processes through the body slowly, so if you take it in reasonably large doses every day, you can saturate your system quite easily, which can lead to crystal formation in soft tissues, which is extremely dangerous. In single extremely large doses, or in regular doses that are small enough for your body to process, it would seem to be very safe however.
- Alex3917 14y ago
  People have been using Ketamine for decades and the bladder damage didn't seem to start until a couple years ago, so it's possibly not due to ketamine itself.
  - ktizo 14y ago
    I know people on the London party scene who got these symptoms over ten years ago. I suspect that it wasn't until there was a culture of people taking large daily doses that this issue became prevalent, as it would be unlikely for this to happen either medically, or among those who were taking this as an occasional psychedelic. It takes chronic long term exposure for these symptoms to occur.
espeed 14y ago
In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. MSG is monosodium glutamate, and there is research to show MSG is toxic -- it's the glutamate that's bad for you, not the sodium. Flooding your body with excess glutamate throws off the brain's delicate balance of this neurotransmitter and leads to excitotoxicity (http://en.wikipedia.org/wiki/Excitotoxicity http://en.wikipedia.org/wiki/Excitotoxicity). The blood-brain barrier protects you from some of it, but the blood-brain barrier is not fully formed in babies, and this is why MSG not allowed in baby food. However, the blood brain barrier can be weakened by any number of reasons in adults, such as when you have a fever. Why would ketamine's release of glutamate be different and good for you in this case?
- D3 14y ago
  Because it's a potent NMDA antagonist which blocks glutamate induced excitotoxicity. Also see: http://en.wikipedia.org/wiki/NMDA_receptor_antagonist#Potential_for_treatment_of_excitotoxicity http://en.wikipedia.org/wiki/NMDA_receptor_antagonist#Potent...
victorbstan 14y ago
In the article, near the end, they suggest that scientists are looking into alternatives that work like Ketamine, but so far none work as fast as K. "Efforts to develop drugs that replicate the effects of ketamine have produced some promising results, but they do not act as quickly as ketamine. Researchers are investigating alternatives they hope can duplicate the efficacy and rapid response of ketamine." So my question is, why not just administer K?
- Jtsummers 14y ago
  Side effects from abuse, and the short term (7-10 day) duration of the effect. If they can isolate the effective properties and recreate them, it's possible to find a drug or drugs that can solve those two problems. Also, it's unlikely that (due to it's potential for abuse) ketamine prescriptions will be handed out anytime soon. So patients can go in for weekly treatment, or researchers can find something more palatable to the current political climate.

216 points by 001sky 14y ago

Orignal is http://www.sciencemag.org/content/338/6103/68 http://www.sciencemag.org/content/338/6103/68 (paywall) _________________ Abstract Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to months. A notable recent discovery shows that ketamine, a N-methyl-d-aspartate receptor antagonist, produces rapid (within hours) antidepressant responses in patients who are resistant to typical antidepressants. Basic studies show that ketamine rapidly induces synaptogenesis and reverses the synaptic deficits caused by chronic stress. These findings highlight the central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response.

shrivats 14y ago
For greater context, note that this is a Review article (that is to say, not an article describing new research, but rather an article synthesizing many recently published results and hypothesizing a theory that could unite them). It's part of a special issue that Science is doing this week that focuses on depression. See http://www.sciencemag.org/content/338/6103/67.full http://www.sciencemag.org/content/338/6103/67.full (not pay-walled) for a discussion of the various depression-centric papers that are in this issue.
- samstave 14y ago
  With great context comes great information!

tokenadult 14y ago

From the press release submitted here: "In large doses, ketamine can cause short-term symptoms of psychosis and is abused as the party drug 'Special K.'" This is a general problem with drugs for mood disorders--the human mood regulatory system is very complicated, and it is possible for patients to engage in behavior that is dangerous to self and to others when they have low mood (are in a depressive episode) or when they have high mood (are in a manic episode). That's why a careful physician always asks about a patient's personal history when beginning treatment of someone seeking treatment for depression, to avoid starting out with treatments likely to trigger mania. Some human beings only get depressed, and never manic, but some can go awry in either direction. I heard a National Public Radio story with interviews of researchers on the same issue as the press release submitted here while on a drive this afternoon. What most excites researchers about the ketamine studies is not a prospect of using ketamine itself as a frequent first-line drug for treating depression, but rather as a model for understanding brain function better and eventually developing new drugs that are even longer-lasting for treating depression and even less likely to trigger mania. Human mood disorders are very diverse--there are probably hundreds of rare genetic variants that increase the risk of mood system disruption under varying kinds of environmental stress--so there surely will not be just one drug that will successfully treat all patients, but rather a gradually growing toolkit of better and better drugs to treat more and more patients with less risk and fewer side-effects. AFTER EDIT: User shrivats just kindly pointed, in a subcomment, to the overall summary of the Science special issue on depression, in which the ketamine research and related research is discussed. A paragraph describing another article in that issue is especially helpful for HN participants: "However, not all is bleak. There are individuals who overcome difficult situations and show astonishing resilience in the face of adverse circumstances and other forms of acute or chronic traumatic stress. Studying them might provide us with clues about what can go right. Southwick and Charney (p. 79) provide an overview of current ideas about why some people are more protected against stress and depression than others and how this knowledge may help us develop better treatments and successful prevention strategies." Several HN participants regularly write about strategies of building resilience to face the stress that many hackers face. Further research on that issue will also be part of the package in future improved treatments for mood disorders.

im3w1l 14y ago

anigbrowl 14y ago

Interesting news, but the potential for abuse is worrisome. Recreational ketamine produces dissociative states similar to heavy drunkenness in the short term, and frequent repeat use is known to damage a part of the brain called Broca's region through cellular overheating, seriously impacting speech formation.

joeyo 14y ago
Interesting. Do you have a citation for the Brock's region damage?
- anigbrowl 14y ago
  Here's a current one, but there are a great many more papers on the subject if you hit Google Scholar or suchlike: http://schizophreniabulletin.oxfordjournals.org/content/early/2011/11/22/schbul.sbr144.short http://schizophreniabulletin.oxfordjournals.org/content/earl... However, the specific condition I was thinking of is 'Olney's lesions' (overview: http://www.camtriplehelix.com/journal/issue/3/breathing-in-the-problem-a-link-between-inhalant-anaesthetics-and-alzheimers/pdf http://www.camtriplehelix.com/journal/issue/3/breathing-in-t...). It should be noted that some critical research has been withdrawn in this area, which I had missed, so that raises questions about the accuracy of my original remarks: http://www.erowid.org/chemicals/dxm/dxm_health1.shtml http://www.erowid.org/chemicals/dxm/dxm_health1.shtml
Homunculiheaded 14y ago
When looking at pharmaceutical drugs that also have a recreation use I think the number one thing to be concerned with is how addictive they are. From what I can find there really isn't any evidence to support the claim that ketamine is very addictive. Also depression is in and of itself dangerous. Even avoiding the entire topic of suicide, depression can lead to a variety of self destructive behaviors and poor decisions. Additionally plenty of people suffering from depression will naturally 'self medicate' with drugs that don't actually address the underlying neurological issues that ketamine might, and certainly can cause physical harm. I think it's somewhat odd that in the 21st century we still aren't comfortable seeing physical and mental illness on the same level. People committing suicide die of an illness in no different a way than people dying of cancer. Yet there is very little in the way of public support of combating suicide the way there is for cancer. There is little debate that opiates (dramatically more risk for abuse) should be used to treat physical pain, and yet people get very nervous about the potential for misuse in a much less risky drug which could provide similar relief to mental anguish.

chunkyslink 14y ago

I used to take quite a few drugs recreationally and I can quite honestly say that Ketamine gave me 'God like' experiences unlike anything else I have ever experienced. Repeatedly (and reproducibly) I could 'see' everything in the universe from the smallest particle to the planets and solar system in one go. I could comprehend nature, science and space and observe everything working as a system, from a point way above it all (it is dissociative after all). It made me euphoric and happy and when coming down from the experience I could (and still can) remember that feeling and how powerful it was / is. Of course to an observer I was basically asleep in a chair. This news doesn't surprise me at all.

alwaysinshade 14y ago
I had a somewhat different experience. I thought that I had stopped breathing and that my heart had ceased (in actual fact my body was numb - I couldn't feel a pulse) so I stood in front of a mirror completely naked for the next 20 minutes staring at my chest. Thankfully reason stepped in and I managed to compute that if my pulse or breathing had ceased, I'd be in a heap on the floor rather than obsessing in front of a mirror. Suddenly I felt calm and proceeded to throw out some cool graphics in Photoshop and made an excellent puff pastry quiche. Again, without clothes. My lesson was that drugs should be experimented with in the company of a friend or partner.
- andersbreivik 14y ago
  * Take Ketamine * Make Quiche Wat.
- deleted 14y ago
  [deleted]
- ktizo 14y ago
  Sounds like quite a risky quiche. Did it come with extra crunchy bits?
  - 001sky 14y ago
    http://en.wikipedia.org/wiki/K-hole http://en.wikipedia.org/wiki/K-hole

soup10 14y ago

Recreational drugs temporarily make people happier? No way... I'm glad the fine minds at Yale are studying such important, ground breaking stuff. I can't wait until this research leads to new antidepressants that turn more people into zombies.

hack_edu 14y ago
The only difference between recreational drugs and prescribed medicine is your doctor's prescription.
- waterlesscloud 14y ago
  And quality control.
  - robbiep 14y ago
    and set and setting
  - D3 14y ago
    But alcohol manufacturing processes have plenty of quality control applied to them. Not to mention that prescription medicines have a high incidence of being used recreationally. This point is moot.
navs 14y ago
I'd rather be a zombie than continue on as I do today
- nitrogen 14y ago
  If you are depressed, until you can find a solution, please use all your intellectual might to fight against the emotional bondage of depression and hold on to the rational knowledge that there remains a better existence out there, and that one day you will find it.
- OldSchool 14y ago

deleted 14y ago

[deleted]

scotty79 14y ago

Was the antidepressant effects of ketamine observed at normal anesthetic dosages (1-2mg/kg)?

sneak 14y ago
The antidepressant effects are found at even half of that.

siganakis 14y ago

Also of interest is the observation that Ketamine (and PCP) are associated with NMDA Antagonist Neurotoxicity (Olney's Lesions), a form of brain damage. Not really something you should want to self medicate with at this point until more research is done. http://www.dextroverse.org/txt/olney.txt http://www.dextroverse.org/txt/olney.txt http://en.wikipedia.org/wiki/Olneys_lesions http://en.wikipedia.org/wiki/Olneys_lesions

civilian 14y ago
I originally majored in biochemistry, so this stuff is a nerdy enjoyment. The levels of ketamine required to form Olney's Lesions are 40mg/kg (given olney.txt), whereas the typical dose to reach a k-hole (the highest recreational level) is 1mg/kg. http://www.erowid.org/chemicals/ketamine/ketamine_dose.shtml http://www.erowid.org/chemicals/ketamine/ketamine_dose.shtml Also: http://en.wikipedia.org/wiki/Olneys_lesions#Controversy http://en.wikipedia.org/wiki/Olneys_lesions#Controversy In addition, the dosage levels of recreational ketamine are lower than the anesthetic dosages of ketamine. Repeated use of ketamine would probably still cause problems though, though the problems would be more along the lines of general drug dependency and not being able to think straight. > Not really something you should want to self medicate with at this point until more research is done. I dunno. Depression can be really dangerous & costly too-- both from suicide and just generally not being happy in life.
- dtf 14y ago
  Ketamine has been known to be "psychologically dependent" with heavy use - I guess the real world might seem a bit dull for some after all the crazy things that happen in the K-hole. But very heavy users can also experience extreme bladder damage, as their tolerance and dosage rise. It's fascinating to see these demonised recreational drugs being researched finally for their beneficial side-effects, sometimes in very small doses. Another one that comes to mind is the reported use of sub-psychoactive doses of LSD to combat the horror of cluster headaches.
  - civilian 14y ago

starpilot 14y ago

> In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. Research at Yale has shown that damage of these synaptic connections caused by chronic stress is rapidly reversed by a single dose of ketamine. There's burgeoning evidence that depression is tied to a lack of neurogenesis (creation of new brain cells), which may also be tied to serotonin levels. Some believe that the reason SSRIs take weeks to have antidepressive effects, even though serotonin levels are restored almost immediately, is that it takes a while for that to stimulate new brain cells. It's far from certain though that serotonin has anything to do with depression or neurogenesis. The atypical antidepressant tianeptine (currently unapproved in the US, but widely used in western europe) apparently reduces serotonin levels while boosting neurogenesis, the study of which is summarized well by Stanford neuroscientist Robert Sapolsky [1]: > … tianeptine prevented many of these stress-induced changes. These included the spectroscopic alterations, the inhibition of cell proliferation, and a significant increase in hippocampal volume (as compared with stress + vehicle animals). Of significance (see below), tianeptine did not prevent the stress-induced rise in cortisol levels. The restoration of hippocampal volume is important because it's been shown that low hippocampal volumes correlate with emotional abuse in adolescents [2] (also by Yale researchers). This was breathtaking for me - bad parenting literally causes brain damage. Special K and tianeptine aren't the only efforts at curing depression through neurogenesis. Neuralstem [3] is testing a drug in humans to treat major depressive disorder by restoring hippocampal volume, with a controlled study to complete early next year. That is the only new drug I'm aware of. Regardless, the serotonin model of depression, the one which produced Prozac etc. isn't the last word, and it's looking more likely that a dearth of new synapses may be the culprit in clinical depression. [1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ [2] http://www.medpagetoday.com/Pediatrics/DomesticViolence/30029 http://www.medpagetoday.com/Pediatrics/DomesticViolence/3002... [3] http://www.neuralstem.com/pharmaceuticals-for-depression http://www.neuralstem.com/pharmaceuticals-for-depression

robbiep 14y ago
On the point of neurogenesis this is also the theorised mechanism of Electroconvulsive therapy for Treatment-resistant depression - it's been interesting watching the evidence for the mechanisms of the 2 different treatments slowly grow

fluxon 14y ago

Yale scientists excitedly, repeatedly explain to anyone in the quad how ketamine vanquishes depression within hours, in, you know, a million million ways (yale.edu) I've read too many Onion headlines to ever read headlines like this again.

kevinalexbrown 14y ago

Here's my shot at "the most revealing job interview question" (not looking for a job, I do neuroscience in a separate area): The review explains why the rapid action of ketamine excites so many researchers: The discovery that ketamine rapidly increases the number and function of synaptic connections has focused attention on synaptogenesis as a fundamental process for the treatment of depressive symptoms and also suggests that disruption of synaptogenesis and loss of connections underlies the pathophysiology of depression. This excites researchers not because ketamine itself would be used to combat depression, but because depression is still extremely symptomatically defined, making it difficult to design treatments for. That's roughly how it's diagnosed in the diagnostic manual used by most psychiatrists: check off a list of symptoms, if you have enough, you're depressed. It's like going to the doctor and explaining that your stomach hurts and they say "well, looks like you have abdominal pain, here's some Advil." Treating the symptoms would be great if only there were a happiness dial in the brain. Indeed, the effect of most anti-depressants is often demonstrated prior to a mechanistic understanding of why they make many patients feel better. Recently there has been substantial evidence of "synaptogenesis" - the formation of new potential connections between neurons - from multiple treatments, including ketamine. So now we have this new picture emerging: depressed patients tend to have atrophied and "less-connected" neurons in some brain areas, and some drugs can reverse it, in particular ketamine can reverse it quite rapidly, and it works in rodents as well as humans. That makes it very amenable to study. The way this often works in the lab is the following. Take some rodents, subject them to unpredictable stress to get them depressed, then give some ketamine. It makes them better. Euthanize the rodents, slice the brains, and note that the non-ketamine ones have less dendritic spines in certain areas ("potential input points to a neuron"), but remarkably, the ketamine ones have more in those areas. The most important step comes next, where you try to find out what ketamine is actually doing, since, again, there's no happiness dial in the brain. Create strains of "knock-out" rodents, where you block the production of certain chemicals or proteins you think ketamine might affect by altering their genetic composition. This step is crucial, because it allows you to find out which effect of ketamine is providing the benefit, because there are many. You can do this both by observing both behavior (does the ketamine not improve mood in the genetically altered rodents?) and in physiology (does the ketamine still increase synaptogenesis in the altered rodents?). In the end you can kind of work out a map of sorts: ketamine does X things to the brain and Y in X are the ones that are important, sometimes in certain combinations. Then you can start creating intelligent drugs that pinpoint those important processes, to avoid the unfortunate side effects of drugs like ketamine. Moreover, you now have a better physiological understanding of depression, instead of just a symptomatic one. To put it in machine-learning language, it's like going from ideal observer analysis like mutual information, to an actual parametric model where you understand the distributions themselves.

agpen 14y ago

If you're going to take ketamine, please be careful, it's a very dangerous drug because studies show repeated exposure puts you at high risk of accidentally liking dubstep.

lutusp 14y ago

> Yale scientists explain how ketamine vanquishes depression within hours Translation: "Yale scientists speculate about how ketamine vanquishes depression within hours" And until there's a strictly designed study with a control group, we'll be no closer to a definitive answer. But considering the drug and its role and target, a control group would be unethical.

lifeisstillgood 14y ago
Err why is a non lethal, not particularly damaging drug going to be an unethical drug trial?
- lutusp 14y ago
  > Err why is a non lethal, not particularly damaging drug going to be an unethical drug trial? Antidepression drugs, indeed all psychoactive drugs, are always a potential ethics issue. Consider the brouhaha that erupted when it was discovered that some antidepression drugs caused people to commit suicide or have suicidal thoughts: http://www.medicinenet.com/script/main/art.asp?articlekey=31649 http://www.medicinenet.com/script/main/art.asp?articlekey=31... A quote: "The FDA has warned that children and adults taking antidepressants can become suicidal in the first weeks of therapy and that physicians should watch patients closely when first giving the drugs or changing dosages. The FDA is asking drug manufacturers to place explicit warnings about the drugs' side effects, including the risk of suicide, on their labels." Any human-administered drug is a potential ethical issue, from vitamins upward. Imagine a study in which an experimental group is given a daily vitamin, and a control group is given a placebo but told they're receiving a vitamin. Several years go by and the relative health of the study participants is closely monitored. Can you not see the ethical issue here? Can you not imagine the lawsuits that would result from the parents of those in the control group who perhaps didn't thrive as expected, or for some completely imaginary consequence having nothing to do with the vitamin study, but sufficient to sue for civil damages? And finally, depression drugs are hardly "non lethal, not particularly damaging". They are a source of great controversy and have been the focus of a number of conflicts over the years.
  - 14y ago

pella 14y ago

Ketamine & autism "Drug Reverses Abnormal Brain Function in Rett Syndrome Mice" http://www.sciencedaily.com/releases/2012/10/121003132418.htm http://www.sciencedaily.com/releases/2012/10/121003132418.ht... "ScienceDaily (Oct. 3, 2012) — A promising study out October 3 in the Journal of Neuroscience showed that in a mouse model of Rett syndrome, researchers were able to reverse abnormalities in brain activity and improve neurological function by treating the animals with an FDA-approved anesthesia drug, ketamine. Rett syndrome is among the most severe autism-related disorders, affecting about one in 10,000 female births per year, with no effective treatments available."

DanBC 14y ago

Hacker News has a few readers who self-experiment with a variety of substances. I'm not trying to stop them, but there are reports of Ketamine abuse being damaging to the bladder. Some people have had their bladders removed. (http://www.bbc.co.uk/news/health-17411492 http://www.bbc.co.uk/news/health-17411492) (http://www.bbc.co.uk/news/uk-17344089 http://www.bbc.co.uk/news/uk-17344089) I have no idea on the dosing needed for harmful effects - is several large doses enough? Would very many small doses be harmful? Some people taking anti-depressants do so for a long time. Most are recommended to take them for at least two years to prevent relapse, but some medications (especially venlafaxine) can be hard to come off. (I've been told that I'll probably be taking venlafaxine for the rest of my life.) So, this news is exciting because better understanding of mental health problems is really important, and better treatments would be fantastic. But please be careful when self-experimenting with possible nootropics.

ktizo 14y ago
My understanding is that ketamine processes through the body slowly, so if you take it in reasonably large doses every day, you can saturate your system quite easily, which can lead to crystal formation in soft tissues, which is extremely dangerous. In single extremely large doses, or in regular doses that are small enough for your body to process, it would seem to be very safe however.
Alex3917 14y ago
People have been using Ketamine for decades and the bladder damage didn't seem to start until a couple years ago, so it's possibly not due to ketamine itself.
- ktizo 14y ago
  I know people on the London party scene who got these symptoms over ten years ago. I suspect that it wasn't until there was a culture of people taking large daily doses that this issue became prevalent, as it would be unlikely for this to happen either medically, or among those who were taking this as an occasional psychedelic. It takes chronic long term exposure for these symptoms to occur.

espeed 14y ago

In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. MSG is monosodium glutamate, and there is research to show MSG is toxic -- it's the glutamate that's bad for you, not the sodium. Flooding your body with excess glutamate throws off the brain's delicate balance of this neurotransmitter and leads to excitotoxicity (http://en.wikipedia.org/wiki/Excitotoxicity http://en.wikipedia.org/wiki/Excitotoxicity). The blood-brain barrier protects you from some of it, but the blood-brain barrier is not fully formed in babies, and this is why MSG not allowed in baby food. However, the blood brain barrier can be weakened by any number of reasons in adults, such as when you have a fever. Why would ketamine's release of glutamate be different and good for you in this case?

D3 14y ago
Because it's a potent NMDA antagonist which blocks glutamate induced excitotoxicity. Also see: http://en.wikipedia.org/wiki/NMDA_receptor_antagonist#Potential_for_treatment_of_excitotoxicity http://en.wikipedia.org/wiki/NMDA_receptor_antagonist#Potent...

victorbstan 14y ago

In the article, near the end, they suggest that scientists are looking into alternatives that work like Ketamine, but so far none work as fast as K. "Efforts to develop drugs that replicate the effects of ketamine have produced some promising results, but they do not act as quickly as ketamine. Researchers are investigating alternatives they hope can duplicate the efficacy and rapid response of ketamine." So my question is, why not just administer K?

Jtsummers 14y ago
Side effects from abuse, and the short term (7-10 day) duration of the effect. If they can isolate the effective properties and recreate them, it's possible to find a drug or drugs that can solve those two problems. Also, it's unlikely that (due to it's potential for abuse) ketamine prescriptions will be handed out anytime soon. So patients can go in for weekly treatment, or researchers can find something more palatable to the current political climate.