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  1. #1
    DF Jedi Robbo's Avatar
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    Info The Ketamine Key for Depression

    The Ketamine Key


    The horse tranquilizer helps depressed patients experience pleasure again.
    Published on October 24, 2014 by [Only registered and activated users can see links. ]in [Only registered and activated users can see links. ]

    [Only registered and activated users can see links. ], a persistent sad mood and lack of ability to experience pleasure, is a symptom of many [Only registered and activated users can see links. ]disorders. It’s debilitating, [Only registered and activated users can see links. ] and often difficult to treat. Most treatments such as [Only registered and activated users can see links. ] and medications take weeks to kick in, which means lengthy hospitalizations or time off work. Current medications do very little for the lack of ability to experience pleasure (called [Only registered and activated users can see links. ]). In fact,[Only registered and activated users can see links. ], the first line medicines for [Only registered and activated users can see links. ], can make that symptom worse by increasing a feeling of numbness.

    The ability to feel pleasure is, in some ways, what makes life worth living. It is also a primary factor in [Only registered and activated users can see links. ] to do things, and a lot of the functional problems that derive from depression are due to lack of motivation or interest. Anhedonia makes it hard to get out of bed, hard to engage in work or fun, hard to care about what happens to ourselves and our loved ones. Anhedonia means you don’t derive as much pleasure from eating, and you don’t look forward to that trip to Bermuda you’ve been planning for a year. Anhedonia is often the very last symptom to get better when one is recovering from depression.

    Traditionally, the neurotransmitter thought to be responsible for experiencing pleasure is [Only registered and activated users can see links. ]. Rodent studies show us that bursts of[Only registered and activated users can see links. ] from the [Only registered and activated users can see links. ] is a key to experiencing reward. These [Only registered and activated users can see links. ] areas are a big part of the reason some engage in addictive behaviors. [Only registered and activated users can see links. ] and [Only registered and activated users can see links. ] are examples of agents that act on the dopamine system in an overwhelming way, causing immediate pleasure, reward, and increase in planning and speeding up of behavior, followed by a crash and feelings of depression, leading to cravings for more. Parkinson’s disease, caused by death of dopamine-producing cells has depression as a key symptom. The dopamine replacement medicines improve both depression and anhedonia in Parkinson's patients. Parkinson’s medicines don’t seem to work for people with depressive disorders not associated with Parkinson’s, however.
    Pharmacologic agents that work on the dopamine system in other ways, such as methylphenidate, sometimes help increase motivation and energy in someone with depression, but it can also cause anxiety, [Only registered and activated users can see links. ], and jitteriness.
    As with everything in the brain, the story isn’t so simple as a single neurotransmitter system like dopamine. Neurotransmitters have complex interactions. Another system using the neurotransmitter glutamate has always been known to be at the heart of depressive disorders. [Only registered and activated users can see links. ]is the major excitatory neurotransmitter in the brain, meaning it is the “on” switch. Problem is, if things are put “on” too aggressively or too much, you get what is called “excitotoxicity” leading to neuron damage and even cell death. There’s some evidence that glutamate overload of glutamate receptors like the NMDA receptor may be responsible for the key symptom of depression, anhedonia. Chronic [Only registered and activated users can see links. ] seems to damage the nerve synapses.
    In a [Only registered and activated users can see links. ] (news coverage [Only registered and activated users can see links. ]), researchers described how they used a [Only registered and activated users can see links. ] of the NMDA receptor and partial dopamine receptor [Only registered and activated users can see links. ], [Only registered and activated users can see links. ] (originally developed as a tranquilizer/anesthetic agent that is now used mostly in veterinary practice and sometimes in children) to rapidly reverse the symptoms of anhedonia in depressed patients. [Only registered and activated users can see links. ] for its ability to quickly relieve depression unlike any other pharmacologic agent we have. It is typically used intravenously, and can cause hallucinations and dissociation (in fact it is also known as the club drug “Special K"). However, it seems to be able to reverse damage to the synapses caused by chronic stress, and relieve the symptoms of depression very quickly, within 30-40 minutes.

    The down side to ketamine (besides lack of FDA approval for depression, the hallucinations, and lack of general availability) is that the effects don’t last. If you are lucky, you get a couple of weeks, then the depression comes back. Researchers and doctors, however, are hoping ketamine could be used as a bridging agent in seriously depressed, hospitalized patients, allowing them to feel better immediately while other, longer acting but much slower onset agents have a chance to get into the system and do their work. The immediate reversal of the key symptom of anhedonia may be an even more important lesson we can learn from the use of ketamine.
    In the latest study, patients with [Only registered and activated users can see links. ], currently depressed, went to the National Institutes of [Only registered and activated users can see links. ]. They were each given an infusion of ketamine or [Only registered and activated users can see links. ], then crossed over to the other treatment/placebo after a two week period. While technically this was a double blinded study, since the ketamine causes immediate drug effects, hallucinations, and dissociation, it was likely the patients knew whether or not they were receiving drug or placebo. Brain metabolic activity was measured using a[Only registered and activated users can see links. ]for 2-3.5 hours after the infusion.
    Scale measures of anhedonia were significantly decreased over several measures across the 14 day period after ketamine infusions, meaning ketamine is the first treatment that can rapidly decrease anhedonia in depressed patients. The researchers were also able to find specific areas of the brain in patients who responded to ketamine that had increased metabolism on the PET scans, specifically the right dorsolateral prefrontal cortex, the dorsal anterior cingulate cortex, the putamen, and some other key areas already known to be associated with depression symptoms. It could be these areas are specifically related to the experience of pleasure and, its counterpart, anhedonia.
    One other fascinating part of the study is that the bipolar patients who were on [Only registered and activated users can see links. ] had a better anti-anhedonic response to ketamine than those who were taking another mood stabilizer called valproic acid. It may be that lithium works together with ketamine to increase the metabolism in particular areas of the brain, restoring the ability to experience pleasure.
    It is suspected that the glutamate system effects of ketamine may lead to dopamine effects downstream, thus reversing anhedonia. The more we can understand about these brain systems and how they interact, the better a chance we have to develop sophisticated tools to fight depression.

    [Only registered and activated users can see links. ]


    Thanks to Robbo

    mij (27th October 2014) 


  2. #2
    DF Super Moderator Over Carl's Avatar
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    Default Re: The Ketamine Key for Depression

    Wouldn't surprise me.

    Since my teens I've always loved a serious drink. Normally won't touch it during the week, but on weekends it's quite typical for me to drink until I drop.

    When I was in my late teens/early twenties, I often used MDMA on the weekends. After a while of doing that, I noticed my preference from alcohol changed, and I actually started to dislike becoming anything more than tipsy.

    Stopped doing the M and my taste for hammering the booze came back and never went away.

    A few weeks ago I ended up reading about [Only registered and activated users can see links. ] which is a psychedelic that has an unusual side effect in that it appears to reset opiate addiction so previous addicts often no longer crave their fix, and their tolerance/immunity that builds up over time also appears to be reset.

    I doubt we will see any efforts made to seriously investigate these kind of treatments until the war on drugs is over. Otherwise if addicts could easily be cured in one low risk treatment, suddently the war would lose a lot of validity.

  3. #3
    DF Jedi blacksheep's Avatar
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    Default Re: The Ketamine Key for Depression

    Trouble with k is it rots your bladder even anaesthesiologists are often ignorant of that fact (told to me by a friend who is an anaesthesiologist talking to another v senior one). Obviously takes sustained and possibly largish doses to do this so wouldn't worry about that when your going in for an op.

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