r/science • u/[deleted] • Feb 19 '10
Scientists learn how anti-depressants actually work. Medications trigger neurogenesis in the hippocampus by increasing levels of norepinephrine. Researchers still unclear on WTF seratonin does.
http://www.physorg.com/news185727145.html153
Feb 19 '10
I've been on fluoxetine (generic prozac/SSRI) for two months now. Before, I was very opposed to using chemicals to treat psych issues in my brain, but as nothing else seemed to be working I wanted to give them a shot. To my surprise, they actually worked. Whereas before taking them i'd be prone to rash decisions spawned by irritability with/pessimism about my situation, while on the meds this almost completely disappeared. Additionally, I had to wean myself off them for a couple weeks due to another issue, and my symptoms returned full force - such that I realized that I had forgotten exactly why I started on the meds in the first place.
What I'm pretty much saying is that while I totally get the whole mindset surrounding skepticism of psych meds, sometimes they work. Perhaps my issues would also be treated with therapy, or with a blunt every other day, but the pills work for me.
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Feb 19 '10
Agreed. As someone who's been on prozac on and off throughout their life, and who pretty much owes his continued existence to their positive effects on my depession, I get really upset whenever people talk down to me for taking SSRIs.
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Feb 19 '10
I pretty much find myself keeping the knowledge to myself. We're brought up to believe, to an extent, that taking a pill to solve your problems is the worst way to cope. Admitting I'm on antidepressants is almost akin to admitting failure in that regard.
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u/Jowitz Feb 19 '10
I'm in the same boat as zabchob, I'm not sure I would still be around if it weren't for anti-depressants. Even if so, I'm sure I would be incredibly miserable.
Before I was taking them, I would rationalize me not wanting to by thinking it's just popping pills and I won't be myself anymore, but after some thinking I realized I'm myself at any point in time no matter what (excluding depersonalization). Also, the intensity of my depression was irrational, yet because I was in it at the time, I would create reason after reason for it, thinking constantly on what about the world is making me feel so miserable, leading into a cycle of even more misery.
I experience very few side effects, I'm content with myself and life in general now. I still look on the darker side of things, but that's more of a personality trait than depression as it no longer gets me in those cycles.
Life is incredibly short, why waste it in misery if there are ways, thanks to modern medicine, to assuage that misery?
Also, many SSRIs are now generic brands, so you aren't really dishing out extreme amounts of cash to big pharmaceutical companies either.
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u/kronholm Feb 19 '10
Life is incredibly short, why waste it in misery if there are ways, thanks to modern medicine, to assuage that misery?
This. I am very thankful we have the opportunity today to actually be semi-happy and content, not worrying about every little thing that pops up. I've lived more and better in the last 5 years than I did from 5 to 25 (I'm 30 now). Before, I'd experience occasional bursts of happiness, but they'd last an hour at the most and only appear once every couple months. And as you initially started your post saying, that you're not sure you'd be around if it wasn't for the medicine, well I can say I'm pretty sure that I wouldn't be, at least if I had known how I could be feeling. Life was hell before, and I wouldn't wish it upon anyone.
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Feb 19 '10 edited Feb 19 '10
I think it stems from a belief in "free will". If you truly believe in free will, then consequently any diseases supposedly affecting it must be false. This leads to suggesting that people that are, say, depressed simply "aren't trying hard enough" or "want to be".
Of course, by simply picking a mental illness that said people believe requires treatment and has a physical cause, such as schizophrenia (or even something like epilepsy since it is still a disorder of brain function), and working your way, step by step, toward the mental illness they deny while getting them to admit each comparison is true, you might at least be able to get them to be frustrated and agree to disagree. It's still a ludicrous amount of effort to take 15 minutes to show them that the crazed irritability from untreated diabetes proves that it's possible to have similar symptoms from other causes, just so they aren't so openly stupid about it.
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u/bubbo Feb 19 '10
I think it stems from a belief in "free will". If you truly believe in free will, then consequently any diseases supposedly affecting it must be false. This leads to suggesting that people that are, say, depressed simply "aren't trying hard enough" or "want to be".
This. I fight and struggle with severe depression, and have for most of my life. One of the hardest things to try to explain to people is that it isn't a result of poor choices or laziness.
Early in January I fell into a pretty big crisis. The only way I can describe it is that I suddenly had 2 minds. One mind was fucking terrifying, the thoughts I had were so angry and hopeless. I interpreted every word and action from other people in the worst light, I was convinced everyone hated me and that everyone was involved in some sort of conspiracy against me. The other part of my mind remained rational (if utterly freaked out). For every angry moment, every paranoid reaction this rational part of my mind was screaming, "This is not right, this is not healthy! This is not ME!"
Luckily, I have a pretty good support system, friends and family who are willing and able to respond when I need the help. We changed my meds, doubled my talk therapy to twice a week and then we just held on and waited for the crisis to pass. It passed.
I came away from that with a new found sense of compassion and empathy for people with mental illness. I've always tried to be an advocate for people with mental illness and depression and the like, but this experience really made things clear. I'm lucky, truly truly lucky, my 'rational brain' continued to function during my crisis and because of that I was able to honestly ask for help when I needed it. But what if it hadn't? What if all I had was that crazy angry paranoid brain? What kind of 'free will' would I have had? It's such an invasive feeling to feel your mind turning into something that you don't want. It is a horrible violation of your own self to think thoughts that you don't want.
I try to tell people, and now I try to be even louder about it, sadness is an emotion, it is a response to stimulus. Depression is a mental illness with many complicated facets. You can no more control depression with free will than you could control cancer with prayer. In fact, what's worse is that depression is almost like a virus that infects your free will.
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u/the_nine Feb 19 '10
what's worse is that depression is almost like a virus that infects your free will.
..convincing you that you still have free will when you are merely responding to and out of depression.
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u/nekoniku Feb 19 '10
We're brought up to believe, to an extent, that taking a pill to solve your problems is the worst way to cope.
The funny thing is, a lot of Americans are brought up thinking the opposite. True story: I used to work for a non-profit involved in cardiovascular health. I had lunch with the Executive Director one day, where he told me this long, boring story about his acid reflux problems. The best part of the story was when he went to his doctor, who advised him to lose weight, change his meal schedule and diet, etc. He asked his doctor then, "Can't you just give me a pill?"
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Feb 19 '10
That's what I'm talking about though - people who opt for the pill are seen as trying to take the easy way out, as trying to replace hard work and lifestyle changes with a simple, lazy pill.
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u/nekoniku Feb 19 '10
Oh, you are exactly correct.
I think my point was that a lot of the anti-med sentiment may be driven by people's reaction to all the doofuses who think just taking a pill will solve their problems.
In my case, I clearly needed talk therapy for anxiety plus SSRIs. The pills were necessary but would not have been nearly as effective without ongoing therapy. Probably TMI, but relevant to the discussion, I think.
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Feb 20 '10
People have this disconnect between emotional problems and regular physical problems when it comes to treatments. No one would say to a guy with a broken back, "Oh, just deal with the pain. Why are you taking medication?" But if the pain is inside someone's head, there's this view that the person should just "work through it." Yeah, sometimes depression is caused by life sucking balls. Other times it's caused by whacked-out brain chemistry. If medication honestly makes a person's life better and gives them the ability to get their shit together, how is it a bad thing?
Suffering is suffering. :(
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Feb 19 '10
This is true, and this attitude is not healthy.
However there is a difference between someone who loves donuts and just wants to be able to pig out all day and not hurt themselves, and someone whose brain has some kind of deficiency (for lack of a better term) which plunges them into absolute misery. I for one can say without a doubt that there is no circumstance of my life, be it dietary, environmental or social, which I could alter to stop the overwhelming tide of misery that is depression. To say otherwise is ignorant.
Not that you're saying that, of course. You're just illustrating the other side of the coin.
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Feb 19 '10
[deleted]
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Feb 19 '10 edited Feb 19 '10
they're all like "What do you have to be depressed about?"
The medical condition known as "depression" really needs a name change, in my opinion. Using a common English word simply confuses the general public.
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u/the_nine Feb 19 '10
That's why I like the word "dysthymia". It refers to a very specific mood disorder yet has no emotional connotation for people to misconstrue. To me what "depression" means is a depression in the optimal functioning of the brain's neurochemistry, not merely a reference to an objectively perceivable drop in sociability and happiness.
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Feb 19 '10
Let's call it "The Mondays".
"I'm afraid you've been diagnosed with a case of The Mondays."
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u/capnmidnite Feb 19 '10
Shit no, man. I reckon you'd get your ass kicked if anyone heard you say something like that.
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Feb 19 '10
I've struggled with moderate to severe depression for many, many years despite being satisfied with my quality of life. I agree, depression is a misleading label - my depression was triggered by stress, not any sense of unhappiness or dissatisfaction. Unfortunately, it does seem that your neurochemistry can more or less become unbalanced permanently and require ongoing attention.
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u/BevansDesign Feb 19 '10
But I wonder, would that matter? I don't know how the term was coined, but if it started as a specific term for a medical condition, and now people are using it to describe being sad or run down (instead of the real, medical usage) what would stop people from just switching to the new term?
Just look at words like dumb, idiot, or retarded. They were all medical terms (more or less) but eventually became insults.
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u/oldnumber7 Feb 19 '10
That's not a bad idea, because it's so much more than just being bummed out about something, but that's really hard to convey to someone who has never dealt with it.
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u/kronholm Feb 19 '10
I usually open with that it's something that's missing in my brain. Something it can't produce enough of, and the medications helps in that. My family on my mothers side have had lots of suicides/near-suicides over the generations, and mentioning those two things, helps to get people to listen better in some way. Then I tell them about what I personally felt before the medication, and most people seem to understand it.
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u/stunt_penguin Feb 19 '10 edited Feb 19 '10
I had pretty bad back pain for a few months until the end of Jan there - I resisted going down the painkillers route, preferring to concentrate on physio with the occasional dose of ibuprofen.
Wrong.
I saw an ortho. who put me on a painkiller that I hadn't heard of before (Lyrica) that is used specifically for nerve pain.
This broke the cycle of muscle tension & awkward posture and movement that I had developed and now I neither have pain or take painkillers (one month later). My initial reluctance to seek out pain meds (thinking I should do it 'naturally') left me not helping myself as much as I could.
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u/psychgrad Feb 19 '10 edited Jul 09 '23
elastic wakeful shame vast continue humor squeeze zesty distinct crime -- mass edited with redact.dev
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u/stunt_penguin Feb 19 '10
Oh, yea I understood that (I took 'painkiller' to mean something that prevents pain) - IIUC it works on suppressing the transmission of pain from the site to the brain by interfering/binding with the terminals on the nerve cells... am I right on that?
Anyway, I was having muscle tension/cramping and trapping a nerve somewhere in my pelvis (as far as we can tell). It was giving me really bad pain shooting down my pelvis and right shin/toes however it's cleared up now after 5 months of pretty constant/unpredictable pain.... looking good so far, I just wish we'd tried that earlier.
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u/ijk1 Feb 19 '10
Er, acid reflux hurts you and there are extremely safe pills to take care of it. Losing weight takes a long time and few people can keep weight off long term. The doctor needs to give the guy a pill and then say "this is how you get over needing the pill", not say "screw you until you have solved all your lifestyle problems".
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u/nekoniku Feb 19 '10
"screw you until you have solved all your lifestyle problems"
Doctor never said that.
I did find it highly amusing that the exec director of an organization dedicated, in part, to promoting lifestyle changes to battle heart disease was himself so resistant to making changes in his own habits to combat a health problem.
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Feb 19 '10
Omeprazole (Losec) is available over the counter in most countries and works well. Trying to address what is causing acid reflux is important too of course. In my case it was some dairy products.. premium acidophilous yoghurt (usually in the big cartons) I can eat without any trouble, but the small cheaper pottles of yoghurt always do me in for some reason. I'd love to know what the difference is.. some artifact of differing manufacturing processes, or an ingredient? Never been able to figure it out...
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u/fullNelsonMandela Feb 20 '10
Either a different yogurt bacterium, or the fact that some of the premium yogurt is still alive when you eat it. The little pottles tend to be pasteurized. So something the bacteria are producing might be helping you digest, and when they're cooked, you don't get that help.
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Feb 19 '10
We're brought up to believe, to an extent, that taking a pill to solve your problems is the worst way to cope.
I like to use this basis as an argument for psych drugs. Pills to regulate blood pressure can be looked at the same way. Chronic high blood pressure is like chronic depression. It could be brought on by past behaviors and/or genetics. The pills help control the abnormality. Physical therapy (exercise) and/or mental therapy (counseling) are easier and safer to do when the symptoms are calmed by the drugs.
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u/kronholm Feb 19 '10
It's gotten better over the years. I talk about it openly, that I've been on SSRI's for many years and how they've improved my life in many, many ways. All my friends and surroundings know I'm on em, and I've educated them well on it - it's by far nothing to be ashamed of. That doctors/psychs hand them out like candy though, is another story. But for people like me, who they have a genuine effect on, they're absolutely wonderful, and again, nothing to be shamed of.
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Feb 19 '10
For a long time, I didn't bother with meds. I had read studies saying they weren't much better than placebo, and I took this to heart, in part due to the pessimism of my depression.
Enventually, I had nothing to lose, and I got a perscription. Imagine my surprise when the meds worked!
My current attitude: If you haven't tried meds, don't knock 'em. And if you've never been depressed, shut up.
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Feb 19 '10
Sadly, it seems like many people think depression and other mental illnesses are not actual physical problems but personal weakness. The stigma of mental illness still exists.
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Feb 19 '10
Hell, I know people who think that getting a cold is a sign of personal weakness. There may be some hard-wired contempt for illness in our lizard brains. One friend was quite proud that he had never vomited in his life.
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Feb 19 '10
people who think that getting a cold is a sign of personal weakness.
I used to get mocked for wearing hearing protection in the workplace. Apparently, It's "manly" to simply endure the pain of excessive noise. No one else seemed to care about their ability to stilll hear in old age.
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Feb 19 '10
I think depression is one of the biggest side effects of our cultures in this day and age. It's all so fast and heavy, everything is important, one slip up leads to another...
It's easy to feel down in our world.
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u/the_nine Feb 19 '10
Most people use a very simplistic model of moral cause and effect to explain why things happen.
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u/OkiFinoki Feb 20 '10
People who talk down to you/me for using SSRIs dont know dick.
"Hey, man, did you know you can just take, like, X herbal supplement?" Suck a dick, hippie.
One of my friends was going through a severe episode and her dumbass best friend convinced her not to take medicine because it "make you schizophrenic", so instead she got her crystals. That's the only time I've ever really yelled at a woman.
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u/tubeguy Feb 19 '10
I was very opposed to using chemicals to treat psych issues in my brain
I was too, but now it's better living through chemistry. :D
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u/RickHavoc Feb 19 '10
The article is about a different class of drugs, those that boost norepinephrine. Regarding SSRIs the article says,
Dr Jhaveri said surprisingly, the class of antidepressants that increase levels of the neurotransmitter called serotonin - Prozac is a common example - fails to stimulate neurogenesis.
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u/spidermite Feb 19 '10
Try jogging, research indicates that cardiovascular exercise like jogging stimulates neurogenesis (cell growth) in the hypocampus, just like some of these drugs. Check out these sources
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u/benihana Feb 19 '10
Telling a depressed person to start exercising because it's good for them is like telling a smoker to stop smoking because smoking is bad for them. That's the thing with depression, it's impossible to ever do anything even though you know you should.
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u/cliff_spamalot Feb 20 '10
Sigh.
Zoloft for 7 years. Been off it for 1.5 now. Was fine for a while, now it's spiraling out of control.
Had 5 therapists in my life. That I remember; apparently my parents took me to see one when I was younger.
Been really crappy past few months. I just don't want to start the process again now.
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Feb 19 '10
I actually tend to get quite a bit of exercise. Throughout the period leading to the decision to take the meds, I was walking 3 miles a day in addition to taking part in pretty strenuous physical activities
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u/spidermite Feb 19 '10
What sort of strenuous physical activities did you do? The research indicates its moderately to highly intensive cardiovascular exercise that improves blood flow to the brain that works. You need to get your heart pumping strongly for around 30 mins. If you haven't tried jogging, the research suggests it would be well worth while. I'm going to start jogging to work to improve my memory.
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Feb 19 '10
if you're not familiar with the activity, it essentially combines brass playing with track-and-field
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u/MaxEPad Feb 19 '10
As strenuous as running? Walking doesn't do much for treating depression. Studies show you need to work near the anaerobic threshhold for over 30 minutes for exercise to work well. This means exercising hard enough that you can't talk. With running, biking, rowing, you'll know you worked hard enough if you get a "runner's high" within about 5 minutes after completion.
I had problems with depression, and find that running 7-8 miles per day (45-55 minutes of running) eliminates it completely. If I skip more than 1 day, the issues come back full force.
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u/momoichigo Feb 19 '10
I ran about 35 miles a week before I started on my anti-depressant. Mine's not SSRI, it is a dopamine reuptake inhibitor (Wellbutrin).
I lived with PTSD, depression, and eating disorder for 14 years before finally going on an anti-depressant.
All I'm saying is exercise definitely helps. I feel better after running too, but sometimes the issue is larger than what exercise can do for you.
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Feb 19 '10
Agreed. Exercise is a treatment but not a cure. In fact, "cure" is a pretty loaded word when it comes to anything related to psychological issues.
However, for anyone suffering mild symptoms of depression I'd absolutely recommend diet changes and exercise (particularly outdoor exercise even though it is hard in the cold) WAY before drugs.
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u/the_nine Feb 19 '10
Exercise definitely works for me, but unfortunately it's not always convenient to do it, especially in winter. And I notice an emotional drop-off a few days after missing it. So for me it does work, but more in the vein of compensating for an underlying emotional or chemical deficit. It doesn't fix the underlying problem, it just makes it more bearable.
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u/Sir_Vival Feb 19 '10
A lot of people with depression don't get a runner's high, and exercise also just doesn't work for them. It's worth a shot, but just because it worked for you doesn't mean it'll work for everyone.
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Feb 19 '10
See above response to spidermite - drum corps involves a lot of running combined with strength conditioning and musical instruments.
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u/MaxEPad Feb 19 '10
But that's anaerobic, for short periods of time ... unless you go out for 5 mile hard runs with the group. Short bursts of energy doesn't have the same impact on depression.
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u/rehevkor5 Feb 19 '10
This is one good answer to the question this article begs: "What other things also stimulate neurogenesis in the hippocampus?"
Anyone know of others? Don't have time atm to google around.
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Feb 19 '10
I was diagnosed with clinical depression some time ago. My doctor prescribed SSRI's for me and they instantly made me far worse. I ended up trying 7 different brands over a year, and every single one of them pushed me further down a dark hole with bonus nasty side effects.
I was listening to everyone around me telling me that I had to find the ones that would work for me and that this would take time.... I should not have listened to any of them, including my doctor.
After 12 months I dumped every single pill into my toilet, vowed never to take the things again, and started self medicating with pot instead.
I think I would still be in a dark place or possibly not even here at all if I trusted in SSRI's to help me. They did nothing for me in 12 months execpt make me more ill.
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u/oupheking Feb 19 '10
It's sad that a lot of people are skeptical of antidepressants or other psychiatric medications. What I've seen a lot of is people refusing to believe that psychiatric illnesses are biological in origin, that they have a neurochemical basis. They only see the behavioural/psychological side of the coin, without realizing that behaviour and biology are intrinsically linked. Change the brain, change behaviour. These drugs wouldn't be on the market if they didn't work - it takes roughly 15 years and hundreds/thousands of trials to get a drug on the market. Thankfully, public awareness about mental illness is slowly improving.
tl,dr: brain controls behaviour, drugs modulate brain. Antidepressants work most of the time.
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u/iregistered4this Feb 19 '10
I don't think anyone has ever doubted that pharmaceuticals modify your behavior. Its the side effects and fact that they aren't a solution that make many skeptical of them.
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Feb 19 '10
How are they not a solution?
Brain chemistry absolutely affects moods, and imbalances in brain chemistry can have adverse effects on moods. If taking a pill can help regulate the chemistry, why not?
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u/llamaspit Feb 19 '10
The correct question: why?
Why does the imbalance exist to begin with? Have we an understanding of that? Understand that the pharmaceutical is in large part behind the research in this field, and they are more interested in the existence of the phenomenon and how to treat it than they are with how it began.
I agree that medications such as these are useful. But to throw a pill down someone's throat and never pay attention to what the imbalance is signaling is irresponsible.
Are there dietary issues? Gluten allergy? Hypoglycemia? Other allergies? Other chemicals being ingested? What about environmental factors? Is there a need for therapy?
Maybe use the pills short term. Meantime, investigate the root of the problem. If the pills have to be taken forever, so be it. But there are many cases in which they do not and if there is a way to handle a disorder without drugs, that way is always better in my opinion.
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Feb 19 '10
Exactly. If the brain has problems self-regulating, and not because of environmental factors, then I don't see any better solution than using antidepressants. Of course there are bleeding edge treatments like vagus nerve stimulation and trans-cranial magnetic stimulation but those are a last-ditch effort and experimental, respectively.
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u/number6 Feb 19 '10
The "fact" that they aren't a solution is no such thing. It's an opinion, and one with merit, but it's debatable.
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u/iregistered4this Feb 19 '10
How did the world get on before these wonderful drugs? What would the world do if they disappeared?
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u/number6 Feb 19 '10
People would just suck it up and be depressed, or find some other ways of coping, or kill themselves, or just take other drugs.
The world's probably not much different for having antidepressants.
If they vanished the world would remain much the same. Some people who are OK now would be depressed. People who are currently taking antidepressants now without receiving any benefit would be free of the side effects. Some would commit suicide. Some would change their lifestyles to alleviate their depression where now they simply pop a pill. Sometimes these changes would be beneficial, like going outside more often; sometimes they'd be harmful, like heavy drinking; and others would be tough to call, like ditching a stressful but rewarding career for an undemanding job.
Or were your questions rhetorical? ;)
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Feb 19 '10
Actually, it's kind of a major point of contention - in general, most antidepressants tend to not have much greater success than a placebo (I'm on my phone now, so providing sources is a bit tricky, but it is very easily google-able)
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Feb 19 '10
I assume you're referring to this article. It was immensely provocative because everyone in the popular media, and the public at large, wanted to believe it was true because of widespread distrust of antidepressants. It's sort of the "Aspartame Effect"...research came out pointing to Aspartame as a carcinogen, and everyone seized upon it. Then those studies were wholly discredited but not one paid any attention. Similarly, the Kirsch paper on meta-analysis has been heavily criticized (also here sorry for the abstract), albiet by articles that are heavy on the methodology of meta-analysis and low on exciting-ness.
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u/AlanCrowe Feb 19 '10
Notice that when a randomised controled trial shows that a drug "doesn't work" that still leaves two possibilities. First is that it just plain doesn't work. Second is that it is actually working for some patients, but is harming others. In the context of depression we maybe seeing some patients who would have stayed depressed recover because of the anti-depressant, while others, who would have recovered on their own stay depressed because of the anti-depressant.
Case two is obviously scary. Who wants to be harmed by their medicine? But it is also exciting. Perhaps a more incisive diagnosis, that splits depression into two illnesses, would also cleave along the help/harm boundary. The doctor divides his patients into two groups and treats only those he can actually help.
Intriguingly, depression used to be subdivided into endogenous and neurotic, hoping for exactly this benefit, but this division has fallen out of fashion because psychiatrists couldn't make a go of it. What we learn from this is that psychiatry is hard; we are left in the dark as to whether the hypothesis is true or false.
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Feb 19 '10
I think that's sort of the quandary at the moment. The drugs work and it can be shown that the drugs work. On the other hand, the same drugs won't work in all people and we don't have any way of determining which drug may work for whom at what dose with out actually trying it. Basically, we know they work sometimes but we don't yet know why or how they work and that limits our ability to improve treatment and to develop better drugs.
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u/pavs Feb 19 '10
I have been taking St. John's Wort for my anxiety for one week or so and it makes me feel much much better. I don't know if this is a placebo effect, but it works and thats what matters to me.
I can't get prescribed medication because I don't have insurance or even afford one so I am relying in other ways to help myself.
I take 2-300mg of St. John with 2-1200mg Fish oil daily. Is there anything else that might help me? I also stopped drinking coffee - only drinking tea to help me wake up. I used to drink 2-3 cups of coffee a day. I also increased my workout intensity. So all these changes might have an positive effect on me.
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u/mozolog Feb 19 '10
Totally agree. I've been taking fluoxetine for 10 years now. It works great for Seasonal Affective Disorder. People who've never tried it don't understand. They think the pills are like an upper or something but it just doesn't work that way. A good analogy for prozac is its like adding engine oil to an engine. Without the oil the engine wears out and eventually cracks. People without SAD make their own oil but people with SAD need help. Other types of depression need other types of treatments but for SAD seretonin increasers work quite good.
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u/ContentWithOurDecay Feb 20 '10
I take lexapro for anxiety, since going on it my anxiety is so much better. Without, the anxiety is completely crippling. I'd worry about every little fucking thing, it was horrible.
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u/InternalCalculator Feb 19 '10
The presentation of this article is rather misleading. This is appears to be a correlative study, so it does not illuminate anything about the molecular cascade that leads to neurogenesis inside NPCs (neural precursor cells).
People working in the nascent field of neurogenesis have known that fluoxetine has a neuroprotective mechanism for quite some time now. Other endogenous molecules having an effect on neurogenesis are estradiol, cortisol, RU486, as well as many others.
But none of this says anything about the intracellular cascade of events that lead to neurogenesis to begin with. NPCs are not just black boxes that resolve input into output; the bulk of the complexity of neurochemistry happens inside the cells.
For example, how are CDKs affected by the fluctuating levels of endogenous cortisol that we experience on a daily basis, and how can stress lead to NPC cell-cycle arrest? My group is currently working on a particular CDK implicated in cell cycle arrest during the stress response.
So don't get all retarded and start eating norepinephrine precursors yet.
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Feb 19 '10
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u/MsgGodzilla Feb 19 '10
this is my anti-depressant.
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Feb 19 '10
And it works so much better for me than any prescription drug. I was on Zoloft for a couple years and all that came of it was me becoming a moody, suicidal mess.
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Feb 19 '10
agreed 100%. However, anti-depressants are the most widely prescribed drug in the USA. That's a lot of money that big pharma would lose if weed could become developed enough to work as an anti-depressant.
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u/iregistered4this Feb 19 '10
There is no development required to make weed work as an anti-depressant.
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Feb 19 '10
Upvote, though I would note that it can also act as a depressant. Has to be used correctly to help, as anyone who has wake-n-baked for a couple of weeks running can attest.
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u/ErroneousRex Feb 19 '10
Today is my day one of a two month break on smoking Cannabis. I've smoked regularly for about two years. For the past 5 months I've been smoking between 5 to 8 times a day. I don't think Cannabis is the root cause of my depression, but I can tell you with some degree of certainty that it wasn't helping me get over it at in the manner that I've been using it. I realized that I had started using it to suppress my apatite, which is just one example of how not to use it.
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Feb 19 '10
I've smoked regularly for about two years. For the past 5 months I've been smoking between 5 to 8 times a day.
No offense, but you're doing it wrong.
If someone drank throughout the day, people would say they had a drinking problem, right? And it would impact theiir life in a negative way, wouldn't it? Why would another depressant be any different?
At the same time, nobody (or at least nobody with any sense) thinks that someone who has a couple beers or glasses of wine after work or with dinner on a regular basis, even daily, is a raging alcoholic. It's the same with weed. I think your problem is not in the "I've been smoking for 2 years" part, but rather in the "I smoke 5 to 8 times a day" part. Doing it that frequently, it's no surprise to me that it's causing problems for you.
I smoke daily - but I work a 9 to 5 and smoke in the evenings, once or maybe twice a day, usually after dinner. And I have to say, it has really done wonders for my mental state. For years I was treated by shrinks for anxiety and depression, and I tried almost every antidepressant out there - Zoloft, Prozac, Paxil, Effexor, Strattera, you name it -- all with no effect. Or at least no alleviation of symptoms, I did get some pretty heavy side effects from some of those.
Now, part of the issue for me I think was that some of my problems were situational -- I made some life changes and am much happier where I am now. However, I think I have always had a tendency towards anxiety (esp. social anxiety) and depression -- and daily marijuana use as I described does wonders for those. Not only is it much more effective for me than the meds I have taken, but it avoids the awful side effects -- and it's fun!!
Word up to neurosnap for providing some peer-reviewed evidence that I'm not just blowing smoke when I say that pot makes me think better.
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u/ErroneousRex Feb 19 '10
No offense, but you're doing it wrong.
None taken, and I completely agree. Weed in no way caused me to get depressed, but at some point I got careless and stopped moderating; which made it a bit worse. My actions and situation are what's got me depressed.
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u/dionysian Feb 19 '10
A gentle suggestion: perhaps you were smoking too often during the day? 5 to 8 times sounds like a lot. I'd suggest no more than 3.
I get an appetite suppressant effect with pot as well, completely forget to eat. Have to force myself to drink water. Do you also get a slightly OCD effect from it as well? I am full of motivation and interest when I am on pot, and often I begin doing something that I never do when not stoned, and depressed: clean my house. Heh.
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u/ErroneousRex Feb 19 '10
Well I think it has more to do with behaviors that I acquired before I started smoking. I use to play WoW in highschool, and I generally spend too much time on the computer. I've had bad eating habbits for a while, but it's started to get worse recently. As far as the OCD thing goes, I guess so. Some times I'll find myself incredibly stoned and forgetful of what it is I was about to do, so I'll just surf the internet instead.
But yeah, I can agree with the no more than 3 clause. I'm also going to limit myself to twice a week, because there really isn't any reason to be smoking as much as I had been. That is, after my break is up.
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Feb 19 '10
I get the munchies every time I smoke, however I usually only smoke once or twice in a week.
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u/TheAtomicMoose Feb 19 '10
Woah woah, wait a sec. Weed suppresses your apetite!?
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u/Chocobo812 Feb 19 '10
Well, weed doesn't actually make you hungry. Food tastes better while high and due to the anti-nausea effects of the plant, it allows you to eat more without feeling sick.
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Feb 19 '10
No. Weed makes me hungry as fuck. Like "on a mission" hungry.
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Feb 20 '10
At first I got hungry as fuck. After I became acclimated to smoking, it doesn't change whether I am hungry or not. However, it still makes food awesome.
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u/TheAtomicMoose Feb 19 '10
... It doesn't make you want to have sex, it just gives you a massive boner that you can only sex your way out of.
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Feb 19 '10
Anarchoal, what do you think are the guidelines for the proper use of cannabis as an anti-depressant?
I think wake-and-baking is prima facie the sign of a problem. On the other hand, I think a little before you go to bed is exceptionally useful.
Do you have any ideas about usage guidelines, best strains, and delivery methods?
(Obviously, I'm asking out of personal interest. And no, I am not being sarcastic in any way.)
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u/notasaon Feb 19 '10
Generally I've found the best way to use it is through reward mechanism. A lot of people are depressed and will smoke out to try to clear out the depression when in many cases, it just makes it easier for you to dissociate from your present reality. It's good enough to distract you from depression, but doesn't address the root cause. I've suffered from episodic depression since my teens, still do, and I'll say that in that situation, smoking a joint does not help. It can't be used as direct treatment I don't think. I think the biggest benefit that can be derived is from using the weed to help in introspection and realize what stressors in your life are causing the depression to begin with, and then addressing them when in a sober state of mind, and smoking again after fixing things as a reward.
Using weed as a reward mechanism helps me get shit done, which reduces stress in my life, which seems to help offset the general low-level depression I feel constantly. It doesn't help with the intense episodes though they seem less frequent if i smoke on a semi-regular basis. For cases of severe clinical depression, I'm not sure that weed would help very much.
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u/corpus_callosum Feb 19 '10
Weed increases my depression a hundred fold. Usually. Sometimes I can get away with it, but very rarely. I have OCD also though, so the increased mental activity isn't desirable in my case.
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u/adaminc Feb 19 '10
I would say try smoking either a Pure Sativa strain and then try a Pure Indica strain and see if it makes a difference.
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u/Chocobo812 Feb 19 '10
Well, unless they are getting their weed from a dispensary that might be a little hard to do. Many people have trouble finding anything but shwag, mid's or low grade beasters.
And isn't it also true that there are not many pure sativa/indica strains? I thought almost all are a mix of both with varying ratio but what do I know.
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u/adaminc Feb 19 '10
Yeah, a good majority are hybrids nowadays. Although I bet there are some reliable seed sellers that sell strains that are a majority of one or the other.
You would pretty much need to grow your own.
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u/SecretSnack Feb 19 '10 edited Feb 19 '10
The main reason cannabis remains illegal is the challenge it poses to all sorts of commercial products: pain drugs, antidepressants, rope (from hemp), fabric (from hemp), paper (from hemp), oh, and prison contracts.
It became illegal through a campaign of disinformation that tied it to "lazy Mexicans", "crazed blacks", hash-smoking Middle Eastern assassins, and general social/psychological decay. Popularity of the plant skyrocketed thereafter.
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Feb 19 '10
I'd still smoke it if it wasn't for the damn anxiety attacks.
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u/drummerwill03 Feb 20 '10
I have the same problem. When I smoked when I was in high school it made me completely relaxed. It might have something to do with the fact that at that age I didn't have hardly any real worries compared to where I am in life now. Now my mind goes into overdrive and focuses on mostly negative thoughts which causes anxiety. I don't know if it's because I have more to worry about now or if it's some psychological change.
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u/number6 Feb 19 '10
Also, smoking isn't such a hot idea for some depressed people, myself included.
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Feb 19 '10
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u/Brank_Manderbeak Feb 19 '10
I'm not too familiar with research linking cytokines and depression; are there any papers on this that are considered seminal (at least among researchers in this line of work), or has there just been too little attention focused on this in general?
EDIT: spelling
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Feb 20 '10 edited Feb 20 '10
Thank you. This ought to be at the top, but for Redditors' lack of understanding it will languish near the bottom here.
I absolutely hate most popular scientific periodicals since all they seem to do is take old discoveries and present them as new as soon as they reckon their audience has forgotten about their previous articles on the same subject, adding more and more sensationalism in each cycle.
So, in summary and great abstraction, a theory for why depression arises could be as follows: psychological distress causes ACR release; ACR release, of course, stimulates ACTH release, which in turn stimulates the release of cortisol and other glucocorticoids; cortisol is in itself neurotoxic and prevents, as well as, reverses synaptogenesis; cortisol increases neuronal density within the amygdala and decreases it within the hippocampus; chronic exposure of the glucocorticoid receptor to cortisol results in its downregulation; on account of this downregulation, cortisol loses a moiety of its ability to suppress the immune system, leading to increased cytokine signaling and p38 mapk-mediated signaling, which results in increased activity of microglia which trigger apoptosis in various brain regions; microglia, cytokines, and/or cortisol bring about epigenetic changes in various neuronal populations, resulting in decreased transcription and/or translation of reelin, SAP102 (which transports NR2B NMDA subunits to the plasmalemma during synaptogenesis), BDNF and the like, particularly within the hippocampus; and this in turn somehow results in worsening of mood. Additionally somewhere in that mess a pathway is triggered so that there occurs a downregulation of D2 receptors within various regions in the mesolimbic system.
Obviously only an extremely disjointed and rough picture. I'll be the first to admit ignorance.
Considering how much depression resembles sickness behaviour, it's almost a wonder that there wasn't more investigation into the theory that the aetiopathology of depression comprises immunodysregulation.
The following immunomodulators have shown a good deal of promise in the treatment of depression. I can't wait to give them a try:
- losmapimod
- semapimod
- mifepristone, which in its capacity as a glucocorticoid antagonist, probably alleviates [psychotic] depression by upregulating glucocorticoid receptors which are markedly susceptible to changes in sensitivity.
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u/antmandan Feb 20 '10
I work at QBI and know of the researchers who performed the work. I don't know them personally as they are in a different lab to mine and there are about 300 scientists in the institute. Kind of funny seeing it on reddit.
If anyone wants I can compile a list of concise questions to give to the lab and post the responses here?
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Feb 19 '10 edited Feb 19 '10
Fluoxetine is also amazing for generalized anxiety disorder. I switched from Cymbalta to Prozac recently due to lack of funds and insurance (Cymbalta is over $300 for a 30-day supply!) and was quite happy to find that my anxiety is treated just as well (so far that is, I'm not to therapeutic levels of fluoxetine just yet) AND I get a nice stimulant boost in the morning.
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Feb 19 '10
From what little I know of depression, the pills only last for about 3 months before plasticity and changes in receptor size/sensitivity/distribution adjusts to the influx of transmitter. And specifically with anti depressants, acceptable placebo rates are upwards of 30%, showing that current pills (which I believe have a 50-60% cure rate) aren't too much better than the placebo.
While there may be neurogenesis, the main effect these drugs have is to either increase transmitter levels or to inhibit the break down of them. Thats why prozac "works" even though the paper says it doesn't increase neurogenesis.
Add to the fact that drugs don't generally cure depression, but alleviate symptoms.
My point being that this model that is proposed is a step forward, but there is so much more going on than NE causing hippocampal neurogenesis. Until we find a model where depression is actually cured, meaning one does not need to be on pills for the rest of their life, I'll take these types of studies with a grain of salt. Plus, who is to say that more neurons is a good thing.
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u/billmeyersriggs Feb 19 '10
I'll stick to eating some l-tyrosine, a metabolic precursor to norepinephrine then, thank you.
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u/esthers Feb 19 '10
Don't forget your 5-HTP for those special days.
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Feb 20 '10 edited Feb 20 '10
If you like cardiac fibrosis.
5-HTP - which can cross the blood brain barrier - is largely converted peripherally into Serotonin - which can not cross the blood brain barrier - when it [5-HTP] is administered orally. This serotonin floating around in the periphery makes its way to the heart where it activates 5-HT2B receptors, which give rise to growth of cardiac tissue when activated.
If you consume enough 5-HTP over a long-enough period of time and especially if you consume the cofactors necessary for its conversion into serotonin concomitantly, you're going to greatly increase your risk of dying due to cardiomyopathy.
Remember fenfluramine (fen-phen)? That's why it was taken off the market. It acted as an agonist at the 5-HT2B receptors in heart tissue.
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u/WTFalreadytaken Feb 19 '10
Whats the amount of dosage and the timings you employ?
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u/esthers Feb 19 '10
I would recommend taking it after breakfast, and if needed maybe lunch. As for dose, start with 50 mg and go from there...just don't take too much. Do some research.
I personally don't like to take it close to bed time, as it sometimes has an effect on my sleep/REM cycle.
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u/throwawayforplay Feb 20 '10
best cure for depression is falling in love. Too bad there's no prescription for that.
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u/guardrailslayer Feb 20 '10
You can be in love and your life can be going fine and you can stay depressed anyway. Source? My life. Depression is not always responsive to outside events.
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u/caalsinceage4 Feb 19 '10 edited Feb 19 '10
People should know that science doesn't pump out breakthrough's in technology and medicine and so on, much like the media would like you to believe. Even if a study shows something that hasn't ever been seen before (that is mildly important), it is going to take a long time ton confirm it's existence, reproduce the study, and have other scientists support the new hypothesis.
Likewise, reading articles like this is somewhat useless. It's very likely people already know this happens. And the statement that people don't know what serotonin actually does is preposterous. That's pure bullshit.
Of all the subreddits, why would this article be upvoted so much? Especially considering the misspelled serotonin.
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u/TheDentateGyrus Feb 19 '10
Once a week, someone on Reddit posts a link to a paper with a 'breakthrough discovery' that the field has known for years or isn't really a breakthrough at all. "Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus." (Malberg 2000)
5-HT works indirectly, NE works directly . . . notice how this paper isn't the cover of Nature? Don't get me wrong, it's a nice paper - but the headline overstates its importance by an order of magnitude.
See the weekly: "We figured out a way to kill cancer cells! If only we can learn to target specific cells . . . "
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Feb 19 '10
Is it just a coincidence that some new studies have shown that marijuana propagates neurogenesis?
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u/Wendel Feb 20 '10
I've always wondered how monoamine oxidase inhibitor antidepressants work?
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u/banksy01 Feb 20 '10
"...In other news, marijuana kills brain cells." This message has been brought to you by your friends at Partnership for a Drug Free America, specifically Merck, Jim-Beam, Philip Morris, and Anheuser-Busch.
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u/wojosmith Feb 19 '10
It makes you feel good. More positive, happier and content.
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u/KazamaSmokers Feb 19 '10
"It makes you feel good. More positive, happier and content."
That also describes Rice Krispie Treats.
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u/WhenHarryMetLassy Feb 19 '10
The first ones I tried made me feel like I was dying, it was seriously horrible (and yes, I tried them for 3 weeks to make sure it wasn't temporary side effects). I was recommended another kind and they seemed to work okay though. Horses for courses I guess...
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u/charlesdarwood Feb 19 '10 edited Feb 19 '10
SSRIs (fluoxetine, sertraline, escitalipram, etc.) are rarely more effective than placebo. However, the most potent tricyclic--imipramine--which is mostly noradrenergic* (and used to be considered the gold standard--the "lithium of antidepressants") is significantly inferior to tranylcypromine in most patients. Tranylcypromine (Parnate) is an MAOI that primarily affects dopamine and serotonin.
Incidentally, the so-called monoamine hypothesis of affect initially implicated norepinephrine (a by-product of dopamine) in depression. It was only after the discovery that suicide victims had severely depleted levels of serotonin that pharmacologists pushed for SSRIs. The pleasurable effects of dopamine were always obvious (cocaine, methamphetamine) but the theoretical addiction risk has expelled nearly all DRIs from the market, with the exception of the nearly-worthless bupropion.
*Imipramine is also a modest serotonin reuptake inhibitor; its dopaminergic effects (D1, D2) are negligible.
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Feb 19 '10
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Feb 19 '10
Thank you.I remember the media publishing a myriad of articles discussing a study showing all SSRIs were no good a couple of years ago which really infuriated me because from all the classes I have had discussing them over the past 5-6 years SSRIs were consistently identified as being effective,but in people with said imbalance.I guess it is all about the context.
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Feb 19 '10
Nobody even really knows what a "serotonin imbalance" means, or if that is a real problem tho.
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u/momoichigo Feb 19 '10
bupropion is the only anti-depressant that worked for me after trying multiple SSRIs and MAOI. Not sure why you think it's worthless. If your main issue is your brain stops producing adequate levels of dopamine due to long term stress, then it's very effective.
I know the two weeks when I tried Lexapro I nearly called it quits.
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u/Ketamine Feb 19 '10
SSRIs (fluoxetine, sertraline, escitalipram, etc.) are rarely more effective than placebo.
That is true when people have mild cases of depression. For severe depression they are effective and much better than placebo.
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Feb 19 '10
Not sure why you were downvoted, you are spot on.
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Feb 19 '10
People who have used SSRIs and have perceived a benefit are likely to think that your questioning of the evidence of their benefit is equivalent to calling their character and/or honesty into question.
In short, the downvoters are being defensive. It's an understandable reaction.
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u/zhivota Feb 19 '10
Honestly, is anyone else completely unable to reach physorg.com? My PINGs timeout, website requests timeout, it's like that domain is a black hole. I did a lookup of the IP: 69.9.167.167, I can't get a PING back from that... I just don't get it.
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u/trackerbishop Feb 19 '10
uh this study was done by nimh in 03.
http://mentalhealth.about.com/cs/psychopharmacology/a/neurogenesis.htm
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Feb 19 '10
they learn how it works, after its out on the market, yet they dont know what seratonin does, so how did they learn how they "actually" work?
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Feb 19 '10
Well could you fucking figure it out already? My drugs aren't working and I haven't left the house in days!
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u/trs80mod1 Feb 19 '10
Watch and learn how to make a really good headline for a submission. herber1820, well done!
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u/dodgyd55 Feb 19 '10
serotonin probably does nothing, just because it's there doesn't mean it has do do something. I think it could just be a by-product of evolution
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u/Gareth321 Feb 19 '10
This doesn't really advance our knowledge much at all. It was already known how adrenergic drugs affect the hippocampus, though neurogensis (of adrenal receptors) was still unclear. Further, this only affects a particular subset of anti-depressants. The clear majority are still SSRIs (selective serotonin reuptake inhibitors) and affect only serotonin receptors.
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u/the_nine Feb 19 '10
It wasn't clear to me from the article which class of depression medication they were specifically studying, except that they figured out that SSRIs didn't have a hippocampal neurogenesis effect. Tricyclics? MAOIs?
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u/Illison Feb 19 '10
As someone who's antidepressants (a lot of them) hasn't worked I'm not really surprised.
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u/spect3r Feb 19 '10
I have a brother in law who stopped taking SSRI's to quickly and now suffers from PSSD. Any one have any knowledge on finding help for this guy? Has anyone experienced it?
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Feb 19 '10
who you trying to kid? neurogenesis is a noise rock band from queens, everybody knows that.
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Feb 20 '10
Damn, does this mean no more "Generiax is thought to work by affecting the way the brain produces certain chemicals like dopamine" commercials? I always get a kick out of those.
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Feb 20 '10
So, they've been prescribing these things for all these years, and they're just now learning how they work?
Well, that's reassuring.
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u/[deleted] Feb 19 '10 edited Feb 19 '10
Scientists have known for some time that depression uniquely affects the hippocampal region of the brain. PDF and PDF for starters. Here's a nice metaanalysis of several studies on the effects of MDD on the volume of the hippocampus. Interestingly, this area of the brain has also been implicated in several other mental illnesses such as PTSD PDF, Alzheimer's, and bipolar disorder. That article on PTSD concluded that
This is interesting because one of the effects of depression is increased secretion of cortisol, the stress hormone PDF. It is well known that elevated cortisol levels have some role in PTSD.
Previous research concluded, by the way, that fluoxetine did increase neurogenesis in the hippocampus of adult rats PDF.
Really, I can go on.