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  1. 5-HT2A
    As soon as the word depression is mentioned, we tend to think of a mental problem that may need treatment with antidepressant drugs, with all their risk of side-effects such as weight gain and loss of libido.

    But what if it actually has a physical cause that could be treated with anti-inflammatory drugs such as aspirin and ibuprofen, or even antibiotics?

    This is the fascinating possibility being explored by scientists at Cambridge University. Their research suggests that, in a significant number of cases, depression could be caused by long-term inflammation in the body.

    The idea has been gathering credibility over the past few years among researchers worldwide. Indeed, the association between low mood and bodily inflammation caused by infections should be familiar to anyone who has ever had a cold and felt miserable, listless and tired.

    Evolutionary psychology suggests that this may once have aided survival, by keeping us safe in our caves because we felt too low to go out when illness was making us both vulnerable to attack and at risk of spreading infection to our tribal fellows.

    Now, a growing body of research has linked depression with inflammation.

    In 2013, for example, investigators at Aarhus University, in Denmark, examined the health records of nearly 3.6 million people and found that those who had inflammation caused by autoimmune conditions, such as arthritis or Crohn’s disease (inflammation of the lining of the digestive system) were 45 per cent more likely to suffer from a depressive condition.

    Furthermore, those who had ever been in hospital for a serious inflammatory infection, such as sepsis or hepatitis, were 62 per cent more likely than normal to suffer from a depressive disorder, according to the study published in the journal JAMA Psychiatry.

    Earlier that year, another team of Danish researchers published a study in the same journal which found that raised levels of C-reactive protein — a substance the body produces in response to inflammation — were associated with an ‘increased risk for psychological distress and depression in the general population’.

    Results such as these presented scientists with a crucial question: do people get depressed simply because an inflammatory illness is making their lives miserable, or is there a hidden physical process that makes inflammation cause depression?

    The latter may be more likely to be true, according to an Australian study reported in the journal BMC Medicine in 2013. This found that giving healthy people drugs that cause inflammation can cause them to suffer all the typical symptoms of depression, such as low mood and lack of motivation.

    Indeed, a quarter of patients who take interferon — a medication used to treat the viral liver infection hepatitis C that, as a side-effect, causes inflammation — develop major depression. Now this link is being investigated in much greater depth by Cambridge University scientists.

    They have been following up on 4,500 children born in the Bristol area in the 1990s. They took blood samples when the children were aged nine to see if they showed evidence of raised levels of inflammation — testing for interleukin-6, a protein that the body releases in response to infections.

    The investigators then followed up the children nine years later, when they were 18, to see if they had suffered from episodes of depression.

    The results, which were published in the journal JAMA Psychiatry last August, showed that the nine-year-olds with high levels of inflammation in their bodies were nearly twice as likely as those with low inflammation levels to become depressed as teenagers.

    Some of us constantly have higher levels of inflammation than others, explains Dr Golam Khandaker, the neuroscientist who led the study. ‘Our immune system acts like a thermostat, turned down low most of the time but cranked up when we have an infection,’ he says.

    ‘In some people the thermostat is always set slightly higher, behaving as if they have a persistent low-level infection — these people appear to be at higher risk of developing depression.’

    The Cambridge team is also investigating the question of just how chronic inflammation could cause depression. Studies of mice suggest the answer may lie in the vagus nerve, which connects the brain to the abdomen.

    When activated by inflammation in the gut, the vagus nerve sends signals to the brain that trigger an increase in toxic chemicals such as nitric oxide, quinolinic acid and kynurenic acid, which are bad for the functioning of nerve cells in the brain — which, in turn, could lead to depression symptoms.

    So what might prompt some people to have high inflammation from childhood, and thus a greater risk of depression in later life?

    Another of the Cambridge investigators, Peter Jones, a professor of psychiatry, told the Mail: ‘We are looking at what influences inflammation in children, such as genetics and low birthweight and also trauma early in life.

    ‘We don’t have the answers yet, but so far the results are looking very interesting.’

    The research also hints at a new way to treat depression — with anti-inflammatory drugs such as ibuprofen or aspirin.

    These might provide a less harmful alternative to commonly used anti-depressant pills such as selective serotonin reuptake inhibitors (SSRIs) like Prozac.

    Prescriptions for antidepressants in Britain have doubled in the past ten years, according to figures published in January. A study by the pollsters YouGov found that nearly one adult in ten is taking pills to help with anxiety or depression.

    Common side-effects include weight gain, loss of sexual desire, insomnia and fatigue. In rarer cases the drugs are believed to raise the risk of suicide, coronary disease and defects in unborn children if taken during pregnancy.

    The conventional thinking is that SSRIs work by increasing levels of the chemical serotonin in the brain. Serotonin is a neurotransmitter, which means it carries signals between different cells in the brain, and is thought to help mood, emotions and sleep.

    But Professor Jones says some of the benefit of anti-depressants may come from the fact that SSRI drugs appear to reduce inflammation in the body as a side-effect.

    The Cambridge scientists are testing whether the antibiotic minocycline might be able to stave off damage resulting from chronic inflammation in the gut by directly reducing the level of toxic chemicals that this causes in the brain.

    Minocycline, usually used to treat acne, has the rare ability to penetrate the brain’s defensive wall, the ‘blood-brain barrier’, and affect the brain’s chemistry.

    The Cambridge team’s hope is that by teasing out the link between inflammation and depression, they may be able to help prevent thousands of deaths among those who suffer from the mood disorder — and prevent people needlessly being on antidepressant drugs.

    ‘Many people with depression die early, and it is widely assumed this is down to suicide,’ says Professor Jones. ‘But only a small proportion of the deaths are suicides. A huge proportion are caused by heart disease, which can also be caused by inflammation.

    ‘It looks as if inflammation could be the common cause, and we need to explore this.’

    By revealing drug therapies for depression that are a far cry from anti-depressants, it may not just be mental distress that the Cambridge team helps to alleviate, but physical conditions such as damaged hearts as well.

    by John Naish

    May 11, 2015



  1. gypsum
    NSAIDs are not sugar pills. They have their own side effects some of which are quite dangerous. I don't understand why someone would prefer them over antidepressants for treating depression.
  2. noddygirl
    This is VERY interesting. I've been looking into Magnesium alot lately which is also said to be an anti inflammatory and antidepressant as well as anxiolytic, among other things. Fish oil pills and vitamin D (D3 in particular I think) also help depression. Anyways, this is really cool. Thank you!
  3. malsat
  4. Replicator
    This article is a great one, I agree.

    I've recently been doing hours and hours of reading on genetically modified organisms (GMO's) and have learned that our bodies may possibly perceive GMO's as hostile or noxious particles. As such, the body facilitates its defensive function --inflammation. Some of us live in this constant state based in the foods we eat.

    This article links up for me on that topic. Thanks very much for providing it!!
  5. DocToxin8
    Small dose aspirin (acetylsalicylic acid; 75-90mg daily) is a regimen of mine,
    but that's cause of it's irreverisble inhibtion of thromboxane A2, reducing clotting and delaying atherosclerotic plaques (perhaps only to a small degree, but why not).
    The COX2 inhibition, although irreversible last a much Shorter time due to resynthesis, which blood platelets are not able to do.
    (Read about the Development of aspirin analogs to reduce thrombosis/inhibit blood platelets:
    http://jpet.aspetjournals.org/content/315/3/1331.full )

    Anyways, if this effect on COX1 will have any impact on Whole body inflammation I am uncertain.
    And upping the dose provides unfavorable effects on COX1 in the gut lining, as well as reduction of
    prostaglandins who provide anti-inflammatory action & favorable effects on blood)

    So too much inhibtion of the COX1 & COX2 has some unpleasant side effects,
    but high dose aspirin compared to SSRI's might be a good trade as long as you don't have any GI issues.
    And you can always separate aspirin if symptoms of GI discomfort arise.

    Hopefully New agents will be developed that target this even better.
    For now, I would not run the COX2 inhibitors (that do not have GI side effects)
    without at least the addition of small dose aspirin. And even then i'd want to investigate it carefully
    before being on it long term.

    Very intresting post. :)

    can you point me to any studies you're Reading that GMO Foods are bad for us?
    I have my doubts about this, but don't deny it's a real possibility.
    I've always viewed GMO as more of an enviromental concern.
  6. DocToxin8
    But then in theory, lots of agents (who inhibit inflammation), at least those able to cross the BBB,
    should be able to reduce depression.

    Might be something to look into.

    Athough I must say one thing,
    it's always so when one finds a New mechanism for damage that one attributes everything to this,
    and inflammation is a hot topic now; it's also linked to cancer.
    SSRI's may have some anti-inflammatory effects, but are that the only reason they work? (in 70% of cases)
  7. Bajeda
    Similar to DocToxin, my review of GMO research has turned up some questionable science by polemicists actively seeking to besmirch GMOs in the public's eye, but nothing of significant concern in validated peer reviewed publications.

    The intellectual property and environmental issues, on the other hand, do some have legitimate bases for concern though I'm sick of reading anything on the subject because it's so sickeningly polarized much of the time.

    On a side note Doc, I got a kick out of your misspelling the reason for your edit! :p

    More on topic, did the paper(s) outline the range of effective doses for the NSAIDs studied?

    I'm wary of the long-term effects of chronic use for many of them, but if taking baby aspirin as has been recommended for cardiovascular health is also sufficient to improve affect in those susceptible this might be something worth looking into.
  8. Replicator
    Sure, Doc. There is little research on GE products because it's a billion dollar industry and most companies refuse to supply their GE products to be studied. Never mind the bashing researchers have historically received when negative results are published.

    I've had my doubts as well regarding impact of GMO's--being a farm girl and raised to understand the small amount of hormones used in beef has a minimal (if any) affect. And also without GE products that we'd be short in feeding the population (I was told). This coupled with the fact that some of my family members livelihood rely solely on GE products, has had me skeptical for many years.

    However, if you google Dr. Mercola, Dr. Judy Carman, PhD / pig study you'll find some provocative results. She did this on her dime and because of this plus a couple of other factors, I beleive the publication to be less biased than some other things I've researched.

    I won't derail this thread any further with all my gmo talk :) but suffice it to say we do not use gmo corn in my home any longer. My laziness is getting my garden back together (damn deer). Some other changes are planned but will have to be folded in gradually as I have 2 small children and a picky husband.

    Please let me know if you have issues accessing the study.
  9. DocToxin8
    OK sorry to derail thread even further with GMO, if this continues let's start a New thread.
    Just wanted to state this;
    Quackwatch claims about Dr.Mercola, where they state his claims are false,
    and that he is also against mass vaccination, among other things.
    (although vaccinations can have side effects, I think one should be VERY carefull when dismissing
    the only tool we have to prevent a host of diseases to overtake our world.
    Lack of proper vaccination cost lives on a scale that make the side effects of vaccinations seem trivial,
    even the serious ones that fuck one up for life. I'm not saying it can't be improved, and very influenced by Money, BUT! ;) )

    This is an article on Mercola's own web site.
    I've scimmed thru some articles, and note that in his articles where he comes with very bold claims,
    there is no links to any studies to back up what he says.
    Saying that Monsanto (which IS a real bastard of a Company) doesn't defend it's Products that are criticized by a book, is turning it upside down.
    Monsanto has allready posted studies caiming their Products to be safe
    (biased studies for the most part I would hazard to Guess),
    then it's up to indepenent researchers to site studies showing the contrary.
    While there may be many studies cited in that book,
    asking them for a response to a book that also seem very biased is not the way to go.
    You cite a study or two showing concerns about their Product and ask the to comment.
    If they deny that, only THEN can you raise alarm bells.

    So on the surface, even if he's perhaps right about some Things,
    he presents himself in such a way that no scientist (or few) will take him seriously.

    That's the really sad part about such issues. As Bajeda said,
    they become so polarized and filled with politics that no true Exchange of knowledge occurs.
    Science turns into political debate, and stop being science.
  10. DocToxin8
    I've also heard paracetamol will dull emotional pain as well.
    Shall check into it.
  11. Isodimorphism
    This is an extremely interesting article, but I'm not sure whether we should be getting excited.

    How many times already have we heard of "breakthroughs" in our understanding of depression that seem to offer a genuine and relatively simple cure for the disease? How many times have we found out that the problem was actually a lot more complicated than we thought?

    I'm not getting my hopes up.
  12. Replicator
    Doc, totally agree with the vaccine comments you have there. I could never begin a thread with that 'm' word though! lol. that could be dangerous for me :/ I want this to keep these comments in context (then I'm done; promise!).

    This one study is just an example of what I've been reading and the smear campaigns that can ensue when one embarks on this type of study. If you were making millions per year on this kind of business (that is GE and the chemicals used to support GE) and had fellows doing the same, you'd be pretty protective of the science (business) as well. Monsanto has grossed 110 billion in less than 10 years on GE alone.

    I'm (trying) to not say one result or side is right or wrong as it relates to GE being harmful; it does cause pause for consideration though. Especially when one has the capacity to understand methodologies, science and process behind the studies. At the end of the day damage to tissue and organs of GE-eating beings were far more diseased than those of non-ge eating beings. This is based on multiple published studies and historical data we've not had previously.

    Even main stream medicine may be catching on--my sister-in-law had a tumor in her brain that had to be removed as it put her vision and life at risk due to the location. She underwent 15 hours of surgery to have it removed. Ten years later she just underwent her second surgery for the exact same type of brain tumor which grew exponentially and aggressively back. She was instructed this time to change diet (reduce meat, more organic, etc).

    The same occurred to a gal that works for me (only her tumor is in her uterus). The difference with this other gal is that she abruptly quit eating all meats and went organic. She's still tumor free almost 10 years post -op. I know this is anecdotal but it adds up in my brain.

    I love spirited debate and am always looking for different perspectives so I will begin a new thread regarding GMO (eventually) as well as dive into the other material you've presented. Kind regards,
  13. best
    @ malsat :
    Acetaminophen is known to metabolize into AM404; a known Inhibitor of Anandamide Hydrolase (FAAH), Anandamide Reuptake, COX-1 & COX-2.

    All of those actions (possibly excluding COX-1 Inhibition) should prevent Anandamide (known endogenous Cannabinoid 1 Agonist , like THC in Marijuana) degration/metabolism, which may partake in some of the emotional pain BLUNTing, no pun intended.
  14. noddygirl
    Wouldn't it be funny if Aspirin and Tylenol, etc became a scheduled substance because people were taking it to "dull their emotional pain?" Haha! ; ) I could see that happening in America.
  15. rawbeer
    I have taken various NSAIDs while suffering episodes of depression. They have never had any noticeable consistent effect on the depression. I have taken them for probably close to a week straight - I know I have taken naproxen sodium for a week straight but can't really say for aspirin or the others.

    I think a lot of the depression going around is caused by the bizarre lifestyle we live, in conditions that put tremendous physical and emotional wear on us. And depression is probably just a normal and healthy response to these toxic conditions. People who can just shut out all of the horrors of life and get through smiling wide are probably more mentally ill than those of us who periodically suffer from depression, because they are living in a world of dulled, repressed emotions and false positivity.

    "Curing" depression from a pharmacological standpoint is really just dulling certain emotions. Our conditions are such that environmental cues trigger negative emotions to a greater degree than positive ones. Rather than address these environmental cues, we try to alter our reaction to them. And the world gets sicker, and we become more dulled and accepting of this sickness, and allow it to grow more and more.

    Changing your environment is almost always much, much harder than chemically altering your emotions. Chemical altering is a hallmark of civilized life. Addiction and drug abuse are almost unknown among non-civilized people. This is the social illness that is civilization, and the Medicine of civilized humanity is alcohol, the Civilized Drug. One that perfectly represents the vicious cycle of causing and curing problems with the exact same technology.

    As we become more civilized, we become more ill, until one day civilization will become terminal, and kill us all. In the meantime, just try to enjoy yourself as you wince and choke back the vomit that is forever perched at the back of your throat as you watch a pageant of horror unfold before your eyes.

    Happy Sunday!
  16. Ih8tramadol
    This is actually true... However, admittedly it can cause gastrointestinal issues up to and including bleeding in the stomach..

    I personally can attest to the fact that tylenol / acetaminophen can blunt your emotions and such, as I personally tried it, but do NOT recommend anyone else do it..
  17. DocToxin8
    @Replicator: PM me when starting a thread on Monsanto & GMO, that would be fun to discuss.

    @Rawbeer: To treat depression with NSAID's alone would mean it has even more effect than SSRI's,
    but I do get your point. It doesn't seem to do nothing magical. Maybe it would have some protective effects,
    maybe New drugs can be developed when the exact mechanism is detected.
    I also do get your point, that depression can not be isolated from Our enviroment,
    but I believe that in some instances drugs can almost single handedly be a Cure for depression and
    other mental problems.
    That doesn't mean psychotherapy (with talking) should not always be offered,
    and the stress of the enviroment reduced.

    Great info!
    NSAIDs does seem to have a big impact on those factors (anadamide reuptake, etc),
    so maybe it's Down to the endocannabinoid system after all.
    If so, Research into cannabinoids should give better fruit,
    but there was a Reference in this article about a greater inhibition of FAAH by ibuprofen in lower pH,
    which happens in inflammation. The reduced pH because of inflammation also reduced the ability
    of fatty acid amidohydrolase / FAAH to degrade ananamide.

    Ibuprofens action on anandamide degradation & FAAH, etc. Relevant for this thread.
  18. best
  19. Ghetto_Chem
    Sorry I didn't get a chance to read the whole thread yet, but I have definitely noticed psychoactive effects from anti-inflammatory substances.

    Apirin I have not. (And that's saying something because I feel alot of things.) But I definitely get something off Ibuprofen, as well as Fish Oil, and Serrapeptase. Three substances that are not supposed to be psychoactive. Ibuprofen will actually have me shaky and pissy for a day or two after it too, like I'm going into withdrawal from it.

    The thing is I can't take any of them for long term as I start to feel off if I do, not sure quite why that is but it happens. Out of all three, Serrapeptase has the most prominent anti-depressant effects that make me feel wonderful with no withdrawal like symptoms even after a week of use. Fish oil makes me a bit more manic, more socially outgoing and energetic but not necessarily feeling "good." Ibuprofen didn't really feel like an anti-depressant at all, more like an opioid actually, helps me sleep and I feel really relaxed and good when I take it, also has a withdrawal to it. (Note: I never even tried Ibuprofen until a few years ago, no other OTC painreliever really makes me feel like that so maybe I just have a low tolerance because I never used it.)

    I definitely think they are onto something with this though. I think anti-inflammatory enzymes like Serrapeptase may be the future for anti-depressant drugs. Look around and I'm not the only one reporting those types of effects from that supplement, it seems to be a wonder drug for alot of people. I just use it very sparingly because I'm worried it may cause catabolism of my muscle, since it breaks down proteins. (Anyone who could ease my worries on that would be greatly appreciated, I've gotten muscle aches on it that make me wonder...)

  20. DocToxin8
    serratiopeptidase taken orally should have no effect on your muscles,
    as it is an enzyme and therefore protein, which should be digested just like any other proteins in your food. This is at least the general theory. Some proteins, or rather peptides (pieces of a protein) might be taken up into systemic circulation but this is generally to a very very small degree.
    Why serratiopeptidase would help inflammation when taken orally I don't know, and found conflicting studies on its antiinflammatory effects, even when given by injection.
    But in any case, I would think it would have no negative effect, and perhaps some positive.
    I've used various enzymes before, but only for the purpose of digesting food faster and more efficiently. The formulations even contained cellulase as well as protease's, amylase and lipase, so with them I could actually digest paper(cellulose). ;) but they did not affect the stomach lining, the only problems they could cause were if you chewed or split the tablet and didn't swallow it right away, as it would start digesting your mouth cavity. And they were only positive for muscle growth, (no evidence to back this) by increasing nutrient uptake from food.

    As for psychological effects from NSAIDs, I remember my grand mother telling she used to take an aspirin to go to sleep, as she felt one aspirin made her tired. Whether that was because it dulled all aches in an old body so she relaxed more, or a direct effect I don't know. But the way she described it, it seemed like a direct effect.
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