osteoporosis, migraine, gastric lesions, PTSD, decreased lifespan, autism, social anxiety, bipolar disease, obesity, alzheimer, chronic pain, cancer, systemic sclerosis, suicide, bleeding in the brain, IBD, sudden infant syndrome (SIDS), tinnitus, addiction, diabetis, violence, ME, CFS, parkinson and more​

The take of the story is that serotonin antagonists, and especially 5-HT3 antagonists like ondansetron would be very good treatment for osteoporosis.

exercise-derived (but probably any other as well) fatigue is fully abolished by inhibiting tryptophan hydroxylase, and thus reducing serotonin in the brain

reduced brain serotonin improved the ability of mice to cool off when their bodies heated up due to the exercise

high fat diets increase serotonin synthesis and levels in plasma and tissues, and serotonin apparently directly contributed to obesity

If these NSAIDs do in fact raise serotonin that would explain why they are bad for the heart, and why aspirin is protective (lowering serotonin) given that is blood thinning effects are not sufficient to explain the protection.

This study claims that serotonin causes release of nitric oxide in the meningeal area of the brain and spinal cord and that is the cause of migraine.

showing both substances producing gastric lesions in rats

serotonin is involved in the formation of traumatic memories when under shock / stress

It appears SSRIs work by forcing the brain to achieve homeostasis, not by modulating serotonin levels.

a number of SSRI drugs caused decrease in lifespan, sometimes up to 80%

High serotonin, on the other hand, was associated with a protocol-like thinking and behavior, which the study calls "flexible, goal-directed responding"

serotonin is implicated in punishment and behavioral inhibition

a small human study with autism that found significant reduction in symptoms from low dose cyproheptadine

anxiety disorders are likely caused by high levels of serotonin rather than low

It looks like the JCV requires the 5-HT2 receptor for successful cell infection and 5-HT2 antagonists may block the virus' propagation.

shows that cyproheptadine can both block infection and inhibit established infection with HIV. In higher doses, cyproheptadine completely eradicated the virus

A new drug was just approved for treating bipolar disorder and schizophrenia in adults, and its effects are basically a combination of cyproheptadine and bromocriptine

The fact that most of these genes are related to serotonin metabolism is considered, of course, irrelevant to the pathology even in light of common medical knowledge that traumatic events elevate brain serotonin.

shows that drug Prozac (and possible other SSRIs) causes irreversible bone loss.

high doses folic acid acted like serotonin antagonist in the breast and inhibited the bone loss process

over 90% of the drugs tested for Alzheimer during the last 10 years have veen utter and abject failure

the latest trial used the drug idalopirdine that is a very specific and direct serotonin antagonist, and was found beneficial for people with Alzheimer's

the study authors state directly that serotonin antagonism can be a viable therapy for Alzheimer's

I, personally, dispute that assumption and think that the SSRI was responsible for both the increased stroke incidence and increased mortality from that stroke, as serotonin is a well known blood-clotting agent.

Blocking serotonin eliminated the chronic pain condition.

the study establishes the key role serotonin plays in the pathogenesis of testicular (and other) cancer and the overexpression of the serotonin-producing enzyme TPH in testicular tumors.

The SSRI drugs act mainly on the so-called serotonin transporter, which is responsbile for de-activating serotonin by removing from the synapse and storing it into the neurons. The SSRI drugs inhibit the activity of the serotonin transporter and thus increase serotonin activity in the brain. Btw, sodium is a co-factor for that transporter, so this is also why low-salt diet increases serotonin activity. This study found that living in poverty as a child results in overmethylation of the gene that codes for the serotonin transporter, thus inhibiting its activity.

This study now adds the condition known as systemic sclerosis or scleroderma to the list of conditions where serotonin plays a causative role.

It showed that triggering flu-like symptoms and the release of endotoxin in the pregnant mother raised serotonin several-fold and caused brain damage and behavioral abnormality in offspring reminiscent of autism.

This news piece shows that the drug terguride (a lisuride derivative) is currently in a large scale human trial after being PROVEN to reverse symptoms of systemic sclerosis

This study now ties maternal stress to the activation of the serotonin gene 5-HTTLPR, which downregulates the activity of the serotonin transporter and thus leads to elevations of brain and plasma serotonin.

The restorative slow wave sleep (SWS) is highly dependent on metabolism and disturbances in oxidative metabolism immediately manifest in SWS. As such, SWS disturbances in SWS have been observed in pretty much all chronic conditions (especially psychiatric ones) and the aging process in general.

This study shows that the activation of the 5-HT2 receptor is crucial for the development of the acute pancreatitis pathology and antagonists at that receptor (cyproheptadine, ritanserin, etc) can successfully treat the condition.

This study adds more weight to the evidence for causative role of serotonin in autism by finding out that children with autism have abnormally high blood serotonin levels.

Finally, I think the even bigger takeaway from the study is that the study found stress to increase levels of serotonin, which then acted as the primary cause of anxiety and depression

And just as in the case of terguride, blocking said 5-HT2B receptor was therapeutic for the established cancer.

This study found that a significant portion of ICU patients with delirium have serotonin syndrome.

Another recent trial found that low dose cyproheptadine prevented most cases of delirium even though it did not do much for very severe cases already in progress.

One of the big takeaways from the study is the explanation of why eating high protein diets has been linked to shorter lifespans. While eating protein itself tends to be dopaminergic due to lowering the ratio of tryptophan to the LNAA, the anticipation of the high protein meal due to enforced starvation apparently activates the serotonergic system in the brain and specifically the 5-HT2 "receptor".

the study found that increasing the perceived value of protein through forced starvation and then letting the animal eat at will activates both the enzyme tryptophan hydroxylase (TPH) and the 5-HT2 serotonin receptor. TPH is the enzyme that synthesizes serotonin from tryptophan. The study found that inhibiting TPH and/or blocking 5-HT2 increase lifespan by almost 100% - i.e. basically doubled it.

This new study seems to point the finger at SSRI drugs, at least when it comes to brain bleeding. While serotonin increases platelet aggregation and can cause ischemic stroke, it also weakens the blood vessel walls and as such can lead to leakage or even rupture of the vessel.

now another study points the finger at the bacteria in the colon as the main regulators of serotonin production through the receptor TLR2

the TLR2 gets activated by the mere presence of bacteria in the colon

This news piece shows that blocking the 5-HT7 receptor is probably a viable pathway for curing IBD.

This new study re-establishes once again ties SIDS to high serotonin levels and suggests that serotonin can actually be used as biomarker to distinguish SIDS from other causes of unexpected infant deaths

This new study shows that SSRI drugs (and thus serotonin) worsens the symptoms of tinnitus.

So, this new study from John Hopkins University found that it is the low levels of serotonin transporter (SERT) and not the actual serotonin levels that are likely causative in dementia.

This new study shows that blocking the serotonin receptor 7 (5-HT7) blocked the cocaine abuse behavior.

Finally, as you can see from the study, the researchers have no problems establishing a causal link between serotonin and aggression (at least in non-human organisms).

That is exactly what the study below found - i.e. bonobos will help a complete stranger seemingly just out of kindness. I remember seeing a study years ago which found that bonobos have lower levels of serotonin than any other of the humanoid apes

SSRI drugs like Prozac (fluoxetine, FLX) actually worsen the effects of prenatal stress in male offspring,

This new study below discovered that while systemic levels of serotonin and its precursors/metabolites do not change, the expression of the 5-HT2A receptor is increased, which results in dramatic increase in serotonergic signalling in the cells that express that receptor.

Apparently, it has been known since the 1980s that the same receptor is increased in suicidal people, which would mean that drugs that agonize 5-HT2A are expected to increase risk of suicide.

The study below found that linoleic acid levels are highest in patients with current migraine attack, and linoleic acid is a potent liberator of serotonin from platelets and, of course, a prostaglandin precursor (also implicated in migraines)

This study shows that the tremor signs are possibly due to decreased availability of the serotonin transporter (SERT).

The study below demonstrates that by elevating serotonin in an organism (this time the study model was a slug) that organism can be made to behave almost automatically and in a very self-harmful (even lethal) way.

I think the importance of this study is the admission that serotonin causes obesity/diabetes in humans, as one of the authors says

the role of serotonin in these pathologies is well-known

elevated serotonin apparently increases patience more in uncertain circumstances,

in times of uncertainty, serotonin increased the (false) belief of mice that they were waiting for a positive outcome (reward/food) when in reality the likelihood of such positive outcome was low

It has been known for a long time that both lithium and methylene blue, both of which are effective for bipolar disorder, improve mitochondrial function in the brain. Lithium is also a known upregulator of serotonin uptake (by increasing SERT activity), but that fact is almost never mentioned in studies reviewing lithium's effects on bipolar disorder and psychosis

the study below discovered that the brains of awake babies have very similar activity to adult brains while in state of dreaming and the brains of animals given LSD

the child-like state of open/full perception can be restored by increasing exposure to novel situations and avoiding authoritarian (I think he called them "stiff") minds

The conclusion - not only are SSRI drugs ineffective but their risks far outweigh even the (mostly) theoretical benefits claimed by Big Pharma.

The study below found that exposure of E. coli to the SSRI drug fluoxetine (Prozac) increased resistance of the bacterium to multiple antibiotics.

Below is the commentary of @haidut on 70 studies regarding serotonin. The links lead to the thread where haidut often provides some direct quotes from the study (and of course the links to the actual studies).I hope that with providing this as a whole it aids in learning in effective way about serotonin. If you little time, you may just can scan through this post, but if you have the time and are critical, the actual studies are just two mouse click away.Out side of the Peat sphere there seems to be still very little awareness of the darker side of serotonin. You may also want to send this thread to someone who is critical and want to read the actual evidence about the role of serotonin in the following diseases:"Not sure if Peat has mentioned this before, but I decided to post it anyway."This study however, goes a step further and claims that. In addition, the study claims that.""Although I have not read anywhere in his articles about this connection, I came upon this study and immediately saw why Ray may be leaning towards a low(er) fat diet. Long story short -. The entire study is good read so I recommend reading it for those that are not bored by biochemical topics.""The effects were observed in the brain, but they probably apply elsewhere given that aspirin is shown to reduce plasma serotonin. There are quite a few studies showing increased risk of heart attacks resulting from chronic intake of acetaminophen and ibuprofen.For instance, ibuprofen also lowers platelets aggregation but is bad for the heart. Ray has said in the past that anti-serotonin drugs are likely to be heart protective.""Ray has written about the connections between serotonin and migraine, but AFAIK he did not name a direct causative agent.The study also implicates a specific serotonin "receptor" where serotonin exerts its action and causes release of NO. The "receptor" is 5-HT2B. A very potent antagonist at that (and others) receptor is cyproheptadine, and not surprisingly there are a number of studies showing that cyproheptadine does indeed reduce migraine symptoms.Finally, if NO is the direct cause of migraine then agents that reduce NO production should be helpful as well. Two of the better known ones are niacinamide and vitamin B12. I think aspirin has some anti-NO action as well."This implies that serotonin inhibits that responsivity. This study seems to confirm that view and makes one wonder how something that inhibits the senses like SSRI can be good for depression.""If there was any doubt that serotonin and histamine are not good for you hen chronically elevated, here is an older study. Look in the section "Production of gastric lesions" for details. If this was known for so long then it is beyond me how drugs like Zelnorm ever got approved for stomach conditions or why SSRI continue to be prescribed for such conditions as well...""The study makes several points. First,. Second, memories do not appear to be stored in the synapses, which implies that in theory lost memories (like in patients with Alzheimers or concussions) can be restored in humans as long as the neurons are still alive. Last, traumatic memories may be a lot more difficult to erase once formed, which is not very good news for people with PTSD.""I remember Ray wrote that when people are under chronic stress, initially they seem to develop incredibly sharp memory. he said that's due to serotonin, which the study seems to corroborate in a way. However, after sufficient time under stress has elapsed the memory forming starts to fail, and those people have a hard time forming even new memories (similar to the movie Memento).""What can I say - Ray is right once again, which we knew from the start. In the words of the actual study - "serotonin is a downer".Again, Ray did say that as well - i.e. drug companies did not really know how their SSRI drugs work.""Not sure why this is not hitting the news everywhere, but I find it particularly telling as to whether serotonin is good of bad for depression.""This study looked specifically at mianserin, but did compare it to other drugs (including cyproheptadine).Interestingly, mianserin increases appetite just like cyproheptadine, which the authors state is what creates a psychological state that makes the organism believe they are in caloric restriction. Unsurprisingly,! I have attached the study and the supplemental info. The supplemental info has the full list of the drugs tested and their effects on lifespan. For a good example of Peat being right on serotonin take a look at cyproheptadine's effects on lifespan (+20%) and compare it to a drug like Sertraline (Zoloft, -80%) or Paroxetine (Paxil, -76%) :) ""Yet another blistering criticism of the serotonin idea and the introduction of the SSRI. It also gives a bit of an explanation as to why the SSRIs became dominant drugs decades after being invented - propaganda!""Ray has written about the uselessness of the authoritarian concept of "protocol" as a guide of behavior, thinking and living in general. Ray's motto instead is that the only valid protocol would be something along the lines of "perceive, think, act". This study seems to establish that low serotonin (high dopamine) is key to being able to act according to Ray's motto.. The paper also cites studies showing that, as well as guilt, shame and depression. Btw, I find it funny that they call the "goal-directed responding" "flexible" while the "stimulus-response habitual response" is viewed as rigid and inflexible.""Once again, a testament to Ray's brilliance in clearly explaining the links between elevated serotonin in the brain and conditions like autism. Other scientists have also worked on the serotonin-autism hypothesis and as a result there has been. Unfortunately, the dose used in that study was rather small, so the effects could have been even more dramatic with the proper dose. However, I think this is the first study that specifically points to serotonin as the direct culprit behind autism, and that blocking the 5-HT2C "receptor" fully reverses neurological damage caused by autism. Known 5-HT2C antagonists include our old friend cyproheptadine (particularly effective at 5-HT2C), as well as mianserin, ketanserin, ritanserin and maybe even lisuride (even though for lisuride only 5-HT2B antagonism has been shown). The co-discoverer of HIV Luc Montagnier has been proposing for years treating autism with antibiotics. Some of the antibiotics he has used have strongly anti-serotonin effects, so the positive results he reported no longer look like a scam when you consider this study.""After decades of prescribing SSRI to treat anxiety, and especially "social" anxiety, evidence is finally being published in bastions of dogma like JAMA that. This makes the prescription of SSRI one of the worst "treatments" for social and other types of anxiety. It is also worth noting that both serotonin synthesis is also enhanced, which suggests overactive TPH1, also implicated in depression, suicide, and various neurological disorders like autism, ALS, AD, etc.""In light of the recent studies I posted showing anti-serotonin compounds to be helpful for a host of infections such as malaria, flu, or even HIV this study is not that surprising. However, it is good to have some extra tools in the arsenal against viral attacks especially when the tool is our good old friend cyproheptadine. ""The JCV is the potantial cause of the dreaded PML condition, which may effect people with "autoimmune" conditions (MS, lupus, rheumatoid arthritis) receiving immune-suppresive therapy.Yet another good use for cyproheptadine. More importantly, I wonder how many other viruses require a serotonin "receptor" for successful infection and if cyproheptadine can be a viable general-purpose antiviral drug.""Now, this study adds to the evidence implicating serotonin in viral pathologies, and. The other compounds the study found effective all had cytotoxicity, while cyproheptadine did not, even in very high doses.""After more than 5 decades of claiming that psychosis conditions like schizophrenia are caused by excessive dopaminergic activity and depression is a deficiency of serotonin, big pharma is doing 180 degrees reversal.- a combination we have discussed on the forum before. Keep in mind that current medical dogma states that the psychosis of conditions like schizophrenia is caused specifically by agonism of the D2 "receptor" and typical first-line therapy drugs for the condition are potent D2 antagonists, sometimes in combination with an SSRI.This newly approved drug is an agonist of the D2 and 5-HT1 "receptors" (like bromocriptine) and antagonist of the 5-HT2 and H1 "receptors" (like cyproheptadine). Sometimes I wonder how can FDA approve two drugs with clearly opposite mechanisms of action without questioning the theory behind one or the other...""I have suspected this for a long time, but the official version to this day is that schizophrenia is primarily a gene-driven disease linked to a "misbehaving" cluster of about 300 genes."Ray has written about the detrimental effects of serotonin on bone health and how serotonin antagonist could be a potential treatment for osteoporosis. This study confirms Ray's points and"As you can see, the study also found that. While folic acid in pregnant or nursing women is certainly not a bad idea, high dose folic acid for other adults may be dangerous. Something like glycine and/or aspirin would be much better.""As I posted in another thread,. This is a pretty solid indication that the theory of Alzheimer's pathology and proposed beneficial pathways on which these drugs were based is solidly wrong.""Aside from the failure of all of these drugs, it is quite common to treat Alzheimer patients with SSRI drugs to "improve" their mood and claims have been made that SSRI would even improve cognition. Nothing short of abomination, considering something as simple as aspirin can probably cure the condition.""As the saying goes, "no matter how beautiful the theory, you have to acknowledge reality sometimes", and so it seems that finally Big Pharma is embarking on the right path. Of course, none of this publicly acknowledged and officially new drugs that act in ways opposite to SSRI or the cholinergic poisons used for the last 20 years, are presented as "modulators" rather than as antagonists. Be that as it may,. While the PR articles dances carefully around the issue of serotonin "modulation". No wonder cyproheptadine disappeared from the pharmacies of Europe and USA. It won't be long before we see it sold as off-label treatment for the low cost of $9,899/month.""The study was done on people with diabetes and the presumption was that it was the diabetes that gave them the stroke, not the SSRI."In yet another confirmation of how "beneficial" for us the "happiness hormone" serotonin is, this study showed that the development of chronic pain syndrome is dependent on serotonin.So, for all those poor people overdosing on Oxycontin, it looks like a little cyproheptadine can go a long way without the risk of killing them.""I have always wondered about this phenomenon and why it is that people with chronic conditions or depression seem to have a problem with excessive itching. It turns out that itching is closely related to pain and as such the release of serotonin. So, rather than scratching your itch you may be better off reaching for the Benadryl or cyproheptadine.""This is a great study for a number of reasons. First, it suggests that DHT is not the evil substances for male reproductive organs. This includes prostate cancer, for which DHT to this day is cite as the main culprit. Second,TPH is actually overexpressed in most cancers but this fact is not widely publicized. This study states that explicitly and I hope this trend will continue. Third, the study shows that inhibiting TPH and thus serotonin synthesis may be a viable treatment for at least this type of cancer. Fourth, if DHT also inhibits TPH in the brain (and I don't see why it would not) and has proven potent anti-depressant effects then the theory of serotonin as a cure for depression is becoming highly untenable. Finally, given the beneficial effects of TPH inhibition on a variety of conditions such as obesity, diabetes, hypertension, pulmonary edema, cystic fibrosis, etc using DHT (mostly by males) would be a great alternative to the number of patented and still experimental TPH inhibitors that come with a host of side effects as well. Given the high conversion of DHEA into DHT in peripheral tissues, this would also explain a good deal of DHEA anti obesity and anti-depressive effects. In fact, recent studies discovered just that - i.e. the beneficial effects of DHEA on insulin sensitivity and metabolism are at least partly due to its conversion into DHT in muscle.""The conditions of learned helplessness and PTSD have many features in common and both of them have been linked to dysfunction of the monoaminergic system. There has been a lot of research over the last decade tying adverse life conditions in childhood to mood and memory problems as an adult. Unfortunately, most of the studies paint serotonin as the "good guy" and a main component of "treatment" for such conditions involves giving SSRI drugs.This result in the same effects as taking an SSRI drug and increases serotonin availability and activity in various brain regions, especially the amygdala. As a result, people with decreased activity of this serotonin transporter display symptoms of depression when presented with threats, but also in normal life situations. The only thing that annoys me about this study is that it does not directly call out serotonin as the bad guy here. But we all know that when career depends on certain status quo, nobody wants to rock the boat too much.""Ray has said numerous times that serotonin is intimately involved in fibrotic conditions of the lungs, and my own research shows that it is involved in many other fibrotic conditions including cirrhosis, cystic fibrosis, and of course carcinoid syndrome.This suggests that lowering serotonin may be therapeutic in this condition for which officially there is no cure and it is eventually fatal.""I posted several studies recently about maternal hypothyroidism and stress being linked to autism, as well as the use of serotonin antagonist to reverse autism pathology in an animal model. This study adds more weight to the serotonin-autism connection."Big Pharma is slowly prepping us for the inevitable admission that serotonin is really not that good for us. Of course, it will not happen publicly but through the approval of drugs that block serotonin and promote dopamine activity.(also known as scleroderma). I posted a study some time ago showing that drugs like lisuride are effective treatment for fibrosis of some organs. Even today, the official position on fibrotic diseases like systemic sclerosis is that they are uncurable, but apparently behind the scenes the truth is different. The German pharmaceutical company Medac , in August, will begin Phase 3 of a clinical trial to access the therapeutic potential of terguride, a disease-modifying drug for the treatment of diffuse cutaneous systemicsclerosis."Given that the link between stress and elevated serotonin is apparently quite well known in pregnancy research, it is baffling that SSRI drugs are prescribed to women to help them "deal with stress" or to "treat" their depression.""I wanted to post this study as a separate thread as it caught my eye with its obvious relevance to Peat's views on sleep and metabolism.It seems that ritanserin is able to reverse the disturbances in SWS by improving metabolism during the night.""As some of you know, pancreatitis is a condition very common among alcoholics and people on SSRI drugs. When it is acute it can be quite deadly and its incidence has been skyrocketing lately, which concided with rising rates of alcohol abuse among middle-class citizens in the Western world. The drug companies continue to deny that serotonin is involved in the pathology of any GI disease, but quietly they are running trials with inhibitors of TPH as treatment for IBS, IBD, and even some GI cancers."I posted a few studies on using anti-serotonin drugs (specifically 5-HT2 antagonists) as a potential treatment for autism.There are a few recent clinical trials with TPH inhibitors for treating IBS and I think these would be prime candidates for treating autism as they target serotonin in the gut, which is where autism is thought to be centered as well.""I guess the fact that such studies are finally starting to come out is a good sign. I don't think this will hurt Prozac sales in any way, but at least now doctors may start to discuss with patients the potential dangers of SSRI, which up until last year were considered to be pure myth. It still baffles me how can FDA approve drugs in the face of evidence that they cause the very problems they are designed to treat. I am beginning to suspect more than just pure idiotism here.... So, there you have it plain and simple - stress makes you depressed and taking an SSRI is a great way to mimic this process ad recreate it pharmacologically.""I think this study should be sent to every pharma executive and brainwashed whitecoat who claims that serotonin is a good hormone promoting happiness and health. Actually, pharma companies have no illusions and know very well what's going on. Hence, the recent acquisition of Pfizer to the commercial rights of terguride - a potent antagonist of 5-HT2B, albeit a lot less effective than something like lisuride or non-selective antagonists like cyproheptadine or ritanserin. Pfizer knows quite well that 5-HT2B is required for the development of fibrosis and that antagonizing that receptor can cure fibrosis. Given that fibrosis is the preceding stage to cancer, it is not surprising at all that the studies below found the 5-HT2B receptor to be required for the development of cancer as well.The drug used in the study was ritanserin, but any other 5-HT2B antagonist such as cyproheptadine, lisuride, and even ketanserin should work just as well.""I have several friends who are ER physicians and one of them works in the ICU as well. The topic of post-surgical delirium has come up many times and all of them vehemently denied that serotonin has anything to do with it. The current view is that the mechanism and cause is unknown and heredity probably has a big role, as well as prior/current substance abuse. The fact that delirium shares most of the signs/symptoms of serotonin syndrome is simply brushed aside as coincidence. Well, once again, serotonin seems to be rearing its ugly head.The sad part is that, just like my doctor friends, the attending doctors completely failed (or ignored) to properly recognize the condition and treat it appropriately with cyproheptadine.I suppose the even sadder part is that many ICU patients are treated with SSRI or other serotonergic drugs to "calm" them down. Given the direct effect of these drugs on inducing serotonin syndrome I wonder if the failure to recognize the connection is pure stupidity or is it being purposefully ignored to avoid implicating blockbuster drugs that make tons of money for the hospital...""This study is actually on the effects of a high protein diet on brain neurotransmitters and lifespan. It was done in fruit flies but the serotonin in those fruit flies are essentially the same in humans. So, the results should hold.Activation of serotonergic receptors has been reliably shown to decrease lifespan while blocking them may extend lifespan in many species. So, the forced (read: stressful) restriction of viable nutrients while allowing the animal to perceive its availability is what leads to the activation of the serotonergic system and shortened lifespan. Yet another example that stress is a major factor in aging! Both of the studies above were done on a worm animal model. This study was done on fruit flies. I would like to see this replicated in higher species like mice, rats, and moneys but I think even this replication across less complex species is important as it suggests the mechanism of lifespan extension is valid. Anyways,This means drugs like cyproheptadine, mianserin, ketanserin, ritanserin and some other non-specific serotonin antagonists can all be used as a part of a life extension strategy.""Over the last few years there have been a number of studies linking SSRI use with increased risk of fracture. Subsequent studies found this link to be definitively causal - i.e. SSRI drugs cause those fractures. However, the mechanism of action was officially ascribed to the medical establishment''s favorite category - "unknown".. Administering an anti-adrenaline drug (a beta blocker) greatly diminished the bone loss. Aside from the fact that a much safer drug like clonidine could have been used, the study also failed to make the connection between serotonin and cortisol. Cortisol is a much bigger factor in bone and tissue loss then adrenaline and serotonin is perhaps the biggest promoter of cortisol synthesis through the upregulation of ACTH. Adrenaline also promotes cortisol synthesis as part of the sympathetic response. It just so happens that the drug clonidine lowers both adrenaline and cortisol, and as such should be a much better option than the dreaded beta blockers that can leave males impotent and women demented. Finally, let's not forget Ray's writings about anti-serotonin drugs being very anabolic to the bone. So, instead of taking an SSRI and then trying to reverse its stimulated bone loss, it's much better to take an anti-serotonin drug as that will not only treat the depression but will also give you bones of steel as well"Not sure why the study considers January to May to be winter months, but this is yet another study that links maternal metabolism (and serotonin) to autism. The official explanation is increased flu infection and lower vitamin D levels in the winter. While these may be contributing factors, I posted a few studies that strong causative link between hypothyroidism and serotonin excess in the mother to autism in children, including successful treatments with serotonin antagonist (mostly animal models).""This is one of the rare human studies using direct intervention for autism. As you can see, there was significant improvement in symptoms with a dose of 300 IU / kg of bodyweight, given daily for 4 months. In addition to the pro-metabolic effects of vitamin D, it is also a known inhibitor of TPH (as I posted in another thread) and as such probably lowers serotonin. Serotonin and the 5-HT2 receptor are directly implicated in autism as I posted in yet another thread, and the beneficial effects of vitamin D in these autistic children probably has something to do with this anti-serotonin activity.""Incidence of GI and brain bleeding events has been increasing over the last 30 years.Aspirin was blamed the increase of both the brain and GI bleeding events. Recent studies seem to have vindicated aspirin a bit, but the question remains about what is causing the increased incidence of brain and GI bleeding.So, an SSRI drug can potentially give a person stroke of both types (ischemic and hemorrhaging) - a remarkably dangerous / bad combination.""A year and a half ago I posted about a study which found that serotonin production in the gut depends on the bacteria living in the colon. At the time, the study was considered controversial as the role of microbiome in serotonin production was thought to be relatively minor. However,. The TLR2 receptor is related to the infamous TLR4 (which is the main endotoxin "receptor") but unlike TLR4,. Thus, any amount of bacteria in the colon will act as agonist at that receptor, and the study below found that TLR2 agonism inhibits the serotonin transporter, which is responsible for the disposal of serotonin. Thus, TLR2 activation results in an effect similar to what the SSRI drugs do in the brain, and these higher gut serotonin levels have been linked to everything from IBD to neurodegenerative disease and even cancer.""It is not common knowledge in research (but not clinical) circles that serotonin is the major cause of the so-called "irritable bowel syndrome" (IBS). As such, there are several large clinical trials using TPH inhibitors to lower serotonin synthesis and thus cure the condition. It is also known that the so-called "inflammatory bowel disease" (IBD) conditions like Chron's and ulcerative colitis (UC) form a continuous spectrum extending from IBS, which means IBS is often a "gateway" disease to developing IBD. This suggests that anti-serotonin drugs should help IBD as well, but that leap of "faith" has not been done yet. The good news is that the role of serotonin in IBD is acknowledged and there are companies pushing in that direction.Drugs that act as 5-HT7 antagonists include bromocriptine, lisuride, metergoline and of course some more selective ones like the one patented by Temple University below. Unfortunately, contrary to what medicine claims, often the more selective a drug is the more systemic its side effects are. The older and tested drugs above should be a much safer (and definitely cheaper) alternative.""This study shows that the activation of the serotonin producing neurons in the brain requires the presence of prostaglandins. Lack of serotonin or lack of prostaglandins prevented the development of emotional response (traumatic memory) to pain. If the multitude of benefits aspirin provides was not enough, now we can add preventing emotional trauma to one of its potential benefits. Other studies have found aspirin to be effective for relieving depression and the proposed mechanism was its anti-inflammatory effect. However, other NSAIDs are largely ineffective for depression, which suggest another mechanism is at play for aspirin. Aspirin was also found to lower plasma serotonin, so this effect combined with its blockade of prostaglandins and the findings of this study provides a much better explanation.""The role of dopamine and serotonin in, respectively, creative and analytical thought processes is well established. So, the title of the study can probably be changed to "Dopaminergic dominance yields more correct solutions compared to serotonin dominance". While too much analysis is definitely a sign of suboptimal metabolism (and often of mood disorders like depression) the performance of the analytical thought was not that far behind than the insightful one. I think analytical thought is simply what remains when metabolism is not sufficient to support creative, inductive thinking - i.e. the analytical thinking is possibly a baseline / survival mode of thought in suboptimal environmental conditions.""In one of his very early interviews Peat was asked about SIDS and its likely cause. He said he was not sure but given the occurrence of SIDS mostly during the night and winter months he thought a pituitary hormone or a neurotransmitter might be involved. I posted some preliminary studies on the forum almost 2 years ago linking high blood serotonin levels to SIDS. However, the pharma industry immediately responded with (possibly fake) studies of their own claiming that, just as in suicide victims, blood serotonin in SIDS victims was actually.""I posted a number of threads on the dangerous "side" effects of the SSRI class of drugs. The reason I put "side" in quotes is that considering their pro-serotonergic profile these are not really side effects but expected results along the main known mechanism of action of those drugs. Serotonin has been known to cause psychosis and homicidal/suicidal behavior for almost a century, but only now its role is beginning to be taken seriously given the recent wave of mass shootings. The article below only quotes the Colorado mass shooting but I suspect in most/all cases involving mass shootings in the USA and the Western world (i.e Norway, UK, etc) the perpetrator was on at least one mind altering drug (usually of the SSRI kind or a dopamine antagonist with similar effects).""Most of the people on this forum know about the connection between gut irritation and tinnitus. Ray said a few times that endotoxin can directly cause tinnitus but I don't think he has talked about the role of serotonin as a causative agent, even tough endotoxin will increase serotonin synthesis in the gut.While the study does not say that serotonin is the actual cause of tinnitus, the fact that dopamine agonists have been used to treat tinnitus in the past suggests that serotonin does have a causative role. If the evidence against SSRI was not already bad enough, now we can add inner ear damage to the list of side effects. The incidence of tinnitus has been skyrocketing over the last 20 years and nobody has been able to explain why. Well, considering the dramatic increase in SSRI prescriptions over the same period I think the culprit now is quite obvious. What is even worse is that, as the study mentions, tinnitus is a major cause of anxiety disorders and SSRI drugs are commonly prescribed for anxiety as well. So, these drugs are probably causing the very disorder they are prescribed to fix. The medical profession is either hopelessly imbecilic or completely corrupt... The morale of the story - eat more salt (to taste) as it increases the uptake of serotonin through the SERT enzyme, thus terminating serotonin's effects. Anti-serotonin drugs (or pro-dopamine) like cyproheptadine may also help.""Some of you may have seen this study in the news lately. However, it is being presented as the exact opposite as what my title says. The media titles all over the Internet proclaim that "John Hopkins study shows low serotonin causes dementia". However, if you look at the actual study you will see that the findings are the exact opposite of what the media claimed.The SERT is a protein that is reponsible for the degradation and increase in uptake of serotonin, and its proper function depends on sodium. The SERT is also the very protein the famous SSRI drugs inhibit. So, another way to rephrase the study findings would be that. But don't expect to see that news headline any time soon. The morale of the story - stay the heck away from SSRI and eat your salt to taste and to the distaste/horror of your cardiologist or GP.""Another study on addiction and its mechanisms, but this one focuses on cocaine which is the second most highly abused drug after alcohol, at least in the US (excluding weed).This would explain why cyproheptadine, which is sometimes administered to cocaine abusers who experience a serotonin syndrome, often completely stops their "addiction". Metergoline would probably be even better as it is a stronger antagonist at 5-HT7. Perhaps even more importantly, this study also shows why cocaine is harmful in the long run, despite its short term stimulating effects - i.e. it is an agonist of 5-HT7. While this specific study only discusses 5-HT7, the publishing lab has quite a few other publications (see first link below) all of which implicate serotonin and its various "receptors" in cocaine addiction. So, it is fair to say that serotonin as a whole drives cocaine abuse and lowering it with dietary or pharmacological means is therapeutic. Just as I mentioned in the alcohol addiction thread a few minutes ago, given that 90%+ of serotonin is produced in the gut, antibiotics and charcoal may be two easily accessible interventions that can curb cocaine abuse.""The bad news for SSRI just keep on piling. Given serotonin's role as a master metabolic inhibitor this findings is not really surprising. There are a number of clinical trials underway with serotonin synthesis (TPH) inhibitors as treatment of obesity, insulin resistance and diabetes II. As of right now these trials are all in stage III indicating they are all successful thus far. This may explain why no new SSRI drugs have been developed in the last decade and efforts are now focused on SNRI/SSRE and even dopamine agonists like pramipexole. FDA is even about to approve MDMA (ecstasy) for treatment of PTSD. The rumor is they will also soon approve ketamine for depression and may even consider micro-dosing LSD for intractable mental conditions. At the same time the ads for SSRI on TV have intensified, which is probably because Big Pharma is desperately trying to squeeze the last few drops of profit from these drugs before they go into oblivion. But don't expect any pharma exec to get sued or go to jail for the millions of people these drugs damaged or drove to suicide/homicide.""The role of serotonin in fibrosis is well-known despite the public lies thrown around by Big Pharma. I posted about the behind-the-scenes acquisition of the serotonin antagonist terguride, which Pfizer is now hoping to be able to treat ANY fibrotic condition (as shown by a recently filed FDA application). Serotonin is closely associated with prolactin and both are known in the transplant industry as growth hormones - i.e. short term rise in their levels can benefit the regeneration of partially resected/removed organs like liver, kidneys, GI tract and spleen. However, chronic rise of their levels is known to cause a number of issues including fibrosis and cancer of the GI tract that collectively lead to the well-known "carcinoid sydrome". For decades mainstream medicine has been denying that serotonin has a causative role in fibrosis and cancer promotion despite the fact that people with the carcinoid syndrome die from fibrosis and not the actual cancer and its metastases. This new study may change some of that preception in the medical circles as it found that serotonin is the primary cause of liver tumor (re)emergence and the development of metastases in colon cancer. I suppose the moment Pfizer see this study it will add yet another "indication" for their blockbuster drug, while continuing to sell SSRI. Hey @aguilaroja I think you will like this. Btw, cyproheptadine has been shown to be therapeutic in liver, colon and other GI tract cancers and that fits perfectly with the study results below. The fact that vitamin K2 is about to be approved by the FDA for both prevention and treatment of liver cancer suggests that at least one of the mechanisms of that vitamin is antagonism to serotonin.""This new study found that the profoundly negative effect of SSRI on behavior is evident even in crabs, and even when they were exposed to very low concentrations of the drug. While the study used Prozac (fluoxetine), the effects span the entire class of SSRI drugs. The levels of SSRI the crabs were exposed to are likely not much different than levels present in tap water in most US counties. Given the recent campaigns to drink more tap and less bottled water, I am wondering how much of the violent crime we see is simply due to chronic, low-grade SSRI poisoning/toxicity. Keep in mind that all processed food is prepared with tap water (unless specified otherwise) and that includes cooked commercial food available in cafeterias, buffets, and "high-end" restaurants.So much for the "happiness hormone"! I am wondering when this link will finally be publicly acknowledged in humans....""I have posted before studies in regards to the link between metabolism, energy and highly valued human qualities like altruism, and helpfulness. As has been confirmed in humans, egalitarian beliefs, altruism and generally friendly behavior towards complete (genetic) strangers requires good metabolism and proper energy production. Bonobos are known as one of the most gregarious ape species, and coincidentally are known to be resistant to aging due to high levels of thyroid hormone. Now, if egalitarian beliefs and altrusim and good thyroid function go hand in hand, and if bonobos maintain high thyroid function throughout their lifetimes then one would expect them to be quite altruistic (without being driven by promise of payoff or somehow coerced into altruism)., which would explain the altruism...and the very high sexuality bonobos are famous for.""The study tries to downplay the risk by claiming that it is only relevant to "old, frail people". However, the specific lung issue linked to SSRI - bronchiectasis - is almost never found as an independent disease but rather almost always as a symptoms of cystic fibrosis. Given serotonin's primary role in development and progression of fibrosis I think the risks of SSRI drugs for ANY age group should immediately become apparent. As it is the case with so many other chronic and debilitating/lethal conditions lately, the rates of cystic fibrosis have been steadily increasing over the last 3 decades, which coincides almost perfectly with the prescription rate increase of SSRI drugs. Of course, instead of acknowledging the public health fiasco of the SSRI drugs, FDA and companies like Pfizer silently push anti-serotonin (5-HT2B) drugs like terguride through the system for quick approval as treatment for these serotonin-driven conditions. The system sells you both the poison and the remedy, and the pubic is oblivious.""By now even the general public has gotten a wind of just how bad the SSRI drugs are. But most of the studies demonstrating negative effects from SSRI use are focused on the health of the patient taking them or the health of the baby whose mother is taking SSRI while pregnant or during breastfeeding. This new study is interesting because it looks at how SSRI usage by the father impacted his future children. As such, it provides direct evidence invalidating the so-called Weismann Doctrine. In other words, medication taken by the father should not be able to influence the risk of disease in his children beyond what his genes already code for. Since taking SSRI increased the risk of ADHD it is obvious that disease risk (in this case) can be changed AND passed on to the next generation without any mutations taking place. But instead of stating that most obvious explanation, the authors say that the reason for the increased risk is due...to the father's pre-existing conditions that necessitated SSRI use in the first place. I don't know how to call this other than pathetic, corrupt muddling of science in defense of profit and status quo!""I am posting this study because it may explain why the incidence of autism is much higher in male than in female offspring. As I posted in a few other threads before, serotonin is one of the likely direct causes of the autism pathology and it is of course elevated during chronic stress. Unfortunately, it is very common for doctors to prescribe SSRI drugs to both the pregnant mother (to prevent postpartum depression) and to the young child if it is showing signs of autism. As the study below shows,and I would not be surprised as a significant number of so-called clinical autism cases are due to the prenatal and postnatal SSRI exposure of both mother and (male) child.""Despite the denials of mainstream medicine that CFS exists as an organic disorder, many studies have been done on the etiology of the fatigue and how it often follows an acute illness, usually of "viral" origin. Due to the fact that the role of serotonin in inducing fatigue is well-known everywhere except in clinical practice, many of those studies have examined the changed in the serotonergic system but the results were inconsistent. No major changes were found in brain tryptophan, serotonin or 5-HIAA levels in CFS patients.Well, most SSRI drugs are actually 5-HT2A agonists. Thus, despite that fact that some of them are antagonists at 5-HT2C (Prozac) their overall effect would be expected to be pro-suicidal, which has been confirmed by vritually all trials and has resulted in blackbox warnings by the FDA. The good news is that the study suggests that something as simple as cyproheptadine or another non-selective serotonin antagonist may be a viable treatment for both CFS and suicidal ideation.""I am hoping that as a result of this study, mainstream medicine will finally start to take the pathogenic role of peripheral serotonin more seriously. More importantly,(which platelet serotonin release). A combination therapy would likely be even more effective, and should be able to protect from the immune over-activation in any infectious or allergic pathology.""The role of serotonin in migraines is becoming more recognized every day. Unfortunately, SSRI drugs are still being used to treat migraines, but more recent studies found that serotonin antagonists like cyproheptadine or mianserin are much more effective.. Thus, aside from drugs like cyproheptadine and aspirin (which affect both serotonin and prostaglandins) another easier OTC remedy could be taking a bigger dose saturated fat like coconut oil, or palmitic/stearic acid in order to block the effects of linoleic acid. Vitamin E could work as well as it has also been shown to directly destroy linoleic acid.""The non-motor signs/symptoms of PD (tremor, drooling, slurred speech, etc) have long been thought to be directly due to dopamine deficiency due to the death of the nigrostriatal dopamine neurons. The common treatment for those signs/symptoms and the motor symptoms as well is usually a dopamine agonist of some sort, or L-DOPA.Lower SERT availability results in elevated intracellular serotonin levels. The commonly prescribed SSRI drugs are SERT inhibitors and sadly they are being prescribed quite often to people with PD. Given that dopamine and dopamine agonists are inhibitors of TPH, they tend to lower serotonin levels, which explains their benefit for PD. If high serotonin is indeed a major cause of dysfunction/pathology in PD then increased salt, protein (which lowers brain serotonin) and keeping endotoxin (and thus serotonin) low could also have pronounced benefit for PD.""I posted a study recently showing that crabs exposed to very low levels of SSRI drugs (as found even in processed sewage) become reckless, aggressive, homicidal and generally psychotic. While this effect of the drugs can easily be ascribed to some peculiar toxicity of the SSRI class molecules, the study below suggests that it is actually serotonin that is responsible for these bizarre behaviors.As the study also says, this zombifying effect of serotonin has been confirmed in other lower species like ampipods and fish. The study even directly names the poison and the remedy - Prozac and cyproheptadineI have also seen studies confirming these effects of serotonin in higher animals and even primates. So, there should be little surprise that modern societies are becoming more and more whacky - i.e2So, if this knowledge is available and well assimilated then something more than incompetence is probably at play at the public policy level. I think that this study below gives a hint what the reason may be - if serotonin turns people into manipulable zombies capable of automatically marching to the orders of the powers that be (even to their own peril/demise), then serotonin and SSRI drugs are the perfect public policy instruments and the dream of every government official on the planet. The powers that be are the "parasite" analog from the study below and we are the unsuspecting "slugs". I find the study ironic precisely because the term "slug" is commonly used in the military and high-ranks of government to describe the working, obedient, slow-moving masses. No wonder LSD is a Schedule I substance and dopaminergic drugs are banned by WADA and officially frowned upon as gateways to "addiction". I think Ray already hinted at the deliberate nature of pro-serotonin propaganda stemming from the realization back in the 1960s that LSD and other serotonergic drugs making people "crazy" and defiant. Strangely enough, the term "oppositional defiant disorder", which is now part of the officially diagnosed mental disorders codified in DSM, was coined back in the early 1970s when civil unrest was at its highest levels. Not long after, the first SSRI drug was synthesized. Do you think this is a coincidence??""This study is presented as groundbreaking and unexpected but in fact big pharma has been quietly working on anti-serotonin therapy for obesity/diabetes for more than a decade.. Apparently, as the scientist says,. Funny, the unsuspecting public never got the memo...But quietly and without much fanfare, pharma companies have started several trials with TPH inhibitors for treating obesity and diabetes, and many others are underway abroad where big pharma does not have to comply with so many regulations. Anyways, I suppose the good news is that even hardcore dogmatics in mainstream medicine can change their mind and improve people's health as a result. Now, the study below talks about reducing gut serotonin as therapeutic and for most scientists this means some sort of inhibition of serotonin synthesis. However, since the main trigger of gut serotonin synthesis is endotoxin, perhaps something as simple as the 5-HT3 antagonist approach mentioned in this thread could work. Unlike 5-HT3 antagonists, of which there are plenty and all are well tested, TPH inhibitors are much harder to come by and even older ones like Fenclonine do not really have much experimental safety track record. Furthermore, I have received reports from several people that even a BCAA/tyrosine combination seems to improve their digestion and help them lose weight, so there is hope that this can still be achieved with dietary serotonin restriction without the use of pharma drugs.""One of the first studies that I came across more than 15 years ago when I first started dabbling in biochemistry was on the roles of serotonin and dopamine in "pathological curiosity" seen in some children, which was thought to often lead to "oppositional-defiance disorder" later on in their lives. The study described elevated dopamine levels in these little "pathologically" curious children and discussed how SSRI therapy quickly brings them under control. The study cited abundance of well-documented reports of their parents gushing with joy about the remarkable patience and obedience that their (formerly) "pathologically" curious children seemed to develop after being put on an SSRI. The study did not go into the details of how the SSRI drugs achieved those effects but I have always suspected that serotonin is involved in the much-lauded ability for delayed gratification. This study below adds evidence in favor of the serotonin-patience hypothesis. More importantly,which is ideal for the purpose of public policy with it always changing course. Even "better",. So, in summary, I think it is fair to say that elevated serotonin gives organisms delusionally positive expectations about the future when in fact the likelihood of such outcome is low. The conspirator in me finds it hard to ignore the remarkable parallels between what the government wants from its subjects (i.e. patience and obedience) and what the SSRI drugs offer.""Yet another nail in the coffin of the "happiness hormone", which may end up being one of the biggest scientific frauds of the 20th century, rivaling the one about estrogen being the "female" hormone.. Over the last decade, most new candidate drugs for bipolar disorder entering clinical trials are serotonin antagonists and several case studies on PubMed show rapid symptomatic relief from cyproheptadine.""Peat wrote in a few articles that serotonin is extremely detrimental for bone growth and that anti-serotonin drugs are anabolic for the bone. Serotonin is the most potent inducer of cortisol synthesis, which is probably the main mechanism behind its bone destructive effects. However, serotonin is also in inflammatory mediator itself and promotes synthesis of other inflammatory mediators like prostaglandins, NO, interleukins, etc. Regardless of the large body of evidence demonstrating the dangers of serotonin, the official version is still that elevating serotonin is one of the best things you can do for your health.. That last finding is great indication that serotonin has a generalized weakening effects on the bone and is not simply a temporary risk factor for bone issues.""Peat wrote a few times on the brain's innate need to dream and how anti-serotonin chemicals like LSD removes the barriers on consciousness imposed by an authoritarian culture. He said that the ability to dream in an awake state is an indication of high metabolic rate and that is a testament to serotonin's negative effect on metabolism - a serotonin antagonist like LSD intensifies greatly a biomarker (awake dreaming) of high metabolism. He has also spoken about the high metabolic rate of young children and their ability to quickly heal from trauma or overcome disease much more easily than adults. ""In confirmation of this statements,. Blake thought that the doors on perception are artificially kept semi-closed for cultural reasons - i.e. the ability to focus and do work for the enrichment of the powers that be. While Blake is not known to have used LSD, he stated several times that. Aside from LSD, other anti-serotonin chemicals also have similar effects. In my experience, while serotonin antagonists like cyproheptadine are not hallucinogenic, they also have quite a liberating effect on openness to new experiences and creative thought. Less sedating alternatives like ondansetron have also been reported in animal studies to increase cognitive ability and creative problem solving.""While the study is nothing new for the forum users here, what makes it important is that it is the largest study ever and includes reviewing all the available literature on the topic to date.Considering that apparently more 85% of people with depression spontaneously recover without any treatment, the case for SSRI use becomes completely untenable."The SSRI exposure was comparable to doses that are commonly prescribed to people with depression. As the study says, the rising incidence of antibiotic resistance worldwide has usually been ascribed to antibiotic overuse by doctors, but this new evidence suggests that additional factors are at play and may even be the major reason for the rising resistance rates. Given the serotonergic effects of the SSRI drugs and the suppressive effect serotonin has on the immune system, the findings should not come as a surprise, even to mainstream medical professionals. However, since SSRI are such a profitable pharmaceutical niche we probably won't see action curbing their use any time soon. The scary part is that SSRI are prescribed to many in-patients to "prevent" depression or mitigate stress as a result of surgery. So, the risk of antibiotic resistance is automatically raises for the most vulnerable group of people. No wonder hospital death rates have been rising steadily since the 1990s when the SSRIs started becoming prescribed on a mass scale."