The Serotonin Delusion

When most people are asked about the role of Serotonin in the body, almost all of them claim that it is part of the happy suite of neurochemicals, and talk of feelings of joy and euphoria. Internet pictures like the one shown below are commonplace, and even cafes have opened touting their food as the substance of happiness, and referencing serotonin.

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A look into the literature dating back decades, as well as that of the politics in science, will show you that quite the opposite is true. Sorry “Serotonin Dealer…”
So exactly where did this erroneous idea come from? Its clearly stated in most textbooks, yet none of them are referenced.

The 1960s was time now referred to as the “Psychedelic Era,” a time of social, musical and artistic change influenced by psychedelic drugs. Psychedelic drug use during this period encouraged unity, the breaking down of boundaries, the heightening of political awareness, empathy with others, and the questioning of authority, and indeed, contempt for it.

Of course, this presents a very threatening situation for those in government, or those willing to control the population.

LSD was brought to attention of the USA in 1949 by Sandoz Laboratories, because they believed it might have clinical applications, It began to be largely understood that LSD exerted dopaminergic effects, and the substance became widely used in pychiatric treatments, and in those with addictions, with marvellous results. It was also understood at this time that dopamine and serotonin functioned in opposition to one another (had opposite effects,)

Sandoz halted LSD production in August 1965 after growing governmental protests at its proliferation among the general populace, having sanctioned research to show that the effects made you “insane.”

So if dopamine and serotonin function in opposite ways, and dopamine makes you crazy, then serotonin must make you “sane.” So the idea of the “hapy neurochemical” was born, and proliferates today.

But There is a Problem for the Serotonin Pushers…

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To this day, the FDA does not recognize the claim that Serotonin is helpful for depression – therefore making such claims is illegal. To date, there has been no trial directly with Serotonin, or drugs that boost Serotonin, that have shown that Serotonin is the actual beneficial agent in treating depression.

In fact, GSK, a major manufacturer of the serotonin promoting SSRI class of drugs, was ordered to pay handsomely in a fraud settlement for claiming so.

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Serotonin happens to be elevated in blood samples from individuals suffering the following presentations:

Fibromyalgia
•Anxiety
•IBS
•Starvation
•Infection
•Migraine
•Inescapable shock
•Chronic social defeat
•Chronic Mild Stress
•Maternal separation and social isolation
•Learned Helplessness (modern human depression)
•Cardiac and Pulmonary Fibrosis
•Eczema and Asthma

And many more undesirable states. Serotonin’s other names include thrombotonin, thrombocytin, enteramine. These historical names derive from its role in the intestine (to stimulate acute peristalsis/diarrhea/elimination) and in blood vessels (to stimulate clotting,) futher indicating this chemical is anything to do with pleasure, and everything to do with shock and emergency response.

It comes as a surprise to many that blood serotonin is at its lowest in individuals who are in love.

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The Literature on Serotonin Presents Many Issues For the Happy Hormone Story….

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The increase of inhibitory serotonin with stress and depression is probably biologically related to the role of serotonin in hibernation, which is an extreme example of “harm avoidance” by withdrawal. But serotonin is also elevated in aggressive phenotypes.

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Serotonin and Aging

Fibrosis of all tissues is a hallmark sign of aging. Serotonin is a primary mediator of fibrosis, and is promoted by stress. Given that being alive longer allows us to be subjected to more stressors, the patterns we see inherent in aging become clear. In fact, while publicly continuing to claim that serotonin is good for us, Pfizer quietly pushed a drug through clinical trials that treats pulmonary and heart fibrosis (and of course it is a serotonin antagonist!)

“…Serotonin stimulates the proliferation of pulmonary artery smooth muscle cells, and induces fibrosis in the wall of pulmonary arteries. Together, this causes vascular remodeling and narrowing of the pulmonary arteries. These changes result in increased vascular resistance and PAH. Due to the potential anti-proliferative and anti-fibrotic activity of terguride, this potential medicine could offer the hope of achieving reversal of pulmonary artery vascular remodeling and attenuation of disease progression.”

In old age, the amount of serotonin in the brain increases. This undoubtedly is closely related to the relative inability to turn off cortisol production that is characteristic of old age.  Most people now understand that cortisol shreds the brain and is implicated in the progression of Alzheimer’s pathology.
In white hair, the amount of serotonin is higher than in hair of any other color. The presence in senile tissues is probably closely associated with the processes of decline. (Sapolsky and Donnelly, 1985).

Serotonin can reduce the production of energy by inhibiting mitochondrial respiratory enzymes (Medvedev, 1990, 1991,) and by reduction of oxygen delivery to tissues by vasoconstriction. It also appears to interfere with the use of glucose (de Leiva, et al., 1978, Moore, et al., 2004). Insulin resistance and decreased energy production is ALWAYS associated with the aging process, and is associated with most all chronic illness we see today.

Serotonin antagonists mianserin and cyproheptadine extend lifespan by up to 30% by mimicking the effects of caloric restriction. Mianserin has been shown to extend maximum lifespan by as much as 40% (in roundworms,) and TRIPLED the duration of the youthful state in these worms.

If this were to be applicable across species, the equivalent to humans is living beyond 120 years of age and being a college student for the first 60 of those years

“…Four compounds increased lifespan by 20%-30%: mianserin, mirtazapine, methioteptin and cyproheptadine. In humans, all four compounds are antagonists of serotonin 2 (5-HT2) receptor”

Unsurprisingly, a number of SSRI drugs caused decrease in lifespan, sometimes up to 80% (!!!)
Nature 450, 553-556 (22 November 2007) doi:10.1038/nature05991

Serotonin and Exercise

It has always been interesting to me clinically that people think of exercise a bit like an army drill, where the more exhausted and sore they are at the end, the better they’ve done for themselves. I have never seen another creature on this planet want to exert themselves beyond their capability when there has been no immediate reward at the of it, such as escaping imminent death! The post exercise “endorphins” (stands for endogenous morphine – and ONLY released in response to discomfort) is so often cited as another benefit, but is anything but. Endorphin, along with serotonin and adrenaline are key players in mediating the stress of exercise on the body.

“The fatigue produced by over-training is probably produced by a tryptophan and serotonin overload, resulting from catabolism of muscle proteins and stress-induced increases in serotonin.
Muscle catabolism also releases a large amount of cysteine, and cysteine, methionine, and tryptophan all suppress thyroid function” (Carvalho, et al., 2000)

Serotonin Clinically

As mentioned above, serotonin is implicated in many acute and chronic presentations, many of which (such as depression or fibromyalgia) are treated first-line by GPs with SSRI drugs that promote MORE of serotonins actions. You really couldn’t make this stuff up. Is it any wonder Fibromyalgia (FIBRO should be the big hint here…) is such a chronic disease mystery to doctors, who’s first line of action makes it worse? It appears that serotonin ANTAGONISTS seem to do pretty well at lowering the symptoms by as much as 40%

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Moreover, tryptophan hydroxylase inhibitors completely eradicate IBS symptoms. Just put that into perspective with how many SSRI patients wind up with IBS and in a spaghetti heap of chronic illness.

So there you have it. Serotonin is not the happy hormone, unless aging, fibrotic cells and a zombified state are something you consider to be a feature of a state of bliss.

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