Serotonin Myths: High Serotonin Blues, Part 3

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This is Part 3 in a series on high serotonin. Check out Part 1 and Part 2 here.

Questions are one of the only things in life that come in unlimited quantities. Ask any four-year-old. I certainly found no shortage of questions when I started looking into the problems of high serotonin. Yes, I said high serotonin. While serotonin deficiency seems to be the blanket diagnosis these days, there’s evidence that too much serotonin may be causing more problems than too little.

So, questions? Yep, there are plenty. Here are some of my own questions about serotonin, and what I’ve drummed up through a little out-of-the-box research.

High Serotonin Q and A

  • If serotonin deficiency doesn’t cause depression, then what does?

There are a number of possible answers, but some of the top contenders are low thyroid function, dopamine deficiency, and hormonal imbalance (such as low progesterone/high estrogen in women). All of these can be interrelated and are largely affected by diet and lifestyle.

  • How do we treat mood disorders outside of increasing serotonin? 

Looking at some of the possible root causes above, some of the best ways to approach mood disorders and depression would be improving metabolic health and balancing hormones. Granted, that’s easier said than done. But again, lifestyle and diet play an enormous role in these areas. (More on that in the future.)

  • Why do tryptophan, 5-HTP and St. John’s Wort make some people feel terrible (like me), but make others feel better?

Believe me, this is a big question of mine. It obviously depends a lot on a person’s specific metabolic state. But one interesting possibility is that high serotonin stimulates the release of stress hormones adrenaline and cortisol. Both of these chemicals can boost your mood and energy in the short term, but can have negative side effects if levels remain chronically high.

  • What about light therapy, getting enough sleep, exercising, and eating well? Don’t all these make you feel better because they raise serotonin levels?

No! That’s a mainstream myth. Pretending that those things only affect serotonin levels is a great example of one-dimensional thinking. For example, being in the sunlight boosts thyroid function, exercising can raise dopamine levels, and eating enough protein can improve liver health. All of those directly impact your moods. And that’s just a couple quick examples. The body is an incredible cascade of hormones, chemicals, energy and cells. Reducing it all to serotonin levels is ignoring the larger picture of mental (and physical) health.

  • How did our ideas about serotonin get turned so upside down? 

Short answer? Follow the money. Around the mid-20th century, there were some concerns about the possible side effects of large doses of LSD (which is a serotonin antagonist). Because LSD is essentially anti-serotonin, some took the idea and ran with it. Suddenly increasing serotonin levels became the shiny new treatment for mood disorders and depression. Pretty soon the pharmaceutical industry was up to its elbows in drugs for increasing serotonin, and pretty much stayed that way for the next several decades. It would be financial suicide for them to backpedal and suddenly question the entire mainstream concept of serotonin.

If you’re anything like me, these brief answers may have triggered even more questions! In that case, you might want to read some interesting articles on serotonin from Dr. Ray Peat (with ample references) here and here.

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  1. I have enjoyed following your series on serotonin. I, too, experienced a few “not good” side effects from things like SamE, 5HTP, and a few others. I’m not depressed but I have occasional anxiety and I used to have horrid panic attacks (impending doom type attacks). I finally had to resort to using some xanax, but over the past 25 years I have hardly used it at all. My doctor gives it to me on a “prn” basis because he knows I don’t/won’t abuse it. But I’ve been desperately looking for another alternative to the stuff, as well as an alternative to atenolol (I use it to keep a steady heart rhythm because I have a prolapsed mitral valve, insignificant). I have decided to give the combo of choline & inositol a try for the anxiety. Still have no answer for the atenolol.

    • It’s definitely not easy to find natural alternatives that work–especially when what works for some people has the opposite effect on others. It’s worth the effort to pay close attention to how individual substances affect you, but it can sometimes be a painstaking and frustrating process.

    • I would talk to your Dr about taking you off the beta-blocker for your MVP. In the end if it is decreasing your quality of life significantly, you should feel free not to take it (though make sure you taper off with the supervision of your Dr). However, if you have significant Mitral regurg it would be in your best interest to stay on it.

      For panic disorder, xanax is very effective PRN, but make sure it is only PRN! You could ask about an SSRI if it is something that is significantly affecting your quality of life (agoraphobic symptoms etc). Also, look up some classes on mindfulness and deep breathing. Then actually put into practice what you learn on a very regular basis.

  2. Have you ever heard of the MAO-A gene? It is something Dr. Amy Yasko tests for on her methylation panel and it can contribute to serotonin imbalances.

    • I haven’t looked into that research yet, but you bring up an interesting point, Dawn. A genetic component could be a very relevant explanation for varied reactions to the same substances. It’s definitely something I want to learn more about!

  3. First let me explain my background. I am a second year medical student who has been through a major depressive episode and am on an SNRI. I am not brainwashed into the thinking of modern medicine and appreciate alternative medical thinking.

    This is going to be a response to Parts 1, 2, and 3 that I just read. A lot of this will be from personal experiences, articles that I have read, and classes. However, I don’t have time to cite everything right now.

    First, I want to clarify that selective serotonin reuptake inhibitors (SSRIs), today’s first line medicine for depression and OCD, do not increase suicidal thinking. Studies have shown an increase in suicidality, which is the talking about suicide. There is way too much confounding (possibility that another variable other than the SSRI is causing the suicidality such as actually receive treating/acceptance of MDD diagnosis etc.) to blame SSRIs for the increase.

    SSRIs at too high of a dose or increase levels of serotonin (5-HT) WILL CAUSE APATHY. This is why I will never recommend supplementing 5-HT directly or indirectly in the diet. Only take antidepressants if a diagnosis calls for it and under the supervision of a trusted physician (note I said trusted physician, I do not trust all physicians). This will ensure that the proper dosage and proper SSRI is given as it is hit or miss. I went through a number of SSRIs before being given an SNRI. I was confident in my ability to judge for myself what was best for me.

    SSRIs are not meant to be a “fix-your-depression-drug.” It is meant to assist a patient when they are restructuring their lives to combat their depression. The biggest things for me were social support, destressors (exercise), improved diet, taking breaks, understanding how and when to express my emotions. Relapses into another major depressive episode are very high for the first year, so an SSRI is usually given for a year’s length and then tapered off. However some people do chronically use SSRIs for necessary reasons.

    SSRIs have a very low potential for overdose. It would be very difficult to do this by accident. To overdose you would purposefully have to stock up on months worth of drugs and/or take them with other medication that you know would result in serotonin syndrome (namely MAOIs).

    Furthermore, 5-HT has definitely been implicated in mood disorders and OCD. When it comes of psychopathology, the mechanism by which the neurotransmitters (nts) work is poorly understood. More than likely it is a very complicated balance of multiple nts in various regions of the brain that may never really be known. The biggest thing with SSRIs is not the fact that it causes higher 5-HT levels, but that it results in growth of the hypothalamus (which is often atrophied in MDD). Once the hypothalamus has grown (probably from 5-HT stimulation), the body can then regulate moods and metabolism without medical intervention.

    Also note with electroconvulsive therapy (ECT). The very controlled use of induced seizures at select areas of the brain result in hypothalamic growth much more quickly than SSRIs and is very effective for more difficult cases of depression/anxiety.

    My two cents on how to not become depressed is to either decrease levels of stress, increase ways of destressing, and better your ability to cope with stress. The body responds to chronic stress with cortisol, which decreases hypothalamic activity and results in atrophy.

    Thanks for bearing with me and a little lesson in psychiatry.

    Also Ms. Walling I have just stumbled upon your blog and have enjoyed / been practicing or now am starting to put into practice many of natural approaches to overall health you mention. So Thank you!

    Also there is a high degree of genetic implication in all mood disorders to respond to a previous comment. MAO-A stands for monoamine oxidase – Type A (guessing there is a B type as well). This gene codes for the enzyme monoamine oxidase, which breaks down 5-HT. Therefore if you have a defective gene/enzyme you wont break down 5-HT as well and will have increase 5-HT signaling. A drug previously used for depression and sometimes for migraines is MAOI or monoamine oxidase inhibitor, which keeps 5-HT from being broken down in the brain.

    ok i am done haha.

    In Christ,

    E.S. McDonald

    • E.S., you are very sadly mistaken. SSRIs *DO* increase suicidal thinking and behavior in some people, namely because the drugs can trigger akathisia and horrifying numbness. I myself endured this nightmare on Zoloft. It is not a high incidence (2-4% of users), but it’s significant. And this isn’t just for depression patients, it’s also for those suffering from OCD and anxiety disorders.

      SSRIs, like 5HTP and melatonin, achieve their effects not because serotonin is some kind of “feel good” chemical. It’s because these substances act as tranquilizers, essentially numbing away the patients’ anxiety or intense emotions. Alcohol and sugar can do the same.

      As for neuronal growth, that is not supported by clinical trials. Just yesterday, a primate-based clinical trial found that Zoloft shrank the hippocampus compared to placebo. Also, a trial of Celexa for agitation in Alzheimer’s patients showed an increase in arrhythmia and worsened cognition vs placebo. You can stop with the shilling for SSRIs – these drugs pose only a small benefit and their long term effects on brain structure and affective disorders in general aren’t looking too rosy.

  4. But Lizzy, you didnt mention how to reverse brain fog. All things serotonin make me worse, but even without any tablets my default is still brain fog. How can I think clearly??

      • You may have the genetic mutation on COMT (fast version COMT, not slow) and therefore, need more dopamine than serotonin. D-phenylalanine is the non-energizing version that you can take at night to open the valve of stress hormones that build up during the day when the COMT gene is expressing. This is only one possibility, since a lack of methyl-folate (active folate) can also cause low dopamine in people with an MTHFR genetic expression. For these folks, eating processed foods made of flour enriched with folic acid (synthetic folate) makes things worse because they can’t metabolize folic acid and it builds up, causing all kinds of symptoms.

        I’ve seen many people with both genetic expressions, which can make mood issues challenging to solve without knowing how to apply the right food and supplements. The good news is that once methylation is working again, it gets a lot easier and moods improve tremendously.

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