Serotonin Needs a New Script
More than just your average "feel good" chemical.
Read time: Approx 5-7 min
Serotonin is not your body’s version of a “good vibes” smoothie. It’s not happiness in liquid form, bottled up and waiting to be released if you just meditate harder or take enough supplements. That’s a convenient fairytale. The real serotonin story is messier, more fascinating, and shows just how inseparable our brains are from our bodies.
This is the tale of a molecule that works in your brain, gut, blood, fascia, and nerves…quietly juggling a dozen roles, while pop culture continues cherry-picking 1960’s papers on its role in “happiness.” Yes, serotonin has a relationship with depression…but saying depression is caused by a lack of serotonin is like saying housefires are caused by a lack of firefighters.
It’s not “false” in that serotonin doesn’t matter. It’s false because the story is incomplete.
What is Serotonin?
Serotonin (5-hydroxytryptophan) is a neurotransmitter, one of the brain’s chemical messengers. It’s made from tryptophan (hence the second half of its chemical name), an amino acid found in foods like turkey, eggs, seeds, tofu, and salmon. The body converts tryptophan into serotonin through a complex process that requires enzymes, B vitamins, and, perhaps the most important ingredient….those lovely bacteria that make up your gut microbiome.
About 90 to 95% of your body’s serotonin is made in the gut, not the brain. That’s right. The colon. The poop chute. The thing you mostly ignore until it backfires after late night Taco Bell…is…a serotonin factory. And while serotonin from the gut doesn’t cross into the brain (#blood-brain barrier), your two nervous systems, central and enteric, still talk to each other (#gut-brain axis). A lot. Which is why stress gives you diarrhea and why your sh*tty diet can make you feel like weaving into oncoming traffic. We’re not just what we eat. We are what we choose to feed the 100 trillion little bugs squirming around in our intestines. Our “feel good” hormones and many metabolic hormones are the byproduct of our gut bacteria. Much like planet Earth and the climate crisis: if we treat them like sh*t, they will pay us back downstream. So maaaybe it will make you rethink those unnecessary antibiotics the next time you’re sick…
Serotonin’s not just floating around, though, waiting for the opportunity to cheer you up... It’s regulating digestion, nausea, pain, sleep, body temperature, heart rate, and how freaked out you feel during existential crises in grocery store parking lots. So think about all of those mysterious symptoms…fatigue, insomnia, pain, worry, emotional numbness…and then think about what you’ve been eating, what you’ve been drinking, and the pills you’ve been swallowing. How’s your gut been feeling?
The Myth of “Low Serotonin”
Let’s return to that well-meaning but outdated theory you’ve probably heard: depression is caused by low serotonin levels.
That’s the monoamine hypothesis, which showed up in the 1960s when psychiatry was really into the idea that you could “fix feelings” with chemicals. And it’s not that this idea is totally wrong…just that it’s reductionist. Saying low serotonin causes depression is like saying climate change is just about plastic straws.
SSRIs (Selective Serotonin Reuptake Inhibitors) like Zoloft, Prozac, and Lexapro are designed to increase serotonin availability between neurons. For many people, they help. Sometimes a lot. Sometimes not at all. Sometimes they help a little, and then they don’t. Sometimes they make things worse. But that doesn’t mean low serotonin caused the problem—it means increasing serotonin had an effect. Those aren’t the same thing.
Think about it this way…
Depression isn’t caused by a lack of serotonin, in the same way that headaches aren’t caused by a lack of ibuprofen.
No one assumes a migraine is your body crying out for more Motrin. We understand pain as a symptom, and we use meds to manage that pain while we figure out what’s going on beneath the surface. Same goes for mood. SSRIs can be part of the puzzle, but they aren’t a cure. They don’t build safety, or heal trauma, or teach your nervous system how to breathe. That's why the addition of therapy is essential.
How Psychedelics Enter The Picture
While SSRIs gently nudge serotonin levels and hope your inner world cooperates, classic psychedelics like psilocybin, peyote, and LSD kick the serotonin system into full-on jazz improvisation. They target the 5-HT2A receptor, a very different serotonin receptor than SSRIs…and they light it up like a Christmas tree.
The result? Something resembling “neural chaos.”…in a good way. The kind that breaks you out of depressive time loops, shatters the internal doomsday monologue, and gives your Default Mode Network (the brain’s “me, myself, and why is everything terrible” center) a much-needed nap.
Psychedelics do more than simply shift thought patterns…they crack open the body.
Under the influence of classic psychedelics, people often experience waves of emotional release, spontaneous shaking, sobbing, or the kind of cathartic snot-cry that your nervous system has likely been stuffing in a closet since 2004. These aren’t “side effects,” rather they’re somatic trauma finally breaking free.
And serotonin? It’s deeply involved in this process. 5-HT2A receptors live everywhere…they’re hanging out in your gut, your fascia, your spinal cord. These receptors help your body literally feel again, especially after years (or decades) of shut-down, numbness, or intellectualizing everything into therapy-speak and data.
Ketamine helps us understand that it's not just serotonin responsible for psychedelic experiences.
Ketamine could care less about your serotonin. Doesn’t even glance at it. Ketamine takes an entirely different path by blocking NMDA receptors in your brain and unleashing a flood of glutamate. This promotes rapid neuroplasticity…kind of like propping open all the windows and letting the breeze blow through your mental attic.
Ketamine can be stunningly effective for depression. It works fast…like, within the hour. It can pull people back from the edge when nothing else will.
But…it can fade quickly for many patients. And it often works by numbing the connection between mind and body.
Many people describe ketamine sessions as dissociative, floaty, or dreamlike. Having experienced it a few times, I would tend to concur. It's quite pleasant, actually, which might speak to some of the concerns that arise around its potentially addictive nature. For folks stuck in trauma loops, this brief dissociation can be a lifesaver—a temporary escape hatch from hell. But it doesn’t usually drop you into your body the way classic psychedelics do. It’s more likely to hand you a flashlight and say, “Here’s the attic. Just don’t look in the basement.”
Without the embodiment…the shivers, the weeping, the gut-punch insight, ketamine can provide intellectual clarity without the physical catharsis. And that’s okay. And for the right person at the right time, that may be what’s needed. But it may explain why its effects often fade faster unless paired with somatic therapy or integration practices that bring you back into your body.
So classic psychedelics are better? Not on their own…
When used through the right channels, with enough stimulation of the right cortical regions, they can help orchestrate a symphony of physical, emotional, and cognitive release. Not a “cure”…But they might loosen the floorboards, shine a light under the rug, and invite your nervous system to have an honest conversation with itself.
SSRIs don’t often do that. Think of them as chemical librarians, quietly moving things around. Psychedelics act more like punk rock therapists…busting down the doors to your internal haunted house, while simultaneously lending a helping hand.
Enough About Drugs…What Else Does Serotonin Do?
A buttload, actually. It’s the quiet multitasker of the body…doing a hundred things in the background, while mood hogs the spotlight.
Digestion:
Serotonin regulates intestinal motility, aka how fast food moves through your gut. Too much? Diarrhea. Too little? Constipation. This is also why a new antidepressant might make your stomach act like it’s auditioning for a horror film. And also why various forms of antidepressants are used in the treatment of functional gut disorders, such as IBS.
Nausea:
Feeling queasy? That’s probably serotonin, too. When the body detects something toxic, serotonin is released in the gut and signals the brain to throw it up or shut it down. This is why serotonin-blocking drugs, such as ondansetron (Zofran), are often used to control nausea.
Pain:
Serotonin can either dull or heighten pain depending on where and how it’s acting. It’s involved in your spinal cord’s pain pathways, and low serotonin levels have been associated with chronic pain conditions like fibromyalgia, migraines, and IBS. That’s right...IBS, physiologically-speaking, is classified as a “pain syndrome.” Think of it as the “migraine of the gut.”
Sleep, Appetite, and Body Temperature:
Serotonin helps regulate melatonin, the hormone that controls sleep. It also influences appetite and thermoregulation. Ever feel shaky, sweaty, and agitated when you’re anxious or depressed? That’s your serotonin system trying to keep things together while your internal thermostat loses its sh*t. Ever crave carbs when you’re feeling down? Serotonin acts on the hypothalamus, activating and inhibiting a collection of neurons (POMC and NPY/AgRP respectively), decreasing the drive to eat. Carbohydrates, specifically, increase insulin…which lowers the amount of competing amino acids floating around in the bloodstream, thereby allowing more tryptophan to cross the blood-brain barrier.
More tryptophan —> more serotonin —> mood boost and appetite suppression
Put simply:
Low serotonin/low mood —> crave carbs —> serotonin rises —> cravings stop
But…it’s a short term fix. Chronic stress, chronic pain, poor sleep, and depression can flatten this feedback loop, making cravings return harder and faster. Now…in this disastrous, toxic, trauma-ridden, hamster wheel of existence we call “modern society,” I wonder why obesity plagues over 40% of the population? Oh, that’s right…it’s a lack of tirzepatide :).
It’s worth mentioning that, paradoxically, many SSRI’s come with a possible side effect of weight gain. What’s going on here? Well…Chronic SSRI use messes with a whole lot more than just appetite. First off, the appetite suppressing effects tend to wane over time in the presence of exogenous serotonin (often by the 8-week mark). Second, our bodies don’t operate in a vacuum…while A influences B and B influences C, E doesn’t like the drop in B and decides to down-regulate D, impacting H, I, and J. And don’t you know it…I and J are entangled with B’s connection to C. And so on…
Chronic SSRI use impacts systemic serotonin levels, not just those housed within the appetite center of the hypothalamus. SSRIs are thought to, in some cases, negatively impact dopamine activity in certain parts of the brain—leading to emotional flatness, reduced reward sensitivity, and increased hedonic food-seeking behavior, affect insulin levels—disrupting multiple metabolic pathways, and reduce brown fat thermogenesis—leading to increased visceral (surrounding the organs) fat storage, which is pro-inflammatory and may increase the risk of insulin resistance in certain populations.
A gentle reminder of how complex and intertwined our neuro-endocrine pathways are (Frontier in Endocrinology 2023)
Can You Boost Serotonin Naturally?
Sort of…But not in the quick-fix, “take this gummy” way wellness influencers might suggest.
Some ways to support serotonin production naturally:
Regular movement: Exercise increases the availability of tryptophan to the brain and enhances serotonin signaling. Even a brisk walk can help.
Sunlight: Natural light triggers serotonin production. This is one reason seasonal affective disorder (SAD) is a thing, and why light therapy can help. As a Wisconsinite, my cynicism increases ten-fold in December, January, and February…
Nutrition: Foods rich in tryptophan, omega-3s, B-vitamins, and protein help fuel serotonin production.
Touch and connection: Physical affection and deep social bonds (that includes your pets) light up serotonin pathways. Your biology wants you to belong.
Meditation and mindfulness: Long-term practices have been shown to enhance serotonin production, in part by reducing chronic stress and inflammation. It also returns us to a more embodied state. Depression often comes with disembodiment—a detachment from the body. People feel numb, disconnected, sluggish, or stuck in their heads. Awareness of subtle body signals can dismantle depressive feedback loops.
None of these are silver bullets, of course…But taken together, they create an environment where your body can do what it’s built to do…regulate, repair, and recover.
So…Why does the serotonin myth continue to echo from clinics worldwide?
Because it’s easy. Because it’s comforting to think your suffering is a chemical accident and not a reflection of an overwhelming world, unmet emotional needs, or trauma no one taught you how to process. Blaming brain chemistry feels cleaner than naming the obvious…heartbreak, or capitalism, or childhood wounds. Pills are easier than grief…and Pharmaceutical companies love that you love those pills. In fact, I think they’d be happy to sell you a few.
And again…medications can help. I still prescribe them to certain patients. They can stabilize, soothe, and save lives. But they’re not topping off a serotonin tank. They’re not “fixing a defect.” They’re a tool. And tools work best when we’re also building something sustainable to fall back to…a life with support, purpose, movement, community, and rest.
Final Thoughts:
Serotonin isn’t a shortcut to joy. Sorry…I wish it were that easy. It’s part of a vast, elegant, overstimulated orchestra of hormones, neurons, bacteria, and memories that make you feel like “you.” Sometimes it’s out of tune. Sometimes it needs support. But it’s not the villain or the hero of your story.
It’s just one player in the complex chemistry of being a person.
So when you feel low, take a break…lean in with compassion. Try not to control your mood…your pain…your insomnia. Our physical bodies are the external manifestations of our inner worlds…we often forget that. Your pain isn’t proof of failure, and your healing probably won't come from a single source. Question the intentions behind anyone trying to sell you otherwise.
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