Don’t Panic—Take 5-HTP

Serotonin Can Help You Cope

Don’t Panic—Take 5-HTP
In one recent study, 5-HTP benefited women the most in
experimentally induced panic attacks
By Dr. Edward R. Rosick

hy do we like scary movies? What drives us to spend our hard-earned dollars to sit in a dark theater while visions of gloom, gore, and terror fill the screen and cause us to scream like 8-year-olds? Social scientists have written whole books on the subject, but my take on it is that we enjoy the neurochemical rush that we get when we’re frightened—it’s a hard-wired biological response to stressful situations that’s part of every human being.

Twenty thousand years ago, there was an evolutionary advantage in running like hell if a saber-toothed tiger was eyeballing you for his evening snack. Our ancestors who hesitated or stayed to see if the beast really meant to eat them … well, they were not our ancestors, come to think of it, because they were summarily removed from the gene pool. Their friends who acted more quickly and wisely had a better chance to live and procreate, leading ultimately to us.

Fight-or-Flight—A Legacy from Our Ancestors

Our ancestors’ gut reaction to mortal peril is now known as the fight-or-flight response—and it’s still in our genes, even though the saber-toothed tiger is long gone. It entails a sudden cascade of physiological changes, taking anywhere from a few milliseconds to a few seconds, that prepare us to either stand and fight, or flee. This phenomenon, originally described by the great American physiologist Walter Cannon, is caused by the release of powerful hormones such as adrenaline, noradrenaline, and cortisol into the bloodstream, causing a variety of striking bodily changes, such as:

  • Dilation of our pupils, so we can see more clearly what may be in the shadows.
  • Erection of our body hair, to make us appear a little larger to predators.
  • Increased heart rate and respiratory rates, to prepare for the explosive action of fighting or fleeing.
  • Restriction of blood flow to our viscera, so that more blood is available to our muscles, as well as to organs with the greatest immediate need, such as our heart and lungs.
  • Metabolism of stored glycogen and fat, to provide extra energy.
  • Opening of our sweat glands, to provide better cooling of our soon-to-be hyperactive bodies.
  • Release of endorphins, the body’s natural painkillers, to help us endure combat.
  • Relaxation of our bladder and bowels, to free us of that burden (and perhaps to dissuade a predator from eating us!).
  • Deactivation of our rational mind and activation of our primitive, reptilian mind—in essence, a shutdown of logical thought in favor of pure instinct—because if you think about it (no pun intended), there’s not much survival advantage in knowing calculus or the political complexities of the Middle East when you’re faced with a life-threatening situation.

The Downside of the Fight-or-Flight Response

Most people would agree that an automatic, gut response to highly stressful life-and-death situations—such as being in the path of a speeding car or trapped in a dark alley by a mugger—is of great advantage. Yet the fact is that most stresses we face today are not of the life-and-death kind—they’re more likely to be a financial or marital crisis, a rotten boss, or the daily traffic gridlock. They may not hurt us in any obvious way, but they sure do unleash the stress hormones on us, and they can still trigger the fight-or-flight response, to some degree.

Unlike our ancestors, though, we’re trapped by our circumstances, unable to either fight or flee—we must “control ourselves,” while frustration, fear, and anger seethe within us. When this happens repeatedly over months and years, it can greatly impair our health. In fact, many scientists now believe that chronic stress and the repeated activation of our fight-or-flight response can lead to a variety of illnesses, including depression, cancer, and heart disease.

That’s bad enough, but in some people, the fight-or-flight response can strike out of the blue, with no consciously perceived stress, let alone threat. Psychiatrists refer to this condition as panic disorder.

Panic Disorder—A Modern Malady

Panic disorder affects at least 3 million American adults—more than the number of people who are afflicted annually by stroke, epilepsy, or AIDS.1 It is a chronic, relapsing condition that can have devastating effects on one’s job, personal relationships, and family life. The hallmark symptom of panic disorder is panic attacks—acute surges of fear or almost paralyzing terror that occur spontaneously, often with no apparent trigger.

Along with the emotional distress, panic attacks have physical symptoms that resemble the fight-or-flight response, including racing or pounding heartbeat, chest pains, difficulty in breathing, trembling, sweating, and chills or hot flashes. On top of all that, patients who present with panic attacks almost always state that they feel like they’re losing their mind.

What Causes Panic Attacks?

Even though all humans are hard-wired for the fight-or-flight response, most do not suffer from panic attacks. We don’t know why some people do, but there are several theories. One is that they’re hypersensitive to small changes in their bodies’ biochemical milieu.* Psychiatric researchers can investigate this theory by inducing panic attacks experimentally, using small quantities of certain substances that are known to be anxiolytic (anxiety-producing) agents.

*For an example of this phenomenon, involving sensitivity to carbon dioxide levels in the air we breathe, see “5-HTP Inhibits Panic Attacks” in the March 2004 issue.

One such agent is cholecystokinin-tetrapeptide (CCK-4), the smallest member of a family of peptide hormones that are found in the gastrointestinal tract and the central nervous system of most mammals, including humans. (See the sidebar.) People with panic disorder are unusually sensitive to CCK-4, but healthy people are susceptible when it’s administered intravenously (it can’t be taken orally, because our stomach acid would destroy it). Naturally, researchers want to find ways to reduce the susceptibility to panic attacks, and they’ve found that one way is with the amino acid 5-hydroxytryptophan (5-HTP), because of its connection with serotonin.

The Many Faces of CCK

Cholecystokinin (CCK) is a family of peptide hormones (consisting of chains of amino acids) that play important roles in the gastrointestinal tract and the central nervous system. In the GI tract (where there are more than two dozen other hormones at work), CCK is secreted by the duodenum in response to partially digested food (chyme) entering from the stomach. It triggers the release of enzymes from the pancreas and bile from the gallbladder to finish the job of digestion (the name cholecystokinin means “to move the gallbladder”). When the food is gone, CCK secretion ceases.

CCK is sometimes called the satiety hormone, because it’s believed to play a role in controlling food intake by signaling the brain (via the bloodstream) when the stomach has had enough; the brain then tells its owner to stop eating.* (It should be obvious, if you look around, that this system is highly fallible!)

*See the sidebar “Phenylalanine for Weight Loss” in the article “Catecholamines Kick Out the Demons of Depression” in the September 2003 issue.

CCK is also widely distributed throughout the central nervous system (including the senile plaques in the brains of Alzheimer’s victims), where it appears to be the most abundant neuropeptide. Our understanding of the roles of CCK in the brain, however, is rudimentary. It appears to modulate the activity of other hormones and of neurotransmitters such as dopamine and serotonin, and it may be involved in various mental disturbances, such as anxiety, depression, and schizophrenia.

This picture of CCK is complicated by the fact that there are numerous members of this family of peptides, and although they have certain features in common, they also differ in their sites and modes of action. The most active form in the central nervous system is CCK-8 (with 8 amino acids in the chain), but most are considerably larger. There are smaller ones too, though, and the smallest is CCK-4. Although it lacks the hormonal activity of its larger cousins, it does affect the brain as an anxiolytic, or anxiety-inducing agent, as discussed in the accompanying article.

Reduced Serotonin Activity May Be to Blame

Serotonin is a vital neurotransmitter that’s involved in a wide variety of behaviors, including aggression, sleep, depression, anxiety, and panic.2 Its immediate precursor in the brain is 5-HTP, which is produced from its precursor, the amino acid tryptophan. Thus our serotonin levels depend on our dietary intake of tryptophan and 5-HTP. Although tryptophan is found in many food proteins, for a while it was unavailable as a nutritional supplement, owing to a misguided FDA ruling. 5-HTP, on the other hand, is not found in foods but is also available as a safe and effective natural supplement.

In people with panic disorder, it’s thought that there is reduced serotonin activity in the brain’s neural synapses (where most serotonin is found).* In fact, one way in which holistically oriented physicians treat panic attacks is with 5-HTP. It is well absorbed orally, with 70% entering the bloodstream, and it easily crosses the blood-brain barrier. Thus it can effectively increase the amount of serotonin produced in the brain.3

*Not all of the brain’s neurons use serotonin as the neurotransmitter—the figure is 0.2%. Since the brain has about 100 billion neurons, that’s about 200 million.

Researchers Use 5-HTP to Counter Panic Attacks

A bit of new light has recently been shed on the prevention of panic attacks.4 In a double blind, placebo-controlled study, researchers in Estonia examined the effects of oral 5-HTP in 32 healthy volunteers (14 men and 18 women, aged 18–32) in whom panic attacks were induced with CCK-4. The degree of panic (anxiety, mostly) was evaluated using the Panic Symptom Scale (PSS), a questionnaire regarding the intensity of 18 panic symptoms, of which 13 are somatic (physical) and 5 are cognitive (mental). The symptoms are rated on a scale from 0 (not present) to 4 (extremely severe). The Visual Analogue Scale (VAS) was used to measure the volunteers’ subjective anxiety at frequent intervals throughout the experiment, and heart rate and blood pressure were also measured frequently.

The volunteers were randomized in such a way that two equally composed groups (seven men and nine women in each group) received a pretreatment of either two 100-mg capsules of 5-HTP or placebo. Ninety minutes later, the panic (anxiety) attack was induced with an IV infusion of CCK-4 (50 mcg added to a saline drip). And 5 minutes after that, the volunteers rated their symptoms on the PSS and VAS.

Attacks that could technically be classified as panic occurred in three members of the 5-HTP group and in seven of the controls, but this difference was not statistically significant, owing to the small number of volunteers in the study. One of the 18 individual panic symptoms—choking—showed a significant decrease with 5-HTP compared with placebo, and there was a downtrend in one other symptom (abdominal distress). On the VAS, there were significant increases in anxiety ratings in both groups after the CCK-4 infusion, but no difference between the two groups.

Women Appear to Benefit More than Men

One interesting result did emerge: an apparent gender difference. When the data were analyzed by gender, it turned out that the panic rate was significantly lower in the 5-HTP-treated women than in the female controls; this was not true of the men, however, in whom the panic rate was equally low in both groups. Furthermore, the cognitive symptoms were significantly lower in the 5-HTP-treated women compared with their controls, but the somatic symptoms were not. In the men, it was the other way around: there was a trend (though not statistically significant) toward lower somatic symptoms, but not cognitive symptoms, in the 5-HTP-treated men compared with their controls.

Thus, the principal finding regarding 5-HTP in this study was a significant reduction in the rate of panic attacks and in the intensity of cognitive symptoms in women versus men; in men the effect was limited to a nonsignificant reduction in the intensity of somatic symptoms. The authors speculated that these apparent gender differences could be due to a greater bioavailability of serotonin (following 5-HTP treatment) in women than in men, owing to the women’s lower rate of serotonin metabolism, which has been observed in other studies. It’s also possible that the two sexes differ in their physiological response to CCK-4.

More Research Needed

The cardiovascular data were puzzling. After the CCK-4 infusion, heart rate increased significantly in both groups—somewhat more so in the 5-HTP group than in the controls. Blood pressure also increased in both groups—significantly more so in the 5-HTP group than in the controls. The authors could not explain this (but the small size of the study may be a clue).

All in all, the results were intriguing but not definitive, and the apparent gender differences may be illusory, because, as the authors admit, the study was too small to allow such differences to be observed with statistical confidence. Larger studies are needed to resolve these questions—but not to validate the well-established efficacy of 5-HTP as a calming agent in general.

5-HTP May Calm Your Anxiety

For most people, the rush of a fight-or-flight response can be an exciting diversion from the dull aspects of everyday life. It can even be fun to have this evolutionarily beneficial response kick in when we’re watching scary movies in the safety and comfort of our home or a movie theater. For people with panic disorder, however, this physiological vestige of our perilous past can be debilitating. For these people, 5-HTP may be just the supplement they need to relieve their anxiety and allow them to join the rest of us in enjoying the fruits of modern life.


  1. Panic disorder treatment and referral. National Institute of Mental Health, 1994. Pub. No. 94-3642.
  2. Bourin M, Baker GB, Bradwejn J. Neurobiology of panic disorder. J Psychosom Res 1998;44(1):163-80.
  3. Birdsall TC. 5-Hydroxytryptophan: a clinically effective serotonin precursor. Alt Med Rev 1998;3(4):271-80.
  4. Maron E, Toru I, Vasar V, Shlik J. The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers. J Psychopharmacol 2004;18(2):194-9.

Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.

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