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Side Effects of 5 HTP

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5 HTP is a common over-the-counter dietary supplement used to increase serotonin levels in the body. Even supplements do have side effects. Read on to find out the side effects of 5 HTP.

What is 5 HT?

5 HT (5-hydroxytryptamine) is also known as serotonin. It is a neurotransmitter synthesized in the body from the amino acid, tryptophan which is then converted to 5 HTP or 5-hydroxy-L-tryptophan.

Serotonin is mostly found in the gut, platelets and central nervous system.

90% of the serotonin produced in the body is found in a group of cells occupying the gastrointestinal tract called enterochromaffin cells. In the gut, serotonin controls the movement of the intestines.

Some of the serotonin secreted from these specialized gastrointestinal cells move into the blood and is stored in platelets. When platelets bind to clots, they release serotonin which then constricts blood vessels promoting clotting and healing.

The rest of the serotonin naturally secreted in the body is found in serotonergic neurons of the central nervous system where it acts as a neurotransmitter for regulating mood, sleep and appetite as well as contributing to memory and learning.

5 HT Receptors

5 HT receptors refers to a family of 7 related receptors each with subtypes.

They are all found in the central and peripheral nervous systems. Except for 5 HT3, all the serotonin receptors are G protein-coupled receptors that produce their effects by increasing or decreasing the levels of cAMP (cyclic adenosine monophosphate) in cells.

5 HT3 is a ligand gated sodium/potassium ions channel that produces its effect by depolarization of the plasma membrane.

Five of the 5 HT receptors produce excitatory responses while two produce inhibitory responses.

5 HT Receptors

5 HT1 – Reduces cAMP levels to cause inhibitory responses

5 HT2 – Increases the levels of inositol triphosphate and diglyceride to produce excitatory responses

5 HT3 – Depolarizes plasma membrane to cause excitatory responses

5 HT4 – Increases cAMP levels to produce excitatory responses

5 HT5 – Decreases cAMP levels to produce inhibitory responses

5 HT6 – Increases cAMP levels to produce excitatory responses

5 HT7 - Increases cAMP levels to produce excitatory responses

These serotonin receptors control the release of neurotransmitters such as epinephrine, norepinephrine, GABA, glutamate, dopamine and acetylcholine. The receptors also control the release of hormones such as cortisol, vasopressin, oxytocin, prolactin and substance P.

Effects of 5 HT

Since 5 HTP is the direct precursor of 5 HT, all the effects of 5 HT are the same as 5 HTP.

The enterochromaffin cells in the gut release serotonin in response to food. This causes the contraction of the intestinal muscles.

When the food contains irritant, these cells increases the secretion of serotonin and cause gut movement to increase. This series of actions leads to diarrhea as the body tries to eliminate the irritant.

Normally the platelets in the veins lining the walls of the gut remove excess 5 HT. However, when the release of serotonin becomes too much for the platelets, a subset of serotonin receptors called 5 HT3 are activated and these cause vomiting.

Therefore, drugs that block the 5 HT3 receptors are used to prevent nausea and vomiting.

The kind of food we eat affect the levels of 5 HT in the gut. This is because the production of serotonin is dependent on the amount of amino acids available.

Those foods that contain more tryptophan than leucine and phenylalanine increase the levels of serotonin because tryptophan is used for synthesizing 5 HT. Therefore, papaya and banana increase serotonin levels but rye bread and whole wheat reduce its production.

In the brain, serotonin binds to another subclass of 5 HT receptors in cells that secrete dopamine. It counters the effects of dopamine which results in the suppression of appetite.

Serotonin also has a significant effect on bone metabolism. Although increased levels of 5 HT reduce bone density, serotonin is actually produced in bone cells although in very small amounts. The 5 HT produced in these cells affect bone mass by interacting with 3 receptors (negatively with one and positively with two).

5 HT also indirectly control blood sugar levels and growth by regulating the secretion and release of insulin and insulin-like growth factor (IGF).

Serotonin also directly serve as a growth factor. For example, the body tries to repair liver damage by increasing the numbers of serotonin receptors such as 5 HT2A and 5 HT2B so that the blood serotonin can promote the required cellular repair in the liver.

The ability of 5 HT to promote tissue repair is also important in the cardiovascular system where it can serve as a growth factor.

However, this effect can be both positive and negative. While serotonin stored in platelets can help stop bleeding and promote healing of damaged vessels, it can also cause the development of excess fibrous connective tissues in any organ of the body.

In the heart, 5 HT as a growth factor may cause cardiac fibrosis.

This effect of serotonin is the reason some medications that act as 5 HT receptor agonist have been withdrawn from the market.

Side Effects of 5 HT

Although 5 HTP has very few side effects on its own, the side effects of 5 HT can be ascribed to it since 5 HTP is directly converted to 5 HT.

Most of the side effects of 5 HTP are gastrointestinal disturbances such as nausea, vomiting, diarrhea and stomach pain.

Serotonin is naturally produced in the body at the needed levels. As with most processes in the body, the production, secretion, action, metabolism and excretion of naturally produced 5 HT is efficiently regulated in the body. However, when the regulation of 5 HT becomes inefficient, it can easily cause some side effects.

Therefore, most side effects of serotonin are caused by drugs that either supply serotonin to the body, increase its normal production in the body or prolong its action.

For example, SSRI or selective serotonin reuptake inhibitors and MAOI or monoamine oxidase inhibitors (these stop the enzymes that break down monoamine neurotransmitters such as serotonin) prolong the action of 5 HT in the central nervous system and, therefore, can cause serotonin side effects.

Another group of drugs that can cause serotonin side effects are 5 HT receptor agonists.

Although 5 HT receptor agonists are not serotonin, they are structurally similar and produce the same effects when they bind to serotonin receptors.

In summary, the drugs that can cause serotonin side effects are those that:

  • Promote the release of 5 HT from nerve endings
  • Prolong the action of 5 HT at nerve endings by blocking the reuptake of the neurotransmitter
  • Mimic 5 HT by binding to serotonin receptors and eliciting similar pharmacological responses

Most of the medications that produce these effects are antidepressants, appetite suppressants and psychedelic drugs.

Neurological Side Effects

The neurological side effects of serotonin are caused by the action of serotonin on the central nervous system.

All the subclass of 5 HT receptors are found in the central nervous system where they control different neurological outcomes from mood and appetite to learning and memory.

The neurological side effects of 5 HT include headache, lethargy, fatigue, insomnia and restlessness.

The set of side effects experienced vary between individuals and also depends on the type of serotonin drugs taken. For example, when too much serotonin binds to most 5 HT receptors, it results in anxiety, nervousness and restless but on the serotonin receptors known as 5 HT5A, too much serotonin cause insomnia and restlessness.

Gastrointestinal Side Effects

Although the effects of serotonin on the central nervous system is the most profound, there is actually more serotonin released from the gastrointestinal tract than in the brain.

Therefore, the side effects of too much 5 HT in the gut include diarrhea, constipation and vomiting reflexes.

However, even from the central nervous system, serotonin can produce gastrointestinal side effects such as nausea and changes in appetite which may lead to weight gain or weight loss.

Sexual Dysfunction

Drugs that increase the levels and activities of serotonin have also been known to cause sexual dysfunctions. This is especially true of SSRIs.

Side effects grouped under sexual dysfunction include reduced sex drive, difficulty reaching orgasm and difficulty getting and maintain erection in men.

Serotonin Syndrome

Serotonin syndrome is an adverse drug reaction that results from the hyperactivity of serotonin receptors in the central and peripheral nervous system. It is potentially lethal and usually caused by drugs that increase the levels of serotonin or its activity at these receptors.

Serotonin syndrome is more accurately described as serotonin toxicity.

Although serotonin syndrome has a known set of symptoms, it is still commonly mistaken for other medical conditions because there are no laboratory tests to guide its diagnosis.

Symptoms of serotonin syndrome range from mild ones such as sweating to serious ones such as seizures. They usually set in rapidly and may need urgent medical attention.

Classification of Serotonin Syndrome Symptoms

Somatic – Twitching, tremor and overactive reflexes

Cognitive – Headache, confusion, hallucination, mania and coma

Autonomic – Hypertension, high body temperature, sweating, nausea and diarrhea

Serotonin syndrome can be caused by a number of drugs including medicinal herbs. The syndrome can be triggered by high doses of these medications or a combination of two or more such medications.

Examples of medications that cause serotonin syndrome are antidepressants (including tricyclic antidepressants and SSRIs), opioids (such as tramadol, oxycodone and fentanyl), psychedelics (such as LSD), central nervous system stimulants (like cocaine), 5 HT1 receptor agonists, herbs (including St. John’s Wort, nutmeg and panax ginseng) as well as other drugs such as levodopa, lithium, chlorpheniramine and dextromethorphan.

Serotonin syndrome can be treated by withdrawing the drugs causing the set of symptoms; by administering serotonin antagonists such as cyproheptadine; by preventing the serotonin drug absorption in the gastrointestinal with activated charcoal; and by treating the urgent and serious symptoms of the syndrome.





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