Hydroxytryptophan (5-)

5-Hydroxytryptophan or 5-HTP is a precursor to the neurotransmitter serotonin and an intermediate in tryptophan metabolism. It is marketed in the United States and other countries as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid.

Pharmacology
5-Hydroxytryptophan is decarboxylated to serotonin (5-hydroxytryptamine) by the enzyme aromatic-L-amino-acid decarboxylase.

The psychoactive action of 5-HTP is thought to derive from its effect on serotonin synthesis. It is believed that an artificially high supply of 5-HTP causes the brain's serotonin-producing neurons to increase production. Increased serotonin production then leads to increased serotonin release.

Some doctors suggest that 5-HTP be administered with a peripheral decarboxylase inhibitor such as carbidopa in order to prevent elevated levels of serotonin in the bloodstream (and their side effects, which include emesis and potentially fibrosis of the heart). Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels.

5-HTP as therapeutic supplement
5-HTP, which is found in infinitesimal amounts in certain foods like turkey and cheese, is often sold as an over-the-counter therapeutic supplement. In this case, it is usually sourced from the seeds of the Griffonia simplicifolia plant. Production of 5-HTP as a supplement increased when a similar serotonin-altering supplement, L-tryptophan, was banned in the United States because of a tainted batch which caused serious side-effects in users. 5-HTP has many advantages over L-tryptophan: being safer to produce and arguably more potent. 5-HTP in supplement form is usually sold in gelatin capsules. These capsules typically contain either 50mg or 100mg of 5-HTP per capsule. It is recommended to take it on an empty stomach before falling asleep, or in smaller doses throughout the day.

Research
Some studies of 5-HTP have been completed which indicate that 5-HTP has potential in the treatment of depression and possibly anxiety, panic disorder, sleep disorders and obesity. In fact, a survey of all published studies of clinical outcomes with 5-HTP indicate that it yields similar results to those obtained for small scale studies of prescription SSRI antidepressants. Additionally, one open study suggests that people with anxious depressive syndrome may see better results from 5-HTP than from an SSRI.

It is unfortunate that the studies to date are incomplete, even if promising, for the treatment of mild to moderate depression. Reviews of these studies do indicate that potential exists for 5-HTP in the treatment of depression, but further trials are stressed as necessary before arriving at any firm conclusion. Some caution and diligence should be exhibited regarding 5-HTP barring further study and review.

Uses
In recent years 5-HTP has been sold by health food companies as an alternative treatment for depression and mood disorders. Its role as an intermediary in the biosynthesis of serotonin indicates that this chemical may indeed be effective in treating these and other serotonin-related disorders, but there is some debate on the conclusions of the clinical trials which have been carried out using the drug.

5-HTP is also used as a supplement by users of MDMA (ecstasy) to help replenish depleted serotonin, in an attempt to alleviate to a degree the depression and overall mental unsettlement in the days following MDMA usage. 5-HTP is less commonly used immediately before the use of MDMA as a means to both further reduce the negative psychological effects of depleted serotonin, and as an attempt to boost the effects of MDMA. Anecdotal reports seem to indicate this is largely placebo with some users reporting a moderate muting of the MDMA effect.

5-HTP also has mild psychoactive effects on REM sleep.

5-HTP supplements instead of SSRIs
Natural healing professionals often recommend 5-HTP supplements instead of standard SSRI/MAOI prescriptions as 5-HTP allegedly accomplishes the same goal without resorting to disturbing the brain's natural metabolic procedures. Instead of interrupting the recycling of serotonin as in the case of SSRIs, and instead of preventing the end consumption of serotonin as in the case of MAOIs, 5-HTP supplements provide more raw material that may be used in the body's natural serotonin production process, as shown in the illustration above.

The body's usual source for manufacturing 5-HTP is tryptophan, an amino acid found in many foods, turkey being the most cited example. Tryptophan was also sold as a supplement in health food stores until a contaminated shipment, which resulted in 1500 cases of eosinophilia-myalgia syndrome and over 30 deaths, prompted the United States Food and Drug Administration to ban it as an over-the-counter supplement. As a response to this ban, health supplement producers decided to market 5-HTP in its place. Recently, however, as noted above, pharmaceutical grade L-tryptophan has become available "over the counter" in the U.S.

Dosage
Though there is no official dosage, most supplement providers recommend 50 mg or 100 mg 5-HTP, one to three times per day. Some suggest 5-HTP should be taken just before bed because it often causes drowsiness. In theory, an overdose could cause serotonin syndrome, although there are no reported cases of hospitalizations due to excessive ingestion of 5-HTP. In dogs, doses of 23.6 mg/kg were found to cause toxic reactions, although the dose response curve for dogs does not necessarily scale to humans. Some users report high doses (300 mg and over) can produce nausea and vomiting.

Side effects
Promoters of 5-HTP claim that it causes fewer side effects than traditional antidepressants. Side effects of 5-HTP may include nausea, constipation, gas, drowsiness, or a decreased sex drive. It can also have adverse interactions with other natural and traditional drugs. Others warn that the long term effects of 5-HTP are not known, and point out that people using any psychiatric drug, natural or otherwise, should be under a doctor's supervision.