5-HTP: Эффективность, побочные эффекты и особенности применения.

5 Hydroxytryptophan (5 HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.

5 HTP's short half life (<2h) may inherently limit its therapeutic potential, as systemic 5 HTP exposure levels will fluctuate substantially even with relatively frequent dosing. Such exposure fluctuations are usually associated with increased adverse event burdens resulting from Cmax (time to maximal systemic concentration) drug spikes, and decreased clinical efficacy resulting from sub therapeutic exposure for large parts of the day, when taken as a single dose unit or at intervals significantly larger than Cmax. It has been proposed that 5 HTP dosage forms achieving prolonged delivery would be more effective, For example, controlled release oxycodone (OxyContin) or morphine (MS Contin) are intended to, via novel delivery mechanisms, permit pain relief for up to twelve hours with an active ingredient which only provides relief for 3–6 hours. However, the inherent variability amongst different people with respect to drug metabolism makes this task challenging.

Potential side effects of 5 HTP include heartburn, stomach pain, nausea, vomiting, diarrhea, drowsiness, sexual problems, vivid dreams or nightmares, and muscle problems. Because 5 HTP has not been thoroughly studied in a clinical setting, possible side effects and interactions with other drugs are not well known. According to the US National Library of Medicine, 5 HTP has not been associated with serotonin syndrome or any serious adverse events in humans. Across multiple studies, 5 HTP has also been reported to not cause any noticeable hematological or cardiovascular changes. 5 HTP had also been associated with eosinophilia, but later studies have not found any causal connection.

When combined with antidepressants of the MAOI or SSRI class, very high parenteral doses of 5 HTP can cause acute serotonin syndrome in rats. It is unclear if such findings have clinical relevance, as most drugs will cause serious adverse events or death in rodents at very high doses. In humans 5 HTP has never been clinically associated with serotonin syndrome, although a case report suggests 5 HTP can precipitate mania when added to an MAOI. When combined with carbidopa (as a treatment for symptoms of Parkinson's disease), 5 HTP causes nausea and vomiting; however this can be alleviated via administration of granisetron. As mentioned below under pharmacology, cases of scleroderma like illness have been reported in patients using carbidopa and 5 HTP. Oral 5 HTP results in an increase in urinary 5 HIAA, a serotonin metabolite, indicating that 5 HTP is peripherally metabolized to serotonin, which is then metabolized. This might cause false positive results in tests looking for carcinoid syndrome. Due to the conversion of 5 HTP into serotonin by the liver, there could be a risk of heart valve disease from serotonin's effect on the heart, as based on preclinical findings. However, 5 HTP has not been associated with cardiac toxicity in humans. It has been suggested that 5 HTP may cause eosinophilia myalgia syndrome (EMS), a serious condition which results in extreme muscle tenderness, myalgia, and blood abnormalities. However, there is evidence to show that EMS was likely caused by a contaminant in certain 5 HTP supplements.

5 HTP is produced from the amino acid tryptophan through the action of the enzyme tryptophan hydroxylase. Tryptophan hydroxylase is one of the biopterin dependent aromatic amino acid hydroxylases. Production of 5 HTP is the rate limiting step in 5 HT (serotonin) synthesis. 5 HTP is normally rapidly converted to 5 HT by amino acid decarboxylase.

After oral administration, 5 HTP is absorbed by the upper intestine. With a decarboxylase inhibitor, the bioavailability of 5 HTP can be higher than 50%.

5 HTP is rapidly absorbed with a tmax of , and rapidly eliminated with a half life of Co administration of a decarboxylase inhibitor (e. g. carbidopa, benserazide) doubles the half life of 5 HTP to ,

5 HTP is decarboxylated to serotonin (5 hydroxytryptamine or 5 HT) by the enzyme aromatic L amino acid decarboxylase with the help of vitamin B6. This reaction occurs both in nervous tissue and in the liver. 5 HTP crosses the blood–brain barrier, while 5 HT does not. Excess 5 HTP, especially when administered with vitamin B6, is thought to be metabolized and excreted.

The psychoactive action of 5 HTP is derived from its increase in production of serotonin in central nervous system tissue. Research shows that co administration with carbidopa greatly increases plasma 5 HTP levels. Other studies have indicated the risk of a scleroderma like condition resulting from the combination of 5 HTP and carbidopa.

There are currently no approved drug products containing 5 HTP approved by the FDA. All available 5 HTP products are nutraceuticals and are as such not regulated or verified for purity, integrity, or clinical efficacy or safety, mandating caution regarding human consumption. As of 25 August 2020, Hungary added 5 HTP to the controlled psychoactive substances list, prohibiting production, sale, import, storage and use, becoming the first country to do so.

5 HTP's short half life is impractical for chronic drug therapy. Research conducted at Duke University in mice have demonstrated that 5 HTP when administered as slow release appears to gain drug properties. Slow release delivery attenuates or abolishes the peaks and valleys in 5 HTP exposure during treatment. Slow release delivery of 5 HTP markedly improved the safety profile of 5 HTP and conferred stable plasma exposure of 5 HTP and strong and sustained enhancement of brain serotonin function. The seeds of the Griffonia simplicifolia, a climbing shrub native to West Africa and Central Africa, are used as an herbal supplement for their 5 HTP content. In one 2010 trial, Griffonia simplicifolia extract appeared to increase satiety in overweight women.