A 2002 review concluded that although the data evaluated suggests that 5-HTP is more effective than placebo in the treatment of depression, the evidence was insufficient to be conclusive due to a lack of clinical data meeting the rigorous standards of the day. More and larger studies using current methodologies are needed to determine if 5-HTP is truly effective in treating depression. In small, controlled trials 5-HTP has also been reported to augment the antidepressant efficacy of the antidepressant clomipramine. A 2020 meta-analysis found oral 5-HTP supplementation had a large effect size on depression symptom severity. However, the included studies were considered relatively weak and the methods and treatment duration varied between the seven studies examined.
5-HTP is sometimes taken by people coming down from MDMA to relieve post-MDMA dysphoria. As 5-HTP is a necessary precursor for the brain to produce more serotonin, and MDMA use depletes a person's natural serotonin levels, it is believed that taking 5-HTP after consuming MDMA will speed up serotonin production. DanceSafe claims that the anecdotal evidence is widespread and that the theory is physiologically reasonable. Backing up this approach is research conducted by Wang, et al. in 2007, which observed that MDMA-induced depletions of 5-HT (serotonin) were restored in rats after administration of 5-HTP, and suggested that this approach might be clinically useful in abstinent MDMA users.
At high doses, or in combination with carbidopa, it has been used off-label to treat obesity (by promoting weight loss).
In clinical trials of various design, 5-HTP has also been reported to treat fibromyalgia,myoclonus,migraine, and cerebellar ataxia. However, these clinical findings, as for all therapeutic findings with 5-HTP, are preliminary and need confirmation in larger trials.
5-HTP's short half-life (<2h) may inherently limit its therapeutic potential, as the systemic 5-HTP exposure levels will fluctuate substantially even with relatively frequent dosing. Such exposure fluctuations are usually associated with increased adverse event burden, 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 the Cmax. It has been proposed that 5-HTP dosage forms achieving prolonged delivery would be more effective, as has been demonstrated many times with other pharmaceuticals with short durations of action. 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. Unfortunately, the inherent variability amongst different people with respect to drug metabolism makes this task more difficult than one might expect.
An unexpected discovery was that 5-HTP is essential for the growth of human parainfluenzavirus in cell culture.
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 Institute of Health TOXNET, 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.
After oral administration, 5-HTP is absorbed by the upper intestine. The mode of absorption is not known, but presumably involves active transport via amino acid transporters. 5-HTP is adequately absorbed via oral cavity. With a decarboxylase inhibitor, the bioavailability of 5-HTP can be higher than 50%.
5-HTP is rapidly absorbed with Tmax of ~1.5h, and rapidly eliminated with a half-life of ~1.5–2 h. Co-administration of a decarboxylase inhibitor (e.g. carbidopa, benserazide) doubles the half-life of 5-HTP, to 3–4 h, and enhances exposure several fold, depending on the dosing regimen.
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. This discovery indicates that 5-HTP slow-release medications represent a new avenue for treatment of brain disorders responsive to serotonergic enhancement.
Though 5-HTP is found in food only in insignificant quantities, it is a chemical involved intermediately in the metabolism of tryptophan, an amino acid found in all unfractionated foods, with lower total amino acid content correlating with increased tryptophan absorption.
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