It is also marketed in many European countries for the indication of major depressive disorder under the trade names Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum.

[19] When combined with antidepressants of the MAOI or SSRI class, very high parenteral doses of 5-HTP can cause acute serotonin syndrome in rats.

[22] 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.

[19][18][17][29] 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.

[34][38] 5-HTP's short half-life (<2 hours)[34] may inherently limit its therapeutic potential,[39] 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,[39] as has been demonstrated many times with other pharmaceuticals with short durations of action.

[44] 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.

[45] 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.

Research conducted at Duke University in mice has demonstrated that 5-HTP when administered as slow-release appears to gain drug properties.

[56] 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.

[55] This discovery indicates that 5-HTP slow-release medications represent a new avenue for treatment of brain disorders responsive to serotonergic enhancement.