Recently, an editorial in Nature Neuroscience pointed out the need for exercising caution in the use of over-the-counter drinks purporting to promote relaxation and containing, among other substances with chronobiotic activity, L-5-Hydroxytryptophan (5-HTP).1 This reality-check certainly raises an issue worth the attention of scientists who deal with, and laymen who dabble in, biological rhythms. Proprietary and patented formulations often project an image of safety, which is augmented by their over-thecounter availability as attractively packaged nutritional supplements. The allure of these bottled shots of bliss may seem undeniable to the general public. An online search of the words "5-HTP relaxation drink" returns . 7 million websites. Websites promoting these drinks do carry limited warnings or disclaimers (in fine print). The actual concentration of constituents is sometimes not provided in the online information leaflets. Certain websites provide a Natural Standard Editorial Board blinded review, 2,3 which summarizes known scientific literature (exhaustively) and mentions likely safe doses. In view of the rising popularity and wide availability of 5-HTP containing drinks, we feel that scientists and the general public alike would profit from an additional nugget of information regarding a previously unforeseen effect of 5-HTP consumption at an inappropriate time, as brought to light by recent literature in the area. 5-HTP crosses the blood -brain barrier upon systemic administration, bypasses the rate-limiting step in serotonin synthesis, elevates brain serotonin, 4 and affects non-REM sleep 5 in rodents, generally promoting wakefulness if administered at light onset, and promoting non-REM sleep with dark onset administration. In a recent study (March 2012), we investigated some of the effects 5-HTP had on the mammalian circadian system, using a nocturnal model. 6 In nocturnal mice, 5-HTP causes phase advances during the mid-subjective day, phase delays during the mid-subjective night and, at certain other times, ambiguous or no apparent phase-shifting effects at all. In this paper, we had expressed concern regarding the potentially detrimental effects caused by temporally inappropriate administration of 5-HTP, especially in cases where the circadian system has been previously subjected to a stressor, for example jet lag, and this is a caveat not mentioned by many, or perhaps any, marketers of these products. Additionally, experiments conducted at our lab using nocturnal field mice 7 indicate that 5-HTP administered in the late subjective night, when combined with light, may actually transiently increase locomotor activity, along with increasing light-induced phase shifts, through possibly arousal-dependent mechanisms most likely involving Dovepress submit your manuscript | www.dovepress.com