Combined treatments of 5-HTP and SSRI seem to have strong synergistic effects on serotonin levels in rats and humans so that some clinicians recommend the use of slow-released 5-HTP in combination with SSRIs (R, R2, R3). However, additional clinical trials are required to demonstrate the safety and effectiveness of this approach, and combinations of 5-HTP and medications should only be used under medical supervision.
“L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. L-5-Hydroxytryptophan acts to inhibit panic, which supports a modulatory role of serotonin in panic disorder.”
In addition to angiogenesis and neurogenesis, cell- and pharmacologically based therapies substantially remodel white matter in the ischemic brain. Treatment of experimental stroke with MCSs, rhEPO, or sildenafil significantly increases axonal density encapsulating the ischemic lesion. Dynamic changes of white matter structure along the ischemic boundary have been imaged in living animals by diffusion tensor imaging (DTI) and fractional anisotropy (FA) measurements. Data from these MRI indices demonstrate that administration of rhEPO or sildenafil augments axonal remodeling and angiogenesis and that both of them are spatially and temporally correlated. Administration of MSCs, rhEPO, and thymosin beta 4 (Tβ4) dramatically increases the number of oligodendrocyte progenitor cells in the corpus callosum, the striatum, and the V/SVZ of the ischemic hemisphere and mature oligodendrocytes in the ischemic boundary adjacent to myelinated axons. These findings suggest that cell- and pharmacologically based therapies promote generation of oligodendrocyte progenitor cells in the ischemic brain that migrate to target axons, where they extend their processes myelinating the axons.

Addiction vulnerability: Concentrations of endogenous oxytocin can impact the effects of various drugs and one's susceptibility to substance use disorders. Additionally, bilateral interactions with numerous systems, including the dopamine system, Hypothalamic–pituitary–adrenal axis and immune system, can impact development of dependence. The status of the endogenous oxytocin system might enhance or reduce susceptibility to addiction through its interaction with these systems. Individual differences in the endogenous oxytocin system based on genetic predisposition, gender and environmental influences, may therefore affect addiction vulnerability.[72] Oxytocin may be related to the place conditioning behaviors observed in habitual drug abusers.
Both the production of oxytocin and response to oxytocin are modulated by circulating levels of sex steroids. The burst of oxytocin released at birth seems to be triggered in part by cervical and vaginal stimulation by the fetus, but also because of abruptly declining concentrations of progesterone. Another well-studied effect of steroid hormones is the marked increase in synthesis of uterine (myometrial) oxytocin receptors late in gestation, resulting from increasing concentrations of circulating estrogen.
It has been reported that deficiencies in the amino acid tryptophan (precursor to 5-HTP) are correlated with depression, as evidence by serum tryptophan in depressed persons.[16][17] Decreased levels of tryptophan in the body can come from various means but are most likely caused by a diet lacking in the amino acid as substrate, or by upregulation of enzymes (most notably indoleamine 2,3-dioxygenase(IDO) and tryptophan 2,3-dioxygenase(TDO)) that degrade tryptophan or direct it to paths that are not serotonin synthesis causing a relative deficiency.[18][19] These enzymes can be upregulated in states of chronic inflammation[18][20] and injection of some pro-inflammatory cytokines has been implicated in depression[21] and increasing the kyurenine:tryptophan ratio, which is indicative of IDO activity being increased.[22] The activity of tryptophan hydroxylase can also be further downregulated in cases of Magnesium or vitamin B6 deficiency, stress, or excessive tryptophan levels.[7]
It has been noted[25] that isolated supplementation of 5-HTP may deplete or reduce the bioactivity of catecholamines such as dopamine[44][45][46] (which extends to L-Tryptphan[45]) and that this relationship also acts in reverse, with supplemental L-Tyrosine possibly able to deplete 5-HTP[47][48] and Serotonin itself,[48] which extends to supplemental L-DOPA which may reduce all intermediate of serotonin synthesis[49][50][51] although L-DOPA may also deplete L-Tyrosine (as it is merely later in the same metabolic chain).[50] Due to excessive levels of either one depleting the other, some authors have suggested that combination therapy of 5-HTP and L-Tyrosine (the furthest back in the metabolic chain while still passing rate limiting enzymes) is a potentially useful avenue for anti-depressive effects.[52]
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 a false positive test in tests looking for carcinoid syndrome.[28][29] 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.[30][31] However, 5-HTP has not been associated with cardiac toxicity in humans.[22][32][33][34]
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