But what about the three-month warning? Dr Rush, while an advocate for the supplement, sees it as a short-term solution, and not something to rely on long-term, for good reason. "Technically taking 5-HTP alone can deplete important brain chemicals such as dopamine and adrenaline. While 5-HTP is aimed at increasing the amount of serotonin in the body, dopamine and adrenaline are also important for positive mental health states. In order to prevent the depletion of important brain chemicals, taking 5-HTP would need to be balanced with amino acids that support the production of dopamine and adrenaline." That's L-Tyrosine, which you eat in soy, chicken and beef, and can also be found in health food shops as a supplement.
The activity of the PAM enzyme system is dependent upon vitamin C (ascorbate), which is a necessary vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner. Many of the same tissues (e.g. ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C.
Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity worldwide. No effective pharmacological treatments are available for TBI because all Phase II/III TBI clinical trials have failed. This highlights a compelling need to develop effective treatments for TBI. Endogenous neurorestoration occurs in the brain after TBI, including angiogenesis, neurogenesis, synaptogenesis, oligodendrogenesis and axonal remodeling, which may be associated with spontaneous functional recovery after TBI. However, the endogenous neurorestoration following TBI is limited. Treatments amplifying these neurorestorative processes may promote functional recovery after TBI. Thymosin beta4 (Tβ4) is the major G-actin-sequestering molecule in eukaryotic cells. In addition, Tβ4 has other properties including anti-apoptosis and anti-inflammation, promotion of angiogenesis, wound healing, stem/progenitor cell differentiation, and cell migration and survival, which provide the scientific foundation for the corneal, dermal, and cardiac wound repair multicenter clinical trials. Here, we describe Tβ4 as a neuroprotective and neurorestorative candidate for treatment of TBI.
It’s a compound that the body needs in order to make serotonin, which is our main “happiness hormone.” Per Dr. Oz, 5-HTP floods the brain with serotonin and helps minimize stress, sadness, anger, and anxiety. “5-HTP targets specific emotions that drive us to overeat,” Dr. Bhatia explains. And as she already mentioned, 5-HTP also reduces physical hunger pangs and emotional cravings. Ideally, the body makes its own 5-HTP from the amino acid tryptophan, found in foods like turkey and bananas. (Why not just eat more turkey or take a tryptophan supplement? If you struggle with mood or weight, it can be a sign that your body has trouble converting tryptophan to 5-HTP.) Besides making it yourself, the only other way to get 5-HTP is from a supplement. One we like is the BRI 5-HTP Supplement ($16 for 120 capules, Amazon).
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.
Again, the three groups of mice were exposed to the stressful experience of social defeat in the cages of other more aggressive mice. This time, six hours after the social stress, the mice were put in a box in which they received a brief electric shock, which startles them but is not painful. Then 24 hours later, the mice were returned to the same box but did not receive a shock.
Thymosin beta-4 is a naturally occurring peptide, and is found ubiquitously in our cells. A range of studies on animal models have indicated several key biological activities for Tβ4, such as “promot[ing] wound repair, tissue protection, and regeneration in the skin, eye, heart and central nervous system”. Only a handful of clinical trials in humans have attempted to explore these roles practically.
Affecting generosity by increasing empathy during perspective taking. In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80% but has no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experimental explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants which role they would be in.
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. 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. These enzymes can be upregulated in states of chronic inflammation and injection of some pro-inflammatory cytokines has been implicated in depression and increasing the kyurenine:tryptophan ratio, which is indicative of IDO activity being increased. The activity of tryptophan hydroxylase can also be further downregulated in cases of Magnesium or vitamin B6 deficiency, stress, or excessive tryptophan levels.
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Monomeric β-thymosins, i.e. those of molecular weight similar to the peptides originally isolated from thymus by Goldstein, are found almost exclusively in cells of multicellular animals. Known exceptions are monomeric thymosins found in a few single-celled organisms, significantly those currently regarded as the closest relatives of multicellular animals: choanoflagellates  and filastereans. Although found in very early-diverged animals such as sponges, monomeric thymosins are absent from arthropods and nematodes, which do nevertheless possess "β-thymosin repeat proteins" which are constructed from several end-to-end repeats of β-thymosin sequences. Genomics has shown that tetrapods (land vertebrates) each express three monomeric β-thymosins, which are the animal species' equivalents (orthologues) of human β4, β10 and β15 thymosins, respectively. The human thymosins are encoded by the genes TMSB4X, TMSB10 and TMSB15A and TMSB15B. (In humans, the proteins encoded by the two TMSB15 genes are identical.) Bony fish in general express orthologues of these same three, plus an additional copy of the β4 orthologue.
Once the baby is born, oxytocin promotes lactation by moving the milk into the breast. When the baby sucks at the mother's breast, oxytocin secretion causes the milk to release so the baby can feed. At the same time, oxytocin is released into the brain to stimulate further oxytocin production. Once the baby stops feeding, the production of the hormone stops until the next feeding.
To untangle the ways different hormones together influence behavior in more naturalistic contexts, we worked with the Tsimane people in Bolivia. Traditional societies like the Tsimane are not living relics of the past, but their lifeways – small, tight-knit communities that produce their own food – can reveal the kinds of situations our hormone systems are well adapted to.
I’ve been on this stuff for lots of years. I really needed it when I was depressed like hell, and I had an emotional pain that simply didn’t go away for 2 decades prior to starting that stack. Did it help? yes. Was it the best intervention possible? probably not. I was able to get off all this stuff with the uridine stack, and I believe it partly fixed a part of my brain that was damaged from this decade long suffering. So this is, why I am now more into brain regeneration and psychotherapeutic interventions (even though I do them myself), and I would only go back to this stack if I was completely fucked up again. There are a lot of side effects, and its a fine line to balance the supplements, to get rid of the side effects…
For those deficient in tryptophan, supplemental tryptophan and 5-HTP could be somewhat effective, although a meta-analysis found barely statistically significant results (Odds Ratio of 1.3-13.2) from a statistically subpar collection of studies, and based on the inclusion criteria it set it had to expand its analysis to both 5-HTP and Tryptophan to get two studies to assess.
Autism. A 1998 study found significantly lower levels of oxytocin in blood plasma of autistic children.7 A 2003 study found a decrease in autism spectrum repetitive behaviors when oxytocin was administered intravenously.8 A 2007 study reported that oxytocin helped autistic adults retain the ability to evaluate the emotional significance of speech intonation.9
Affecting generosity by increasing empathy during perspective taking. In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80% but has no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experimental explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants which role they would be in.13
In January 1955, adreno-corticotrophic hormone (ACTH) was included in the very first Poisons Schedules. It was included in Schedule 4, Part A, which is equivalent to the current Schedule 4 of the Poisons Standard. Provisions for a repeated script must be authorised by an authorised prescriber, including general practitioners, veterinarian or dentist (if required for the purposes of the dental profession or are permitted to be prescribed by a dentist).
TB-500 has been used extensively for race horses to prevent adhesions from forming, although it is not a prescription veterinary drug. It’s an injectable peptide with limited human use. Mostly, it’s limited to humans who like to experiment, although reports of human use of thymosin dates back as far as 1974 – when a young girl became the first person to receive injections of thymosin because she was diagnosed without a functioning thymus gland.
Trust is increased by oxytocin. Disclosure of emotional events is a sign of trust in humans. When recounting a negative event, humans who receive intranasal oxytocin share more emotional details and stories with more emotional significance. Humans also find faces more trustworthy after receiving intranasal oxytocin. In a study, participants who received intranasal oxytocin viewed photographs of human faces with neutral expressions and found them to be more trustworthy than those who did not receive oxytocin. This may be because oxytocin reduces the fear of social betrayal in humans. Even after experiencing social alienation by being excluded from a conversation, humans who received oxytocin scored higher in trust on the Revised NEO Personality Inventory. Moreover, in a risky investment game, experimental subjects given nasally administered oxytocin displayed "the highest level of trust" twice as often as the control group. Subjects who were told they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting risk aversion. When there is a reason to be distrustful, such as experiencing betrayal, differing reactions are associated with oxytocin receptor gene (OXTR) differences. Those with the CT haplotype experience a stronger reaction, in the form of anger, to betrayal.
According to recent research, this hormone “is now believed to be involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterine contraction, milk ejection, maternal behavior, social bonding, stress and probably many more, which makes oxytocin and its receptor potential candidates as targets for drug therapy. From an innocuous agent as an aid in labor and delivery, oxytocin has come a long way in being touted as the latest party drug.”4
Hey I have used Tb 500 alot and can tell you injecting it in your fat around your stomach or in your large muscles near the injury is fine. I would never inject it into a wounded area because of possiblity of making the area worse by infection or trama from the needle. Dosage is tough I would say for a 200 pound person you need at least 5mg twice a week. Mixing it with GH releasing peptides seems to make it stronger as well. It’s definitely worth the month just finding legit stuff can be tricky.
As shown in Figure 1, thymic hormones also modulate the production of hypothalamus pituitary hormones and neuropeptides. Initial experiments revealed that neonatal thymectomy promotes a decrease in the number of secretory granules in acidophic cells of the adenopituitary . In the same vein, athymic nude mice display low levels of various pituitary hormones, such as PRL, GH, LH and FSH . With regard to thymic peptides, thymosin beta-4, when perfused intraventricularly, stimulates LH and LHRH secretion . Similar results were obtained with another thymic peptide, thymulin, in perfused or fragmented pituitary preparations . The administration of thymopoietin (another chemically-defined thymic hormone) in children with Hodgkin’s disease increased GH and cortisol serum levels . Moreover, thymopentin (the synthetic biologically active peptide of thymopoietin) enhances in vitro the production of ACTH and beta-endorphin . In addition, thymulin exhibits an in vitro stimulatory effect on perfused rat pituitaries, enhancing PRL, GH, TSH and LH release . Using short-term cultures of pituitary fragments, an increase in ACTH secretion occurs after in vitro thymulin addition, with no changes in GH levels and significant reductions in PRL release . A further thymosin peptide was recently isolated with the task in stimulating IL-6 release from rat glioma cells . By contrast, thymosin alpha-1 is apparently able to down regulate TSH, ACTH and PRL secretion in vivo with no modifications on GH levels . These inhibitory effects seem to occur through hypothalamic pathways. Indeed, the production of the corresponding releasing hormones by hypothalamic neurones decreased after in vitro addition of thymosin alpha-1 in medial basal hypothalamic fragments .
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To evaluate the indirect effect of Tβ4 peptide on RANKL-induced osteoclastogenesis, mouse BMMs were incubated with RANKL and CM, prepared from HPDLCs treated with H2O2 and different concentrations of Tβ4, and allowed to differentiate into osteoclasts. As shown in Fig 6, Tβ4 peptide dose-dependently decreased the number of osteoclasts and TRAP activity. To determine whether the reduction in osteoclast generation by Tβ4 could be due to effects of Tβ4 peptide on viability of the BMMs, a cytotoxicity assay was performed. The viability of BMMs was not significantly affected by Tβ4 peptide (data not shown).
5-HTP has been linked in very rare instances to a condition known as EMS, or eosinophilia-myalgia syndrome, which combines extreme muscle tenderness with abnormalities in the blood. A contaminant that was found in some tryptophan supplements in the late 1980s, and was linked to a small number of EMS cases, was also found in some 5-HTP supplements. It’s important to talk with your doctor before you begin taking 5-HTP or any other supplement, and to make sure you’re getting your supplements from a reliable provider.
Suggested doses vary depending on the source – some sellers will encourage higher use! One site suggests starting with a dose of 0.25mg. If side-effects (see above) are not proving troublesome, the site advises users to attempt to increase daily dosage. After 2-3 weeks of daily use, or when the desired level of pigmentation has been achieved, people who use Melanotan II should start a maintenance phase of two injections per week.
Chae, H. S., Kang, O. H., Choi, J. G., Oh, Y. C., Lee, Y. S., Jang, H. J., Kim, J. H., Park, H., Jung, K. Y., Sohn, D. H., and Kwon, D. Y. 5-hydroxytryptophan acts on the mitogen-activated protein kinase extracellular-signal regulated protein kinase pathway to modulate cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 cells. Biol Pharm Bull 2009;32:553-557. View abstract.
Ingroup bonding: Oxytocin can increase positive attitudes, such as bonding, toward individuals with similar characteristics, who then become classified as "in-group" members, whereas individuals who are dissimilar become classified as "out-group" members. Race can be used as an example of in-group and out-group tendencies because society often categorizes individuals into groups based on race (Caucasian, African American, Latino, etc.). One study that examined race and empathy found that participants receiving nasally administered oxytocin had stronger reactions to pictures of in-group members making pained faces than to pictures of out-group members with the same expression. This shows that oxytocin may be implicated in our ability to empathize with individuals of different races and could potentially translate into willingness to help individuals in pain or stressful situations. Moreover, individuals of one race may be more inclined to help individuals of the same race than individuals of another race when they are experiencing pain. Oxytocin has also been implicated in lying when lying would prove beneficial to other in-group members. In a study where such a relationship was examined, it was found that when individuals were administered oxytocin, rates of dishonesty in the participants' responses increased for their in-group members when a beneficial outcome for their group was expected. Both of these examples show the tendency of individuals to act in ways that benefit those considered to be members of their social group, or in-group.
The CCI model we used causes cortical tissue loss. Traditionally, the target for neuroprotective treatment of TBI is to reduce the lesion volume.39,40 A major limitation of neuroprotection strategies is the short time window between injury and treatment. In the vast majority of preclinical TBI studies, the treatment compounds provide neuroprotection only when administered early (usually several hours after brain injury).11 The administration of a compound early in the clinical setting is not practical.41 The neuroprotective effects demonstrated in rodents may diminish if the treatment compounds are given in the clinical setting beyond the short neuroprotective window. We are able to stimulate recovery of neurological function without altering the lesion volume, which has also been demonstrated in our experimental studies of stroke,19,42,43 and is in essence, enhancement of neurorecovery.19 The extended 24-hour window for treatment which improves neurological recovery, without altering CCI cortical volume, is a major benefit of the neurorestorative therapy. Recently, we evaluated the efficacy of delayed Tβ4 treatment on spatial learning and sensorimotor functional recovery in rats after TBI induced by CCI.34 Briefly, TBI rats received Tβ4 at a dose of 6 mg/kg or a vehicle (saline) administered i.p. starting at 24 hours after injury and then every third day for 2 weeks. The dose of Tβ4 was selected based on our previous studies in animal models of stroke and EAE.25,27 Tβ4 did not alter lesion volume (14.2 ± 3.9% for saline treatment vs. 15.7 ± 3.6% for Tβ4 treatment). TBI caused neuronal cell loss in the ipsilateral CA3 and DG examined 35 days after injury compared to sham controls. Tβ4 treatment initiated 24 hours post injury significantly reduced cell loss in these two regions compared to saline controls. Tβ4-treated TBI rats showed significant improvement in spatial learning (MWM test) and sensorimotor (mNSS test) functional recovery compared to the saline-treated TBI rats.34
The pamphlet, titled "Melanotan-2: Safe enhanced tanning" says although the drug is not approved by the Therapeutic Goods Administration (Australia's drug watchdog) and that studies into its effects are under way, it "is safe" and and its use "well documented". It says people can be referred to a "suitable doctor who is trained to prescribe MT2" so the pharmacy can dispense it to them.
Uterine contractions. These are important for cervical dilation before birth and causes contractions during the second and third stages of labor. Oxytocin release during breastfeeding causes mild but often painful uterine contractions during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition is normal.16
This sounds very promising and I have a question I’m sure you haven’t heard before. It’s regarding healing. I’m about 230 and avid lifter as well as running occasionally. But I’ve had severe injuries to my l3-s1 for years a d yes I’ve tried some stuff before as far as lifting. But when I was 2 I had encephalitis. I survived it back in 74 which most didn’t however the treatment had left me with migraines and seizures as a child and was told my adult teeth would be very weak when they grew in. So I’m 44 and most of my teeth have broken and I’ve been looking for alternatives to implants. You said both the products mentioned in this article would improve healing and I’ve heard stem cells are capable of regrowing teeth. Would this work for me and how or where would I inject it or maybe do a oral form and let it sit in my mouth for a bit? Never really thought about this but I’ve tried so many clinical trials and been turned down each time. Any info would be greatly appreciated thank you in advance.
There is also a positive feedback involved in the milk-ejection reflex. When a baby sucks at the breast of its mother, the stimulation leads to oxytocin secretion into the blood, which then causes milk to be let down into the breast. Oxytocin is also released into the brain to help stimulate further oxytocin secretion. These processes are self-limiting; production of the hormone is stopped after the baby is delivered or when the baby stops feeding.
Ok Ben. Thanks. Started the TB 500 for my elbows. Got the 5mg of TB 500 and reconstituted it with 3 cc/ml. of water (3 syringes full) Just about filled the file. Now based on injecting just under .1 cc/ml or just under 10 (8) units for a dose of around 250. How long did that vial last you? Seems like there is a lot left and the amount injected is small. Is my dose and math right?
Melanotan II can be of unknown quality and subject to contamination and stability concerns with use of multi-dose vials. There is no experience with the product other than through unregulated channels. There are health risks from the substance itself and its route of administration – documented in medical literature, case reports as well as reports from NSW PIC.
These studies demonstrate that in the animal model of TBI, early (6 hours post injury) treatment with Tβ4 i.p. at doses of 6 and 30 mg/kg reduces cortical lesion volume and hippocampal cell loss and improves functional recovery, suggesting its potential as a neuroprotective therapy for TBI. More importantly, delayed (24 hours post injury) treatment with Tβ4 administered i.p. at a dose of 6 mg/kg does not reduce lesion volume but significantly improves functional outcome in rats.34 Tβ4-induced angiogenesis, neurogenesis and oligodendrogenesis may contribute to functional recovery.34 Therefore, our data suggest that promoting endogenous neurorestorative processes using Tβ4 provides a novel therapeutic option for TBI. It should be noted that systemic administration of Tβ4 is safe and well-tolerated by animals and humans.26 Further investigation of the molecular mechanisms underlying Tβ4-mediated neuroprotection and neurorestoration is warranted.
Low oxytocin levels have been linked to autism and autistic spectrum disorders (e.g. Asperger syndrome) – a key element of these disorders being poor social functioning. Some scientists believe oxytocin could be used to treat these disorders. In addition, low oxytocin has been linked to depressive symptoms and it has been proposed as a treatment for depressive disorders. However, there is not enough evidence at present to support its use for any of these conditions.
A study published last year in Biological Psychiatry was the first to assess whether people with variations in their oxytocin-receptor gene have a harder time maintaining romantic relationships than those who don’t. Hasse Walum, a graduate student at Karolinska Institute in Stockholm, and his colleagues took advantage of Swedish twin studies that included thousands of participants, their genetic information and their answers to questions about how affectionate they were with their romantic partners. They found that women with a specific variation weren’t as close to their partners as women without it: they kissed their partners less and didn’t desire physical proximity as often. These women were also more likely to report having had a marital crisis. Although researchers don’t know exactly how this variation affects the oxytocin system, it may result in a lower number of oxytocin receptors in the brain. People with fewer receptors would be less sensitive to the hormone’s effects.
Cardiac effects: oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting cardiomyocyte differentiation. However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies.
RegeneRx is continuing with pre-clinical research, in collaborative arrangements with the National Institutes of Health, accumulating data on the effects of Tb4 and aiming for an IND application (Investigational New drug App-lication) to proceed with clinical studies. Phase I clinical trials will determine the ability of Tb4 to repair ulcers in diabetic patients and to reduce inflammation and accelerate recovery from burns and abrasions to the cornea.
Friedman, J., Roze, E., Abdenur, J. E., Chang, R., Gasperini, S., Saletti, V., Wali, G. M., Eiroa, H., Neville, B., Felice, A., Parascandalo, R., Zafeiriou, D. I., Arrabal-Fernandez, L., Dill, P., Eichler, F. S., Echenne, B., Gutierrez-Solana, L. G., Hoffmann, G. F., Hyland, K., Kusmierska, K., Tijssen, M. A., Lutz, T., Mazzuca, M., Penzien, J., Poll-The BT, Sykut-Cegielska, J., Szymanska, K., Thony, B., and Blau, N. Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. Ann Neurol. 2012;71(4):520-530. View abstract.