In conclusion, this study is the first study to demonstrate that down-regulation of Tβ4 was observed in an in vitro model of H2O2-stimulated PDLCs. Tβ4 activation had anti-inflammatory effects via MAPK and NF-κB pathways in PDLCs and anti-osteoclastogenic effects via MAPK, NF-κB, and Wnt5a pathways in BMMs. These findings supported the fact that Tβ4 peptide could possibly be used in the development of a therapeutic drug for periodontitis and osteolytic disease.
During clinic trials for its use as a tanning agent, melanotan II was found to be a potent stimulator of male erections. A new drug based on melanotan II, bremelanotide, was developed to take advantage of this property. It has been noted across several studies to increase rigidity and duration of male erection, as well as male sexual desire. It has also been shown to increase female sexual desire in patients with sexual arousal disorder.
In the experiments, an epithelial wound was made in the corneas of sedated rats. A Tb4 solution was applied at several concentrations to the injured eyes in one group of rats while another group was treated with a solution without Tb4. Following 12, 24 and 36 hours, the eyes were tested by microscopic observation for epithelial growth over the injured site. Investigators found the Tb4 accelerated corneal wound repair at doses of Tb4 similar to those found to repair skin wounds. When tested 24 hours after treatment, the rate of accelerated repair was proportional to the concentration of Tb4, with the highest dose (25 microgram) showing a threefold acceleration of epithelial cell migration, compared to untreated. Treatment with Tb4 showed anti-inflammatory effects, helping resolve the injury. An application to human cells in a model of human corneal cells in culture showed that Tb4 enhanced epithelial cell migration in vitro.
It has been shown that oxytocin differentially affects males and females. Females who are administered oxytocin are overall faster in responding to socially relevant stimuli than males who received oxytocin.[75][86] Additionally, after the administration of oxytocin, females show increased amygdala activity in response to threatening scenes; however, males do not show increased amygdala activation. This phenomenon can be explained by looking at the role of gonadal hormones, specifically estrogen, which modulate the enhanced threat processing seen in females. Estrogen has been shown to stimulate the release of oxytocin from the hypothalamus and promote receptor binding in the amygdala.[86]
If cupid had studied neuroscience, he’d know to aim his arrows at the brain rather than the heart. Recent research suggests that for love to last, it’s best he dip those arrows in oxytocin. Although scientists have long known that this hormone is essential for monogamous rodents to stay true to their mates, and that it makes humans more trusting toward one another, they are now finding that it is also crucial to how we form and maintain romantic relationships.
Oxytocin affects social distance between adult males and females, and may be responsible at least in part for romantic attraction and subsequent monogamous pair bonding. An oxytocin nasal spray caused men in a monogamous relationship, but not single men, to increase the distance between themselves and an attractive woman during a first encounter by 10 to 15 centimeters. The researchers suggested that oxytocin may help promote fidelity within monogamous relationships.[109] For this reason, it is sometimes referred to as the "bonding hormone". There is some evidence that oxytocin promotes ethnocentric behavior, incorporating the trust and empathy of in-groups with their suspicion and rejection of outsiders.[66] Furthermore, genetic differences in the oxytocin receptor gene (OXTR) have been associated with maladaptive social traits such as aggressive behavior.[110]
While the structure of oxytocin is highly conserved in placental mammals, a novel structure of oxytocin was recently reported in marmosets, tamarins, and other new world primates. Genomic sequencing of the gene for oxytocin revealed a single in-frame mutation (thymine for cytosine) which results in a single amino acid substitution at the 8-position (proline for leucine).[117] Since this original Lee et al. paper, two other laboratories have confirmed Pro8-OT and documented additional oxytocin structural variants in this primate taxon. Vargas-Pinilla et al. sequenced the coding regions of the OXT gene in other genera in new world primates and identified the following variants in addition to Leu8- and Pro8-OT: Ala8-OT, Thr8-OT, and Val3/Pro8-OT.[118] Ren et al. identified a variant further, Phe2-OT in howler monkeys.[119]

I have bee suffering from severe symptoms of post concussion syndrome for several.months after a car accident. The use of TB500 has been the only trratment ease my symptoms and give me my life back. I ceased use last week after 3 weeks and had reoccuring concussion symptoms. As such? I recommenced injections as of last night. Have you read much about the impact of TB500 on brain injury as I’d love to know if more prolonged use would have a permanent impact/remedy for me? Thanks for your time and interest.
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Hi Ben, I have been using TB-500 for minor injury repair assistance for more than 2 years. I have found it to be extremely effective for minor strains to calves, hamstring, shoulder etc. Luckily I have not had to try it for any major injuries. When I first used it I was blown away by how effectively it worked – even to the point that I began to doubt the seriousness of the original injury. When injured I dose at 5mg per week for four weeks then take at least four weeks break. The only side affect I have noticed is a little light headed feeling which passes pretty quickly. I am in my late 40’s and I train hard. TB-500 allows me to train through minor injuries which is great. Love your work
We have evaluated the efficacy of early Tβ4 treatment on spatial learning and sensorimotor functional recovery in rats after TBI induced by unilateral CCI.34 In brief, TBI rats received Tβ4 at a dose of either 6 or 30 mg/kg (RegeneRx Biopharmaceuticals Inc, Rockville, MD) or a vehicle control (saline) administered i.p. starting at 6 hours after injury and then at 24 and 48 hours. Spatial learning was performed during the last five days (31-35 days post injury) using the modified Morris water maze (MWM) test, which is extremely sensitive to the hippocampal injury.35-37 Tβ4-treated TBI rats showed significant improvement in spatial learning when compared to the saline-treated TBI rats. Tβ4 treatment also significantly reduced the swim latency to reach the hidden platform by rats post TBI compared to saline treatment. Using the modified Neurological Severity Score (mNSS) test, our data show that significantly improved scores were observed after TBI in the Tβ4-treated group compared to the saline-treated group. Our data also show that Tβ4 reduced the incidence of both right forelimb and hindlimb footfaults in TBI rats.34 Histological data show that early Tβ4 treatment reduced cortical lesion volume by 20% and 30% for 6 mg/kg and 30 mg/kg, respectively, and reduced hippocampal cell loss. These findings suggest that TB4 provides neuroprotection even when the treatment was initiated 6 hours post injury. In addition, 6-hour Tβ4 treatment promotes neurogenesis in the dentate gyrus (DG) of the hippocampus,38 which may contribute to improvement in spatial learning.

Fortunately for the players, despite the appending doom touted by the media, the current research suggests Tβ4 is safe. 23 non-clinical toxicology studies have been performed “that demonstrate the safety of Tβ4 for its current and planned uses in man”. Significantly, a human clinical trial in healthy volunteers found “intravenous administration of Tβ4 appears to be safe and well-tolerated by all subjects with no dose limiting toxicity or serious adverse events reported”. Admittedly, this trial is limited in that it only followed subjects for a period of 28 days, and thus there is a need for further research if Tβ4 is ever to be developed as a medication.


However, the Food and Drug Administration and its equivalents in other countries have issued repeated advisory notices about Melanotan II, urging consumers to stop using and purchasing this unapproved product. David Carter of the United Kingdom's Medicines and Healthcare Products Regulatory Agency was unequivocal in his denunciation, warning would-be buyers against being "fooled into thinking that Melanotan offers a shortcut to a more even tan." Liverpool John Moores University researcher Michael Evans-Brown cautioned that the peptide may be linked to dyspepsia and various cardiovascular problems, such as increases in blood pressure, while others have noted it appears to stimulate the growth of moles on the body.
I was just diagnosed with achilles tendonosis in both of my achilles. I am an avid lifter as well as city leagues for football and basketball, I live in Montana so I hike a lot and participate In obstacle course races. My achilles have ground me to a halt over the last 3 months months. I have been referred to a surgeon for a Tenex procedure on both achilles. I am only 32 the last thing I want is have both of my achilles cut into. I’m looking at the TB-500 and BPC-157 to hopefully avoid surgery. I have done my research but am getting conflicting numbers as far as dosing. I am roughly 240 pounds and 6’5 could u recommend a dosage and cycle? Also I was wondering where the most effective injection site would be? Do I need it directly into the achilles itself or is local good enough?
It has been shown that oxytocin differentially affects males and females. Females who are administered oxytocin are overall faster in responding to socially relevant stimuli than males who received oxytocin.[75][86] Additionally, after the administration of oxytocin, females show increased amygdala activity in response to threatening scenes; however, males do not show increased amygdala activation. This phenomenon can be explained by looking at the role of gonadal hormones, specifically estrogen, which modulate the enhanced threat processing seen in females. Estrogen has been shown to stimulate the release of oxytocin from the hypothalamus and promote receptor binding in the amygdala.[86]
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.
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone and dynorphin, for example, that act locally. The magnocellular neurosecretory cells that make oxytocin are adjacent to magnocellular neurosecretory cells that make vasopressin. These are large neuroendocrine neurons which are excitable and can generate action potentials.[124]

In the prairie vole, oxytocin released into the brain of the female during sexual activity is important for forming a pair bond with her sexual partner. Vasopressin appears to have a similar effect in males.[57] Oxytocin has a role in social behaviors in many species, so it likely also does in humans. In a 2003 study, both humans and dog oxytocin levels in the blood rose after five to 24 minutes of a petting session. This possibly plays a role in the emotional bonding between humans and dogs.[58]
Exogenous Tβ4 can function like a hormone on cells in terms of its ability to modulate their biological behavior. Since one of the primary roles of Tβ4 in cells is the sequestration of actin monomers, and the protein is not secreted, previously indicated that it was unlikely that Tβ4 could have a hormonal function [42]. However, other studies have shown that the intracellular level of Tβ4 or its mRNA can be significantly and rapidly altered by external stimuli and that change in the level of Tβ4 often are correlated with cell differentiation [18, 43]. In the present study, exogenous Tβ4 peptide activate intracellular Tβ4, which results suggested that exogenous Tβ4 spontaneously enter the cytoplasm through rapid internalization, and acts their functions same as endogenous one [8, 18].
I was just diagnosed with achilles tendonosis in both of my achilles. I am an avid lifter as well as city leagues for football and basketball, I live in Montana so I hike a lot and participate In obstacle course races. My achilles have ground me to a halt over the last 3 months months. I have been referred to a surgeon for a Tenex procedure on both achilles. I am only 32 the last thing I want is have both of my achilles cut into. I’m looking at the TB-500 and BPC-157 to hopefully avoid surgery. I have done my research but am getting conflicting numbers as far as dosing. I am roughly 240 pounds and 6’5 could u recommend a dosage and cycle? Also I was wondering where the most effective injection site would be? Do I need it directly into the achilles itself or is local good enough?
The full-length Tβ4 polypeptide has been shown to be effective in reducing inflammation [44]. It is also reported that only the 4-AA, amino-terminal peptide of Tβ4, known as Ac-SDKP, can block inflammation [45]. In this study, we used a synthetically human peptide produced copy of a naturally occurring, highly conserved 43-amino acid (MW = 4964 Da) water soluble acidic peptide, originally isolated from bovine thymus tissue [46]. This peptide is produced by Fmoc solid-phase peptide synthesis in accordance with the current Good Manufacturing Practice (cGMP) regulations (21 CFR 210 and 211) of the FDA [47]. An effective healer, Tβ4 can be administered topically on the surface of cells and systemically, through injection [9–11]. In this study, Tβ4 activation by Tβ4 peptide inhibited H2O2-induced production of NO and PGE2, expression of COX-2 and iNOS, and mRNA expression of TNF- α, IL-1β, -6, -8, and -17 in cultured PDLCs. These findings suggested that Tβ4 activation possessed anti-inflammatory activity in PDLCs. These results were consistent with previous in vivo and in vitro studies [9–15]. MAPK is a proline-directed serine/threonine kinase consisting of three-enzyme modules; its targets, inducing ERK, JNK and p38 kinases, are important in cellular signal transduction pathways and exert an anti-inflammatory response [48, 49]. NF-κB is a major transcription factor involved in the release of proteins that mediate the inflammatory response, and the degradation and phosphorylation of Iκ-Bα are necessary to release NF-κB from the cytoplasmic NF-κB/Iκ-Bα complex and allow its subsequent translocation to the nucleus of the cell [50]. In this study, Tβ4 peptide down-regulated the H2O2-triggered activation of the ERK and JNK MAPKs and the NF-κB in PDLCs. These results suggested that the ERK and JNK MAPKs and the NF-κB pathway may be involved in the anti-inflammatory effects of Tβ4 activation in PDLCs. Consistent with our findings, Tβ4 treatment decreased TNF-α-induced NF-κB activation in human corneal epithelial cells [51].
In mammals, many mysteries remain. Oxytocin is difficult to measure reliably in the brain, making it hard to know exactly where, when and how much is normally released; nor do scientists understand precisely how it works to alter behaviour. “What we need to start thinking about is the more fundamental role that oxytocin plays in the brain,” Young says. The determination to find out has been strengthened by a growing move in neuroscience to characterize circuits that are important in brain operations. “That's the level that's critical for understanding how the brain is regulating behaviour,” says Thomas Insel, director of the US National Institute of Mental Health in Bethesda, Maryland, who has studied oxytocin in voles.
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;71:520-530. View abstract.
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).

There is no long-term side effects ever reported, but there is post injection effects while using Melanotan 2, typically these effects appear during the first few days of dosing and will become increasingly less obvious as the body adjusts to the peptide. These effects include: hot flush in face, mild nausea, decreased appetite, and increased sex drive. In order to combat nausea, an anti-histamine product can be taken until the body gets used to it. But most common way to deal with this is to take the dose before bed.
I’ve used powdered 5-HTP a couple times now, it doesn’t taste great and it’s resulted in an unpleasant stomach upset that lasted 45–60 minutes. For that reason I’ll likely not continue to use it. I did not find it’s effect on mood remarkable enough that I would want to put up with the stomach upset. My go to Nootropics for mood are Rhodiola and Phenibut and my go to Biohacks for mood are meditation and no fap, I don’t feel the need to use a whole lot more mood promoting strategies.
Our nutrition team created these easy mix-and-match menus using the same guidelines that helped 5-HTP dieters lose weight at top speed during the University of Rome study. The idea here is simple: You’ll eat balanced meals that keep you feeling energized and awesome, but you’ll also watch portions so you’re not overeating out of habit. While using these menus, be sure to drink plenty of water and add any other zero-cal beverages you like. You’re also encouraged to season meals to your liking with unlimited herbs, spices, vinegar, mustard, and citrus juice. As always, get a doctor’s OK before trying any new plan.
In 20 persons undergoing alcohol withdrawal taking 5-HTP (5mg) alongside Glutamine (150mg) and D-Phenylalanine (300mg) and some minerals such as Calcium and Magnesium, it was noted that after 40 days of nutritional therapy (in a hospital setting) that all withdrawal symptoms assessed via SCL-90-R except for anxiety noted a greater reduction with nutritional support relative to placebo.[1]
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.[50][51] However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies.[49]
Cells were pretreated with indicated concentrations of Tβ4 peptide for 2 hours, post-incubated with 200 μM H2O2 for 48 hours, and then conditioned medium (CM) was collected. Mouse BMMs were cultured with CM in the presence of M-CSF (30 ng/mL) and RANKL (100 ng/mL), as described in Materials and methods. After 5 days, cells were fixed and stained for TRAP as a marker of osteoclasts (A), and the number of TRAP-positive multinucleated cells (MNCs) was scored (B). TRAP osteoclast activity was assayed using the TRAP cytochemical stain technique (C). * Statistically significant differences compared with the control, p<0.05. The data presented were representative of three independent experiments.
But Carter and other scientists are concerned by reports from the physicians and parents of children with autism spectrum disorder who say that they are already using oxytocin off-label — before it has been thoroughly tested. “We do not understand how the hormone works yet, or have enough information about what happens when it's given repeatedly,” Carter says. “This is not a molecule that people should be self-administering or playing with.”

Animal studies have found high levels of both stress and oxytocin in voles that were separated from other voles. However, when the voles were given doses of oxytocin, their levels of anxiety, cardiac stress, and depression fell, suggesting that stress increases internal production of the hormone, while externally supplied doses can help reduce stress.


The N-terminal half of β-thymosins bears a strong similarity in amino acid sequence to a very widely distributed sequence module, the WH2 module. (Wasp Homology Domain 2 - the name is derived from Wiskott-Aldrich syndrome protein).[11][12] Evidence from X-ray crystallography shows that this part of β-thymosins binds to actin in a near-identical manner to that of WH2 modules, both adopting as they bind, a conformation which has been referred to as the β-thymosin/WH2 fold. β-thymosins may therefore have evolved by addition of novel C-terminal sequence to an ancestral WH2 module.[13] However, sequence similarity searches designed to identify present-day WH2 domains[14] fail to recognise β-thymosins, (and vice versa) and the sequence and functional similarities may result from convergent evolution.[15]

Melanotan 2 works by stimulating the release of the pigment melanin from the skin. Less UV exposure is necessary with Melanotan 2 compared to “normal tanning”, and the tan that occurs with tanning injections is deeper and longer lasting than an individual’s “normal tan”. Melanotan works best (has the most noticeable effects) on people with fair skin tones.

We had previously reported that successful hunters experienced a surge in testosterone that lasted from the moment they made a kill until their return home – a “winner effect,” rewarding them for their work. Testosterone reinforces the hunting activity and simultaneously helps with muscle regeneration afterwards - similar to the elated feeling we might have after doing sports or other exercise.
Uterine contraction 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.[4]
Melanotan II has reported toxicity effects from therapeutic and overdose exposures including: renal dysfunction, rhabdomyolysis, sympathomimetic overdrive, change in size and pigmentation of pre-existing moles, rapid increase in the number of new moles associated with causing melanomas, posterior reversible encephalopathy syndrome, refractory priapism, stretching and yawning syndrome, shortness of breath, chest pain, abdominal cramping and pain, dizziness and lethargy. XXXXXX alone has received 28 calls about melanotan II since 2006.
RegeneRX Biopharmaceuticals is focusing on the commercialization of Tb4 “For the treatment of injured tissue and non-healing wounds, to enable more rapid repair and/or tissue regeneration.” Especially needy are diabetics who suffer from poor blood circulation and loss of sensation of pain that keeps their wounds unnoticed and unattended for days, leading to ulcers that may not heal. Other hard healing wounds are pressure ulcers in patients who are bed ridden and often receive skin grafts as treatment, or reconstructive surgery.
Stimulation of milk ejection (milk letdown): Milk is initially secreted into small sacs within the mammary gland called alveoli, from which it must be ejected for consumption or harvesting. Mammary alveoli are surrounded by smooth muscle (myoepithelial) cells which are a prominant target cell for oxytocin. Oxytocin stimulates contraction of myoepithelial cells, causing milk to be ejected into the ducts and cisterns.

Dietary supplements containing 5-HTP are claimed to help promote feelings of happiness and general well-being as well as a wide range of other positives such as appetite control, reduced anxiety, and improved mood, sleep and feelings of relaxation. However, there is no conclusive evidence showing that it is effective, and there is no clear "therapeutic" dose of 5-HTP.
Melanotan II has reported toxicity effects from therapeutic and overdose exposures including: renal dysfunction, rhabdomyolysis, sympathomimetic overdrive, change in size and pigmentation of pre-existing moles, rapid increase in the number of new moles associated with causing melanomas, posterior reversible encephalopathy syndrome, refractory priapism, stretching and yawning syndrome, shortness of breath, chest pain, abdominal cramping and pain, dizziness and lethargy. XXXXXX alone has received 28 calls about melanotan II since 2006.
Thymosin beta 4 is a small 43 amino acid protein (a peptide) that was originally identified in calf thymus, an organ that is central in the development of immunity. Tb4 was later found in all cells except red blood cells. It is highest in blood platelets that are the first to enter injured areas, in wound healing. Tb4 is also detected outside cells, in blood plasma and in wound and blister fluids.

In all groups, [intravenous tryptophan] impaired memory and psychomotor performance significantly. In conclusion, cognitive deficits in [bipolar patients] following [intravenous tryptophan] may reflect a central 5-HT vulnerability in frontal brain areas. Independent of [intravenous tryptophan], cognitive deficits in [bipolar patients] provide evidence for a trait marker for [bipolar disorders].

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