Oxytocin has been of keen interest to neuroscientists since the 1970s, when studies started to show that it could drive maternal behaviour and social attachment in various species. Its involvement in a range of social behaviours2, including monogamy in voles, mother–infant bonding in sheep, and even trust between humans, has earned it a reputation as the 'hug hormone'. “People just concluded it was a bonding molecule, a cuddling hormone, and that's the pervasive view in the popular press,” says Larry Young, a neuroscientist at Emory University in Atlanta, Georgia, who has been studying the molecule since the 1990s.
Jump up ^ Vargas-Pinilla P, Paixão-Côrtes VR, Paré P, Tovo-Rodrigues L, Vieira CM, Xavier A, Comas D, Pissinatti A, Sinigaglia M, Rigo MM, Vieira GF, Lucion AB, Salzano FM, Bortolini MC (January 2015). "Evolutionary pattern in the OXT-OXTR system in primates: coevolution and positive selection footprints". Proceedings of the National Academy of Sciences of the United States of America. 112 (1): 88–93. Bibcode:2015PNAS..112...88V. doi:10.1073/pnas.1419399112. PMC 4291646. PMID 25535371.
MAPKs and NF-κB played pivotal roles in the development of osteoclasts downstream of RANK signaling . In this study, we demonstrated that Tβ4 activation by Tβ4 peptide inhibited RANKL-induced p38, ERK, JNK MAPK, and NF-κB signaling pathways. These results suggested that Tβ4 activation might inhibit osteoclast differentiation via inhibition of the signaling cascades MAPK/NF-κB/NFATc1.
Therefore, this study was designed to investigate whether Tβ4 was up-regulated in patients with periodontitis, and this study was also designed to investigate whether Tβ4 inhibition or activation suppressed the osteoclastic differentiation in mouse bone marrow-derived macrophages (BMMs) and inflammatory response in periodontal ligament cells (PDLCs) as well as on their signaling pathways.
Established immortalized human PDLCs  that maintain the characteristics of primary PDLCs by transfecting human telomerase reverse transcriptase (hTERT) were used. These cell line were kindly provided by Professor Takashi Takata (Hiroshima University, Japan). Cells were cultured in α-MEM supplemented with 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin in a humidified atmosphere of 5% CO2 at 37°C. For the experiments, the cells were seeded into culture dishes and then cultured in α-MEM containing 10% FBS for 2 days until 70% confluent, and, then, the media was replaced by serum-free medium in order to minimize any serum-induced effects on PDLCs. Subsequently, the cells were exposed to H2O2 and human Tβ4 peptide (RegeneRx Biopharmaceuticals Inc., Rockville, MD). All treatments were performed in triplicate and approved by the local ethics committee.
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.
Tβ4 is a multifunctional regenerative small peptide containing 43-amino acids, and it is the major G-actin-sequestering molecule in eukaryotic cells.21 Tβ4 has pro-survival and pro-angiogenic properties, protects tissue against damage, and promotes tissue regeneration.22,23 It also plays a key role in corneal, epidermal and cardiac wound healing.21 Tβ4 participates in axonal path-finding, neurite formation, cell proliferation, and neuronal survival.24-26 Our previous studies show that Tβ4 reduces inflammation and stimulates remyelination and improves functional recovery in animal models of experimental autoimmune encephalomyelitis (EAE) and stroke.25,27 In summary, these pleiotropic properties make Tβ4 an ideal candidate for treatment of TBI.
Drug interaction: Impact on effects of alcohol and other drugs: According to several studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs (opiates, cocaine, alcohol), and reduces withdrawal symptoms. MDMA (ecstasy) may increase feelings of love, empathy, and connection to others by stimulating oxytocin activity primarily via activation of serotonin 5-HT1A receptors, if initial studies in animals apply to humans. The anxiolytic Buspar (buspirone) may produce some of its effects via 5-HT1A receptor-induced oxytocin stimulation as well.
Thymosins were discovered in the mid 1960’s, when Allan Goldstein from the Laboratory of Abraham White at the Albert Einstein College of Medicine in New York studied the role of the thymus in development of the vertebrate immune system. Since then, Dr. Goldstein founded a company that creates thymosin alpha 1 for the purpose of increasing immune cell activity, and thymosin beta 4 (TB-500) to promote wound repair and healing.
Romantic attachment: In some studies, high levels of plasma oxytocin have been correlated with romantic attachment. For example, if a couple is separated for a long period of time, anxiety can increase due to the lack of physical affection. Oxytocin may aid romantically attached couples by decreasing their feelings of anxiety when they are separated.
Mouse bone marrow macrophage (BMMs) of 5-week-old female ICR mice (Charles River Laboratories, Seoul, South Korea) were used as previously described . Animals were maintained in accordance with the National Institute of Toxicological Research of the Korea Food and Drug Administration guideline for the humane care and use of laboratory animals Institutional Animal Care and Use Committee (IACUC) approval was obtained from Kyung Hee University (Seoul, Korea). Briefly, bone marrow of tibiae and femurs of mice were flushed with α-MEM. After removing erythrocytes with hypotonic buffer, cells were cultured in α-MEM containing 10% FBS for 24 h and adherent cells were discarded. Non-adherent bone marrow cells were transferred onto 100-mm non-coated petri dishes at 5×106 cells per dish and cultured in the presence of M-CSF (30 ng/ml) for 3 days. Condition medium (CM) was obtained from HPDLCs treated with 200 μM H2O2 or Tβ4 (0.5, 1 and 5 μg/mL) for 2 days. To evaluate the osteoclastogenic activity of CM from HPDLCs, we added the CM mixture (60% CM plus 40% fresh α-MEM without M-CSF or RANKL) or rh-Tβ4 to pre-osteoclast-stage cells and further cultured the cells for up to 5 days to achieve mature osteoclast differentiation BMMs (1.5 × 105 cells/well) and PDLCs (1.5 × 104 cells/well) were co-cultured for 7 days in the presence of M-CSF (30 ng/ml), RANKL (100 ng/mL), H2O2 (200 μM) or Tβ4 (0.5, 1 and 5 μg/mL) in α-MEM, supplemented with10% in 48-well plates under 5% CO2 atmosphere.
Recent preclinical studies by us and others have revealed that endogenous neurorestoration is present after TBI, including neurogenesis, axonal sprouting, synaptogenesis, and angiogenesis, which may contribute to the spontaneous functional recovery.13-18 In addition, treatments that promote these neurorestorative processes have been demonstrated to improve functional recovery after brain injury.19,20 However, clinical trials in TBI have primarily targeted neuroprotection, and trials directed specifically at neurorestoration have not been conducted. The essential difference between neuroprotective and neurorestorative treatments is that the former target the lesion that is still not irreversibly injured and the latter treat the intact tissue.19 Thus, neurorestorative treatments can be made available for a larger number of TBI patients.
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 .
MT 1 and MT 2 are synthetic analogues of the alpha-melanocyte stimulating peptide hormone Alpha-MSH. This hormone aids skin cells to produce greater quantities of Melanin. Therefore MT-1 and MT-2 mimic this hormone and encourage the production of more Melanin. Melanin is a dark pigment in the skin that can provide some protection from the UV rays of the sun.
Oxytocin is known as the hormone that promotes feelings of love, bonding and well-being. It's even being tested as an anti-anxiety drug. But new research shows oxytocin also can cause emotional pain. Oxytocin appears to be the reason stressful social situations, perhaps being bullied at school or tormented by a boss, reverberate long past the event and can trigger fear and anxiety in the future. That's because the hormone actually strengthens social memory in the brain.
During the 2000s, the Melanotan II peptide and the metabolite derived from it, the erectile dysfunction-focused Bremelanotide (also known as PT-141), were patented and then licensed to biotechnology companies hoping to develop them into profitable prescription drugs. However, these companies also offer the peptides for direct sale to researchers. These transactions occupy a legal gray area, since the peptides are banned for human use outside clinical trials. While they can be purchased from various websites specializing in research chemicals, the purchaser usually has to affirm prior to final sale that the peptide "will not be used for human consumption" and is being acquired for "research purposes only."
Horvath, G. A., Stockler-Ipsiroglu, S. G., Salvarinova-Zivkovic, R., Lillquist, Y. P., Connolly, M., Hyland, K., Blau, N., Rupar, T., and Waters, P. J. Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms. Mol.Genet.Metab 2008;94:127-131. View abstract.
To explore whether Tβ4 peptide-induced anti-inflammatory and anti-osteoclastogenesis were dependent on the up-regulation of Wnt5a, the effects of recombinant human (rh) Wnt5a (500 ng/mL) and Wnt5a-specific siRNA were assessed. Pretreatment of Wnt5a siRNA reversed the inhibitory effects of Tβ4 peptide on H2O2-induced iNOS and COX-2 expressions, NO and PGE2 productions, osteoclastogenic cytokines, and RANKL expression (Fig 10A–10E). In contrast, pretreatment with rhWnt5a enhanced the anti-inflammatory effects of Tβ4 peptide whereas control siRNA showed no effect on PDLCs. In accordance with anti-inflammatory results, Tβ4 peptide-suppressed osteoclast number and TRAP activity in BMM cells were reversed by exogenous treatment with Wnt5a siRNA but enhanced by rh-Wnt5a (Fig 11A–11C).
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.
TB-500 and Thymosin Beta-4 are not exactly the same, although you’ll often see the two names used interchangeably in the peptide world (AKA broscience bodybuilding forums). It’s much harder to get your hands on true Thymosin Beta-4, whether for research use, equine enhancement, athletic performance enhancement or bodybuilding. But TB-500’s peptide sequence shares most of the properties of Thymosin Beta-4, and it’s more economical to produce, thus easier to find.
Autism. A 1998 study found significantly lower levels of oxytocin in blood plasma of autistic children. A 2003 study found a decrease in autism spectrum repetitive behaviors when oxytocin was administered intravenously. A 2007 study reported that oxytocin helped autistic adults retain the ability to evaluate the emotional significance of speech intonation.
Oxytocin is a versatile actor, whose resume includes all sorts of jobs in sex, reproduction, social behaviour and emotions. It can increase trust among people and make them more cooperative (this works in meerkats, too). It can increase the social skills of autistic people. It’s released during orgasm. It affects lactating breasts, contracting wombs and the behaviour of sheep mothers towards their newly born lambs. The list goes on: drug addiction, generosity, depression, empathy, learning, memory.
So far, few studies have definitively linked autism to problems in oxytocin signalling. Some of the clearest evidence emerged in February, from a team led by neurogeneticist Daniel Geschwind of the University of California, Los Angeles. The group showed that mice that lacked a working copy of the Cntnap2 gene — which has been implicated in a small subset of human autism cases — had fewer oxytocin-containing neurons in the hypothalamus and socialized less with other mice than did control mice15. After receiving doses of oxytocin every day for two weeks, the mice behaved normally again. “Until this, there was no evidence that there was a subtype of autism that had to do with oxytocin deficits,” Geschwind says.
5-HTP appears to reduce food intake secondary to increasing satiety, although most studies are currently conducted in women (in regards to 5-HTP being related to serotonin, this may be relevant; see our creatine page and the Depression section for more information). At least one study that was mixed gender supports the notion it benefits both genders, however
A critical step in wound healing is angiogenesis. New vessels are needed to supply nutrients and oxygen to the cells involved in repair, to remove toxic materials and debris of dead cells and generate optimal conditions for new tissue formation. Another important step is the directional migration of cells into the injured area, joining up to repair the wound. This requires an attractant that will direct the cells to the wound and propel them to the site. These critical steps in wound healing are regulated by beta 4, as seen in the following experiments.
James Bates* who recently started taking it for panic attacks, said, "A friend who had anxiety recommended 5-HTP to me. I used to take beta-blockers and Valium but the doctors have got funny about giving them to me. I needed an alternative and didn't fancy getting back on Prozac. I've only been taking the supplements for a month but so far, it's helped a lot. I've only had two panic attacks, whereas usually I'd have four or five."
Sexual activity: The relationship between oxytocin and human sexual response is unclear. At least two uncontrolled studies have found increases in plasma oxytocin at orgasm – in both men and women. Plasma oxytocin levels are notably increased around the time of self-stimulated orgasm and are still higher than baseline when measured five minutes after self arousal. The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate sperm and egg transport.
In years past, oxytocin had the reputation of being an "uncomplicated" hormone, with only a few well-defined activities related to birth and lactation. As has been the case with so many hormones, further research has demonstrated many subtle but profound influences of this little peptide, particularly in regards to its effects in the brain. Oxytocin has been implicated in setting a number of social behaviors in species ranging from mice to humans. For example, secretion or administration of oxytocin in humans appears to enhance trust and cooperation within socially-close groups, while promoting defensive aggression toward unrelated, competing groups.
About three months after quitting, I did have a major relapse, which was falling back into old habits for about two weeks. And the whole time I knew what was happening, I knew how dangerous it was, but I couldn't stop myself. I felt like I couldn't connect to anyone without drinking. I couldn't talk to my friends, I couldn't be open and honest with anybody in my life without already having had a few drinks. It was a really disconnected, really unpleasant feeling. That's what I couldn't sit with and I couldn't cope with that feeling, so I went back to drinking.
It turns out the love hormone oxytocin is two-faced. Oxytocin has long been known as the warm, fuzzy hormone that promotes feelings of love, social bonding and well-being. It's even being tested as an anti-anxiety drug. But new Northwestern Medicine® research shows oxytocin also can cause emotional pain, an entirely new, darker identity for the hormone.
Don’t take it by itself, you want to take it with a meal. The half life seems to vary; some people just need to take a single dose daily whereas some break it up into several doses. The dosage range is pretty wide, from 50 to 900 milligrams. Many report the antidepressant effect desired from lower doses, so start low with this one. Do not use a liquid form of 5-HTP.
5-HTP is sold over the counter in the United States, Canada, the Netherlands, and the United Kingdom as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. It is also marketed in many European countries for the indication of major depression under the trade names Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum.