Shopping Cart

You have 0 items

Oxytocin Nasal Spray – The Biochemistry – Research Summary

Posted by Anonymous on October 22, 2015  /   Posted in Khemcorp Originals, Overcoming Social Anxiety, Oxytocin

We read some interesting stuff about Oxytocin in current Stanford University clinical trials. If they were doing it, it must be a pretty big deal right.

Is Oxytocin Therapy a Social Anxiety Cure All?

No. Like any hormone, it is regulated and controlled in the body with precision, and most people would not get magical effects from Oxytocin therapy.

Like any hormone Oxytocin elevates certain parameters such as trust and bonding, but too much of a good thing can lead to bad things.

As we all know too much Testosterone isn’t a healthy thing.

Perhaps we can all benefit from a small boost of Oxytocin, but really it’s probably most beneficial to people who may be deficient in Oxytocin production, or in which elevated levels of Oxytocin would correct some social deficiencies like in autism or people with serious social anxiety.

Does Oxytocin Pass the Blood Brain Barrier (BBB)?

There has been a question of whether large peptides pass the blood brain barriers, but there is evidence showing that oxytocin does pass the BBB nasally, however, how large molecules traverse the mucous membrane maintains a mystery.

There a few pointers to why it does cross the BBN:

  1. Stanford research probably can’t base it’s clinical trials upon something that has no chance on entering the brain.
  1. Some people forget that Oxytocin nasal sprays are already prescribable by doctors, but only for inducing labor and not for other off-label uses.

Autism is a pervasive developmental disorder characterized by core deficits in social behavior and communication, and the presence of repetitive or stereotyped behaviors. It is one of three recognized disorders in the autism spectrum which affects an estimated 1 in 88 children in the United States. At present, pharmacotherapies target only associated features of autism, with no effective drug treatments for the social impairments. Several lines of evidence now suggest that the neuropeptide oxytocin (OT) may be an effective treatment for the core social deficits in autism. Here we will test the effects of twice daily intranasal OT (24 IU) over a 4-week period for enhancing social deficits in male and female children aged 6-12 years with autism. This research has high potential to lead to the development of more effective treatments and earlier interventions for children with autism.

Double-blind, Randomized, Placebo Controlled Trial of Intranasal Oxytocin Treatment for Social Deficits in Children With Autism.

http://med.stanford.edu/clinicaltrials/trials/NCT01624194

What Makes the Mucous Membrane (The Nose) Special for Peptide Administration?

The mucous membranes is special in that it’s different to other filter membranes in the body. The Blood Brain Barrier (BBB) is leaky in the ventral hypothalamus. This is how neuropeptides such as Oxytocin and ADH (Vasopressin) travel. It is a possible route of entry from circulation.

The neuropeptide oxytocin has become a subject of great interest in studies investigating human social cognition. Single intranasal administration of the hormone has been reported to have positive behavioral effects, such as increasing trust or facilitating social approach, 45-80 min after administration. However, little is still known about the long-term pharmacokinetics of oxytocin nasal spray application in humans. This study addressed the question how long oxytocin plasma levels remain elevated following nasal spray administration. Our data confirms previous findings that oxytocin administered as a nasal spray enters the blood circulation, elevating oxytocin plasma levels for a limited time. Our findings suggest that this time window differs between individuals, but that, for the used dose, it does not extend beyond 150 min post administration. The data further provides preliminary evidence that intranasal oxytocin has an enhancing effect on testosterone in healthy men.

Neuropeptides. 2012 Oct;46(5):211-5. doi: 10.1016/j.npep.2012.07.001. Epub 2012 Aug 11.
Oxytocin plasma concentrations after single intranasal oxytocin administration – a study in healthy men.
Gossen A1, Hahn A, Westphal L, Prinz S, Schultz RT, Gründer G, Spreckelmeyer KN.

There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin levels significantly increased in both plasma and CSF

Sci Rep. 2013 Dec 6;3:3440. doi: 10.1038/srep03440.
Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans.
Striepens N1, Kendrick KM, Hanking V, Landgraf R, Wüllner U, Maier W, Hurlemann R.

The Russian anxiety drug Selank is another peptide spray that has prominent effects intranasally.

There are however limitations to the nasal spray mechanism. First of all the spray must be optimized for absorption, in both it’s composition and the molecule itself (modified to absorb better). Secondly the mucous membrane has a very small surface area and is also very fragile to damage, meaning high concentrations may damage the mucous membrane, thus this limits the amount of peptides that can traverse at any given time.

The mechanism of a nasal spray should not be confused with blood infusions (IV) or oral digestion, both which have significant barriers to Oxytocin entering the brain. The nasal and the sublingual route has a much higher probability of entering the brain.

Where is Oxytocin Produced? What Does It Do in the Body and Mind? The Function of Oxytocin.

Oxytocin is a nine amino acid CNS neuropeptide. It is produced in the supraoptic and paraventricular nuclei of the hypothalamus (that’s a mouthful). Basically, it is made in the brain.

Psychological stimuli trigger the release of Oxytocin in nerve terminals. 

This means Oxytocin is naturally produced from a variety of external social interactions and touch stimuli such as hugs, handshakes, eye contact and so on. This plays a huge part in brain development, and why complete brain development cannot happen without social communication at a young age.

This would explain why people who do not have contact with others regularly fall into despair or other mental illnesses.

Like any other neurological communication molecule in the brain, it is extremely regulated and it is used in various parts of the brain, and cannot really be explained completely in simple terms without going into receptor terminology only understandable by neurologists.

Oxytocin is very straightforward compared to Vasopressin because in that it is massively linked to social bonding and social skills, as well as various natural communication skills.

Oxytocin receptors are all over the brain when Oxytocin touches these receptors a feeling or response is activated, usually to do with communication, reciprocity and most importantly love, and interlinks with dopamine and endorphins which form “happiness”

Oxytocin’s functions in the brain is so vast that we should just pretty much quote research material:

Furthermore, oxytocin and its receptors are involved in a plethora of social and affective, physiological and pathophysiological behaviors, ranging from attachment security, mating [41], paternal behavior and motherhood [33] to autism [4244] and obsessive–compulsive disorder [45]. In addition, the neuropeptide also modulates learning, memory and intelligence as shown in animal and human investigations [46,47].

Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy

Cedric Viero,1 Izumi Shibuya,2 Naoki Kitamura,2 Alexei Verkhratsky,3,4 Hiroaki Fujihara,5 Akiko Katoh,5 Yoichi Ueta,5 Hans H Zingg,6 Alexandr Chvatal,3,7 Eva Sykova,7,8 and Govindan Dayanithi3

Obviously this means that a malfunction in Oxytocin production would seriously hamper social development and social cognition, and have huge implications for autism and it’s confounding disorder social anxiety. We will go into detail into this in another post.

Oxytocin Nasal Spray Research Expanded

So it’s only natural that scientists figured out that in some scenarios an artificial increase in Oxytocin would be extremely beneficial in improving deficiencies in social development or social cognition as listed above. Time to bring out the research quotes:

A recent study demonstrated that a nasal spray of oxytocin raised the trust (in a stranger) of people playing a money game [35]. Furthermore, the spray was said to reduce the activities of the amygdala and caudate nucleus, regions of the brain implicated in emotions, fear conditioning and social cognition on the one hand, and learning, memory and feedback processing on the other hand [36,37]. Nevertheless, the role of oxytocin in ordinary relationships and real-life circumstances is still unclear. However, such findings could bring some hope in the treatment of social disorders such as phobia and autism [38].

Another demonstration of the direct role of the oxytocin receptor in the socialization of normal patients was provided by Lucht et al., though with a reduced sample size. They could associate oxytocin receptor haplotypes with affect regulation, social interaction (social and emotional loneliness) and cognition (intelligence) [40].

The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task.

Israel S, Lerer E, Shalev I, Uzefovsky F, Riebold M, Laiba E, Bachner-Melman R, Maril A, Bornstein G, Knafo A, Ebstein RP

PLoS One. 2009 May 20; 4(5):e5535.

To finish off – The potential development of drugs targeting oxytocin receptors are immense, this would mean a molecule that can activate oxytocin receptors without being oxytocin itself. This has however been difficult to produce, but if it is done it would be a very effective social anxiety drug.

Here are some very interesting chemicals to watch out for:

WAY-162,720 ([119], which is a brain-penetrant oxytocin receptor antagonist when administered peripherally), WAY-267,464 (agonist, which has been successfully introduced as an anxiolytic in mice, see [122], US patent assigned to Wyeth Corp, [50,123]) and Compound 27 (agonist, EC50= 33 nM, 25 times more selective over vasopressin receptors, [124]). Compound 27 has been classified in the list of drugs putatively having a central effect, but this should be taken carefully since its biological actions are still under investigation.

Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents.

Manning M, Stoev S, Chini B, Durroux T, Mouillac B, Guillon G

Prog Brain Res. 2008; 170():473-512.

I hope you enjoyed the read.

– Khemcorp

Research References:

1. Theodosis DT, Poulain DA. Activity-dependent neuronal-glial and synaptic plasticity in the adult mammalian hypothalamus.Neuroscience. 1993;57:501–535. [PubMed]

2. Theodosis D, Poulain D, Oliet S. Activity-dependent structural and functional plasticity of astrocyte-neuron interactions. Physiol Rev. 2008;88:983–1008. [PubMed]

3. Febo M, Shields J, Ferris C, King J. Oxytocin modulates unconditioned fear response in lactating dams: An fMRI study.Brain Res. 2009;1302:183–193. [PMC free article] [PubMed]

4. Young L, HH Z. Oxytocin. In: Pfaff EaD AM, editor.Molecular mechanisms of hormones actions on behavior. San Diego, CA: Academic Press; 2009. pp. 783–802.

5. Ostrowski N. Oxytocin receptor mRNA expression in rat brain: Implications for behavioral integration and reproductive success.Psychoneuroendocrinology. 1998;23:989–1004. [PubMed]

6. Adan R, Van Leeuwen F, Sonnemans M, et al. Rat oxytocin receptor in brain, pituitary, mammary gland, and uterus: Partial sequence and immunocytochemical localization. Endocrinology.1995;136:4022–4028. [PubMed]

7. Veinante P, Freund-Mercier M. Distribution of oxytocin- and vasopressin-binding sites in the rat extended amygdala: A histoautoradiographic study. J Comp Neurol. 1997;383:305–325.[PubMed]

8. Gimpl G, Fahrenholz F. The oxytocin receptor system: Structure, function, and regulation. Physiol Rev. 2001;81:629–683.[PubMed]

9. Neumann ID. The advantage of social living: Brain neuropeptides mediate the beneficial consequences of sex and motherhood. Front Neuroendocrinol. 2009;30:483–496. [PubMed]

10. Reidpath D, Chan K, Gifford S, Allotey P. ‘He hath the French pox’: Stigma, social value and social exclusion. Sociol Health Illn.2005;27:468–489. [PubMed]

11. Kosfeld M, Heinrichs M, Zak P, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005;435:673–676.[PubMed]

12. Kirsch P, Esslinger C, Chen Q, et al. Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci.2005;25:11489–11493. [PubMed]

13. Domes G, Heinrichs M, Gläscher J, Büchel C, Braus D, Herpertz S. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry. 2007;62:1187–1190.[PubMed]

14. DiCicco-Bloom E, Lord C, Zwaigenbaum L, et al. The developmental neurobiology of autism spectrum disorder. J Neurosci. 2006;26:6897–6906. [PubMed]

15. Israel S, Lerer E, Shalev I, et al. The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task. PLoS One. 2009;4:e5535.[PMC free article] [PubMed]

16. Lucht M, Barnow S, Sonnenfeld C, et al. Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:860–866. [PubMed]

17. Kavaliers M, Choleris E, Agmo A, et al. Inadvertent social information and the avoidance of parasitized male mice: A role for oxytocin. Proc Natl Acad Sci U S A. 2006;103:4293–4298.[PMC free article] [PubMed]

18. Hollander E, Novotny S, Hanratty M, et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology. 2003;28:193–198.[PubMed]

19. Hollander E, Bartz J, Chaplin W, et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry.2007;61:498–503. [PubMed]

20. Yamasue H, Kuwabara H, Kawakubo Y, Kasai K. Oxytocin, sexually dimorphic features of the social brain, and autism.Psychiatry Clin Neurosci. 2009;63:129–140. [PubMed]

21. Leckman J, Goodman W, North W, et al. The role of central oxytocin in obsessive compulsive disorder and related normal behavior. Psychoneuroendocrinology. 1994;19:723–749. [PubMed]

22. de Wied D, Diamant M, Fodor M. Central nervous system effects of the neurohypophyseal hormones and related peptides.Front Neuroendocrinol. 1993;14:251–302. [PubMed]

23. Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein R. Association between the oxytocin receptor (OXTR) gene and autism: Relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry. 2008;13:980–988. [PubMed]

24. Yoshida M, Takayanagi Y, Inoue K, et al. Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci. 2009;29:2259–2271.[PubMed]