Researchers at the University of Oslo have tested a new device for delivering hormone treatments for mental illness through the nose. This method was found to deliver medicine to the brain with few side effects.
About one out of every hundred Norwegians develop schizophrenia or autism in the course of their lifetime. Moreover, at any one time some 20,000 people are receiving treatment for these problems. Many psychiatric disorders such as autism, schizophrenia and bipolar disorder are characterised by poor social functioning.
Oxytocin is a hormone that influences social behaviour and has shown promise for the treatment of mental illness.
Researchers at UiO have now discovered that low doses of oxytocin may help patients with mental illness to better perceive social signals. As part of this project, they have collaborated with the company OptiNose, who have developed a new device designed to improve medicine delivery to the brain via the nose.
Regulates social behaviour
Oxytocin has historically been known to play a crucial role in child rearing as it facilitates pregnancy, birth, and the release of milk during nursing. Further, oxytocin helps regulate cardiac functions and fluid levels. More recent research has revealed the importance of oxytocin for social behaviour.
Oxytocin is a neuropeptide and was discovered in 1953. Peptides are a group of molecules that consist of a chain of amino acids. Amino acids are also known as the building blocks of proteins, which we find in all types of cells. Oxytocin is produced in the hypothalamus, which is the brain’s coordinating centre for the hormone system.
Medicine through the nose
Because of oxytocin’s role in social behaviour, researchers have explored the possibility of administering the hormone for the treatment of mental illness. As oxytocin is a relatively large molecule, it has trouble crossing the barrier between the brain and circulating blood. Thus, researchers have administered oxytocin to patients through the nose as this route offers a direct pathway to the brain that bypasses this barrier.
However, researchers have a poor understanding of how oxytocin reaches and affects the brain. The most effective dose for treatment has also received little research attention.
Professor Ole A. Andreassen and his research team have collaborated with OptiNose on a project that evaluated two different doses of oxytocin and on how they affect the way in which social signals are perceived.
Low doses work best
Sixteen healthy men received two different doses of oxytocin, along with placebo. Volunteers were also given an intravenous dose of oxytocin, for a comparison of the effects of oxytocin in circulating blood. The research showed that only those administered a low dose of oxytocin experienced an effect on how they perceived social signals.
Professor Ole A. Andreassen explains: “The results show that intranasal administration, i.e. introducing oxytocin through the nose, affects the function of the brain.
As no effect was observed after intravenous treatment, this indicates that intranasally administered oxytocin travels directly to the brain, as we have long believed. The fact that we have shown the efficacy of a low dose of oxytocin on social perception is even more important.
A dose that is lower, but that still influences behaviour, will entail a lower risk of affecting other regulatory systems in the body. Very high doses of oxytocin could, in fact, have the opposite effect on social behaviour.”
The scientists also discovered that individuals with larger nasal cavities had a stronger response to a low dose of oxytocin.
Breathing helps
OptiNose uses a new technology to distribute medicine to the brain, making use of the user’s breath to propel medicine deep into the nasal cavity.
The device administers oxytocin high up into the patient’s nasal cavity. When the medicine is targeted deep inside the nose, it enables brain delivery along nerve pathways from the uppermost part of the nasal cavity. Conventional nasal spray devices are not suited to consistently deliver medicine high up enough into the nose.
The device also expands the nasal cavity, facilitating nose-to-brain medicine delivery. As the user exhales into the device, this closes the soft palate and prevents the medicine from being lost down the throat.
Since less medicine is lost along the way, patients can take smaller doses and accordingly experience fewer side effects.
May yield new treatments
The next step in the research is to carry out the same tests on people with mental illness.
“We are now running tests in volunteers diagnosed with autism spectrum disorders,” says Dr Quintana.
“We hope that this research project is the first step in the development of a series of new medicines that may be of great help to more people with mental illness,” concludes Professor Andreassen.
Funding: The research was supported in part by the Indiana State Department of Health (Grant #204200 to RS), National Institutes of Health (Grant # NS073636 to RS), and Indiana CTSI Collaboration in Biomedical Translational Research Pilot Program Grant (Grant #RR025761 to RS). Funding for the LSM710 was provided by NIH NCRR Shared instrumentation Grant 1 S10 RR023734-01A1.
Source: Thomas Olafsen – UiO
Image Source: The image is credited to UiO
Original Research: Full open access research for “Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment” by D S Quintana, L T Westlye, Ø G Rustan, N Tesli, C L Poppy, H Smevik, M Tesli, M Røine, R A Mahmoud, K T Smerud, P G Djupesland and O A Andreassen in Translational Psychiatry. Published online July 14 2015 doi:10.1038/tp.2015.93
Abstract
Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment
Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered’ nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.
“Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment” by D S Quintana, L T Westlye, Ø G Rustan, N Tesli, C L Poppy, H Smevik, M Tesli, M Røine, R A Mahmoud, K T Smerud, P G Djupesland and O A Andreassen in Translational Psychiatry. Published online July 14 2015 doi:10.1038/tp.2015.93
