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Oxytocin Intranasal Treatment for socialization, obesity, pain, and substance abuse

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Oxytocin is a hormone secreted by the posterior lobe of the pituitary gland, a pea-sized structure at the base of the brain. Sometimes known as the “cuddle hormone” or the “love hormone,” oxytocin promotes feelings of devotion, trust, and bonding and is released through physical touches, such as hugs, and also linked to the intensity of orgasms during sexual activity.

2013 review noted all of oxytocin’s possible relationship-enhancing effects, which were said to include:

  • Fostering pro-relationship mindsets and behaviors
  • Enhancing the processing of bonding cues
  • Facilitating improved communication
  • Empathy
  • Trust
  • Fidelity

For females, it is the neuropeptide responsible for inducing labor contractions in pregnant women and also the “let down reflex,” which stimulates the production of milk during breastfeeding. Oxytocin is synthesized in the hypothalamus and stored in the posterior pituitary where it can be released when needed.

Chapter 16 Nutritional Aspects of Pregnancy and Breastfeeding Vicky Pehling

 Figure 1: Chapter 16- Nutritional Aspects of Pregnancy and Breastfeeding. Vicky Pehling

  1. suckling stimulates nerves in the nipple and areola that travel to the hypothalamus
  2. In response, the hypothalamus stimulates the posterior pituitary to release oxytocin and anterior pituitary to release prolactin
  3. Oxytocin stimulates lobules in the breast to let down (release) milk from storage. Prolactin stimulates additional milk production

Oxytocin Uses In Childbirth

In general, oxytocin should not be used to start labor unless there are specific medical reasons. However, the FDA approves the use of oxytocin for pregnant women who have complications of childbirth, such as:

  • Cardiovascular-Renal Disease
  • Eclampsia
  • Preeclampsia
  • Premature Rupture of Membranes (PROM)

It can also be used to reduce and control postpartum uterine bleeding with minimal side effects, namely nausea, vomiting, and headaches.  

Alternative Uses of Oxytocin

In recent years, it has been suggested that oxytocin may prove beneficial for a number of clinical conditions beyond those approved by the FDA.

Oxytocin uses studied outside of FDA indication include: 

Chronic / Acute Pain – Numerous randomized studies have shown promising results of oxytocin use for chronic and acute pain. In addition to activating its own receptors and decreasing pain signals, oxytocin binds to opioid receptors and stimulates endogenous opioid release in the brain. In addition to relieving pain, oxytocin lowers serum cortisol and can produce a calming effect and improve mood.(1)

Oxytocin can also modulate pain by counteracting with psychological features such as calming the emotion of pain or removing the cognitive attention to pain.

Autism Spectrum Disorder (ASD) – Oxytocin has been implicated in the regulation of repetitive and affiliative behaviors and stress reactivity. Therefore, it is expected to be a potential therapeutic resource for the social core symptoms of ASD, since this neuropeptide can modulate human social behavior and cognition. (2)

Hypoactive Sexual Desire Disorder (HSDD) – HSDD is attributed to an imbalance in central sexual excitatory (dopamine, norepinephrine, melanocortin, and oxytocin) and sexual inhibitory (serotonin, opioid, endocannabinoid, and prolactin) pathways. For some, treatment with oxytocin nasal spray has shown to improve the sexual quality of life significantly.

Post-Traumatic Stress Disorder (PTSD) – Research findings indicate that repeated intranasal oxytocin offers promising early preventive intervention for PTSD for individuals at increased risk for PTSD due to high acute symptom severity.(3)

Obesity / Weight Loss – Scientists suspect that one element of the obesity epidemic is that the brains of obese people respond differently to images of delicious, calorically dense foods. Studies have shown that oxytocin reduces activation in the hypothalamus, an area of the brain that controls hunger, and increases activation in areas of the brain associated with impulse control. Thus, some believe that the hormone creates less of a need to eat, reduces the compulsion to eat for fun, and improves impulse control when it comes to actually reaching for that second slice of cake.(4

Addiction & Withdrawal – Oxytocin has also been used as a potential mediator and regulator of drug addiction. Several studies have shown good outcomes in cocaine, opioid, and cannabis addiction. In a placebo-controlled trial the administration of oxytocin demonstrated efficacy in reducing withdrawal symptoms, anxiety and need for lorazepam in subjects with alcohol dependence undergoing detoxification.(5)

The ‘Cuddle Hormone’ Might Help America Take On the Obesity Epidemic

A man and a woman cuddle on a rock.

Scientists suspect that one element of the obesity epidemic is that the brains of obese people respond differently to images of delicious, calorically dense foods. Obese individuals’ brains seem to light up at the sight of donuts, pizza, and other calorie bombs, even when they’re no longer hungry.

Some studies have suggested that this heightened activity might predispose people to overeating. Today, nearly 40 percent of American adults are obese, and obesity is predicted to become the leading cause of cancer among Americans, replacing smoking, within five or 10 years. (It’s still not clear yet which comes first—the obesity or the overactive brain activity.) “Part of the reason for the obesity epidemic is that people eat when they’re not hungry,” says Elizabeth Lawson, an associate professor of medicine at Harvard Medical School and a neuroendocrinologist at Massachusetts General Hospital.

A remedy for this over-activation in the brain might come from an unexpected source: oxytocin, the brain chemical often associated with love and social relationships. Oxytocin is sometimes called the “cuddle hormone” because it’s released during sex, childbirth, and breastfeeding. People who are in the early stages of falling in love have higher levels of oxytocin than normal. The drug ecstasy also increases concentrations of the hormone in the blood.

Oxytocin has a variety of other surprising functions. A form of the chemical, Pitocin, induces labor, and another form might help treat stomach pain. Early studies have suggested that the hormone might boost social skills among kids with autism. Now Lawson and other researchers are investigating whether oxytocin might also prevent overeating.

Lawson and her colleagues recently showed images of high-calorie foods to 10 overweight and obese men. She found that the regions of the brain involved in eating for pleasure lit up when the men viewed the images. A dose of oxytocin, compared with a placebo, weakened the activity in those regions, and it also reduced the activity between them. Meanwhile, oxytocin didn’t have that effect when the men viewed images of low-calorie foods or household items. Lawson’s colleagues presented the research, which has not yet been published in a peer-reviewed journal, last month at Endo 2019, the Endocrine Society’s annual meeting.

“One of the key ways oxytocin works in limiting the amount of food that we eat is that it speeds up the satiety process, or reaching fullness,” says Pawel Olszewski, an associate professor of physiology at the University of Waikato, in New Zealand, who was not involved with Lawson’s study. “Then, oxytocin works through brain areas that are associated with the pleasure of eating, and it decreases our eating for pleasure.

That’s just one of the ways oxytocin shows potential as an obesity treatment. Previously, Lawson and her colleagues found that the hormone improves insulin sensitivity and encourages the body to use fat as fuel. Lawson’s other studies have shown that oxytocin reduces activation in the hypothalamus, an area of the brain that controls hunger, and increases activation in areas of the brain associated with impulse control. To Lawson, the results together suggest that the hormone creates less of a need to eat, reduces the compulsion to eat for fun, and improves impulse control when it comes to actually reaching for that second slice of cake. Oxytocin, in other words, appears to make food seem less rewarding.

Other researchers have found that oxytocin might weaken alcoholics’ dependence on alcohol, drawing parallels to the hormone’s effects on how some obese people’s brains perceive food. A study published in the journal PLOS this month showed that oxytocin cut the desire to drink among alcohol-dependent rats. It’s not clear what this anti-drinking element of oxytocin has to do with its love-hormone properties, if anything.

So why can’t we just pick up bottles of oxytocin at CVS? For one thing, most of these studies have been very small; 10 is a minuscule sample size. They’ve been largely conducted on men, so future research would need to be expanded to women. The mechanism behind oxytocin’s effects on eating behavior and metabolism needs to be clarified, and the safety of using the hormone long term needs to be established.

The way that Lawson’s and many other studies have been conducted is by putting oxytocin in a nasal spray and attempting to shoot it directly toward the brain. But it’s not clear how much of the drug the person is actually getting through this kind of application, and researchers are still working on making it more precise. To answer some of these questions, Lawson is currently conducting an NIH-funded randomized controlled trial that will administer oxytocin to obese men and women for eight weeks.

Finally, even if all these studies are successful, it’s important to remember that there are myriad reasons—social, economic, biological, cultural—that people become obese, addicted to food, or addicted to other substances. An oxytocin treatment might only work for some of them, and even if it did, not all obese people desire to lose weight. “Its effectiveness may depend on the reason for why the obese individual is obese,” Olszewski says.

Still, a drug that helped even a fraction of America’s 93 million obese people would be a major breakthrough. If all this research bears results, many years from now, there may be another reason to love the love hormone.

Oxytocin may treat abdominal pain

Australian researchers have found a key to treating chronic abdominal pain may lie in a hormone that induces labour and encourages social bonding.

The researchers, led by The University of Queensland’s Professor Paul Alewood from and the University of Adelaide’s Dr Stuart Brierley, have developed a version of the hormone oxytocin to treat chronic abdominal pain associated with conditions such as irritable bowel syndrome.

Oxytocin is known as ‘the love drug’ for its ability to enhance social interactions including maternal behaviour, partnership and bonding.

Professor Alewood, from UQ’s Institute for Molecular Bioscience, said the molecule they had developed – a version of oxytocin with improved stability – showed significant potential in alleviating abdominal pain.

“It can potentially survive in the digestive tract until it reaches the gut,” he said.

“This molecule acts on oxytocin nerve receptors in the bowel, which display increased sensitivity in conditions such as irritable bowel syndrome.”

Professor Alewood said it had no effect on healthy gut tissue, which was an important advantage in drug development where minimising side effects is crucial.

Chronic abdominal pain is a major health problem, with irritable bowel syndrome alone affecting around 11 per cent of the Western population.

Despite the high number of sufferers, there are currently no drugs that directly treat abdominal pain.

Oxytocin spray boosts social skills in children with autism

Treatment with the hormone oxytocin improves social skills in some children with autism, suggest results from a small clinical trial. The results appeared today in the Proceedings of the National Academy of Sciences1.

Oxytocin, dubbed the ‘love hormone,’ enhances social behavior in animals. This effect makes it attractive as a potential autism treatment. But studies in people have been inconsistent: Some small trials have shown that the hormone improves social skills in people with autism, and others have shown no benefit. This may be because only a subset of people with autism respond to the treatment.

In the new study, researchers tried to identify this subset. The same team showed in 2014 that children with relatively high blood levels of oxytocin have better social skills than do those with low levels2.

In their new work, the researchers examined whether oxytocin levels in children with autism alter the children’s response to treatment with the hormone. They found that low levels of the hormone prior to treatment are associated with the most improvement in social skills.

“We need to be thinking about a precision-medicine approach for autism,” says Karen Parker, associate professor of psychiatry at Stanford University in California, who co-led the study. “There’s been a reasonable number of failed [oxytocin] trials, and the question is: Could they have failed because all of the kids, by blind, dumb luck, had really high baseline oxytocin levels?”

The study marks the first successful attempt to find a biological marker that predicts response to the t

herapy.

“This study is suggestive of a hormonal-based biomarker for oxytocin treatment, which makes sense and is a promising step forward,” says Adam Guastella, professor of psychology at the Brain and Mind Centre at the University of Sydney in Australia, who was not involved in the study.

Hormone help:

The researchers enrolled 34 children with autism, aged 6 to 12 years. Parents gave their children a nasal spray twice a day for four weeks; 16 children got a spray containing oxytocin, and 18 got a spray with placebo. (Two of the children in the oxytocin group later dropped out of the study.)

The researchers measured oxytocin levels in the children’s blood at the start and end of the trial. They assessed the children’s social skills using a parent questionnaire called the Social Responsiveness Scale (SRS) and used other tests to assess the drug’s effects on repetitive behaviors and anxiety levels.

Based on SRS scores alone, oxytocin treatment did not lead to a statistically significant improvement in social skills. But when the researchers built a statistical model that accounted for the children’s oxytocin levels at the trial’s start, they found that the children who received oxytocin improved more on the SRS than did those on the placebo. The children with the lowest initial blood levels of oxytocin generally showed the most improvement.

Some children who received the placebo also showed an improvement in their social skills. These children also showed a rise in oxytocin levels over the course of the study. This indicates that simply participating in the study boosted their oxytocin levels, and may underlie their improvement, Parker says. Boosting oxytocin levels in other ways — say, through a behavioral intervention — could also be beneficial, she says.

The treated children showed no decrease in repetitive behaviors or anxiety, suggesting that the findings are specific to social skills. The therapy had no serious side effects.

Looking ahead:

Oxytocin levels vary naturally among people, and may even change throughout the day. The researchers tried to mitigate some of this variability by drawing each child’s blood at roughly the same time each day.

Still, the change in oxytocin levels in the placebo group could be a result of natural variation and might not be meaningful, says Linmarie Sikich, associate director of the Duke Center for Autism and Brain Development in Durham, North Carolina, who was not involved in the study.

Researchers also note that the trial did not assess oxytocin’s long-term effects. “Should oxytocin be found effective, no one is going to use it for four weeks and stop. We have to make sure that long-term administration is safe,” says co-lead researcher Antonio Hardan, professor of psychiatry and behavioral sciences at Stanford University.

Confirming oxytocin’s effectiveness as an autism treatment requires larger, longer-term studies. With that goal in mind, Sikich and her colleagues have enrolled nearly 300 people with autism in a placebo-controlled 24-week trial of the hormone. The placebo and treatment groups will then receive treatment for another six months.

The team is measuring the participants’ blood levels of oxytocin before, during and after treatment. They are also monitoring factors that alter the expression of the oxytocin gene, and of other genes involved in the same pathway.

Oxytocin reduces caloric intake in men.

OBJECTIVE:

Preclinical studies indicate that oxytocin is anorexigenic and has beneficial metabolic effects. Oxytocin effects on nutrition and metabolism in humans are not well defined. It was hypothesized that oxytocin would reduce caloric intake and appetite and alter levels of appetite-regulating hormones. Metabolic effects of oxytocin were also explored.

METHODS:

A randomized, placebo-controlled crossover study of single-dose intranasal oxytocin (24 IU) in 25 fasting healthy men was performed. After oxytocin/placebo, subjects selected breakfast from a menu and were given double portions. Caloric content of food consumed was measured. Visual analog scales were used to assess appetite, and blood was drawn for appetite-regulating hormones, insulin, and glucose before and after oxytocin/placebo. Indirect calorimetry assessed resting energy expenditure (REE) and substrate utilization.

RESULTS:

Oxytocin reduced caloric intake with a preferential effect on fat intake and increased levels of the anorexigenic hormone cholecystokinin without affecting appetite or other appetite-regulating hormones. There was no effect of oxytocin on REE. Oxytocin resulted in a shift from carbohydrate to fat utilization and improved insulin sensitivity.

CONCLUSIONS:

Intranasal oxytocin reduces caloric intake and has beneficial metabolic effects in men without concerning side effects. The efficacy and safety of sustained oxytocin administration in the treatment of obesity warrants investigation.

Oxytocin Study for Alcohol Withdrawal

Background: We recently showed in a placebo-controlled trial (n=11) that oxytocin (OXY) (24 IU insufflation bid) demonstrated efficacy in reducing withdrawal symptoms, anxiety and need for lorazepam in subjects with alcohol dependence undergoing detoxification (Pedersen et al, ACER 37:484, 2013).

Methods: The current pilot study tested for safety and efficacy of OXY compared to placebo (PBO) in subjects admitted to a residential community detoxification center. Effects on withdrawal and on subsequent drinking behavior, craving and anxiety were examined. Subjects with alcohol dependence and a history of withdrawal were enrolled within 48 hours of admission and received 4 insufflations of OXY (24 IU per dose) or PBO on Day 1, 3 doses on subsequent inpatient days and then bid dosing on outpatient days. Subjects were also recruited post-detox for the drinking trial and received similar dosing except no qid dosing on Day 1. Subjects were followed for 12 weeks as outpatients and received Medical Management.

Results: 115 subjects were prescreened to give 30 subjects fully screened to yield 19 randomized subjects. 8 subjects (4 OXY) form the detox inpatient group with the outpatient group consisting of 9 subjects (6 OXY) who completed at least 4 weeks of medication. Subjects receiving OXY during detox had a mean reduction in CIWA of 2.8 in the 48 hrs post-randomization vs an increase of 1.0 on PBO (p=.025) and used a mean of 2.25 mg lorazepam vs 5.25 mg lorazepam with PBO (p=.076). During the outpatient phase both the OXY and PBO groups had large reductions in heavy drinking days and large increases in abstinent days with decreased craving and anxiety but no significant OXY/PBO differences were found. No serious adverse events were seen, 2 OXY subjects complained of nose irritation and 2 subjects stopped meds (1 PBO for hives and 1 OXY for burning in the nose).

Conclusions: The finding of a significant reduction in alcohol withdrawal symptoms with less lorazepam use in the OXY vs PBO condition is compatible with our initial trial and is of therapeutic interest given that OXY does not have the deleterious profile of sedation and addiction liability associated with the benzodiazepines. The failure to find an OXY vs PBO effect on drinking behavior, anxiety or craving post-detox is difficult to interpret given the limited power of the trial. Tolerability of OXY was reasonable. Additional OXY trials in alcohol dependence are warranted.

In the future, there will be a pill for falling in love

Oxytocin could help treat alcohol use disorder

Oxytocin could help treat alcohol use disorder

by Public Library of Science

Oxytocin
Spacefilling model of oxytocin. Created using ACD/ChemSketch 8.0, ACD/3D Viewer and The GIMP. Credit: Wikipedia.

The neuropeptide oxytocin blocks enhanced drinking in alcohol-dependent rats, according to a study published April 16 in the open-access journal PLOS Biology led by Drs. Tunstall, Koob and Vendruscolo of the National Institutes of Health, and Drs. Kirson and Roberto of The Scripps Research Institute. Targeting the oxytocin system, the authors note, may provide novel pharmaceutical interventions for the treatment of alcohol-use disorder.

Administering oxytocin can decrease consumption, withdrawal symptoms, and drug-seeking behavior associated with several drugs of abuse, and shows promise as a pharmacological approach to treat drug addiction. But first, researchers need to understand how oxytocin mediates these effects in animal models.

To address this question, Tunstall and colleagues tested the hypothesis that oxytocin administration could normalize the maladaptive brain changes that occur in alcohol dependence and thereby reduce alcohol drinking in an established rat model of alcohol dependence.

The authors investigated oxytocin’s effects on dependence-induced alcohol consumption and altered signaling of the inhibitory neurotransmitter GABA in the central nucleus of the amygdala (CeA)—a key brain region in the network affected by alcohol dependence.

The experiments demonstrated that oxytocin administered systemically, intranasally or into the brain blocked excess drinking in alcohol-dependent but not in normal rats. Moreover, oxytocin blocked GABA signaling in the CeA. Taken together, these results provide evidence that oxytocin likely blocks enhanced drinking by altering CeA GABA transmission.

These results provide evidence that aberrations in the oxytocin system may underlie alcohol use disorder and that targeting this system, possibly by intranasal administration, could prove a promising therapy in people who misuse alcohol.