Oxytocin: Too Much of a Good Thing?

BalesThere's been plenty of research showing that when people inhale oxytocin, they tend to have more positive social behavior: trust, generosity, empathy and communication. But if taking one whiff of oxytocin can make you nicer, will taking oxytocin regularly keep you nicer? If you take a bigger dose, will it make you even nicer?

U.C. Davis researchers wanted to find out the long-term effects of taking oxytocin, so they studied prairie voles, the monogamous rodents that first demonstrated the positive effects of this brain chemical.

 The U.C. Davis research team, led by Karen L. Bales, treated a group of 89 male prairie voles with low, medium or high doses of inhaled oxytocin. The medium dose was roughly equivalent to the amount given to human subjects in lab studies.

They began giving the prairie voles one daily dose of oxytocin when they were weaned at 21 days old, and continued to give it to them through day 42, the time they reach sexual maturity.

"We were trying to approximate ages 12 to 17 in humans," Bales told me in an email. Because so many parents of children with autism spectrum disorder are turning to oxytocin products they've bought over the internet in hopes of increasing their kids' sociability, the short-lived voles offer a way to model the possible effects of long-term dosing of an adolescent.

 The study also wanted to look at possible dose-dependent differences: If one dose creates an effect, it doesn't necessarily follow that a different dose will create the same effect. In fact, she cites research showing that in schizophrenic patients, 20 IU of oxytocin increased emotion recognition, while a dose of 10 IU actually decreased it.

There was one troubling result: The male voles treated with low or medium doses of oxytocin were actually less likely to bond with a female -- and this effect lasted two weeks after treatment stopped. That could be equivalent to years in a human life.

 The female voles in the study also seemed to be less interested in mothering.

 Bales thinks that this effect could be attributable to down-regulation of the oxytocin receptors or oxytocin-producing neurons; that is, with external oxytocin flooding the receptors, they might become desensitized, while the oxytocin-producing brain cells might lower their production because it's not needed. It also could be attributable to changes in the vasopressin system, she suggests. Vasopressin is another brain chemical very similar to oxytocin that seems to be more important in male bonding.

 She says, "I originally thought that we would see the most changes with the highest dose of oxytocin, and that would be because of flooding oxytocin receptors and binding to vasopressin receptors.  But since we had the most changes at the lowest dose, that seems less likely.  Males do seem to be especially sensitive to developmental exposure to oxytocin...perhaps because they rely less on it normally?"

 Bales' work is with prairie voles, not people. But so far, what vole research taught us about oxytocin is quite applicable to humans. We think we're so different from this tiny, humble creature. But in fact, the genetic difference between Homo sapiens and other mammals is very small.

 It's not clear how applicable the results of this study might be to older humans, but certainly the body's receptors are constantly in a state of flux, responding to external changes. And it's well known that treatment with a hormone can cause the body to produce less of it.

 Bales plans to do more studies using voles of different ages, and also to look at different lengths of treatment.

 Meanwhile, if you are self-experimenting with oxytocin, it's a good idea to keep your dosing acute: once in a while with plenty of time for your body to go back to its natural state.

 Here's the ref: Bales, K.L. et al. Chronic Intranasal Oxytocin Causes Long-Term Impairments in Partner Preference Formation in Male Prairie Voles. Biological Psychiatry 2012.

Testosterone for Female Orgasm: Phase II Trials

Trimel says it's had favorable results from trial of TBS-2 to treat female anorgasmia. The testosterone product is a low-dose gel you place inside the nose to increase libido.  http://www.marketwatch.com/story/trimel-to-present-anorgasmia-fsd-phase-ii-clinical-trial-results-2011-12-16-731200

Trimel will also discuss CompleoTRT, a similar product for men, designed to treat  low testosterone,  at a conference on February 14 in Toronto.

Using Trimel's testosterone delivery system, you place a small amount of gel inside the nose, where it's absorbed and goes into the blood stream. 

According to the company, when used on women to treat lack of orgasm, "The Phase I/II study further demonstrated positive physiological effects related to orgasm with a physical response seen within 30 minutes of dosing."

Here's a video showing how the gel delivery system works:



Compleo TRT from Trimel Pharmaceuticals on Vimeo.

Childbirth Drug Could Have Off-Label Uses

Monash University researcher Dr. Michelle McIntosh hopes to create an aerosol delivery system for oxytocin to replace oxytocin injections commonly used to stop bleeding after delivery of a baby.  She's received a grant from the Bill and Melinda Gates Foundation to develop this drug delivery method, which could eliminate the need for sterile needles and their disposal, as well as for keeping oxytocin refrigerated.

According to the Monash University press release,

“Oxytocin is an ideal candidate for delivery via the lungs. It is a highly potent drug, so only a small amount would be required to enter the systemic circulation. And its demonstrated absorptiveness in the nose and mouth suggests a passage through the huge absorptive surface of the lung is unlikely to present obstacles,” added Dr McIntosh.

Of course, inhaled oxytocin also affects the social circuits in the brain. Psychiatrists and psychotherapists are already testing oxytocin inhalants to help with a variety of psychiatric disorders, and this system could also make it easier for them.

And then, there are all the people out there dying to try oxycin ...


Oxytocin Project: Women in a State of Collaboration

The Oxytocin Project, launched by BraveHeartWomen.com, aims to inspire women around the world to connect and collaborate. Founder Ellie Drake talks about oxytocin as a spiritual state.

According to the press release, "Drake’s goal is to teach women to live in a state of Oxytocin which enables women to be more creative, powerful and successful. ... To succeed, women need to feel safe, to maintain a state of calmness and security, and to follow their inner nature that promotes a ‘tend and befriend’ approach to collaboration. In other words, they need to be in a state of Oxytocin ..."

It may not be a scientifically accurate message -- oxytocin ebbs and flows throughout the day, and the feeling of connection seems to be triggered by changes in oxytocin levels in the brain.

Nevertheless, it's an emotionally resonant message, and I am all for Drake's efforts to get women to recognize that our strenghts may be different from men's and as valuable.

Dose Soldiers with Oxytocin?

Don't blame me, I didn't make up this inflammatory angle.

It's the work of David Gutierrez of NaturalNews.com.

A recent study seemed to show that oxytocin increases the sense of solidarity in a military unit, which would make soldiers more ready to defend each other.

According to The Telegraph,

"Our study shows that oxytocin not only plays a role in modulating cooperation and benevolence, but also in driving aggression," said researcher Carsten De Dreu of the University of Amsterdam.

Prior research has shown that oxytocin, also known as the "love hormone," contributes to protectionist behavior, especially in mammalian mothers. De Dreu and colleagues wanted to explore whether the hormone might also play a role in making men more aggressive toward outsiders. De Dreu calls the pairing of in-group solidarity and out-group aggression "parochial altruism," or the "tend and defend" response.

If I love you more, I will be more likely to hate anyone who hurts you. Makes sense.

Still, it's unlikely that the military will have soldiers whiffing oxytocin any time soon. I think amphetamines are working just fine for them.

More Info on Ecstasy and PTSD

A small, phase 2 pilot study found that MDMA, also known as Ecstasy, might help treating people with post-traumatic stress disorder.

Michael Mithoefer, MD, a psychiatrist in private practice in Mount Pleasant, South Carolina, was the lead author on the study, 20 people received MDMA or placebo along with two days  of "experimental" therapy. The idea was to use the drug to reduce subjects' fear and reactivity to traumatic events.

Mithoefer told Medscape

"We didn't want to just test the drug," explained Dr. Mithoefer. "We wanted to test the drug's ability to catalyze psychotherapy. It's important that people realize that MDMA should be used in the right way, and that it's not a stand-alone solution for PTSD."

He found that subjects didn't need to take the drug every time they had therapy, nor for a long period of time. It was able to get them over the therapeutic hump enough to make progress; they could then continue to progress on their own.

Keith Young, MD, vice chair of research in the Department of Psychiatry at Texas A&M Health Science Center College of Medicine, who was interviewed for the article, noted that the effects shown might be due to the release of oxytocin that MDMA causes, and that it might be better to simply dose PTSD patients with oxytocin.

The study was paid for by Multidisciplinary Association for Psychedelic Studies (MAPS).

See two earlier posts on the use of Ecstasy to treat PTSD:

Ecstasy Helps PTSD Treatment

Ecstasy Could Be PTSD Breakthrough

Oxytocin for Chronic Headache?

with Jasvir Singh

Oxytocin therapy may help  patients with chronic headaches, which is 3 percent of the U.S. population. There is no current effective treatment, so this would be a real breakthrough.

Trigemina Inc.  is a start-up company that is examining new opportunities for treating pain. One of these new opportunities is intranasal oxytocin. They are conducting a study  comparing intranasal oxytocin with placebo for treating debilitating, recurrent headaches.

There's just a bit more information in their press release

With studies underway looking at oxytocin to treat social anxiety disorder, autism, schizophrenia and autism, it certainly seems that oxytocin could be a wonder drug.

Oxytocin Could Be Weaponized, Expert Warns

Malcolm Dando's op-ed piece in Nature this week has gotten attention for his warning that biologists seldom understand the military implications of their research.

Analee Newitz on io9 quotes Dando using oxytocin sprays as an example of this:

Some companies are already marketing oxytocin on the back of studies showing that a nasal squirt of the hormone increases trust in humans. Even though the effectiveness of commercial sprays is doubtful, such research opens up the possibility of a drug that could be used to manipulate people's emotions in a military context. Discussions with more than 2,000 practising life scientists in 13 countries over the past few years have taught me that few have considered such possible uses of their work.

Red Orbit has another article about Dando's op-ed.

In writing my book about oxytocin's role in human emotion, I spoke to most of the top oxytocin researchers. They were well aware about people's self-experimentation. Sue Carter of the University of Illinois said at that their clinic, which treats kids with autism spectrum disorder, many parents told her they'd tried over-the-counter oxytocin sprays, or else asked about it.

Awareness of the issue of self-dosing and entrepreneurial companies using biology research for profit and/or military weapons development isn't much use, of course. Biologists have to do the basic experimentation; the best way they can protect their research is to patent whatever they can.

Oxytocin Hype and Backlash

I read New York magazine, and they have a regular item called something like "We ride the shifting curve of expectations." They chart where cultural events like books and films fall on the cycle from hype to backlash against the hype.

In the past couple of weeks, I've watched oxytocin follow a similar path. Because I look at every news article and study regarding oxytocin, as well as all the blog posts discovered by a couple blog search tools, I can see what studies spark news coverage, and what kinds of memes spread.

Oxytocin hype has been rampant for the past three weeks. As far as I can tell, it got started with study led by Thomas Baumgartner at the University of Zurich showing that inhaling oxytocin increased people's willingness to trust other players in an economic game, even after they'd been shafted once. This is the team at the University of Zurich that did the very first human oxytocin studies showing that oxytocin increased trust. (Read my blog post about the previous research here.)

In this study, "We find that subjects in the oxytocin group show no change in their trusting behavior after they learned that their trust had been breached several times while subjects receiving placebo decrease their trust."

Some genius copywriter translated this to, "Oxytocin Makes Us Trust after Betrayal," leading to a spate of stories about how "Spray Said to Turn People into Pushovers." And it also led to my appearance on the Fox Morning With Mike and Juliet show.

Not to be outdone, Markus Heinrichs, who leads the Zurich team, talked to reporters (but did not, I believe, actually publish anything new) about their work using oxytocin to treat social anxiety disorder, which has been under way for several years. That sparked another news rush.

They mostly followed the lines of this one, Scientists Find Childbirth Wonder Drug That Can Cure Shyness, kindly sent to me by Blaine. Is that a sexy headline or what? The articles finally recognized the work of Paul Zak, who has been giving oxytocin to humans for several years, without a lot of notice. I didn't blog all these articles, partly because they were so ubiquitous and partly because I was finishing the manuscript of my book, ta daaa!

Already, though, oxytocin hype has faded into the final cycle, backlash. In part this is simply because news reporters have to come up with new stories every day. Once you've written a story hyping the prospects of oxytocin -- or worse, when your competitors have and you haven't -- where do you go from there but to write another one decrying the first. Ideally, at least in the olden days when I started my career as a journalist, you were supposed to find naysayers to quote in every story. But that was then.

The Neurocritic links to an ABC News story now insisting, "Researchers Balk at Media Reports Hyping 'Love Drug' Hormone's Effects."

And Paul Zanucci of American Sentinel calls it, "The Oxytocin Nightmare to Come -- Drugging America." I agree with his premise, and have been saying for a while that oxytocin will be the next Prozac. That is, while oxytocin-based or oxytocin-like drugs will be developed for social anxiety disorder and ASD, it will eventually be prescribed for much milder psychological situations. Zanucci writes,

Every time someone blows their nose, there’s a new prescription written for nasal sprays and antihistamines even though products like Zyrtec can now be bought OTC in generic form.  Every time someone is stressed out by work, another prescription is written for anti-anxiety medication.  People are happy as clams to pay $30 to $50 for the latest in pharmaceutical living, not considering that their insurance is paying another $300 behind the scenes and that their cost for insurance is going to go up again next year.

Nevertheless, I think calling this a nightmare is way too anti-hyperbolic. I'd much rather we revise labor, birth and parenting practices to allow individuals to form a healthy oxytocin response naturally. But our society is probably too sick and mechanistic for that. In which case, a nation of loved-out citizens who inhale oxytocin several times a day would be preferable to our extant war-mongering, paranoid, crabby society.

At any rate, I think we can shortly expect oxytocin to fall off the news cycle for at least a few months.

Get Oxytocin Safely in Clinical Trials

In response to a recent comment, I took a new look at the database of clinical trials that are recruiting subjects for oxytocin studies, available at ClinicalTrials.gov. I see that Daniel Feifel of the University of California San Diego is recruiting subjects for two studies to test oxytocin on symptoms of schizophrenia.

And it looks like Evdokia Anagnostou of Eric Hollander's Mt. Sinai team is recruiting for a couple of studies of adults with ASD, although it's hard to tell if the database is current.

Meanwhile, the National Institutes of Mental Health is recruiting for a study of people without psychiatric diagnoses on "Identifying the Role of Oxytocin and Vasopressin in the Functioning of Neurocognitive Systems Involved in Mood Disorders."

We can expect more and more of these as #1 scientists strive to learn more and more about the neurochemical basis of emotion and #2 pharm companies look for new classes of drugs they can sell.