One Molecule for Love, Trust, and Morality?

Separating Hype from Hope in the Oxytocin Research Explosion
by Brenda Patoine

April, 2013

BRIEFING PAPER

Ann Whitman                                                                                  
(212) 223-4040
awhitman@dana.org
     

A nasal spray that will make men more faithful, increase generosity toward others, even boost teamwork in athletes? If one is to believe all the recent headlines around oxytocin, a hormone produced in the brain and variously dubbed the “love chemical,” the “trust hormone,” and, in a new best-selling book, the “moral molecule,” one might think scientists have discovered the panacea to everything from adulterous spouses to serious psychiatric disorders. Not to mention the answer to a used-car salesman’s dream.

The “world’s first trust-enhancing spray,” which purportedly contains oxytocin, is sold on a website that greets visitors with a sultry female voice promising increased sales, more love, and greater accomplishments–all for under $30. It’s this kind of snake-oil salesmanship that worries scientists like Dana Alliance member Martha Farah, Ph.D., a neuroethicist and director of the Center for Neuroscience & Society at the University of Pennsylvania, because it takes nuggets of bona fide science and blows them into unsupportable–even outrageous–claims. Farah, having just completed a forthcoming review paper on the ethics of oxytocin, finds the research “fascinating and slightly creepy.”

“There is a lot of hype out there,” Farah confers. But she is quick to add: “Oxytocin research does deserve the attention it’s been getting, because it represents a beautiful example of how neuroscience can illuminate important aspects of psychology and even what one might call the ‘human experience.’”

Farah is not alone in her cautious enthusiasm about oxytocin. As research on oxytocin has exploded–more than 40 clinical trials are underway investigating oxytocin as a potential treatment for a range of behavioral and psychiatric disorders–some scientists are ringing a warning bell about how little is really known about the brain chemical everyone suddenly seems to love.

“There’s a lot of ‘neurojunk’ around oxytocin,” says Dana Alliance member Patricia Churchland, Ph.D., a neurophilosopher and professor emeritus at the University of California-San Diego. “There is a misperception to the effect that by increasing levels of oxytocin, you make people more pro-social, more altruistic, nicer, kinder, and so forth. The evidence for that is really shockingly thin.”

What is clear is that oxytocin plays important roles in reproduction, childbirth, and maternal bonding, roles that have been studied extensively since the 1960’s and 1970’s. (Oxytocin was discovered and synthesized in the early 1950’s, work that earned Vincent du Vigneaud, Ph.D., the 1955 Nobel Prize in Chemistry.) In the 1990’s, research by behavioral neuroendocrinologist Sue Carter, Ph.D., now at RTI International in North Carolina, added pair bonding to the list of oxytocin roles. She and others have studied prairie voles, a rodent species that is unusual because it pairs for life. Prairie voles, it turns out, have exceedingly high levels of endogenous oxytocin compared to other vole species that are promiscuous.

These findings set off a new wave of research aimed at elucidating oxytocin’s role in mating behavior–and likely earned the neurochemical its first nickname as the “love molecule.” Then, about 10 years ago, Swiss neuroeconomist Ernst Fehr, Ph.D., published a paper in Nature showing that people who received a sniff of oxytocin nasal spray were more trusting–willing to entrust significantly more money to strangers in a role-playing game. Thus came the “trust molecule” moniker. Since then, many more researchers have dived into oxytocin research, and hundreds of studies have linked it to a wide array of pro-social and altruistic behavior–work that has helped oxytocin earn its latest alias as the “moral molecule.”

This research has also caught the attention of psychiatrists and clinicians. Nearly every psychiatric disorder impacts social behavior in one way or another, and there is a dearth of drug therapies that effectively treat these social symptoms. Now, Big Pharma is paying attention to oxytocin as well.

In 2009, Australian researchers published a small study of 16 boys with autism, finding modest improvements in social cognition tasks such as recognizing emotional states from faces. The floodgates were opened, and dozens more studies have investigated the potential of oxytocin administration for improving social symptoms in a wide array of mental disorders, with some promising though preliminary results. Clinical trials are currently underway in autism and other psychiatric conditions, including but not limited to alcoholism, substance abuse, social anxiety, dementia, and schizophrenia.

Most notably, a large, government-funded trial is now recruiting participants for a placebo-controlled, double-blinded study investigating oxytocin’s potential for the social deficits of autism spectrum disorders. Led by Linmarie Sikich, M.D., of the University of North Carolina, Chapel Hill, the trial seeks to enroll 300 children aged 3-17, who will each receive a daily dose of oxytocin nasal spray for six months.

The study, the largest one to date, is being promoted heavily by autism advocates and has, according to some reports, sent many parents of autistic children–desperate for something that might help their kids–seeking out oxytocin online in order to administer it to their children themselves, outside of a clinical trial. This is a troubling trend, say researchers.

Karen Bales, an oxytocin researcher at the University of California, Davis, is one scientist who has raised a cautionary flag. Her concern is that no one knows the effects of repeatedly dosing children with oxytocin during critical developmental years. Her own research over the last decade in prairie voles has found long-term neurobehavioral effects after even a single dose of oxytocin. Last year, she published a report[1] showing that prairie voles who were administered oxytocin daily during adolescence exhibited abnormal mating behavior as adults. Other work showed that happily mated female prairie voles became promiscuous after receiving oxytocin.

Churchland calls it the “Goldilocks phenomenon.” With oxytocin, it seems, “too little is not so great, and too much is not so great; it has to be just right. The problem is, we don’t really know what ‘just right’ is,” she says.

Churchland recently co-authored a paper[2] (with Piotr Winkielman, Ph.D.) examining research reports on oxytocin, finding troubling methodological problems with many published studies. Untangling oxytocin’s role in human social behavior is a challenge, she says, because it is released in the brain but found in many parts of the body, and because it interacts in complex, largely unknown ways with myriad other hormones and biochemicals that modulate neuronal behavior. Moreover, oxytocin is highly unstable and does not readily cross the blood-brain barrier, making accurate measurement of brain levels extremely difficult.

In human studies, investigators typically use intranasal sprays to administer oxytocin, then observe any changes in behavior in the study subjects. This methodology has been used in studies that have variously shown, for example, that after oxytocin administration people tend to be more generous and trusting in role-playing games, men will physically avoid an attractive woman who is not their romantic partner, and members of a sports team play better together. Sorting out whether those behaviors are truly caused by fluctuations in oxytocin levels in the brain is another matter entirely, and Churchland for one is not convinced by the data she’s seen.

“It’s really important to separate the hype from the science, because the real complexity that’s involved in all of the roles oxytocin seems to play has not been entirely researched yet,” she says. “There is so much we don’t know.”

Even with so many unanswered questions, it’s clear that oxytocin is an important molecule–maybe even a critical linchpin–in the complicated neurobiology of social behaviors. What’s also clear is that it doesn’t act in a vacuum, but interacts with many other hormones and peptides to exert its effects in the brain and body.

“Neurochemicals can’t do anything on their own,” Churchland says. “They depend on the right kind of neurons and the right kind of circuits to achieve certain kinds of effects. It’s not a story of oxytocin alone.”

Farah echoes this caution. As a neuroethicist she is particularly interested in the potential nonclinical “enhancement” applications of oxytocin, such as to improve child-rearing or marital stability, military interrogations, or business and workplace applications.

“It might be tempting to look at the fascinating results of oxytocin research in humans and call oxytocin ‘the moral molecule’ or the ‘love molecule,’ but if you’ve been paying attention to the last few decades of behavioral neuroscience research, you should be prepared to discover that oxytocin is just one part–albeit an important part–of the physiology of morality and love,” says Farah.

“It’s frustrating to see the science oversimplified in the media, and even by some researchers,” she adds. “You would think we’d have learned our lesson by now.”

Published April 2013


[1] Bales KL, Perkeybile AM, Conley OG, Lee MH, Guoynes CD, Downing GM, Yun CR, Solomon M, Jacob S, Mendoza SP. Chronic Intranasal Oxytocin Causes Long-Term Impairments in Partner Preference Formation in Male Prairie Voles. Biol Psychiatry. 2012 Oct 15.

[2] Churchland PS, Winkielman P. Modulating social behavior with oxytocin: How does it work? What does it mean? Hormones and Behavior 2012; 61:392-399.