HealthDay News — Intranasal application of oxytocin, a hormone released by the pituitary gland during sex, childbirth and other instances of social bonding, enhanced the painkilling effect of placebo in a clinical trial, researchers have found.

Men who were exposed to painful heat stimuli on their forearms rated the analgesic effect of a placebo cream greater after they received intranasal oxytocin compared with a snorted saline solution, at a difference of 5.76 points out of 60 (95% CI 0.59-10.93, P=0.03), according to Ulrike Bingel, MD, of the department of neurology at the University Hospital of Essen in Germany, and colleagues.

“To our knowledge, our study provides the first experimental evidence that placebo responses can be pharmacologically enhanced by the application of intranasal oxytocin,” they reported in Journal of the American Medical Association.

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They hypothesize the hormone may have increased the placebo response by making the instructions the physician provided patients more believable, and also by reducing anxiety and stress. 

Earlier research has associated the release of oxytocin, also known as the “love hormone,” with psychological traits including trust, empathy and socialization.

In the current study, Bingel and colleagues randomly assigned 75 healthy male volunteers to receive 40 IU of intranasal oxytocin (N=37) or saline solution. After 45 minutes, two identical inert ointments were applied to each of the participant’s forearms. One cream was described as an anesthetic, whereas the other was described as an inert control. Participants were also told the cream would take effect in 15 minutes.

A calibration procedure identified the individual stimulation intensity at which a 20-second painful heat stimulus was perceived as a 60 on a 100-point visual analogue scale (VAS, 0=no pain, 100=unbearable pain). Heat was then applied 10 times at the 60-point VAS intensity for 20 seconds at a time in one-minute cycles. Participants were asked to rate the pain on each forearm after each application.

Pain ratings for the placebo site were significantly lower compared with the control site across both treatment groups, despite identical thermal stimulation, the researchers found.

For the “control” cream, the mean pain rating was 59.96 in the oxytocin group and 58.31 in the saline group. For the “active” cream, pain ratings were 47.11 for the oxytocin group versus 51.23 in the saline group.

In the oxytocin group, the placebo analgesic response was significantly higher compared to the saline group. The placebo response was calculated by subtracting the “active” cream rating from the “control” cream rating, which came out to 12.84 points in the oxytocin group (95% CI 8.67-17.01) and 7.08 points in the saline group (95% CI 3.84-10.31).

There were no significant differences between the groups related to temperature levels needed to induce a VAS score of 60 (46° C [115° F] in both groups) or in anxiety or depression levels at baseline.

“Further studies are needed to replicate our findings in larger clinical populations, identify the underlying mechanisms, and explore moderating variables such as sex or aspects of patient-physician communication,” the researchers concluded.


  1. Kessner S et al. JAMA 2013; 310: 1733-1734.