Vasopressin Boosts Placebo Analgesic Effects in Women: A Randomized Trial



      Social cues and interpersonal interactions strongly contribute to evoke placebo effects that are pervasive in medicine and depend upon the activation of endogenous modulatory systems. Here, we explore the possibility to boost placebo effects by targeting pharmacologically the vasopressin system, characterized by a sexually dimorphic response and involved in the regulation of human and nonhuman social behaviors.


      We enrolled 109 healthy participants and studied the effects of intranasal administration of an arginine vasopressin 1A and 1B receptor agonist against 1) no treatment, 2) oxytocin, and 3) saline in a randomized, placebo-controlled, double-blind, parallel design trial using a well-established model of placebo analgesia while controlling for sex differences.


      Vasopressin agonists boosted placebo effects in women but had no effect in men. The effects of vasopressin on expectancy-induced analgesia were significantly larger than those observed in the no-treatment (p < .004), oxytocin (p < .001), and saline (p < .015) groups. Moreover, women with lower dispositional anxiety and cortisol levels showed the largest vasopressin-induced modulation of placebo effects, suggesting a moderating interplay between pre-existing psychological factors and treatment cortisol changes.


      This is the first study that demonstrates that arginine vasopressin boosts placebo effects and that the effect of vasopressin depends upon a significant sex by treatment interaction. These findings are novel and might open up new avenues for clinically relevant research due to the therapeutic potentials of vasopressin as well as the possibility to systematically control for influences of placebo responses in clinical trials.


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      • Sex, Drugs, and the Neurobiology of the Placebo Effect
        Biological PsychiatryVol. 79Issue 10
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          If you have ever been engaged in clinical research, you may have had this experience: the first six patients on the open trial of a new compound respond brilliantly, but then the next six patients completely fail to respond, shattering your fantasies of discovering a therapeutic cure. Or perhaps you have observed that initial published findings demonstrating the efficacy of the next novel treatment are not subsequently replicated—another victim of the dreaded placebo response! In this issue of Biological Psychiatry, Colloca et al.
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