Trial reportNeuroimmunomodulation2026
Experimental Approach to Inducing Anti-Histaminergic Placebo Effects: A Randomized Controlled Trial in Healthy Volunteers.
Trial report in Neuroimmunomodulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAllergies are an increasingly widespread health problem and prior evidence suggests that psychological factors are involved in their occurrence and alleviation. This study aimed to investigate how placebo treatment can reduce type-I allergic symptoms in a skin prick test in healthy volunteers.
methodsHealthy volunteers of all genders were included in the study (N = 88) and were randomized into three groups: (i) a classically conditioned group receiving the anti-histaminergic drug cetirizine as unconditioned stimulus (US) and a novel gustatory stimulus as conditioned stimulus (CS), (ii) a context-control group receiving cetirizine (US) and water as CS and (iii) an open-label placebo group. In the spirit of the ethical application of placebo, participants were not blinded with regard to the study question. Histamine skin prick tests were conducted at baseline, after five acquisition trials, before evocation, as well as after three and five evocation trials. Self-rated itch and wheal size measurements served as outcome parameters.
resultsItch was significantly reduced after medication and (open) placebo intake. Wheal size was only reduced significantly after medication intake during acquisition. After 9 days of washout, itch ratings were lower in participants who had received open-label placebo compared to those who had initially received cetirizine. During the evocation week, the decline in wheal size did not reach statistical significance and there was no significant differential effect of group allocation. Reported expectations of symptom relief at the last visit correlated positively with reductions of wheal size, but results were substantially influenced by outliers. Expectations of relief could partially be explained by participants' prior experiences and group allocation.
conclusionParticipants of all groups experienced a reduction in itch, while wheal size was only reduced in those participants with high expectations. These expectation effects align with prior research but should be carefully tested in future studies. Taken together, these results support the theory of differing mechanisms between patients with lived experience and healthy participants. Future studies should investigate the underlying neuropsychological mechanisms of expectation-induced anti-histaminergic effects.
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