Evidence from pain research shows that the effectiveness of active pharmacological treatments can be enhanced by placebo effects. The "open drug administration" is superior to hidden drug administration. In a RCT we aimed to show that the targeted use of placebo effects increases the efficacy of an antihistamine (dimetindene) infusion in participants with atopic dermatitis. We openly infused dimetindene (drug) in full sight with information (intervention group 1: OPEN-DRUG+INST), openly infused drug with an additional classical conditioning learning experience (intervention group 2: OPEN-DRUG+INST+COND) or infused drug without any information or sight, i.e., hidden administration (control group 1: HIDDEN-DRUG). Control group 2 received a placebo infusion (saline) declared as dimetindene and also experienced the conditioning experience (PLAC+INST+COND). Itch was experimentally induced with histamine via a skin prick test. Outcome was assessed at the subjective (primary endpoint: experimental itch intensity, numeric rating scale), and objective level (secondary endpoint: wheal size, mm ). Experimental-induced itch intensity decreased in all groups but at different rates (p<0.001). The groups with the open administration, whether it was dimetindene or placebo, had significantly stronger reductions in itch compared to the HIDDEN-DRUG group (OPEN-DRUG+INST+COND: p<0.001; OPEN-DRUG+INST: p=0.009; PLAC+INST+COND: p<0.001). Additional drug conditioning mediated via expectation led to a stronger reduction of itching (p=0.001). Results on wheal size were similar (p=0.048), however, no significant difference between the HIDDEN-DRUG group and the PLAC+INST+COND group (p=0.967) was found. We conclude that specifically generated targeted placebo effects can significantly increase the action of a drug (dimetindene) and should be used in clinical practice.