There is evidence that the placebo response accounts for a substantial proportion of symptom improvement in pharmacological treatments. Concerning insomnia drug trials, there is a lack of studies addressing the proportion of the placebo response on drug response and its underlying mechanisms. Therefore this dissertation had two main purposes. First, to compare treatment efficacy of different drug classes addressing primary insomnia and their impact on subjective and objective outcomes by conducting a meta-analysis based on 31 randomized controlled trials (RCTs) including 3820 patients (study 1). Additionally symptom improvement in the placebo control condition was assessed for 32 RCTs including 3969 patients to compare its efficacy on objective versus subjective outcome measures, and to determine its proportion in the response to pharmacological treatments (study 2). Effect size estimates for the total sample of pooled drug classes suggest a small to moderate effect for subjective as well as for objective outcomes. Our results indicate that 63.56% of the drug responses are achieved even in the placebo groups. Second, since conditioning is supposed to be a potential mechanism of the placebo response we applied a paradigm of behavioral conditioning to 39 healthy participants using effects on sleep architecture as the objective outcome (study 3). In that proof of principle study we were unable to demonstrate that REM-sleep suppression triggered by amitriptyline is simply accessible to conditioning and could be evoked through a placebo pill intake in an evocation phase. Instead of the expected REM-sleep suppression in the evocation night, we observed more REM-sleep in the amitriptyline group. This result indicates that while simple conditioning does not seem to explain these effects, more complex influences (e.g. conditioning of the drug-antagonistic response or rebound) could be involved.