Conditioning cortisol in humans: design and pilot study of a randomized controlled trial.

BACKGROUND: Conditioning of physiological responses can be achieved by repeatedly pairing a previously neutral conditioned stimulus with the administration of a pharmacologically salient unconditioned stimulus. This type of conditioning has been effective for specific immune and endocrine responses, but results with regard to conditioning of cortisol, a key stress-regulatory parameter, are currently unclear. This paper describes a pharmacological conditioning design, optimized for the examination of effects of cortisol conditioning under both basal conditions and in response to stress. METHODS: A double-blind randomized controlled conditioning paradigm aimed at conditioning of cortisol is conducted in 48 healthy female volunteers. During the acquisition phase, a gustatory stimulus (conditioned stimulus) is paired with hydrocortisone (100 mg, capsulated, unconditioned stimulus) three times before being administered together with placebo during three evocation sessions. To investigate possible effects of cortisol conditioning in response to stress, participants are exposed to the Trier Social Stress Test during the third evocation session. Primary outcome measure of this study is the mean area under the curve of salivary cortisol during the first two evocation sessions. As secondary outcomes, self-reported affect and stress as well as alpha-amylase are investigated. A pilot study was conducted to ensure that this design is feasible to be used in a larger study. DISCUSSION: This study design provides an innovative opportunity to examine the conditioning of cortisol under basal conditions and in response to stress. Also, the possible effect of cortisol conditioning on secondary outcomes of self-reported affect and alpha-amylase can be investigated. If cortisol could successfully be conditioned, this would be of conceptual relevance, showing that hypothalamic pituitary adrenal (HPA) axis regulation can be influenced by associative learning processes. Eventually, this could also have important clinical implications for understanding and treating stress-related disorders in which HPA axis dysregulation might play a role. TRIAL REGISTRATION: Nederlands Trial Register, NTR4651. Registered on 29 July 2014.

[Placebo and nocebo effects on itch : Methodological and clinical implications]. / Placebo- und Noceboeffekte bei Pruritus : Methodologische und klinische Implikationen.

Patients often experience positive (placebo) or negative (nocebo) treatment effects due to the positive or negative expectations they have about the treatment. Placebo and nocebo effects have only relatively recently received attention for itch. Experimental studies indicate that, in line with research in other areas, such as pain, learning via verbal suggestion and conditioning plays a key role in placebo and nocebo effects on itch. Results on contagious itch emphasize the role of observational learning and suggest that itch sensations might be particularly susceptible to suggestion and therefore placebo and nocebo effects. Substantial itch reductions in the placebo arms of clinical trials suggest that placebo effects are also important for clinical practice. In this article, an overview is given of how placebo and nocebo effects on itch can optimally be used in research and for the treatment of itch.

Expectations about the effectiveness of pain- and itch-relieving medication administered via different routes.

BACKGROUND: Placebo effects on pain have been found to vary in size for different routes of medication administration (e.g. oral vs. injection). This has important implications for both clinical research and practice. To enhance our understanding of these differential placebo effects, research on the underlying expectations about multiple routes and symptoms other than pain is vital. METHODS: A cross-sectional, Internet-based survey was conducted in a representative sample of the Dutch population (n = 508). Respondents rated the expected effectiveness of pain- and itch-relieving medication in six forms, representing oral, injection and topical routes of administration. RESULTS: Injected medication was expected to be most effective for relieving pain, and topical medication for relieving itch. Furthermore, exploratory analyses showed that injections were expected to have the most rapid onset and long-lasting effects, and to be most frightening and expensive, while topical medication was expected to be the safest and the easiest to use, and oral medication was expected to have the most side effects. Higher expected effectiveness was moderately associated with expectations of more rapid onset and long-lasting effects, and better safety and ease of use. Associations of expected effectiveness with respondent characteristics (e.g. medication use and personality characteristics) were statistically small or nonsignificant. CONCLUSIONS: Expected effectiveness of medication differed depending on route of administration and targeted symptom. These findings have important implications for the design and interpretation of clinical trials and suggest that medication effects might be enhanced by prescribing medicine via the route that patients expect to be most effective for their complaint. SIGNIFICANCE: Differences in the expected effectiveness of medication depend on the route of administration (oral, injection, topical) and targeted symptom (pain, itch). These findings have important implications for clinical practice and the design and interpretation of clinical trials.