How do side effects influence perceived drug effectiveness?

At the initial study session participants will meet with the researcher (Masters student) who will use a scripted cover story to mask the actual psychological investigation of the study. Deception is necessary to ensure the validity and integrity of the study. If participants were aware of the true psychological aims of the study to investigate how side effects impact placebo-nocebo responses, this may influence their own expectations and responses to the medication. The cover story is based on research that increasing levels of oxygen in the brain can improve memory formation in healthy young adults (Moss & Scholey, 1996). Following the scripted introduction to the research session written informed consent will be collected. Baseline and follow up questionnaires will gather information including demographic, mood state, perceived sensitivity to medications, symptom reports, standardized memory function tasks, lung function, breathing sensations, and following administration of a nasal spray participants' perceptions of the efficacy of the medication on memory function and breathing status will be collected. Participants will be told they will be randomized to take either a nasal spray medication containing the active ingredient Salbutamol (a bronchodilator) in a pediatric equivalent dose, or a control medication not containing the active ingredient. As a cover story, participants will also be told that we believe by improving lung function more oxygen will be delivered to the circulatory system which will result in elevated oxygen levels in the brain, with the flow on effect of improving memory formation. In order to maintain the cover story participants will perform two standardized memory function tasks and a spirometer lung function test before and after taking the nasal spray medication. In reality all nasal sprays in the experimental groups will contain graduated dilutions of capsaicin (originally 3% in sesame oil) as the active placebo ingredient in order to induce local side effects. The nasal spray solutions are mixed in a university bio-engineering laboratory by a senior technician, and tested with a focus group representative of the target population. Participants will be randomized to one only of the four intervention groups and will take one dose only of either nil, low, medium or high (relative to each other) doses of the solution containing capsaicin. The doses of 3% capsaicin in sesame oil (microlitre) and saline (ml) are diluted as follows: High group - 0.0165 microlitre/1ml Medium group - 0.0041250 microlitre/1ml Low group - 0.00103120 microlitre/1ml Nil - saline only Treatment will involve participants self-administering one dose of the solution as one spray only into each nostril. Each spray of the applicator will deliver 0.01ml of solution. Participants will also be told the spray may also cause minor side effects including a prickling sensation in the nose, elevated heart rate, headache, tremor, feeling jittery, dry mouth, dry or irritated nose and throat, chest discomfort, nausea, drowsiness, dizziness and light headedness. Participants will be asked to gently inhale the medication and to sit quietly for 15 minutes in order for the medication to take effect. After this resting period follow up measures and tests will be administered in the same order as prior to administration of the nasal spray. Following the research session participants will be told any medication effect will dissipate within two hours. The active placebo contains graduated dilutions of 3% capsaicin (in sesasme oil) in saline. While high concentrations of capsaicin have an analgesic effect, the concentrations we deliver are minimal and not harmful. Th solutions will cause a slight prickling sensation in the nasal pathway. A previous study of 144 participants has shown that a similar formula is well tolerated and causes no adverse effects aside from mild prickling sensations (Rief & Glombiewski, 2012). In our own recent study looking at the effect of price on place and nocebo effects conducted last year, we found at the dose similar to that used in the high side effect group in this study that the spray caused transient nasal prickling and irritated nose symptom reports for a few minutes following the nasal spray administration. No other adverse events were reported. Following the analysis of results, all participants will be emailed a debriefing sheet with full disclosure of the actual study aims, and an offer to meet with the researchers to discuss any concerns a participant may have regarding the study protocol.