HOW DO THEY ADD UP? THE INTERACTION BETWEEN THE PLACEBO AND TREATMENT EFFECT : A SYSTEMATIC REVIEW.

Aim: The placebo effect and the specific effect are often thought to add up (additive model). Whether this is true or whether there is an interaction between the two, can modify the external validity of a trial. This assumption of additivity was tested by Kleijnen et al. in 1994 but the data produced since then has not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held. Methods: We searched Medline and Psychinfo up to 10/01/2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in BPD with analysis of variance or covariance. Results: 30 studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity). Conclusion: Evidence of additivity between placebo and specific features of treatments was rare in our sample. For ailments that are placebo-responsive, pragmatic trials should be preferred to increase their external validity.

The impacts of caffeine administration, expectancies, and related stimuli on coffee craving, withdrawal, and self-administration

Background: Caffeine is the most commonly consumed psychoactive substance, yet its potential reinforcing properties have been understudied. Aims: This study examined the impact of caffeine administration and expectancy on coffee-related craving, withdrawal, and cue reactivity via a balanced-placebo design. Methods: Following 18-h caffeine abstinence, 65 daily coffee consumers (54% male) received either caffeine-containing (100 mg) or placebo gum, along with either accurate or inaccurate information regarding the gum’s caffeine content. Participants were exposed to neutral and coffee-related stimuli using different sensory modalities (visual and combined auditory/olfactory). Craving, withdrawal, and heart rate were assessed at baseline and after each cue presentation. Following the cue-reactivity assessments, participants were provided with an opportunity to self-administer units of coffee. Results: Caffeine expectancy was associated with reduced subjective withdrawal 30 min following the gum administration but was not significantly impacted by actual caffeine administration. The presentation of coffee-related cues was found to increase self-reported craving and heart rate, regardless of the expectation that caffeine had been administered. Visual, but not auditory/olfactory, cue reactivity appeared blunted when participants received a prior dose of caffeine. Prior caffeine ingestion also reduced the probability of subsequent coffee self-administration. Conclusion: To our knowledge, this is the first examination of the impact of caffeine administration and expectancy on cue-elicited coffee craving and coffee consumption. Although there was some evidence that caffeine expectancy and administration were found to impact subjective withdrawal and self-administration respectively, neither was found to exert strong consistent effects on cue reactivity.

Improved 1000-m Running Performance and Pacing Strategy With Caffeine and Placebo: A Balanced Placebo Design Study

Purpose: To investigate the placebo effect of caffeine on pacing strategy and performance over 1000-m running time trials using a balanced placebo design. Methods: Eleven well-trained male middle-distance athletes performed seven 1000-m time trials (1 familiarization, 2 baseline, and 4 experimental). Experimental trials consisted of the administration of 4 randomized treatments: informed caffeine/received caffeine, informed caffeine/received placebo, informed placebo/received caffeine, and informed placebo/received placebo. Split times were recorded at 200, 400, 600, 800, and 1000 m, and peak heart rate and rating of perceived exertion were recorded at the completion of the trial. Results: Relative to baseline, participants ran faster during informed caffeine/received caffeine (d = 0.42) and informed caffeine/received placebo (d = 0.43). These changes were associated with an increased pace during the first half of the trial. No differences were shown in pacing or performance between baseline and the informed placebo/received caffeine (d = 0.21) and informed placebo/received placebo (d = 0.10). No differences were reported between treatments for peak heart rate (η2 = .084) and rating of perceived exertion (η2 = .009). Conclusions: The results indicate that the effect of believing to have ingested caffeine improved performance to the same magnitude as actually receiving caffeine. These improvements were associated with an increase in pace during the first half of the time trial.