Are all placebo effects equal? Placebo pills, sham acupuncture, cue conditioning and their association.

Jian Kong,Randy L Gollub,Mark Vangel,Jordan W Smoller,Rosa Spaeth,Amanda Cook,Ted J Kaptchuk,Irving Kirsch,Brian Claggett,Sam Eldabe

doi:10.1371/journal.pone.0067485

Abstract

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.

Highlights

Placebo treatments and healing rituals have been used since the beginning of human history [1,2]
Post hoc analysis among the 4 experimental conditions showed that both genuine acupuncture and placebo pills produced significant post-treatment pain threshold increases (+0.79, 95% CI:[+0.25, +1.33], p = 0.004; and +0.74,95%CI: [+0.19, +0.1.29], p = 0.008 respectively) relative to rest control
We investigated the analgesic effects produced by placebo Tylenol, sham acupuncture, genuine acupuncture and a rest control condition, as well as the association between the effects of verbal suggestion on evoked placebo treatments, electroacupuncture, and conditioning cue effects

Summary

Introduction

Placebo treatments and healing rituals have been used since the beginning of human history [1,2]. Medical rituals, have equivalent effects remains unknown This raises the question: Do patients who respond to one placebo intervention tend to respond to other placebo interventions?. In a previous clinical trial [5] of chronic pain patients, we found that sham acupuncture reduced pain significantly more over time than did placebo pills, while placebo pills offered more short-term benefits of improving pain-disturbed sleep over sham acupuncture. It showed that not all placebo treatments are equal. This clinical trial involved multiple, concurrent experimental arms and was not designed to answer the question of whether individuals who tend to respond to sham acupuncture tend to respond to placebo pills

Methods

Results

Conclusion