Opioid-Mediated Placebo Responses Boost Pain Endurance and Physical Performance: Is It Doping in Sport Competitions?

Abstract

The neurobiological investigation of the placebo effect has shown that placebos can activate the endogenous opioid systems in some conditions. So far, the impact of this finding has been within the context of the clinical setting. Here we present an experiment that simulates a sport competition, a situation in which opioids are considered to be illegal drugs. After repeated administrations of morphine in the precompetition training phase, its replacement with a placebo on the day of competition induced an opioid-mediated increase of pain endurance and physical performance, although no illegal drug was administered. The placebo analgesic responses were obtained after two morphine administrations that were separated as long as 1 week from each other. These long time intervals indicate that the pharmacological conditioning procedure has long-lasting effects and that opioid-mediated placebo responses may have practical implications and applications. For example, in the context of the present sport simulation, athletes can be preconditioned with morphine and then a placebo can be given just before competition, thus avoiding administration of the illegal drug on the competition day. However, these morphine-like effects of placebos raise the important question whether opioid-mediated placebo responses are ethically acceptable in sport competitions or whether they have to be considered a doping procedure in all respects.

Placebo-Induced Changes in Excitatory and Inhibitory Corticospinal Circuits during Motor Performance

“…Existing evidence about the neural underpinnings of placebo modulations in motor performance derives from studies in Parkinson's disease (de la Fuente-Fernández et al, 2001;Pollo et al, 2002;Benedetti et al, 2004;Lidstone et al, 2010). Our study appears to represent the first direct demonstration that placebo can rapidly modulate the excitability of the corticospinal system in physiological conditions.…”

“…This effect is based on the recipient's belief about the efficacy of the applied treatment and derives from expectation and learning processes (Montgomery and Kirsch, 1997;Benedetti et al, 2003). Placebo effects can be obtained not only in clinical contexts to alleviate pain or reduce motor symptoms in Parkinson's disease (de la Fuente-Fernández et al, 2001;Benedetti et al, 2003;Benedetti et al, 2004;Mercado et al, 2006;Lidstone et al, 2010;Keitel et al, 2013), but also in healthy and physiological situations to modulate motor performance (Clark et al, 2000;Beedie and Foad, 2009). For instance, well-trained cyclists who thought to have taken caffeine, increased their output in the final test compared with baseline, even though they received a placebo (Beedie et al, 2006).…”

Placebo-mediated, Naloxone-sensitive suggestibility of short-term memory performance

“…Placebo-mediated changes in opioid-signalling were also shown in relation to muscular endurance (Benedetti, Pollo, and Colloca, 2007) and the regulation of emotions (Eippert, Bingel, Schoell, Yacubian, and Buchel, 2008;Petrovic, Dietrich, Fransson, Andersson, Carlsson, and Ingvar, 2005).…”

“…Over the last three decades, the role of opioid-signalling for placebo-mediated suggestion has been firmly established in diverse contexts ranging from pain to motor and mental disorders and emotions (Benedetti, Pollo, and Colloca, 2007;Eippert et al, 2008;Kennedy et al, 2006;Liberzon et al, 2007;Oken, 2008;Petrovic et al, 2005).…”

The use of genes for performance enhancement: doping or therapy?

“…The expressed molecules are neuropeptides that bind to opioid receptors, promoting analgesic effects and, therefore, pain relief. In order to increase the pain threshold, copies of these genes might be inserted, with expression being targeted to the nervous system (44). This promising possibility has been preliminarily studied using animal models (45).…”