Inducing placebo respiratory depressant responses in humans via opioid receptors

Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that place bos may also produce respiratory depressant responses, a typical side-effec t of narcotics, when a subject had a prior experience of respiratory depres sion in the course of narcotic treatment, in the present study, we report t hat the placebo respiratory depression can be induced after repeated admini strations of the partial opioid agonist buprenorphine. The placebo respirat ory depressant effect that resulted from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone, indicating that it was mediated by endogenous opioids. These findings show that placebos act, via the activation of opioid receptors, not only on pain mechanisms but on the respiratory centres as well, thus mimicking a typical side-effect of narcot ics. In addition, the experimental procedure we used did not produce any ex pectation of respiratory depression and, similarly, the subjects did not no tice any sign of respiratory discomfort. Thus, the placebo respiratory depr ession elicited in the present study cannot be explained on the basis of co gnitive or motivational mechanisms. Rather, it appears to be a sequence eff ect due to learning, thus suggesting a conditioning mechanism mediated by e ndogenous opioids.