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Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors


Placebo analgesia is mediated by both opioid and nonopioid mechanisms, but so far nothing is known about the nonopioid component. Here we show that the specific CB1 cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (rimonabant or SR141716) blocks nonopioid placebo analgesic responses but has no effect on opioid placebo responses. These findings suggest that the endocannabinoid system has a pivotal role in placebo analgesia in some circumstances when the opioid system is not involved.

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Figure 1: The CB1 cannabinoid receptor antagonist rimonabant blocks nonopioid placebo analgesia.


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This work was supported by grants from Istituto San Paolo di Torino and Regione Piemonte (Turin, Italy) and from the Volkswagen Foundation (Hannover, Germany).

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F.B. planned and conducted the experiments, analyzed the data and wrote the manuscript. M.A. and R.R. analyzed the data and contributed to the writing of the manuscript. C.B. conducted the experiments and contributed to the writing of the manuscript.

Corresponding author

Correspondence to Fabrizio Benedetti.

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The authors declare no competing financial interests.

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Supplementary Figure 1, Supplementary Tables 1–4 and Supplementary Methods (PDF 214 kb)

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Benedetti, F., Amanzio, M., Rosato, R. et al. Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nat Med 17, 1228–1230 (2011).

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