Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors

• Published in: Nature medicine Vol. 17; no. 10; pp. 1228 - 1230
• Main Authors: Benedetti, Fabrizio, Amanzio, Martina, Rosato, Rosalba, Blanchard, Catherine
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2011; Nature Publishing Group
• Subjects: 631/378/2620/410; 631/92/436/108; Analgesia; Analgesics; Analgesics, Non-Narcotic - metabolism; Biomedical and Life Sciences; Biomedical research; Biomedicine; brief-communication; Cancer Research; Chromatography, Liquid; Humans; Infectious Diseases; Mass Spectrometry; Metabolic Diseases; Molecular Medicine; Molecular Structure; Neurobiology; Neurosciences; Pain Threshold - physiology; Physiological aspects; Piperidines - chemistry; Piperidines - pharmacokinetics; Piperidines - pharmacology; Placebo Effect; Pyrazoles - chemistry; Pyrazoles - pharmacokinetics; Pyrazoles - pharmacology; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; Italy
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.2435

The placebo response involves a perceived effect of a drug that was not really received by the subject. Fabrizio Benedetti and colleagues demonstrate that the placebo response to NSAIDs in reducing pain is mediated by the endocannabinoid system in humans. 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.