Endogenous opioid and cannabinoid systems are thought to act synergistically regulating antinociceptive and reward mechanisms. To further understand the human implications of the interaction between these two systems, we investigated the role of the common, functional missense variant Pro129Thr of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, on psychophysical and neurotransmitter (dopaminergic, opioid) responses to pain and placebo-induced analgesia in humans. FAAH Pro129/Pro129 homozygotes, who constitute nearly half of the population, reported higher placebo analgesia and more positive affective states immediately and 24 h after placebo administration; no effects on pain report in the absence of placebo were observed. Pro129/Pro129 homozygotes also showed greater placebo-induced μ-opioid, but not D2/3 dopaminergic, enhancements in neurotransmission in regions known involved in placebo effects. These results show that a common genetic variation affecting the function of the cannabinoid system is serving as a probe to demonstrate the involvement of cannabinoid and opioid transmitters on the formation of placebo effects.
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We wish to acknowledge the nuclear medicine technologists of the PET Center at the University of Michigan for the assistance in PET data acquisition and reconstruction. Funding: work was supported by R01 DA 022520, R01 DA027494 and the Phil F Jenkins Foundation (JKZ). MMJ was supported by the Spanish Ministry of Education (MMJ: AP2008–03742).
The authors declare no conflict of interest.
JKZ, CSS and DG were responsible for the study design and procured the study funding; JKZ and CSS collected data; MP, MMJ and CH analyzed the data; MP and JKZ wrote the manuscript.
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Peciña, M., Martínez-Jauand, M., Hodgkinson, C. et al. FAAH selectively influences placebo effects. Mol Psychiatry 19, 385–391 (2014). https://doi.org/10.1038/mp.2013.124
- placebo effect
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