title: FAAH selectively influences placebo effects.
abstract: 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 D(2/3) 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.
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Peciña
authors.affiliation: Research Institute on Health Sciences-IUNICS, Palma de Mallorca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Jauand
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hodgkinson
authors.affiliation: School of Dentistry, University of Maryland, Baltimore, MD, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Stohler
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Goldman
authors.affiliation: 1] Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA [2] Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA [3] Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000339:Affect; D000581:Amidohydrolases / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D010147:Pain Measurement; D015990:Placebo Effect; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017450:Receptors, Opioid, mu; D000099252:Fatty Acid Amide Hydrolases; C581293:DRD2 protein, human
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