Limits...
FAAH selectively influences placebo effects.

Peciña M, Martínez-Jauand M, Hodgkinson C, Stohler CS, Goldman D, Zubieta JK - Mol. Psychiatry (2013)

Bottom Line: Endogenous opioid and cannabinoid systems are thought to act synergistically regulating antinociceptive and reward mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.

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.

Show MeSH

Related in: MedlinePlus

Figures represent voxel-by-voxel brain effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND after placebo administration during pain. Upper left: regional effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND in the thalamus (THA) after placebo administration during pain. Lower right: Pearson correlation between Δ μ-opioid BPND after placebo administration in the thalamus and Δ in pain ratings after placebo administration. Abbreviations: DLPFC: dorsolateral prefrontal cortex; dACC: dorsal anterior cingulate cortex; NAc: nucleus accumbens; THA: thalamus; MPQ: McGill Pain Questionnaire.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4222079&req=5

Figure 1: Figures represent voxel-by-voxel brain effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND after placebo administration during pain. Upper left: regional effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND in the thalamus (THA) after placebo administration during pain. Lower right: Pearson correlation between Δ μ-opioid BPND after placebo administration in the thalamus and Δ in pain ratings after placebo administration. Abbreviations: DLPFC: dorsolateral prefrontal cortex; dACC: dorsal anterior cingulate cortex; NAc: nucleus accumbens; THA: thalamus; MPQ: McGill Pain Questionnaire.

Mentions: Analyses of the molecular imaging data showed that FAAH genotype had a selective effect on opioid-mediated placebo analgesia, but not on pain-induced opioid system responses or dopaminergic function. We studied the relationship of FAAH genotype variation to μ-opioid and DA D2/3 receptor BPND measures both at baseline and following activation of these neurotransmitter systems during the pain challenge, using a t-test and mixed model analysis of variance, respectively, applied on a voxel-by-voxel basis. No effects of Pro129Thr were observed for baseline μ-opioid and DA D2/3 receptor BPND, or for pain-induced activation of μ-opioid or DA D2/3 neurotransmission, as might be expected based on the lack of genotype effects on subjective psychophysical responses to the pain challenge. We then tested for an effect of FAAH genotype variation on placebo-induced μ-opioid and DA D2/3 system activation. FAAH Pro129/Pro129 homozygotes showed greater endogenous opioid system activation during placebo administration (for all regions, p <0.05 after FDR correction for multiple comparisons) in areas of the prefrontal cortex, including the dorsolateral prefrontal cortex (DLFPC), the dorsal and ventromedial prefrontal cortex (d/v MPFC), the lateral and medial orbitofrontal cortex (l/m OFC), the inferior frontal gyrus (IFG), the dorsal, rostral and subgenual anterior cingulate cortex (d/r/sg ACC), the anterior and posterior insula (a/p INS) and the hippocampus and parahippocampal gyrus. Subcortically, regions where an effect of FAAH genotype variation was observed included the nucleus accumbens (NAc), extending posteriorly to the mammillary region (MR), the dorsal and ventral putamen (d/v PUT) and the anterior and posterior thalamus (a/p THA) (Fig. 1, Table 2). No significant effect of FAAH genotype variation was found for the opposite contrast. No effects of FAAH genotype variation on placebo-induced DA D2/3 system activation were obtained.


FAAH selectively influences placebo effects.

Peciña M, Martínez-Jauand M, Hodgkinson C, Stohler CS, Goldman D, Zubieta JK - Mol. Psychiatry (2013)

Figures represent voxel-by-voxel brain effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND after placebo administration during pain. Upper left: regional effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND in the thalamus (THA) after placebo administration during pain. Lower right: Pearson correlation between Δ μ-opioid BPND after placebo administration in the thalamus and Δ in pain ratings after placebo administration. Abbreviations: DLPFC: dorsolateral prefrontal cortex; dACC: dorsal anterior cingulate cortex; NAc: nucleus accumbens; THA: thalamus; MPQ: McGill Pain Questionnaire.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4222079&req=5

Figure 1: Figures represent voxel-by-voxel brain effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND after placebo administration during pain. Upper left: regional effects of FAAH Pro129Thr (Pro129/Pro129 > Thr 129 carriers) on Δ μ-opioid BPND in the thalamus (THA) after placebo administration during pain. Lower right: Pearson correlation between Δ μ-opioid BPND after placebo administration in the thalamus and Δ in pain ratings after placebo administration. Abbreviations: DLPFC: dorsolateral prefrontal cortex; dACC: dorsal anterior cingulate cortex; NAc: nucleus accumbens; THA: thalamus; MPQ: McGill Pain Questionnaire.
Mentions: Analyses of the molecular imaging data showed that FAAH genotype had a selective effect on opioid-mediated placebo analgesia, but not on pain-induced opioid system responses or dopaminergic function. We studied the relationship of FAAH genotype variation to μ-opioid and DA D2/3 receptor BPND measures both at baseline and following activation of these neurotransmitter systems during the pain challenge, using a t-test and mixed model analysis of variance, respectively, applied on a voxel-by-voxel basis. No effects of Pro129Thr were observed for baseline μ-opioid and DA D2/3 receptor BPND, or for pain-induced activation of μ-opioid or DA D2/3 neurotransmission, as might be expected based on the lack of genotype effects on subjective psychophysical responses to the pain challenge. We then tested for an effect of FAAH genotype variation on placebo-induced μ-opioid and DA D2/3 system activation. FAAH Pro129/Pro129 homozygotes showed greater endogenous opioid system activation during placebo administration (for all regions, p <0.05 after FDR correction for multiple comparisons) in areas of the prefrontal cortex, including the dorsolateral prefrontal cortex (DLFPC), the dorsal and ventromedial prefrontal cortex (d/v MPFC), the lateral and medial orbitofrontal cortex (l/m OFC), the inferior frontal gyrus (IFG), the dorsal, rostral and subgenual anterior cingulate cortex (d/r/sg ACC), the anterior and posterior insula (a/p INS) and the hippocampus and parahippocampal gyrus. Subcortically, regions where an effect of FAAH genotype variation was observed included the nucleus accumbens (NAc), extending posteriorly to the mammillary region (MR), the dorsal and ventral putamen (d/v PUT) and the anterior and posterior thalamus (a/p THA) (Fig. 1, Table 2). No significant effect of FAAH genotype variation was found for the opposite contrast. No effects of FAAH genotype variation on placebo-induced DA D2/3 system activation were obtained.

Bottom Line: Endogenous opioid and cannabinoid systems are thought to act synergistically regulating antinociceptive and reward mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.

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.

Show MeSH
Related in: MedlinePlus