MDMA Increases Cooperation and Recruitment of Social Brain Areas When Playing Trustworthy Players in an Iterated Prisoner's Dilemma

Gabay, Anthony S.; Kempton, Matthew J.; Gilleen, James; Mehta, Mitul A.

doi:10.1523/jneurosci.1276-18.2018

Cited by 31 publications

(36 citation statements)

References 46 publications

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“…MDMA-induced changes in subjective effects, as measured by the ASC, and plasma oxytocin levels can be found in Gabay et al. (2019) (respectively in Fig.…”

Section: Resultsmentioning

confidence: 93%

Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA

et al. 2019

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One of the main limitations of pharmacological fMRI is its inability to provide a molecular insight into the main effect of compounds, leaving an open question about the relationship between drug effects and haemodynamic response. The aim of this study is to investigate the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on functional connectivity (FC) using a novel multimodal method (Receptor-Enriched Analysis of functional Connectivity by Targets - REACT). This approach enriches the resting state (rs-)fMRI analysis with the molecular information about the distribution density of serotonin receptors in the brain, given the serotonergic action of MDMA. Twenty healthy subjects participated in this double-blind, placebo-controlled, crossover study. A high-resolution in vivo atlas of four serotonin receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and its transporter (5-HTT) was used as a template in a two-step multivariate regression analysis to estimate the spatial maps reflecting the whole-brain connectivity behaviour related to each target under placebo and MDMA. Results showed that the networks exhibiting significant changes after MDMA administration are the ones informed by the 5-HTT and 5-HT 1A distribution density maps, which are the main targets of this compound. Changes in the 5-HT 1A -enriched functional maps were also associated with the pharmacokinetic levels of MDMA and MDMA-induced FC changes in the 5-HT 2A -enriched maps correlated with the spiritual experience subscale of the Altered States of Consciousness Questionnaire. By enriching the rs-fMRI analysis with molecular data of voxel-wise distribution of the serotonin receptors across the brain, we showed that MDMA effects on FC can be understood through the distribution of its main targets. This result supports the ability of this method to characterise the specificity of the functional response of the brain to MDMA binding to serotonergic receptors, paving the way to the definition of a new fingerprint in the characterization of new compounds and potentially to a further understanding to the response to treatment.

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“…MDMA-induced changes in subjective effects, as measured by the ASC, and plasma oxytocin levels can be found in Gabay et al. (2019) (respectively in Fig.…”

Section: Resultsmentioning

confidence: 93%

Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA

et al. 2019

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“…Participants were recruited to participate in a study examining the effects of MDMA on social cognition ( Gabay et al, 2019 ). Briefly, baseline blood samples were obtained 15 min before MDMA/placebo administration on two separate occasions, spaced on average 9.30 days apart (SD = 5.70 days; range: 7–31 days).…”

Section: Methodsmentioning

confidence: 99%

Salivary and plasmatic oxytocin are not reliable trait markers of the physiology of the oxytocin system in humans

Martins

Gabay

Mehta

et al. 2020

eLife

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Single measurements of salivary and plasmatic oxytocin are used as indicators of the physiology of the oxytocin system. However, questions remain about whether they are sufficiently stable to provide valid trait markers of the physiology of the oxytocin system, and whether salivary oxytocin can accurately index its plasmatic concentrations. Using radioimmunoassay, we measured baseline plasmatic and/or salivary oxytocin from two independent datasets. We also administered exogenous oxytocin intravenously and intranasally in a triple dummy, within-subject, placebo-controlled design and compared baseline levels and the effects of routes of administration. Our findings question the use of single measurements of baseline oxytocin concentrations in saliva and plasma as valid trait markers of the physiology of the oxytocin system in humans. Salivary oxytocin is a weak surrogate for plasmatic oxytocin. The increases in salivary oxytocin observed after intranasal oxytocin most likely reflect unabsorbed peptide and should not be used to predict treatment effects.

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“…Dataset B. Participants were recruited to participate in a study examining the effects of MDMA on social cognition (17). Briefly, baseline blood samples were obtained 15 min before MDMA/placebo administration on two separate occasions, spaced on average 9.30 days apart (SD = 5.70 days; range: 7-31 days).…”

Section: Methodsmentioning

confidence: 99%

Are single peripheral measurements of baseline oxytocin in saliva and plasma reliable biomarkers of the physiology of the oxytocin system in humans?

Martins

Gabay

Mehta

et al. 2020

Preprint

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Background: Single measurements of salivary and plasmatic oxytocin are used as indicators of the physiology of the oxytocin system. However, questions remain about whether they are sufficiently stable to provide valid biomarkers of the physiology of the oxytocin system, and whether salivary oxytocin can accurately index its plasmatic concentrations. Methods: Using radioimmunoassay, we measured baseline plasmatic and/or salivary oxytocin from two independent datasets. Dataset A comprised 17 healthy men sampled on four occasions approximately at weekly intervals. We administered exogenous oxytocin intravenously and intranasally in a triple dummy, within-subject, placebo-controlled design and compared baseline levels and the effects of routes of administration. Dataset B comprised baseline plasmatic oxytocin measurements from 20 healthy men sampled on two separate occasions. Additionally, in dataset A, we tested whether salivary oxytocin can predict plasmatic oxytocin at baseline and after intranasal and intravenous oxytocin administration. Results: Single measurements of plasmatic and salivary oxytocin showed poor reliability across visits in both datasets. Intranasal administration of exogenous oxytocin increases salivary oxytocin, but intravenous administration of a considerable dose does not produce any changes. Saliva and plasma oxytocin did not correlate at baseline or after administration of exogenous oxytocin. Conclusions: Our findings question the use of single measurements of baseline oxytocin concentrations in saliva and plasma as valid biomarkers of the physiology of the oxytocin system in humans. Salivary oxytocin is a weak surrogate for plasmatic oxytocin. The increases in salivary oxytocin observed after intranasal oxytocin most likely reflect unabsorbed peptide and should not be used to predict treatment effects.

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MDMA Increases Cooperation and Recruitment of Social Brain Areas When Playing Trustworthy Players in an Iterated Prisoner's Dilemma

Cited by 31 publications

References 46 publications

Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA

Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA

Salivary and plasmatic oxytocin are not reliable trait markers of the physiology of the oxytocin system in humans

Are single peripheral measurements of baseline oxytocin in saliva and plasma reliable biomarkers of the physiology of the oxytocin system in humans?

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