Dataset Information

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity.

ABSTRACT:

Background

The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.

Methods

In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level-dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.

Results

Marked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.

Conclusions

The MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug's characteristic subjective effects arise from its modulation of spontaneous brain activity.

SUBMITTER: Carhart-Harris RL

PROVIDER: S-EPMC4578244 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity.

Carhart-Harris Robin L RL Murphy Kevin K Leech Robert R Erritzoe David D Wall Matthew B MB Ferguson Bart B Williams Luke T J LT Roseman Leor L Brugger Stefan S De Meer Ineke I Tanner Mark M Tyacke Robin R Wolff Kim K Sethi Ajun A Bloomfield Michael A P MA Williams Tim M TM Bolstridge Mark M Stewart Lorna L Morgan Celia C Newbould Rexford D RD Feilding Amanda A Curran H Val HV Nutt David J DJ

Biological psychiatry 20140110 8

<h4>Background</h4>The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.<h4>Methods</h4>In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA ad ...[more]

PMID: 24495461

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Project description:Background and purposeThe arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method.Materials and methodsNinety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than ±10 mL/min/100 g.ResultspCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean ± 2 standard deviations) were -4 ± 14 mL/min/100 g in the young subjects and 6 ± 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 ± 8 mL/min/100 g; elderly, 54 ± 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 ± 10 mL/min/100 g; elderly, 48 ± 10 mL/min/100 g; P < .001).ConclusionsThe limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

Dataset Information

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity.

Background

Methods

Results

Conclusions

Publications

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity.

Similar Datasets

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