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
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Author(s)
Type
Journal Article
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.
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.
Date Issued
2015-10-15
Date Acceptance
2013-12-16
Citation
Biological Psychiatry, 2015, 78 (8), pp.554-562
ISSN
1873-2402
Publisher
Elsevier
Start Page
554
End Page
562
Journal / Book Title
Biological Psychiatry
Volume
78
Issue
8
Copyright Statement
© 2015 The Authors. This article is available under the terms of the Creative Commons Attribution License (CC BY).
You may distribute and copy the article, create extracts, abstracts, and other revised versions, adaptations or derivative works of or from an article (such as a translation), to include in a collective work (such as an anthology), to text or data mine the article, including for commercial purposes without permission from Elsevier. The original work must always be appropriately credited.
You may distribute and copy the article, create extracts, abstracts, and other revised versions, adaptations or derivative works of or from an article (such as a translation), to include in a collective work (such as an anthology), to text or data mine the article, including for commercial purposes without permission from Elsevier. The original work must always be appropriately credited.
License URL
Sponsor
Medical Research Council (MRC)
Grant Number
MR/J00460x/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Neurosciences
Psychiatry
Neurosciences & Neurology
Amygdala
5-HT
fMRI
Hippocampus
MDMA
PTSD
Serotonin
POSTTRAUMATIC-STRESS-DISORDER
CENTRAL-NERVOUS-SYSTEM
MDMA-ECSTASY
PREFRONTAL CORTEX
NEGATIVE EMOTIONS
MEMORY IMPAIRMENT
HUMANS
RECEPTORS
ANXIETY
PRETREATMENT
Publication Status
Published