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

Robin L.  Carhart-Harris; Kevin  Murphy; Robert  Leech; David  Erritzoe; Matthew B.  Wall; Bart  Ferguson; Luke T.J.  Williams; Leor  Roseman; Stefan  Brugger; Ineke  De Meer; Mark  Tanner; Robin  Tyacke; Kim Wolff; Ajun  Sethi; Michael A P Bloomfield; Tim M. Williams; Mark  Bolstridge; Lorna  Stewart; Celia Morgan; Rexford D. Newbould; Amanda Feilding; H. Val  Curran; David J. Nutt

doi:10.1016/j.biopsych.2013.12.015

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

Robin L. Carhart-Harris, Kevin Murphy, Robert Leech, David Erritzoe, Matthew B. Wall, Bart Ferguson, Luke T.J. Williams, Leor Roseman, Stefan Brugger, Ineke De Meer, Mark Tanner, Robin Tyacke, Kim Wolff, Ajun Sethi, Michael A P Bloomfield, Tim M. Williams, Mark Bolstridge, Lorna Stewart, Celia Morgan, Rexford D. NewbouldAmanda Feilding, H. Val Curran, David J. Nutt

UCL University College London

Research output: Contribution to journal › Article › peer-review

98 Citations (Scopus)

217 Downloads (Pure)

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.

Original language	English
Pages (from-to)	554–562
Number of pages	8
Journal	Biological psychiatry
Volume	78
Issue number	8
Early online date	2014
DOIs	https://doi.org/10.1016/j.biopsych.2013.12.015
Publication status	Published - 15 Oct 2015

Keywords

MDMA
PTSD
AMYGDALA
SEROTONIN
5-HT
HIPPOCAMPAL
fMRI

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The Effects of Acutely Administered_CARHART-HARRIS Accepted 16Dec2013 GOLDFPVFinal published version, 3.66 MBLicence: CC BY

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Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., Williams, L. T. J., Roseman, L., Brugger, S., De Meer, I., Tanner, M., Tyacke, R., Wolff, K., Sethi, A., Bloomfield, M. A. P., Williams, T. M., Bolstridge, M., Stewart, L., Morgan, C., ... Nutt, D. J. (2015). 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. Biological psychiatry, 78(8), 554–562. https://doi.org/10.1016/j.biopsych.2013.12.015

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title = "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{\textquoteright}s characteristic subjective effects arise from its modulation of spontaneous brain activity.",

keywords = "MDMA, PTSD, AMYGDALA, SEROTONIN, 5-HT, HIPPOCAMPAL, fMRI",

author = "Carhart-Harris, {Robin L.} and Kevin Murphy and Robert Leech and David Erritzoe and Wall, {Matthew B.} and Bart Ferguson and Williams, {Luke T.J.} and Leor Roseman and Stefan Brugger and {De Meer}, Ineke and Mark Tanner and Robin Tyacke and Kim Wolff and Ajun Sethi and Bloomfield, {Michael A P} and Williams, {Tim M.} and Mark Bolstridge and Lorna Stewart and Celia Morgan and Newbould, {Rexford D.} and Amanda Feilding and Curran, {H. Val} and Nutt, {David J.}",

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language = "English",

volume = "78",

pages = "554–562",

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Carhart-Harris, RL, Murphy, K, Leech, R, Erritzoe, D, Wall, MB, Ferguson, B, Williams, LTJ, Roseman, L, Brugger, S, De Meer, I, Tanner, M, Tyacke, R, Wolff, K, Sethi, A, Bloomfield, MAP, Williams, TM, Bolstridge, M, Stewart, L, Morgan, C, Newbould, RD, Feilding, A, Curran, HV & Nutt, DJ 2015, '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', Biological psychiatry, vol. 78, no. 8, pp. 554–562. https://doi.org/10.1016/j.biopsych.2013.12.015

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. ; Murphy, Kevin ; Leech, Robert et al.
In: Biological psychiatry, Vol. 78, No. 8, 15.10.2015, p. 554–562.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Carhart-Harris, Robin L.

AU - Murphy, Kevin

AU - Leech, Robert

AU - Erritzoe, David

AU - Wall, Matthew B.

AU - Ferguson, Bart

AU - Williams, Luke T.J.

AU - Roseman, Leor

AU - Brugger, Stefan

AU - De Meer, Ineke

AU - Tanner, Mark

AU - Tyacke, Robin

AU - Wolff, Kim

AU - Sethi, Ajun

AU - Bloomfield, Michael A P

AU - Williams, Tim M.

AU - Bolstridge, Mark

AU - Stewart, Lorna

AU - Morgan, Celia

AU - Newbould, Rexford D.

AU - Feilding, Amanda

AU - Curran, H. Val

AU - Nutt, David J.

PY - 2015/10/15

Y1 - 2015/10/15

N2 - 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.

AB - 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.

KW - MDMA

KW - PTSD

KW - AMYGDALA

KW - SEROTONIN

KW - 5-HT

KW - HIPPOCAMPAL

KW - fMRI

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DO - 10.1016/j.biopsych.2013.12.015

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Carhart-Harris RL, Murphy K, Leech R, Erritzoe D, Wall MB, Ferguson B et al. 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. Biological psychiatry. 2015 Oct 15;78(8):554–562. Epub 2014. doi: 10.1016/j.biopsych.2013.12.015