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
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.
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London. Electronic address: r.carhart-harris@imperial.ac.uk.
Robin L
RL
Carhart-Harris
Cardiff University Brain Research Imaging Centre (KM), School of Psychology, Cardiff University, Cardiff, London, United Kingdom.
Kevin
K
Murphy
Division of Brain Sciences, Faculty of Medicine.
Robert
R
Leech
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
David
D
Erritzoe
Institute of Neurology (MBW),; Imanova (MBW, IDM, MT, RDN), Centre for Imaging Sciences, London.
Matthew B
MB
Wall
Clinical Psychopharmacology Unit (BF, LS, CM, HVC), University College London, London; University College London, London.
Bart
B
Ferguson
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
Luke T J
LT
Williams
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
Leor
L
Roseman
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
Stefan
S
Brugger
Imanova (MBW, IDM, MT, RDN), Centre for Imaging Sciences, London.
Ineke
I
De Meer
Imanova (MBW, IDM, MT, RDN), Centre for Imaging Sciences, London.
Mark
M
Tanner
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
Robin
R
Tyacke
School of Biomedical Sciences (KW), Kings College London, London, United Kingdom.
Kim
K
Wolff
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
Ajun
A
Sethi
Psychiatric Imaging Group (MAPB), MRC Clinical Sciences Centre, Institute of Clinical Science, Imperial College London, London.
Michael A P
MA
Bloomfield
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
Tim M
TM
Williams
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
Mark
M
Bolstridge
Clinical Psychopharmacology Unit (BF, LS, CM, HVC), University College London, London; University College London, London.
Lorna
L
Stewart
Clinical Psychopharmacology Unit (BF, LS, CM, HVC), University College London, London; University College London, London.
Celia
C
Morgan
Imanova (MBW, IDM, MT, RDN), Centre for Imaging Sciences, London.
Rexford D
RD
Newbould
The Beckley Foundation (AF), Beckley Park, Oxford.
Amanda
A
Feilding
Clinical Psychopharmacology Unit (BF, LS, CM, HVC), University College London, London; University College London, London.
H Val
HV
Curran
Centre for Neuropsychopharmacology (RLC-H, DE, LTJW, LR, SB, RT, AS, TMW, MB, DJN) and C3NL (RL), Division of Brain Sciences, Faculty of Medicine, London, London.
David J
DJ
Nutt
D000328:Adult; D000339:Affect / Q000502:physiology*; D000679:Amygdala / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D010100:Oxygen / Q000097:blood*; D017397:Prefrontal Cortex / Q000187:drug effects; D018490:Serotonin Agents / Q000008:administration & dosage*; D013702:Temporal Lobe / Q000187:drug effects; D055815:Young Adult
D018490:Serotonin Agents; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D010100:Oxygen
5-HT; Amygdala; Hippocampus; MDMA; PTSD; Serotonin; fMRI