OPEN Foundation

B. Ferguson

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.

Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., … & Tanner, M. (2014). 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. http://dx.doi.org/10.1016/j.biopsych.2013.12.015

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Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study

Abstract

Background: Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) can promote pro-social effects which may alter interpersonal perceptions.

Aims: To explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people’s faces and co-operative behaviours.

Method: An independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings.

Results: Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3.

Conclusions: Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy.

Stewart, L. H., Ferguson, B., Morgan, C. J. A., Swaboda, N., Jones, L., Fenton, R., … & Curran, H. V. (2014). Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study. Journal of Psychopharmacology, 28(11), 1001-1008. https://dx.doi.org/10.1177/0269881114544775

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

Abstract

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

Methods
MDMA was orally administered to 25 physically and mentally healthy individuals in a double-blind, placebo-controlled, balanced-order study. Arterial spin labelling (ASL) 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. Participants underwent two ASL and two BOLD scans in a 90 minute scanning session and the MDMA and placebo study days were separated by one week.

Results
MDMA produced marked increases in positive mood. Only decreased CBF was observed after MDMA and this was localised 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 MDMA’s global subjective effects. 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.

Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., … Nutt, D. J. (2014). The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labelling and Blood Oxygen Level-Dependent Resting-State Functional Connectivity. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2013.12.015
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21 March - Ketamine Discussion with Celia Morgan, Filip Tylš & Will Barone

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