Hoshi, R; (2006) The neuropharmaceutical, cognitive and mood effects of +3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'. Doctoral thesis , UCL (University College London).

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Abstract

This thesis investigates the sub-acute and long-term neuropharmacological, cognitive and mood effects of ecstasy use. The first Positron Emission Tomography (PET) study used the 18F-dopa ligand to assess presynaptic dopaminergic function in ex-ecstasy users, poly-drug controls and drug-naive controls. Increased F-dopa uptake was found in the putamen of ex-ecstasy users compared to controls. This could suggest a compensatory upregulation of the dopaminergic system. The second PET study used the 11CDASB ligand to assess 5- HT transporter density in ex-ecstasy users, poly-drug controls and drug-naive controls. No significant group differences indicated recovery of 5-HT transporter density following cessation of ecstasy use, replicating several very recent studies. Studies 3 and 4 assessed cognitive function and aggressive cognitive bias respectively in ex-ecstasy users, current ecstasy users, poly-drug controls and drug- naive controls. A general tendency towards impaired learning and memory in all 3 drug using groups suggested that drug use in general rather than ecstasy use per se could be responsible. In addition, recent drug use was associated with poorer memory performance and impaired response inhibition. No group differences were observed in aggressive cognitive bias. However, Study 5, using the same task with over 100 participants showed increased aggressive interpretative bias (and increased self-rated aggression and depression) 4 days after acute ecstasy use. No evidence of gender differences was found. Study 6 built on findings with serotonergic challenges to explore transient 5-HT depletion. As predicted, on the night of ecstasy use participants showed subtly elevated fear recognition accuracy and the reverse 4 days later. In summary, evidence of recovery of serotonergic function following cessation of ecstasy use should be viewed alongside long-lasting alterations in dopaminergic function. Cognitive 'deficits' are less apparent when ecstasy users are matched with controls for use of all other recreational drugs. 'Mid-week' lowering of mood is now one of the most replicated findings within the ecstasy literature.

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