MDMA ("Ecstasy") and its association with cerebrovascular accidents: preliminary findings.
OBJECTIVE
Abuse of the popular recreational drug "Ecstasy" (MDMA) has been linked to the occurrence of cerebrovascular accidents. It is known that MDMA alters brain serotonin (5-HT) concentrations and that brain postsynaptic 5-HT(2) receptors play a role in the regulation of brain microvasculature. Therefore, we used brain imaging to find out whether MDMA use predisposes one to cerebrovascular accidents by altering brain 5-HT neurotransmission.


METHODS
The effects of MDMA use on brain cortical 5-HT(2A) receptor densities were studied using [(123)I]R91150 single-photon emission CT in 10 abstinent recent MDMA users, five former MDMA users, and 10 healthy control subjects. Furthermore, to examine whether changes in brain 5-HT(2A) receptor densities are associated with alterations in blood vessel volumes, we calculated relative cerebral blood volume maps from dynamic MR imaging sets in five MDMA users and six healthy control subjects.


RESULTS
An analysis of variance revealed that mean cortical [(123)I]R91150 binding ratios were significantly lower in recent MDMA users than in former MDMA users and control subjects. This finding suggests down-regulation of 5-HT(2) receptors caused by MDMA-induced 5-HT release. Furthermore, in MDMA users, low cortical 5-HT(2) receptor densities were significantly associated with low cerebral blood vessel volumes (implicating vasoconstriction) and high cortical 5-HT(2) receptor densities with high cerebral blood vessel volumes (implicating vasodilatation) in specific brain regions.


CONCLUSIONS
These findings suggest a relationship between the serotonergic system and an altered regulation of 5-HT(2) receptors in human MDMA users. MDMA users may therefore be at risk for cerebrovascular accidents resulting from alterations in the 5-HT neurotransmission system.
Reneman
L
L
Department of Nuclear Medicine (Graduate School of Neurosciences), Academic Medical Center, Amsterdam, The Netherlands.
Habraken
J B
JB
Majoie
C B
CB
Booij
J
J
den Heeten
G J
GJ
D000328:Adult; D001810:Blood Volume / Q000187:drug effects; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D010880:Piperidines / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012016:Reference Values; D020521:Stroke / Q000139:chemically induced*; D014055:Tomography, Emission-Computed
D013287:Illicit Drugs; D010880:Piperidines; C105020:R 91150; D011985:Receptors, Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine