Altered neuroendocrine and behavioral responses to m-chlorophenylpiperazine in 3,4-methylenedioxymethamphetamine (MDMA) users.
BACKGROUND
(+/-) 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug of abuse and a brain serotonin neurotoxin in animals. Growing evidence indicates that humans are also susceptible to MDMA's neurotoxic effects, although few functional consequences of MDMA-induced 5-HT damage have been identified.


OBJECTIVE
The present study sought to determine whether possible differences between MDMA users and control subjects could be unmasked by utilizing a pharmacological challenge with the mixed 5-HT agonist, meta-chlorophenylpiperazine (m-CPP). It was postulated that 5-HT neurotoxicity in MDMA users would be associated with altered 5-HT responsivity, exemplified by altered physiological and behavioral responses to m-CPP.


METHODS
Twenty-five MDMA users who had not taken MDMA for at least 3 weeks and 25 controls received intravenous placebo (normal saline) and m-CPP (0.08 mg/kg) in a fixed order, single blind design. Repeated measures of mood, physical symptoms, and blood samples for neuroendocrine analyses were collected during the 90 min after each infusion.


RESULTS
MDMA users reported more positive and fewer negative emotions and physical symptoms following m-CPP than controls, and were significantly less likely to report an m-CPP-induced panic attack. Male MDMA users had diminished cortisol and prolactin responses to m-CPP.


CONCLUSIONS
The present data indicate that MDMA users have alterations in 5-HT neuronal function, possibly as a consequence of MDMA-induced brain serotonin neural injury.
McCann
U D
UD
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1272, USA. umccann@helix.nih.gov
Eligulashvili
V
V
Mertl
M
M
Murphy
D L
DL
Ricaurte
G A
GA
D000328:Adult; D000339:Affect / Q000187:drug effects; D001007:Anxiety / Q000523:psychology; D001519:Behavior / Q000187:drug effects*; D005260:Female; D006213:Hallucinogens / Q000009:adverse effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D009490:Neurosecretory Systems / Q000187:drug effects*; D010879:Piperazines / Q000097:blood; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000097:blood; D016037:Single-Blind Method
D006213:Hallucinogens; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D011388:Prolactin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015068:1-(3-chlorophenyl)piperazine; D006854:Hydrocortisone