Altered neuroendocrine and behavioral responses to m-chlorophenylpiperazine in 3,4-methylenedioxymethamphetamine (MDMA) users

Psychopharmacology (Berl). 1999 Nov;147(1):56-65. doi: 10.1007/s002130051142.


Rationale: (+/-) 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.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Affect / drug effects
  • Anxiety / psychology
  • Behavior / drug effects*
  • Female
  • Hallucinogens / adverse effects*
  • Humans
  • Hydrocortisone / blood
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / adverse effects*
  • Neurosecretory Systems / drug effects*
  • Piperazines* / blood
  • Prolactin / blood
  • Serotonin / physiology*
  • Serotonin Receptor Agonists* / blood
  • Single-Blind Method


  • Hallucinogens
  • Piperazines
  • Serotonin Receptor Agonists
  • Serotonin
  • Prolactin
  • N-Methyl-3,4-methylenedioxyamphetamine
  • 1-(3-chlorophenyl)piperazine
  • Hydrocortisone