Hypothalamic-pituitary-adrenal axis responses to stress in subjects with 3,4-methylenedioxy-methamphetamine ('ecstasy') use history: correlation with dopamine receptor sensitivity.
Gilberto Gerra, Sara Bassignana, Amir Zaimovic, Gabriele Moi, Monica Bussandri, Rocco Caccavari, Francesca Brambilla, Enzo Molina
Psychiatry Research September 30, 2003 DOI: 10.1016/s0165-1781(03)00175-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | 15 MDMA users without other drug dependencies or prolonged alcohol abuse and 15 control subjects |
| Duration | 3 weeks after MDMA discontinuation for stress test; 4 weeks after MDMA discontinuation for bromocriptine challenge and psychometric measures |
| Measures | ACTH, cortisol, growth hormone (GH) response to bromocriptine, Tridimensional Personality Questionnaire, Minnesota Multiphasic Personality Inventory, Buss-Durkee Hostility Inventory |
| Topics | MDMA |
| Key findings | MDMA users showed significantly higher basal ACTH and cortisol levels but blunted ACTH and cortisol responses to a psychosocial stressor, along with reduced dopamine D2 receptor sensitivity compared with controls. HPA axis responsiveness correlated directly with GH response to bromocriptine and inversely with aggressiveness and novelty seeking. The authors propose these findings may reflect a complex neuroendocrine dysfunction associated with MDMA use, though pre-existing dopamine dysfunction cannot be excluded. |
Abstract
Fifteen 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') users who did not have other drug dependencies or prolonged alcohol abuse and 15 control subjects were studied. All the subjects were exposed to the same psychosocial stressor (Stroop Color-Word Interference Task, public speaking and mental arithmetic in front of an audience) 3 weeks after MDMA discontinuation. Plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol were measured immediately before the tests began and at their end, 30 min later. Growth hormone (GH) responses to the dopaminergic agonist bromocriptine and psychometric measures (Tridimensional Personality Questionnaire, Minnesota Multiphasic Personality Inventory, Buss-Durkee Hostility Inventory) were also obtained 4 weeks after MDMA discontinuation for the same subjects. ACTH and cortisol basal levels were significantly higher in ecstasy users than in control subjects. In contrast, ACTH and cortisol responses to stress were significantly blunted in MDMA users. The sensitivity of dopamine D2 receptors, reflected by GH responses to bromocriptine challenge, was reduced in MDMA users compared with controls. The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis (ACTH and cortisol delta peaks) correlated directly with GH areas under curves in response to bromocriptine, and inversely with psychometric measures of aggressiveness and novelty seeking. No correlation was found between hormonal measures and the extent of MDMA exposure. Reduced D2 receptor sensitivity, HPA basal hyperactivation and reduced responsiveness to stress may represent a complex neuroendocrine dysfunction associated with MDMA use. The present findings do not exclude the possibility that dopamine dysfunction partly predated MDMA exposure.
Comparable studies
Other observational and cohort studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subjective Reports of the Effects of MDMA in a Clinical Setting Individuals who took MDMA in a clinical setting | 1986 | Observational study | |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| The Psychological and Physiological Effects of MDMA on Normal Volunteers Older, more educated, drug-experienced individuals | 1986 | Observational cohort | |
| Cognitive performance in recreational users of MDMA or 'ecstasy': evidence for memory deficits Young people who were regular or novice MDMA users, or non-users | 1998 | Observational cohort | n = 30 |
Citations in the library
Cited by 24
- Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research Human Psychopharmacology: Clinical and Experimental July 1, 2013
- MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress Journal of Psychopharmacology March 1, 2006
- Dance Clubbing on MDMA and during Abstinence from Ecstasy/MDMA: Prospective Neuroendocrine and Psychobiological Changes Neuropsychobiology 2008
- Cortisol and 3,4-Methylenedioxymethamphetamine: Neurohormonal Aspects of Bioenergetic Stress in Ecstasy Users Neuropsychobiology 2009
- Hair MDMA Samples Are Consistent with Reported Ecstasy Use: Findings from a Study Investigating Effects of Ecstasy on Mood and Memory Neuropsychobiology October 20, 2010
and 19 more in the library
Cites 7
- Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics July 1, 1999
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- RETRACTED: Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ("Ecstasy") Science September 27, 2002
- Localization of MDMA‐induced brain activity in healthy volunteers using low resolution brain electromagnetic tomography (LORETA) Human Brain Mapping August 27, 2001
- Serotonergic function after (±)3,4-methylene-dioxymethamphetarnine (‘Ecstasy’) in humans International Clinical Psychopharmacology 1998
and 2 more in the library