Pharmacogenetic studies of change in cortisol on ecstasy (MDMA) consumption
Kim Wolff, Eva-Maria Tsapakis, Carmine Maria Pariante, Robert W Kerwin, Mary L. Forsling, Katherine Jean Aitchison
Journal of Psychopharmacology October 3, 2011 DOI: 10.1177/0269881111415737 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational field study Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Self-nominating regular clubbers (30 males, mean age 23 years) |
| Topics | MDMA |
| Citations | 37 |
| Key findings | Plasma cortisol increased after clubbing, with significantly greater increases in MDMA-positive participants (736.9 ± 83.2 vs. 350.9 ± 34.5 mmol/l, p = 0.001). The low-activity COMT Met/Met genotype was positively associated with MDMA-induced cortisol change in the whole sample, and CYP2D6 genotype was associated with cortisol change in MDMA-positive subjects; no association was found with 5-HTTLPR. The authors suggest these associations may indicate HPA axis dysregulation from chronic MDMA use, moderated by genetic polymorphism. |
Abstract
In this study we investigate the association of cytochrome P450 enzyme CYP2D6, catechol-O-methyl transferase (COMT, Val158Met) and serotonin transporter promoter (5-HTTLPR) genotypes on change in cortisol concentration following 3, 4-methylenedioxy-methamphetamine (MDMA, 'ecstasy') consumption. Forty-eight subjects (30 males, mean age 23 years), self-nominating regular clubbers provided 'in the field' pre- and post-clubbing biological samples and associated information. Of the 39 subjects who provided a post-clubbing urine sample, 21 were positive for MDMA. Plasma cortisol concentrations increased in subjects (n = 48) tested for cortisol, with changes being significantly greater in the MDMA-positive group (736.9 ± 83.2 vs. 350.9 ± 34.5 mmol/l, p = 0.001). We found a positive association between the low activity COMT genotype (Met/Met) and MDMA-induced change in cortisol and also between this and change in cortisol in the whole sample (p = 0.039, Bonferroni corrected). For CYP2D6, there was an association between genotype and change in cortisol, confined to subjects with MDMA-positive urine post-clubbing (p = 0.003, Bonferroni corrected). There was no association with 5-HTTLPR genotype. These associations suggest that chronic use of MDMA may lead to HPA axis dysregulation and that the magnitude of this may be moderated by genetic polymorphism, and warrant further investigation in a larger sample of those who consume the drug on a regular basis.
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 18
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant? Frontiers in Genetics 2012
- Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): The Influence of Gender and Genetics (CYP2D6, COMT, 5-HTT) PLoS One October 24, 2012
- How MDMA's Pharmacology and Pharmacokinetics Drive Desired Effects and Harms The Journal of Clinical Pharmacology January 16, 2014
- Acute Effects of 3,4-Methylenedioxymethamphetamine and Methylphenidate on Circulating Steroid Levels in Healthy Subjects Neuroendocrinology 2014
and 13 more in the library
Cites 8
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics July 1, 1999
- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics. Psychopharmacology May 2004
- Hypothalamic-pituitary-adrenal axis responses to stress in subjects with 3,4-methylenedioxy-methamphetamine ('ecstasy') use history: correlation with dopamine receptor sensitivity. Psychiatry Research September 30, 2003
and 3 more in the library