Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study
Sj Kish, Paul S. Fitzmaurice, Lj Chang, Yoshiaki Furukawa, Junchao Tong
Journal of Psychopharmacology October 2, 2008 DOI: 10.1177/0269881108097724 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study Case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | High-dose MDMA user (post-mortem brain) |
| Topics | MDMA Serotonin |
| Keywords | Serotonin transporter Pharmacology Hallucinogen |
| Citations | 31 |
| Key findings | High-dose MDMA exposure was associated with substantial reductions in serotonin transporter and tryptophan hydroxylase protein levels in multiple brain regions. |
Abstract
Evidence that the widely used methamphetamine analog MDMA (3,4-methylenedioxymethamphetamine, ecstasy) might damage brain serotonin neurones in humans is derived from imaging investigations showing variably decreased binding of radioligands to the serotonin transporter (SERT), a marker of serotonin neurones. However, in humans, it is not known whether low SERT binding reflects actual loss of SERT protein itself. As this question can only be answered in post-mortem brain, we measured protein levels of SERT and that of the rate-limiting serotonin-synthesizing enzyme tryptophan hydroxylase (TPH) in autopsied brain of a high-dose MDMA user. As compared with control values, SERT protein levels were markedly (−48% to −58%) reduced in striatum (caudate, putamen) and occipital cortex and less affected (−25%) in frontal and temporal cortices, whereas TPH protein was severely decreased in caudate and putamen (−68% and −95%, respectively). The magnitude of the striatal SERT protein reduction was greater than the SERT binding decrease typically reported in imaging studies. Although acknowledging limitations of a case study, these findings extend imaging data based on SERT binding and suggest that high-dose MDMA exposure could cause loss of two key protein markers of brain serotonin neurones, a finding compatible with either physical damage to serotonin neurones or downregulation of components therein.
Comparable studies
Other case reports and case series on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA Individuals whose deaths were associated with MDMA or MDEA use | 1987 | Case series | n = 5 |
| Pathology of deaths associated with "ecstasy" and "eve" misuse. Young white men aged 20 to 25 who died after using ring-substituted amphetamines (MDMA... | 1996 | Case series | n = 7 |
| 'Eve' and 'Ecstasy' Individuals who died after using MDMA or MDEA | 1987 | Case series | n = 5 |
| A Method of Conducting Therapeutic Sessions with MDMA Clients with clear therapeutic purpose, excluding those with serious functional... | 1998 | Case study | n = 2 |
| Diversity of Psychopathology Associated with use of 3,4-Methylenedioxymethamphetamine (‘Ecstasy’) Psychiatric patients presenting between 1990 and 1992 whose symptoms developed in the... | 1994 | Case series | n = 13 |
Citations in the library
Cited by 12
- Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study Brain May 17, 2010
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- 3,4-methylenedioxymethamphetamine (MDMA): current perspectives Substance Abuse and Rehabilitation November 1, 2013
- Can MDMA Play a Role in the Treatment of Substance Abuse? Current Drug Abuse Reviews June 1, 2013
- Illicit Stimulant Use in Humans Is Associated with a Long-Term Increase in Tremor PLoS One December 18, 2012
and 7 more in the library
Cites 10
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- A Voxel-Based PET Investigation of the Long-Term Effects of “Ecstasy” Consumption on Brain Serotonin Transporters American Journal of Psychiatry July 1, 2004
- A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers Journal of Psychopharmacology March 1, 2006
- Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user Neurology July 25, 2000
- Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects Journal of Psychopharmacology March 1, 2006
and 5 more in the library