In vivo detection of short- and long-term MDMA neurotoxicity?a positron emission tomography study in the living baboon brain
Ursula Scheffel, Zsolt Szabó, William B. Mathews, Paige Finley, Robert F. Dannals, Hayden T. Ravert, Katalina Szabo, Jie Yuan, George A. Ricaurte
Synapse June 1, 1998 DOI: 10.1002/(sici)1098-2396(199806)29:2<183::aid-syn9>3.0.co;2-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study Case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | Baboon |
| Intervention | MDMA |
| Dose | 5 mg/kg, s.c., twice daily for four consecutive days |
| Duration | 4-day treatment; PET scans at 13, 19, and 40 days post-MDMA, and at 9 and 13 months |
| Topics | MDMA |
| Keywords | Baboon Neocortex Positron emission tomography Dopamine transporter Neurotoxicity Pharmacology Endocrinology |
| Citations | 146 |
| Key findings | MDMA caused large, regionally variable decreases in serotonin transporter binding in the baboon brain, with some regions showing partial recovery and others persistent loss after over a year. |
Abstract
The present study evaluated short- and long-term effects of MDMA (3,4-methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN 5652, a potent 5-HT transporter ligand, as well as [11C]RTI-55, a cocaine derivative which labels both 5-HT and dopamine transporters. Following baseline PET scans with [11C](+)McN5652, [11C](-)McN5652 (the inactive enantiomer of the active enantiomer [11C](+)McN5652) and [11C]RTI-55, a baboon was treated with MDMA (5 mg/kg, s.c., twice daily for four consecutive days). PET studies at 13, 19, and 40 days post-MDMA revealed decreases in mean radioactivity levels in all brain regions when using [11C](+)McN 5652, but not with [11C](-)McN5652 or [11C]RTI-55. Reductions in specific [11C](+)McN5652 binding (calculated as the difference in radioactivity concentrations between (+) and (-)[11C]McN5652) ranged from 44% in the pons to 89% in the occipital cortex. PET studies at 9 and 13 months showed regional differences in the apparent recovery of 5-HT transporters, with increases in some brain regions (e.g., hypothalamus) and persistent decreases in others (e.g., neocortex). Data obtained from PET studies correlated well with regional 5-HT axonal marker concentrations in the CNS measured after sacrifice of the animal. The results of these studies indicate that PET imaging of the living nonhuman primate brain with [11C](+)McN5652 can detect changes in regional 5-HT transporter density secondary to MDMA-induced neurotoxicity. Using PET, it should also be feasible to use [11C](+)McN5652 to determine whether human MDMA users are also susceptible to MDMA's neurotoxic effects.
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 52
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
- Reducedin vivobinding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users The British Journal of Psychiatry July 1, 1999
- Cortical Serotonin Transporter Density and Verbal Memory in Individuals Who Stopped Using 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") Archives of General Psychiatry October 1, 2001
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Clinical Studies Neuropsychobiology 2000
and 47 more in the library
Cites 12
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") Journal of Neuroscience August 1, 1995
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
and 7 more in the library