Brain serotonin synthesis in <scp>MDMA</scp> (ecstasy) polydrug users: an alpha‐[<sup>11</sup>C]methyl‐<scp>l</scp>‐tryptophan study
Bibliographic record
Abstract
Abstract 3,4‐Methylenedioxymethamphetamine ( MDMA , ecstasy) use may have long‐term neurotoxic effects. In this study, positron emission tomography with the tracer alpha‐[ 11 C]methyl‐ l ‐tryptophan ( 11 C‐ AMT ) was used to compare human brain serotonin (5‐ HT ) synthesis capacity in 17 currently drug‐free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional 11 C‐ AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized 11 C‐ AMT trapping in pre‐frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized 11 C‐ AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized 11 C‐ AMT trapping in the brainstem and pre‐frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre‐existing 5‐ HT alterations pre‐disposing people to use MDMA cannot be ruled out, regionally decreased 5‐ HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5‐ HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms. image Animal studies showed that MDMA (3,4‐methylenedioxymethamphetamine, ecstasy) exposure alters brain serotonin neurotransmission. Whether these effects are permanent is unknown. The present human study found that, compared to controls, young adult MDMA users had lower serotonin synthesis in parts of the frontal cortex, and greater serotonin synthesis in other regions, including the brainstem. The strength of these effects correlated with severity of use. The findings may indicate that MDMA can be neurotoxic but the brain may also have the capacity to regenerate, depending on the specific brain region. Longitudinal studies are needed to test the clinical relevance of these findings.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".