Journal of Nuclear Medicine - Damage caused by MDMA reversible?

I have not had time to go over this with any great deal of thought, but a related site already has some info on this, and as its more up our alley I thought i'd post it.

Have we finally seen Ricaurte and his U.S. government-funded (and influenced) goons blown out of the water? Lets hope so.

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Long Term Ecstasy Users Don’t Have Brain Damage

Government backed scientists in Germany published new research this week, which failed to find any significant or lasting harm to the brains of heavy ecstasy users.

While the study of past and present heavy users (who averaged 827 and 793 pills respectively) uncovered tiny differences in SERT densities (relating to potential seratonin damage) between current and non-users, the differences disappeared altogether when former heavy users were compared to non users.

“These results were particularly interesting in that they dramatically contradict an American study done by George Ricuarte (funded by the US government) which used similar brain scan techniques and ecstasy users with a similar level of lifetime use, but which claimed to have found massive (as much as 90%) loss of SERT,” said an editorial in the hugely prestigious Journal of Nuclear Medicine.

“This huge discrepancy is both unexplained and troubling, as Ricuarte's claims were used both to justify outlawing ecstasy in the US and as justification for sentencing increases,” the journal added.

http://jnm.snmjournals.org/cgi/content/full/44/3/375

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Journal of Nuclear Medicine Vol. 44 No. 3 375-384
© 2003 by Society of Nuclear Medicine

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Clinical Investigations

Long-Term Effects of "Ecstasy" Use on Serotonin Transporters of the Brain Investigated by PET
Ralph Buchert, PhD1, Rainer Thomasius, MD2, Bruno Nebeling, PhD1, Kay Petersen, PhD2, Jost Obrocki, MD2, Lars Jenicke, MD1, Florian Wilke1, Lutz Wartberg2, Pavlina Zapletalova, MS2 and Malte Clausen, MD1
1 Department of Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
2 Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Alterations of the serotonergic system due to ecstasy consumption have been extensively documented in recent literature. However, reversibility of these neurotoxic effects still remains unclear. To address this question, PET was performed using the serotonin transporter (SERT) ligand 11C-(+)-McN5652 in a total of 117 subjects subdivided into 4 groups: actual ecstasy users (n = 30), former ecstasy users (n = 29), drug-naive control subjects (n = 29), and subjects with abuse of psychoactive agents other than ecstasy (n = 29). Methods: About 500 MBq 11C-(+)-McN5652 were injected intravenously. Thirty-five scans were acquired according to a dynamic scan protocol of 90 min using a full-ring whole-body PET system. Transaxial slices were reconstructed using an iterative method. Individual brains were transformed to a template defined earlier. Distribution volume ratios (DVRs) were derived by application of a reference tissue approach for reversible binding. Gray matter of the cerebellum served as reference. SERT-rich brain regions—mesencephalon, putamen, caudate, and thalamus—were selected for the evaluation of SERT availability using volumes of interest predefined in the template. Results: Compared with drug-naive control subjects, the DVR in actual ecstasy users was significantly reduced in the mesencephalon (P = 0.004) and the thalamus (P = 0.044). The DVR in former ecstasy users was very close to the DVR in drug-naive control subjects in all brain regions. The DVR in polydrug users was slightly higher than that in the drug-naive control subjects in all SERT-rich regions (not statistically significant). Conclusion: Our findings further support the hypothesis of ecstasy-induced protracted alterations of the SERT. In addition, they might indicate reversibility of the availability of SERT as measured by PET. However, this does not imply full reversibility of the neurotoxic effects.

Full Article?

You haven't got the full article have you Biscuit? Seems to require fee paying registration for access.

Tis here: Long-Term Effects of "Ecstasy" Use on Serotonin Transporters of the Brain Investigated by PET

Ta very much Babydoc

Sounds like the US Government has finally been caught with it's pants down after yet another bullshit study. anything funded by the US government seems to draw skeptisism these days

Interesting read, good work Biscuit

*bump*

Well done BISKI!!!!


Thanks BT!

hehehe... Just goes to show hey!

Still, it doesn't defend stupid use of any chemical! Which is also a +!

ah, Ricaurte is a biased weasel. we are just learning about the brain's capacity for regeneration, new neuronal growth stimulating agents, etc. and cases of stroke / head trauma victims recovering sometimes full cognitive function with parts of the brain missing/irreversibly damaged points to holographic distribution of function, add morphogenics and we've got a lot to discover yet...

*bump*

will read this on my way into uni tomorrow, methinks.

Can someone who understands all the scientific mumbo jumbo give a rough summary in laymans terms?

Abstract:

Buchert R, Thomasius R, Nebeling B, Petersen K, Obrocki J, Jenicke L, Wilke F, Wartberg L, Zapletalova P, Clausen M , "Long-Term Effects of 'Ecstasy' Use on Serotonin Transporters of the Brain Investigated by PET", J. Nucl. Med. 44(3), 375-84, (2003).

Alterations of the serotonergic system due to ecstasy consumption have been extensively documented in recent literature. However, reversibility of these neurotoxic effects still remains unclear. To address this question, PET was performed using the serotonin transporter (SERT) ligand (11)C-(+)-McN5652 in a total of 117 subjects subdivided into 4 groups: actual ecstasy users (n = 30), former ecstasy users (n = 29), drug-naive control subjects (n = 29), and subjects with abuse of psychoactive agents other than ecstasy (n = 29).

METHODS: About 500 MBq (11)C-(+)-McN5652 were injected intravenously. Thirty-five scans were acquired according to a dynamic scan protocol of 90 min using a full-ring whole-body PET system. Transaxial slices were reconstructed using an iterative method. Individual brains were transformed to a template defined earlier. Distribution volume ratios (DVRs) were derived by application of a reference tissue approach for reversible binding. Gray matter of the cerebellum served as reference. SERT-rich brain regions-mesencephalon, putamen, caudate, and thalamus-were selected for the evaluation of SERT availability using volumes of interest predefined in the template.

RESULTS: Compared with drug-naive control subjects, the DVR in actual ecstasy users was significantly reduced in the mesencephalon (P = 0.004) and the thalamus (P = 0.044). The DVR in former ecstasy users was very close to the DVR in drug-naive control subjects in all brain regions. The DVR in polydrug users was slightly higher than that in the drug-naive control subjects in all SERT-rich regions (not statistically significant).

CONCLUSION: Our findings further support the hypothesis of ecstasy-induced protracted alterations of the SERT. In addition, they might indicate reversibility of the availability of SERT as measured by PET. However, this does not imply full reversibility of the neurotoxic effects.

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Translation:

There's been a lot of talk about how ecstasy affects the serotonin system. However, nobody really knows so far whether the observed neurotoxic effects are reversible. In order to check it out, we studied 117 people using PET scanning (a method of looking at the function of parts of the body using radioactively labelled chemicals); 30 were ecstasy users, 29 ex-users, 29 people who've never used drugs, and 29 people who extensively use other drugs than ecstasy.

METHODS: A short-lived radioactive tracer that's specific to the serotonin system was injected into each subject. Each patient was whole-body PET scanned for 90 mins to observe where the radioactive chemical went in the body after injection, and images of the chemical location were reconstructed by computer. Bunch of technical details about scanning protocols. Certain regions of the brain were identified in each subject as being serotonin related, and these regions were compared between subjects.

RESULTS: In current ecstasy users, less of the radioactive chemical was located in a couple of the serotonin specific areas of the brain, compared to people who've never used drugs. The results for ex-users were very close to the results of people who've never used drugs. The results for people with polydrug use were almost the same too; while being slightly higher even than the non-drug users, it was not a statistically significant result (i.e., there's no real conclusion that can be drawn from this).

CONCLUSION: We find that ecstasy does have an impact on the serotonin system, supporting the results of other studies in this area. Our results also indicate that these changes might be reversible based on the availability of the radiolabelled tracer in PET scans. However, this does not imply full reversibility of the neurotoxic effects.

Click to expand...

BigTrancer

You beat me to it BT! Oh well, here it is anyway

Some terms:

Ligand Molecule (bio or chemical) which binds to the receptor, enzyme, carrier molecule, etc

SERT Serotonin Transporter (carrier) molecule ( a large "folded" protein) which "presents" the ligand to the receptor

11C-(+)-McN5652 proprietary Compound, many of which are indicated only by number. This contains a radioactive isotope of carbon (11C). There are literally hundreds of such compounds used in neural research, particularly with 5HT (serotonin) receptors of which there are 14 subtypes currently known. Compounds are sought which display a high preference (affinity) for single types i.e. it only binds with 1 receptor type.

Mbq mega Bequeral, a unit of disintegration. 1 Bq = 1 disintegration/sec.

PET Positron Emission Topography. Using the emissions of the decaying C11 a map is made of the areas where the compounds go. A reference is essential and the tissue is likely taken from a fresh cadaver.


SERT densities are usually considered a measure of normal serotonin activity (roughly speaking). In this case, it is measured by how many 11C-(+)-McN5652 molecules actually bind to the transporter. Put simply, in a perfect world; No transporter -No binding. SERT will be present in less amounts in areas either low in serotonin availability, or if receptor density is low.


The way in which drugs, neurotransmitters etc work is by repeatedly binding with the receptor, transporter etc. The rates of binding, affinity, efficacy and how quickly enzymes break the chemical down, determine the actions, duration etc of the drug (or labeling chemical). To avoid mistakingly counting as SERT, other places the molecule may go, the rate of binding reversibility was used to distinguish these from SERT binding. The obtained specific area DVR's indicate how many active transporters are in each area.


What the report concludes is that users have lower SERT levels than non-users (controls), ex-users have higher SERT levels than users but slightly lower than controls. As should be seen, this report does not necessarily rubbish all past claims of neurotoxicity. Indeed it supports many of these findings. What is at odds, when looking at some claims of reports from those such as Richaurte, is that this damage may not be as long term as stated. Richaurte said he found evidence of damage in monkey brains exposed to a single dose of MDMA that lasted >7 years.

One of the best papers to read if you can get it is:

"A Review of Central 5-HT receptors and their function" by Nicholas M Marnes and Trevor Sharp published in neuropharmacology #38, 1999

Click to expand...

Be warned though. It starts off OK but gets very deep. It took me awhile to get through the 70 odd pages, but if serotonin is your thing.....

[Edit: corrected definition of MBq, p_d]

Thanks phase_dancer:

In this case I think MBq is 10^6 Bq, or megabequerel... as a side note the Curie is a convenient measure of radioactivity where 1 Ci = 3.7 x 10^10 Bq, used because the Bequerel (or as I like to call it, the buggerall) only represents 1 disintegration per second... which is bugger all really.

BT

Oops! my mistake, of course it's Mega Bequerel. Thanks BT, above post corrected.