Dear awarren,
First off, please let me state that I am not a doctor and I am by no means qualified to give professional health care advice.
May I please present some preliminary research that suggests that MDMA may be neurotoxic (it seems the evidence strongly suggests MDMA may be neurotoxic in humans but has not been proven to be conclusively as potentially damaging as the case is with METH)?
Three related peer reviews:
Psychopharmacology (Berl). 2007 Jan;189(4):407-24. Epub 2006 Mar 16.
3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings.Baumann MH, Wang X, Rothman RB.
Clinical Psychopharmacology Section, Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. mbaumann@intra.nida.nih.gov
RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate. OBJECTIVE: The present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons, (2) the use of "interspecies scaling" to adjust MDMA doses across species, (3) the effects of MDMA on established markers of neuronal damage, and (4) functional impairments associated with MDMA-induced 5-HT depletions. RESULTS: MDMA is a substrate for monoamine transporters, and stimulated release of 5-HT, NE, and DA mediates effects of the drug. MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1-2 mg/kg), suggesting that there is no reason to adjust doses between these species. Typical doses of MDMA causing long-term 5-HT depletions in rats (e.g., 10-20 mg/kg) do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis. MDMA-induced 5-HT depletions are accompanied by a number of functional consequences including reductions in evoked 5-HT release and changes in hormone secretion. Perhaps more importantly, administration of MDMA to rats induces persistent anxiety-like behaviors in the absence of measurable 5-HT deficits. CONCLUSIONS: MDMA-induced 5-HT depletions are not necessarily synonymous with neurotoxic damage. However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.
PMID: 16541247 [PubMed - indexed for MEDLINE]
J Psychopharmacol. 2006 Mar;20(2):194-210.
Ecstasy: are animal data consistent between species and can they translate to humans?Easton N, Marsden CA.
School of Biomedical Science, University of Nottingham, Queen's Medical Centre, UK. neil.easton@nottingham.ac.uk
The number of 3,4-methylenedioxymethamphetamine (ecstasy or MDMA) animal research articles is rapidly increasing and yet studies which place emphasis on the clinical significance are limited due to a lack of reliable human data. MDMA produces an acute, rapid release of brain serotonin and dopamine in experimental animals and in the rat this is associated with increased locomotor activity and the serotonin behavioural syndrome in rats.MDMA causes dose-dependent hyperthermia, which is potentially fatal, in humans, primates and rodents. Subsequent serotonergic neurotoxicity has been demonstrated by biochemical and histological studies and is reported to last for months in rats and years in non-human primates. Relating human data to findings in animals is complicated by reports that MDMA exposure in mice produces selective long-term dopaminergic impairment with no effect on serotonin. This review compares data obtained from animal and human studies and examines the acute physiological, behavioural and biochemical effects of MDMA as well as the long-term behavioural effects together with serotonergic and dopaminergic impairments. Consideration is also given to the role of neurotoxic metabolites and the influence of age, sex and user groups on the long-term actions of MDMA.
PMID: 16510478 [PubMed - indexed for MEDLINE]
Addiction. 2006 Mar;101(3):348-61.
Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage?Gouzoulis-Mayfrank E, Daumann J.
Department of Psychiatry and Psychotherapy, University of Cologne, Germany. e.gouzoulis@uni-koeln.de
BACKGROUND: The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine: MDMA and some analogues) causes selective and persistent neurotoxic damage of central serotonergic neurones in laboratory animals. Serotonin plays a role in numerous functional systems in the central nervous system (CNS). Consequently, various abnormalities including psychiatric, vegetative, neuroendocrine and cognitive disorders could be expected in humans following MDMA-induced neurotoxic brain damage. AIMS: In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies with drug users. The aim of this paper was to review this literature and weigh the strength of the evidence for persistent brain damage in ecstasy users. METHODS: We used Medline to view all available publications on 'ecstasy' or 'MDMA'. All available studies dealing with ecstasy users entered this analysis. FINDINGS AND CONCLUSIONS: Despite large methodological problems the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial restitution may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive, particularly memory, impairments with heavy ecstasy use. However, the evidence cannot be considered definite and the issues of possible pre-existing traits or the effects of polydrug use are not resolved. RECOMMENDATIONS: Questions about the neurotoxic effects of ecstasy on the brain remain highly topical in light of its popularity among young people. More longitudinal and prospective studies are clearly needed in order to obtain a better understanding of the possible long-term sequelae of ecstasy use in humans.
PMID: 16499508 [PubMed - indexed for MEDLINE]
I am not sure what pharmacological course of action is best for your particular case, if any, but before taking any supplements or medicines, the safest usual course of action is to have a professional evaluate your case specifics. Why? Well, to start, if you are already taking some particular medicines, supplements, eating a particular diet, or exercising, smoking, drinking, &c. -- or your genetic profile may perhaps indicate that you may have a predisposition to e.g. cancer or heart disease (e.g. your family members were afflicted with such diseases) -- it's probably smartest to disclose all of these factors to your doctor first because there may be particular elements in your diet or lifestyle that perhaps may be more or equally dangerous to compensate for. In addition, there are possible negative interactions and side effects from many drugs and supplements. I'd probably suggest that you start by working with a licensed health care practitioner that specializes in addiction and maybe one that specializes in integrative medicine.
If you are already a heavy drinker of alcoholic beverages, smoke cigarettes, and you do not exercise at all, then it might be equally (or perhaps more) important to quit smoking, drinking so heavily, and perhaps begin exercising appropriately as these elements may be more important to worry about taking this or that pill that has never been proven to induce neurogenesis in humans.
However, that said, there may be some therapies that may have potential to help recovering drug addicts regain "normal" neurological function (if it's true that they may have lost some).
Although most of this evidence may be preliminary (i.e. in rats, mice, small or specialized populations -- i.e. not drug addicts per se), I am reasonably confident that some drugs/supplements/therapies that have shown potential particular neurogenesis effects in rodents and other species -- through the proper clinical trials, of course -- could theoretically be later proven to be effective for the same uses in humans with brain damage inflicted by drug abuse or other types of brain trauma (such as stroke or injury).
If you are a recovering drug addict, you may also find the following topic of interest:
Drug Abuse Strikes 1 in 10 Americans
Take care.
Here's a quick update on the potential neurotoxicity potential of MDMA. I am quoting myself because it seems I made a statement above that suggests that MDMA might not be neurotoxic; this new evidence published in the today in the media and in AJP a bit earlier might suggest otherwise.
MedPage Today: News Source
Low-Dose Ecstasy Use Linked to Decline in Verbal Memory
By Judith Groch, Senior Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
June 04, 2007
MedPage Today Action Points
o Explain to patients who ask that even a low cumulative dose of Ecstasy (over six to seven weeks, for example) can cause a decline in verbal memory in new users.
Review
AMSTERDAM, The Netherlands, June 4 -- New users who took the street drug Ecstasy for a mean 1.6 months at low cumulative doses showed a decline in verbal recall and recognition.
There is growing evidence that Ecstasy, the street name for ±-3,4-methylenedioxy-methamphetamine (MDMA), is potentially neurotoxic in human beings, wrote Thelma Schildt, M.Sc., of the University of Amsterdam, and colleagues in the June issue of the Archives of General Psychiatry.
However, they said, most studies have been done on frequent Ecstasy users and there have been no human data regarding the sustained neurocognitive effects of a single or low dosage use of the drug among novice users.
To examine that question, the researchers conducted a prospective cohort study, part of the Netherlands XTC Toxicity study. The original sample consisted of 188 healthy, Ecstasy-naive volunteers (mean age, 22) who said they had considered starting to use Ecstasy in the near future.
The initial enrollment took place from April 10, 2002 to April 28, 2004, with a follow-up within three years.
Of the original 188 subjects, 58 started using Ecstasy (mean cumulative dose, 3.2 tablets; median cumulative dose 1.5 tablets in a mean period of 1.6 months). The average follow-up was over 11.1 months.
They were compared with 60 subjects who had never used Ecstasy and were matched for age, sex, intelligence, and use of substances other than Ecstasy.
Subjects were paid for their participation, depending on the number of assessment sessions. Differences in cognition between Ecstasy users and non-users were adjusted for differences in use of cannabis and other recreational drugs.
At the initial examination, the two groups showed no statistically significant differences in any of the neuropsychological test scores, the researchers said.
At follow-up, however, scores for change on immediate and delayed verbal recall and verbal recognition were significantly lower in those who'd taken Ecstasy compared with the non-users. The changes, the researchers noted, were still within the normal range.
For example, on the Rey Auditory Verbal Learning Test (RAVLT), which tests the immediate recognition of words, the change score for the Ecstasy users was 0.86, compared with 3.90 for the nonusers.
The mean recognition of words score at the initial examination for the Ecstasy users was 29.95 (SD 0.2) and 29.66 at follow-up, with 22.4% of subjects showing a decline.
The initial score for the non-users was 29.88 and at follow-up 29.93, with 6.7% of subjects showing a decline (P=0.02).
There were no significant differences on other test scores, the researchers reported. At follow-up, the Ecstasy users reported to have used a mean of 3.2 tablets (range 0.5-50 tablets; median 1.5 tablets) in a mean period of 1.6 months during the average follow-up of 11.1 months. Mean follow-up for the non-users was 19.1 months.
The assessment took place on average 11.8 weeks after the last Ecstasy use, unlike the much shorter durations in other studies, the researcher noted.
At follow-up, the Ecstasy users also reported having used more cannabis and cocaine in the previous year than the non-Ecstasy users. The non-users also drank less alcohol at follow-up, the researchers reported.
The current findings are consistent with numerous previous studies that reported a specific negative effect of Ecstasy use on verbal memory, the researchers said.
In this study, they noted, the association between Ecstasy dose and verbal memory performance was rather weak. This was not surprising, they said, given the relatively low doses that were used and the short duration of Ecstasy use.
No differences between the two groups were observed on other neurocognitive tests, nor was sex a factor, the researchers said. Some explanations include a possible combined effect with cannabis, a possibility that cannot be excluded.
Another possible confounding effect might have been depression, leading to higher levels of sensation-seeking. Yet, this would not explain why only verbal memory test scores were affected, whereas scores on other highly demanding tests were not affected, the investigators wrote.
It can be hypothesized, they said, that the medial temporal lobes, particularly the hippocampal area, are specifically vulnerable to Ecstasy. It is possible, they said, that the main underlying factor is depletion of serotonin, involved in several cognitive functions, but possibly especially relevant to learning and memory, while attention remains unaffected.
The researchers acknowledged several limitations of the study, including the prospective design, which limited evidence of causality. There was also a potential confounding of lifestyle differences, the pattern of drug use and its environment, and the lack of control of the purity of the amount of MDMA in the tablets.
Moreover, they said, the sample was not representative of the general population of young adults, which might limit the generalizability of the results.
A final limitation, the researchers said, is that the study did not answer the question of whether the observed short-term effects will remain after quitting the drug. Monitoring this cohort would be worthwhile, they said.
Although the performance of the group of Ecstasy users was still within the normal range and the immediate clinical relevance of the observed deficits is limited, the researchers concluded, the long-term consequences cannot be excluded.
This study was supported by a grant from the Netherlands Organization for Health Research and Development as part of their Addiction Program. No financial disclosures were reported.
Primary source: Archives of General Psychiatry
Source reference:
Schilt T, et al "Cognition in Novice Ecstasy Users With Minimal Exposure to Other Drugs: A Prospective Cohort Study" Arch Gen Psychiatry 2007; 64: 728-736.
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Primary source:
News Source: Archives of General Psychiatry
Cognition in Novice Ecstasy Users With Minimal Exposure to Other Drugs
A Prospective Cohort Study
Thelma Schilt, MSc; Maartje M. L. de Win, MD, PhD; Maarten Koeter, PhD; Gerry Jager, PhD; Dirk J. Korf, PhD; Wim van den Brink, MD, PhD; Ben Schmand, PhD
Arch Gen Psychiatry. 2007;64:728-736.
Context Ecstasy (street name for [±]-3,4-methylenedioxymethamphetamine [MDMA]) use has been associated with cognitive deficits, especially in verbal memory. However, owing to the cross-sectional and retrospective nature of currently available studies, questions remain regarding the causal direction and clinical relevance of these findings.
Objective To examine the relationship between Ecstasy use and subsequent cognitive performance.
Design A prospective cohort study in Ecstasy-naive subjects with a high risk for future first Ecstasy use, as part of the Netherlands XTC Toxicity study. The initial examination took place between April 10, 2002, and April 28, 2004; follow-up was within 3 years after the initial examination.
Setting and Participants One hundred eighty-eight healthy Ecstasy-naive volunteers (mean age, 22 years) were recruited. Of these, 58 subjects started using Ecstasy (mean cumulative dose, 3.2 tablets; median cumulative dose, 1.5 tablets). They were compared with 60 persistent Ecstasy-naive subjects matched on age, sex, intelligence, and use of substances other than Ecstasy. Differences in cognition between Ecstasy users and Ecstasy-naive subjects were adjusted for differences in cannabis and other recreational drug use.
Main Outcome Measures Change scores between the initial examination and follow-up on neurocognitive tests measuring attention, working memory, verbal and visual memory, and visuospatial ability.
Results At the initial examination, there were no statistically significant differences in any of the neuropsychological test scores between persistent Ecstasy-naive subjects and future Ecstasy users. However, at follow-up, change scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-naive subjects. There were no significant differences on other test scores.
Conclusions Our findings suggest that even a first low cumulative dose of Ecstasy is associated with decline in verbal memory. Although the performance of the group of incident Ecstasy users is still within the normal range and the immediate clinical relevance of the observed deficits is limited, long-term negative consequences cannot be excluded.
Author Affiliations: Amsterdam Institute for Addiction Research (Ms Schilt and Drs Koeter and van den Brink), Amsterdam, the Netherlands; Departments of Psychiatry (Ms Schilt and Drs Koeter and van den Brink), Radiology (Dr de Win), and Neurology (Dr Schmand), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre, Utrecht, the Netherlands (Dr Jager); and Bonger Institute of Criminology (Dr Korf) and Department of Psychology (Dr Schmand), University of Amsterdam, Amsterdam, the Netherlands.
It seems to probably not be a good idea to take this drug if you care about your brain.
There may be, however -- future treatments to help recovering MDMA addicts restore brain function, if it's true they may have lost some. I imagine high resolution MRIs might be required to determine the degree of damage inflicted and also to determine if any damaged regions may be restored to normal. However, future potential therapies for recovering drugs addicts are not -- at least at this time -- indicated for and therefore it may require alterations to
DSM so doctors may prescribe such drugs without fear of malpractice suits.
It would likely take a lot of work to get these changes implemented; however, with the current size of the METH epidemic and the rate that it seems to be growing, the future demand for therapies to restore cognitive function should make the effort profitable for the pharmaceutical companies involved in such work.
Take care.