A prospective cohort study on sustained effects of low-dose ecstasy use on the brain

[EvS]

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.8+/-3.1 years) in two sessions before and after first ecstasy use (1.8+/-1.3 tablets). Interval between baseline and follow-up was on average 8.1+/-6.5 months and time between last ecstasy use and follow-up was 7.7+/-4.4 weeks. Using 1H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (-6.2%), dorsolateral frontal cortex (-4.0%), and superior parietal cortex (-3.0%) (all significant at p<0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity (+3.7% on the Barratt Impulsiveness Scale) and decreased depression (-28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that incidental ecstasy use leads to extensive axonal damage. However, sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas, although it is not known whether this effect is permanent. Additional studies are needed to replicate these findings.

http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

epartment of Radiology, Academic Medical Center, University of Amsterdam, Feb 2007.

Interesting and good news! Look at that whopping 30% decrease in depression!

The downside: However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (-6.2%), dorsolateral frontal cortex (-4.0%), and superior parietal cortex (-3.0%).

Hmmmm..

 

[Ringfinger]

can someone tell me what that means?

 

[indelibleface]

You might get more involved responses in Advanced Drug Discussion. Moving...

(ADD mods: feel free to move it back if it ain't worthy.)

 

[Jamshyd]

I find it rather unprofessional that they're researching the effects of "ecstasy". What are they using for their research, street pills that could contain anything from MDMA to dried and ground-up dogshit?

 

[LuxEtVeritas]

^ good point, unless the randomness of street X is something that is intrinsic to the goal

 

[Cthulhu]

How does a study like this get approved by the ethics board? To administer an arguably toxic substance to human subjects, "naive" ones? Isn't extensive research on animals required first to rule out potential lasting damage? - it's not even like there are possible benefits for a life-threatening malady, as with experimental AIDS drugs. I can understand investigating LSD, with its absence of toxicity and extreme safety, as a therapeutic agent, but ecstasy? And then the study produces evidence in favor of some lasting impairment of neurological function. I could be overreacting, I'm just surprised.

 

[fastandbulbous]

How does a study like this get approved by the ethics board?

Same way they approve giving small amounts of nerve gas agents to voilunteers; minimal harm with a potential for much greater benefits from the research. If they banned use with volunteers of anything that might have a toxic profile the pharmaceutical industr's bringing new drugs to the market would stop completely.

The most important thing is that the subjects have volunteered to undergo these trials and it's not like the US military testing agents without consent

 

[Cthulhu]

Same way they approve giving small amounts of nerve gas agents to voilunteers; minimal harm with a potential for much greater benefits from the research.

Well thats my point - the purpose of this study wasn't to determine potential benefits, it was to determine potential brain damage. Yeah, decreased depression
was shown, but I doubt anyone is considering marketing ecstasy as a long-term, regular use treatment for depression.

I would prefer to see more research on the nature of the toxicity of mdma and is metabolites, on the biological/neurological aspects and possibilities for neutralizing that toxicity. Then maybe therapeutic research would be more reasonable.

 

[Beenhead]

Same way they approve giving small amounts of nerve gas agents to voilunteers; minimal harm with a potential for much greater benefits from the research. If they banned use with volunteers of anything that might have a toxic profile the pharmaceutical industr's bringing new drugs to the market would stop completely.

The most important thing is that the subjects have volunteered to undergo these trials and it's not like the US military testing agents without consent

so did the Brits there buddy! I was actually just reading an article about Sarin gas, or Mustard, I cant remember. There was a story where the British Military told some Royal Army engineer he was going to be a subject in a trial for the cure for the common cold, and they subjected him to Sarin gas!
Needless to say he died...

 

[fastandbulbous]

The British never had an MKULTRA program, just testing on squaddies (seen the film, they only received 50ug from the boffins at Porton Down unlike the up to 10mg doses of LSD they gave US military subjects at Edgewood arsenal (that's accordinbg to a BBC documentary,'Bad Trip to Edgewood')

 

[evlove]

The downside: However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter...

Increased fractional anisotropy of the white matter on diffusion weighted imaging is actually a good thing. It suggests greater white matter integrity. If you had poorly myelinated axons, water would diffuse in every direction (isotropic), but in healthy white matter tracts you want the diffusion to be mainly along the axis of the axon (anisotropic).

This is a cohort study, so the investigators were not administering ecstacy, rather they followed a group of participants who were likely to use ecstacy and did MRI and other tests at baseline and at a later point in time. This is a naturalistic design that is commonly used to investigate potentially harmful exposures, specifically because it would be unethical to investigate the negative effects of a substance in a randomized clinical trial design. Similarly, they do not study the effects of smoking on lung cancer by making subjects smoke, they follow people who already smoke.

Participants

Between April 2002 and April 2004, 188 young adults (77 M, 111 F, age 21.73.0 years) were included in the study. They had never used ecstasy, but were selected on a relatively high probability to start using ecstasy in the near future. Subjects were recruited using a combination of targeted site sampling, advertisement through a website on the project, and snowball sampling referrals. Main inclusion criteria were intention to probably or certainly use ecstasy for the first time in near future and/or having friends who already used ecstasy. Exclusion criteria were: ecstasy use in the past (at baseline), age below 18 or above 35 years, severe physical or mental illness, use of psychotropic medications such as serotonin reuptake inhibitors, pregnancy, use of intravenous drugs, and contraindications for MRI (eg, claustrophobia, pacemaker). Subjects had to abstain from psychoactive substances for at least 2 weeks and from alcohol for at least 1 week before examinations. This was checked by urine drug screening (enzyme-multiplied immunoassay for amphetamines, ecstasy, opiates, cocaine, benzodiazepine, cannabis, and alcohol).

They also address the question of purity.

A limitation of the present study is the uncertainty about variances in dosage and purity of ecstasy tablets, although pill-testing confirms that in the Netherlands more than 95% of the tablets sold as ecstasy contain MDMA as the only (91.2%) or major (4.2%) component