Ecstasy Long Term Effects On The Brain – Liesbeth Reinemann, Jan BA. Hebraken, Charles BL. Majoy, Jan Buij and Gerard J. Dan Heaton
Abuse of the popular recreational drug “ecstasy” (MDMA) has been linked to an increased incidence of cerebrovascular accidents. It is known that MDMA alters brain serotonin (5-HT) concentrations and that brain postsynaptic 5-HT.
Ecstasy Long Term Effects On The Brain
The receptors play a role in the regulation of the brain microvasculature. Therefore, we used brain imaging to determine whether MDMA use predisposes to cerebrovascular accidents by altering brain 5-HT neurotransmission.
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I] R91150 single-photon emission CT in 10 abstinent recent MDMA users, five former MDMA users, and 10 healthy control subjects. In addition, to investigate whether changes in the brain 5-HT
As receptor density is associated with changes in blood vessel volume, we calculated relative cerebral blood volume maps from dynamic MR imaging sets in five MDMA users and six healthy control subjects.
I] R91150 binding ratios were significantly lower in recent MDMA users than in former MDMA users and control subjects. This finding suggests a down-regulation of 5-HT
Receptors in human MDMA users. MDMA users may therefore be at risk of cerebrovascular accidents as a result of alterations in the 5-HT neurotransmission system.
The Negative Mdma Health Effects
Recently, several case reports have linked abuse of the popular recreational party drug 3, 4-methylenedioxymethamphetamine (MDMA, or “Ecstasy”) to the incidence of cerebrovascular accidents (1–8). The brain region most vulnerable to the vascular effects of MDMA is the globus pallidus, an area rich in serotonin (5-HT) nerve terminals (9, 10). Considerable evidence has accumulated over the years strongly pointing to the involvement of 5-HT and 5-HT.
Receptors in the regulation of brain microcirculation (11–12). MDMA induces the release of 5-HT from serotonergic neurons. However, abuse of this drug eventually leads to loss of serotonergic neurons, leading to 5-HT depletion and compensatory up-regulation of postsynaptic 5-HT.
The receptor. Several reports have therefore suggested that MDMA abuse may predispose to cerebrovascular disease as a result of MDMA-induced effects on brain 5-HT concentrations and 5-HT.
Receptors (2, 9, 10, 13). Advances in neuroimaging techniques, such as single-photon emission CT (SPECT), have made it possible to study 5-HT.
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The receptors are specific and reversible, as shown by inhibition of binding by retanserin and displacement by ketanserin (14). In addition, by using cerebral blood volume (CBV) maps calculated from dynamic MR imaging sets, it is now possible to study relative CBV (rCBV) in the brain (15, 16), subtracting regional vasospasm rCBV values. and vasodilatation will increase. CBV values (17).
Receptor density, and, using MR imaging sets, to determine whether these effects are associated with changes in rCBV in abstinent recent MDMA users, former MDMA users, and healthy control subjects.
Fifteen participants who reported previous heavy use of MDMA (mean age, 26 years) and 10 age-matched control subjects (mean age, 23 years) ( Table 1 ) were enrolled in the SPECT study. Eligibility criteria for the MDMA group were past use of at least 50 pills of MDMA. Ten participants had recently used this drug (MDMA group) and five former MDMA users had abstained from using MDMA (former MDMA group; Table 1 ). Eligibility criteria for the MDMA group were a drug-free interval of 1 week to 2 months before the study. Because animal studies have shown that 5-HT. down-regulation of
The cut-off point of the drug-free interval for the former MDMA group was established at 2 months, given that the receptors remained intact for at least 1 month after the last administration of MDMA (18). The control group consisted of healthy subjects with no self-reported use of psychoactive drugs, including MDMA. Recruitment was done through advertisements in local newspapers. Participants agreed to abstain from psychotropic medication use for at least 1 week prior to the study, and underwent urine drug screening (with enzyme-linked immunoassay for amphetamines, barbiturates, benzodiazepine metabolites, cocaine and metabolites, marijuana, and opiates). ) was asked to do. Before admission. After examination of urine samples, exclusion criteria were a positive drug screen, pregnancy, serious medical or neuropsychiatric illness requiring informed consent, claustrophobia, a cardiac pacemaker or surgical clip, and neuropsychiatric illness in which 5-HT is implicated. All participants gave written informed consent.
Reduced 3,4 Methylenedioxymethamphetamine (mdma, Ecstasy) Initiated Oxidative Dna Damage And Neurodegeneration In Prostaglandin H Synthase 1 Knockout Mice
For SPECT studies, a Streichman Medical Equipment 810X tomographic system was used (Streichtman Medical Equipment, Inc., Medfield, MA). The transaxial resolution of this camera is 7.6 mm full-width at half-maximum of a line source in air, and the axial resolution is 13.5 mm. Each acquisition consisted of 15 slices in a 128 × 128 matrix with a slice spacing of 5 mm and a scanning time of 3 min per slice. The energy window was set at 135 to 190 kV. Subjects lie in the supine position with the head parallel to the orbitomattal line, and are positioned such that the scanning volume initially includes the cerebellum. Acquisition of images began 2 h after intravenous injection of approximately 140 MBq [
I]R91150 (radiolabeling as described by Busato and colleagues [ 14 ]), a time at which specific binding is maximal and stable up to 8 h after injection. For evaluation of scans, reviewers were blinded to subject status. For analysis of [
I]R91150 binding, a standard template with regions of interest (ROIs), was created manually from coregistered MR images. For positioning, we used these MR images as a guide. Core registration of MR images and SPECT scans was performed using the Hermes Multi Modality software package (Nuclear Diagnostics, Stockholm, Sweden). The template, including ROIs for the frontal, parietal, and occipital cortices, was placed on the three consecutive highest SPECT slices. An additional template was created with an ROI for the cerebellum. The mean signal density (number of pixels per pixel of frontal, parietal, and occipital cortices) of the left and right cortices and the cerebellum was determined. ROI analysis was performed by an investigator who was unaware of the participants’ history. Arising in the cerebellum, 5-HT is thought to be free
Receptor, was used as a reference for background radioactivity (nonspecific binding plus free ligand). The ROI/cerebellum activity ratio was calculated as a relative measure of specific binding to 5-HT
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RCBV maps were calculated from dynamic MR imaging sets obtained with echo-planar spin-echo imaging after intravenous injection of gadolinium-based contrast material. MR images were acquired at 1.5 T. MR imaging was performed, on average, 6 h before SPECT studies. An 18-gauge catheter was inserted into a large peripheral vein before MR imaging was performed. A saline drip was used to maintain venous patency. Gadopentetate dimeglumine (0.2 mmol/kg) was power-injected through the angiocatheter at a rate of 5 mL/s. A series of images (40 series of 12 slices in 64 seconds) before, during, and after injection was obtained using a lipid-suppressed spin-echo-planar pulse sequence (TR/TE = 800/54) of 1202 milliseconds. was obtained at intervals. of the opposite agent. Lipid suppression was used to suppress subcutaneous fat. We used a 128 × 128 × 12 matrix with a voxel size of 1.8 × 1.8 × 6.0 mm. After data collection, rCBV maps were derived on a voxel-by-voxel basis from dynamic imaging sets (using software developed at the MGH-NMR Center, Charlestown, MA) ( 20 , 21 ). Because the sensitivity contrast rCBV mapping method yields relative rather than absolute values of rCBV, comparison across subjects is facilitated by reference to an internal standard. Similar to previous studies (22, 23), normal white matter was used as this reference. To calculate rCBV/white matter, ROIs of different brain regions (left and right frontal and occipital cortices, white matter, putamen, and globus pallidus) were defined on the rCBV maps by a radiologist unaware of the participants’ history. was The ratio was calculated by dividing the mean rCBV of the brain region by the unilateral mean white matter. Because rCBV maps enable quantification of vascularization in relative terms ( 22 ), a high rCBV ratio indicates high rCBV, or vasodilatation, whereas a low rCBV ratio indicates vasoconstriction ( 17 ).
I] R91150 radioligand binding across groups was assayed by one-way analysis of variance. Differences in rCBV values between groups were analyzed using an unpaired Student’s test
I]R91150 radioligand binding and rCBV values in specific brain regions were examined with Spearman’s rank correlation, as this has the advantage that it does not specifically assess a linear association but a more general association. does A
A value less than .05 was considered significant with a two-tailed test. We analyzed all data with SPSS version 9.0 software (Statistical Package for the Social Sciences, Chicago, IL).
Short And Long Term Effects Of Mdma Abuse
Participants in the MDMA and ex-MDMA groups consumed, on average, 139 ± 129 pills of MDMA and 218 ± 201 pills, respectively (Table 1). Participants in MDMA and ex-MDMA had not used MDMA, on average, for 7 ± 5 weeks and 18 ± 15 weeks, respectively, prior to this investigation. All participants were right-handed.
Receptor binding ratios in the MDMA group were significantly lower than those in the ex-MDMA and control groups (
Receptor binding ratios were higher in the ex-MDMA group than in the control group, although this difference was not statistically significant (Table 1, Figures 1 and 2).
I] R91150 binding ratio in cortex: control subjects compared with MDMA and ex-MDMA users. The cortical binding ratio was calculated as cortical binding / binding in the cerebellum.
Physical And Psychological Ecstasy Effects
In addition to SPECT studies, we performed dynamic MR imaging in a random sample of participants
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