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An investigation into the neuronal activity induced by direct and indirect 5-HTâ‚‚ agonists as indicated by Arc mRNABeveridge, Thomas James Ramsey January 2003 (has links)
No description available.
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Contribuição individual dos enatiômeros isolados da 3,4-metilenodioximetanfetamina (MDMA) comparativamente com a mistura racêmica no estresse oxidativo hepático, renal e estriatal de ratos / Individual contribution of single MDMA enantiomers of 3,4- methylenedioxymetamphetamine (MDMA) compared to racemic mixture in liver, kidney and striatal rats toxicityBósio, Graziela Costa 09 February 2012 (has links)
A 3,4-metilenodioximetanfetamina (MDMA, ecstasy), derivada da anfetamina, é uma droga largamente utilizada para fins recreacionais devido à sensação de euforia, energia e desejo de socialização. Apesar de ter a reputação de ser uma droga segura, um número crescente de relatos clínicos e estudos experimentais indica que a MDMA pode produzir toxicidade no SNC, rim, fígado e coração. Embora esteja contida nos comprimidos de ecstasy como racemato (uma mistura de 50% de seus enantiômeros), sua biotransformação é enantioseletiva; em ratos, o enantiômero R é biotransformado mais rapidamente que o S. Como a biotransformação de MDMA é capaz de produzir metabólitos reativos, muito provavelmente, a forma R tenha um maior potencial para gerar ERO/ERN e dano oxidativo nos tecidos do que a forma S. Nos seres humanos ocorre o inverso. Portanto, o presente trabalho teve como objetivo avaliar a contribuição individual de cada enantiômero da MDMA isoladamente, tendo como referência a mistura racêmica, no estresse oxidativo hepático renal e estriatal de ratos. Ratos Wistar machos adultos (180-220g) foram divididos em quatro grupos: controle (salina), MDMA racêmico, R-MDMA e S-MDMA. (2 doses consecutivas de 10 mg/kg no intervalo de 24h, gavage). Parâmetros de estresse oxidativo serão utilizados como a medida da formação de malonaldeído, a determinação de níveis de glutationa reduzida e a atividade da glutationa-S-transferase. Os enantiômeros da MDMA racêmica foram separados por meio da cromatografia em fase líquida de alta eficiência em fase estacionária quiral. Os enantiômeros obtidos mostraram um alto grau de pureza e um bom rendimento. Nossos resultados mostraram que o conteúdo hepático de glutationa total dos ratos do grupo R,S-MDMA e do grupo R-MDMA, foi significativamente menor do que os do controle e os do S-MDMA, revelando que é o enantiômero R que contribui para a depleção de glutationa hepática induzida pela mistura racêmica. A alta reatividade do enantiômero R no fígado também pode ser constatada nos animais tratados apenas com R-MMDA, uma vez que houve uma produção significativamente aumentada de MDA, comparativamente aos outros grupos tratados e o controle. O conteúdo renal de glutationa total foi significantemente menor para todos os grupos tratados quando comparados com o controle. Com relação ao estriado, apenas os animais tratados com o isômero S isoladamente mostraram uma queda significativa da atividade da GST em comparação aos demais grupos tratados e controle. Tomando todos esses dados em conjunto, esse trabalho mostrou que os enantiômeros isolados da MDMA podem atuar de formas distintas no que se refere ao estado redox, principalmente no fígado, uma vez que o isômero R foi o que mais contribuiu para um dano oxidativo. / MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine derivate that is largely used for recreational purpose due to its feeling of euphoria, energy and the desire to socialize. Although MDMA has the reputation of being safe, a growing number of clinical reports and experimental studies indicate that MDMA can produce toxicity in the CNS, kidney, liver and heart.Although MDMA is present in ecstasy tablets as a racemate (a 50% mixture of its enantiomer) it has an enantioselective metabolism; in rats, the S-enantiomer is metabolized faster than the R-enantiomer and it is the more active pharmacological form. As the MDMA biotransformation can produce reactive metabolites, probably the R form has a greater potential to generate ROS / ERN and oxidative damage in tissues than the S. In humans, the opposite occurs. Therefore, this aim of the present study was to evaluate the individual contribution of single MDMA enantiomers, compared to racemic mixture in liver, kidney and striatal rats oxidative stress. Adult male Wistar rats (180- 220g) will be divided into four groups: control treatment (saline), racemic MDMA, R-MDMA and S-MDMA (two consecutive doses 24h apart with 10mg/kg, gavage). Oxidative stress status parameters will be used to measure malondialdehyde formation, the reduced glutathione levels determination and the glutathione-S-transferase activity. The enantiomers of racemic MDMA were separated by liquid chromatography high-efficiency chiral stationary phase. The enantiomers showed a high degree of purity and a good recovery. Our results showed that the total glutathione content in liver of rats in R,S-MDMA and R-MDMA group was significantly lower than the control and S-MDMA, revealing that the R-enantiomer that contributes to hepatic glutathione depletion induced by the racemic mixture. The high reactivity of the R enantiomer in the liver can also be observed in animals treated with R-MMDA, since there was a significantly increased production of MDA, compared with other treated and control groups. The total glutathione content in kidney was significantly lower for all treated groups compared with control. With respect to the striatum, only animals treated with the S isomer alone showed a significant decrease in GST activity compared to other treatment and control groups. Taking all these data together, this study shows that the isolated enantiomers of MDMA can act differently with regard to the redox state, mainly in the liver, since the R isomer was the largest contributor to oxidative damage.
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Contribuição individual dos enatiômeros isolados da 3,4-metilenodioximetanfetamina (MDMA) comparativamente com a mistura racêmica no estresse oxidativo hepático, renal e estriatal de ratos / Individual contribution of single MDMA enantiomers of 3,4- methylenedioxymetamphetamine (MDMA) compared to racemic mixture in liver, kidney and striatal rats toxicityGraziela Costa Bósio 09 February 2012 (has links)
A 3,4-metilenodioximetanfetamina (MDMA, ecstasy), derivada da anfetamina, é uma droga largamente utilizada para fins recreacionais devido à sensação de euforia, energia e desejo de socialização. Apesar de ter a reputação de ser uma droga segura, um número crescente de relatos clínicos e estudos experimentais indica que a MDMA pode produzir toxicidade no SNC, rim, fígado e coração. Embora esteja contida nos comprimidos de ecstasy como racemato (uma mistura de 50% de seus enantiômeros), sua biotransformação é enantioseletiva; em ratos, o enantiômero R é biotransformado mais rapidamente que o S. Como a biotransformação de MDMA é capaz de produzir metabólitos reativos, muito provavelmente, a forma R tenha um maior potencial para gerar ERO/ERN e dano oxidativo nos tecidos do que a forma S. Nos seres humanos ocorre o inverso. Portanto, o presente trabalho teve como objetivo avaliar a contribuição individual de cada enantiômero da MDMA isoladamente, tendo como referência a mistura racêmica, no estresse oxidativo hepático renal e estriatal de ratos. Ratos Wistar machos adultos (180-220g) foram divididos em quatro grupos: controle (salina), MDMA racêmico, R-MDMA e S-MDMA. (2 doses consecutivas de 10 mg/kg no intervalo de 24h, gavage). Parâmetros de estresse oxidativo serão utilizados como a medida da formação de malonaldeído, a determinação de níveis de glutationa reduzida e a atividade da glutationa-S-transferase. Os enantiômeros da MDMA racêmica foram separados por meio da cromatografia em fase líquida de alta eficiência em fase estacionária quiral. Os enantiômeros obtidos mostraram um alto grau de pureza e um bom rendimento. Nossos resultados mostraram que o conteúdo hepático de glutationa total dos ratos do grupo R,S-MDMA e do grupo R-MDMA, foi significativamente menor do que os do controle e os do S-MDMA, revelando que é o enantiômero R que contribui para a depleção de glutationa hepática induzida pela mistura racêmica. A alta reatividade do enantiômero R no fígado também pode ser constatada nos animais tratados apenas com R-MMDA, uma vez que houve uma produção significativamente aumentada de MDA, comparativamente aos outros grupos tratados e o controle. O conteúdo renal de glutationa total foi significantemente menor para todos os grupos tratados quando comparados com o controle. Com relação ao estriado, apenas os animais tratados com o isômero S isoladamente mostraram uma queda significativa da atividade da GST em comparação aos demais grupos tratados e controle. Tomando todos esses dados em conjunto, esse trabalho mostrou que os enantiômeros isolados da MDMA podem atuar de formas distintas no que se refere ao estado redox, principalmente no fígado, uma vez que o isômero R foi o que mais contribuiu para um dano oxidativo. / MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine derivate that is largely used for recreational purpose due to its feeling of euphoria, energy and the desire to socialize. Although MDMA has the reputation of being safe, a growing number of clinical reports and experimental studies indicate that MDMA can produce toxicity in the CNS, kidney, liver and heart.Although MDMA is present in ecstasy tablets as a racemate (a 50% mixture of its enantiomer) it has an enantioselective metabolism; in rats, the S-enantiomer is metabolized faster than the R-enantiomer and it is the more active pharmacological form. As the MDMA biotransformation can produce reactive metabolites, probably the R form has a greater potential to generate ROS / ERN and oxidative damage in tissues than the S. In humans, the opposite occurs. Therefore, this aim of the present study was to evaluate the individual contribution of single MDMA enantiomers, compared to racemic mixture in liver, kidney and striatal rats oxidative stress. Adult male Wistar rats (180- 220g) will be divided into four groups: control treatment (saline), racemic MDMA, R-MDMA and S-MDMA (two consecutive doses 24h apart with 10mg/kg, gavage). Oxidative stress status parameters will be used to measure malondialdehyde formation, the reduced glutathione levels determination and the glutathione-S-transferase activity. The enantiomers of racemic MDMA were separated by liquid chromatography high-efficiency chiral stationary phase. The enantiomers showed a high degree of purity and a good recovery. Our results showed that the total glutathione content in liver of rats in R,S-MDMA and R-MDMA group was significantly lower than the control and S-MDMA, revealing that the R-enantiomer that contributes to hepatic glutathione depletion induced by the racemic mixture. The high reactivity of the R enantiomer in the liver can also be observed in animals treated with R-MMDA, since there was a significantly increased production of MDA, compared with other treated and control groups. The total glutathione content in kidney was significantly lower for all treated groups compared with control. With respect to the striatum, only animals treated with the S isomer alone showed a significant decrease in GST activity compared to other treatment and control groups. Taking all these data together, this study shows that the isolated enantiomers of MDMA can act differently with regard to the redox state, mainly in the liver, since the R isomer was the largest contributor to oxidative damage.
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The pattern of memory and perceptual dysfunctions in recreational ecstasy usersBrown, John Anthony, John.Brown@anu.edu.au January 2006 (has links)
There is a growing body of evidence that the main psychoactive ingredient of the recreational drug ecstasy (methylendioxymethamphetamine; MDMA) causes lasting changes to the serotonin system in both animals and humans, including the hippocampus (involved in memory) and the occipital lobe (involved in visual perception). Previous studies have often found memory deficits in ecstasy users. However, the results have been far from consistent across studies. None of the methods used to date have adequately isolated the hippocampal component of memory from the contribution of other brain regions. Three memory studies were conducted in this thesis to clarify which components and processes of memory are in deficit in ecstasy users.¶
In the first memory study, ecstasy users (n=32) did not differ from non-drug using controls (n=29) on implicit memory (automatic non-conscious retrieval, as revealed by a stem-completion task), or explicit memory (conscious recollection, as revealed by stem-cued recall). In the second memory study, no significant differences were found between ecstasy users (n=30) and non-drug using controls (n=34) on tests designed to clarify the findings on explicit memory, or on two standard neuropsychological tests of long-term memory (prose recall and Auditory Verbal Learning Test) that allowed greater use of elaborative processing at study. In the third memory study, a number of tests were applied that differed in their elaborative processing demands, including the California Verbal Learning Test, Visual Paired Associates, and Verbal Paired Associates. Ecstasy users (n=32) had poorer recall, and made less strategic use of elaborative processing compared to both cannabis-using controls (n=33) and non-drug using controls (n=33). Also, on a novel test of elaborative processing (Verbal Triplet Associates), both cannabis users and ecstasy users had memory deficits on the first trial, but only ecstasy users had a significant learning deficit over successive trials. On the basis of the localisation of the components and processes of memory in literature, it was concluded that long-term memory deficits in ecstasy users may reflect changes in elaborative processes localised in the frontal lobes, or global deficits, rather than just changes to the memory functions of the hippocampus.¶
With regard to visual perception, no studies have been published to date that have examined MDMA-related changes to the behavioural functioning of the occipital lobe in humans. In the current thesis, this was investigated using the tilt aftereffect illusion. In accordance with expectations, ecstasy users had a larger tilt aftereffect compared to non-drug using controls (n=34). Unexpectedly, this result was only obtained for a subset of 12 ecstasy users (out of n=30) who had not used amphetamines in the recent past. It was concluded that the results for ecstasy users who had not recently used amphetamines were consistent with the proposal that ecstasy-related serotonergic changes in the occipital lobe broaden the tuning bandwidth of orientation sensitive neurons, and that the recent use of amphetamines appears to counteract that effect.
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Development and Initial Evaluation of an Ecstasy Craving QuestionnaireDavis, Alan Kooi 10 July 2012 (has links)
No description available.
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MDMA and Glutamate: Implications for Hippocampal GABAergic NeurotoxicityHuff, Courtney L., M.S. 02 June 2016 (has links)
No description available.
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Imaging brain activity in conscious monkeys following oral MDMA ("Ecstasy").Harder, Josie A., Brevard, M.E., Ferris, C.F., Meyer, J.S. January 2006 (has links)
No / Recreational use of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") poses worldwide potential health problems. Clinical studies show that repeated exposure to low oral doses of MDMA has toxic effects on the brain, altering cognitive and psychosocial behavior. Functional magnetic resonance imaging in conscious marmoset monkeys was used to evaluate the sensitivity of the brain to an oral dose of MDMA (1 mg/kg). Following MDMA administration, the midbrain raphe nuclei and substantia nigra, major sources of serotonin and dopamine, were activated as were the hippocampus, hypothalamus and amygdala. The corticostriatal circuit of dorsal thalamus, sensorimotor cortex and basal ganglia showed a robust, coherent activation pattern. Two key reward areas, the nucleus accumbens and prefrontal cortex, and most other cortical regions showed little activation. The visual cortex, however, showed intense activation without applied visual stimuli. These data identify brain areas and functional circuits sensitive to a recreational dose of MDMA, some of which may be vulnerable to long-term intermittent exposure to this drug.
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Phenomenology of MDMA Solo SessionsHills, Jack 31 July 2023 (has links)
No description available.
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The Role of Metabolism in Ecstasy-Mediated Serotonergic NeurotoxicityErives Quezada, Gladys Vanessa January 2009 (has links)
3,4-(±)-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative commonly used as a recreational drug. Although the selectivity of MDMA for the serotonergic system in rat and humans is well established, the specific mechanism associated with MDMA-induced neurotoxicity is not fully understood. The long-term neurotoxicity of MDMA appears to be dependent upon systemic metabolism since direct administration of MDMA into the brain fails to reproduce the neurotoxic effects seen following peripheral administration, indicating that the parent compound alone is unlikely to be responsible for the neurotoxicity. MDMA is O-demethylenated to the catechol metabolite N-methyl-α-methyldopamine (N-Me-α-MeDA) and N-demethylated to MDA by cytochrome (s) P450 (CYP450). Thioether (glutathione and N-acetylcysteine) metabolites of N-Me-α-MeDA and α-MeDA are neurotoxic and can be found in rat brain following s.c. injection of MDMA. Because multidose administration of MDMA is typical of drug intake during rave parties, we investigated the effects of multiple doses of MDMA on the concentration of neurotoxic thioether metabolites in rat brain. Administration of MDMA at 12-h intervals for a total of four injections led to a significant accumulation of the N-Me-α-MeDA thioether metabolites in striatal dialysate. In contrast, acute release of 5-HT concentrations was decreased. Since isoenzymes of the CYP2D subfamily (30% metabolism), and the CYP2B or CYP3A1 isoforms, catalyze the low and high KM O-demethylenation reactions, respectively, we subsequently examined the potential role of CYP2D1 in both a genetic and pharmacological model. The data is consistent with the hypothesis that systemic metabolism of MDMA contributes to MDMA-induced serotonergic neurotoxicity via the 20) generation of reactive metabolites. In both the genetic and pharmacological models of CYP2D1 deficiency, attenuation of MDMA-mediated decreases in brain 5-HT concentrations were in the same range (30-40%). Finally, we examined the contribution of various transporters using genetic and pharmacological models to investigate the mechanisms regulating the concentration of thioether metabolites in MDMA neurotoxicity. The data suggest that by regulating various transporters and brain concentrations of the neurotoxic thioether metabolites of MDMA, may subsequently modulate the degree of neurotoxicity. However, further studies are necessary to understand the precise mechanism by which Mrp’s and Oat1 transporters modulate MDMA-neurotoxicity. Taken together, these studies are consistent with the view that neurotoxicity of MDMA requires systemic metabolism to form α-MeDA and N-Me-α- MeDA by CYP2D6. Therefore, It is likely that neurotoxicity is mediated by the formation of systemic neurotoxic metabolites.
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Psicoterapia asistida con LSD, Psilocibina y MDMA. Descripciones realizadas por los terapeutas en torno a los procesos clínicosTartakowsky López, Ingrid 12 1900 (has links)
Magíster en Psicología Clínica de Adultos / En
la
presente
investigación
cualitativa
se
describen
las
psicoterapias
asistidas
con
LSD,
psilocibina
y
MDMA,
a
partir
de
entrevistas
realizadas
a
algunos
terapeutas
que
las
llevan
a
cabo
con
sus
pacientes.
Para
ello
se
ha
indagado
en
ciertos
aspectos
que
articulan
la
clínica,
tales
como
sus
fases,
sus
objetivos,
la
cura,
el
terapeuta,
el
vínculo
entre
paciente
y
terapeuta,
el
lugar
de
trabajo
y
las
técnicas
que
se
utilizan;
entre
las
que
se
encuentran
los
usos
de
sustancias
psicoactivas.
Utilizando
una
metodología
de
análisis
de
contenido,
se
han
observado
diversos
tipos
de
psicoterapias
asistidas
con
fármacos,
así
como
algunas
de
las
dimensiones
que
las
atraviesan:
política,
real
y
corporal.
También
se
ha
realizado
una
clasificación
de
los
efectos
catalizadores
que
comparten
la
LSD,
la
psilocibina
y
la
MDMA,
y
que
pueden
ser
de
interés
para
ser
utilizados
en
psicoterapia.
Además,
destaca
el
cuerpo
como
una
dimensión
en
la
que
convergen:
la
emergencia
de
las
problemáticas
del
sujeto,
con
los
efectos
potenciadores
de
las
drogas
y
las
formas
de
intervención
del
terapeuta.
Así
mismo
resaltan
ciertos
elementos
del
lugar
de
trabajo
como
vehiculizadores
de
las
experiencias
que
acontecen
con
dichas
sustancias,
como
son
el
elemento
sonoro
y
el
espacio
exterior,
los
que
bajo
un
cierto
ordenamiento
encausan
al
sujeto
hacia
lo
terapéutico.
También
se
han
realizado
algunas
reflexiones
y
vínculos
entre
los
postulados
de
Sigmund
Freud
y
Stanislav
Grof
respecto
de
los
estados
de
conciencia
y
su
emergencia
en
el
campo
psicoterapéutico.
Además,
se
han
encontrado
diversas
convergencias
y
divergencias
entre
el
marco
analítico
y
el
de
terapias
asistidas
que
se
realiza
hoy
en
día.
Asimismo
han
aparecido
cuatro
aspectos
que
son
propios
de
la
clínica
y
que
permiten
diferenciar
las
experiencias
terapéuticas
de
las
recreacionales
que
se
pueden
llegar
a
tener
con
LSD,
psilocibina
y
MDMA.
Estas
consideraciones
permiten
concluir
que
es
en
la
relación
que
establece
un
sujeto
con
su
estado
modificado
de
conciencia
donde
residen
las
posibilidades
terapéuticas,
y
no
tanto
en
los
efectos
directos
de
la
sustancia
que
se
ingiere.
Del
mismo
modo,
lo
encontrado
en
este
estudio
muestra
de
qué
maneras
las
terapias
asistidas
han
evolucionado
tomando
los
planteamientos
freudianos
hasta
emerger
de
la
forma
que
las
caracteriza
en
la
actualidad
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