Effects of (±) 3,4-methylene–dioxymethamphetamine (ecstasy) on dopamine system function in humans (original) (raw)
Related papers
Biological Psychiatry, 2000
Background: Fifteen (Ϯ)3,4-Methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse, and 15 control subjects were included in the study. Methods: Prolactin (PRL) and cortisol (CORT) responses to the serotonergic agonist d-fenfluramine (D-fen), clinical psychobehavioral changes, and psychometric measures were evaluated 3 weeks and then 12 months after MDMA discontinuation. Results: MDMA users showed significantly reduced PRL and CORT responses in comparison with control subjects at 3 weeks (respectively, p Ͻ .001; p Ͻ .005). The responses of PRL to D-fen were unmodified at 12 months after prolonged abstinence and were significantly reduced in comparison with controls (p Ͻ .001). In contrast, CORT responses in MDMA users were restored after 12 months of abstinence, with significantly higher responses to D-fen, in comparison with 3-week responses (p Ͻ .05). MDMA users' high scores on the Novelty Seeking (NS) scale on the Tridimensional Personality Questionnaire (TPQ) appeared unchanged by long-term abstinence. In contrast, Buss Durkee Hostility Inventory (BDHI) (Buss and Durkee 1957) direct and guilt scores decreased significantly after 12 months of abstinence. PRL AUCs at 12 months were inversely correlated with the measures of MDMA exposure (r ϭ Ϫ.538).
Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans
Psychopharmacology, 2002
Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used phenethylamine. Reports have described the effects of MDMA in a controlled laboratory setting, but the full range of effects of MDMA in humans is still not completely characterized. Objectives: To describe the physiological, subjective, and hormonal changes after single doses of MDMA in a laboratory setting and examine relationships between these effects. Methods: Eight MDMA-experienced volunteers each received placebo, 0.5 mg/kg, and 1.5 mg/kg oral doses of MDMA in a double-blind crossover study. Results: The 1.5 mg/kg dose (comparable to that typically used by most participants) produced significant subjective effects, peaking at about 2 h after dosing, including some effects commonly associated with stimulant drugs, hallucinogens, and entactogens. MDMA significantly increased plasma cortisol, prolactin, and dehydroepiandrosterone (DHEA) levels. Increase in plasma cortisol after the 1.5 mg/kg dose correlated with increased heart rate, rate-pressure product, and drug liking. Rise in DHEA correlated with euphoria. Conclusions: A typically used dose of MDMA produced effects commonly associated with stimulants and hallucinogens. Subjects liked MDMA. Correlations between cortisol and DHEA levels and some physiological and psychological effects are consistent with animal data suggesting that hormones modulate some responses to drugs of abuse.
Psychiatry Research, 2003
... Contact Information , E-mail The Corresponding Author , a , Sara Bassignana b , Amir Zaimovic a , Gabriele Moi a , Monica Bussandri a , Rocco Caccavari a ... asked to identify rapidly the colors in which words were printed (eg the word 'red' printed in the color green, the correct ...
Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users
Drug and Alcohol Dependence, 2000
Twelve heavy recreational ecstasy drug users (30-1000 occasions), 16 light ecstasy users (1 -20 occasions) and 22 non ecstasy user controls, with group mean ages around 21 years, were compared. Three self-rating questionnaires were completed when drug-free: the SCL-90 (an outpatient psychiatric symptom checklist), the impulsiveness venturesomeness and empathy (IVE) scale; and the uplifts, hassles, stresses and cognitive failures questionnaire. Heavy Ecstasy users reported significantly higher scores than controls on the following SCL-90 factors: paranoid ideation, psychoticism, somatisation, obsessionality, anxiety, hostility, phobic anxiety, altered appetite and restless sleep, together with greater IVE impulsiveness. Light ecstasy users generally produced intermediate scores, with significantly higher scores than controls on two factors and significantly lower scores than heavy ecstasy users on another two. Previous reports have described various psychiatric and psychobiological disorders in recreational ecstasy users, but it is not known how typical they are, being mainly based on individual case studies. This is the first study to describe psychological problems in a non clinical sample of young recreational ecstasy users. However, our ecstasy users were polydrug users, with both groups showing significantly greater usage of amphetamine, LSD and cocaine, than the controls. These other illicit drugs probably contributed to their adverse psychobiological profiles, while there is also the possibility of pre-existing differences between ecstasy users and non users. However, since repeated MDMA can cause serotonergic neurotoxicity in laboratory animals and man, these problems may reflect reduced serotonin activity induced by regular ecstasy use.
European Journal of Pharmacology, 2013
Although the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is often described as a selective serotonergic neurotoxin, some research has challenged this view. The objective of this study was to determine the influence of MDMA on subsequent levels of two different markers of dopaminergic function, the dopamine transporter (DAT) as well as dopamine and its major metabolites. In experiment I, adult male Sprague-Dawley rats were administered either a low or moderate dose MDMA binge (2.5 or 5.0 mg/kg  4 with an inter-dose interval of 1 h) or saline, and were killed 1 week later. The moderate dose dramatically reduced [ 3 H]WIN 35,428 binding to striatal DAT by 73.7% (P r 0.001). In experiment II, animals were binged with a higher dose of MDMA (10 mg/kg  4) to determine the drug's effects on concentrations of serotonin (5-HT), dopamine, and their respective major metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum and frontal cortex 1 week later. As expected, MDMA significantly reduced 5-HT and 5-HIAA (Z50%) in these structures, while only a marginal decrease in dopamine was noted in the striatum. In contrast, levels of DOPAC (34.3%, P o 0.01) and HVA (33.5%, P o 0.001) were reduced by MDMA treatment, suggesting a decrease in dopamine turnover. Overall, these findings indicate that while serotonergic markers are particularly vulnerable to MDMA-induced depletion, significant dopaminergic deficits may also occur under some conditions. Importantly, DAT expression may be more vulnerable to perturbation by MDMA than dopamine itself.
…, 2004
Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are illicit drugs that are increasingly used in combination. The acute and long-term effects of MDMA/METH combinations are largely uncharacterised. Objectives: The current study investigated the behavioural, thermal and neurotoxic effects of MDMA and METH when given alone or in combined low doses. Methods: Male rats received four injections, one every 2 h, of vehicle, MDMA (2.5 or 5 mg/ kg per injection), METH (2.5 or 5 mg/kg per injection) or combined MDMA/METH (1.25+1.25 mg/kg per injection or 2+2 mg/kg per injection). Drugs were given at an ambient temperature of 28°C to simulate hot nightclub conditions. Body temperature, locomotor activity and head-weaving were assessed during acute drug administration while social interaction, anxiety-related behavior on the emergence test and neurochemical parameters were assessed 4-7 weeks later. Results: All treatments acutely increased locomotor activity, while pronounced head-weaving was seen with both MDMA/METH treatments and the higher dose METH treatment. Acute hyperthermia was greatest with the higher dose MDMA/ METH treatment and was also seen with MDMA but not METH treatment. Several weeks after drug administration, both MDMA/METH groups, both METH groups and the higher dose MDMA group showed decreased social interaction relative to controls, while both MDMA/ METH groups and the lower dose MDMA group showed increased anxiety-like behaviour on the emergence test. MDMA treatment caused 5-HT and 5-HIAA depletion in several brain regions, while METH treatment reduced dopamine in the prefrontal cortex. Combined MDMA/ METH treatment caused 5-HT and 5-HIAA depletion in several brain regions and a unique depletion of dopamine and DOPAC in the striatum. Conclusions: These results suggest that MDMA and METH in combination may have greater adverse acute effects (head-weaving, body temperature) and long-term effects (decreased social interaction, increased emergence anxiety, dopamine depletion) than equivalent doses of either drug alone.
Effects of 3,4-methylenedioxymethamphetamine administration on retinal physiology in the rat
PloS one, 2011
Twelve (9/) 3,4-methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse (group A), and 12 control subjects (group B) were included in the study. Prolactin (PRL) and growth hormone (GH) responses to the dopaminergic agonist bromocriptine (BROM) and psychometric measures were evaluated 3 weeks after MDMA discontinuation. PRL decreased both in A and B subjects after BROM suppression, without any significant difference between the two groups. PRL responses to BROM in MDMA users were in the normal range. In contrast, GH responses to BROM stimulation were found significantly reduced in ecstasy users, in comparison with control subjects (P B/0.001; F0/6.26). MDMA users showed higher scores on the Novelty Seeking (NS) scale at the Three dimensional Personality Questionnaire (TPQ), on direct aggressiveness subscale at Buss Durkee Hostility Inventory (BDHI), on subscale D (depression) at Minnesota Multiphasic Personality Inventory (MMPI 2) and on Hamilton Depression Rating Scale (HDRS) than control subjects. PRL areas under the curves (AUCs) showed a significant inverse correlation with NS scores both in A and B subjects. GH AUCs directly correlated with NS scores in healthy subjects, but not in MDMA users. No other psychometric measure correlated with hormonal responses. GH AUCs were inversely correlated with the measures of MDMA exposure (r 0/(/0.48; P B/0.01). Lower GH response to BROM in A subjects (MDMA users) could reflect reduced D2 receptor sensitivity in the hypothalamus, possibly due to increased intrasynaptic dopamine concentration. Although the hypothesis of dopaminergic changes associated with a premorbid condition cannot be completely excluded, the inverse correlation between DA receptors sensitivity and the extent of ecstasy exposure may suggest a direct pharmacological action of MDMA on brain dopamine function in humans. #