Journal of psychopharmacology
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J. Psychopharmacol. (Oxford) · Mar 2006
ReviewThe confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview.
The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine -- MDMA) is neurotoxic upon central serotonergic neurons in laboratory animals and possibly also in humans. In recent years, several studies reported alterations of serotonergic transmission and neuropsychiatric abnormalities in ecstasy users which might be related to MDMA-induced neurotoxic brain damage. To date, the most consistent findings associate subtle cognitive, particularly memory, deficits with heavy ecstasy use. ⋯ The interactions between MDMA and cannabis use may be more complex: cannabis use is a well-recognized risk factor for neuropsychiatric disorders and it was shown to contribute to psychological problems and cognitive failures in ecstasy users. However, at the cellular level, cannabinoids have neuroprotective actions and they were shown to (partially) block MDMA-induced neurotoxicity in laboratory animals. In future, longitudinal and prospective research designs should hopefully lead to a better understanding of the relation between drug use and subclinical psychological symptoms or neurocognitive failures and, also, of questions around interactions between the various substances of abuse.
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J. Psychopharmacol. (Oxford) · Mar 2006
ReviewEcstasy: are animal data consistent between species and can they translate to humans?
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. ⋯ 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.
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J. Psychopharmacol. (Oxford) · Mar 2006
Intensity dependence of auditory evoked dipole source activity in polydrug ecstasy users: evidence from an 18 months longitudinal study.
Numerous animal studies have been able to demonstrate neurotoxic damage to central serotonergic systems after exposure to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). It has been suggested that a high loudness dependence of auditory evoked potentials (LDAEP) and, particularly, of the tangential N1/P2 source activity is associated with a low functioning of serotonergic activity. Therefore, the LDAEP may be used as a non-invasive indicator for a possible neurotoxic damage caused by the long-term use of ecstasy in recreational users. ⋯ This feature of information processing is potentially related to the neurotoxic potential of ecstasy. However, alternative interpretations of these data refer to possible preexisting traits and the potential impact of other illicit drugs, particularly amphetamine, since ecstasy users typically exhibit polydrug use patterns. Thus, further research with larger sample sizes and prospective study designs are needed to definitively establish a causative link between ecstasy use and neurotoxicity-related dysfunctions in sensory processing.
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J. Psychopharmacol. (Oxford) · Mar 2006
ReviewMood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective.
Although 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a known serotonergic neurotoxin in different animal species, there is to date no conclusive evidence of its neurotoxicity in humans. MDMA use was associated with impairments of psychological well-being, verbal memory and altered serotonergic functioning in a number of cross-sectional studies. Due to inherent methodological limitations, such as the notorious polydrug use of ecstasy users and lack of control of possible pre-existing differences between ecstasy users and control participants, researchers have called for well-controlled, prospective longitudinal studies to shed more light on the issue of MDMA neurotoxicity to the human brain. ⋯ However, this measure may not necessarily be a valid indicator of the number or integrity of serotonergic neurons. Ex-ecstasy users' verbal memory showed no sign of improvement even after over 2.5 years of abstinence and thus may represent persistent functional consequences of MDMA neurotoxicity. However, alternative causes such as pre-existing group differences cannot be completely ruled out in spite of the longitudinal design.
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J. Psychopharmacol. (Oxford) · Mar 2006
ReviewMDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress.
Many recreational ecstasy/MDMA users display neuropsychobiological deficits, whereas others remain problem free. This review will investigate some of the drug and non-drug factors which influence the occurrence of these deficits. Acute and chronic MDMA usage are both important. ⋯ This is consistent with the animal literature, where high ambient temperature and other metabolic stimulants boost the acute effects of MDMA, and cause greater serotonergic neurotoxicity. In conclusion, the neuropsychobiological effects of MDMA are modulated by a wide range of drug and non-drug factors. These multiple influences are integrated within a bioenergetic stress model, where factors which heighten acute metabolic distress lead to more neuropsychobiological problems.