Makes MDMA possible at home

"Ecstasy": psychotropic effects, complications, secondary effects

Although the health risks of "ecstasy" are increasingly being reported in the media, there is currently hardly any work that documents the state of international research. The present work closes a gap here and provides information on the most important research findings.

Epidemiological studies and early warning systems in the field of drugs indicate an exponential increase in the consumption of the fashion drug ecstasy. In parallel with this development, there are increasing reports of deaths and severe psychiatric, neurological and internal complications attributed to the use of ecstasy. In this article, the most important research findings on ecstasy are briefly outlined (10) and our research activities at the University Hospital Eppendorf are presented.

Definition of terms
"Ecstasy" is a collective term for various substances with a very similar spectrum of activity. These include the most important representatives MDMA (methylenedioxymethamphetamine) as well as the compounds MDEA (methylenedioxyethylamphetamine) and MDA (methylenedioxyamphetamine). If the term "ecstasy" is used in this work, following the general usage, no differentiation between these substances can be derived from it. This collective term also includes combinations of active ingredients which, under certain circumstances, may also contain amphetamines or hallucinogens. The term MDMA is only used here if the test results explicitly refer to this substance.

Although there is currently no representative survey on ecstasy use in the group of adolescents and young adults, various studies indicate that ecstasy use has increased significantly in this group in recent years. Data from the Federal Criminal Police Office show that the number of ecstasy tablets seized rose by 300 percent in 1993 compared to the previous year and by more than 200 percent in 1994. While the growth rate of first-time heroin users from 1993 to 1994 was only 1.5 percent, the proportion of first-time ecstasy users increased by 46.7 percent in the same period (2).
Looking at all epidemiologically relevant data together, one must suspect fundamental changes in the German drug scene. While the use of narcotic drugs is on the decline, ecstasy and other activating drugs are being used more and more frequently. The consumers seem to be essentially limited to the group of 15 to 25 year olds.

Psychotropic Effects
MDMA is a psychotropic substance that induces both an ampethamine-typical activation and a hallucinogenic effect. The psychotropic effect of MDMA sets in after about 20 to 60 minutes (75 to 150 mg MDMA) and is characterized by a sudden lightening of mood and euphoria. The peak of euphoria is reached about an hour after the start of the effect. After another two hours, the psychotropic effects subside. The text box positively experienced acute effects summarizes the psychotropic effects rated positively by the consumers that can be triggered by the intake of MDMA. In contrast, the negative psychotropic effects are listed in the text box Negatively experienced acute effects (4, 7).

Psychiatric Findings
A major danger of ecstasy abuse lies in the potential psychiatric complications and side effects (Table 1). Cases of behavioral disorders, panic, derealization and depersonalism disorders, depressive syndromes, drug-induced, paranoid and atypical psychoses have been reported in the literature (5, 6). "Flashbacks" can also occur after consuming ecstasy, which last from a few minutes to several days (6, 9). The incidence of such complications can be determined in relation to all of them
No statements have been made to ecstasy users so far. It can be assumed that existing predispositions for mental illnesses play an important role in the occurrence of the psychiatric complications and consequential effects described, in the sense of the "diathesis-stress model". In an unknown number of cases, it can be assumed that the use of ecstasy has the function of a "trigger" in triggering severe psychological disorders (for example psychotic decompensations). What remains unclear in the investigations, however, is the importance to be attached to the simultaneous abuse of other drugs. However, there is some evidence that taking cannabis and ecstasy at the same time increases the risk of psychotic decompensations. In addition, a tendency towards overdosing seems to favor the occurrence of psychiatric complications. It is striking that after a single dose of ecstasy there are hardly any reports of psychiatric complications, most of which only occur after a cumulative dose of 40 to 50 tablets.
Possible contamination of the MDMA tablets with other addictive substances play a subordinate role in the triggering of psychiatric illnesses, since highly pure MDMA was often found in affected patients and most disorders can also be induced in animal experiments. The test results speak for a rapid development of tolerance towards MDMA; the positive effects quickly decrease in favor of the negative. Consumers counteract this trend through cyclical usage patterns by inserting drug-free intervals.
In our experience and that of other research groups, some users use ecstasy to cope with intrapsychic conflicts and other life stresses. This subgroup, the
Ecstasy, also used regularly and alone during the week, is most at risk of developing psychological dependence; According to current knowledge, however, ecstasy does not cause any physical dependence.
In this context, however, it should be borne in mind that in rare cases ecstasy can function as a "gateway drug" into a serious substance-related addiction. In addition, it must be taken into account here that most ecstasy users are polytoxicomaniac, i.e. use a large number of other addictive substances (for example cannabis, amphetamines, LSD or cocaine) in addition to ecstasy.

Neurological and neurobiological findings
The most frequently described neurological disorders associated with the use of ecstasy are cerebral seizures (text box Neurological Complications). Territorial cerebral infarctions, cerebral haemorrhages and corneal epitheliopathies are reported much less frequently in the literature. The occurrence of these complications does not seem to have a simple linear relationship with the dose of ecstasy taken; this speaks for the importance of individual vulnerabilities.
MDMA is a substance that intervenes directly in neurotransmitter metabolism. In animal experiments it could be shown that MDMA leads to an increase in the serotonin concentration in the synaptic gap; MDMA presumably causes a release of serotonin from the presynaptic vesicles, an inhibition of the degrading enzyme MAO-A and an inhibition of the restoration of serotonin in the presynaptic terminal (1). In addition to serotonin, MDMA also influences the activity of the dopamine neurotransmitter system; however, this is far less powerful than the serotonergic system. A release of serotonin triggered by MDMA probably also indirectly leads to an increased release of dopamine.
Studies on monkeys have shown that the high-dose administration of MDMA leads to irreversible damage to the serotonergic neurotransmitter system. The formation of the hippocampus, which is important for memory processes and the development of fear, turned out to be the most affected (8). In the rat experiment, however, the irreversibility of the damage could not be demonstrated. In this context it is interesting that in test animals with a very low serotonin concentration compared to non-damaged control animals, no deviations in behavior were found.

Internal findings
In the vegetative region there is an increase in heart rate and blood pressure about an hour after taking ecstasy. In this acute poisoning phase, the users reported the side effects of intoxication listed in Table 2. In the post-acute phase, disorders such as nausea, trismus, or bruxism can persist and then be associated with psychophysical exhaustion, arterial hypotension, and muscle pain (4, 7).
A triad consisting of hyperthermia, rhabdomyolysis and disseminated intravascular coagulation was found in the number of deaths associated with the abuse of ecstasy. The overheating of the body, the high loss of fluids and the inadequate compensation for this through fluid intake are seen as conditional factors for the development of this disorder. In addition, MDMA intervenes directly in the central temperature regulation. The severity of this disorder is obviously independent of the ingestion dose. Ecstasy users also suffered from acute kidney failure and others from non-infectious hepatitis (3). The nephro- and hepatotoxic effects of MDMA have now been proven. Cases of circulatory dysregulations, cardiac arrhythmias, ventricular fibrillation and sudden cardiac death are also described.

Current research
We are currently conducting a representative survey of psychiatric, child and adolescent psychiatric clinics, drug and educational counseling centers and social psychiatric services on ecstasy consumption. A total of 1,400 institutions were contacted nationwide. Among other things, this survey is intended to provide information on the frequency, age structure and gender distribution of ecstasy users in these institutions. In addition, this study aims to shed light on the reasons (psychological and physical symptoms) that were responsible for the contact with the institutions mentioned; this study is currently in the final evaluation phase.
The overview of the current state of research makes it clear that ecstasy is a first-rate health policy challenge that requires further scientific clarification; Interesting individual findings are available for the psychiatric, neurological and internal medicine areas, which, however, have so far been insufficiently related to one another in terms of an integrative perspective. An interdisciplinary study that we will begin in the winter of 1996/97 with funds from the Federal Ministry of Health aims at this deficit. On the one hand, this study should provide information about the relationships between the three levels of analysis and, on the other hand, enable the development of a risk classification system that predicts the degree of risk of individual groups of ecstasy users with regard to psychological and organic disorders.
A main aim of our investigation is to identify those personality and neurosis-specific predictors that are associated with an increased health risk. The results of the investigation should also contribute to the development of preventive measures.
As part of a psychiatric-psychodynamic diagnosis, the ecstasy users that we recruit in techno discotheques are first examined with regard to their personality and neurosis structure. This is followed by a clinical device-based diagnosis, with the help of which neurological and internal disorders are recorded. For this we use positron emission tomography (PET), among other things. Since the existing animal studies are based on morphological analyzes that were carried out post mortem, with our study we make an important contribution to the verification of animal experimental findings on living people. In addition, as far as we know, our study is currently the only one that examines a relatively unselected sample of MDMA users of this size in an interdisciplinary manner.
How this article is cited:
Dt Ärztebl 1997; 94: A-372-376
[Issue 7]

1. Battaglia G, Yeh SJ, De Souza EB: MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain serotonin neurons. Pharmacol Biochem Behav 1988; 29: 269-274
2. Federal Criminal Police Office: Narcotics Annual Report 1994. Wiesbaden, 1996
3. Henry JA: Ecstasy and the dance of death. Br Med J 1992; 305: 5-6
4. Liester MB, Grob CS, Bravo GL, Walsh RN: Phenomenology and sequelae of 3,4 methylenedioxymethamphetamine use. J Nerv Ment Dis 1992; 180: 345-352
5. McCann UD, Ridenour A, Shaham Y, Ricaurte GA: Serotonin neurotoxicity after (±) 3,4 methylenedioxymethamphetamine (MDMA; "Ecstasy"): a controlled study in humans. Neuropsychopharmacol 1994; 10: 129-138
6. McGuire PK, Cope H, Fahy TA: Diversity of psychopathology associated with use of 3,4-methylenedioxymethamphetamine ("Ecstasy"). Br J Psych 1994; 165: 391395
7. Peroutka SJ, Newman H, Harris H: Subjective effects of 3,4-methylenedioxymethamphetamine in recreational users. Neuropsychopharmacol 1988; 1: 273-277
8. Ricaurte GA, Martello AL, Katz JL, Martello MB: Lasting effects of (±) -3,4methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: neurochemical observations. J Pharmacol Exp Therap 1992; 261: 616-622
9. Schifano F, Magni G: MDMA ("Ecstasy") abuse: psychopathological features and craving for chocolate: a case series. Biol Psych 1994; 36: 763-767
10. Thomasius R, Schmolke M, Kraus D: MDMA - ("Ecstasy") consumption: an overview of psychiatric and medical consequences. Fortschr Neurol Psychiat 1997; (in print)

Author's address:
Priv.-Doz. Dr. med. Rainer Thomasius
Dr. phil. Christian Jarchow
Psychiatric and nervous clinic at the University of Hamburg
University Hospital Eppendorf
Martinistrasse 52
20246 Hamburg