ENTACTOGENS: MDA, MDMA and MDEA

History

This history begins in 1912, when the German company Merck asked for a patent on it. (note 114) The patent was allowed to expire without being used. They cropped up again when the US army showed an interest in hallucinogens and commissioned research in 1953/54 on MDA, MDMA and other substances as a truth serum. They proved to be unsuitable for this purpose. The results of this research were not published until 1973 (note 115). MDA became popular in the Sixties, while MDMA was first identified as a street drug in 1972. (note 116)

In 1978 Shulgin and Nichols (note 117) published a scientific article on the structure and effects of MDA, MDMA and other substances. This knowledge had already been available for some time, however. Among those who knew about it were a number of psychotherapists who increasingly applied MDMA as a psychotherapeutic aid. (notes 118, 119) In 1981 it acquired its present name, Ecstasy (XTC). This was when its recreational use (as a stimulant) started in the ,United States. Soon afterwards its use rapidly spread outside the United States as well. In Dallas, where alcohol was prohibited at the Southern Methodist University, students bought legal MDMA as a substitute, paying by credit card. The US consumption rose from 10,000 doses in the whole year of 1976 to 30,000 doses a month in 1985. (note 120) At the same time the Drug Enforcement Administration (DEA) reported that 30,000 doses a month were being used in the state of Texas alone. A 1987 survey revealed that 40% of students on the campus of Stanford University had used MDMA.(note 121) In 1985 MDMA was prohibited by the Drug Enforcement Administration, when it was given the same status as heroin and LSD.

MDMA was also used by Baghwan followers and spread to Europe. The setting for its use there was different. It was first used on Ibiza, where the combination of XTC with dancing to deafening electronic music in an exotic nightlife atmosphere was invented. It spread from there to England and the Netherlands in particular, where a new youth culture emerged which is now spread all over Europe: the 'raves'.

A large number of substances are sold under the name of XTC, including amphetamine, ketamine, PCP, and caffeine, as~well as a range of 'normal' medicines as pure fakes.(note 122) We shall now review the main entactogens, whether they are sold as XTC or not.

METHYLENEDIOXIAMPHETAMINE (MDA)

Shulgin (note 123) describes the hallucinogenic effect of MDA as follows: 'it produces eyesclosed hallucinations of a commanding sort. There is quite consistently a recollection of past events, of childhood memories, a reliving of earlier times that appear to be, as far as can be documented, quite accurate.'

MDA seemed to be unique in that it reinforces mainly emotions and empathy to a high degree and creates a strong emotional link with others present. It was these effects which made MDA popular as a recreational drug. MDA also has a clear sympathomimetic activity.

The usual dose is between 80 and 160 mg, and the effect lasts for 8 to 12 hours. In connection with the search for a truth drug, this substance was administered by the US army to a number of test persons, in some cases without their knowledge. In one case, a psychiatric patient, the intravenous injection of 500 mg was fatal. (note 124)

METHYLENEDIOXIMETAMPHETAMINE (MDMA)

'The first effect is very fast, within half an hour of consumption. Most test persons report that the plateau of the effect begins within another half hour to one hour. The symptoms of~intoxication have largely vanished after another two hours, apart from the slight remains of sympathomimetic stimulation, which can last for a number of hours more. There are few physical symptoms of intoxication, and psychological postsymptoms are virtually absent. In qualitative terms, the drug seems to elicit an easily controllable changed state of consciousness with emotional and sensual overtones. In terms of effect, it can be compared with marihuana, psilocybin without the hallucinatory component, or low doses of MDA.' (note 117)

Ten years later, an anonymous informant, a respectable fifty year old, described the effect as follows:

'The drug removes all your neuroses. It takes away the fear of response. There is an overwhelming sense of peace, you are at peace with the world. You feel open, clear, tender. I can't imagine that anyone is angry under its influence, or selfish or mean of defensive. You have lots of insight into yourself, real insight, which you hold on to after the experience is gone.' (note 125)

METHYLENEDIOXIETHYLAMPHETAMINE (MDEA)

This variant hardly differs from MDMA. It is a bit milder: the dose is around 135 mg and it takes effect for 3 to 5 hours. The main difference from MDMA is that 'the special, magic effect and the affective transfer seem to be absent'. (note 124)

The sympathomimetic effects of the entactogens

Downing (note 126) and Hayner & McKinney (note 127) registered the following effects: increase of blood pressure and pulse rate, unchanged consciousness, thinking remained clear, no hallucinations, intact shortterm memory, dilation of pupils, light motor coordination disturbances (especially high tension in the jaw muscle), increased sensual awareness, only occasionally sexual arousal, nausea can occur, loss of appetite, normal electrocardiogram. Conclusion: 'this study indicates no significant immediate or subsequent neurobehavioral consequences from the use of MDMA within the parameters examined'. All these effects can probably be explained from the stimulating effect of MDMA.

This also accounts for the postsymptoms which have been described, tiredness and exhaustion, depression, in a few cases more prolonged psychosis, except depression which sometimes ensues for a shorter period.

The problems that are most frequently presented are: anxiety, accelerated heart beat, and in serious cases paranoia. The treatment is symptomatic. It is usually sufficient to explain that these are the effects of an overdose and that these effects disappear when the effect of the drug has been spent. `Talk down', as applied in LSD reactions, helps in by far the most cases. It is over once the drug has ceased to take any effect.

In a few cases in which the anxiety remains, clients may come back for a few counselling sessions, which are not usually continued for more than a week unless the client has other drug or emotional problems. (note 128)

Finally, it has been claimed that MDMA reduces resistance to infections. (Viral) bronchial infections have been referred to in the US (note 129), while Dutch users report infections of the urinary tract among female users. (note 130)

The fact that there is a debate on the possible hallucinogenic effect of MDMA is probably caused by the fact that users regularly report (mild) hallucinations, but it is never certain that they really have been using MDMA, for they might have bought low doses of LSD or MDA thinking it was XTC. There are also indications that a small part of the MDMA is converted into MDA in the body. (note 131) This conversion is not significant in the case of regular doses, but this might cause hallucinations if taken in large doses.

A number of medical publications and the mass media have drawn attention to a number of deaths among users. The following acute complications have been described: (notes 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143)

cardiac complications

hyperthermia/hyperpyrexia (overheating) resulting in rhabdomyolysis, diffuse intravasal clotting and collapse of the kidneys;

hepatotoxicity

psychoses.

The cardiac complications all occurred among persons with already existing, though sometimes unidentified, cardiac problems. Hyperthermia with all kinds of potentially lethal complications has been known for a long time as a rare complication of amphetamine overdose, probably based on an individual 'idiosyncratic' sensitivity. (note 144) Hepatotoxicity is a new phenomenon in relation to amphetaminelike substances, but psychoses are well known as usually temporary complications in people who are predisposed toward them.

There are indications from experiments with animals that MDMA damages the serotoninergic nerve ends.(note 145) It has not been possible to demonstrate that this is the case with humans.(note 146) A number of test persons who had used XTC an average of 95 times in 5 years did have significantly lower concentrations of an indicator of the serotonin function in the brain, but no data are available on what the level was before they started taking XTC. These test persons were significantly less impulsive and hostile and showed more selfcontrol than the control group which had not used XTC.(note 147) Since the latter features are behavioral aspects which are assumed to be mediated by serotonin, this may be an indication that chanqes miqht have taken place in the serotonin content, but it is a matter of opinion whether these changes, if they occurred at all, should be viewed in a negative light. Besides, many people are prescribed chronic drugs like the related fenfluramine, a drug which reduces the appetite, whose neurotoxic effects have been described in the same way, or fluoxetine (Prozac), whose longterm effects have never even been investigated.

It should be obvious that, however dramatic these complications may be at the individual level, they are very rare if they are related to the estimated scale of XTC use.

Operational mechanism of the entactoqens

MDMA increases the secretion of serotonin in the synapses and inhibits the reuptake of serotonin. MDA and amphetamine also have this effect, but MDMA and MDA inhibit the serotonin reuptake five times as much as amphetamine, and at least 20 times as much as DOM, a genuine hallucinogen. MDA and MDMA are reasonably powerful as inhibitors on the noradrenaline reuptake, which is the main cause of the sympathomimetic effect of MDMA.

MDA inhibits the reuptake of dopamine. MDMA does so to a much lesser degree, and DOM does not do so at all. This too is proof that in this respect MDA and MDMA belong to a completely different category of substances from the genuine hallucinogens. (note 148)

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