Info on ecstasy

Naomi
verrell

Summary

Ecstasy was initially perceived as a drug with few adverse

effects, as amphetamine had been until the mid-1960's. As
with amphetamine, however, widespread use resulted in
reports of confusion, anxiety, panic attacks, depression,
sleeping difficulties, depersonalisation, derealisation,
hallucinations, flashbacks, paranoia, psychosis, tolerance
and dependency syndromes, and subsequent addiction to
sedatives. However, many of these reports are based on
single case studies or short, uncontrolled series, in which no
evidence is provided that the pill taken was in fact ecstasy,
that other drug use was not significant and that urine
samples were free of other drugs and their metabolites, that
the condition would not have occurred by chance, that the
person was not predisposed to the condition and other
factors. Animal studies have shown that large quantities of
ecstasy can result in persistently low serotonin levels.
Attempts to relate these chemical changes to adverse
effects ignore the role of psychological changes due to the
emotional effects of ecstasy, which can upset the balance of
the mind by releasing disturbing material from the
unconscious. Although this effect can be used as an aid to
psychotherapy, the same release may result in anxiety,
depression, insomnia and nightmares. Psychological
explanations must be considered along with chemical
changes as many, although by no means all, of the adverse
effects appear to follow just one or two doses rather than
chronic dosing. Heavy weekend users tend to have midweek
problems such as low mood and irritability and may develop
a dependency syndrome. This chapter also contains the first
comprehensive discussion of treatment options for ecstasy-
related problems.
Introduction

Like other potent mind-altering drugs, the use of ecstasy has

been associated with impaired mental health and impaired
judgement. While under the influence of the drug, users may
sometimes experience confusion, disorientation, anxiety,
panic attacks, depression, insomnia, depersonalisation,
derealisation, perceptual disorders and hallucinations,
paranoia and psychotic phenomena. It is possible that some
of these effects may continue for a period after cessation of
the drug.1

The term 'ecstasy' has now widened its meaning to embrace

a class of drugs which includes MDMA, MBDB, MDE, MDA,
MDEA and 2CB, amongst others. These drugs differ from
each other in their various effects and thus, unless otherwise
stated, the term 'ecstasy' where used in this review refers to
MDMA only. This review is intended for non-specialists and
specific references are only given for controversial issues.
This review is not a list of all known reports: additional
reports may be found in the annotated bibliography.

There was little interest in ecstasy until the mid-1970s when

the chemist Alexander Shulgin introduced ecstasy to those
with an interest in drug-assisted psychotherapy. The
psychotherapists considered the drug to be moderate in its
effects, which were principally characterised by feelings of
empathic understanding for others and a release of
emotions. They generally reported that the drug had
potential for overcoming 'blocks' in psychotherapy and
enhancing insights, particularly insights concerning
relationships.2

By the early 1980s, ecstasy had moved off the couch and
out into the wider community. The 1990s has seen the
widespread use of ecstasy as a recreational drug, resulting in
increasing reports of an apparent association between
ecstasy use and a diverse range of psychological symptoms
and psychiatric disorders.3,4 It was also reported that large
doses of MDMA repeatedly injected into laboratory animals
lowered the levels of a chemical messenger in the brain
called serotonin, and to a lesser extent dopamine, and
damaged the nerve terminals from which serotonin was
released.5,6,7 These effects were dose related and recovery
was incomplete.6 There is some limited evidence of
serotonin deficits in human ecstasy users. The relevance of
these studies to humans taking one or two ecstasy tablets
occasionally has been questioned 8,9, but the animal studies
do suggest that persons taking large quantities of ecstasy for
several days may be at some risk of persistently low
serotonin. As low serotonin has been linked to depression
and anxiety, it has been suggested that heavy users of
ecstasy may be at increased risk of developing psychological
problems of this nature.

Many investigators consider animal studies to have

relevance to human use: 'The loss of 5-HT (serotonin) axons
in monkeys is greater than that in rats that were given a
fourfold higher dose of MDMA and, therefore, MDMA is far
more toxic in the primate than in the rat... in view of the
extensive destruction of 5-HT terminals at doses that are
approximately twice that commonly used for recreational
purposes by humans, MDMA may have a relatively small
margin of safety, and it would be prudent to consider this
drug potentially hazardous for human use..'.10 Molliver et al.
(1989) remark on the similarity between serotonergic axons
damaged by ecstasy and those seen in Alzheimer's disease,
where the most consistent receptor change is often loss of
presynaptic serotonergic receptors11, although the greatest
biochemical change is loss of acetylcholine.

In terms of explaining adverse reactions to ecstasy the focus

has been to a very large extent upon possible brain chemical
changes as described above. There has been a tendency to
ignore the fact that ecstasy releases emotions and can have
marked effects upon the psychodynamic balance of the
mind. A core concept in psychodynamics is that anxiety
provoking material 'unacceptable' to waking consciousness
is repressed into the unconscious, from where it may make
itself known via dreams and other methods. 'Defences' are
erected against this material. Some psychotherapies may
involve bringing such material to the surface so that it can
be 'worked through' and discharged. In this context it is
valuable to recall that ecstasy was used in psychotherapy to
remove 'blocks' and defences.12

What happens if these defences against disturbing material

in the psyche are removed in a non-psychotherapeutic
context? There may be little possibility for working through
the material or containing it. A possible consequence may be
the range of symptoms associated with the neuroses:
anxiety, depression, insomnia and nightmares for example,
and these are of course precisely the symptoms most
commonly associated with ecstasy use. The observation that
duration and dosage are not currently linked to the
probability of developing such symptoms (e.g. Wodarz and
Boning, 1993) tends to support an examination of
psychological causes, and suggests that the current focus
upon neurotransmitter changes may be misguided,
particularly in view of the remarkable lack of change in the
behaviour of animals following chronic, high dose injection of
ecstasy. Many of the communications received from persons
who have had adverse psychiatric sequelae in association
with the use of ecstasy describe only taking a few doses.
Nevertheless, it is still possible that large and rigorous
studies will eventually demonstrate a link between at least
some adverse effects and dosage/duration of ecstasy use.
What are the risks in numerical terms?

At the present time, the actual risk of developing a serious

psychiatric condition following use of ecstasy is unknown.
The degree of publicity which accompanies a possibility such
as depression obviously has no scientific relevance in
determining the actual risk, although it may lead to a
tremendous distortion in the minds of the public as to what
that risk may be, as has now been seen with respect to the
risk of death. The relative risk of any particular outcome
should be determined by dividing the total number of
outcomes of that type by the total number of doses
consumed (risk exposures). A guide to estimating the total
number of doses consumed between 1985 and the present
may be found elsewhere in this book. Many case reports
make no attempt whatsoever to provide a statistical
perspective, but it is necessary to tolerate this deficiency as
such estimates are very difficult to provide. We do not know
how many cases of ecstasy associated psychiatric
disturbance are treated by the medical community but never
reported, and even more inaccessible are those which occur
but are never treated at all.

Another method of gaining perspective on the general

importance of ecstasy-induced mental disorder is to spend
several weekends in the casualty (emergency room)
departments of a large inner city hospital, and also the
emergency clinic of a psychiatric hospital. This pragmatic
investigation will produce a clear conclusion: the drug which
is principally associated with suicidal depression, homicide,
cognitive deficits and psychosis in this society is alcohol, by
an enormous margin. It is likely to be several weeks before a
single case associated with consumption of toxicologically
proven ecstasy is seen, and even longer before a case is
seen which does not involve other drugs and a personal or
family history of pre-existing psychiatric disorder.

Nevertheless, one study of self-reported immediate and long-

term effects (months or years after ingestion) in 500 people
resulted in high levels of reported adverse psychological
effects 37: immediate effects: paranoia, 20%; anxiety 16%,
depression 12% long-term/recurring effects:
depersonalisation (defined later) 54%; insomnia 38%;
depression 38%; flashbacks 27%. Two double-blind, placebo
controlled assessments of MDEA users (n=14) with non-
using controls reported one case of toxic psychosis, a severe
dysphoric reaction and one anxiety disorder.38 It must be
noted this study involved MDEA, and not MDMA.

Anxiety disorders and panic attacks

As stated previously, we are currently limited to a handful of

case reports. However, the majority of communications from
persons who have suffered adverse effects in association
with taking ecstasy suggests that the leading theme may be
anxiety disorders rather than depression, and this impression
is confirmed by the published clinical reports in which forms
of anxiety disorder appear to be more common than
depression. It is possible that the serotonergic terminals
involved in anxiety control are a distinct subset from those
principally involved in mood control, and that ecstasy may
preferentially affect the former. However, it is more likely
that the real explanation lies in the psychological effects of
ecstasy in terms of impairing psychic defences against
anxiety generating material in the unconscious as discussed
previously.

Depersonalisation and derealisation

Depersonalisation refers to the feeling that one is not 'real',
and that one is detached and unable to feel emotion.40 It is
very unpleasant. Sufferers may feel that they are separated
from the world by a glass wall. Derealisation is where the
environment appears to be unreal and devoid of the usual
emotional component. People may be described as
'cardboard-like'. Although these phenomena have been
reported in association with ecstasy use,30 they may be due
to fatigue and may be seen as symptoms in a wide range of
disorders, including depression, anxiety, schizophrenia and
temporal lobe epilepsy. Depersonalisation and derealisation
disorder may also occur spontaneously, so once again care is
necessary in drawing a cause and effect conclusion from an
association which may be accidental.

Depression

A brief period of low mood associated with the 'come-down'

is common, although experienced users will tend to avoid
this by taking other drugs. Chronic ecstasy use is also
sometimes followed by a longer lasting depression.50
However, it is unclear whether the chronic use of ecstasy
might not have been a form of self-medication of a pre-
existing depression, or latent depression, rather than
actually causative of depression.

Depression may be predicted on theoretical grounds due to

links between mood and serotonin. However, rats and
monkeys with extensively damaged cortical serotonergic
nerve terminals generally show little difference, or only very
modest differences, in their behaviour relative to control
animals. It is possible that this is because ecstasy appears to
preferentially alter one type of serotonin terminal, and not
those of a second system in the brain.10 One conclusion
from the data so far is that it is probably this second system
which controls mood, appetite, sleep, and sex drive.
Serotonin levels are low for a week in this second system,
but the structural changes are generally not seen.10 This
matches the weekly cycle of what has actually been
observed in humans. It is clear that further studies are
required.

Flashbacks

Flashbacks have been described by ecstasy users.51 Some

flashbacks may be a form of post-traumatic stress disorder
(PTSD), which is a psychological condition in which
flashbacks and sleep disturbance result from severe
psychological trauma. Flashbacks appear to be more likely
following very traumatic drug experiences, which adds
weight to the suggestion that some flashbacks are in fact
PTSD, or at least anxiety related. One of the three cases
cited by Creighton et al. (1991) involved a woman who had
been abducted and raped while under the influence of
MDMA. The other two cases involved heavy daily cannabis
use and LSD-like features which Creighton et al. suggest may
have been due to such substances in the pills. This once
again demonstrates the importance of polydrug use in these
limited series reports.

The Tenth International Classification of Diseases 53

classifies PTSD as 'a delayed or protracted response to a
stressful event or situation (ICD-10) of an exceptionally
threatening or catastrophic nature'. A small number of
ecstasy experiences may be very stressful and perceived as
catastrophic by the consumer. ICD-10 notes that pre-existing
personality traits such as being compulsive or a past history
of neurosis increases the probability of subsequent
development of PTSD and aggravates its course. 'Typical
symptoms include episodes of repeated reliving of the
trauma in intrusive memories ('flashbacks') or dreams...
there is usually a state of autonomic hyperarousal' (ICD 10).
Other flashbacks may be a form of psychological 'conversion
disorder', where anxiety with a neurotic basis is 'converted'
into psychological symptoms, just as it may be converted
into physical symptoms such as a 'paralysed' arm.

The likelihood that flashbacks are in fact due to persisting

changes in the brain is considerably reduced by the
observation that a wide array of drugs, with radically
different mechanisms of action in the brain (e.g. LSD and
ketamine), have also been linked to flashbacks. Ketamine
use is as likely to result in flashbacks as LSD use.36,54,55 It
is also noteworthy that persons who have never taken any
illicit drugs but who are prone to severe anxiety and panic
attacks may describe visual and other phenomena which
bear a marked resemblance to the flashbacks described by
some drug users. The similarity of the conditions which
provoke such flashbacks also indicates a psychological
rather than a neurochemical origin.

In conclusion, the currently available evidence suggests that

flashbacks are probably not the result of 'brain damage' or
the improbable theory that there are 'lingering drug
quantities' in the brain. Flashbacks are most usefully
understood as PTSD and a form of neurosis of the
dissociative conversion/anxiety disorder type.

Sleep disturbance

Insomnia for several days after taking ecstasy is relatively

common, but in a few cases this has persisted for months
with excessive dreaming and sometimes nightmares.1 A
persistent reduction in stage 2 sleep has been verified in a
sleep laboratory, although the subjects in this investigation
were not considered to be suffering from sleep disorders.56

Medication
The client may be self-medicating an underlying disorder
which should be treated separately, such as depression, an
anxiety disorder, a personality disorder or an incipient
psychosis. If such a condition is identified or suspected,
treatment should be as for the underlying condition
(antidepressants, antipsychotics, lithium, carbamazepine
etc.)

Conclusions

It is clear that large-scale, rigorous, well designed studies are

required to establish the true levels of serious adverse
psychological effects from taking ecstasy. The results from
animal neurotoxicity studies, in combination with the
tendency to use higher doses of the drug, suggest that there
are grounds for concern. However, current indications are
that many of the disorders which have been reported may be
related to psychological events rather than neurotoxicity. The
cause and effect conclusions often drawn by single case
studies must be viewed with caution, but this does not
necessarily mean that they are incorrect or that these
studies should be disregarded. There is still a widespread
tendency to diagnose persons as suffering from conditions
induced by illicit drug taking when they are in fact suffering
from conditions such as schizophrenia and manic-depression.
This tendency is strengthened by the natural inclination on
the part of the sufferer to seek an explanation for their
condition 'external' to themselves, over which they have
some control. Our understanding of the actual relative risk
from this drug is at an early stage.