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Mental Health Problems Associated With
the Use of Ecstasy (MDMA), and Their Treatment

Karl L. R. Jansen, MD, PhD,  MRCPsych

K@BTInternet.com
 

  Like other mind-altering drugs,  Ecstasy was  perceived as a drug with
few adverse effects when first introduced. However,  as it spread off the
couch and into the community,   use of the drug became linked with a
variety of mental health problems. When used as an aid to psychotherapy in
the mid-1970's,  the therapists considered the effects of Ecstasy to be
characterised by feelings of empathic understanding for others and a
release of emotions. However, there have now been reports of  confusion,
anxiety, amnesia, panic attacks, depression, mania (excessive excitation),
suicide, insomnia, nightmares, depersonalisation (the person feels that
they are not real), derealisation (a feeling that the surroundings are
unreal), hallucinations, flashbacks, post-traumatic stress disorder,
post-hallucinogen perceptual disorder, paranoia and other persistent false
beliefs, other types of psychosis, automatic or repetitive behaviour,
dissociative  disorders, irritability and aggression with mood swings,
tolerance,  dependence and increased risk of problems with other drugs
(e.g. Jansen, 1997; McCann et al.,1996; Spatt et al., 1997).

The reader may have noted that this  is a remarkably long, diverse and
non-specific list.  When widespread consumption of a drug  results in  a
non-specific  list of  problems  embracing a large slice of general
psychiatry, as has happened with Ecstasy, we may to some extent be
recording the mental disorder which usually exists in  the general
population, some of which has been wrongly  attributed to consumption of a
drug (and some of which, of course, has been quite correctly attributed.)
The more mental health problems are attributed to a drug, as the sample
size grows to reflect the general population, the more wary  we should be
of  false decisions about cause and effect. The  association may be
entirely  coincidental. Some of these reports  have more to do with the
psychology of the person reporting them than with any particular effect of
the drug upon the mind and/or the brain.

Animal studies have shown that large quantities of Ecstasy can result in
persistently low serotonin levels. However, attempts to explain the adverse
effects linked with Ecstasy use in terms of neurochemical changes ignore
the role of psychological changes due to the emotional effects of the drug.
Ecstasy could potentially upset the balance of the mind by releasing
disturbing material from the unconscious. The release of such material can
be useful in psychotherapy, but there may also be some risk of developing
neurotic symptoms such as  anxiety, insomnia and nightmares. Psychological
explanations may be highly relevant as many of the adverse effects were
reported after just one or two modest doses, in addition to some of these
reports being due to an entirely  false attribution to the drug.
Widespread use eventually leads to a  lack of  connection, in some cases,
between the dose size and frequency and the reporting of neurotic symptoms.
For example,  a typical case would be a person who took half a pill once
and now reports 2 years of panic attacks, attributed to taking the pill
(which may not even contain a psychoactive dose of MDMA on laboratory
testing). With a primarily physical cause, one would usually  expect to see
at least some link between the development of  symptoms  and the dose size
and frequency.  Neurochemical factors  may be reponsible for midweek
problems such as low mood and irritability following heavy weekend use.

The 1990's has seen general  recreational use, resulting in reports of an
apparent link  between Ecstasy use and a diverse range of mental health
problems (McGuire et al.,1994; Kemmerling et al., 1996).  It was reported
that large doses repeatedly injected into animals lowered serotonin levels,
and to a lesser extent dopamine, and damaged the nerve terminals from which
serotonin was released. The relevance of these studies to humans taking one
or two doses occasionally has always been doubtful, but persons taking
large quantities for several days may be at  risk.  As low serotonin has
been linked to depression and anxiety, it has been suggested that heavy
users may be at increased risk of  developing these disorders. Against this
theory are the observations that low serotonin is linked with aggressive
behaviour and yet heavy Ecstasy users are believed to be rather less
aggressive than average, rather than more aggressive.

Explanations for adverse reactions to Ecstasy have thus  focussed on
possible brain chemical changes, often ignoring the fact that Ecstasy
releases emotions and may alter the psychodynamic balance of the mind.
Psychodynamics maintains that anxiety provoking material 'unacceptable' to
waking consciousness is repressed into the unconscious, and that 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. Ecstasy was used in therapy to remove such defences.  What
happens if  defences against disturbing material in the psyche are
constantly being removed in a non- therapeutic context? The results will
partly depend on the set and setting. While no eventual harm may result,
and the defences may rebuild themselves as the drug wears off,  it is also
possible that the some of the 'liberated' material cannot be easily
squashed back in. There may be little chance  of 'working through' the
material or containing it. Possible consequences include the range of
symptoms associated with the neuroses: anxiety, mood disorders,  insomnia,
nightmares, and dissociative 'conversion' disorders (i.e. hysteria, where
mental anxiety may be 'converted' into a physical or psychological
symptom).

The  frequent lack of lasting changes in animal behaviour (other than a
behavioural tolerance to the drug) following chronic, high dose injection
of Ecstasy also indicates that an exclusive focus upon neurochemistry to
explain adverse effects is probably misguided. Many of the communications
received from persons who have suffered mental health consequences linked
with the use of Ecstasy describe taking only a few doses.

 Where psychosis (delusions,  hallucinations, thought disorder) is
concerned, it is more likely that neurochemical factors are important. The
release of dopamine in a similar manner to amphetamine could possibly lead
to a link between long-term, high dose Ecstasy  use and the development of
a brief, paranoid  psychotic illness as may sometimes be seen with
amphetamine itself. An excess of dopamine is sometimes thought to be
involved in producing paranoid symptoms, as predicted by  'the dopamine
hypothesis of schizophrenia'.

Problems with the Reports

The limited information  we have is largely in the form of  the personal
accounts, interviews, single case reports  and short  series in which there
is no control group (a 'matched' group which is exactly the same as the
Ecstasy group except that the controls have not taken the drug. Matching
the two groups on use of other drugs is particularly important).
There are several key issues to bear in mind when considering reports of
this type:

Was the drug taken actually MDMA?

Authors who allege that a person took MDMA should attempt to present
toxicological proof to support this claim (tests of the tablets taken or at
least a urine test) as many pills contain other drugs such as MDEA, MDA,
MBDB, MDE, 2CB, ketamine, amphetamine, LSD, pseudoephedrine and
pharmaceutical agents (Saunders, 1995, 1997).
Some pills contain no psychoactive substances at all. MDEA (MDE) has a
shorter duration of action (2 hours) and is more amphetamine-like, having
less emotional effects. MBDB is quite similar to MDMA but is described by
some as less intense with a greater 'cognitive' component as distinct from
'empathogenic/emotional', MDA is more psychedelic (LSD-like) and is
considered to be more toxic. 2CB is more psychedelic than MDMA but less so
than MDA (Shulgin and Shulgin, 1992). Amphetamine is a very common
additive, and the links between amphetamine use and a brief paranoid
psychosis, for example, are well established (e.g. Connell, 1958; Bell,
1965). MDEA is  very common in the UK, may be closer to amphetamine in its
effects than MDMA, and may possibly show a more similar profile to
amphetamine in terms of adverse effects. Ketamine, another common additive,
 has been given to experimental subjects to produce a 'model schizophrenia'
and can be profoundly hallucinogenic (Jansen, 1993, 1999).
The tendency of the moment to attribute problems to Ecstasy rather than
other drugs  is due to a 'psychology of negative effects reporting' which
is in the mind of the media-influenced doctor as well as the patient.

The Role of Poly Drug Use

 The overwhelming majority of persons who take Ecstasy also use other
drugs, a point  rarely emphasised in reports attributing a  disorder to
Ecstasy use, where use of other drugs is often dismissed in a few lines.
The concurrent use of large amounts of cannabis, LSD, alcohol, cocaine
ketamine  and/or amphetamine, for example, is often pushed into the
background. A very large number of habitual, weekend Ecstasy users are also
daily or near daily users of cannabis, which makes the 'come down' and mood
cycle less apparent. This is an important factor to bear in mind when
conducting research in this area. The use of cannabis has been linked to
relapse in
schizophrenia (Mathers and Ghodse, 1992).
For example, there is a case report of persisting depersonalisation
syndrome after ingesting Ecstasy only once (Wodarz and Boning, 1993). It
was subsequently pointed out that this patient had a history of daily
alcohol and cannabis use, and serious doubt was cast upon the role of
Ecstasy in the case (Gouzoulis and Hermle, 1993).

The Role of Set and Setting

'Set' refers to the personality, early imprinting, learning, past
experiences (including

previous drug experiences), temperament, mood, motivations, attitudes and
(very important) the

expectations of the drug user,  while  'setting' refers to the conditions
of use, including the
physical, social and emotional environment, and the behavior, understanding
and empathy of the other persons present. A pleasant set and setting are
more likely to have a positive outcome, while an unpleasant set and setting
are more likely to have a negative outcome.
In general, Ecstasy effects are  less susceptible to the influence of set
and setting than psychedelic drugs such as LSD. Nevertheless, expectations
do play an important part in all drug effects, and there are many who wish
to dance because they have been conditioned to associate this with Ecstasy,
irrespective of the actual content of the pill they have swallowed, just as
many persons reclining in quiet gardens will declare their love to the
others present for the same reason.

These issues are important because a large percentage of the 'bad
reactions' to LSD, psilocybin and mescaline may be attributed to a 'bad'
set and setting,  but this it is possible that this is less likely to be
true for Ecstasy. However, the role of expectations is significant, as
discussed above, and expectations can sometimes lead to a negative outcome.
For example, from a statistical perspective, serious physical effects from
Ecstasy are rare. Nevertheless, a perception on the part of the consumer
that they are experiencing such effects has increased considerably in the
wake of fear spread by the media, as a result of which there has been an
increase in the number of persons presenting with the false belief that
they are in physical extremis (but no reduction in the number of users,
emphasising the futility of the standard media approach). The real
diagnosis is more likely to be panic which can be treated with a quiet
room, the passage of time, reassurance and possibly drugs such as
lorazepam.  Many of these 'cases' recover while waiting to see the doctor.

What Are the Risks In Numerical Terms?

The actual risk of developing a serious psychiatric condition following the
use of Ecstasy is unknown, but is likely to be relatively low once the
person has recovered from the acute effects of the drug. The relative risk
of any particular outcome should be determined by dividing the total number
of outcomes of that type which actually occur by the total number of doses
consumed (risk exposures). 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 are never treated at all.

Another method of gaining perspective on the general importance of
Ecstasy-induced mental disorder is to tour  emergency rooms and the wards
of psychiatric hospitals. This pragmatic investigation will produce at
least one  clear conclusion: the drug which is principally associated with
sudden death, suicidal depression, homicide, cognitive deficits,
schizophrenic relapse 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 (Cohen, 1995). The  immediate
effects reported included paranoia, 20%; anxiety 16%, and depression 12%;
while the  long-term/recurring effects reported included depersonalisation
(defined later) 54%; insomnia 38%; depression 38% and flashbacks 27%.
Two double-blind, placebo controlled assessments of MDEA users (n=14)
compared with non-using controls reported one case of toxic psychosis, a
severe dysphoric reaction and one anxiety disorder (Hermle et al., 1993).
It must be noted this study involved MDEA, and not MDMA.

Other Confounding Variables: The Issue of Causality

Many of the published reports draw cause and effect conclusions which are
not justified by the data presented, i.e. they conclude that Ecstasy
consumption caused the symptoms rather than being associated with the
symptoms.
We have already considered the use of other drugs in addition to Ecstasy,
that the pill swallowed was not Ecstasy at all, and variations in the set
and setting of use as possible explanations for an apparent association.
Other matters to consider are:

--the probability of a chance association.
It is important to recognise that, among the large group of drug users
within the general population, a proportion will become mentally ill
regardless of any supposed psychotomimetic properties of drugs.
(Poole and Brabbins, 1996, p137).
Depression and anxiety are common conditions in the general population. It
is a statistical certainty that many persons who take Ecstasy will develop
depression regardless of drug use. The one year incidence of major
depression in the general population is 80-200 per 100,000 for men and
240-600 per 100,000 for women (Gelder et al., 1995).
Anxiety, panic attacks and all of the other symptoms associated with
Ecstasy use also have an incidence, sometimes substantial, in the
non-Ecstasy using population.

--poor pre-morbid adjustment: a poor adjustment to life circumstances is
associated with an increased likelihood of drug use, and a worse prognosis
when major mental illness develops. Drug use may be a symptom of  impending
or actual mental illness as a result of 'self-medication' of distress, or
due to impaired judgement.
-Preexisting mental illness and a family history of mental illness: such a
history is common in persons who develop psychiatric illness in apparent
association with drug use.
-Preexisting neurochemical, genetic and personality differences: Each year
brings new reports linking inherited genes to to behavioural patterns,
including alcoholism and the need for high levels of stimulation (both of
which may involve dopamine receptors).
It is possible that persons who take drugs  may have pre-existing,
genetically determined 'under-functioning' of serotonergic and/or
dopaminergic systems, and this 'under-functioning' increases the likelihood
of depression and anxiety, and creates an inner drive towards taking drugs
which provide relief. Thus retrospective studies of the serotonin and
dopamine systems in high dose, chronic Ecstasy users, in comparison with
non-using controls, may be seriously confounded by pre-existing differences
between the two groups. This is a point which those doing cerebrospinal
fluid measures of serotonin, and d-fenfluramine challenge tests, can rarely
take into account.

The Role of the Media - Lessons from LSD

 The media have played a highly significant role in the psychology of
adverse drug effect reporting. We will briefly examine the historical case
of LSD,  as this has implications for Ecstasy.

In the 1960's, an astonishing range of mental and physical disorders were
attributed to LSD use.
However,  although LSD use is now at very high  levels, LSD is no longer
generally accepted  as a major cause of this extended list of complaints
(LSD use: 12% in 15-16 year olds in the U.K.,  McMiller and Plant, 1996
published in the British Medical Journal;  10% in persons aged 16-29 ,
President of the Council, 1998 -U.K. Government official report). One issue
which attracted  much media attention was  that of 'flash-backs' and
chronic hallucinosis following LSD. While precise figures are difficult to
calculate, these do not appear to be common  conditions in the 1990's,
despite both the high level of media interest in them in the past and high
current  levels of LSD use. Most psychiatrists are now unlikely to see many
cases of true LSD- induced chronic hallucinosis attributable to LSD use
alone, and which are not in fact the more common alcoholic hallucinosis,
schizophrenia which has only a coincidental relationship with LSD use, a
form of dissociative conversion syndrome ('hysteria') or post-traumatic
stress disorder (PTSD) following a traumatic LSD experience, or are due to
ongoing drug use of some other kind such as cannabis, alcohol or
amphetamines. Most of the persons currently bringing lawsuits related to
being given LSD in the 1960's are probably suffering from PTSD. In most of
this case material, the set and setting were extremely unfavorable and
there was no informed consent. It was the behaviour of the persons giving
the LSD which sometimes played a major role in  later mental health
difficulties.With occasional  exceptions, LSD has  largely disappeared from
the pages of psychiatric journals and tabloid newspapers  except when there
is a major interception by the police.

Unfortunately, psychiatrists in the 1960's and 1970's were as influenced by
the media emphasis upon LSD as were the general public, and sometimes
diagnosed persons as suffering from conditions induced by LSD  when they
were in fact suffering from schizophrenia,  manic-depression, dissociative
conversion disorders (i.e. 'hysteria') , PTSD, neuroses, and problems due
to use of other drugs.
 
The 1990's  saw  a remarkable re-run in the U.K. of  1960's-style media
hysteria based around the drug Ecstasy. A single death, that of Leah Betts
who had drunk too much water after swallowing a pill,  was front page news
for months. It was rarely pointed out that the actual risk of death in
association with taking Ecstasy, from all causes, was in the region of 1 in
650,000 to 1 in 3 million risk exposures (see Saunders, 1995, 1997). In the
same week that Leah Betts died, an average of 1000 people died from the
health consequences of alcohol, and over 2000 people died from the health
consequences of smoking in the U.K.  In that week, alcohol was involved in
at least 30% of the reported motor vehicle deaths, suicides and murders.
There was a  complete loss of perspective on the 'killer drug' Ecstasy.
Ecstasy hysteria has now started to quieten down a little, although it will
take a few more years for the dust to settle.
This type of media and political attention, regardless of the drug, almost
always results in an increase in the number of persons presenting to
hospitals and doctors with the belief that they are suffering serious
effects from taking the drug in question. It is worth noting that the
number of users, however, does not usually go down as a result of this
particular type of  adverse publicity. Not only did Ecstasy use increase
after the campaign which used her photograph and the line: 'Sorted: It took
just one Ecstasy pill to kill Leah Betts', but drug manufacturers brought
out a special commemorative pill called 'the Leah'.

It can thus be argued that the activities of some branches of the media
serve to make a drug more widely known, may actually increase use of a drug
as a result, and almost certainly increase the burden of inappropriate
referrals to the health service.

The lessons from LSD and Ecstasy are that we should not jump to hasty and
unscientific cause-and-effect conclusions with a mind-set produced by the
fashions, media and zeitgeist of the times.

The Adverse Psychological Effects of MDMA

As noted above, current research evidence is sparse and retrospective
(which means that it is carried out by looking back into the past after the
side-effect has appeared rather than giving a person the drug to see what
will happen), generally uncontrolled (there is no properly matched group
for comparison who have not taken the drug), generally lacks toxicological
confirmation of the drugs taken, and  we are usually not told what happened
next: the course of the disorder and the long-term outcome for the person.
This is very important to exclude underlying schizophrenia or
manic-depression for example. The studies  rarely relate the person's
mental state to the toxicological results (e.g. continuing presence of drug
metabolites in the urine), and depend heavily on single case studies but
nevertheless frequently conclude cause- and- effect relationships from what
may be chance associations, although it is also possible that the cause-
and- effect relationship is true.

Psychosis

Ecstasy may  produce a state of intoxication which mimics a paranoid
psychosis (Kemmerling et al., 1996; Williams et al., 1993), but this does
not usually last for more than a few days, and appears to be relatively
rare. Although Ecstasy is not a hallucinogen in most people, it can cause
hallucinations on occasion, especially in higher doses. I have myself seen
a person in a state of toxic delirium after taking no more than 200mg of
pure MDMA and no other drugs. She was completely disoriented, had marked
difficulty walking (she collapsed several times injuring herself), and
spent several hours trying to pick up nonexistent objects from the floor
and talking to people who were not present. There was no history of
psychosis, although her mother had suffered  from depersonalisation
disorder (see below). She was an experienced Ecstasy user with no previous
phenomena of this nature. She experienced depersonalisation on a single
dose of fluoxetine ('Prozac').

Ecstasy may sometimes alter the clinical picture in a pre-existing
psychosis. Some people with schizophrenia or manic-depression will also
take Ecstasy, especially as the peak age of onset of schizophrenia is
20-30, a age group in which experimentation with drugs is relatively
common. It is unknown whether or not Ecstasy can specifically induce a
relapse of pre-existing schizophrenia or manic -depression, beyond the
increased risk of relapse attached to any substantial emotional stressor.
Ecstasy experiences are typically emotional events, and for this reason
alone one would expect to see an association with increased risk of relapse
in schizophrenia. This is implied by the extensive studies concerning the
effects of high levels of 'emotional expression' ('E.E.') on the risk of
relapse.

Ecstasy releases dopamine in a similar manner to amphetamine and cocaine
(Nichols and Oberlender, 1989) and as such might be expected to increase
the risk of psychotic illness in a similar manner. Some investigators
report that they have repeatedly observed clear links between the onset of
psychotic symptoms and the use of Ecstasy (McGuire and Fahy, 1991). This
latter study is based on two cases, other substances were involved, and
there was no toxicological confirmation of pill content. However, there are
several other reports (Schifano, 1991;1994; Williams et al., 1993; Winsock,
1991; Nunez-Dominguiez, 1991) and taken together the evidence is indicative
of a risk. The size of that risk is unknown at the present time, but is
likely to be relatively small.

Can Ecstasy cause a true 'drug-induced psychosis'? As distinct from the
categories above, Poole and Brabbins (1996) have argued that this term
should be restricted to psychotic symptoms arising in the context of drug
intoxication but persisting beyond elimination of the drug and its
metabolites from the body. Such a psychosis should only recur on
re-exposure to the drug, and must have a different course and outcome from
the major functional psychoses (i.e. schizophrenia, manic-depression et
al.).

Decisions about classifying Ecstasy effects  should be made by those  who
can distinguish intoxication , in other words the effects which are
experienced by most persons who have taken that drug, from psychosis and
other adverse effects. If the majority of persons have a particular effect
when given Ecstasy, then this effect  is  intoxication and not an adverse
effect.  Psychotic beliefs (delusions) must be incompatible with what is
held to be true and possible in the person's  particular culture or
religous sect for example. Thus beliefs that one is being persecuted by a
witch are not psychotic in large parts of Africa, but may raise concerns
when they develop in an elderly woman in New York, with no previous
interest in witchcraft. In both African and New Yorker, the further belief
that there are microphones inside all of the lightbulbs in  the house, and
cameras in the bathroom, causes immediate concern regardless of the social
circle's belief or otherwise in witchcraft.

 Poole and Brabbins (1996) argued that the common assumption that a
specific, amphetamine-induced psychosis meeting these criteria has been
established is in doubt. The most cited study is that of Connell (1958),
although actually reading this work indicates that he did not describe such
a syndrome.  Connell actually demonstrated that the psychosis only occured
with  intoxication, confirmed by  measures of amphetamines in the blood.
According to these authors, psychosis wholly due to amphetamines tends to
resolve as the urine clears. Where the psychosis does not resolve,
long-term follow-up studies usually find schizophrenia or manic-depression
rather than a condition caused by amphetamine. However, Sato (1992) has
reported that chronic use of metamphetamine produces a lasting
vulnerability to a paranoid delusional psychosis with schizophrenia-like
hallucinations, which does extend beyond the excretion of the drug in the
urine, and that re-use of methamphetamine and alcohol, and stressors, lead
to recurrence of a psychosis with clinical features matching the previous
methamphetamine linked episodes.
I have reported on a person who injected 250mg MDMA powder up to 4 times
daily, intravenously for 6 months, without experiencing any psychotic
phenomena, but became acutely psychotic on injecting dexamphetamine
(Jansen, 1998). This suggests that we should be cautious in making
generalisations from amphetamine data to Ecstasy, tempting as this may be.

Drug  use may sometimes be a signal of psychological distress, rather than
a cause of that distress. People may try to 'medicate' themselves with
drugs during the early stages of a psychosis or relapse, so the drug use is
not causal but symptomatic. They  may also be more likely to use drugs when
ill as a result of impaired judgement.

Anxiety Disorders and Panic Attacks

We are currently limited to a handful of case reports (Greer and
Tolbert,1986; Whitaker-Azmitia & Aronson, 1989; McCann et al.,  1996;
Pallanti & Mazzi, 1992,McGuire et al., 1994, Hermle et al., 1993;
Kemmerling et al., 1996; Jansen, 1997).
The communications I have received from persons who have suffered adverse
effects suggest  that anxiety disorders are commoner than depression as a
long-term outcome, and this is confirmed by the published reports in which
forms of anxiety disorder currently appear to be more common  than
depression, once tha acute effects of the drug have passed one week later.
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 feelings that one is not 'real', detached,
unable to feel emotion and .
separated from the world by a glass wall. Derealisation is where the
environment appears unreal and meaningless. People may be described as
'cardboard-like'.
 These phenomena have been reported in association with Ecstasy use (Wodarz
and Boning, 1993), but there are many other possible explanations such as
fatigue, depression, anxiety, schizophrenia, temporal lobe epilepsy and,
most likely of all, other drugs such as ketamine which is particularly
associated with this effect because of the questions which it raises
concerning the nature of reality and the self.
 'Depersonalisation and derealisation disorder' may also occur
spontaneously.

Depression and Mania

A brief period of low mood associated with the 'come-down' is common
(Curran, 1998). There is also sometimes a longer lasting depression
(Benazzi & Mazzoli, 1991; McCann et al., 1996), but the drug use may have
been a form of self-medication of a pre-existing depression, or a latent
depression, rather than actually causative of depression. Depression may be
predicted on theoretical grounds due to links between mood and serotonin.
However, animals with extensively damaged cortical serotonergic nerve
terminals generally show little difference, or only very modest
differences, in their behaviour relative to control animals several weeks
later. 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 (Molliver et al., 1989). It may be 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 (Molliver et al., 1989). This matches the weekly
cycle of what has actually been observed in humans.

Cognitive deficits (Impaired memory, attention and concentration)

Research into persisting (as distinct from acute) drug-induced problems
with memory, attention and concentration is very difficult to do well. The
number of alternative explanations for any  problem is always high. For
example, it is essential to control for the use of other drugs,
particularly regular cannabis smoking and excessive alcohol consumption,
and for the effects of any mood disorder upon cognition. It is crucial that
all claims of persistent problems should be accompanied by evidence that
the urine tests of the subjects were clear of  all drugs and their
metabolites, including cannabis metabolites which can take at least 4 weeks
to dissapear from urine in chronic smokers. It is not possible to test for
alcohol use in this way, but liver function tests should be normal.
Reports of subtle memory deficits which not accompanied by published urine
test data may be due to cannabis. A report of subtle memory deficits in
association with Ecstasy use has been made by Krystal and Price, 1992, and
there is a related report by Parrot et al., 1998.

Persistent problems are those which are still present once all drug
breakdown products (metabolites) have been completely eliminated from the
body. The self-report of subjects re their personal drug use is often
inaccurate, and is unacceptable for research of this nature. Despite the
best of intentions, people often  lapse and use various drugs while taking
part in studies, and then deny this to the experimenters as they do not
wish to dissapoint them or be excluded from the study. It is not enough for
authors to say that subjects were asked to abstain from drugs for several
weeks. Nor is it enough to say that urine tests were carried out. The
actual results of the drug tests must be published, along with the rest of
the report.

When I was studying long-term high-dose Ecstasy users, many of the urine
tests were positive
for cannabis. I recall carrying out a 6 hour neuroendocrine test at the
laboratory one Saturday morning. I left the room for a few minutes and on
my return found both subjects had risen from their beds - where they were
supposed to be lying still - and were leaning out the window smoking
cannabis. It seemed better science, in the end, not to publish these tests
due to the extent of the 'uncontrolled' variables and contamination of the
data from various sources.

It is also important to eliminate the effect which disorders of mood, such
as depression, disorders of anxiety, and other mental health problems may
have on testing cognition. It is well recognised that depression and
anxiety impair memory, attention and concentration. Where investigators
have not excluded these factors, they may contribute significantly to the
results of a study as these disorders have well known effects upon
cognition.
 
If subjects have been told to abstain from all drugs before cognitive
testing takes place, a withdrawal syndrome may result ('cold turkey') which
could confound tests conducted during this withdrawal period. For example,
even stopping a regular coffee intake can result in headaches, fatigue and
impaired function. There is some controversy concerning the effect of
abstaining from long-term daily cannabis use. Irritation and anxiety are
sometimes noted.

A control group which is a genuine match for the subjects is essential. It
is particularly important to carefully match for the use of other drugs. In
many drug studies, there is a subtle bias for the control group to have
used less drugs and to be more high functioning than the subjects.

Other aspects of thinking which should be considered are abstract thinking,
the ability to detect patterns, learn by experience, plan ahead and follow
through with plans. These  functions are to some extent controlled by the
frontal lobe of the brain. Frontal lobe ability to learn from experience
and detect patterns  can be tested using the Wisconsin card-sorting test.

Proto-oncogenes

A major growth area in the last 10 years has been studying how drugs switch
on certain genes within the cell nucleus, which then produce a range of
proteins. Some of these proteins may also form the basis of  memory. When a
long-term memory  is formed the brain can be said to be 'permanently
altered'. Therefore,  drug experiences which are remembered have produced
lasting brain changes like all other memories.
So far, so normal. However, some types of  psychological experience, such
as major emotional trauma, produce memory traces and changes in the brain
which may not be healthy as they have pathological effects  upon mental
health. Thus psychological events can result in changes to the hardware of
the brain. Post-traumatic stress disorder (PTSD) may be an example of a
condition in which organic brain change can result, producing problems with
memory, learning, attention, anxiety and depression (Van der Kolk, 1997).
PTSD can also produce  episodic hallucinations for a period (Kaufman,
1997).

When a drug binds to a receptor on the cell wall, this can switch on a
signalling system inside  the cell. This signalling system sometimes sends
a messenger to the DNA inside the nucleus. Certain genes on the DNA are
then switched on,  and these genes start the process which results in the
construction of new proteins. It is also possible that the signalling
system is switched off , and that production of certain  proteins is thus
switched off. This may prevent the formation of certain memories.

When a person takes Ecstasy  frequently, there may be a significant effect
upon the production of particular proteins, even if  no obvious structural
changes can be seen like those in rat studies.
Of course, switching on a gene to produce a protein is a normal process and
not the same as damage, unless it is a protein in some way  associated with
damage such as the 'heat shock protein'. Even the signifance of this
protein is unclear. It may actually protect the cell from serious injury.

The type of genes initially switched on or switched off by drugs are called
'proto-oncogenes', but this is for historical reasons. Cancer is not an
issue here. These proto-oncogenes produce proteins with names such as Fos
and Jun. Fos proteins may indicate little more than cell activation.

The Pandora's Box Syndrome (PBS); Busy Head Syndrome

Persons who have taken large quantities of drugs such as LSD, ecstasy and
ketamine for a prolonged period may develop a mental state which involves a
high level of internal, 'mental' imagery but no perceptual disorder. It is
as if perforations have been made in the defences which usually separate
conscious from unconscious processes, resulting in material percolating
through the conscious mind where it would not normally be found. I have
named this syndrome after the legend of Pandora's box: once opened it
proved impossible to push back in all that flew out. The condition is not
serious. It does not prevent the afflicted person from going to work or
going about the normal business of life. However, attention and
concentration are impaired, which
may lead to an apparently poor memory due to failure to attend to new
information. The person may be said to have 'lost their edge' or 'lack
focus'.

Flashbacks, Post-Hallucinogen Persistent Perceptual Disorder (PHPPD),
 Post-Traumatic Stress Disorder (PTSD).

Flashbacks have been described by Ecstasy users (Creighton et al., 1991;
McGuire & Fahy, 1992). The term 'flashbacks'  is widely used but rarely
defined. Researchers who use this term should describe exactly what they
mean. The term commonly refers to episodes of a few seconds duration in
which the person re-experiences some of the subjective effects of taking
the drug in question, after an intervening period of normality. This is
clearly very different from the media-generated impression that a flashback
is a complete, unprovoked re-living of the full drug experience. The term
'flashback' covers a potentially wide range of possibilities and should be
subdivided into categories.

'Posthallucinogenic persistent perceptual disorder' (PHPPD) describes more
or less continous phenomena, with no intervening period of normality. For
example, chronic LSD users
 with PHPPD were  said to describe trails of light, and images following
movement of their hands, which were persistent and  aggravated by any form
of psychoactive drug use,
and distinguished from flashbacks by being chronic in nature versus the
episodic nature of flashbacks.

Explanations for Flashbacks

The likelihood that flashbacks are due to persisting changes in the brain
is unlikely but not impossible. We can learn more about drug-related
flashbacks by considering another condition in which flashbacks occur:
post-traumatic stress disorder (PTSD). The Tenth International
Classification of Diseases (ICD-10, World Health Organisation,1992) defines
PTSD  as  a delayed and/or protracted response to a stressful event of an
exceptionally threatening or catastrophic nature, which is likely to cause
distress in almost anyone. A small number of Ecstasy experiences may be
very stressful and perceived as catastrophic. '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).
Predisposing factors such as personality problems or a history of neurosis
may make the development of  PTSD more likely, or aggravate its course, but
they are neither necessary nor sufficient to explain it.

ICD-10 describes the typical symptoms of PTSD as including 'episodes of
repeated reliving of the trauma in intrusive memories ('flashbacks') or
dreams', a sense of numbness and emotional bluntening, detachment from
other people, a loss of the ability to derive pleasure from the life, and
avoidance of reminders of the trauma. There is usually a state of
hyperarousal (rapid heart rate, sweaty palms, 'very jumpy') and insomnia,
and there is often accompanying anxiety and depression with excessive use
of alcohol and other drugs. The condition follows the trauma after a
latency period of a few weeks to months, has a fluctuating course and
recovery can be expected in the majority of cases.

Flashbacks are more likely following very traumatic drug experiences. 1of
the 3 cases cited by Creighton et al. (1991) involved a woman who had been
abducted and raped while under the influence of  MDMA. The other 2 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, again
demonstrating the importance of polydrug use.

A detailed study of those who describe 'flashbacks' after Ecstasy will be
required to establish how many of these features are seen. There is a view
that some forms of PTSD actually involve underlying brain changes, albeit
of a resolving nature. It may be the extreme stress which produces this
change rather than a neurochemical effect specific to the drug, as a
wide array of drugs, with quite different mechanisms of action in the brain
(e.g. LSD and ketamine) have also been linked to flashbacks.
 
Other drug-related flashbacks may be a form of psychological 'conversion
disorder' (formerly known as hysteria), 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. It is worth noting 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 some resemblance to the flashbacks described by some drug users.

Persons who experience flashbacks do recognise that the phenomenon arises
within themselves, and frequently attribute them to drugs. If the person
does not view the symptoms in this way, they probably do not have
drug-related flashbacks.

In conclusion, the currently available evidence suggests that
Ecstasy-related  flashbacks are probably not the result of
specific,drug-induced 'brain damage' as such although the possibility has
not been excluded, and are not the result of 'lingering drug quantities '
in the brain. Flashbacks are most usefully understood as a form of PTSD or
a form of neurosis of the dissociative conversion/anxiety disorder type.
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.

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 (McCann et al., 1991). A minor but 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 or in distress (Allen, McCann, & Ricuarte,
1993).

Ecstasy - A Stepping Stone to Other Drugs ?

The use of ketamine may be  associated with the use of other drugs for a
variety of purposes, particularly to overcome the stimulant effects and
allow sleep (i.e. to come down), or to prolong and strengthen the stimulant
effects and avoid sleep. For the first purpose, temazepam, alcohol and
cannabis are often used, and there has been a rapid growth in smoking
heroin ('brown') for this purpose in the U.K. due to a massive increase in
supply. For the second, amphetamines and cocaine. There is also a link
between taking Ecstasy and a desire to smoke excessively, which may be
related to the effect of these drugs upon dopamine pleasure systems in the
brain. Respiratory illnesses are a common result when the smoker is moving
from a hot dance environment to the cold night outside.

Tolerance and Dependence

The use of almost any substance may become compulsive and excessive in some
individuals and there are certainly a few people who have taken Ecstasy on
a daily basis, regardless of tolerance effects, for prolonged periods
(Jansen, 1998; McGuire and Fahy, 1991). I have described the case of a
person who injected 250mg of  MDMA powder intravenously, up to four times a
day. for 6 months. Eventually, 250mg taken orally had almost no effect on
them at all (Jansen, 1998).
It is far more common, however, for 'problematic' Ecstasy use to involve
consumption of 20-40 pills of the drug in binges lasting from Thursday
night until Monday morning, with 4 'recovery' days in between.

The 'love effect'  fades with repeated use, and the effects may become more
amphetamine-like (Peroutka, 1990; McCann and Ricaurte, 1991). This may
partially explain some of the escalation in dose levels seen in recent
years, as some users will be vainly attempting to recover the mental state
which they experienced initially - now impossible due to neurochemical and
psychological changes in the brain and mind resulting from repeated use.
Other reasons for escalating dose levels are the substantial drop in price,
and possibly an observation from animal research that under-functioning of
serotonergic nerve terminals can result in increased use of
amphetamine-like substances for pharmacological reasons (Lyness et al.,
1981)

The day after taking Ecstasy, if they have had a reasonable amount of
sleep, not consumed large quantities of other drugs, and not gone clubbing,
many users feel  elevated in mood. However, by the third day low mood,
which may be quite severe, and irritability are common. This continues into
the fourth day, with relative recovery of mood occurring on the fifth. The
cycle frequently repeats itself with Ecstasy use on the 5th, 6th and 7th
days. Thus some persons may be said to be
continually affected by the drug, even if they only take it in the
weekends.
It is not necessary to take a drug every day before a dependency syndrome
can be identified,
nor is physical withdrawal essential.  The possibility that Ecstasy may be
associated with tolerance, psychological dependence and withdrawal
syndromes will surprise those 'Apollonian' users who only take the drug
occasionally in controlled circumstances (as distinct from
the Dionysian, 3 day party, 'neck em',  stack em' and go' group). In this
context it is valuable to recall the history of amphetamine itself. In the
late 1930's, the American Medical Association approved the use of
amphetamine for a wide range of disorders, and the pharmaceutical company
Smith, Kline & French reassured physicians that 'no serious reactions had
been observed'. Between 1932 and 1946, the pharmaceutical industry found 39
licensed uses for amphetamine, including the treatment of schizophrenia and
tobacco smoking (review: Lukas, 1985). It was not until the late 1960's,
after numerous case reports, that it was officially accepted that
amphetamines were addictive and that amphetamine-associated paranoid
psychosis was relatively common among heavy users.

The extreme fatigue, excessive sleeping and then anxiety, insomnia and
depression which follow cessation of chronic amphetamine use are regarded
as a bona fide withdrawal syndrome. Which aspects of this picture chronic,
high dose ecstasy users may share has not yet become apparent.
Ecstasy has an effect on dopaminergic systems which is similar to that of
stimulants associated with dependency, and activates dopamine-based
pleasure systems in a manner resembling amphetamine and cocaine ( Nichols
and Oberlender, 1989).
It was once believed that Ecstasy would be free of any dependency risk
because of the rapid loss of the empathogenic 'loved up' effect with
repeated use (Peroutka, 1990). However, while loss of this effect may lead
to declining use in an older group who take ecstasy for its empathogenic
properties, younger users in the dance culture may come to appreciate the
more amphetamine-like qualities, and have different expectations. This
group rarely take pure compounds and may have been conditioned from the
outset to expect amphetamine-like effects from a 'pill', as many pills are
in fact amphetamine or MDEA, rather than MDMA (review: Saunders, 1995), and
also because polydrug use is very common, with many of those who party
throughout the weekend deliberately taking amphetamine and other drugs in
addition to ecstasy, a milieu in which the particular effects which
distinguish ecstasy from other pleasurable stimulants are diminished.
The animal evidence suggests dependency potential, and presumed changes in
serotonergic nerve terminals do not result in  reduced frequency of MDMA
self-injecting behaviour in monkeys  (Lamb and Griffiths, 1987). In fact,
impaired serotonergic function has been  linked to increased self
administration of amphetamine  because of a complex interaction between
serotonergic systems and dopamine pleasure systems in the brain's pleasure
centres (Lyness et al., 1981).

A questionnaire investigation of 100 ecstasy users in Sydney found that 2%
of the sample considered themselves to be 'dependent' (Solowij et al.,
1992). The value of such a self-report is questionable however. 47% of
respondents in the study expressed the belief that it was possible to
become dependent on ecstasy.

Treatment
Most Ecstasy  -associated problems resolve over time without special
treatment. Where outside help is sought, the approach should address
biological, psychological, social, and spiritual issues. The person should
be encouraged to be responsible for themselves, in tandem with professional
assessment and advice.

For problems which do not involve psychosis, non-drug (as in prescribed
medicine) approaches are a  good  long-term investment in terms of
remaining well, avoiding side-effects, and placing the locus of control
inside the person rather than outside. It should be possible for most
literate persons to at least buy a self-help book on overcoming anxiety,
panic attacks, depression and sleeping problems. There are many such books,
allowing the sufferer to take greater responsibility for themselves.

It is best to avoid  automatically accepting the conclusions of the person
themselves and/or their family, who may be only to ready to make an
attribution to drug use -vastly preferable to a diagnosis of schizophrenia
or bipolar disorder (manic-depression) which suggests that something more
fundmental and potentially uncontrollable is amiss.

It is also worth bearing in mind that people who develop psychotic symptoms
in the context of Ecstasy use may be more prone to schizophrenia and mania
in any case, i.e. they may have an inherent pre-disposition unmasked by the
effects of the drug, or the drug may have precipitated a relapse in a
pre-existing condition. Most people can absorb vast quantities of all types
of drugs without ever stepping over the line between intoxication and
psychosis.The reverse error is also possible.  A wrong diagnosis of
schizophrenia or mania may result in  inappropriate treatment with
antipsychotic drugs and a risk of comittal to a psychiatric hospital.

To talk-down or to medicate?

In an acute situation, while the person is still affected by the drug,
there are three main options: doing nothing (which is the usual approach,
most people recover while waiting to see a doctor), 'talking down', and
medication.  It must be established that the person is physically safe and
has not taken unknown quantities of  suppressant drugs such as alcohol,
opiates, sedatives, tranquillisers or barbiturates. If  they have,
psychological care must be secondary to physical concerns and these may
involve monitoring and nursing in an appropriate unit to ensure physical
safety.

The diagnosis of  most persons seen by health and emergency services is
likely to be panic which can be treated with a quiet room, the passage of
time, reassurance and possibly lorazepam (a fast acting relative of
Valium), if they have not also taken 'suppressant' drugs such as alcohol,
opiates, barbiturates, GHB,other benzodiazepines in unknown ammounts, etc.
In these cases it may be  safer not to give any additional sedatives, and
to monitor the person closely.
Many of  the ordinary  'cases' recover while waiting to see the doctor.

Because of the  link between traumatic drug experiences and subsequent
'flashbacks' and PTSD,
 the use of 'talking down' (non-judgemental verbal reassurance in a low
stimulation environment) requires serious re-evaluation. If a person who
has taken a psychedelic or dissociative drug is having a very  unpleasant
experience, and has sought professional help, early consideration should be
given to administration of lorazepam as an intramuscular injection, to
relieve anxiety, possibly with oral diazepam to follow. This will
substantially lower the risk of post-traumatic stress disorder, flashbacks,
and a host of anxiety-related conditions. In other words, the person should
remain in the unpleasant state for as brief a period as possible to reduce
the risk of subsequent mental health problems. There is a  view that a
person may profit by a negative experience, and should walk through a
valley of suffering to achieve enlightenment. Until this view is
evidence-based, and the two approaches have been compared in formal
studies, it is better practice to relieve suffering and reduce the risk of
after-effects using benzodiazepines. This would appear to be the most
ethical course where the person has not signed up for a 'night sea journey
of the soul', is seeking help,  and where there is no pre-existing
therapeutic alliance  with those attempting to help them. This last issue
is particularly important, and differentiates drug-assisted psychotherapy
from persons who are presenting in a crisis and seek relief, not attempts
at acute psychotherapy to which they have not given informed consent,
attempted by persons they have just met.

This raises the issue of where such treatment should take place. Attendance
at hospital is likely to elevate anxiety levels considerably and contribute
further to general distress. It would seem more appropriate in these cases
for a doctor to call at the address where the person is located rather than
for the person to be taken to hospital, unless potentially dangerous
mixtures of drugs are involved which threaten physical safety (see above).
This is far less traumatic for the patient. Too few people consider calling
a service to the house rather than attending hospital.

Antipsychotic drugs such as chlorpromazine and haloperidol should
definitely not be used, regardless of agitation or psychosis. It is not
widely appreciated that the antipsychotic effects of drugs such as
haloperidol usually take several weeks to become manifest. Anti-psychotic
drugs should also be avoided because their anti-cholinergic and numerous
other side-effects will be additive with those of Ecstasy and whatever else
the person may have consumed. The increasing likelihood that several
substances have been taken is another strong argument against the use of
haloperidol. Haloperidol is also a cause of the rare neuroleptic malignant
syndrome which may be may be linked to the over-heating syndromes
associated with several Ecstasy-related deaths (Ames & Wirshing,1993). It
is  more sensible and much safer to use lorazepam or the longer-acting
diazepam. These drugs have a shorter action, are specifically designed to
relieve anxiety,  and do not have the many side-effects of haloperidol.
Antipsychotics are sometimes resorted to after benzodiazepines because the
the latter have not been given in adequate dose, and hence do not appear to
be effective. Benzodiazepines are usually relatively  safe compounds, the
overdose limit is high, and a person who has taken any form of stimulant
can usually absorb a substantial quantity of diazepam and lorazepam with
little relative risk. With the assistance of an anesthetist, consideration
should sometimes be given to a complete 'knock-out' medicine such as
midazolam which will rapidly induce sleep and can be injected, or the
heavily sedating clonazepam if  the person is very agitated. The range of
benzodiazepines is wide enough to render antipsychotic drugs irrelevant and
outdated for the acute treatment of drug-related mental health problems.

Psychotherapy

This can be considered for persistent effects once the acute situation has
passed.
For some conditions, there will be a place for counselling, psychotherapy
and cognitive/behavioural therapy.
 Denial can  be dealt with using facts from the person's life rather than
research findings, e.g. 'Lets examine the effect that taking 10 E's every
weekend is having on your studies...on your finances...on the way you feel
by Wednesday afternoon...on your life in general now that you have been
arrested and charged with intent to supply because you bought  a big bag of
pills to save money...on your having a relationship with a violent
nightclub bouncer...on your increasing tendency to smoke 'brown' (heroin)
for the comedown...'
This approach may be more effective than discussions about serotonergic
terminals.
Where the symptoms have a strongly neurotic character, psychodynamic
psychotherapy or formal psychoanalysis are worth considering. The approach
involves a gradual exploration of the unconscious, and a 'working through'
of difficult material. The focus is not usually upon the drug- taking
behaviour itself.

Medication

The person 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 identifed or
suspected, treatment should be as for the underlying condition
(antidepressants, antipsychotics, lithium, carbamazepine etc.)
-Antidepressants
Antidepressants such as fluoxetine ('Prozac') and paroxetine can be useful
treatments for depression, anxiety, panic attacks, and  sleep disorders
(see Windhaber et al., 1998)
Serotonin reuptake inhibitors such as fluoxetine will prevent the
neurotoxicity of MDMA in animal studies if taken within 3 hours of the MDMA
dose. 50% of the depletion is blocked at 6 hours, but there is no
protective effect at 12 hours. (Schmidt, 1989). However, these animal
studies generally involve massive doses of fluoxetine, and their relevance
to the human situation is unknown.  Fluoxetine after MDMA may reduce sleep
disorders and restlessness.
-Benzodiazepines (Lorazepam, Temazepam, Diazepam ('Valium'))
As noted above, after the acute crisis has passed it is usually best to try
non-drug approaches first. Basic 'sleep hygiene' includes avoiding caffeine
completely after midday. Many health food stores will carry books on
achieving natural sleep. If all else fails, insomnia may be treated with a
short course of temazepam or zopiclone.
 If non-drug methods fail to bring panic attacks within reasonable control,
these may be  treated with lorazepam. Severe chronic anxiety may be treated
with intermittent courses of diazepam
in the short term.  All of these drugs are potentially addictive and are
best not used for more than a few weeks at a time. However, some doctors
feel that this means they should not be used at all, leaving their patients
to suffer. There is  a place for the judicious prescription of these drugs
in persons who do not benefit from  non-drug approaches, rather than
leaving them in a state of high distress because of the long-term risk of
dependence.
Antidepressants are also useful for treating anxiety.
-Antipsychotic Drugs
 If it becomes clear  over the course of time, with psychotic symptoms
failing to resolve after several days,  that an antipsychotic drug is
required , the drug of choice is olanzepine which is sedating, and can be
taken once only at night.

When carrying out an assessment, it is important to bear in mind that a
'drug induced psychosis' should not be diagnosed simply because a patient
with a psychosis has also been using drugs. Incorrect attribution of
psychotic symptoms to the use of Ecstasy may result in persons with
schizophrenia or manic-depression not receiving proper care and education
about their illness. They are not prescribed long-term medications or
lithium to prevent relapses, are not adequately engaged with services, and
their families are not appropriately educated. The result is a very high
relapse rate. It is thus important to take a careful history, speak with
relatives, and avoid jumping to hasty conclusions. There may be  an
underlying psychiatric disorder which is associated with drug use by
chance.
Urinanalysis is essential when psychotic symptoms occur in association with
drug use. It is also important to note that the overwhelming majority of
Ecstasy users are polydrug consumers, and care must be taken not to
attribute symptoms to the wrong drug.

Meditation, Relaxation, Martial Arts and Physical Exercise

Relaxation exercises may be useful for persons with anxiety problems. Tapes
are widely available. Meditation involves learning to attend to a single
stimulus without allowing the attention to wander. This is useful for a
range of disorders, particularly 'busy head syndrome'. Some people are
deterred from meditation by the association of this discipline with
quasi-religious groups. It is not necessary to join a group to meditate
effectively, nor is teaching required or any form of religious affiliation.
Martial arts are also useful for strengthening the 'signal over noise'
ratio, and improving attention and concentration. They are demanding, and
require a complete change of lifestyle from weekend long raving. They can
also meet high stimulus needs, provide an 'endorphin rush', and encourage
self-control. Most forms of physical exercise and gymn work can be valuable
in persons who wish to stop the regular use of psychostimulants.

Antioxidants and Food Supplements: Tryptophan and Tyrosine

Some  users also take high doses of antioxidants such as vitamin C
and vitamin E. There is some evidence that free radicals may be involved in
the neurotoxicity process. Tyrosine and tryptophan may elevate levels of
serotonin but the use of tryptophan is severely restricted in some the
countries due to a contaminated batch. Bananas and chocolate are  rich
sources of tryptophan, and it is a valid suggestion that persons taking
ecstasy may profit by eating these foods. It is also possible to obtain a
product called '5-HTP Serotonic'. 5-HT is another term for serotonin, and
5-HTP is actually one step closer to serotonin in the biochemical pathway
than tryptophan. This product may be obtained from Life Enhancement
Products, P.O. Box 751390, Petaluma, California CA 94975-1390.

Conclusions

The true levels of serious, adverse psychological effects linked to taking
Ecstasy  are unknown. Many of the disorders which have been reported may be
 related to both psychological and neurochemical events. The cause and
effect conclusions  drawn by single case studies must be viewed with
caution, but this does not mean that these studies should be disregarded.
There is still a widespread tendency to diagnose persons as suffering from
Ecstasy or psychedelic-induced psychosis when they are actually suffering
from conditions such as schizophrenia,  manic-depression,  borderline
personality disorder or  problems related to the use of different drugs
such as alcohol. This tendency is strengthened by the natural inclination
on the part of the  sufferer to seek an explanation 'external' to
themselves, over which they can have some control.
 

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