Adverse Psychological Effects of Ecstasy use and Their Treatment
By Dr. Karl Jansen
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.
The relevance of the amphetamine literature
The empathogenic effects of ecstasy have led to the suggestion that it is
a member of a new class of psychoactive compounds, which have been labelled
'entactogens' or 'empathogens'.12,13 While formulation of a new class of
compounds may be warranted the psychological effects, MDMA is nevertheless
a partial derivative of amphetamine and has many physical effects in common
with the amphetamine group (see later), which leads to the suggestion that
susceptible persons may be at risk of the same adverse effects as have been
reported for amphetamine, in both a physical and a psychiatric sense. 14
This is likely as both types of drug have similar effects on dopamine, and
these effects are believed to play a role in the development of psychosis
for example.15,16,17,18,19
While the possible range may be similar, clearly the probabilities will
be different. In other words, it would not be correct to say that ecstasy
is as likely to cause certain adverse effects as amphetamine, and vice versa.
This chapter will consider the pros and cons of some of the arguments set
out in this introduction. Much of the information we have about adverse
reactions to MDMA is in the form of single case studies and short, uncontrolled
series. There are several key issues to bear in mind when considering publications
of this nature:
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 sold as 'ecstasy' have been shown to contain other drugs
instead, sometimes in dangerous combinations. Other drugs commonly found
instead of MDMA are MDEA, MDA, MBDB, MDE, 2CB, Ketamine, amphetamine, LSD,
pseudoephedrine and pharmaceutical agents.20 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
far more psychedelic (LSD-like) and is considered to be more toxic. 2CB
is more psychedelic than MDMA but less so than MDA.21 Amphetamine is a very
common additive, and the links between amphetamine use and paranoid psychosis,
for example, are well established.22 MDEA is also very common in the UK
20, is closer to amphetamine in its effects than MDMA, and may possibly
show a more similar profile to amphetamine in terms of adverse effects.
Ketamine has been given to experimental subjects to produce a 'model schizophrenia'
and can be profoundly hallucinogenic.23
It is thus clear that some of the adverse effects which have been attributed
to ecstasy may be due to 'dodgy E' rather than pure MDMA.
The role of poly drug use
The 'pure' ecstasy user is a very rare entity. The overwhelming majority
of persons who take ecstasy also use other drugs, and some of these drugs
are clearly identified with a risk of mental health consequences. This point
is rarely emphasised in the case reports attributing a psychiatric disorder
to ecstasy use, where other drugs use is often dismissed in a few lines.
The concurrent use of large amounts of cannabis, LSD, alcohol 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.24,25,26,27 There has
been increasing attention given to ketamine in the media recently,28,29
and it will be of interest to observe whether eventually case reports will
appear associating mental illness with ketamine use, while ecstasy is relegated
to the 'other drugs taken' list, warranting no further discussion. For example,
there is a case report of persisting depersonalisation syndrome after ingesting
ecstasy only once.30 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.31
The importance of poly drug use has been confirmed by a study of drugs taken
at raves.32 The OPCS Psychiatric Morbidity Survey 33 surveyed 10,500 UK
households. 504 people used one of the listed illicit drugs in the preceding
year, and had used that drug more than five times in total. 10% had used
ecstasy and polydrug use was the norm amongst persons who preferentially
chose ecstasy. The preferred other drugs were cannabis, hallucinogens, amphetamines
and hypnotics. Alcohol was not included in the study. McMiller and Plant
(1996) have recently reported on a major study of drug taking in 15 and
16 year old school children, pupils born in 1979, from 70 schools across
the United Kingdom. The percentage reporting use of 'Ecstasy (MDMA)' was
7.3% (293 persons out of 3999) of girls and 9.2% of boys (326/3555), less
than the LSD figures which were about 12% and 17% in girls and boys respectively.
This comparison with the LSD figures is of interest when we consider the
similarities between the media generated 'LSD hysteria' of the 1960s and
the media generated 'ecstasy hysteria' of the 1990s. Although LSD is a more
popular drug now than ever, it appears to no longer be seen as a major threat
to the mental health of the nation by the media, and has largely disappeared
from the pages of psychiatric journals and tabloid newspapers. This suggests
that the way in which the media deal with drug issues sometimes has little
rational basis. This seems particularly likely when we ponder the fact that
over one million people in the UK have died of smoking related illness in
the last 10 years, at least 400,000 have died of alcohol related illness,
at least 2,500 from heroin and related opiates, and at least 1200 from sniffing
solvents, while the number of people who have died in association with taking
the 'killer drug' ecstasy numbers a modest 60.34
The role of set and setting
This term 'set' refers to the personality, past experiences (including previous
drug experiences) mood, motivations, attitudes and expectations of the subject
while 'setting' refers to conditions of use, including the physical environment
and the 'set' of other people 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. However, ecstasy effects are less
susceptible to the influence of set and setting than psychedelic drugs such
as LSD. Thus ecstasy is a more predictable drug.
Although ecstasy appears to energise the taker in a nightclub setting where
fast music is played, in this context it is also likely that the drug consumed
is not actually a full dose of pure MDMA, but rather a combination in which
amphetamine features prominently, or where amphetamine has been taken deliberately
together with MDMA. It is also possible that the drug is actually MDEA.
Persons who have taken a substantial dose of pure MDMA in these settings
may often be seen either standing on the sidelines or sitting in the quieter
areas, possibly engaged in emotional conversations with others. Enthusiastic
dancers sometimes avoid the emotional effects of MDMA by only taking small,
stimulant doses at regular intervals p; for example, half a tablet periodically
through the night. Careful examination of what actually takes place at raves,
and who is taking what, generally indicates that pure MDMA in the 120mg
dose range is quite consistent in its effects, producing similar results
in the gardens of California as it does at the 25,000 person Tribal Gathering
rave in the UK. 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 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,35,36
but this is less likely to be true for ecstasy. However, the role of expectations
is significant, as discussed above. Expectations can also have a negative
outcome. For example, from a statistical perspective, serious physical effects
from ecstasy are relatively 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. The real diagnosis is more 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). Many of these
'cases' recover while waiting to see the doctor.
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.
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. In general,
it is useful to consider whether the criteria suggested by Strassman (1984)
and Poole and Brabbins (1996) are met for research of this nature before
concluding that ecstasy did in fact cause the mental disorders described.
Strassman's review does not include ecstasy, but is focused on LSD. Nevertheless,
the core principles are the same: 'there is a tendency for people with poorer
premorbid adjustment, a history of psychiatric illness and/or treatment,
a greater number of exposures to psychedelic drugs, drug-taking in an unsupervised
setting, a history of poly drug abuse, and self-therapeutic and/or peer-pressure-submission
motive for drug use, to suffer these complications'.36
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 confounding variables, i.e. possible explanations
for an association. Other such variables 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'.39 Depression
and anxiety are common conditions in the general population. It is a statistical
certainty that a substantial percentage of persons who take ecstasy will
develop depression regardless of whether they took ecstasy or not. 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.40 It is interesting to
note a comment by Gelder et al.: 'it is not certain why consistently higher
figures are reported for women: possible reasons are (a) women's greater
readiness to report symptoms and (b) the abuse of alcohol by some depressed
men which may lead to a diagnosis of alcoholism rather than depressive disorder.'
Thus drug use influences the determination of incidence levels of psychiatric
conditions, and vice versa. This statement also suggests how difficult it
can be to accurately estimate the incidence of depression itself in a population.
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 circumstances
and life in general 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 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 genes to receptor subtypes, and subsequently
to behavioural patterns. It is possible that persons who take large quantities
of psychostimulants may have preexisting, 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 becoming over-involved with drugs which provide temporary
relief from the problem. Thus retrospective studies of serotonergic parameters
in high dose, chronic ecstasy users, in comparison with non-using controls,
may be confounded by preexisting differences between the two groups. The
present state of knowledge is that duration and dosage of ecstasy use do
not appear to predict the probability of developing most psychological difficulties.30
This may change with further research. However, if true then this would
tend to argue against such difficulties being due to structural damage to
serotonergic nerve terminals.
The adverse psychological effects of MDMA
A review of adverse reactions due to ecstasy has been presented by McCann
et al. (1996). As noted in the introduction, current research evidence is
sparse and retrospective, generally uncontrolled, generally lacks toxicological
confirmation of the drugs taken, lacks data on course and outcome, rarely
relates mental state to toxicological results, and depends heavily on single
case studies but nevertheless frequently concludes cause and effect relationships
from what may be chance associations, although it is also possible that
the cause and effect relationship is true.
Psychotic phenomena
With respect to serious mental illness such as prolonged psychosis, there
is currently a dearth of accurate statistics. Ecstasy may rarely produce
a state of intoxication which mimics a psychosis, such as paranoia,4,41
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 (toxicologically confirmed). 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').
The use of ecstasy may sometimes alter the clinical picture in a pre-existing
psychosis such as schizophrenia. This is referred to as a pathoplastic effect.
Some people with schizophrenia or manic-depression will also take ecstasy,
especially as the peak age of onset of schizophrenia is 20-30. It has not
been clearly established whether or not ecstasy can specifically induce
a relapse of preexisting 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 serious
mental illness. Ecstasy releases dopamine in a similar manner to amphetamine
and cocaine 13 and as such might be expected to increase the risk of psychotic
illness in a similar manner to other psychostimulants, although possibly
not to the same extent. Some investigators report that they have repeatedly
observed clear links between the onset of psychotic symptoms and the use
of ecstasy.42 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 reports41,43,44,45,46 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.). The drugs for which there
is at least some scientific evidence of such a syndrome are amphetamines,
cocaine and cannabis. Ecstasy may eventually be included in this group.
Anxiety disorders and panic attacks
As stated previously, we are currently limited to a handful of case reports.1,3,4,38,47,48,49
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.
Cognitive deficits
(Impaired memory, attention and concentration)
Research into drug-induced cognitive deficits is difficult to do well. The
number of possible confounding variables is high. For example, it is essential
to control for the use of other drugs, particularly regular cannabis smoking,
and for the effects of any mood disorder upon cognition. If subjects have
been told to abstain from all drugs for several weeks, a withdrawal syndrome
may result which could confound tests conducted during this period. All
claims of cognitive deficits should be accompanied by evidence that the
urine tests of the subjects were clear of drugs and their metabolites, particularly
cannabis metabolites which can take at least 4 weeks to disappear from urine.
Reports of subtle memory deficits which not accompanied by urine test data
may be due to cannabis use.
A report of subtle memory deficits in association with ecstasy use has been
made by Krystal and Price, 1992.
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'. The imagery is intensified by the same factors as intensify flashbacks,
principally anxiety generating situations. This is consistent with a psychodynamic
explanation.
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
Ecstasy p; a stepping stone to other drugs?
The use of ecstasy is associated with the use of other drugs to modify the
unpleasant
'come-down'. Temazepam has become very popular for this purpose recently,
and was rescheduled as a controlled drug. Temazepam belongs to the 'Valium
class', although it is much shorter acting. Tolerance and dependence can
develop relatively quickly. Of much greater concern is the spread of heroin
smoking through the dance culture. Heroin addiction is rapidly increasing
in the U.K. 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, dependence and withdrawal
The use of almost any substance may become compulsive and excessive in some
individuals and there are certainly those who have taken ecstasy on a daily
basis, regardless of tolerance effects, for prolonged periods.23,29,42 It
is far more common, however, for 'problematic' ecstasy use to involve consumption
of the drug in 48 hour weekend binges with 4-5 days in between. The experience
of the 'love effect' from ecstasy rapidly fades with repeated use, and the
effects become increasingly like those of amphetamine.57,1 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 p; 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 an observation from animal
research that under-functioning of serotonergic nerve terminals results
in increased use of amphetamine-like substances for pharmacological reasons
which lie beyond the scope of the present discussion.58,59
The day after taking ecstasy, if they have had a reasonable amount of sleep,
not consumed large quantities of cannabis, and not gone clubbing, a substantial
number of users feel quite elevated in spirits. However, this cheerful mood
has generally started to crumble by the second day, and 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 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. With repeated use, the effects
of ecstasy come to increasingly resemble those of amphetamine, and the patterns
of use may begin to have the appearance of a dependency problem, particularly
in persons who are taking 25 pills Thursday to Monday month after month.
It is not necessary to take a drug every day before a dependency syndrome
can be identified, nor is physical withdrawal essential to the diagnosis.53,60,61
The possibility that ecstasy may be associated with tolerance, 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 1930s, 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.62 It was not until the late 1960s, 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.53,60,61
This picture took decades to form. With respect to ecstasy, deleterious
effects upon serotonin were found in 1985, and it is really the 1990s which
has seen an increasing frequency of reported psychiatric complications.4
As noted above, the concept that a 'withdrawal syndrome' requires clear-cut
'physical' manifestations of dependence has been largely discarded, although
some controversy in the area continues. 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.13 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.57 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,20 and also because
polydrug use is very common,33 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.63
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.
A questionnaire investigation of 100 ecstasy users in Sydney found that
2% of the sample considered themselves to be 'dependent'.65 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 of psychological and psychiatric adverse effects
A multi-levelled, individually tailored, dogma-free approach is generally
the best,
combining biological, psychological and social methods. There is virtually
no literature which specifically deals with the treatment of psychological
and psychiatric adverse effects due to ecstasy.29 Accordingly, many of the
references are to methods originally developed for amphetamine and cocaine
dependence. Nevertheless, the principles are similar across the 'psychostimulant
group'.
An initial assessment is followed by a decision about which of the available
services is most suitable.66 Apart from those with severe psychiatric and
physical complications, ecstasy users are most likely to remain in the community.
The management of disorders which can be classified and treated as would
be normal were they not drug-induced will not be considered further here.
The reader is referred to standard works on adult general psychiatry (e.g.
Gelder, Gath & Mayou 1995).
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 affective disorder not receiving proper care and education about their
illness. They are not prescribed depot medications or lithium, 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 to
ensure that there is not 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.
Counselling, psychotherapy and cognitive/behavioural therapy
A non-judgmental attitude may be helpful at the outset to create a trusting
relationship, as some of the clients have difficulties with authority figures.67,68,69
However, Rogerian-style unconditional positive regard and empathy are typical
effects of ecstasy, and it is reasonable to suppose that some users may
occasionally respond better to firm limit setting and reality orientation.
Denial is an important defence mechanism: 'Everyone knows E's and Whiz aren't
addictive, I can stop anytime'. 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.
There is a general account of problems which may be encountered in Zweben,
1989.
The cognitive-behavioural approach focuses on problem behaviours, as distinct
from nondirective therapies which concentrate on feelings and relationships.
Cognitive aspects include explaining the causes of relapse and the conditioning
mechanisms which lead to the sudden appearance of craving in some situations.
The place, people and objects associated with the primary "reward"
can become conditioned stimuli for drug use by classical conditioning. Therapy
may attempt to change the "behaviour eliciting" properties of
key stimuli.70,71
Motivational interviewing can be a very valuable technique (see Miller &
Rollnick, 1991), and relapse prevention is important.72,73
Psychodynamic psychotherapy
This approach may be suitable for persons whose symptoms have a strongly
neurotic character, and who are not too seriously impaired. 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. Persons with a clear history of childhood trauma may do well. There
is a valuable account of psychodynamic, 'object relations' based approaches
to treating the stimulant dependent in Wallace, 1991.74,75,76
Meditation, relaxation and martial arts
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. Lawrence LeShan's
brief account 'How to Meditate' 77 is all that is required. See also Gorski,
1990.
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.
Okinawan Goju-Ryu karate is particularly suitable, providing high intensity,
little physical contact, high stimulation training environments. In fact,
most forms of physical exercise and gym work can be valuable in persons
who wish to stop the regular use of psychostimulants.
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.)
Antidepressants
Antidepressants such as fluoxetine ('Prozac') may be useful. 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.5 However,
these studies generally involve massive doses of fluoxetine. Fluoxetine
after MDMA has been reported as able to reduce sleep disorders and restlessness.
Antioxidants and Food Supplements: Tryptophan and Tyrosine
Some ecstasy 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,78 but the use of tryptophan is severely restricted in the
UK and other countries due to a contaminated batch. It may only be prescribed
by a medical practitioner on a named patient basis. 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.
Benzodiazepines
(Lorazepam, Temazepam, Diazepam ('Valium')
Insomnia may be treated with a short course of temazepam. Panic attacks
are often treated with lorazepam. Severe chronic anxiety may be treated
with intermittent courses of diazepam. All of these drugs are potentially
addictive. Accordingly, they are best not used for more than a few weeks
at a time. Antidepressants such as fluoxetine and sertraline are also useful
for treating anxiety. If the person can not tolerate these, clomipramine
is a good alternative. The brain's anxiety mechanisms may play a specific
role in the neurobiology of stimulants, which suggests that benzodiazepines
may be useful in the early stages of withdrawal.79,80
Haloperidol and other antipsychotics
Antipsychotic drugs such as haloperidol and chlorpromazine are not a good
first choice in ecstasy-associated anxiety and psychosis. In general, such
symptoms associated with ecstasy use are short-lived. It is thus better
practice to administer benzodiazepines for at least the first few days,
as the antipsychotic effect of dopamine antagonists such as haloperidol
usually takes several weeks to become manifest, by which time symptoms will
have resolved in most cases. Haloperidol and chlorpromazine have numerous
serious and unpleasant side-effects, and the neuroleptic malignant syndrome
may be linked to the hyperthermic syndromes associated with several ecstasy-related
deaths.81
Complementary therapies
It is sometimes worth considering acupuncture,82 homeopathy, massage and
other types of bodywork, and aromatherapy.
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.
©Dr. Karl L. R. Jansen MB.ChB., M.Med.Sci., D. Phil. (Oxon), MRCPsych
1997.
Dr. Karl Jansen is currently writing a book about ketamine. If you would
like to share your ketamine experience/knowledge/opinion, write to: Dr.
Karl Jansen, 63-65 Denmark Hill, London SE5 8AZ e-mail: K@BTInternet.com
'This work should be cited as: Jansen, K.L.R. (1997) Adverse psychological
effects associated with the use of Ecstasy (MDMA) and their treatment. In:
Ecstasy Reconsidered (Saunders, N. ed.) pp112-128. Nicholas Saunders, 14
Neal,s Yard, London WC2 9DP, United Kingdom. The copyright for this chapter
is held by Dr.Karl Jansen who has no objection to the free reproduction
of this work, as long as the above information is included.'
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