Ecstasy Guide

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

by Karl L. R. Jansen, MD, PhD, MRCPsych

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.

REFERENCES

Allen, R. P., McCann, U.D. & Ricuarte, G. A. (1993) Persistent effects of MDMA on Human Sleep. Sleep 16, 560-564

Ames, D. & Wirshing, W.C. (1993) Ecstasy, the serotonin syndrome and the neuroleptic malignant syndrome - a possible link. J. American Medical Association 269, 869.

Bell, D. S. (1965) Comparison of amphetamine psychosis and schizophrenia. British Journal of Psychiatry 111, 701-707.

Benazzi, I. & Mazzoli, M. (1991) Psychiatric illness associated with ecstasy. Lancet 338, 1520.

Brabbins, C, & Poole, R. (1996) Drug induced psychosis. British Journal of Psychiatry 168, 135-138.

Cohen, R.S. (1995) Subjective reports on the effects of the MDMA (Ecstasy) experience in humans. Prog. Psychopharmacol. Biol. Psychiat. 19, 1137-1145.

Connell, P. H. (1958) (UK) Amphetamine psychosis. Institute of Psychiatry Maudsley Monographs Number 5, Oxford University Press.

Creighton, F.J., Black, D.L. and Hyde, C.E. (1991) Ecstasy Psychosis and Flashbacks. British Journal of Psychiatry 159, 713-715.

Curran HV, Travill RA (1997) Mood and cognitive effects of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'): week-end 'high' followed by mid-week low. Addiction 92(7):821-831

Gelder, M. Gath, D. and Mayou, R. (1995) Concise Oxford Texbook of Psychiatry, Oford Univeristy Press, Oxford, pp149-150.

Gouzoulis,E. and Hermle, L. (1994) Die Gefarhen von Ecstasy. Nervenartz 64: 478-480.

Greer, G. and Tolbert, R. (1986) Subjective Reports of the Effects of MDMA in a clinical setting. J. Psychoactive Drugs 18, 319-327.

Hermle, L., Spitzer, M., Borchardt, D., Kovar, K. A. and Gouzoulis, E. (1993) Psychological effects of MDE in normal subjects. Neuropsychopharmacology 8: 171-176

Jansen, K. L. R (1993). Non-medical use of ketamine. British Medical Journal, 306, 601-602.

Jansen, K.L. R. (1997) Adverse psychological effects associated with the use of Ecstasy (MDMA) and their treatment.In: Saunders, N. (Ed) Ecstasy Reconsidered, Neal's Yard Desk Top Publishing Studio, 14 Neal's Yard, London WC2H 9DP, UK; pp 112-133.

Jansen, K.L.R., Griffiths, P. & Vingoe, L. (1997a) Amphetamines: Mode of action, health consequences of use and other harms. In: The Use of Amphetamines, Ecstasy and LSD in the European Union: A Data Synthesis. Eds. Griffiths, P.& Vingoe, L. The National Addiction Centre, London, pp49-70. (copies of this report are available from Paul Griffiths or Louisa Vingoe, National Addiction Centre, Addiction Sciences Building, 4 Windsor Walk, Denmark Hill, London SE5 8AF; p.griffiths@iop.bpmf.ac.uk).

Jansen, K.L.R., Griffiths, P. & Vingoe, L. (1997b) LSD: mode of action, health consequences of use and other harms. In: The Use of Amphetamines, Ecstasy and LSD in the European Union: A Data Synthesis. Eds. Griffiths, P.& Vingoe, L., The National Addiction Centre, London, pp95-113 (obtaining copies: see Jansen, K.L.R., Griffiths, P. & Vingoe, L. (1997a) above).

Jansen, K.L. R. (1998) Ecstasy (MDMA) Dependence. Drug and Alcohol Dependence (in press).

Jansen, K. L. R. (1999) Ketamine, Dreams and Realities (in press).

Kaufman J, Birmaher B, Clayton S, Retano A, Wongchaowart B (1997) Case study: trauma-related hallucinations. J Am Acad Child Adolesc Psychiatry 1997 Nov;36(11):1602-1605

Kemmerling, K., Haller, R. & Hinterhuber, H. (1996) das neuropsychiatrische Risiko von 3,4 methylenedioxymethamphetamin ('Ecsatsy'). Neuropsychiatrie 10: 94 - 102.

Krystal, J. H. and Price, L. H. (1992) Chronic 3,4 methylenedioxymethamphetamine (MDMA) use: effects on mood and neurophysiological function? Am. J. Drug Alcohol Abuse 18, 331-341.

Lamb, R. J. and Griffiths R. R. (1987) Self-injection of d,1-3-4-methylene ioxymethamphetamine (MDMA) in the baboon. Psychopharmacology 91, 268-272.

Lukas, S.E. (1985) Amphetamines: Danger in the fast lane. The Encylopaedia of Psychoactive Drugs. Chlesea House Publishers, New York.

Lyness W. H., Friedle, N.M., & K.E. Moore (1981) Increased self-administration of d-amphetamine after destruction 5-hydroxytryptaminergic (serotonergic) nerves. Pharmacology Biochemistry and Behaviour 12, 937-941.

Mathers, D. C. & Ghodse, A. H. (1992) Cannabis and psychotic illness. Brit. J. Psychiatry 161, 648-653.

McCann, U. D., Shiyoko, O. S. and G. S. Ricuarte (1996) (USA) Adverse reactions with 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') Drug Safety 1996 Aug. 15 (2) 107 - 115

McGuire, P. , Cope, H. & Fahy, T.(1994) Diversity of psychopathology associated with the use of 3,4-methylenedioxymethamphetamine (Ecstasy) British J Psychiatry 165, 391-395

McGuire, P. and Fahy, T.(1992) Flashbacks following MDMA. British J Psychiatry 160, 276.

McGuire, P. and Fahy, T.(1991) Chronic paranoid psychosis after misuse of MDMA ('Ecstasy') British Medical Journal 302, 697.

Mc Miller, P. and Plant, M. (1996) Drinking, Smoking, and illicit drug use among 15 and 16 year olds in the United Kingdom. British Medical Journal 313, 394-397.

Molliver, M. E., Mamounas, L.A. and M. A. Wilson (1989) Effects of neurotoxic amphetamines on serotonergic neurons: immunocytochemical studies In: Pharmacology and Toxicology of Amphetamine and Related Designer Drugs, ED.s K. Asghar, E De Souza, NIDA Research Monograph 94, Maryland, pp270-304.

Nichols, D.E. and Oberlender,R. (1989) Sructure-activity relationships of MDMA-like substances. In: Pharmacology and Toxicology of Amphetamine and Related Designer Drugs, ED.s K. Asghar, E De Souza, NIDA Research Monograph 94, Maryland, pp01-29.

Nunez-Dominguiez, LA (1994) Psychosis because of ecstasy. Addicciones, vol. 6, no. 3, pp. 301-307

Pallanti, S. & Mazzi, D. (1992) MDMA (Ecstasy) Precipitation of panic disorder. Biol.Psychiat. 32, 91-95.

Parrott AC, Lees A, Garnham NJ, Jones M, Wesnes K (1998) Cognitive performance in recreational users of MDMA of 'ecstasy': evidence for memory deficits. J Psychopharmacol 1998;12(1):79-83

Peroutka, S. J. (1990) Recreational use of MDMA. In: Ecstasy: the clinical, pharmacological and neurotoxicological effects of the drug MDMA. (Ed. S.J. Peroutka)., Kluwer Academic Publishers, Massachussets,pp53-63.

Poole, R. and Brabbins, C. (1996) Drug induced psychosis. British J. Psychiatry 168, 135-138.

President of the Council (1998) Tackling Drugs to build a better Britain. The government's ten year strategy for tacklilng drugs misuse. London: Her Majesty's Stationary Office. http://www.official-documents.co.uk/document/cm39/3495/3945.htm NOTE: the drug use statistics are in a guide which accompanies the main publication.

Sato, M. (1992) A lasting vulnerability to psychosis in patients with previous metamphetamine psychosis. In: Kalivas P. H. and Samson, H. H,.The Neurobiology of Drug and Alcohol Addiction, Annals of the New York Academy of Sciences 654, 160-170.

SAUNDERS, Nicholas. Nicholas Saunders died in a car accident in January, 1998. However, his books can still be obtained by writing to 'Nicholas Saunders', 14 Neal's Yard, London WC2H 9DP, United Kingdom. Fax +44-171-836-3537.

Saunders, N. E. (1995) Ecstasy and the Dance Culture, 2nd edition. Neal's Yard Desk Top Publishing Studio, 14 Neal's Yard, London WC2H 9DP, UK

Saunders, N.E. (1997) (Ed) Ecstasy Reconsidered, Neal's Yard Desk Top Publishing Studio, 14 Neal's Yard, London WC2H 9DP, UK . (ISBN: 0 9530065 0 6).

Schifano, F. (1991) Chronic atypical psychosis associated with MDMA (Ecstasy) abuse. Lancet 338: 1335.

Schifano, F. & Magni, G. (1994) ('Ecstasy') abuse: Psychopathological features and craving for chocolate: A case series.Biol.Psychiat.vol. 36, no. 11, pp. 763-767

Schmidt, C. J.. (1989) Acute and long-term neurochemical effects of methylenedioxymethamphetamine in the rat In: Ecstasy: the clinical, pharmacological and neurotoxicological effects of the drug MDMA. (Ed. S.J. Peroutka)., Kluwer Academic Publishers, Massachussets,pp179-195

Shapiro, H. (1996) (UK) Drug Deaths. Druglink Factsheet 19, ISDD, Waterbridge House, 32 Loman Street, London SE10EE

Shulgin, A. and Shulgin, A. (1992) PIHKAL: A Chemical Love Story. Transform Press, Berkeley, California.

Solowij, SH, Faillace, L & N Lee (1992) Recreational MDMA use in Sydney: a profile of Ecstasy users and their experiences with drugs. Brit. J. Addict. 87, 1161-1172.

Spatt J, Glawar B, Mamoli B (1997) A pure amnestic syndrome after MDMA ("ecstasy") ingestion. J Neurol Neurosurg Psychiatry 62(4):418-419

Van der Kolk BA (1997) The psychobiology of posttraumatic stress disorder. J Clin Psychiatry 1997;58 Suppl 9:16-2

Whitaker-Azmita , P.M. & Aronson, T.A. (1989) 'Ecstasy' (MDMA)-Induced Panic. Am. J. Psychiat. 146: 119

Williams, H., Meager, D. and Galligan, P. (1993) MDMA (Ecstasy). A case of possible drug induced psychosis. Ir. J. Psychol. Med. 162: 43 - 44.

Windhaber J, Maierhofer D, Dantendorfer K (1998) Panic disorder induced by large doses of 3,4-methylenedioxymethamphetamine resolved by paroxetine. J Clin Psychopharmacol 18(1):95-96

Winstock, A. R. (1991) Chronic paranoid psychosis after misuse of 3,4 methylenedioxymethamphetamine. Brit. Med. J. 302, 1150-1151.

Wodarz N. and Boning, J. (1993) Ecstasy-induziertes psychotisches Depersonalisation sysndrom. Nervenartz 64: 478-480.

World Health Organisation(1992) The ICD-10 classification of mental and behavioral disorders: clinical descriptions and diagnostic guidelines. World Health Organisation, Switzerland, pp70-83.

dr. holland

moody bitches weekends at bellevue the pot book ecstasy guide

moody bitches weekends at bellevue the pot book ecstasy guide

Contact Info
jholland@inch.com
(212) 358-5808