Problems with Reports of MDMA Use and Consequences

The limited information we have is largely in the form of personal accounts, interviews, single case reports, and short case series in which there is no control group. (A control group is a group that is exactly the same as the MDMA 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 drug test). Pills may contain other drugs, such as MDE, MDA, MBDB (N-methyl-1 -[3,4-methylenedioxyphenyl]-2-butanamine), 2CB (4-Bromo-2,5 -Dimethoxyphenethylamine), ketamine, amphetamine, LSD, pseudoephe-drine, or other pharmaceutical agents (Saunders 1995, 1997). Some pills contain no psychoactive substances at all. MDE has a shorter duration of action (two hours) and is more of a stimulant, with fewer emotional effects. MBDB is similar to MDMA, but the effects are described as less intense, with a greater cognitive component as distinct from an empathogenic/emotional one. 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 1991). Amphetamine is a very common additive in Ecstasy tablets, and the links between amphetamine use and a brief period of paranoid psychosis are well established (Connell 1958; Bell 1965). MDE is very common in the United Kingdom. It may be closer to amphetamine in its effects than to MDMA and may possibly have a profile more similar to amphetamine in terms of adverse effects. Ketamine, another common additive, has been given to experimental subjects to produce model schizophrenia; it can be profoundly hallucinogenic (Jansen 1993, 2001). The current tendency in the United

Kingdom to attribute problems to MDMA rather than to 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 ofPolydrug Use

The majority of persons who take Ecstasy also use other drugs, a point that rarely is emphasized in reports attributing a disorder to MDMA use. In such reports use of other drugs often is dismissed in a few lines. The concurrent use of large amounts of cannabis, LSD, alcohol, cocaine, ketamine, or amphetamine, for example, often is pushed into the background. Many habitual weekend Ecstasy users are also daily or near daily users of cannabis. 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 persistent depersonalization syndrome after ingestion of only one Ecstasy pill (Wodarz and Boning 1993). It subsequently was pointed out that this patient had a history of daily alcohol and cannabis use, and serious doubt was cast upon the role of MDMA in the case (Gouzoulis 1994).

The Role of Set and Setting

"Set" refers to the personality, early imprinting and learning, past experiences (including previous drug experiences), temperament, mood, motivations, attitudes, and expectations of the drug user. "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. An optimistic set and pleasant setting are more likely to have a positive outcome, while a fearful set and unpleasant setting are more likely to have a negative outcome. In general, MDMA 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. There are many who want to dance simply because they have been conditioned to associate dancing with Ecstasy use, irrespective of the actual content of the pill they have swallowed. Expectations sometimes can lead to a negative outcome. For example, from a statistical perspective, serious physical effects from MDMA are rare. Nevertheless, a perception on the part of consumers that they are experiencing such effects has increased considerably in the wake of fear spread by the media. As a result, there has been an increase in the number of persons seeking treatment with the false belief that they are in physical extremis. The real diagnosis is likely to be panic.

The Probability of a Chance Association

Many of the published reports draw cause and effect conclusions that are not justified by the data; that is, they conclude that Ecstasy consumption caused— rather than was associated with—the symptoms. It is important to recognize 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). Depression and anxiety are common conditions in the general population. It is a statistical certainty that many persons who take MDMA will show signs of 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 MDMA use also have an incidence, sometimes substantial, in the general 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 it may be due to impaired judgment. Preexisting mental illness and a family history of mental illness are common in persons who show signs of psychiatric illness in apparent association with drug use.

Preexisting Neurochemical, Genetic, and Personality Differences

Each year brings new reports linking inherited genes to behavioral patterns, including alcoholism and the need for high levels of stimulation (thrill seeking), both of which are thought to involve dopamine receptors. It is possible that persons who take drugs may have preexisting, genetically determined underfunctioning of serotonergic or dopaminergic systems, and this less than optimal functioning increases the likelihood of depression and anxiety and creates an inner drive to take drugs that provide relief. Thus, retrospective studies of the serotonin and dopamine systems in long-term users of highdose Ecstasy, compared with non-using controls, may be seriously confounded by preexisting differences between the two groups (Jansen and Forrest 1999). This is a point that researchers taking cerebrospinal fluid measures of serotonin or its metabolites and performing ¿/-fenfluramine challenge tests rarely take into account.

The Role of the Media

The media have played a highly significant role in the psychology of adverse drug effect reporting. There is the historical case of LSD, which has implications in terms of the situation with MDMA. In the 1960s and 1970s, an astonishing range of mental and physical disorders was attributed to LSD use. Psychiatrists were as influenced by the media's emphasis on LSD as the general public. Sometimes persons with schizophrenia, bipolar disorder (manic-depression), dissociative conversion disorders (such as hysteria), PTSD from a traumatic LSD experience, neuroses, and problems stemming from the use of other drugs were diagnosed as having conditions induced by LSD. Although LSD use is now at very high levels in the United Kingdom (10 to 12 percent among fifteen- to twenty-nine-year-olds) (McMiller and Plant 1996; President of the Council 1998), LSD is no longer generally accepted as a major cause of an extended list of complaints.

The 1990s saw a remarkable rerun in the United Kingdom of 1960s-style media hysteria based on 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 rarely was pointed out that the actual risk of death from all causes in association with taking MDMA was in the region of 1 in 650,000 to 1 in 3 million risk exposures (Saunders 1995,1997). In the same week that Leah Betts died, an average of a thousand people died from the health consequences of alcohol, and more than two thousand people died from the health consequences of cigarette smoking in the United Kingdom. In that week, alcohol played a part in at least 30 percent of reported motor vehicle deaths, suicides, and murders. There was a complete loss of perspective on the "killer drug Ecstasy." This type of media and political attention, regardless of the drug,

almost always results in an increase in the number of persons seen at hospitals and by doctors in the belief that they are suffering serious effects from taking the drug in question.

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