Nicole K Lee
Turning Point Alcohol and Drug Centre Inc.,Victoria
- Psychostimulant use, especially heavy use, has been associated with dependence; adverse effects on neurological, neuropsychological and physiological functioning and mental health; high levels of injecting and sexual risk-taking behaviour; and pharmacological risks concerning drug content and purity.
- Lack of knowledge about contents of pills is a significant pharmacological risk and although users operate with a range of 'safeguards' to reduce risk, users tend to become increasingly blasÚ over time.
- Many of the risks associated with psychostimulant use are influenced by the context of use.
- Users are often na´ve to the risks associated with using psychostimulants and many believe that these drugs are relatively safe and benign.
- Users should be made aware of the potential health and other risks and given information to reduce the possible harms associated with psychostimulant use.
Drug contents and purity
Risks of injecting
Blood borne viruses and sexual risk-taking behaviour
Psychostimulant exposure during pregnancy
Mental health risks
Conclusion Top of page
IntroductionThe prevalence of psychostimulant use has increased (see Chapter 2: Prevalence and patterns of psychostimulant use) and some psychostimulants are perceived as relatively safe drugs by some users. Consequently, there is a growing body of literature examining the risks associated with varying levels of psychostimulant use. Risk domains reviewed in this chapter include neurological, neuropsychological, physiological, psychiatric, injecting, sexual and social risks. Research suggests that there are some significant risks associated with psychostimulant use, especially from heavy use. However, available evidence is sparse and often inconclusive.
NeurotoxicityRisk of brain toxicity and receptor changes have been the subject of much research in the psychostimulant area, particularly for ecstasy. Chapter 3: Pharmacology of psychostimulants, details the literature on neurotoxic effects of psychostimulants.
Evidence of neurotoxicity has come mainly from animal studies and evidence in humans is inconclusive. Neurotoxic risks associated with psychostimulant use may include short- and long-term disruption to brain neurotransmitters that can result in significant health risks, such as hyperactivity, mental confusion, agitation, fever, tachycardia and tremor (known as the 'serotonin syndrome'), the effects of which can be fatal. Monoamine depletion can also lead to low mood, anhedonia and lethargy post-use ('come down'). Similar deficits have been identified after methamphetamine use. Neurotoxic effects appear to persist for extended periods post-administration in animals (Parrott, 2002).
Given the risk of neurotoxic effects, users should limit their intake, especially new users, and be aware of possible signs of neurotoxic effects. Harm minimisation messages should include a psychoeducational component about the possible effects of psychostimulants.
Neuropsychological risksSome identified long-term effects of ecstasy use include memory and neurocognitive deficits. Parrott (2002) has summarised the literature identifying significant memory deficits on neuropsychology tests in heavy long-term users and in young ecstasy users, particularly in immediate and delayed memory recall.
There has been a substantial amount of research into the neurocognitive deficits experienced by ecstasy users and evidence suggests that even in early and light users there is some evidence of attentional and working deficits (see Gowing, 2002). These may reflect serotonergic changes (Parrott, 2002) and may be permanent (Kalant, 2001).
Other cognitive functioning does not appear to be consistently affected, although there is some evidence that executive functioning (including decision-making, reasoning and problem-solving) may be reduced and that impulsivity may be increased (Kalant, 2001). However, some researchers have indicated that caution must be exercised in interpreting the data concerning long-term cognitive effects, as ecstasy use is most often seen in the context of polydrug use and the role of concomitant cannabis use in cognitive impairment has yet to be adequately described (Croft, Mackay, Mills & Gruzelier, 2001). Functional consequences of long-term use of ecstasy will remain uncertain until large epidemiological studies have been conducted (Gowing, Henry-Edwards et al., 2002).
Kosten, Malison and Wallace (1996) have described two broad categories of neuropsychological deficits from cocaine use. Mood changes, including depression, are likely to be a result of abnormalities in catecholamine receptors and are probably reversible, although in some cases have been found to be long lasting and may trigger an underlying propensity for mood disorder. Cognitive deficits may be due to neural loss (Kosten et al., 1996) and include an increase in theta brain activity and cerebral atrophy as a result of lowered cerebral blood flow leading to cognitive deficits even after use has ceased (Daras, 1996). The most common deficits are spatial learning, concentration and recent memory, but abnormalities have been found in motor tasks, including parkinsonian-like symptoms, such as motor deficits (Kosten et al., 1996).Top of page
Physiological risksThere are significant toxic effects from psychostimulant use. These are discussed in detail in Chapter 3: Pharmacology of psychostimulants.
Primary physiological toxicity effects of ecstasy use include liver toxicity (including jaundice); cardiovascular toxicity (including hypertension and tachycardia resulting in heart failure); brain haemorrhage; and cerebral toxicity leading to seizures and disruption of respiration and circulation (Kalant, 2001). Hyperthermia and disturbance of metabolite balance are also commonly reported effects (Gowing, Henry-Edwards et al., 2002).
Volkow, Fowler and Ding (1996) have noted that the most frequent complication of cocaine use is cardiac toxicity, including myocardial infarction and fatal arrhythmias as a result of release of adrenaline and noradrenaline and the inhibition of noradrenaline reuptake. Daras (1996) noted that the risk of these cardiovascular events is substantially increased by the concurrent use of alcohol, which is a common pattern of polydrug use (Topp, in press). Hypertension is an acute effect that appears to subside (Daras, 1996).
Neurovascular complications of cocaine use that have been documented include ischaemic and haemorrhagic stroke, probably as a result of dose-related rises in arterial pressure and heart rate, as a result of inhibited reuptake of noradrenaline. Headaches, seizures and abnormal movements such as tics and choreoathetoid have also been documented (Daras, 1996).
Physiological effects of amphetamines include hyperthermia (Callaway & Clark, 1994) and seizures (Alldredge et al., 1989; Hanson et al., 1999). Cardiovascular toxicity (including ventricular arrhythmias, acute myocardial infarction and cardiomyopathies) have been noted (Bashour, 1994; Costa et al., 2001; Hung et al., 2003). Cerebrovascular problems may also occur such as stroke, aneurysm and cerebral haemorrhage (Biller et al., 1987; Buxton & McConachie, 2000; Chen et al., 2003; Moriya & Hashimoto, 2002; Perez et al., 1999; Sloan & Mattioni, 1992; Yen et al., 1994).
Risk reduction strategies should include a psychoeducational component to increase awareness and understanding of physiological risks of psychostimulant use. These effects are usually dose related, but low doses have also been known to produce acute physiological symptoms (see Chapter 3: Pharmacology of psychostimulants).
The effects of hyperthermia and metabolite imbalances can be exacerbated by the context of use, such as the rave or dance party environment. Users should be made aware of strategies to reduce these risks, including drinking appropriate amounts of water, reducing other concomitant drug use (including alcohol) and ensuring breaks from dancing.
Drug contents and purityA significant pharmacological risk that may lead to additional complications, as with most illicit drugs, is the variable and unknown contents of street psychostimulant products. Content is highly variable across time and for individual doses. Until very recently, the majority of tablets seized in Australia as ecstasy have been found to be primarily methamphetamine (IDRS, 2002) and although the percentage of ecstasy in seizures has increased, it is still estimated to be only around 50% (IDRS, 2002). Often tablets sold as ecstasy have been found to contain a variety of other drugs such as ketamine (IDRS, 2002).
Hansen, Maycock and Lower (2001) surveyed 31 ecstasy users in Perth, Western Australia about the risks of using MDMA. One of the primary risks identified was lack of knowledge of the contents of the drug. They found that users relied on 'acceptable safeguards' to reduce risk (e.g. using a regular supplier and using with friends). They also found that over time, users became more blasÚ about their use and the risks involved, suggesting that regular and accurate psychoeducational interventions targeted at high-risk groups may be useful. Pill testing, although advocated by some as a harm reduction measure, is unreliable and subjective (Winstock, Griffiths & Stewart, 2001) and not likely to reduce the harms associated with unknown pill contents.
The purity of psychostimulants is variable and changeable. In Australia, the Illicit Drug Reporting System (IDRS) has documented changes in purity over several years and found that the purity of cocaine is relatively high (Darke, Kaye & Topp, 2002a) and the purity of methamphetamine, although much lower, has been increasing (IDRS, 2001).Top of page
Risks of injectingIn addition to the usual risks of injecting (such as blood borne virus transmission and vein care), there are some specific risks to injectors of psychostimulants.
Injecting of ecstasy is rare (see Chapter 2: Prevalence and patterns of psychostimulant use) and potential strategies to reduce initiation to injecting may be useful for ecstasy users, especially if they are likely to or currently inject other drugs (see Chapter 5: Psychosocial interventions) for an overview of strategies to reduce initiation to injecting).
However, injection of cocaine and methamphetamine is much more common. Following a survey among users of cocaine, van Beek et al. (2001) noted that the prevalence of injecting use of cocaine had recently increased. This is a particular problem given the short half-life of cocaine, making injecting typically more frequent than other drugs. Injectors tend to be former heavy snorters or injectors of other drugs who have added cocaine to their repertoire (Topp, Day & Degenhardt, in press).
van Beek et al. (2001) noted that because of the short half-life of cocaine, the initial rush was often quickly followed by a rapid reduction in brain concentration, experienced as a 'crash', easily remedied by further use. They concluded that this pattern of use may result in binges lasting several days. Respondents in this study averaged 15 injections per day on their highest use days, with some injecting up to 60 times a day. The authors noted that the frequency of cocaine injecting resulted in problems with vein access and other skin problems, with thrombosed veins, unexplained cuts and bruises and abscesses frequently reported by injecting users. Compulsive skin picking and scratching in response to tactile hallucinations were also reported by chronic users. The authors also noted that cocaine users were at high risk of re-using needles when availability was limited, particularly because the nature of cocaine often induced a feeling of invincibility. Social support appears to reduce injecting risk and interventions that increase non-using social supports may be useful (Stein, Charuvastra & Anderson, 2002).
Topp, Degenhardt, Kaye and Darke (2002) have noted that base amphetamine, due to its consistency, has been associated with increased vascular damage among amphetamine users. In addition, Kaye and Darke (2000) noted that because amphetamine use tends to be a social activity, there may be more opportunities for needle sharing than for other drug users. In this study, social dysfunction was related to degree of dependence among injecting users. Since injecting has a higher dependence potential than other forms of use (Gossop, Griffiths, Powis & Strang, 1992), injecting users are also at higher risk of both dependence and declining social functioning.
It is generally considered rare for injecting users to return to non-injecting practices. However, non-injectors may benefit from strategies aimed towards preventing initiation into injecting (see Chapter 5: Psychosocial interventions for a review).
Blood borne viruses and sexual risk-taking behaviourSeveral studies have shown that psychostimulant users have higher levels of sexual risk-taking behaviour than non-users. Lenton et al. (1997) noted that young inexperienced users were largely unaware of the higher risk of unsafe sex whilst using psychostimulants.
Klitzman, Greenberg, Pollack and Dolezal (2002) found that gay ecstasy users tended to have more partners and more unprotected anal sex than non-users. These researchers and others (e.g. Binson, Woods, Pollack, Paul et al., 2001) have also noted that psychostimulant users are more likely to use 'sex-on-premises' venues than those who did not. This is an important finding as most new human immunodeficiency virus (HIV) infections in Australia are a result of unsafe sexual activity (National Centre for HIV Epidemiology and Clinical Research, 2002), particularly by men who have sex with men (MSM). In addition, Malbergier and Guerra de Andrade (2001) noted that cocaine dependence was more prevalent among users with HIV infection than those without HIV infection. Together, these results suggest that use of psychostimulants may be associated with an increase in sexual risk-taking behaviour and hence risk for blood borne virus (BBV) infection, as both are high in psychostimulant users.
van Beek et al. (2001) have identified sexual risk-taking behaviour as a special concern among cocaine users in Sydney. They noted that feelings of invincibility may lead to increased willingness to engage in unsafe sex and to take other sexual risks. Of particular concern was the high proportion (27%) of sex workers in their study. Most said they engaged in sex work to pay for cocaine and most used while they were sex working. The authors suggest that this pattern increases the likelihood of a cycle of using to work and working to use that may be difficult to break. According to some key informants, this may also increase willingness to engage in unsafe sex in order to get the work needed to pay for their use.Top of page
Psychostimulant exposure during pregnancyThere has been a relatively substantial amount of research into the effects of prenatal exposure to psychostimulants. Chapter 11: Psychostimulant use in pregnancy and lactation in this monograph details the studies in this area. Briefly, animal and human studies have found that although there is some transfer of psychostimulants from mother to foetus, there is little evidence of long-term effects on the child, neither in utero nor during development.
As noted in Chapter 11, while many drugs can induce pharmacological effects in the foetus during pregnancy, the number of drugs able to cause congenital malformations is small. Many factors (e.g. pattern of drug use or dose in relation to gestational age) influence potential drug effects on the foetus rather than drug use per se.
Binge administration of psychostimulants during pregnancy should be avoided and if drug use occurs once daily or less frequently, infant exposure to the drug can be minimised by breast-feeding just prior to the dose and avoiding feeding for a minimum of two to three hours after the dose. If drug use occurs more frequently (many times per day or in a binge), breast-feeding should be avoided during these times.
In a systematic review, Frank, Augustyn, Knight, Pell and Zuckerman (2001) concluded that there was no evidence of a consistent relationship between prenatal cocaine use and growth, intellectual development or language in early childhood, confirming the findings of earlier reviews (Lutiger, Graham, Einarson & Koren, 1991). They noted some evidence that motor development was impaired, but this did not extend past seven months and may have been related to tobacco exposure. Furthermore, there were no parent or teacher reported effects on child behaviour, but there was some evidence to suggest decreased attentiveness and emotional expressiveness.The authors concluded that in children under six years of age there was no clear evidence of toxic effects of cocaine use pre-birth and much of the deficits previously attributed to prenatal cocaine exposure are likely to be a result of exposure to other drugs, including tobacco and alcohol.
Hurt et al. (2001) also found that inner city children with and without prenatal cocaine exposure performed poorly on developmental tests and concluded that test scores reflect the socio-economic conditions of these children rather than the effects of prenatal cocaine exposure. Likewise, Ho, Karimi-Tabesh and Koren (2001) found that users of ecstasy were likely to have a cluster of socio-economic risk factors that increased a range of risks for the unborn child and to isolate ecstasy effects was difficult.
Das Eiden (2001) observed that mother-infant interactions may be diminished in cocaine exposed infants. The author suggested that interventions focusing on enhancing the quality of these interactions may be helpful for this population.
Flavin (2002) noted the significant socio-economic, emotional and physical disadvantage of cocaine using women. They suggested that such women were willing and able to engage in harm reduction activities, including reducing or quitting use. They further suggested that drug use treatment, as well as prenatal and maternal care, should be targeted at this group.
DependenceAlthough psychostimulant use tends to be characterised by intermittent rather than daily use, a clear dependence syndrome has been described (e.g. Topp & Mattick, 1997b). Withdrawal is a key but not necessary feature of dependence (see Chapter 7: Psychostimulant withdrawal and detoxification for a review of withdrawal). Amphetamine dependence has been identified as a key factor in prompting users to moderate use and seek treatment (Hando, Topp & Hall, 1997). The reader is referred to Chapter 1: Background to the monograph for an outline of the diagnostic criteria for dependence. Regular users (several times a week) are considered to be heavy users and are likely to manifest at least some symptoms of dependence. Top of page
Mental health risksPsychostimulants have been implicated in a range of mental health problems and there has been an increasing interest in these sequelae. Issues related to comorbidity of mental health and psychostimulant use are reviewed in Chapter 10: The psychiatric comorbidity of psychostimulant use. Mental health effects such as these appear to be more often documented for amphetamine users than cocaine and ecstasy users.
In a review of the psychiatric case study literature, Soar, Turner and Parrott (2001) found that there were a substantial number of cases where ecstasy users had developed psychiatric symptoms, including psychotic symptoms (29%), anxiety and panic attacks (26%), delusions, hallucinations, illusions (26%) and depression (16%). These symptoms occurred with as little as one occasion of use and usually without a family or personal history of mental illness. Some of these case studies presented evidence that symptoms were potentially long term, continuing long after ecstasy use ceased. They also presented evidence from studies that showed that a significant proportion of users experienced subclinical symptoms. Clearly, however, there needs to be caution in interpreting these data, given the anecdotal nature of the studies and the likelihood of publishing bias (e.g. a bias towards publishing unusual or particularly interesting cases). These data do, however, support the commonly held view that there is a significant relationship between ecstasy use and psychiatric symptoms, although polydrug use and polydrug dependence may also influence the interpretation of these results.
In a longitudinal study, Lieb et al. (2002) conducted detailed assessments with 2,462 adolescents and young adults over a 4-year period and found that ecstasy users were significantly more likely to attract a psychiatric diagnosis (according to DSM-IV criteria), including other substance use disorders, than both non-drug users and other drug users. They reported higher rates of prescription medication use than non-users, but not higher rates of health service utilisation. Interestingly, analyses showed that, in the majority of cases, these psychiatric symptoms occurred prior to ecstasy use, suggesting that adolescents and young people with symptoms of mental disorders are at an increased risk of using ecstasy.
van Beek et al. (2001) noted that after a binge the crash, often increasingly more intense each time, is characterised by depression, fatigue and sleeping difficulties. Similar patterns of use and effects have been identified for amphetamine users, although the half-life of amphetamines is substantially longer that cocaine. In this group, depression and suicidal behaviour have been identified as significant risks during the 'crash' period (Kamieniecki et al., 1998).
Most respondents in the van Beek et al. study reported paranoia, hallucinations, depression, anxiety and obsessiveness. Other psychological problems identified by these users included low self-esteem, an altered sense of reality and feelings of hopelessness. The study did not identify any users who reported psychosis, but key informants reported that psychosis was common and problematic among users in treatment. In addition, because of the significant paranoia and irritability common in cocaine users, referral to mental health services is often a difficult process. Informants noted that symptoms typically subsided when treated or when cocaine use ceased but often reoccurred when use resumed.
Back et al. (2001) note that post-traumatic stress disorder (PTSD) is highly prevalent among cocaine users, with studies reporting up to 45% for lifetime diagnosis. Nearly a quarter would meet criteria for a current diagnosis of PTSD, significantly higher than the general population at around 8%. They also note a number of studies that have shown that cocaine use is associated with more severe psychiatric symptomatology, higher rates of DSM-IV Axis II (personality disorder) psychopathology and higher risk of re-victimisation. In a study of exposure therapy for cocaine users with PTSD, Brady, Dansky, Back, Foa and Carroll (2001) found that dropout rates were high but those who completed treatment reduced both cocaine use and PTSD symptoms.
Several studies have identified a higher than usual risk of suicidal behaviour among cocaine users. Roy (2001) compared a group of cocaine users who had attempted suicide with cocaine users who had never attempted suicide and found that suicide attempters were more likely to be female, have a family history of suicide, had more childhood trauma, comorbid substance use and depression and had particular personality characteristics, including introversion, neuroticism and hostility. However, in a study of IDUs, Malbergier and Guerra de Andrade (2001) concluded that depression was associated with suicide attempts but not with cocaine use in both HIV positive and HIV negative users.
Field, Diego and Sanders (2001) noted that adolescents at risk for depression were, among other factors, more likely to use cocaine and cannabis. However, in this study their relationship with parents and other indicators of wellbeing accounted for a majority of the variance.
In a review of adverse effects of psychostimulants, Kamieniecki et al. (1998) noted a particularly high prevalence of mental health symptoms among amphetamine users. For example, these authors noted that between 50% and 90% reported symptoms of depression, between 60% and 80% reported anxiety symptoms and between 30% and 80% had experienced symptoms of psychosis.
Israel and Lee (2001) and Kratofil, Baberg and Dimsdale (1996) both presented several case studies of self-mutilation after amphetamine use. In each case this was attributed to psychosis. Self-mutilation behaviours have also been seen in animal studies (Kratofil et al., 1996). Kratofil et al. (1996) noted that the behaviour was commonly motivated by religious, sexual and 'neurotic' themes, such as self-punishment and control. Self-mutilation included enucleation (amputation) of limbs and eyes, genital mutilation, stabbing and cutting injuries. The behaviours appear to be relatively rare and virtually unknown among women who use psychostimulants, but are probably under-reported (Israel & Lee, 2001).
Other mental health and psychological symptoms that have been noted as a result of psychostimulant use include agitation and anxiety, paranoia, hostility and aggression, confusion, delirium and hallucinations (especially auditory and tactile) (Baker & Lee, in press; Topp, in press).Top of page
Social risksStrote, Lee and Wechsler (2002) conducted a survey of ecstasy use among college students. They noted that, although they spent less time studying, ecstasy users were not academic under-achievers and were as satisfied with education as non-using students.
Riley, James, Gregory, Dingle and Cadger (2001) identified four main risks for young people using ecstasy: driving on drugs, unprotected sex, over indulgence and injecting. They found that 85% of ecstasy users reported concurrent polydrug use, 30% had unprotected sex while using, 35% reported driving while intoxicated and nearly 1% reported injecting.
In a survey of users, van Beek et al. (2001) identified a number of significant social risks. 60% of respondents admitted to committing crimes they wouldn't normally engage in whilst using, 77% agreed that it made people socially unreliable and 64% believed that cocaine use interferes with relationships. Cocaine use has also been associated with violent injury (Chermack & Blow, 2002; Macdonald & Wells, 2001) as has amphetamine use (Wright & Klee, 2001).
Similarly, Winstock, Griffiths and Stewart (2001) found that dance music enthusiasts in London used substantial doses of multiple substances, including alcohol at hazardous levels. Over 5% of the sample injected, primarily amphetamines and heroin. They noted that purchasing patterns (an average of eight pills bought at a time) and the prevalent selling-on put users at risk of legal consequences. They also noted use patterns that put users at high risk of dependence.