Disorders Relating to the Use of Amphetamine and Cocaine

Disorders relating to the use of amphetamine and cocaine.

Topics covered: 

  • Introduction
  • Clinical features
    • Are amphetamine and cocaine addictive?
  • Classification
  • Diagnosis
  • Epidemiology
  • Aetiology
  • Course and prognosis
    • Course
    • Other drug use
    • Prognosis
    • Complications
  • Treatment
    • Evidence
    • Management
  • Prevention 
  • References


Amphetamine and cocaine are classed as stimulant drugs, although the distinction between stimulants and depressants can be criticized on the grounds that the same drug may have both actions in turn. (1) This does indeed occur with amphetamine and cocaine, but the initial desired effects are increased energy and activity, along with elevation in mood. These effects appear to be mainly due to the enhanced central transmission of dopamine and noradrenaline (norepinephrine), with a similar enhancement of serotonin playing a less certain role.

Pharmaceutical preparations of amphetamine were previously widely used for the treatment of depression and obesity, and until the 1970s most misuse of the drug related to such medications. In the period since then of increasing recreational drug use, the powder preparation of ‘street' amphetamine (commonly known as ‘speed' or ‘whizz') has largely displaced the pharmaceutical forms to become one of the most common drugs of misuse in many countries. The powder is typically very impure and constitutes a racemic mixture of D- and L-isomers, with the L-form being relatively inactive. In some countries a more potent street preparation of methylamphetamine is encountered, known as ‘ice'. The various forms of the drug may be misused by swallowing (either on its own or in a drink), snorting, or injecting.

The coca shrub is indigenous to several countries in South America, where it is traditional to chew the leaf. Use of the derived cocaine powder has spread to the United States and elsewhere, again most notably since the 1970s. The powder may be injected, sometimes along with heroin, by polydrug users, but probably the best-known usage is by snorting, the image of which became associated with successful executive lifestyles. Cocaine has become more dangerous as usage has gradually transferred in many countries to the ‘crack' form, which is made from cocaine hydrochloride powder in a simple chemical process, and is more potent in its effects and withdrawal effects. Very rapid increases in blood levels of the drug can be achieved by smoking crack, and this is the usual route, although it is injected by committed intravenous drug users.

Of the two drugs, cocaine has generally been much more investigated than amphetamine in terms of epidemiology, effects, and treatment approaches, while there has been a particular interest in the links between amphetamine use and a psychosis resembling schizophrenia.

Clinical features

The effects and withdrawal effects of amphetamine and cocaine can be considered together, as the main features are equivalent. However, amphetamine has a slower onset of action than cocaine and a longer elimination half-life, while crack is the most quickly absorbed of the cocaine preparations. This is reflected not only in the generally more intense effects of cocaine than amphetamine, but in the timescales involved. Thus an amphetamine user may experience desired effects, unwanted mental effects, and withdrawal features over the course of a few days, while a crack user can report the same sequence occurring in a matter of hours or even less. 

The list of effects can be seen as merging from the desired to the undesired. On the whole, these drugs are taken in situations where stimulation is the aim, with sleep not wished for and eating regarded as a hindrance. Mood is elevated, but characteristically this progresses to suspicion, in which true paranoid symptoms may be experienced. This is usually recognized by the individual as indicating that the episode of use should be terminated, but if use persists symptoms may become severe, or a more confused state develop. After stopping the drugs there are typically withdrawal effects of depressed mood, hyperphagia, and hypersomnia; no consensus exists as to whether such features are best viewed as ‘rebound' symptoms, a truer withdrawal syndrome, or simply users catching up on sleeping and eating after a period without either.

Such withdrawal features have been delineated most closely in relation to cocaine. A three-stage process has been described: (2) initially agitation, anorexia, and acute craving; second, excessive tiredness, depression, and hyperphagia; finally, a normalization of most features, but a return of craving when triggered by environmental cues. This was the description before the escalation in crack use, and it is widely held that depression, craving, and agitation in particular are much more severe with this form of the drug. While environmental cues are clearly relevant in precipitating the use of any drug, a powerful surge of craving on encountering situations associated with previous use appears particularly characteristic of cocaine and crack. (3) The three-stage description of withdrawal features suggests that this phenomenon may occur after months or even years of abstinence.

Are amphetamine and cocaine addictive?

It is commonly observed that amphetamine and cocaine are non-addictive, or cause psychological but not physical dependence. Such observations rest on a distinction in which the condition of addiction, or physical dependence, requires visible bodily withdrawal symptoms, but critics claim that this is of limited meaning now that there is an understanding of the neurobiological basis of drug withdrawal states. The current classification systems do retain some distinctions between physical and psychological dependence, and the issue is largely one of definition and semantics. The credibility of the label ‘non-addictive' is certainly tested when individuals are encountered who have injected amphetamine 10 or more times every day for many years, or who spend vast amounts of money using crack in a highly compulsive manner.


Importantly, the list of diagnoses in ICD-10 is a standard one to be used across all psychoactive substances, with the second digit of the code number simply changed according to substance, and so the list itself does not imply that all those conditions can be caused by amphetamine or cocaine. The DSM-IV listing is somewhat more specific, in that the diagnoses are selected from a wider general list of conditions which can apply to the range of substances. In this way the DSM-IV classification recognizes that cocaine and amphetamine can produce states of dependence and withdrawal, as well as psychosis, affective disorders, and the other conditions included. In both systems there are some more specific subcategories such as intoxication with perceptual disturbances, and categories for ‘other' or ‘unspecified' substance-related conditions.


The use of amphetamine or cocaine can be detected by drug screening of a plain urine sample. Laboratory testing is the usual option, while instant testing kits of high specificity and sensitivity are also available. The importance of urine testing as a relatively simple procedure to employ, in any setting, in cases where drug use is suspected must be emphasized, as it is surprisingly often neglected. A limitation of this method, however, is that most drugs of misuse only remain detectable in urine for a few days at maximum, and with cocaine this may be as little as 24 h. In contrast, most drugs stay in the hair for as long as that is present. Although this method of hair analysis has the advantage that drug use may be detected over the period during which hair has grown, it has not been incorporated into routine clinical practice. (4)

Clearly self-reports of drug use are often reliable, especially when it is known that they are to be backed up by testing, but a history may be unavailable in, for example, psychotic states. Testing is therefore indicated, although there may be particular problems of compliance. Where a positive result is obtained in a patient with a psychiatric condition, it is important to realize that drug use may be incidental rather than necessarily causative. (5)


In most countries, the use of illicit drugs is most common among those of young age, male gender, and lower socio-economic status, in areas with high rates of other social problems. Stimulant use in general reflects this, although of the drugs of misuse, cocaine has been exceptional in the extent of usage by more affluent individuals. With cocaine snorting by that group generally in decline, the transition to the crack form appears to have brought cocaine more into line with other drugs, in terms of the users's general characteristics.

The biggest epidemic of cocaine use outside South America has been in the United States, where it peaked in the mid-1980s. (6,7) Household surveys at that time estimated that approximately one-tenth of the population had used the drug; the same epidemiological method has charted the subsequent general decline in occasional use, but an increase in more dependent use of crack. Cocaine use in other countries does not appear to have spread as widely as was predicted from experience in the United States. In Australia, the population prevalence of cocaine use has remained at around 2 per cent, much of it among inner-city polydrug users, (8) and the United Kingdom picture is similar. Among other factors, it is considered that a rapid rise in cocaine problems is relatively unlikely in countries where there is an established ready availability of amphetamine, as a similar and generally cheaper drug.

Even in areas where it is known that stimulant use is common, such users tend to present relatively rarely to treatment services. This relates to the priority that is generally given to opiate misusers and methadone treatment, and is an important issue for service planners—it also has the effect that treatment statistics will always particularly underestimate stimulant problems. In the United Kingdom, consistently more individuals who are using amphetamine and cocaine as secondary drugs rather than main drugs of preference present to services. Therefore, such statistics in turn overestimate polydrug use, although it is clear from all sources that stimulant users do commonly take other drugs, notably sedatives of various kinds to alleviate withdrawal effects (see the section on course and prognosis below).


Broadly the same familial, social, and psychological factors are relevant in the aetiology of amphetamine and cocaine misuse as in other forms of drug misuse. Overall, approximately two-thirds to three-quarters of drug misusers have an underlying personality disorder, (9) usually of the antisocial type, but the figure has been found to be somewhat lower for stimulant misusers than for those dependent on opiates. (10) This may be partly methodological, to do with the difficulty in distinguishing true personality characteristics from behaviours inherent in the activity of highly dependent drug misuse, but is probably also a reflection of the use of stimulant drugs by a generally broader population.

Course and prognosis


A far greater proportion of amphetamine and cocaine misuse than opiate misuse is recreational in nature, with few significant complications occurring. It is assumed that the vast majority of those who are identified in school and teenage surveys as having used stimulants simply give them up in due course, although little systematic data is available. Complications and involvement with treatment services are more likely where there is dependent usage, and there may be psychiatric contact in episodes of psychosis. A very small proportion of amphetamine injectors progress to high-dose daily usage, while the heavy use of cocaine appears to be less sustainable and is therefore usually periodic in nature.

Other drug use

After being stimulated with amphetamine or cocaine, many individuals will use sedative drugs such as alcohol, benzodiazepines, or cannabis to ‘come down' from their drug. Increasingly heroin is being used for this purpose, sometimes to the point of becoming dependent on the opiate, and even requiring methadone treatment. The use of cocaine in particular is commonly encountered as a secondary form of drug misuse in methadone patients, (11) with some individuals appearing to switch their preferred illicit drug from heroin to cocaine when treatment is established.


The drug misuse literature in general would suggest that stimulant use is more likely to progress and become problematic in individuals with associated personal or social difficulties, or psychiatric disorder including personality disorder. (9) There is limited evidence from studies of cocaine misuse treatment that prognosis may be better in women, (12) or when a ‘significant other' participates in treatment. (13)


Many of the complications of amphetamine and cocaine misuse are complications of drug misuse in general, including those related to injecting. The range includes general physical decline, weight loss, dental problems, infective complications ranging from abscesses to hepatitis and infection with the human immunodeficiency virus (HIV), reduced fetal growth in pregnancy, mood disturbances, and various social problems. Complications in the following areas are somewhat more specific to stimulant misuse:

  • cardiovascular—hypertension, arrhythmias, myocardial infarction, cerebrovascular accident
  • obstetric—premature labour, placental abruption
  • psychiatric—anxiety, depression, aggressive behaviours, psychosis.

The cardiovascular problems relate to increased catecholamine secretion produced by stimulants, and were seen at a high rate in the United States cocaine epidemic.(14) With obstetric complications, it is difficult to separate the effects of drugs from other risk factors such as poor diet, smoking, or adverse social conditions, but there appears to be a particular link between stimulants and placental abruption. (15) There are also various psychiatric disorders that are particularly associated with amphetamine and cocaine misuse.

Anxiety is common in relation to the agitation produced by the drugs, while depression is a classic withdrawal effect. An assessment of the true significance of these features therefore requires withdrawal from drugs, while in acute presentations both can be extremely distressing, often requiring pharmacological treatments (see below). Aggressive behaviour may be due to an underlying personality disorder, but it is also characteristic of withdrawal from crack cocaine where severe craving is experienced. Psychosis is such a well-known complication of stimulant misuse that one possible problem is that of overdiagnosis. (5) Psychosis produced by amphetamine usually lasts longer than that due to cocaine, but in either case symptoms can be expected to subside if drug use ceases. A diagnosis of drug-induced psychosis is therefore dubious if definite psychotic symptoms persist when urine drug screens have become negative, although there is no consensus as to the stage at which an alternative diagnosis such as schizophrenia needs to be made. (16)



There is little evidence in support of any specific clinical treatment in amphetamine and cocaine misuse. The majority of studies are from the United States and concern cocaine, many investigating those medications that may alleviate withdrawal effects. (6,7) Some positive findings have been reported, mainly from uncontrolled studies, relating to the use of the dopaminergic agents bromocriptine and amantadine, and also fluoxetine and other medications. Most studied has been desipramine, with a meta-analysis indicating some benefit in promoting abstinence from cocaine. (17) Inpatient programmes and psychological treatments basically represent modifications of those approaches used across all forms of drug misuse.


Faced with the severe limitations in treatment for these forms of drug misuse that have high morbidity and mortality, drug services have had to consider how best to achieve some benefits in terms of practical management. (18) The factors that appear important in such provision are:

  • specific outreach programmes
  • harm-reduction approaches
  • rapid response where necessary
  • targeted use of pharmacological treatments
  • admission in severe cases.

To engage stimulant users at all can require specific outreach aimed at the subcultural groups in whom usage is common. Basic harm-reduction measures must be offered, including drug information, education about health risks, advice to reduce damaging injecting practices, and the provision of clean injecting equipment. Counselling of a supportive or more behavioural kind may be provided by various types of agency.

The periodic nature of stimulant problems means that rapid response can be important, for instance in states of acute crack withdrawal or psychiatric disturbance. Use of tranquillizers and antipsychotic medications may be necessary for various presentations, while fluoxetine appears to be increasingly favoured over other antidepressants, due to a possible anticraving effect and good acceptability. Inpatient admission is required relatively frequently in cases where no long-term measure is able to make much impact between acute crises. The possibility of any substitute prescribing in stimulant misuse is highly controversial, with some services seeing a role for oral dexamphetamine in heavily dependent amphetamine users experiencing extreme problems from injecting. (19)

Drug-induced psychosis

The two aspects of management of this complication are the treatment of psychotic symptoms and the withdrawal of the drug which is thought to be causative. The latter can be very problematic other than as an inpatient, and is not guaranteed even then. In practice, ongoing semi-psychotic states in individuals who have not completely stopped drug use are common, and treatment may have to be attempted in such circumstances. The use of antipsychotic medications does not differ significantly from that in psychoses not produced by drugs.


The prevention of drug misuse lies largely outside the clinical domain, in the areas of education and enforcement. One experimental clinical development in cocaine misuse is a vaccine whereby limited exposure produces anticocaine antibodies to subsequently block the drug's effects. (20)


1. Nutt, D.J. (1996). Addiction: brain mechanisms and their treatment implications. Lancet, 347, 31–6.

2. Gawin, F.H. and Kleber, H.D. (1986). Abstinence symptomatology and psychiatric diagnoses in cocaine abusers: clinical observations. Archives of General Psychiatry, 43, 107–13.

3. Weddington, W.W., Brown, B.S., Haertzen, C.A., et al. (1990). Changes in mood, craving, and sleep during short-term abstinence reported by male cocaine addicts. Archives of General Psychiatry, 47, 861–8.

4. McPhillips, M.A., Strang, J., and Barnes, T.R.E. (1998). Hair analysis. New laboratory ability to test for substance use. British Journal of Psychiatry, 173, 287–90.

5. Poole, R. and Brabbins, C. (1996). Drug induced psychosis. British Journal of Psychiatry, 168, 135–8.

6. Withers, N.W., Pulvirenti, L., Koob, G.F., and Gillin, J.C. (1995). Cocaine abuse and dependence. Journal of Clinical Psychopharmacology, 15, 63–78.

7. Nathan, K.I., Bresnick, W.H., and Batki, S.L. (1998). Cocaine abuse and dependence. Approaches to management. CNS Drugs, 10, 43–59.

8. Hando, J., Flaherty, B., and Rutter, S. (1997). An Australian profile on the use of cocaine. Addiction, 92, 173–82.

9. Seivewright, N. and Daly, C. (1997). Personality disorder and drug use: a review. Drug and Alcohol Review, 16, 235–50.

10. Verheul, R., van den Brink, W., and Hartgers, C. (1995). Prevalence of personality disorders among alcoholics and drug addicts: an overview. European Addiction Research, 1, 166–77.

11. Rawson, R.A., McCann, M.J., Hasson, A.J., and Ling, W. (1994). Cocaine abuse among methadone maintenance patients: are there effective treatment strategies? Journal of Psychoactive Drugs, 26, 129–36.

12. Kosten, T.A., Gawin, F.H., Kosten, T.R., and Rounsaville, B.J. (1993). Gender differences in cocaine use and treatment response. Journal of Substance Abuse Treatment, 10, 63–6.

13. Higgins, St., Budney, A.J., Bickel, W.K., and Badger, M.S. (1994). Participation of significant others in outpatient behavioural treatment predicts greater cocaine abstinence. American Journal of Drug and Alcohol Abuse, 20, 47–56.

14. Galanter, M., Egelko, S., De Leon, G., Rohrs, C., and Franco, H. (1992). Crack cocaine abusers in the general hospital: assessment and initiation of care. American Journal of Psychiatry, 149, 810–15.

15. Hulse, G.K., Milne, G., English, D.R., and Holman, C.D.J. (1997). Assessing the relationship between maternal cocaine use and abruptio placentae. Addiction, 92, 1547–51.

16. Flaum, M. and Schultz, S.K. (1996). When does amphetamine-induced psychosis become schizophrenia? American Journal of Psychiatry, 153, 812–15.

17. Levin, F.R. and Lehman, A.F. (1991). Meta-analysis of desipramine as an adjunct in the treatment of cocaine addiction. Journal of Clinical Psychopharmacology, 11, 371–8.

18. Seivewright, N. (1999). Treatment of non-opiate misuse. In Community treatment of drug misuse: more than methadone, Chapter 4. Cambridge University Press.

19. Bradbeer, T.M., Fleming, P.M., Charlton, P., and Crichton, J.S. (1998). Survey of amphetamine prescribing in England and Wales. Drug and Alcohol Review, 17, 299–304.

20. Fox, B.S. (1997). Development of a therapeutic vaccine for the treatment of cocaine addiction. Drug and Alcohol Dependence, 48, 153–8.