International Journal of Drug Policy 9 (1998) 339–344

Prescribing amphetamine to amphetamine users as a harm reduction measure

Philip M. Fleming
Consultant Psychiatrist, Portsmouth City Drug and Alcohol Service, Kingsway House, 130 Elm Grove, Southsea,
Hampshire PO5 1LR, UK
Received 1 April 1998; received in revised form 1 June 1998; accepted 1 July 1998
1 This paper is based on a presentation given at the 9th
International Conference on the Reduction of Drug Related Harm held in Sao Paulo, Brazil, 15–19 March 1998. 0955-3959:98:$ - see front matter © 1998 Elsevier Science B.V. All rights reserved.
PII S0955-3959(98)00046-2 340 P.M. Fleming : International Journal of Drug Policy 9 (1998) 339–344

Amphetamine misuse is a widespread problem in many countries. This paper briefly reviews the history of
amphetamine prescribing, considering experience particularly in Sweden and the UK. The current extent of
amphetamine prescribing in the UK is described. From this and from the personal experience of the author,
guidelines for prescribing are described. These consider the indications and contraindications, goals of treatment,
dosage and form, monitoring and how long treatment should continue. The effectiveness of such prescribing is
reviewed and the need for more research in this area as well as the need for services targeted at amphetamine users
is noted.


Amphetamine misuse is a widespread problem
in many countries (Yoshida, 1997; World Drug
Report, 1997). It has been the principal drug of
misuse in Japan and Sweden for many years. The
US has had an amphetamine problem since the
1960’s and there is some evidence of a resurgence
in its use particularly on the West Coast. Currently
in the UK and Australia amphetamine is
the most frequently used illegal drug after
cannabis.

Many users just take the drug on a recreational
basis but there are increasing numbers of heavy
dependent users. Many of these people inject the
drug (Peters et al., 1997) with the attendant risks
of HIV and hepatitis C infection and there are
other physical and mental health sequelea of
heavy amphetamine use. Criminal activity, violence,
and social disruption are all associated with
heavy use (Farrell et al., 1997).

In spite of widespread use and the morbidity
associated with heavy use of the drug, there has
been relatively little recent research into amphetamine
misuse (Klee, 1992). This contrasts
markedly with the efforts put into research into
cocaine and heroin misuse. This paper looks at
one aspect of the treatment of amphetamine misusers
that of substitute prescribing. It is important
to emphasise that amphetamine prescribing
should be only one option in a range of treatment
approaches to amphetamine misuse. It is one that
is, uniquely, available in the UK.

2. History of amphetamine prescribing
Amphetamine was available as an over the
counter medicine from the 1930’s onwards. It was
used to treat nasal congestion, but there were
early reports of its being misused for its stimulant
and its fatigue delaying effects. During the Second
World War it was widely distributed to troops to
enhance their performance and to delay fatigue.
In the 1950’s doctors prescribed amphetamines as
a treatment for depression and for the treatment
of obesity. The misuse of amphetamine amongst
young people began to be seen in Japan in the late
1940’s and 50’s and in Sweden in the 1950’s. The
phenomenon appeared in the US and UK in the
1960’s.

In Sweden following a large media campaign in
favour of liberalisation of drug policy an experiment
with legal prescription of central stimulants
and opiates for injection was initiated in April,
1965 (Kall, 1997). The idea was to stop the need
to commit crime by supplying the drugs the users
wanted and then to gradually reduce the dose and
get them off the drugs. The experiment was
deemed a failure as there was much leakage onto
the black market and users were not getting off
the drugs and it was ended after 2 years following
the death of a young girl from an overdose of
morphine and amphetamine (Bejerot, 1970).

There were two reports of amphetamine prescribing
in the UK in the 1960’s. In 1968 there
was widespread methylamphetamine misuse in
London that was brought to an end after a few
months following the withdrawal of the drug
from retail pharmacies. A special clinic was set up
to provide treatment for these misusers and 12
patients received prescriptions of methylamphetamine
for injection (Mitcheson et al., 1976).

The results of this trial were considered to be a
failure. A second report on amphetamine misusers
treated with oral amphetamine at a clinic in London
in 1968:69 concluded that such prescriptions
were unlikely to be effective (Gardner and Connell,
1972). These experiences were influential for
nearly two decades in the UK in discouraging
amphetamine prescribing as a treatment.

3. Current situation in the UK
An increase in the amount of illicitly available
amphetamine sulphate in the UK in the 1980’s
resulted in an increase in the number of problematic
amphetamine users. These did not often
present to drug services, which were principally
geared to the treatment of opiate users. The system
for registering addicts at the Home Office did
not include amphetamine users so there was no
measure of the numbers who might require treatment.
It was the setting up of the first needle
exchange schemes in 1987 that brought to light
the problem of injecting amphetamine use. In
some places more amphetamine users were accessing
these exchanges than opiate users (Stimson et
al., 1988). A number of drug services in the UK
(including our own in Portsmouth) began to prescribe
amphetamine to heavy dependent injecting
users (Standing Conference on Drug Abuse,
1989).

Over the past 10 years the number of services
that prescribe amphetamine has gradually increased
in England and Wales—there is no amphetamine
prescribing reported in Scotland. This
has occurred as a pragmatic response to the problem
users that have presented to services but in
the absence of much in the way of scientific
evidence to support it. Neither has there been any
agreed prescribing protocols to guide practice.

The current legal position in the UK with respect
to prescribing amphetamine is covered by
the Misuse of Drugs Act. Amphetamine is included
under Schedule 2, which requires amongst other things that practitioners conform to certain regulations in the writing of prescriptions.

However, any fully registered doctor, either hospital
or general practitioner may prescribe amphetamine.
In practice such prescribing is almost always undertaken by specialist agencies usually with their own specialist medical staff or sometimes working with local general practitioners.
There is also a requirement to inform a regional
database on anonymised forms of any drug misuser
seeking treatment.

Results from a 1995 survey of community
pharmacists in England and Wales (Strang and
Sheridan, 1997) concluded that that there were
an estimated 900–1000 patients receiving amphetamine
for the treatment of addiction, 97%
in the form of oral preparations. (This compares
to an estimated 400 patients receiving heroin
prescriptions and 70000 receiving methadone).

We undertook a survey of specialists in drug
dependence in England and Wales in 1996 to
obtain some information about amphetamine
prescribing practices (Bradbeer et al., 1998). We
identified 201 doctors and sent them a short
questionnaire and obtained a 74% response rate.
Of 149 doctors responding, 69 (46%) were prescribing
amphetamine. A larger percentage, 60%,
agreed that there was a role for the prescription
of amphetamine. In addition we have been in
touch with several colleagues who have experience
of amphetamine prescribing and have asked
them about their practice in more detail. This
information forms the basis for the following
discussion.

4. Prescribing guidelines
4.1. Indications
Prescribing should be limited to primary amphetamine
users with heavy problematic use. In
the UK this will mean using more than 1 g of
street amphetamine sulphate a day. In practice
heavy users may take 3 or 4 g a day and will
usually have been taking amphetamine regularly
for at least several months. Of users presenting
to services 50% are injecting the drug (Department
of Health, 1996) and this is the main
group for whom substitute prescribing is reserved
though some services will consider prescribing
for heavy non-injecting users.
The aim is to prescribe only to those users
who are dependent on the drug. It used to be
considered that though users may become psychologically
dependent on amphetamine there
was no physical dependence and thus no indication
for substitute prescribing. Recent work has
shown that both the physical and psychological
dependence on amphetamine in regular users has
been underestimated and that this is a powerful
drive for continued use of the drug (Dackis and
Gold 1990; Topp et al., 1995; Topp and Darke,
1997; Cantwell and McBride, 1998)

4.2. Contraindications
These include a history of mental illness, hypertension,
heart disease or pregnancy. The issue
of mental illness is not always clear cut as heavy
amphetamine users often experience paranoid
feelings and indeed occasional psychotic
episodes. The UK practice generally is to avoid
amphetamine prescriptions if there has been an
episode of frank psychosis even if this has been
associated with drug use, as these sometimes
presage the development of a schizophrenic
illness.

4.3. Goals of treatment
These are no different from methadone substitution
treatment and are principally harm reduction
goals. These include a reduction and
eventual cessation in injecting activity, and a
move to safer injecting practices; reduction in
the use of street drugs; improvements in physical
and mental health; improved social functioning
and this includes a reduction in criminal activity
(Lintzeris et al., 1996). Heavy amphetamine misusers
are often chaotic in their behaviour and
the initial aim is to try and stabilise them and
reduce the risks they pose to themselves and
others.

4.4. Dosage and form
There is not enough in the way of clinical
studies to be able to make very definitive statements
about dosage. In the UK, the average
purity of street amphetamine sulphate is 5% (Institute
for the Study of Drug Dependence, 1997).
However, recently amphetamine ‘base’ has been
available which is of much higher purity and this
makes it difficult to assess the amount of active
drug that a misuser has been taking. The frequency
distribution of amphetamine analyses performed
on seized drug by the Forensic Science
Service in London in 1997 show the modal values
remain between 2 and 4%. The mean value is
raised in comparison to earlier years because of
the small number of higher purity samples, for
example 7.6% of samples contained more than
40% amphetamine (personal communication). In
general the aim should be to minimise withdrawal
symptoms rather than to give an equivalent dose
to that used illegally. The pharmacy study found
a mean dose for oral amphetamine of 41 mg
daily. Our survey gave a mean upper limit of 66
mg. Many practitioners had an upper limit of 60
mg although some prescribed higher doses i.e.
80–100 mg in some cases. Paranoid symptoms
were rarely reported as side effects even with the
higher dosages. On those occasions when paranoid
symptoms were seen it was usually the case
that subjects had used illicit amphetamine on top
of their prescribed dose.

Concerning the form in which dexamphetamine
is dispensed, our preference is for an elixir prepared
from amphetamine sulphate powder that is
taken orally and is dispensed on several days a
week. This minimises the opportunity for diversion.
We have had no reports of users injecting
the elixir. Most colleagues prescribe oral preparations
more often in the form of tablets than in a
liquid. The half-life of amphetamine depends on
the pH of the urine, and Sherman alkalinised the
urine to increase the half-life of amphetamine
(Sherman, 1990). The average half-life is about 12
h and most practitioners find a single morning
dose is effective.

4.5. Monitoring
This is most commonly by urinalysis for the
presence of other drugs, and inspection of injection
sites. Recently developed techniques allow
for the distinction to be made between prescribed
and illicit amphetamine in the urine (Tetlow and
Merrill, 1996). In addition monitoring should include:
mental state, blood pressure and weight
and general social stability.

4.6. How long should prescribing continue?
Once again there is little to guide us, and there
are differing views amongst practitioners. There is
some uncertainty about the long-term effects of
amphetamine on the brain (Gawin and
Ellinwood, 1988) which has led us to advise that
prescriptions should be time limited. However
some specialists argue that if users are showing
benefit from a prescription—that is that some of
the goals of prescribing are being met—and they
relapse if the prescription is withdrawn the balance
of advantage lies in continuing the prescription.
If there is no progress towards any of the
goals of treatment then there is little purpose in
continuing the prescription. This can be stopped
immediately or tailed off. Rates of reduction vary:
5 mg reduction every 1–2 weeks is often used.

5. Issues

5.1. Is amphetamine prescribing effective as a
harm reduction measure?
Most of the published reports are of observational
and follow up studies and clinical experience
and there is little in the way of controlled
clinical trials. Klee reports on a study in the
Northwest of England of 43 clients presenting to
drug treatment services with amphetamine-related
problems matched with controls (Klee, 1997).
Both groups were followed up for six months.
From the treatment group 43% were prescribed
amphetamine and it was amongst these that the
greatest decline was seen in use of street amphetamine,
injecting activity and criminal activity.

McBride et al. (1997) compared a treatment
group who received amphetamine with a control
group who fulfilled the same criteria but who had
attended the same service before dexamphetamine
prescribing began. The treatment group used less
illicit drugs and showed reduction in injecting
activity and had more contact with services.
In addition to these studies there are a number
of reports of follow up studies of patients who
have received dexamphetamine prescriptions
(Sherman, 1990; Fleming and Roberts, 1994;
Pates et al., 1996). These have also showed similar
benefits. Thus there is an increasing body of clinical
work showing the benefit of amphetamine
prescribing in the treatment of dependent amphetamine
users. These benefits are principally in
the area of harm reduction.

5.2. Other benefits from prescribing
The perception of many amphetamine users is
that current services have little to offer them
(Farrell et al., 1997) although if such services did
target them they would be more likely to attend.
The existence of an amphetamine prescribing programme
sends out a message that amphetamine
problems are taken seriously. Our own experience
(Fleming and Roberts, 1994) has been that following
the establishment of such a programme we
had a significant increase in self-referrals with
amphetamine problems. Interestingly many of
these people were not seeking a prescription but
were looking for help in reducing and modifying
their use of the drug. This is help that a drug
service should be providing. Experience with a
prescribing service is that in addition to attracting
users to services, providing a prescription helps to
keep users in treatment (McBride et al., 1997).

5.3. The need for more research
Klee noted the lack of research interest into
amphetamine misuse (Klee, 1992). Whilst the reports
so far have suggested benefits for amphetamine
prescribing there is clearly a need for
more controlled studies (Mattick and Darke,
1995). The guidelines outlined above have been
developed pragmatically from clinical experience.
In this era of clinical effectiveness they need to be
firmly based on evidence and this is only going to
come from adequate clinical trials. What is lacking
at present is any longer term controlled studies
into the effect of amphetamine prescribing. We
know little about the natural history of heavy
amphetamine use and even less about whether a
prescription will modify this.

5.4. Services targeted at amphetamine misusers
In the UK drug services have historically been
directed at opiate users and the needs of stimulant
users have been neglected. There is a need therefore
to develop specific services targeted at this
group (Klee, 1997). As mentioned above services
that have offered substitute amphetamine prescribing
have found that they attract more amphetamine
users to their service not all of them
necessarily seeking a prescription. Services should
offer help with modifying patterns of use, and
general harm reduction advice as well as substitution
treatment where this is indicated.

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