The British Journal of Psychiatry (2007) 191: 279-281. doi: 10.1192/bjp.bp.107.035212
© 2007 The Royal College of Psychiatrists
Uppers keep going up
Hamid Ghodse, PhD, DSc, FRCPsych(Hon)
International Centre for Drug Policy (ICDP), St Georges,
University of London, London SW17 ORE, UK. Email:
hghodse{at}sgul.ac.uk
Declaration of interest H.G. is a member (past President) of the
United Nations International Narcotics Control Board in Vienna.

ABSTRACT
Amphetamine-type stimulants are the second most widely used
drugs in the
world. Overprescription results in diversion for
recreational use and the
development of dependence. The internet
plays a significant role in global
misuse of amphetamine-type
stimulants, permitting uncontrolled dispensing by
online pharmacies
and providing information on techniques for illicit
manufacture.

INTRODUCTION
Amid increasing concern about the misuse of methamphetamine,
it is
important to remember that misuse of amphetamine-type
stimulants is not a new
phenomenon (
Ghodse & Kreek,
1998).
Indeed, there is a long history of dependency and misuse of
this class of drugs, with widespread consumption by armies
and the industrial
work-force during the Second World War.
During the 1960s and 1970s
amphetamines were increasingly prescribed
as antidepressants and anorectics
and misuse became common,
particularly in the USA where demand was so great
that several
billion amphetamine tablets were manufactured every year
(
Addiction Research Foundation,
1987).
Many people who had initially received amphetamines on prescription became
dependent and refused to discontinue their use
(Ghodse, 2002a).
Others started consuming them specifically for their stimulant properties. For
example, they were utilised by students and by long-distance lorry drivers to
promote wakefulness, and were also used for recreational purposes.
Initially the major source of amphetamines was the legitimate
pharmaceutical industry, with overprescribing leading to diversion of surplus
tablets to the illicit market. In addition, there was criminal procurement by
theft and falsification of prescriptions. The scale of misuse was such that in
the 1960s, the US Food and Drug Administration estimated that half of the
amphetamines manufactured found their way into illicit channels of
distribution (Sadusk,
1968).
The twin problems of overprescribing and misuse became so serious that
national and international control measures became inevitable (Ghodse,
2002a,b;
Karen & Laidler, 2002). In
the UK, for example, there was a voluntary ban on prescribing amphetamines by
medical practitioners. The inclusion of amphetamines in the 1971 International
Convention on Psychotropic Drugs resulted in a reduced flow of legally
manufactured amphetamines to the illicit market. During the 1980s the legal
manufacture of amphetamine and dexamphetamine was stable at around 50 kg and
350 kg annually respectively. However, demand for amphetamines for drug misuse
remained high and was increasingly met by illicitly manufactured amphetamines
rather than by overspill of prescribed drugs.
After this period of relatively low medical use it increased again, and by
2004 some 25 million people worldwide used amphetamines, with more than 60%
living in Asia. In 2005, approximately 12.9 tons of amphetamine (60 million
defined daily doses) were manufactured legally in the USA for direct medical
use, 76 times more than in 1991 (United
Nations, 2006). The annual prevalence of amphetamine use is
highest in Oceania, followed by North America, and East and South-East Asia.
There are an estimated 2.7 million users in Europe, with the UK continuing to
be the largest market (United Nations
Office on Drugs and Crime, 2006).

STIMULANTS USED AS ANORECTICS
In a society which is increasingly preoccupied with weight and
obesity, the
introduction of controls on amphetamine prescription
led to the search for and
production of other anorectic drugs
(e.g. fenfluramine, phentermine,
fenproporex and mazindol).
Following the publication in 1992 of the results of
a weight
control study utilising fenfluramine and phentermine for long-term
treatment (
Weintraub, 1992),
there was a resurgence in the
use of anorectic drugs, leading to a peak of
consumption in
the US in 1996 when nearly 20 defined daily doses were consumed
per 1000 inhabitants per day. This was followed by the familiar
pattern of
wide availability and misuse, with an illicit market
driven by diversion from
licit channels.
The withdrawal of fenfluramine from the market in the USA and the
associated reduction in consumption of phentermine, which was often prescribed
in tandem, heralded a downward trend in the use of amphetamine-type stimulants
and by 2005 consumption was one-fifth of the level 10 years earlier. Other
countries have experienced similar trends over a somewhat later period.

METHYLPHENIDATE
A new trend in the misuse of amphetamine-type stimulants developed
during
the early 1990s with global manufacture of methylphenidate
increasing tenfold
from 2.8 tons in 1990 to 28.8 tons in 2005
(
United Nations, 2006). This
was a result of its increased
use in the treatment of attention-deficit
hyperactivity disorder
(ADHD) (
Mayer,
1996;
Ghodse,
1999). Initially, this occurred
in the USA, which is still the
main consumer of these substances,
but the same phenomenon has been observed
in other countries,
including Australia, Canada, New Zealand, Switzerland and
the
UK. Serious concerns have been raised about the possible overdiagnosing
of
ADHD and consequent overprescribing of methylphenidate to
children
(
International Narcotics Control Board,
1999).
Such a high rate of prescribing leads to a range of associated problems,
including theft of methylphenidate from unregistered locations, such as
schools and homes where large quantities of methylphenidate may be available,
free from the accountability requirements placed on licensed handlers. Not
surprisingly, there is evidence of diversion of methylphenidate for illicit
use and reports of its misuse by adolescents and young adults orally or by
crushing and snorting. It is taken for its stimulant effects, appetite
suppression, increased focus/attentiveness and euphoria in a way that echoes
the use of amphetamine on campuses in the 1960s
(Woodworth, 2000).

METHAMPHETAMINE
More recently, there is evidence of increased misuse of illicit
methamphetamine in many parts of the world, although this remains
patchy.
Historically, most methamphetamine misuse has been
reported from the USA,
where it is now perceived as the most
serious drug misuse problem. Worryingly,
it is spreading throughout
the USA, albeit unevenly but especially in rural
and semi-rural
areas. Evidence of this comes from admission rates for
methamphetamine
misuse which have reached 323.6 per 100 000 population aged
12
years or over (
Lineberry & Bostwick,
2006). In South-East
Asia, Japan, the Philippines, Republic of
Korea and Thailand,
methamphetamine is also the drug of choice, and in some
European
countries (e.g. Czech Republic, Baltic States), methamphetamine
misuse now exceeds misuse of amphetamine. Manufacture and trafficking
have
also been reported from South Africa, providing further
evidence of spread
beyond the traditional areas
of production in North America and
Asia. This is particularly
worrying because methamphetamine misuse is
associated with
serious adverse effects and is very difficult to treat because
of protracted craving.
In the USA, strict regulation of precursors, such as ephedrine and
pseudoephedrine, used in the illicit manufacture of methamphetamine led to a
reduction in domestic production, but this was more than counterbalanced by
smuggling from clandestine laboratories in Mexico. Similarly, in Australasia,
rising methamphetamine misuse is fuelled by clandestine manufacture,
predominantly in South-East Asia. There is now growing concern that illicit
manufacturers are bypassing international controls on ephedrine and
pseudo-ephedrine. They are purchasing large quantities of proprietary flu and
cold remedies, which contain these substances, and which, as medicinal
preparations, are not subject to international control
(Ghodse, 2002b;
Karen & Laidler, 2002).

THE INTERNET
More recently, the internet has become an important component
of the
illicit market, with online pharmacies advertising and
selling controlled
substances without prescription through
regular mail channels. The scale of
this activity is huge and
the US Customs Service reportedly seized nearly 10
000 packages
containing prescription drugs during 1999, about 4.5 times as
many as in 1998 but undoubtedly representing only a small fraction
of
prescription drugs entering the USA via this route.
In addition, websites provide practical advice on how to obtain
prescription drugs from different countries, listing pharmacies and physicians
which offer medications without prescription and ship them directly to the
customer. In 2005, US law enforcement officers arrested 18 illegal internet
pharmacy owners and suspended the registration of 20 doctors and 22
pharmacies. It was found that those arrested operated 4600 illegal internet
pharmacy sites, handling 15 000 customers each week and that 3000 orders for
controlled substances were dispensed each day
(Tandy, 2005).
Finally, with modern computer technology and chemists increasing
willingness to share their knowledge, information on the manufacture of
illicit drugs (i.e. drug recipes) is now available to anyone with computer
access. Indeed, it is estimated that less than 10% of suspects arrested for
illicitly manufacturing methamphetamine are trained chemists.

PREVENTIVE MEASURES
Given the acknowledged harm associated with the misuse of amphetamine-type
stimulants and the difficulty of treating dependence, the importance
of
preventive measures is obvious. Most involve the application
of principles
that are relevant to all types of substance misuse.
In view of the historical link between overprescription and misuse, the
medical profession bears an important responsibility to prescribe
appropriately and to undertake initiatives to promote good practice.
Psychiatrists, in particular, should play a role in educating healthcare
professionals as well as the wider public to achieve a culture of rational
prescribing of these and other psychotropic drugs.
However, the diversion and smuggling of amphetamine-type stimulants will
only be counteracted by intensified cooperation between law enforcement and
drug regulatory authorities, including the establishment of mechanisms for the
prompt exchange of information among national authorities, and particularly
between the countries into which these products are smuggled and the suspected
source countries. Proposed approaches include the prevention of diversion from
domestic distribution by strict implementation of the prescription
requirement; control of international trade; and the prevention of
irresponsible marketing and prescribing. Compliance with the United Nations
Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic
Substances of 1988, which controls nine substances (precursors) used in the
illicit manufacture of amphetamine-type stimulants, is also essential.
Worldwide, there are now more than a billion internet users and legislation
and resources for law enforcement in this area are currently inadequate. In
relation to substance misuse it is essential that governments ensure that
appropriate laws are introduced to deal with crimes committed in an electronic
environment. These should be harmonised internationally to ensure that
offences, sanctions and standards of proof are similar to prevent the growth
of data havens. Law enforcement agencies responsible for fighting drug-related
crime must be provided with the technical and legislative means to develop an
appropriate response capacity for internet crime, and measures must be
introduced to license and oversee online pharmacies that operate or deliver
prescription drugs. Specifically, the online sale of narcotic drugs and
psychotropic substances, including amphetamine-type stimulants, should be
prohibited altogether, since it circumvents the existing national and
international control system.

CONCLUSIONS
The history of amphetamine-type stimulants over the past 70
years
demonstrates a remarkably cyclical and repetitive pattern,
with a series of
new drugs being introduced for therapeutic
purposes. Now, with approximately
35 million users, they have
become the second most widely used drugs in the
world. Enthusiastic
overprescription has contributed to recreational misuse
for
their stimulant properties, the development of dependence and
diversion to
the illicit market. Typically, the introduction
of a new therapeutic agent has
been accompanied by claims of
an absence of liability for misuse/dependence,
but initial
optimism has invariably been followed by a disappointing
realisation
that the new drug is being misused, with consequent growth in
demand for treatment. Between the late 1990s and 2004, demand
for
amphetamine-type stimulant treatment, expressed as a percentage
of all
drug-related treatment demand, increased from 12 to
19% in Oceania, from 12 to
17% in Asia, from 5 to 12% in North
America, from 8 to 10% in Europe and from
3 to 6% in Africa
(
United Nations Office
on Drugs and Crime, 2006). What is clearly
different now is the
global nature of misuse, with the internet
facilitating illicit trade and
widespread clandestine manufacture
on a previously unimaginable scale. This
makes a coordinated
global response an absolute necessity.

ACKNOWLEDGMENTS
Mrs Gisela Wieser-Herbeck of the International Narcotics Control
Board is
acknowledged for providing information about the use
of amphetamine-type
stimulants.

REFERENCES
- Addiction Research Foundation (1987)
Drugs and Drug Abuse (2nd edn), pp. 141
–142. ARF, Toronto.
- Ghodse, A. H. (1999) Dramatic increase in
methylphenidate consumption. Current Opinion in
Psychiatry, 12, 266
–268.
- Ghodse, A. H. (2002a) Drugs
and Addictive Behaviour: A Guide to Treatment (3rd edn).
Cambridge University Press.
- Ghodse, A. H. (2002b) E-drugs: the ATS
epidemic drugs. In Bridging the Gap: A Global Alliance Perspective
on Transnational Organised Crime 2002, pp. 205
–215. Hong Kong Police Force.
- Ghodse, A. H. & Kreek, M. J. (1998)
Resurgence of abuse of amphetamine type stimulants. Current Opinion
in Psychiatry, 11, 245
–247.[CrossRef]
- International Narcotics Control Board (1999)
Annual Report for 1998. UN Publications.
- Karen, A. & Laidler, J. (2002) The local
and global dimension of the ATS epidemic. In Bridging the Gap: A
Global Alliance Perspective on Transnational Organised Crime
2002, p. 237.
- Lineberry, T. W. & Bostwick, J. M. (2006)
Methamphetamine abuse: a perfect storm of complications. Mayo
Clinic Proceedings, 81, 77
–84 77–84[Abstract/Free Full Text]
- Mayer, S. (1996) Warning against overuse of
drugs for inattentive children. BMJ,
313, 770.[Free Full Text]
- Sadusk, J. P. (1968) Size and extent of the problem.
JAMA, 196, 707
–709.
- Tandy, K. P. (2005) Operation Cyber X Press
Conference (US Drug Enforcement Administration news release, 21 September
2005).
http://www.dea.gov/pubs/pressrel/pr092105b.html
- United Nations (2006) Psychotropic
Substances, Statistics for 2005 (E/INCB//2000/3). United
Nations.
- United Nations Office on Drugs and Crime (2006) World Drug
Report. Vol. 1: Analysis. United Nations Office on Drugs and Crime.
http://www.unodc.org/pdf/WDR_2006/wdr2006_volume1.pdf
- Weintraub, M. (ed.) (1992) Long-term weight
control study: the National Heart, Lung, and Blood Institute funded multimodal
intervention study. Clinical Pharmacological Therapy,
5, 581
–646.
- Woodworth, T. (2000) DEA Congressional Testimony
(May 16 2000).
http://www.dea.gov/pubs/cngrtest/ct0516ct051600.htm
Received for publication January 5, 2007.
Revision received May 1, 2007.
Accepted for publication May 3, 2007.