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Recent advances in addiction research

A. Hamid Ghodsea and George A. Ricaurteb

Department of Psychiatry & Addictive Behaviour, Centre for Addiction Studies, St likely to bene®t from the various types of available
George's Hospital Medical School, London, UK, and bDepartment of Neurology,
Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA substance abuse therapies. Speci®cally, it appears crucial
to consider differences among the various drug classes,
Professor A. Hamid Ghodse, Department of Psychiatry & Addictive Behaviour, Centre
for Addiction Studies, St George's Hospital Medical School, 6th Floor Hunter Wing, as well as differences among target treatment groups,
Cranmer Terrace, London, SE17 0RE, UK because the ef®cacy of treatment may well vary between
Tel: +44 0208 672 9944; fax: +44 0208 725 2914
individuals who are considered to be at low risk and
Current Opinion in Psychiatry 2001, 14:163±165 those at high risk, due either to genetic or environmental
in¯uences. Finch (pp. 173±177), for example, details
# 2001 Lippincott Williams & Wilkins
®ndings of recent studies on social and cultural factors
that may in¯uence substance abuse, its consequences,
and its responsiveness to treatment. She highlights the
results of a recent Canadian study that indicated that the
The present issue of Current Opinion in Psychiatry perceived ill-health effects of smoking are greater among
contains an array of timely reviews that address a series groups with lower socioeconomic status [1]. Whether
of salient issues in the substance abuse ®eld. The perceived or real, this interesting ®nding serves to
reviews re¯ect the full and remarkable breadth of remind us that the adverse effects of drugs of abuse
approaches that are presently in use to further our may differ among individuals in different social or
understanding of drug abuse, its determinants, treatment cultural milieus. The fact that homelessness, stressful
options, treatment outcomes and consequences. work environment, and cultural norms and expectations
can in¯uence the use and abuse of psychoactive
Starting with prevention, London (pp. 207±211) notes substances should come as no surprise. However, these
that approaches that combine environmental and beha- are factors that are sometimes overlooked when trying to
vioural interventions with educational campaigns are understand and modify substance abuse and its deter-
often most effective, and emphasizes that measurable minants.
changes in outcome can now be documented. Clearly,
the effectiveness of various approaches, alone or in Substance abuse during pregnancy poses particular
combination, is ideally suited to controlled outcomes challenges for treatment, and some of these are
research, which must account not only for the interven- summarized by Jones and Johnson (pp. 187±193).
tion strategy, but also for the selection and evaluation of Despite the availability of selected effective pharma-
outcome variables. cotherapies (e.g. buproprion or nicotine replacement for
tobacco dependence), there is an understandable reti-
McNulty and Kouimtsidis (pp. 201±205) emphasize the cence of medical personnel to use drug-based therapies
compelling evidence that drug abuse treatment is in pregnant women for fear of potential adverse foetal
effective. They also comment on the wide range of consequences. In this regard, that there are also effective
markers of treatment success, such as detoxi®cation, behavioural±cognitive therapies deserves special atten-
protracted abstinence, reduced crime, diminished risk tion [2]. However, in certain situations (i.e. alcoholism),
behaviour and improved performance, among other the bene®ts of drug therapy may outweigh the risks of
indices. In some respects, it is not unreasonable to have exposing the developing brain to drugs during preg-
such a wide range of measures, because the best nancy, particularly in the light of the recently documen-
outcome measures for one drug class (e.g. opiates) may ted neurotoxic effects of prenatal alcohol exposure on
not generalize to another (e.g. stimulants), and because the developing central nervous system [3].
the available treatment modalities (e.g. substitution
therapies) may differ. Hence tailoring of outcomes Stimulant abuse by pregnant women is a vexing and
research to individual drug classes may be appropriate, growing problem, as illustrated by the ®ndings of
recognizing that certain common elements of evaluation Romano and Harvey [4] of learning and motor perfor-
may also be necessary. mance de®cits in animals with a history of prenatal
cocaine exposure. However, the relative paucity of
The authors also draw attention to the need to identify knowledge about the effects of stimulant abuse,
reliable prognostic indicators of which patient groups are particularly methamphetamine, during pregnancy is
164 Substance misuse

regrettable, and recent efforts by the National Institute drugs (whose effects are typically limited to axon
on Drug Abuse in the USA to stimulate research in this terminals) must be approached empirically and with
area [5] are laudable. Additional data are needed, not caution. In this regard, diffusion tensor imaging for
only on the teratogenic and long-term effects of studying particular axonal trajectories (e.g. medial
stimulant abuse during pregnancy, but also on novel forebrain bundle, ansa lenticularis) would appear to hold
approaches toward designing safe and effective stimulant special promise. However, sensitivity is an issue with
abuse pharmacotherapies. In this context, early reports this technique also. For instance, it is not yet clear
that the use of methadone for the treatment of opioid- whether it is suf®ciently sensitive to allow study of
dependent pregnant women is associated with better individual neuronal projections, such as the nigrostriatal
outcomes are encouraging, but neonatal withdrawal dopamine projection, either acutely after toxic drug
symptoms are not insigni®cant problems. Whether exposure, or chronically in the context of neurodegen-
buprenorphine represents a signi®cant step forward in erative illness.
the treatment of pregnant opiate-dependent women
remains to be seen. As highlighted by Jones and Johnson Ernst and Chefer also comment on the strengths of
in their review, more systematic research on substance neurone-speci®c positron emission tomography and
abuse treatment during pregnancy is sorely and urgently single-photon emission tomography imaging, emphasiz-
needed. ing two critically important points. First, they emphasize
the importance of distinguishing between the acute
Another group of substance misusers that attracts effects of drugs in the outcome measure (e.g. cocaine
particular attention is health care professionals. The effects on ligand binding to the dopamine transporters)
review of Bennett (pp. 195±200) suggests that, despite versus more enduring drug-induced neuronal changes
limitations in ascertainment methods, a signi®cant that are perhaps re¯ective of the addiction process or
fraction (up to 10±15% in one study) of physicians will drug-induced neuronal injury. Second, they underscore
develop a chemical dependency during their lifetime. the importance of fully characterizing the cohort to be
Interestingly, there is some indication that substance use studied, not only with respect to drug history (single
and abuse may vary according to specialty, with drug or polydrug abuse) and neuropsychiatric status, but
psychiatrists reporting some of the highest prevalence also with regard to genotype. In this vein, the ®ndings of
rates in one study [6]. Needless to say, this is a Heinz et al. [7] in alcoholic persons with changes in
signi®cant problem that, as emphasized by the author, serotonin transporter density are particularly noteworthy,
merits increased attention, both with regard to imple- as they hint at the importance of combining molecular
menting preventive measures and to minimizing the genetics with neurone-speci®c imaging in the study of
threat to patient care. substance abuse and its determinants or consequences.

New technologies are now being applied to substance Clinical genetics is another ®eld in which rapid
misuse research, and the ®ndings of recent neuroimaging advances are being made, with recent advances in
studies and the new vistas that they provide into brain our understanding of the genetics of substance abuse
changes associated with substance abuse are discussed vulnerabilities. The complexity of the drug abuse
by Ernst and Chefer (pp. 179±185). In addition to vulnerability trait is underscored, as is the fact that
highlighting the strengths of recently developed imaging there is probably a dynamic interplay between
technologies [e.g. functional magnetic resonance ima- genomic and environmental in¯uences. Perhaps not
ging and magnetic resonance spectroscopy (MRS)], surprisingly, the available genome-scanning results are
those authors adroitly underscore some of the potential not consistent with a single-gene model; instead, they
limitations of these modalities. For example, we are suggest polygenic models, in which multiple allelic
reminded that, although MRS can reliably report on variants contribute to addiction vulnerability. Whether
regional levels of N-acetylaspartate (NAA) and a few this re¯ects heterogeneity of the samples studied to
other brain chemicals in the living brain, it has limited date (users and abusers of licit and illicit substances
sensitivity (in the millimolar range). With regard to MRS, are often considered together), or whether substance
it is also worth remembering that its resolution is such abuse vulnerability is dictated by core tendencies that
that we cannot yet be entirely sure whether NAA is are unrelated to a particular drug class is not yet clear.
solely of neural origin, whether NAA reductions However, it seems safe to predict that, with the
(absolute or in relation to creatine) are always indicative advent of expedited genomic scanning made possible
of neural injury (acute or chronic), or whether NAA by recently developed array technology, we will soon
measures can detect neuronal injury that spares the have a clearer picture of the genetic substrates of
nerve cell body (i.e. is limited to axons and axon substance abuse vulnerability. Coupled with growing
terminals). Thus, the use of MRS to document the insight into environmental factors that in¯uence drug-
neurotoxic effects of methamphetamine and related taking behaviour, this genomic data has great potential
Addiction research: editorial comment Ghodse and Ricaurte 165

2 Jones HE, Haug NA, Stitzer ML, Svikis DS. Improving treatment outcomes
for enhancing our understanding of drug abuse for pregnant drug-dependent women using low-magnitude voucher incen-
determinants and developing even more effective tives. Addict Behav 2000; 25:263±267.
3 Ikonomidou C, Bittigau P, Ishimaru MJ, et al. Ethanol-induced apoptotic
neurodegeneration and fetal alcohol syndrome. Science 2000; 287:1056±
The huge range of topics and methodologies presented 1059.
in this section are a tribute to all of the contributing
4 Romano AG, Harvey JA. Prenatal cocaine exposure: long-term deficits in
authors, who are to be commended for their scholarly learning and motor performance. Ann NY Acad Sci 1998; 846:89±108.
work, and for their willingness to share with us their own
unique perspective of their ®eld. 5 Marwick C. NIDA seeking data on effect of fetal exposure to methamphe-
tamine. JAMA 2000; 283:2225±2226.

6 Hughes P, Storr C, Brandenburg N, et al. Physician substance misuse by

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