Elementary particles for models of drug dependence : 10th Okey Memorial Lecture presented at the Institute of Psychiatry, London on 19th March 1997

Abstract

I begin by thanking the Institute of Psychiatry and the Psychiatry Research Trust for inviting me to present this lecture, the tenth given to preserve the memory of Thomas Okey. I am very pleased to see Mrs Okey with us today and continuing to support this important venture for dissemination of knowledge and ideas on drug dependence. This is also my inaugural lecture following conferment of the title Professor of Behavioural Pharmacology, and I am aware that inaugural lectures are intended to entertain as well as inform; I am also aware that I am as good at masquerading as an entertainer as the lead singer of the group East 17 would be masquerading as a psychopharmacologist. In fact, East 17 has claimed to know rather more about effects of drugs that I know about entertaining, so I will move straight on to consideration of one way in which laboratory psychopharmacologists can approach the problem of non-medical drug use. Current definitions of drug dependence in authoritative psychiatry manuals are not very helpful. One approach is exemplified by the DSM-IV criteria for substance dependence that may be very useful as a diagnostic check-list, but they are rather weak in terms of identifying basic processes amenable to study under controlled laboratory conditions. Another approach is the brain disease model which currently finds favour in some quarters. This model states unequivocally that dependence is a disease of the brain, that chronic exposure to drugs triggers changes at the molecular or cellular level that produce a sudden switch into a drug-dependent state which forms the basis for craving. Craving is then presented as an entity of central importance and even as the basis of a molecular target for drug treatment. If dependence is simply a brain disease then, taking into account the prevalence of tobacco and alcohol dependence as well as that of illicit drugs, it is a brain disease from which 40% or more of the population suffers. Is such a concept useful? This oversimplified model also presents drug dependence as an all-or-none state instead of as a continuum from low to high degrees of dependence, it elevates craving to almost mythical importance as the determining factor and it does nothing to integrate the contributions of the several psychological and behavioural processes already known to influence drugseeking. Craving, the urge to take a drug, may be not the cause of drug-seeking but the consequence of multiple factors operating upon an individual, as expressed in the multi-element models of dependence that I shall be talking about today. Turning to multi-element models, we see some of their characteristics in Fig. 1 that is derived from Stolerman (1992). These postulate that dependence is the result of multiple effects of drugs, that it is graded with respect to the degree of severity, that reasons for drug use vary among different people, that different factors are of more or less importance at different stages in the cycle of acquisition, maintenance, extinction and relapse to drug-taking behaviour. Importantly, the relevant psychopharmacological effects of abused drugs are seen as malleable, as variable according to both genetic influences and as a result of the previous history of the individual and current environmental circumstances. Equally important is the need to recog* Tel.: +44 171 9193370; fax: +44 171 7405305 1 The text of the lecture has been revised to render it stylistically appropriate for publication. The content has not been changed substantially from that presented.