I n t h i s i s s u e...As already described in the Editorial, we felt that it wasof great importance to address the various problemsrelated to recent developments in addictive behaviors.However before turning to modern-day issues in addic-tion, we wished firstly to place it in a historical context.This was the task performed by Marc-Antoine Crocq, inthe first State of the art article (p 355). The theme of hisarticle is: The historical and cultural aspects of mansrelationship with addictive drugs.Recent scientific discoveries in the area of drug depen-dence, and the targets and mechanisms of action ofaddictive substances, have required a biologicalapproach. To this end we invited a contribution fromMary Jeanne Kreek; this is the second State of the artof this issue (p 363), and it focuses on perspectives fromthe Laboratory of the Biology of Addictive Diseases andrelated National Institutes of Health/National Institute onDrug Abuse Research Center.The variety and extent of available substances of abusehas changed the clinical picture of substance addiction.Addictions to a single substance have to a large extentgiven way to multiple addictions. The need for individu-als to satisfy their addictive personalities, and the ensu-ing generalized psychological dependence, thus pre-dominate over the addiction to a given substance. Thisnew scenario of substance addiction is clearly changingaddictive behaviors in general.The predominant trend appearing in modern times isbased on the weakening of barriers and of moral, social,and religious taboos, and thus on the resulting increasein opportunities and permissiveness. Psychologicaldependence now takes center stage in the clinical pictureof addiction, and in this context, addictive behavior isincreasing in keeping with the discovery of new sub-stances, or the abuse of substances designed for medic-inal use.We have attempted to target the areas about which weare asking the most questions. So, two Translationalresearch papers follow the State of the art. The firstone, by Martin P. Paulus (p 379) looks at the neural basisof reward and craving, and the second, from Peter W.Kalivas (p 389), provides a review of the neurocircuitryand glutamate neuroplasticity of cocaine and ampheta-mine-like stimulants.There are two Clinical research papers. The first one, byHenning Krampe, Sabina Stawicjki, Margret R. Hoehe,and Hannelore Ehrenreich (p 399) presents OLITAOut-patient Long-Term Intensive Therapy for Alcoholics. Thesecond, by Natalya M. Kogan and Raphael Mechoulam (p413) presents a review of the use and effects of cannabi-noids, both as a drug of addiction in healthy subjects andas a possible therapeutic option in certain diseases. The first Pharmacological aspects article, by Tracie J.Gardner and Thomas R. Kosten (p 431), provides a verycomprehensive look at the treatment options for sub-stance abuse, and the challenges that still remain in thisfield. Nadia S. Hejazi (p 447), in the second Pharmaco-logical aspects article, examines the pharmacogeneticsof addictive behaviors. And in the third Pharmacologi-cal aspects paper, Herbert D. Kleber (p 455) discussesthe range of pharmacologic options available for treat-ment of opioid dependence, and the associated detoxi-fication and maintenance options.Finally, the Poster by Margret Hoehe (p 471) presentsindividual differences in response to addictive substances,and the search for predisposing genetic aspects.As previously stated, this issue does not claim to discussexhaustively the theme of addictive behaviors, but ratherto examine specific problems posed in this field in currenttimes. We would like to warmly thank the variousauthors who have provided brilliant contributions to thisissue.Jean-Paul Macher, MD; Margret Hoehe, MD, PhD