PREFACE TO THE SPECIAL ISSUE ARTICLES ON ALCOHOL AND CANNABIS

GIANCARLO COLOMBO*

C.N.R. Institute of Neuroscience, Section of Cagliari, Cagliari, Italy

* Correspondence: C.N.R. Institute of Neuroscience, Section of Cagliari, Viale Diaz, 182, I-09126 Cagliari (CA), Italy. Tel.: +39 070 302227; Fax: +39 070 302076; E-mail: colomb{at}unica.it

In recent years, accumulating lines of experimental evidence have suggested that the endocannabinoid system is a major player among the neurotransmitter systems involved in the neurobiology of alcohol. This progress has been originated from a series of important findings, including, among others, the discovery and the subsequent cloning of specific receptors for cannabinoids in the CNS, the identification of endogenous ligands and enzymes involved in ligand biosynthesis and inactivation, the synthesis of potent agonists and antagonists and the development of mice with deletions of genes that encode for cannabinoid receptors or enzymes involved in cannabinoid metabolism. When applied to the research field alcohol, these lines of information have led to some understanding of the involvement of the endocannabinoid system in the regulation of different alcohol-related phenomena including tolerance, vulnerability, reinforcement, consumption and metabolism. Novel, potentially effective pharmacotherapeutic strategies based on cannabinoid CB1 receptor antagonists have been generated from this research.

Owing to an increasing interest in this research field, the journal Alcohol and Alcoholism dedicates a special issue to alcohol and cannabis with the intention of providing a review of the research findings collected to date as well as presenting new research data. This issue begins with a comprehensive review by Fernando Rodríguez de Fonseca and colleagues from the Universidad Complutense, Madrid, Spain, on the physiology and pharmacology of the endocannabinoid system. This paper aims to provide the reader with basic information on the endocannabinoid system, allowing a further appreciation of the subsequent papers focusing on alcohol.

Over the years, Balapal Basavarajappa and Appa Hungund from the Nathan Kline Institute for Psychiatry Research, New York, USA, have made a considerable experimental effort towards understanding the involvement of the endocannabinoid system in the development of tolerance to alcohol. They have also profitably investigated the effect of alcohol exposure on the binding characteristics of the cannabinoid CB1 receptor and on the synthesis and levels of endocannabinoids. Their paper reviews these different lines of experimental evidence. Basavarajappa and Hungund also describe some recent, interesting data suggesting the involvement of the cannabinoid CB1 receptor system in the mesolimbic dopaminergic mediation of the reinforcing properties of alcohol.

Jorge Manzanares and colleagues from the Hospital Universitario 12 de Octubre, Madrid, Spain, contribute with an extensive review on the ‘cross-talk’ between the endogenous cannabinoid and opioid neurotransmitter systems, focusing on the contribution of this interaction to the mediation of several effects of alcohol, vulnerability to the development of alcohol dependence and, possibly, definition of new medications for the treatment of alcoholism.

Iain McGregor and colleagues from the University of Sydney, Australia, have conducted a number of interesting studies demonstrating that different cannabinoid CB1 receptor agonists stimulated, while the cannabinoid CB1 receptor antagonist, SR 141716 (rimonabant), inhibited, the motivation to consume alcohol in a rat model of alcoholism. These data are briefly reviewed in their paper. Further, McGregor and colleagues report the results of a series of recent experiments where they extended their pharmacological studies with cannabinoids to the reinstatement of self-administration of alcohol in rats, an elegant and validated model of the relapse episodes that occur in human alcoholics.

SR 141716 has long been the only cannabinoid CB1 receptor antagonist used in pharmacological studies on alcohol-related behaviours. All studies unequivocally reported its ability to reduce the appetitive and consummatory aspects of alcohol-drinking behaviour in rats and mice tested under multiple experimental procedures. In the present issue, Gian Luigi Gessa and colleagues from the C.N.R. Institute of Neuroscience, Cagliari, Italy, report how the recently synthesized cannabinoid CB1 receptor antagonist, SR 147778, closely replicated the reducing effect of SR 141716 on alcohol intake and motivational properties of alcohol in a rat model of excessive alcohol consumption. These results feature SR 147778 as a new interesting research tool and, possibly, a novel therapeutic strategy.

Over the last few years, cannabinoid CB1 receptor knockout mice have been used extensively in the research field of alcohol. As predictable from the results of pharmacological studies using cannabinoid CB1 receptor antagonists, CB1 knockout mice generally consumed less alcohol and displayed a lower preference for alcohol than their wild-type counterparts. Frédérick Lallemand and Philippe De Witte from the Catholic University of Louvain, Louvain-la-Neuve, Belgium, apart from reviewing the literature data on alcohol-related behaviours in these mice, provide new, important research data demonstrating that CB1 knockout mice may have some alterations in alcohol absorption/distribution.

In conclusion, I wish to express my gratitude to the Chief editors for dedicating a journal issue to this research subject and to all the authors for their excellent and timely contributions.





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