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Contents

Editorial Pp. 1-2

Putative Role of Brain Acetaldehyde in Ethanol Addiction Pp. 3-8
Xin-sheng Deng and Richard A. Deitrich
[Abstract] [Full Text Article]

Associative Learning, the Hippocampus, and Nicotine Addiction Pp. 9-19
Jennifer A. Davis and Thomas J. Gould
[Abstract] [Full Text Article]

Incorporating Coping into an Expectancy Framework for Explaining Drinking Behaviour Pp. 20-35
Penelope A. Hasking and Tian P.S. Oei
[Abstract] [Full Text Article]

The Impact of Excessive Alcohol Use on Prospective Memory: A Brief Review Pp. 36-41
Thomas M. Heffernan
[Abstract] [Full Text Article]

Are Some Drinkers Resistant to Hangover? A Literature Review Pp. 42-46
Jonathan Howland, Damaris J. Rohsenow and Erika M. Edwards
[Abstract] [Full Text Article]

Alterations in Homocysteine Metabolism Among Alcohol Dependent Patients – Clinical, Pathobiochemical and Genetic Aspects Pp. 47-55
Ulrich C. Lutz
[Abstract] [Full Text Article]

Alcohol Abuse, Immunosuppression, and Pulmonary Infection Pp. 56-67
Ping Zhang, Gregory J. Bagby, Kyle I. Happel, Caroline E. Raasch and Steve Nelson
[Abstract] [Full Text Article]

Neurobiological and Psychosocial Processes Associated with Depressive and Substance-Related Disorders in Adolescents Pp. 68-80
Uma Rao and Li-Ann Chen
[Abstract] [Full Text Article]

The Chronic Effects of Cannabis on Memory in Humans: A Review Pp. 81-98
Nadia Solowij and Robert Battisti
[Abstract] [Full Text Article]

The Influence of Marijuana Use on Neurocognitive Functioning in Adolescents Pp. 99-111
Alecia D. Schweinsburg, Sandra A. Brown and Susan F. Tapert
[Abstract] [Full Text Article]

Abstracts

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Editorial: Current Drug Abuse – Time to be Reviewed

Literature that makes note of addiction and drug abuse goes back to ancient times. Alcohol was used in Egypt since the time of the Pharaohs [1] and ancient Greeks were already experienced with alcohol abuse and alcoholism [2, 3]. Ancient Greeks were also familiar with cannabis, and myths talk about nepenthes: a mysterious drug against any type of pain [4]. Throughout history, the use and abuse of alcohol and drugs has been playing a role in society.

In 1929, one of the first scientific papers in the field of addiction was published in the January issue of Science [5]. The paper revealed that a Committee on Drug Addiction was appointed in the USA to study the increasing problems related to drug addiction. Their most important goal was to substitute all existing addictive medicinal drugs such as morphine and cocaine by non-addictive alternatives with an equal clinical efficacy. To this extend the Universities of Virginia and Michigan took a leading role in developing and testing a series of new chemical compounds that should replace the addictive drugs.

Although the aims of the Committee were very ambitious, and cocaine has been largely banned from the medical profession, a search of the scientific literature reveals only few articles on addiction. In fact, until the end of the 1980s research on addiction resulted in about 100 scientific papers yearly or less, focusing primarily on treatment and prevention. As is evident from Fig. 1, during the 1990s addiction research expanded rapidly.

Fig. (1).
Until the 1990s, articles on addiction and drug abuse were scattered among the scientific literature. Thereafter the number of Universities and institutes involved in addiction research grew significantly, and currently there are about 30 international peer-reviewed journals devoted to drug abuse and addiction. The number of review papers and meta-analyses increased as well during the last decade.

To summarize the accumulative number of research papers that is currently emerging, the Journal Current Drug Abuse Reviews aims to publish the highest quality reviews and meta-analyses on all latest advances on alcohol and drug abuse and addiction. The Journal has a multidisciplinary scope and covers all the latest and outstanding developments in neurobiology, neuropsychopharmacology, addiction, behavioral effects, prevention, and treatment strategies on abuse of alcohol and both illicit and prescription drugs. The goal of the Journal is to be a reference source for anyone who wants a systematic overview of the available scientific evidence on topics related to drug abuse and addiction.

This inaugural issue comprises a number of superb reviews that are all related to three main topics: alcohol, learning and memory, and adolescence. I will highlight some of these reviews, because they address topics that have been somewhat overlooked by researchers over the last decades. For example, one review discusses the fact that some drinkers never report having an alcohol hangover, whereas this would be expected after a session of heavy drinking. The alcohol hangover is an exciting yet puzzling phenomenon since it remains to be elucidated why these symptoms are present after alcohol and it metabolites (e.g., acetaldehyde) are eliminated from the body. Unlike alcohol intoxication, the pathology of alcohol hangover has received very little scientific attention and studies that have been performed often yield inconclusive results [6]. The lack of scientific interest in the intriguing issue of alcohol hangovers is remarkable, since almost every drinker is familiar with the unpleasant hangover effects that may arise the day after an evening of excessive drinking, and the ways these symptoms may affect performance of (or even participation in) planned activities the day after drinking. The debate on alcohol hangovers will continue until research provides us with a clear view of its pathology. Simple explanations as if hangover is equivalent to dehydration or caused by the presence of acetaldehyde have proven to be insufficient to explain the general feeling of misery the day after excessive drinking. Hence, although experienced by many drinkers, it is still unknown what causes the alcohol hangover, a fact that is illustrated by the lack of effective hangover cures [7]. Until the pathology of hangovers is elucidated, the reasons why some drinkers never experience alcohol hangovers will probably remain a mystery.

Smoking and drinking remain popular among youth as is experimenting with other drugs. Adolescent drug abuse is a major problem as it may have serious consequences for themselves and those in their environment. These negative effects are not limited to short-term effects but may last much longer. For example, the adolescent brain is still in development and this process may be affected by drug use. This inaugural issue of Current Drug Abuse Reviews presents a review of the impact of adolescent cannabis use on brain functioning. Adolescents demonstrate persisting deficits related to heavy cannabis use for at least six weeks following discontinuation, particularly in the domains of learning and memory and working memory. The effects of chronic cannabis use on memory functioning are discussed in another review. Learning and remembering are psychological abilities that can be compromised by the use of alcohol and drugs. An important aspect of everyday remembering is prospective memory, which refers to the cognitive ability of remembering to carry out an intended action at some future point in time. Although it is obviously an important ability, researchers have paid little attention to prospective memory in their research. The inaugural issue of Current Drug Abuse Reviews comprises a concise review on the impact of excessive alcohol use on prospective memory.

Finally, I want to acknowledge that Current Drug Abuse Reviews would not have been established without the help of many people. First of all I would like to thank my Associate Editors – Patricia Conrod, Leslie Jacobsen, Sherry Stewart, and Maree Teesson – for their invaluable support in getting the Journal started. I am also very grateful for the members of our excellent International Editorial Advisory Board who helped a great deal with reviewing submissions and proposing welcome ideas to improve Current Drug Abuse Reviews. Finally, I would like to thank Mahvish Yousuf and Matthew Honan from Bentham Science Publishers for their support and believe that Current Drug Abuse Reviews is an important resource for anybody working in the field of or interested in drug abuse and addiction.

REFERENCES

[1] El-Guebaly N, El-Guebaly A. Alcohol abuse in ancient Egypt. The recorded evidence. Int J Addict 1981, 16: 1207-1221.

[2] Leibowitz JO. Acute alcoholism in Greek and Roman Medicine. Br J Addict 1957, 62: 83-86.

[3] Rolleston JD. Alcoholism in classical antiquity. British Journal of Inebriation 1927, 24: 101-120.

[4] Arata L. Nepethes and cannabis in ancient Greece. Janus Head 2004, 7: 34-49.

[5] White C. Committee on Drug Addiction of the National Research Council. Special correspondence. Science 1931, 73 (1882): 97-98.

[6] Verster JC, Van Duin D, Volkerts ER, Schreuder AHCML, Verbaten MN. Alcohol hangover effects on memory functioning and vigilance performance after an evening of binge drinking. Neuropsychopharmacology 2003, 28: 740-746.

[7] Pittler MH, Verster JC, Ernst E. Interventions for preventing or treating alcohol hangover: systematic review of randomized trials. Br Med J 2005, 331:1515-1518.

Joris C. Verster
(Editor-in-Chief)
Utrecht Institute for Pharmaceutical Sciences (UIPS)
Section Psychopharmacology (W038A)
Faculty of Science
University of Utrecht
P.O. Box 80082
3508 TB Utrecht
The Netherlands
E-mail: J.C.Verster@uu.nl

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Putative Role of Brain Acetaldehyde in Ethanol Addiction
Xin-sheng Deng and Richard A. Deitrich

[Full Text Article]

The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence (addiction) is reviewed. Although the role of AcH in EtOH addiction has been controversial, there are data showing a relationship. AcH can be formed in the brain tissues through the peroxidatic activity of catalase and by oxidation via other oxidizing enzymes such as cytochrome P-4502E1. Significant formation of AcH occurs in vitro in brain tissue at concentrations of EtOH that can be achieved by voluntary consumption of EtOH by rodents. AcH itself possesses reinforcing properties, which suggests that some of the behavioral pharmacological effects attributed to EtOH may be a result of the formation of AcH, and supports the involvement of AcH in EtOH addiction. Modulation of aldehyde dehydrogenase (ALDH) and brain catalase activity can change EtOH-related addictive behaviors presumably by changing AcH levels. Moreover, some condensation reaction products of AcH may promote some actions of EtOH and its consumption. On the basis of the findings, it can be concluded that AcH may mediate some of the CNS actions of EtOH including tolerance and dependence, although further exploration the involvement of AcH in EtOH addiction is warranted.

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Associative Learning, the Hippocampus, and Nicotine Addiction
Jennifer A. Davis and Thomas J. Gould

[Full Text Article]

The abuse liability of nicotine is comparable to or greater than that of a variety of addictive substances. However, the reinforcing and/or rewarding properties of addictive substances other than nicotine far outweigh the reinforcing and/or rewarding effects associated with nicotine use. These data suggest that, in addition to the intrinsic reinforcing effects of nicotine, other factors may contribute to nicotine addiction. One such factor is associative learning, or rather, the ability of nicotine to alter learning and memory processes that may underlie addiction. The present paper presents an overview of the role of learning in nicotine addiction. In addition, recent advances in the identification of behavioral processes, neural substrates, and cellular and molecular substrates that underlie nicotine-associated alterations in learning are reviewed. Particular attention has been paid to research that describes the role of the hippocampus and hippocampus-dependent learning processes in nicotine addiction.

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Incorporating Coping into an Expectancy Framework for Explaining Drinking Behaviour
Penelope A. Hasking and Tian P.S. Oei

[Full Text Article]

Expectancy Theory has offered much in the way of understanding alcohol use and abuse, and has contributed greatly to prevention and treatment initiatives. However although many cognitive-behavioural treatment approaches are based on expectancy constructs, such as outcome expectancies and self-efficacy, high relapse rates imply that expectancy theory may be too narrow in scope, and that additional variables need to be examined if a comprehensive understanding of drinking behaviour, and better treatment outcomes, are to be achieved. We suggest that the coping strategies an individual employs present one such set of variables that have largely been neglected from an expectancy framework. Although coping skills training is routinely used in prevention and treatment of alcohol problems, coping research has suffered from a poor theoretical framework. In this paper we review the existing research relating expectancies, self-efficacy and coping to drinking behaviour and propose a model which explains both social and dependent drinking, by incorporating coping into an expectancy theory framework. We also outline research and clinical implications of the proposed model.

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The Impact of Excessive Alcohol Use on Prospective Memory: A Brief Review
Thomas M. Heffernan

[Full Text Article]

Research into the cognitive consequences of chronic excessive alcohol use continues to grow. Despite this, little research has investigated what impact excessive alcohol use might have upon everyday remembering. An important aspect of everyday remembering is prospective memory (PM), which refers to the cognitive ability of remembering to carry out an intended action at some future point in time. The majority of the studies which have focused on what impact excessive alcohol use has upon PM in teenagers and young adults have consistently found that the excessive drinkers reported more lapses in their short term (e.g., forgetting to lock one’s door upon leaving home) and long term (e.g., forgetting to post a letter on time) aspects of everyday PM, when compared to low-dose alcohol users or non-users. It is concluded from this review that PM deficits should be added to the growing list of neuropsychological sequelae associated with excessive alcohol use. The magnitude of the effects of alcohol on PM depends upon the amount of alcohol consumed and how long one has been drinking. Major limitations of these studies include their reliance upon the use of self-report measures of PM, the issue of polydrug use complicating the picture, the need to control for the co-morbidity of other conditions - such as depression, and better drug-screening methods. Therefore, further studies need to employ objective measures alongside self-report measures of PM, incorporate better controls for the use of other drugs and mood states, as well as extending the focus of the research to study what effect different patterns of alcohol use might have upon PM, e.g., what impact binge drinking has upon everyday PM. These findings have educational and applied relevance within the alcohol field.

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Are Some Drinkers Resistant to Hangover? A Literature Review
Jonathan Howland, Damaris J. Rohsenow and Erika M. Edwards

[Full Text Article]

To assess the incidence of hangover we: (1) reviewed the experimental and survey literature; (2) performed secondary analyses on two large population surveys; and (3) calculated the incidence of hangover among young adults participating in several randomized trials we conducted on the aftereffects of heavy drinking. Survey data included adults admitted for alcohol detoxification, community adults who ever got “tipsy” or “high”, adolescents in high school who ever drank heavily, adults who drank heavily in the past 12 months, and university students. Most of the experimental trials brought participants to intoxication. The consistency of findings across study designs, populations, and referenced time period suggests that around 23% of the population may be resistant to hangover. Since propensity for hangover may affect drinking patterns, further research on the consequences and predictors of hangover insensitivity is warranted.

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Alterations in Homocysteine Metabolism Among Alcohol Dependent Patients – Clinical, Pathobiochemical and Genetic Aspects
Ulrich C. Lutz

[Full Text Article]

Addiction research focusing on homocysteine metabolism and its association with aspects of alcohol dependence has revealed important findings. Recent literature on this topic has been taken into account for the review provided.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the homocysteine metabolism. Plasma homocysteine levels are influenced by the single-nucleotide polymorphism (SNP) MTHFR C677T. Besides genetic factors, environmental factors have an impact on homocysteine plasma levels too. Thus, chronic alcohol intake is associated with elevated homocysteine plasma concentrations. Elevation of plasma homocysteine concentration is considered as a predictor for the occurrence of alcohol withdrawal seizures and – as homocysteine is a cardiovascular risk factor – might contribute to the higher risk for myocardial infarction among alcohol dependent patients.

Homocysteine acts as an N-methyl-D-aspartate (NMDA) receptor agonist and has excitotoxic effects. Furthermore, it has been demonstrated that homocysteine has neurotoxic effects especially on dopaminergic neurons. As the rewarding effects of alcohol are mediated by the dopaminergic system, a homocysteine-dependent impairment of the reward system possi-bly leads to an altered drinking behaviour according to the deficit hypothesis of addiction. Homocysteine is involved in the metabolism of methyl groups and DNA-methylation plays a role in regulation of gene expression. Therefore it has been suggested that homocysteine is an important epigenetic factor. It remains to be determined whether alcohol dependent patients benefit from homocysteine lowering strategies, e.g., via supplementation of folate, vitamin B6 and B12. In this respect it is not clear yet, if a supplementation therapy can reduce the risk for the occurrence of alcohol withdrawal seizures.

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Alcohol Abuse, Immunosuppression, and Pulmonary Infection
Ping Zhang, Gregory J. Bagby, Kyle I. Happel, Caroline E. Raasch and Steve Nelson

[Full Text Article]

Excessive alcohol consumption predisposes the host to a wide range of infectious complications, particularly pulmonary infections. Factors that contribute to the development of pulmonary infections in alcohol-abusing patients include dysfunction of the protective barriers in the respiratory tract, aspiration of oropharyngeal contents, nutritional deficiencies, liver disease, and impairment of host defense mechanisms. This review discusses the complex host-pathogen interactions in the airways with an emphasis on how alcohol consumption adversely affects these mechanisms and predisposes the host to infections. Potential immunomodulatory strategies for enhancing host defense function in alcohol-consuming patients are also discussed.

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Neurobiological and Psychosocial Processes Associated with Depressive and Substance-Related Disorders in Adolescents
Uma Rao and Li-Ann Chen

[Full Text Article]

Adolescents are at heightened risk for the development of both depressive and substance-related disorders. These two disorders frequently co-occur in adolescents and are associated with significant morbidity and mortality. Given the substantial economic and psychosocial burden associated with the comorbid condition, the identification of causal mechanisms associated with their co-occurrence is of great public health importance. Although there is significant under-standing of the environmental and neurobiological factors involved in depression and addictive disorders considered separately, the mechanisms underlying the comorbid illness have not been investigated carefully. The purpose of this review is to summarize the extant literature on genetic, environmental and neurobiological processes involved in the etiology of de-pressive and substance-related disorders in adolescents and adults. It is important to note that the data on common neuro-biological systems that link addictive and depressive disorders are primarily from research with adult animals and humans. Given the ongoing maturation of these systems throughout adolescence and early adult life, it is not clear how these neurobiological processes influence the development and progression of both disorders. A better understanding of the pathophysiological mechanisms leading to the onset and course of these disorders during adolescence will be helpful in developing more effective preventive and treatment strategies not only for this population but also for adult patients with early-onset illness.

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The Chronic Effects of Cannabis on Memory in Humans: A Review
Nadia Solowij and Robert Battisti

[Full Text Article]

Memory problems are frequently associated with cannabis use, in both the short- and long-term. To date, reviews on the long-term cognitive sequelae of cannabis use have examined a broad range of cognitive functions, with none specifically focused on memory. Consequently, this review sought to examine the literature specific to memory function in cannabis users in the unintoxicated state with the aim of identifying the existence and nature of memory impairment in cannabis users and appraising potentially related mediators or moderators. Literature searches were conducted to extract well-controlled studies that investigated memory function in cannabis users outside of the acute intoxication period, with a focus on reviewing studies published within the past 10 years. Most recent studies have examined working memory and verbal episodic memory and cumulatively, the evidence suggests impaired encoding, storage, manipulation and retrieval mechanisms in long-term or heavy cannabis users. These impairments are not dissimilar to those associated with acute intoxication and have been related to the duration, frequency, dose and age of onset of cannabis use. We consider the impact of not only specific parameters of cannabis use in the manifestation of memory dysfunction, but also such factors as age, neurodevelopmental stage, IQ, gender, various vulnerabilities and other substance-use interactions, in the context of neural efficiency and compensatory mechanisms. The precise nature of memory deficits in cannabis users, their neural substrates and manifestation requires much further exploration through a variety of behavioural, functional brain imaging, prospective and genetic studies.

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The Influence of Marijuana Use on Neurocognitive Functioning in Adolescents
Alecia D. Schweinsburg, Sandra A. Brown and Susan F. Tapert

[Full Text Article]

Marijuana use is common in adolescence, yet neural consequences have not been well delineated. This review seeks to ascertain whether heavy marijuana use in adolescence is associated with persistent neurocognitive abnormalities, and whether adolescents are more vulnerable to the impact of chronic marijuana use than adults.

Among heavy marijuana using adults, neurocognitive deficits are apparent for several days following use, but may disappear after one month of abstinence. Studies of adolescent heavy users have identified impairments in learning and work-ing memory up to six weeks after cessation, suggesting persisting effects, yet raise the possibility that abnormalities may remit with a longer duration of abstinence.

Given ongoing neuromaturation during youth, adolescents may be more vulnerable to potential consequences of marijuana use than adults. This is supported by rodent models, which show greater memory impairments in animals exposed to cannabinoids as adolescents relative to those exposed as adults. Further, adult humans who initiated use in early adoles-cence show greater dysfunction than those who began use later. Together, these results suggest that adolescents are more vulnerable than adults to neurocognitive abnormalities associated with chronic heavy marijuana use; however, the impact of preexisting risk factors is unknown.

Adolescents demonstrate persisting deficits related to heavy marijuana use for at least six weeks following discontinuation, particularly in the domains of learning, memory, and working memory. Further, adolescents appear more adversely affected by heavy use than adults. Longitudinal studies will help ascertain whether preexisting differences contribute to these abnormalities.