ABSTRACT
In the last decade, there has been an upsurge of interest in understanding the mechanisms of behavior change (MOBC) and effective behavioral interventions as a strategy to improve addiction-treatment efficacy. However, there remains considerable uncertainty about how treatment research should proceed to address the MOBC issue. In this article, we argue that limitations in the underlying models of addiction that inform behavioral treatment pose an obstacle to elucidating MOBC. We consider how advances in the cognitive neuroscience of addiction offer an alternative conceptual and methodological approach to studying the psychological processes that characterize addiction, and how such advances could inform treatment process research. In addition, we review neuroimaging studies that have tested aspects of neurocognitive theories as a strategy to inform addiction therapies and discuss future directions for transdisciplinary collaborations across cognitive neuroscience and MOBC research.
Subject(s)
Behavior Therapy/methods , Behavior, Addictive , Neuroimaging/methods , Neurosciences , Substance-Related Disorders , Behavior, Addictive/physiopathology , Behavior, Addictive/psychology , Behavior, Addictive/therapy , Brain/pathology , Brain/physiopathology , Cognition , Humans , Psychological Theory , Randomized Controlled Trials as Topic , Recurrence , Research Design , Substance-Related Disorders/physiopathology , Substance-Related Disorders/psychology , Substance-Related Disorders/therapy , Treatment OutcomeABSTRACT
To assess safety and tolerability, we administered valacyclovir, an oral anti-viral medication that inhibits erythrocyte sickling in vitro, to 14 subjects with sickle-cell anemia for 1 week at a standard dose of 1,000 mg every 8 hr. No clinically significant adverse effects occurred. In 11 subjects in steady state, the mean hemoglobin concentration was almost constant while the absolute reticulocyte count decreased in eight (P = 0.1) and the overall mean fell slightly although not significantly (10%, P = 0.2). These results suggest that valacyclovir is safe and well tolerated in patients with sickle-cell anemia and that a longer duration of therapy merits investigation.
Subject(s)
Acyclovir/analogs & derivatives , Anemia, Sickle Cell/drug therapy , Antisickling Agents/therapeutic use , Antiviral Agents/therapeutic use , Erythrocytes, Abnormal/drug effects , Valine/analogs & derivatives , Acyclovir/therapeutic use , Adolescent , Adult , Female , Hemoglobins/analysis , Humans , Male , Maximum Tolerated Dose , Prodrugs , Prospective Studies , Safety , Survival Rate , Treatment Outcome , Valacyclovir , Valine/therapeutic use , Young AdultABSTRACT
As a result of an in vitro screening effort the antiviral agent acyclovir was found to inhibit aggregation of hemoglobin S and the sickling of erythrocytes from individuals with sickle cell disease. Sickling of the erythrocytes was significantly inhibited at 200 microg/ml under essentially anaerobic conditions, considerably more hypoxic than the conditions in which sickling occurs in sickle cell patients. The structurally related guanine-based antiviral agents ganciclovir, valacyclovir, and penciclovir were also tested. Valacyclovir and ganciclovir showed comparable anti-sickling activity at concentrations similar to that of acyclovir. An examination of the shared structural characteristics of the four guanine derivatives linked anti-sickling activity to the presence of an oxygen atom alpha to the N9 of the guanine moiety. These findings suggest a new approach in the search for new agents for the treatment of patients with sickle cell disease.
