Role of Kappa-Opioid Receptors in Stress and Anxiety-Related Behavior.

Role of kappa-opioid receptors in stress and anxiety-related behavior.

Psychopharmacology (Berl). 2013 Jul 9;
Van’t Veer A, Carlezon WA

Accumulating evidence indicates that brain kappa-opioid receptors (KORs) and dynorphin, the endogenous ligand that binds at these receptors, are involved in regulating states of motivation and emotion. These findings have stimulated interest in the development of KOR-targeted ligands as therapeutic agents. As one example, it has been suggested that KOR antagonists might have a wide range of indications, including the treatment of depressive, anxiety, and addictive disorders, as well as conditions characterized by co-morbidity of these disorders (e.g., post-traumatic stress disorder) A general effect of reducing the impact of stress may explain how KOR antagonists can have efficacy in such a variety of animal models that would appear to represent different disease states.Here, we review evidence that disruption of KOR function attenuates prominent effects of stress. We will describe behavioral and molecular endpoints including those from studies that characterize the effects of KOR antagonists and KOR ablation on the effects of stress itself, as well as on the effects of exogenously delivered corticotropin-releasing factor, a brain peptide that mediates key effects of stress.Collectively, available data suggest that KOR disruption produces anti-stress effects and under some conditions can prevent the development of stress-induced adaptations. As such, KOR antagonists may have unique potential as therapeutic agents for the treatment and even prevention of stress-related psychiatric illness, a therapeutic niche that is currently unfilled. HubMed – addiction


Spicing things up: synthetic cannabinoids.

Psychopharmacology (Berl). 2013 Jul 9;
Spaderna M, Addy PH, D’Souza DC

Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally.The availability, acute subjective effects-including self-reports posted on Erowid-laboratory detection, addictive potential, and regulatory challenges of the Spice phenomenon are reviewed.Spice is sold under the guise of potpourri or incense. Unlike delta-9-tetrahydrocannabinol, the synthetic cannabinoids present in Spice are high-potency, high-efficacy, cannabinoid receptor full agonists. Since standard urine toxicology does not test for the synthetic cannabinoids in Spice, it is often used by those who want to avoid detection of drug use. These compounds have not yet been subjected to rigorous testing in humans. Acute psychoactive effects include changes in mood, anxiety, perception, thinking, memory, and attention. Adverse effects include anxiety, agitation, panic, dysphoria, psychosis, and bizarre behavior. Psychosis outcomes associated with Spice provide additional data linking cannabinoids and psychosis. Adverse events necessitating intervention by Poison Control Centers, law enforcement, emergency responders, and hospitals are increasing. Despite statutes prohibiting the manufacture, distribution, and sale of Spice products, manufacturers are replacing banned compounds with newer synthetic cannabinoids that are not banned.There is an urgent need for better research on the effects of synthetic cannabinoids to help clinicians manage adverse events and to better understand cannabinoid pharmacology in humans. The reported psychosis outcomes associated with synthetic cannabinoids contribute to the ongoing debate on the association between cannabinoids and psychosis. Finally, drug detection tests for synthetic cannabinoids need to become clinically available. HubMed – addiction


Personality as a Predictor of Unprotected Sexual Behavior Among People Living with HIV/AIDS: A Systematic Review.

AIDS Behav. 2013 Jul 9;
Shuper PA, Joharchi N, Rehm J

The present investigation involved a systematic literature review to (1) identify associations between personality constructs and unprotected sex among people living with HIV/AIDS (PLWH); (2) assess patterns of direct versus indirect personality-risky sex associations; and (3) explore possible differences in personality-risky sex associations among PLWH versus non-infected populations. Among the 26 studies yielded through the systematic search, sensation seeking and sexual compulsivity were the constructs most frequently examined, with fewer studies investigating traditional personality typologies. Personality constructs that were more conceptually proximal to the sexual act, such as sexual compulsivity and sex-related sub-components of sensation seeking, showed relatively direct associations with unprotected sex, whereas more conceptually distal constructs such as generalized impulsivity demonstrated only weak or indirect associations. Associations were also frequently mediated by other risk factors, including perceived responsibility and substance use. These findings have implications for the development of interventions to reduce high risk sexual behavior among PLWH. HubMed – addiction


Prescription of topiramate to treat alcohol use disorders in the Veterans Health Administration.

Addict Sci Clin Pract. 2013 Jul 8; 8(1): 12
Del Re AC, Gordon AJ, Lembke A, Harris AH

As a quality improvement metric, the US Veterans Health Administration (VHA) monitors the proportion of patients with alcohol use disorders (AUD) who receive FDA approved medications for alcohol dependence (naltrexone, acamprosate, and disulfiram). Evidence supporting the off-label use of the antiepileptic medication topiramate to treat alcohol dependence may be as strong as these approved medications. However, little is known about the extent to which topiramate is used in clinical practice. The goal of this study was to describe and examine the overall use, facility-level variation in use, and patient -level predictors of topiramate prescription for patients with AUD in the VHA.Using national VHA administrative data in a retrospective cohort study, we examined time trends in topiramate use from fiscal years (FY) 2009–2012, and predictors of topiramate prescription in 375,777 patients identified with AUD (ICD-9-CM codes 303.9x or 305.0x) treated in 141 VHA facilities in FY 2011.Among VHA patients with AUD, rates of topiramate prescription have increased from 0.99% in FY 2009 to 1.95% in FY 2012, although substantial variation across facilities exists. Predictors of topiramate prescription were female sex, young age, alcohol dependence diagnoses, engagement in both mental health and addiction specialty care, and psychiatric comorbidity.Veterans Health Administration facilities are monitored regarding the extent to which patients with AUD are receiving FDA-approved pharmacotherapy. Not including topiramate in the metric, which is prescribed more often than acamprosate and disulfiram combined, may underestimate the extent to which VHA patients at specific facilities and overall are receiving pharmacotherapy for AUD. HubMed – addiction