Addiction Rehab: Inhibition of FAAH and Activation of PPAR: New Approaches to the Treatment of Cognitive Dysfunction and Drug Addiction.

Inhibition of FAAH and activation of PPAR: New approaches to the treatment of cognitive dysfunction and drug addiction.

Filed under: Addiction Rehab

Pharmacol Ther. 2013 Jan 16;
Panlilio LV, Justinova Z, Goldberg SR

Enhancing the effects of endogenously-released cannabinoid ligands in the brain might provide therapeutic effects more safely and effectively than administering drugs that act directly at the cannabinoid receptor. Inhibitors of fatty acid amide hydrolase (FAAH) prevent the breakdown of endogenous ligands for cannabinoid receptors and peroxisome proliferator-activated receptors (PPAR), prolonging and enhancing the effects of these ligands when they are naturally released. This review considers recent research on the effects of FAAH inhibitors and PPAR activators in animal models of addiction and cognition (specifically learning and memory). These studies show that FAAH inhibitors can produce potentially therapeutic effects, some through cannabinoid receptors and some through PPAR. These effects include enhancing certain forms of learning, counteracting the rewarding effects of nicotine and alcohol, relieving symptoms of withdrawal from cannabis and other drugs, and protecting against relapse-like reinstatement of drug self-administration. Since FAAH inhibition might have a wide range of therapeutic actions but might also share some of the adverse effects of cannabis, it is noteworthy that at least one FAAH-inhibiting drug (URB597) has been found to have potentially beneficial effects but no indication of liability for abuse or dependence. Although these areas of research are new, the preliminary evidence indicates that they might lead to improved therapeutic interventions and a better understanding of the brain mechanisms underlying addiction and memory.
HubMed – addiction

Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study.

Filed under: Addiction Rehab

Drug Alcohol Depend. 2013 Jan 17;
Dreifuss JA, Griffin ML, Frost K, Fitzmaurice GM, Potter JS, Fiellin DA, Selzer J, Hatch-Maillette M, Sonne SC, Weiss RD

BACKGROUND: Prescription opioid dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome. METHODS: A secondary analysis of data from a large multisite, randomized clinical trial, the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study (POATS) was undertaken to examine baseline patient characteristics (N=360) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence. Baseline predictor variables included self-reported demographic and opioid use history information, diagnoses assessed via the Composite International Diagnostic Interview, and historical opioid use and related information from the Pain And Opiate Analgesic Use History. RESULTS: In bivariate analyses, pre-treatment characteristics associated with successful opioid use outcome included older age, past-year or lifetime diagnosis of major depressive disorder, initially obtaining opioids with a medical prescription to relieve pain, having only used opioids by swallowing or sublingual administration, never having used heroin, using an opioid other than extended-release oxycodone most frequently, and no prior opioid dependence treatment. In multivariate analysis, age, lifetime major depressive disorder, having only used opioids by swallowing or sublingual administration, and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome. CONCLUSIONS: This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids. Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients’ response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone.
HubMed – addiction

Striatal Ups and Downs: Their Roles in Vulnerability to Addictions in Humans.

Filed under: Addiction Rehab

Neurosci Biobehav Rev. 2013 Jan 16;
Leyton M, Vezina P

LEYTON, M., Vezina, P. Striatal Ups and Downs: Their Roles in Vulnerability to Addictions in Humans. NEUROSCI BIOBEHAV REV XX(X) XXX-XXX, 2013. Susceptibility to addictive behaviors has been related to both increases and decreases in striatal function. Both profiles have been reported in humans as well as in animal models. Yet, the mechanisms underlying these opposing effects and the manner in which they relate to the behavioral development and expression of addiction remain unclear. In the present review of human studies, we describe a number of factors that could influence whether striatal hyper- or hypo-function is observed and propose a model that integrates the influence of these opposite responses on the expression of addiction related behaviors. Central to this model is the role played by the presence versus absence of addiction related cues and their ability to regulate responding to abused drugs and other rewards. Striatal function and incentive motivational states are increased in the presence of these cues and decreased in their absence. Alternations between these states might account for the progressive narrowing of interests as addictions develop and point to relevant processes to target in treatment.
HubMed – addiction

Pilot Randomized Trial of Bupropion for Adolescent Methamphetamine Abuse/Dependence.

Filed under: Addiction Rehab

J Adolesc Health. 2013 Jan 16;
Heinzerling KG, Gadzhyan J, van Oudheusden H, Rodriguez F, McCracken J, Shoptaw S

PURPOSE: To perform a pilot clinical trial of bupropion for methamphetamine abuse/dependence among adolescents. METHODS: Nineteen adolescents with methamphetamine abuse (n = 2) or dependence (n = 17) were randomly assigned to bupropion SR 150 mg twice daily or placebo for 8 weeks with outpatient substance abuse counseling. RESULTS: Bupropion was well-tolerated except for one female in the bupropion group who was hospitalized for suicidal ideation during a methamphetamine relapse. Adolescents receiving bupropion and females provided significantly fewer methamphetamine-free urine tests compared to participants receiving placebo (p = .043) and males (p = .005) respectively. CONCLUSIONS: Results do not support the feasibility of additional trials of bupropion for adolescent methamphetamine abuse/dependence. Future studies should investigate the influence of gender on adolescent methamphetamine abuse and treatment outcomes.
HubMed – addiction

Expression, Purification, and Structural Analysis of Intracellular C-Termini from Metabotropic Glutamate Receptors.

Filed under: Addiction Rehab

Methods Enzymol. 2013; 520C: 257-279
Seebahn A, Sticht H, Enz R

Glutamate is the most important excitatory neurotransmitter in the mammalian central nervous system (CNS). Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors (GPCRs) that guide several intracellular signal cascades thereby controlling multiple physiological tasks, such as neuronal excitability, learning, and memory. Consequently, these receptors are discussed in the context of several CNS-associated diseases, including addiction for drugs, Alzheimer’s disease, Fragile X syndrome, night blindness, or schizophrenia. Although increasing structural information is available for the extracellular and transmembrane domains of GPCRs, data describing the nature of intracellular receptor domains are largely missing. Indeed, in all available crystal structures of neurotransmitter receptors, their intracellular domains were omitted. Most intracellular mGluR C-termini are alternatively spliced and contain multiple binding sites for interacting proteins. Therefore, analyzing their structure can identify molecular mechanisms of receptor regulation. Recently, we analyzed the conformation of the intracellular C-termini of mGluR6, mGluR7a, and mGluR8a. Here, we describe an array of biochemical, biophysical, and computational techniques suited to elucidate the nature of these highly interesting receptor domains.
HubMed – addiction

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