Addiction Rehab: Therapeutic Potential of Monoacylglycerol Lipase Inhibitors.

Therapeutic Potential of Monoacylglycerol Lipase Inhibitors.

Filed under: Addiction Rehab

Life Sci. 2012 Nov 7;
Mulvihill MM, Nomura DK

Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown benefitial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects that discourage their chronic usage, including cognitive deficits and gastrointestinal toxicity, respectively. Recent studies have uncovered that the serine hydrolase monoacylglycerol lipase (MAGL) links the endocannabinoid and eicosanoid systems together through hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) to provide the major arachidonic acid (AA) precursor pools for pro-inflammatory eicosanoid synthesis in specific tissues. Studies in recent years have shown that MAGL inhibitors elicit anti-nociceptive, anxiolytic, and anti-emetic responses and attenuate precipitated withdrawal symptoms in addiction paradigms through enhancing endocannabinoid signaling. MAGL inhibitors have also been shown to exert anti-inflammatory action in the brain and protect against neurodegeneration through lowering eicosanoid production. In cancer, MAGL inhibitors have been shown to have anti-cancer properties not only through modulating the endocannabinoid-eicosanoid network, but also by controlling fatty acid release for the synthesis of protumorigenic signaling lipids. Thus, MAGL serves as a critical node in simultaneously coordinating multiple lipid signaling pathways in both physiological and disease contexts. This review will discuss the diverse (patho)physiological roles of MAGL and the therapeutic potential of MAGL inhibitors in treating a vast array of complex human diseases.
HubMed – addiction


Early prediction of clinical and functional outcome in schizophrenia.

Filed under: Addiction Rehab

Eur Neuropsychopharmacol. 2012 Nov 6;
Agid O, Siu CO, Pappadopulos E, Vanderburg D, Remington G

The objective of this paper was to investigate the prognostic and predictive value of a small panel of independent and clinically important factors based on symptom improvement, baseline cognitive impairment, and weight change during the early treatment phase. METHODS: The study sample was based on a double-blind, 6-month continuation study of ziprasidone and olanzapine (N=94). We developed a parsimonious 6-month GAF prediction function using a logistic regression model, and evaluated its predictive accuracy and performance using bootstrap estimates of c-statistics and error in predicted probability. RESULTS: At up to 6 months of follow-up, 52 (55%) of all subjects treated with ziprasidone or olanzapine met the responder criterion of ?50% improvement in GAF. At Week 2 (acute phase), the majority of ziprasidone (75%) and olanzapine (70%) patients showed greater than 25% improvement in the BPRS psychotic symptom subscale score. These early psychotic symptom responders (Week 2) showed significantly greater improvement in global functioning than early non-responders at all time points (Week 6 and Month 6) (all p’s<0.05), confirming early response as an indicator of continued responsiveness to treatment over at least 6 months. A multivariate prediction function based on baseline neurocognitive scores and GAF, early reduction of psychotic symptoms at 2 weeks, and percentage of weight change observed at 6 weeks (All p's <0.05), showed statistically acceptable predictive performance (boostrap c-statistics=0.8598). CONCLUSIONS: Our findings suggest that a parsimonious model incorporating a psychotic symptom assessment score, baseline neurocognitive performance, and risk of weight gain can be developed for predicting patients' likelihood of achieving favorable, long-term treatment outcomes. HubMed – addiction


[Behavioral addictions.]

Filed under: Addiction Rehab

Presse Med. 2012 Nov 6;
Guillou-Landréat M, Grall-Bronnec M, Vénisse JL

Each addictive disorder has specific characteristics. It is essential to consider them in order to improve the treatment. However, the combination of behavioral addictions and substance use disorders is valid, as showed by the next version of the DSM. During the treatment, it is important to evaluate cross, but also longitudinal, considering the current problematic behavior, but also the problematic behaviors that occurred in the past and that may occur in the future. There is indeed a significant risk of switching addiction. The relapse prevention must consider this risk and be inclusive.
HubMed – addiction


Multidimensional family therapy lowers the rate of cannabis dependence in adolescents: A randomised controlled trial in Western European outpatient settings.

Filed under: Addiction Rehab

Drug Alcohol Depend. 2012 Nov 7;
Rigter H, Henderson CE, Pelc I, Tossmann P, Phan O, Hendriks V, Schaub M, Rowe CL

BACKGROUND: Noticing a lack of evidence-based programmes for treating adolescents heavily using cannabis in Europe, government representatives from Belgium, France, Germany, The Netherlands, and Switzerland decided to have U.S.-developed multidimensional family therapy (MDFT) tested in their countries in a trans-national trial, called the International Need for Cannabis Treatment (INCANT) study. METHODS: INCANT was a 2 (treatment condition)×5 (time) repeated measures intent-to-treat randomised effectiveness trial comparing MDFT to Individual Psychotherapy (IP). Data were gathered at baseline and 3, 6, 9 and 12 months thereafter. Study participants were recruited at outpatient secondary level addiction, youth, and forensic care clinics in Brussels, Berlin, Paris, The Hague, and Geneva. Participants were adolescents from 13 through 18 years of age with a recent cannabis use disorder. 85% were boys; 40% were of foreign descent. One-third had been arrested for a criminal offence in the past 3 months. Three primary outcomes were assessed: (1) treatment retention, (2) prevalence of cannabis use disorder and (3) 90-day frequency of cannabis consumption. RESULTS: Positive outcomes were found in both the MDFT and IP conditions. MDFT outperformed IP on the measures of treatment retention (p<0.001) and prevalence of cannabis dependence (p=0.015). MDFT reduced the number of cannabis consumption days more than IP in a subgroup of adolescents reporting more frequent cannabis use (p=0.002). CONCLUSIONS: Cannabis use disorder was responsive to treatment. MDFT exceeded IP in decreasing the prevalence of cannabis dependence. MDFT is applicable in Western European outpatient settings, and may show moderately greater benefits than IP in youth with more severe substance use. HubMed – addiction



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