Drug and alcohol dependence
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Drug Alcohol Depend · Dec 2009
ReviewRisk management of drug products and the U.S. Food and Drug Administration: evolution and context.
This paper summarizes the background and origins of pharmaceutical risk management and minimization principles and approaches as reflected in FDA statute, policy, and practice. It describes the history of early "risk management" programs, such as the patient package inserts (PPIs) introduced for oral contraceptives in 1976 and medication guides developed for products with safety concerns over the past decade. Exemplary products and programs that include restricted distribution systems such as the early clozapine "blood for drug" program are discussed. The principles and tools described in the US Food and Drug Administration (FDA) risk management guidances of 2005 are likely to be relied upon as the REMS (Risk Evaluation and Mitigation Strategies) mandated by the FDA Amendments Act (FDAAA) of 2007 are implemented.
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Drug Alcohol Depend · Nov 2009
Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception.
Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids. Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC. ⋯ Although THCV bound to the CB(1) receptor with similar affinity as Delta(9)-THC, it had no effects when administered alone, but antagonized the antinociceptive effects of Delta(9)-THC when both drugs were given in combination. Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching. These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC.
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Drug Alcohol Depend · Nov 2009
Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: risk factors and lives saved.
The small size of previous studies of mortality in opioid dependent people has prevented an assessment of the extent to which elevated mortality risks are consistent across time, clinical and/or patient groups. The current study examines reductions in mortality related to treatment in an entire treatment population. ⋯ Mortality among treatment-seeking opioid-dependent persons is dynamic across time, patient and treatment variables. The comparative reduction in mortality during buprenorphine induction may be offset by the increased risk of longer out-of-treatment time periods. Despite periods of elevated risk, this large-scale provision of pharmacotherapy is estimated to have resulted in significant reductions in mortality.
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Drug Alcohol Depend · Sep 2009
Using propensity scores to adjust for selection bias when assessing the effectiveness of Alcoholics Anonymous in observational studies.
The effectiveness of Alcoholics Anonymous (AA) is difficult to establish. Observational studies consistently find strong dose-response relationships between AA meeting attendance and abstinence, and the only experimental studies favoring AA have been of 12-step facilitation treatment rather than of AA per se. Pending future randomized trials, this paper uses propensity score (PS) method to address the selection bias that potentially confounds the effect of AA in observational studies. ⋯ These results confirm the robustness of AA effectiveness overall, because the results for higher abstinence associated with AA attendance following propensity score adjustment remained significant, and the reduction in the magnitude of AA's effect was moderate. However, the effect modification by propensity scores in both PS stratification and PS matching approaches seems to suggest that AA may be most helpful, or matter more, for those with a lower propensity to attend AA. Conversely, for those with a high propensity to go to AA (operationalized as higher motivation, greater problem severity, more prior AA and treatment exposure, etc.), attending AA may not make as much of a difference. It will be important that future studies replicate our results, as this is the first paper to use propensity score adjustment in this context.
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Drug Alcohol Depend · Sep 2009
Comparative StudyComparing overdose mortality associated with methadone and buprenorphine treatment.
To compare overdose mortality associated with methadone and buprenorphine treatment for opioid dependence. ⋯ In this short-term study, buprenorphine was associated with lower overdose risk than methadone.