PubMed · 16128710
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Sten Rönnberg. 2005. Steps toward responsibility.. https://doi.org/10.1111/j.1360-0443.2005.01202.x
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Despite an estimated heritability of ~50%, genome-wide association studies of opioid use disorder (OUD) have revealed few genome-wide significant loci. We conducted a cross-ancestry meta-analysis of OUD in the Million Veteran Program (N = 425,944). In addition to known exonic variants in OPRM1 and FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1 and KCNN1. A meta-analysis including other datasets identified a locus in TSNARE1. In total, we identified 14 loci for OUD, 12 of which are novel. Significant genetic correlations were identified for 127 traits, including psychiatric disorders and other substance use-related traits. The only significantly enriched cell-type group was CNS, with gene expression enrichment in brain regions previously associated with substance use disorders. These findings increase our understanding of the biological basis of OUD and provide further evidence that it is a brain disease, which may help to reduce stigma and inform efforts to address the opioid epidemic.
Impulsivity in drug addicts have been associated with impatience in intertemporal choice, i.e., high degrees to which delayed rewards are discounted, indicating the importance of reducing the degree of discounting in drug addicts. Intertemporal choice (delay discounting) has been attracting attention in neuropsychopharmacology and behavioral neuroeconomics. Recently, behavioral economists have reported that impatience/impulsivity in intertemporal choice is increased if a delay period is presented as a sum of divided time-blocks, which is referred to as subadditive discounting (i.e., "total patience" over the delay period is larger than the "sum of patience" over divided delay periods). This finding implies that abstinent drug addicts may more readily relapse into addiction if an abstinence period is presented as a series of shorter abstinent periods, rather than a single block of a long abstinence period. Therefore, understanding of neuropsychological processing underlying subadditive discounting is important for establishing medical treatments of drug addiction, although to date, no study has addressed this question. In this study, we propose that time-estimation following Weber-Fechner law, formerly introduced for explaining hyperbolic discounting, may also explain subadditive discounting. Our present hypothesis also predicts that possibility of relapse into drug dependence can be decreased by helping abstinent patients to perceive time-duration of an abstinence/withdrawal period precisely.
Tobacco use is dominated by cigarette smoking. Most toxicity due to cigarette smoking is related to the burning process. Several observations suggest that unburned or oral tobacco is less harmful than cigarette smoking. Up to now, physicians have advised a policy based on two ideas: (i) young people should not start smoking and (ii) the only choice for smokers is to quit. However, numerous smokers cannot or do not want to give up; eventually, one out of two lifelong smokers will die from smoke-related diseases. Thus, it is legitimate to ask if alternate nicotine containing product use would be better than cigarette smoking and limit the tobacco death toll. However, the logic leading to the concept of tobacco harm reduction (THR) turns out to be much more complex than it looks at a first glance.