Change is possible: the history of the international drug control regime and implications for future policymaking.

The article, based upon an extensive literature review, reconstructs and analyzes the parallel evolution of the international drug control regime and the world opiate market, assessing the impact of the former on the latter until the rise of present-day mass markets. It shows that, since its inception, the regime has focused almost entirely on matters of supply. However, that focus has not always meant "prohibition"; until 1961, the key principle of the regime was "regulation." Given the different forms drug control policy has taken in the past, the authors conclude it may be amenable to new forms in the future.

Illicit synthetic opioid consumption in Asia and the Pacific: Assessing the risks of a potential outbreak.

BACKGROUND: Illegally manufactured potent synthetic opioids (IMPSO) like fentanyl have contributed to rises in overdose deaths in parts of North America and Europe. While many of these substances are produced in Asia, there is little evidence they have entered markets there. We consider the susceptibility to IMPSO's encroachment in markets in the Asia-Pacific region. METHODS: Our analysis focuses on Australia, China, India, and Myanmar. Using a mixed-methods approach comprising interviews, literature review, and secondary data analyses, we examine factors facilitating or impeding incursion of IMPSO. Finally, we illustrate the potential for IMPSO fatalities in Australia. RESULTS: Australia reports some signs of three facilitating factors to IMPSO's emergence: 1) existing illicit opioid markets, 2) disruption of opioid supply, and 3) user preferences. The other three countries report only existing illicit opioid markets. While diverted pharmaceutical opioids are a noted problem in Australia and India, heroin is the dominant opioid in all four countries. There are divergent trends in heroin use, with use declining in China, increasing in India, and stable in Australia and Myanmar. If IMPSO diffused in Australia as in North America from 2014 to 2018, and our assumptions generally hold, deaths from IMPSO could range from 1500-5700 over a five-year period. CONCLUSIONS: This analysis and illustrative calculations serve as an early indication for policymakers. With the exception of Australia, many countries in the region fail to properly record overdose deaths or monitor changes in local drug markets. Early assessment and monitoring can give officials a better understanding of these changing threats.

Recent advances in nonalcholic fatty liver disease.

PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances in defining the clinical features, pathophysiology, natural history, and treatment of nonalcoholic fatty liver disease. RECENT FINDINGS: Nonalcoholic fatty liver disease is present in approximately 30% of the US population. A histologic grading and staging system has been developed and validated. Nonalcoholic fatty liver disease increases the risk of developing the metabolic syndrome. The presence and severity of nonalcoholic fatty liver disease correlates with the severity of obesity, fat distribution, age, and presence of other features of the metabolic syndrome. Fifteen to 20% of subjects with nonalcoholic steatohepatitis develop cirrhosis. Hepatic steatosis is associated with an increase in both free fatty acid delivery to the liver for re-esterification and increased de-novo lipogenesis. Several mechanisms of hepatocyte injury and death including free fatty acid toxicity, increased free cholesterol, cytokine-mediated injury and activation of the unfolded protein response have been defined. While many therapeutic targets have been identified and pilot studies performed, a definitive treatment for nonalcoholic steatohepatitis remains to be established. SUMMARY: Nonalcoholic fatty liver disease is a widely prevalent disease that is critically linked to insulin resistance and the metabolic syndrome. While much new information on the pathogenesis and natural history of nonalcoholic steatohepatitis is available, an effective therapy remains to be established.

Research as due diligence: What can supply-side interventions accomplish and at what cost?

Supply-side interventions, which we define as laws, regulations, enforcement activities, and other measures that extend from drug production to dealing, feature prominently in drug policy and related expenditures internationally, but have undergone relatively little rigorous, empirical evaluation. We argue for filling the knowledge gap and highlight three areas of particular concern: first, the policy community knows less than it should about the efficacy of supply-side interventions; second, it lacks sufficient understanding of the scope, magnitude, and practical implications of adverse consequences that accompany such interventions; third, it lacks tools to gauge the balance of benefits and costs, both monetary and non-monetary. Our interest has been in developing a harm-based approach to address these concerns and we put forward a "harm assessment framework" for that purpose.

If supply-oriented drug policy is broken, can harm reduction help fix it? Melding disciplines and methods to advance international drug-control policy.

Critics of the international drug-control regime contend that supply-oriented policy interventions are not just ineffective, but, in focusing almost exclusively on supply reduction, they also produce unintended adverse consequences. Evidence from the world heroin market supports their claims. The balance of the effects of policy is yet unknown, but the prospect of adverse consequences underlies a central paradox of contemporary supply-oriented policy. In this paper, we evaluate whether harm reduction, a subject of intense debate in the demand-oriented drug-policy community, can provide a unifying foundation for supply-oriented drug policy and speak more directly to policy goals. Our analysis rests on an extensive review of the literature on harm reduction and draws insight from other policy communities' disciplines and methods. First, we explore the paradoxes of supply-oriented policy that initially motivated our interest in harm reduction; second, we consider the conceptual and technical challenges that have contributed to the debate on harm reduction and assess their relevance to a supply-oriented application; third, we examine responses to those challenges, i.e., various tools (taxonomies, models, and measurement strategies), that can be used to identify, categorize, and assess harms. Despite substantial conceptual and technical challenges, we find that harm reduction can provide a basis for assessing the net consequences of supply-oriented drug policy, choosing more rigorously amongst policy options, and identifying new options. In addition, we outline a practical path forward for assessing harms and policy options. On the basis of our analysis, we suggest pursuing a harm-based approach and making a clearer distinction between supply-oriented and supply-reduction policy.

The global diversion of pharmaceutical drugs. India: the third largest illicit opium producer?

AIMS: This paper explores India's role in the world illicit opiate market, particularly its role as a producer. India, a major illicit opiate consumer, is also the sole licensed exporter of raw opium: this unique status may be enabling substantial diversion to the illicit market. METHODS: Participant observation and interviews were carried out at eight different sites. Information was also drawn from all standard secondary sources and the analysis of about 180 drug-related criminal proceedings reviewed by Indian High Courts and the Supreme Court from 1985 to 2001. FINDINGS: Diversion from licit opium production takes place on such a large scale that India may be the third largest illicit opium producer after Afghanistan and Burma. With the possible exceptions of 2005 and 2006, 200-300 tons of India's opium may be diverted yearly. After estimating India's opiate consumption on the basis of UN-reported prevalence estimates, we find that diversion from licit production might have satisfied a quarter to more than a third of India's illicit opiate demand to 2004. CONCLUSIONS: India is not only among the world's largest consumer of illicit opiates but also one of the largest illicit opium producers. In contrast to all other illicit producers, India owes the latter distinction not to blatantly illicit cultivation but to diversion from licit cultivation. India's experience suggests the difficulty of preventing substantial leakage, even in a relatively well-governed nation.