We investigate the impacts of state legalization of products containing cannabidiol (CBD), a non‐psychoactive alternative to marijuana, on opioid prescribing rates. Research suggests that legalized ...medical marijuana may reduce opioid prescriptions, though no empirical link between CBD and opioids has been ascertained. Using county‐level prescribing rates between 2010 and 2019, as well as state‐level morphine milligram equivalent (MME) consumption of 8 common opioids, we estimate that state adoption of limited access cannabis product (CBD) laws leads to no change in opioid prescribing rates. Using supply‐side access measures for access to CBD through legal and open dispensaries, we find that the ability to purchase CBD legally leads to 6.6% to 8.1% fewer opioid prescriptions at pre‐legalization means, which suggests that access to CBD products is essential when evaluating the impacts of legalization; synthetic control model estimates suggest that legal and open dispensaries reduce opioid prescribing rates by nearly 3.5% 2 years post‐legalization. We also find that mandating CBD be purchased with an ID or through a patient registry offsets most potential benefits of CBD legalization. Our results provide the first empirical evidence that: (i) state legalization of prescription CBD alone does not reduce opioid usage; (ii) regulations limiting purchasing, such as ID laws, negate nearly all of the benefits of demand‐side legalization; and (iii) supply‐side access, either via interstate purchasing or legal and open dispensaries, are vital in using pain‐management substances to fully combat the opioid epidemic.
High-throughput and virtual screening are widely used to discover novel leads for drug design. On examination, many screening hits appear non-drug-like: they act noncompetitively, show little ...relationship between structure and activity, and have poor selectivity. Attempts to develop these peculiar molecules into viable leads are often futile, and much time can be wasted on the characterization of these "phony" hits. Despite their common occurrence, the mechanism of action of these promiscuous molecules remains unknown. To investigate this problem, 45 diverse screening hits were studied. Fifteen of these were previously reported as inhibitors of various receptors, including beta-lactamase, malarial protease, dihydrofolate reductase, HIV Tar RNA, thymidylate synthase, kinesin, insulin receptor, tyrosine kinases, farnesyltransferase, gyrase, prions, triosephosphate isomerase, nitric oxide synthase, phosphoinositide 3-kinase, and integrase; 30 were from an in-house screening library of a major pharmaceutical company. In addition to their original targets, 35 of these 45 compounds were shown to inhibit several unrelated model enzymes. These 35 screening hits included compounds, such as fullerenes, dyes, and quercetin, that have repeatedly shown activity against diverse targets. When tested against the model enzymes, the compounds showed time-dependent but reversible inhibition that was dramatically attenuated by albumin, guanidinium, or urea. Surprisingly, increasing the concentration of the model enzymes 10-fold largely eliminated inhibition, despite a 1000-fold excess of inhibitor; a well-behaved competitive inhibitor did not show this behavior. One model to explain these observations was that the active form of the promiscuous inhibitors was an aggregate of many individual molecules. To test this hypothesis, light scattering and electron microscopy experiments were performed. The nonspecific inhibitors were observed to form particles of 30-400 nm diameter by both techniques. In control experiments, a well-behaved competitive inhibitor and an inactive dye-like molecule were not observed to form aggregates. Consistent with the hypothesis that the aggregates are the inhibitory species, the particle size and IC(50) values of the promiscuous inhibitors varied monotonically with ionic strength; a competitive inhibitor was unaffected by changes in ionic strength. Unexpectedly, aggregate formation appears to explain the activity of many nonspecific inhibitors and may account for the activity of many promiscuous screening hits. Molecules acting via this mechanism may be widespread in drug discovery screening databases. Recognition of these compounds may improve screening results in many areas of pharmaceutical interest.
This paper examines the causal effect of earning a GED or vocational degree on future illicit drug use, employing random assignment into the United States' most comprehensive education and vocational ...training program for at-risk youth - Job Corps - as a source of exogenous variability in degree attainment. Nonparametric bounds under relatively weak monotonicity assumptions are constructed to allow the random assignment to violate the exclusion restriction when used as an instrument. We also use a fixed effect model and propensity score weighting to supplement the results. The results from different methods suggest that degree attainment may have the most significant effect in reducing the illicit drug use of blacks, while the results for whites and Hispanics are less conclusive.
Recreational cannabis and opioid distribution Raman, Shyam; Maclean, Johanna Catherine; Bradford, W. David ...
Health economics,
April 2023, Letnik:
32, Številka:
4
Journal Article
Recenzirano
Twenty‐one U.S. states have passed recreational cannabis laws as of November 2022. Cannabis may be a substitute for prescription opioids in the treatment of chronic pain. Previous studies have ...assessed recreational cannabis laws' effects on opioid prescriptions financed by specific private or public payers or dispensed to a unique endpoint. Our study adds to the literature in three important ways: by (1) examining these laws' impacts on prescription opioid dispensing across all payers and endpoints, (2) adjusting for important opioid‐related policies such as opioid prescribing limits, and (3) modeling opioids separately by type. We implement two‐way fixed‐effects regressions and leverage variation from eleven U.S. states that adopted a recreational cannabis law (RCL) between 2010 and 2019. We find that RCLs lead to a reduction in codeine dispensed at retail pharmacies. Among prescription opioids, codeine is particularly likely to be used non‐medically. Thus, the finding that RCLs appear to reduce codeine dispensing is potentially promising from a public health perspective.
Legalization of use and retail sales of recreational marijuana in U.S. states and the associated potential increase in access to marijuana and normalization of its use by adults could lead to ...increased use by adolescents. Studies have found that states with legal recreational marijuana have higher rates of adolescent use and frequency of use compared to states without legal use. We examined changes in student office discipline referrals (ODRs) for substance use offenses in Oregon middle and high schools before and after the legalization of recreational marijuana relative to comparison schools in other states. We found that rates of substance use related ODRs in middle schools increased by 0.14 per 100 students (30% of the mean) with legalization relative to comparison schools. This increase was moderated by the presence of a marijuana outlet within one mile of the school. We found no statistically discernible changes in high school ODRs. Marijuana use in adolescence has been linked to negative health and social consequences, including academic problems, mental health issues, and impaired driving. Potential adverse impact on adolescents and investments in school‐based prevention programs could be important considerations for policymakers and public health officials when evaluating marijuana legalization.
Understanding the relationships between human genetic factors, the risks of developing major diseases and the molecular basis of drug efficacy and toxicity is a fundamental problem in modern biology. ...Predicting biological outcomes on the basis of genomic data is a major challenge because of the interactions of specific genetic profiles with numerous environmental factors that may conditionally influence disease risks in a nonlinear fashion. 'Global' systems biology attempts to integrate multivariate biological information to better understand the interaction of genes with the environment. The measurement and modeling of such diverse information sets is difficult at the analytical and bioinformatic modeling levels. Highly complex animals such as humans can be considered 'superorganisms' with an internal ecosystem of diverse symbiotic microbiota and parasites that have interactive metabolic processes. We now need novel approaches to measure and model metabolic compartments in interacting cell types and genomes that are connected by cometabolic processes in symbiotic mammalian systems.
Using US panel data on young workers, we demonstrate that those who receive performance pay are more likely to consume alcohol and illicit drugs. Recognizing that this likely reflects worker sorting, ...we first control for risk, ability, and personality proxies. We further mitigate sorting concerns by introducing worker fixed effects, worker-employer match fixed effects, and worker-employer-occupation match fixed effects. Finally, we present fixed effect IV estimates. All of these estimates continue to indicate a greater likelihood of substance use when a worker receives performance pay. The results support conjectures that stress and effort increase with performance pay and that alcohol and drug use is a coping mechanism for workers.
Several studies have concluded that legalizing medical marijuana can reduce deaths from opioid overdoses. Drawing on micro data from the National Survey on Drug Use and Health, a survey uniquely ...suited to assessing patterns of substance use, we examine the relationship between recreational marijuana laws (RMLs) and the misuse of prescription opioids. Using a standard difference‐in‐differences (DD) regression model, we find that RML adoption reduces the likelihood of frequently misusing prescription opioids such as OxyContin, Percocet, and Vicodin. However, using a two‐stage procedure designed to account for staggered treatment and dynamic effects, the DD estimate of relationship between RML adoption and the likelihood of frequently misusing prescription opioids becomes positive. Although event study estimates suggest that RML adoption leads to a decrease in the frequency of prescription opioid abuse, this effect appears to dissipate after only 2 or 3 years.
Kriminalitet povezan s ilegalnim drogama odavno je predmetom različitih vrsta istraživanja - ponajprije usmjerenih na iznalaženje mogućnosti za njegovu prevenciju. Jedan od koncepata kroz koji se ...može promatrati ova povezanost jest i koncept kriminalne karijere. Ovaj se rad bavi povezanošću dobi i činjenja kaznenih djela povezanih s ilegalnim drogama kroz koncept kriminalne karijere. Glavni rezultati pokazuju kako ispitanici najčešće čine kazneno djelo krađe s ciljem pribavljanja sredstava za kupovanje ilegalnih droga te kako sudionici pod utjecajem droge najčešće čine kaznena djela krađe, odnosno razbojništva, neovisno o promatranoj dobi. U radu se nadalje prikazuje i povezanost drugih aspekata povezanosti kriminaliteta droga i određenih dobnih skupina, što je od važnosti prilikom izučavanja ovoga fenomena u svrhu prevencije, ali i penološkog tretmana počinitelja spomenutih kaznenih djela.
PDF
