The model includes a linear time variable to account for broader trends like growth in lobbying from distributed solar. I estimate multilevel models with random effects at the firm, state, and year levels to account for the hierarchical structure of the data. In column of Table 2, the outcome variable is a binary measure of whether a firm lobbied in a particular state-year .In column , the outcome variable is the total number of lobbying registrations attributed to a particular firm . For this specification, I estimate a negative binomial model since the outcome is an over dispersed count variable . Finally, in column , the outcome is logged lobbying expenditures for the limited sample of states for which these data are available. Across specifications, results, presented in Table 2, indicate that firm lobbying in a state is increasing in its installed TPO capacity in that state and its installed capacity in other states . The coefficients in column indicate that a doubling of in-state capacity is associated with an 8-percentage point increase in the likelihood of an installer lobbying, while a doubling of out-of-state capacity is associated with a 5-percentage point increase likelihood of an installer lobbying in any particular state. Results from the negative binomial model also indicate that both in-state and out-of-state capacity matter for lobbying. The coefficient of .47 in column suggests that a 1 percent increase in in-state capacity installed for a firm is associated with a .47 percent increase in number of retained lobbyists in that state ; the coefficient of .48 indicates that a 1 percent increase in out-of-state capacity is associated with a .48 percent increase in number of retained lobbyists in a given state . I recover consistent results in the limited sample of states using logged lobbying expenditures as the outcome in a linear model. The coefficients suggest that a doubling of in-state capacity is associated with a 71 percent increase in lobbying expenditures,hydroponic shelf system while a doubling of out-of-state capacity is associated with an 85 percent increase in lobbying expenditures in any particular state.

By showing that firm lobbying in any particular state depends on firm economic strength both within that state and across the states, these findings also suggests that policy in one state affects lobbying in another. That’s because state policy affects installer business growth , which in turn drives installer lobbying across the states due to the horizontal mobilization of firms. A particularly important case of cross-state feedback is where firms apply growth in states with favorable policy environments to seek to shape policy in potential new markets. To examine this dynamic, I track the economic and political presence across the states over time for the two largest and most politically active rooftop solar firms over the period: Sunrun and SolarCity. As illustrated by Table 3, both firms significantly expanded their political and economic presence from 2014 to 2016. While there is certainly significant overlap in the states where the firms were economically and politically active, both firms hired lobbyists in a number of states in which they were not selling systems. In 2016, for instance, SolarCity lobbied in 10 states in which it was not actively selling systems; Sunrun lobbied in 11 states where it did not have an economic presence. In many cases, these firms hired lobbyists in advance of economic expansion to particular states . To summarize, I have shown that: 1) favorable rooftop solar policy leads to rooftop solar industry growth, 2) rooftop solar industry growth leads to greater lobbying from rooftop solar industry both in the states where growth takes place as well as in other states, 3) rooftop solar firms have in a number of cases sought to influence policy in states where they are not yet active, and 4) installer lobbying is associated with more favorable policy, particularly in places where the industry has less of an economic presence. Taken together, the empirical analyses trace out a causal process whereby adoption of favorable rooftop solar policies in leading states affected the interest group politics—and ultimately policy decisions—in other states. Of course, the empirical analysis is not without its limitations. In particular, establishing causal inference in policy feedback and interest group influence research is a major challenge . In this case, neither policy enactment nor interest group lobbying is randomly assigned, nor are there apparent natural experiments to leverage.

Yet, by bringing together a multitude of both state- and firm-level data, this paper provides evidence in support of the proposed theoretical framework, and an empirical setup on which scholars working across different policy areas can build. In addition, the evidence presented does not rule out that traditional diffusion mechanisms of learning and competition have also shaped state-level rooftop solar policy and politics. It clearly demonstrates, however, that these traditional mechanisms are not the whole story. An analysis of interdependent policy making in this case that failed to consider the effects of state policies on the resources installers had at their disposal to engage politically in other states would be incomplete. Moreover, it is likely that the dynamics of cross-state policy feedback on interest group politics studied here can also serve to facilitate mechanisms of learning and competition. For instance, when installers lobbied in states where they had yet to establish an economic presence, they likely initiated a learning process among state lawmakers. Future research building on this paper might seek to refine methods for distinguishing the types of policy feedback spillovers explored here from traditional diffusion mechanisms. The standard policy diffusion designs are limited in their ability to parse mechanisms , and the feedback dynamics studied here will not always lead to diffusion in a strict sense. Broadly speaking, studying intergovernmental policy feedback in a federal context requires close attention not just to patterns of policy adoption in different units, but also to the political engagement of organized interests across the federal system. Scholars might pay particularly attention to two particular types of groups: first, groups with federated structures that can swiftly leverage resources from one jurisdiction to influence policy in another; and second, business interests seeking to expand. Studying the intergovernmental effects of policies on interest group politics also likely requires examinations over longer periods of time than conventional policy diffusion approaches. Diffusion mechanisms like learning and competition might manifest quickly—since they depend only on the beliefs of lawmakers—while the intergovernmental feed backs studied here depends on long-run shifts to interest group systems.

Indeed, the case of rooftop solar examined here is likely an outlier in the speed by which state policies gave rise to new interests. By adopting this empirical approach, scholars can further extend the theoretical framework developed in this paper. A natural extension is vertical policy feedback . The organized interests that benefit from, and are strengthened by, particular state-level reforms might, in addition to advocating for the propagation of those reforms across the states, advocate for the national-level adoption of those or aligned reforms. These effects have likely been limited in the case of distributed solar, where key decisions are made at the state level. Indeed, while SolarCity, Sunrun, Vivint, SunPower, and SunEdison spent just under 9 million dollars lobbying in the 15 states that collected expenditure data between 2015 and 2017, they collectively spent just 2.25 million dollars lobbying the federal government over the same period . But there is some anecdotal evidence that the growth of the distributed solar lobby, driven in part by state-level decisions,cannabis drying racks commercial has been important to the national politics of issues like tariffs on solar panels and the Solar Investment Tax Credit . Future research might also consider the conditions under which strategic actors intentionally leverage state policy as a political tool in building a political coalition for broader reform—or seeking to dismantle opposing organized interests . Importantly, politicians often face a collective action problem in their efforts to use policy for political gain. Even when a broader party or interest group benefits from a particular policy, individual lawmakers can have incentive to defect . This collective action problem is particularly pronounced for politicians seeking to use state policy for national-level political gain . As a result, we might expect federated groups with political operations across sites and levels of government to be most equipped to strategically harness dynamics of intergovernmental policy feedback . While this paper demonstrates the force of intergovernmental feed backs on interest group politics, these mechanisms are likely more limited in other cases. The aggressive growth strategy of installers, combined with the crucial role of state policy in driving growth, provided a strong incentive for installers to mobilize politically across the states. At the same time, even as rooftop solar firms have mobilized, incumbent electric utilities have been able to prevent pro-solar reforms across a number of states, and in some cases, roll them back . Forward looking incumbents engaged across sites and levels of government in the federal system can, in this way, use the political system to prevent competitors from gaining strength. Moreover, in policy areas like immigration or marriage equality, where sub-national policy decisions are less likely to engender major shifts in the broader interest group landscape, we are unlikely to observe strong policy feedback spillovers operating through organized interests. But at the same time, there are a broad swath of policy issues for which the mechanisms I explore here are likely quite relevant. Indeed, the emergence of supportive interests with a stake in new policy regimes is a fundamental feature of sustainable policy reforms .

These mechanisms are particularly relevant to the politics of the energy transition, where liberal leaning states have led the way, but where there are significantly more greenhouse gas emissions to be abated in conservative-leaning areas. While rooftop solar is just a small piece of the energy transition, similar ideas apply to other elements like utility-scale renewables and energy efficiency . In general, policy feed backs in energy governance tend to be quite powerful, since policies that replace fossil fuel infrastructure with clean energy infrastructure also replace fossil fuel interests with clean energy interests . More broadly, states play important regulatory roles across a number of policy areas, and their decisions can affect the political resources of organized interests active in other states. For instance, in the education system, state policy has been instrumental to the steady growth of charter schools in recent years, which in many states and districts now pose a meaningful challenge to the traditional public-school model—as well as to the teachers unions that draw strength from that model. As charter schools have grown, so has the charter school lobby, as wealthy foundations have allied with charter networks to push forward policies across the states, and also in local and federal politics . The general scope conditions for these types of effects are quite broad. Sub-national policies must give rise to new organized interests or significantly influence the capacities of existing interests. And the organized interests affected by sub-national policies must leverage newfound strength to mobilize horizontally across the federal system. Though this paper focuses specifically on the effects of state policies on business interests, elements of the proposed perspective also likely apply to other types of organized interests , as well as to sub-national jurisdictions apart from the US states .There are reasons to think, in addition, that these types of dynamics are at play even in some areas where we do not observe shifts to policy or interest group landscapes: they can be baked into the status quo. The period of rooftop solar policy and politics I study saw massive policy and interest group changes over a relatively short period of time, which renders the dynamics of policy feedback across the states highly visible. Similar mechanisms, though, can enforce policy stability across the federal system. Many powerful organized interests draw strength from policies in place in jurisdictions across the federal system and use their resources to block threatening policies at multiple sites and levels of government . These dynamics are difficult to study since they tend to lead to non-action. But studying policy areas in flux like rooftop solar can provide insight into forces of stability. Drawing on policy feedback literature and literature on congressional representation, I argue that, because of this institutional configuration, sub-national policy adoption can affect national representation.

The second core mechanism is competition . Because federal units compete for mobile businesses and residents, sub-national governments can be pressured to adopt attractive policies pursued in other units—or risk losing tax revenue and economic activity.The policy diffusion perspective has been highly fruitful. It has shed light on the degree to which policy decisions by governments are interdependent and explored several compelling mechanisms that drive this interdependence. But, I argue, this perspective is incomplete. It fails to fully account for the role of interest groups in the policy process—and how prior policy decisions across the federal system shape interest group politics. Policy diffusion scholarship focuses primarily on re-election motivated lawmakers who learn and compete because they, broadly speaking, want to produce good policy outcomes for their constituents. Yet, we know that much more goes into policy decisions besides lawmakers seeking good policy. Significant policy reforms usually represent just the final outcomes at the tail end of hard-fought political battles—which generally continue post-enactment in the implementation phase. These battles can draw a diverse array of interest groups like businesses, unions, and citizens groups, as well as government bureaucrats. Painting a complete picture of policy interdependence in American federalism therefore requires considering how prior policy decisions adopted across the federal system construct and empower political actors engaging across the federal system. That is the approach taken in this dissertation. I focus primarily on organized economic interests,indoor vertical garden system whose engagement is among the strongest drivers of policy decisions in American politics broadly , and who are particularly important in considering policy reforms that affect sectors of the economy.

Literature studying “policy feedback” has demonstrated the powerful ways in which the public policy landscape affects the representation of organized economic interests in the political system . For instance, the public policy landscape shapes the types of firms that grow and prosper—and as a result, which have the capacity to influence politics . Similarly, public policies like collective bargaining rules affect the ability of unions to grow and maintain membership, which in turn influences their political sway . Shifts 1 In the international sphere, Elkins and Simmons similarly categorize diffusion as either “adaptation to altered conditions” and learning. in policy, therefore, can affect the power of different organized economic interests in the political system. In a federal system of government in which states have significant authority and interest groups are active at multiple sites and levels of government, I argue that policy feedback effects on interest group politics can also generate powerful policy inter dependencies—in some cases driving the spread of policies across jurisdictions. More specifically, state-level reforms can increase the political power of interest group coalitions supporting the geographic and jurisdictional expansion of those reforms. These dynamics can play out, first, horizontally across the states. State-level reforms that benefit existing organized interests, or give rise to new ones, also tend to strengthen them politically. The groups that benefit from particular state-level reforms are likely to also benefit from the propagation of those reforms to other states. Thus, these groups might apply newfound strength to propagate reforms horizontally through lobbying and other political activities. The political implications of state-level reforms are not restricted to other states. The groups that benefit, and are politically strengthened, by a state-level reform might also leverage newfound strength to advocate for aligned reforms at the federal level. The geographic structure of representation in Congress provides a key avenue for this type of vertical, state-national feedback. Members of Congress represent geographically demarcated districts that are embedded in state policy landscapes.

Shifts to those landscapes precipitated by state policy reforms can in turn affect the political pressures that members face. More specifically, to the extent that state policy reforms influence state political economies, this can affect the ability of organized economic interests to engage in politics and make demands on their representatives. Finally, reforms achieved at the state level can affect the national interest group politics by drawing new actors into pro-reform coalitions. This dynamic is particularly relevant in considering the engagement of philanthropists, a growing topic of study in political science . State policy experiments can provide a proof-of-concept of the legitimacy of some set of reforms, and thus draw philanthropic investment. Once invested, foundations might use their financial resources to fund advocacy groups working to propagate those new policies. In the empirical portion of the dissertation, I apply this new theoretical perspective on policy interdependence in American federalism to three policy cases: rooftop solar policy, marijuana policy, and charter school policy. These are each areas in which state governments have taken the lead on driving forward policy reforms with major implications for sectors of the economy, and where, as I show, state government action has had implications for the interest group politics in the broader federal system.Even more so than in the case of rooftop solar, state actions have precipitated a major shift in marijuana policy over the past 20 years. Since California pioneered legalization of marijuana for medical use in 1996, 32 other states and Washington D.C. have followed suit. As of 2020, 15 states had also legalized marijuana for recreational use. This represents a profound shift from the policy regime associated with the War on Drugs that was initiated in the 1970’s. And, like in the case of rooftop solar, these policy shifts have also engendered shifts in the interest group politics. In particular, the advent of adult-use legalization, pioneered by Colorado and Washington in 2012, has driven rapid growth in the marijuana industry from just 3.5 billion dollars of revenue in 2014 to over 13.5 billion dollars of revenue in 2019.

This has led the industry to develop a greater political presence, both in the states and at the federal level. The costs from federal prohibition have led the industry, unlike in the case of rooftop solar, to focus to a greater extent on federal policy than propagating reforms across the states. Federal lobbying from marijuana industry rose from just $45,000 in 2012 to $6 million in 2019. And members of Congress representing legalizing states have, I show, become critical allies in efforts to liberalize federal marijuana policy and resolve costly state-federal legal tension. Take Cory Gardner , for instance. There is little in Gardner’s record prior to 2012 that would indicate he would become an important marijuana proponent. Yet, during his tenure in the Senate , Gardner became a central figure in federal marijuana policy. In 2018, Gardner vowed to block judicial nominees in the Senate until he received a commitment that the federal government would not prosecute marijuana industry . In the 116th Congress, Gardner sponsored core marijuana-related legislation including the SAFE Banking Act and the STATES Act. It is no coincidence that Gardner represents the state of Colorado,clone rack which has one of the strongest marijuana industries in the country. Indeed, interview evidence suggests that the sway of marijuana industry and marijuana voters in Jared Polis’s successful 2018 bid for governor was a major reason why Gardner, who anticipated a tough re-election in 2020 , made marijuana such a priority. To test whether the relationship between state-level legalization and representation in Congress generalizes, I leverage exogenous variation in likelihood of legalization generated by variation across the states in ballot initiative rules. This exogenous variation is necessary due to the inferential challenges in estimating the effects of state policy on national representation. Broadly speaking, to the extent that state policy decisions and representation in Congress are both shaped by factors like a state’s overall ideology, I would expect a correlation between state policy and national representation without any causal relationship. Variation in the availability of citizen initiatives across the states helps to overcome this causal identification problem in the case of marijuana policy. A number of states adopted procedures allowing citizens to enact statutes or constitutional amendments directly through statewide ballot initiatives in the Progressive era of the early 20th century. In the current era, ballot initiatives have been a critical tool for marijuana policy reform. The ability to bypass state legislatures is important because, as one advocate told me, citizens tend to be much more liberal on marijuana issues than their representatives in state legislatures. As a result, legalization efforts have been concentrated in states that allow ballot initiatives, and whether states allow initiatives strongly predicts legalization both for medical and recreational use. At the same time, whether states allow initiatives is not correlated with other factors generally associated with congressional behavior such as measures of ideology. And more importantly, whether states allow initiatives is not associated with member behavior on marijuana issues prior to the wave of state legalization initiated by California in 1996. This suggests that availability of the initiative is a valid instrument for estimating the effect of state legalization on national representation in the contemporary period.

I study the 116th Congress, which, as one journalist put it, was “the first Congress in history where, going into it, it seem[ed] that broad marijuana reforms [were] actually achievable” . Broadly speaking, I find evidence that state legalization affected national representation. Members of Congress representing legalizing states were more likely to sponsor or co-sponsor key pro-marijuana pieces of legislation. They were also more likely to cast certain pro-marijuana roll-call votes. Bringing quantitative evidence and elite interviews together to investigate mechanisms, I find the most support for the role of growing industry influence in legalizing states, but also find some support for the role of the initiative vote in signaling constituent preferences. I find little support for the potential alternative hypothesis that effects were driven by positive shifts to public favorability wrought by legalization. Like in the other two cases, state policy decisions regarding charter schools have driven major shifts to a sector of the economy and society: K-12 education. Charter schools, independent but publicly funded, have grown steadily since the early 2000’s. As Finn, Manno, and Wright write: “Aside, perhaps, from mayoral control, chartering is by far the most significant manifestation of structural and governance innovation in public education…” . In 1999, there were just 507 charter schools operating. By 2017, nearly 7000 charter schools were enrolling over 3 million students—about 7 percent of overall public K-12 enrollment. Charter schools owe their existence to the adoption of “charter laws” across 40 states between 1991 and 2003, which allowed new schools to form apart from the traditional district structure. Unlike in the case of marijuana policy, but like the rooftop solar case, charter school growth presents an existential threat to powerful organized economic interests—teachers unions. Charter schools generally have much lower rates of unionization than traditional public schools. The charter sector’s growth, despite opposition from unions and other incumbent education interests, is notable. It has depended in part, I argue, on the development of a nationally-scoped network of pro-charter advocacy groups—which have on several occasions gone toe-to-toe with powerful teachers unions. In the paper, I examine the role of prior state policy decisions in seeding this pro-charter interest group network. A key difference between the charter school policy case and the other cases studied is in the types of organized interests driving the sustainability and spread of reforms. In rooftop solar policy and marijuana policy, the story is relatively straightforward: state policy decisions gave rise to new industries that leveraged their economic growth to develop greater political influence. While charter growth precipitated by state policies has similarly generated new political interests in the form of large charter networks like Success Academy and KIPP, the political power of these organizations is highly limited. Since charter schools are mostly non-profits with limited revenue streams generally funneled into operations, the political activity of these charter networks has been modest compared to large marijuana and rooftop solar firms. Given that limitation, the financial backing of philanthropists like the Gates Foundation and the Walton Family Foundation has been crucial to building the pro-charter advocacy network. But foundations’ investments in charter advocacy did not arise in a vacuum. Drawing on elite interviews, I show that state policy decisions in the 90’s promoting charter growth in leading states like Minnesota and California were instrumental to generating support from philanthropists and building the pro-charter group coalition.

The timing of follow-up visits was anchored to the date of the participant’s baseline assessment . “Pre-pandemic” observations were any assessment occurring between study entry and March 19, 2020, the date of the first state-issued stay-at-home order, so each youth could contribute multiple assessments. Among youth contributing pre-pandemic data to analyses , there were an average of 3.0 pre-pandemic assessments . During the COVID-19 pandemic, participants were invited to complete three web-based surveys in June 2020 , December 2020 , and June 2021 . Of the 348 participants included in analyses, 237 completed the June 2020 survey, 213 completed the December 2020 survey, and 195 completed the June 2021 survey. Completers of the prepandemic and during-pandemic assessments were sociodemographically similar . Among the youth contributing during pandemic data to analyses , there were an average of 2.2 during-pandemic observations. Altogether, 60 youth contributed only pre-pandemic data, 67 youth contributed only during pandemic data, and 221 youth contributed both pre- and during pandemic data. Analyses were conducted in R v4.1.2 . We estimated the impact of the COVID-19 pandemic by comparing observations of same-age youth assessed at four different time points: prepandemic , June 2020, December 2020, and June 2021. Conceptually, we used the prepandemic data to construct a reference curve for the expected drinking or nicotine use as a function of age, then compared that reference curve to the observed drinking and nicotine use as a function of age at each survey wave during the pandemic. In this way, we sought to distinguish the effects of the pandemic from age-related changes in drinking or nicotine use that would have occurred even outside the pandemic context. We restricted the sample to participants ≤ age 15.8 years at study entry to reduce potential cohort effects on drinking and nicotine use introduced by study entry criteria or by secular changes in drinking or nicotine use among U.S. young adults between 2016 and 2021 . If cohort effects were present, they would be confounded with the effect of the COVID-19 pandemic .

Preliminary analyses showed date of birth was not predictive of drinking or nicotine use in the restricted sample after controlling for age,vertical farming equipment suppliers suggesting any remaining cohort effects were minimal . In addition, we restricted observations to those of participants ages 18.8–22.4 years old at each time point, to ensure we had observations covering the same age span at each of the four assessment time points and avoid extrapolation beyond the common region of support . Outcomes included the proportion of young adults drinking or using nicotine, the number of days drinking or using nicotine among those reporting any use, and the typical number of drinks per drinking day . Regressions were fit in the geepack package , clustering observations on participant, specifying an exchangeable correlation structure, and using robust standard errors. For dichotomous dependent variables, a logistic link function was used. Model specification included fixed effects for sex, race, ethnicity, study site, age at observation, age-at-observation-squared, and time point of assessment. Participant sex, race, ethnicity, and study site were included as covariates given previous work has established they predict alcohol and nicotine use . Age at observation was included to implement our age-based identification strategy ; both linear and quadratic effects were included to account for nonlinear developmental changes in alcohol and nicotine use across this age range . Time point of assessment was a four-level categorical variable , represented by dummy variables with prepandemic as the reference level. Follow-up models investigated whether the effect of the COVID-19 pandemic varied as a function the impact of the pandemic on participants’ financial security. We expanded the primary model described above by adding the main effect of financial impact and terms capturing the interaction of financial impact with time point. We then tested the statistical significance of the interaction via a Wald test .

Regression models compared drinking and nicotine use at the three during-pandemic time points to drinking and nicotine use pre-pandemic. Fig. 1, Panel A graphs the model-estimated means for a 20-year-old participant across time points, which are interpreted next. Compared to pre-pandemic , significantly fewer participants reported any past-month drinking in June 2020 and December 2020 , with the difference no longer being statistically significant in June 2021 . Compared to pre-pandemic, those reporting any past-month drinking drank on 1.83 more days in June 2020 , with the difference no longer being statistically significant in December 2020 or June 2021 . Compared to pre-pandemic, there were no significant differences at any of the three during-pandemic time points in the number of drinks on a typical drinking day or the binge drinking or nicotine use outcomes . Tables 2 and 3 reports the corresponding effect sizes. Compared to pre-pandemic, 4–5% fewer participants engaged in past month binge drinking in June 2020 and December 2020, though neither difference was statistically significant . We did not find evidence that the degree to which the pandemic impacted participants’ financial security moderated the pandemic’s impact on drinking outcomes . We found evidence that the degree to which the pandemic impacted participants’ financial security moderated the pandemic’s impact on the number of days using nicotine among past-month users but not the prevalence of past-month nicotine use . Fig. 1, Panel B graphs the interactions for the nicotine use outcomes. Among those reporting any past-month nicotine use, participants who experienced moderate-to-extreme financial impact increased the number of days using nicotine while those with no financial impact decreased the number of days using nicotine in June 2020 . We investigated changes in drinking and nicotine use from prepandemic baseline over the first 15 months of the COVID-19 pandemic in a sample of 348 emerging adults ages 18–22 years old. Compared to pre-pandemic, in June 2020, fewer young adults reported past-month drinking, but those who did were drinking on more days. Compared to pre-pandemic, in December 2020, fewer young adults reported past-month drinking, but those who did were no longer drinking on significantly more days. By follow-up in June 2021, on average, there were no significant differences from pre-pandemic patterns of alcohol and nicotine use.

Findings are consistent with previous short-term studies showing a pandemic related increase in the number of days drinking. In our data, this change reflected a different distribution of drinking across the population: compared to pre-pandemic, fewer young adults were drinking, but those who did drank more frequently. While two previous studies found decreases in binge drinking , we did not find a statistically significant change in the number of days of binge drinking at any time point in the current study. However, the non-significant reduction we observed in binge drinking in June and December 2020 was directionally consistent with these previous studies. In addition, the time frame of measurement may explain the discrepancy: those two previous studies focused on changes earlier during the pandemic, in March and April 2020, whereas another study focusing on changes in June and July 2020 also found no significant change in binge drinking. As in one previous study , we did not find an average effect of the pandemic on nicotine use. However, this appeared to obscure opposing changes among those who suffered vs. did not experience impacts on their financial security. Relative to pre-pandemic, in June 2020, those with past-month nicotine use had increased the number of days using if they experienced financial impact and had stable or decreased number of days using if they denied experiencing financial impact . Loss of job or reduction in work hours could increase smoking during periods of boredom at home or to cope with the attendant stress . This pattern is consistent with the larger literature documenting how the pandemic may exacerbate health disparities based on pre-existing socioeconomic advantage . However, moderation of multiple outcomes was tested, so the current findings should be regarded as preliminary and await replication. This study had limitations. First,grow lights shelves findings may not generalize beyond emerging adults ages 18–22 years old . Second, for nicotine use, we did not measure the quantity used each day, which could have changed. Third, we did not consider other substances such as cannabis. Fourth, the mode of assessment differed from the prepandemic to during-pandemic assessments, potentially introducing differences.Fifth, secular changes in the rates of alcohol or nicotine use among young adults between 2016 and 2021 could be confounding the effect of the pandemic, potentially introducing bias.Sixth, pre-pandemic responses on a free-response scale had to be mapped onto the discrete response options , potentially limiting precision. Seventh, we assessed the degree to which the pandemic impacted individuals’ financial security but not the form of this impact . Eighth, pre-pandemic observations were not anchored to the months of June and December, so seasonal effects could explain part of the observed differences. We reported here the most extended follow-up to date of pandemic related changes in drinking and nicotine use in emerging adults. The study had several further strengths. We used seven years of prepandemic assessments and a rigorous age-based design to identify the pandemic’s impact over and above typical developmental changes. We incorporated three assessments spanning the first 15 months of the pandemic to study whether early changes in drinking and nicotine use persisted. Participants spanned five sites across the U.S and multiple racial and ethnic backgrounds. Finally, we focused on a critical developmental period associated with elevated risk for problematic use . In summary, in a heterogeneous group of young adults, pandemic related changes in drinking patterns were no longer detectable in June 2021. Pandemic-related increases in nicotine use occurred only for participants who reported greater impact of the pandemic on their financial security—these subgroup effects were no longer statistically significant in June 2021, though a large effect size for past-month nicotine use remained. Thus, those whose financial security has been adversely impacted by the pandemic may reflect a vulnerable group worth targeting for supports to manage drinking and nicotine use.

Continued follow-up beyond summer 2021 is necessary to verify that the pandemic’s effects on drinking and nicotine use have indeed faded and understand the pandemic’s long-run impacts of substance use trajectories into adulthood. Parkinson’s Disease treatment has been based on dopamine replacement therapy for 35 years. Yet, side effects resulting from long-term use of DA agonists, namely dyskinesias and on–off responses, are prompting investigations of alternative neurotransmitter manipulations to modulate basal ganglia function and normalize motor activity. Dyskinesias often result from lesion or disturbance affecting the transcortical loop or indirect pathway, with disruption of balance between excitation and inhibition in the globus pallidus pars externa-subthalamic nucleus-globus pallidus pars interna circuit. Thus, dyskinesias reflect altered patterns of neuronal firing in this circuit, which result in the improper selection of specific motor programs and, eventually, in the development of hyperkinetic movements . Endocannabinoids, the endogenous ligands of cannabinoid receptors, are synthesized upon demand by neurons in response to depolarization , and, once released, diffuse backwards across synapses to suppress pre-synaptic GABA or glutamate release . Because of these properties, the endocannabinoid system may offer new pharmacological targets for the treatment of neurologic conditions characterized by abnormal firing patterns. One application of cannabinoidbased therapeutics would be for dyskinetic syndromes, hyperkinetic disorders characterized by changes in pattern, synchronization, mean discharge rates, and somatosensory responsiveness of neurons in the direct and indirect extrapyramidal motor circuits . Further applications of cannabinoid-based therapeutics may extend to treatment of seizure disorders, changes in behavioral or cognitive state resulting from hypersynchronous excessive neuronal discharges in other, for example, limbic, cortical or thalamic circuits. To test the hypothesis that endocannabinoids act as endogenous antidyskinetic agents with modulatory effects on abnormal basal ganglia circuits, we examined endocannabinoid production in specific areas of the basal ganglia of rats infected with Borna disease virus and how cannabinoid agonists and antagonists affect their motor behaviors. Borna disease virus is a negative strand RNA virus epidemiologically linked to patients with neuropsychiatric disorders and Parkinson’s-plus syndromes . After infection, BD rats develop an extrapyramidal disorder with spontaneous dyskinesias, hyperactivity, stereotypic behaviors, partial DA deafferentation, DA agonist hypersensitivity, and Huntington’s-type striatal neuropathology . Our investigations revealed elevations in the endocannabinoid anandamide in the subthalamic nucleus of BD rats, associated with increased metabolic activity in this key basal ganglia relay nucleus.

A higher score on our composite measure was associated with being female, being unemployed, having greater medication load and lower mania symptomatology. Similarly, studies in BD show that poor sleep is associated with worsening BD symptoms , among other correlates. Based upon LASSO regression, TST and NA most contributed to the correlation with medication load which may be reflective of the sedating properties of many psychotropic medications . PS contributed most to the correlations with employment, and mania symptoms, which may relate to sleep fragmentation and variability that has previously been shown to be associated with these variables . Because wrist actigraphy is easily administered and is less invasive compared to an inlab sleep evaluation and is easier to get longitudinal measures over the span of weeks, it is important for future research to identify other approaches that could reduce these voluminous data to actionable insights, especially for treating patients with BD where management of sleep is paramount. Clinicians could utilize a composite measure to identify patients with poor sleep overall and triage these patients to appropriate sleep treatment options based upon their individual sleep metrics. In the future, as such accelerometry data becomes available in many different populations, it may soon be possible to identify when poor sleep begins to emerge with the possibility of predicting a mood episode to offer just-in-time clinical interventions. More research is needed to develop tools using these data for future prediction of events for clinical monitoring. Our study has some limitations. First, our analysis was cross-sectional and retrospective. Research should explore ways that changes in sleep quality longitudinally may be incorporated in this composite measure. Second, we focused on the means of sleep parameters as our main purpose was to examine an intuitive composite score for poor sleep. Future studies may want to identify whether night-to-night variability in sleep or circadian patterns can improve a composite measure . Third, in the absence of published norms for actigraphic sleep measures for healthy individuals of comparable age to our BD sample, we used our own HC sample as the normative group.

To the extent that our HC sample was relatively small and participants were not selected on the basis of having no reported sleep abnormalities,grow trays 4×4 this may have introduced some bias into the composite scores. It may be important for future studies to compare this method to other approaches which do not use a normative sample . Fourth, our sample size was small and given the number of correlates assessed with the composite score, there is a possibility of significant findings due to chance alone. However, our study evaluates a potential way to combine actigraphic measurements, and future studies with larger samples may help examine this further. Finally, we did not have measures of sleep apnea which may contribute to disturbed sleep . However, sleep apnea is often undiagnosed , and in a clinical setting, clinicians may need to base their assessment of sleep on wrist actigraphy alone. In conclusion, we found that while a sleep composite measure based upon actigraphy measures was correlated with patient characteristics similar to that in other studies, it does not add more information beyond individual sleep metrics alone and future research might benefit from selecting individual sleep metrics based on theory rather than use a composite measure approach. While our approach may have limited utility in BD, it may be important for research to examine this in other clinical groups, including those with other serious mental illnesses. As sleep becomes more frequently measured by actigraphy, efforts to improve the use and applicability of these unique data will be important for understanding the dynamics of sleep in those with BD.With the introduction of combination antiretroviral therapy mortality among HIV-infected patients diminished significantly. However, some patient subgroups have different survival patterns, and have shown less decline in death rates.These include patients with psychiatric or substance use disorders, which are highly prevalent among patients treated for HIV/AIDS.There is also a high cooccurrence between psychiatric and substance use disorders among the HIV-infected,as in other populations; and severity is greater in each type of disorder when there is cooccurrence.Together they place individuals at elevated risk for poor health outcomes. Because psychiatric and substance use disorders frequently co-occur, it is important to examine the combined impact of these disorders among people with HIV infection. Research among HIV-infected patients has shown an association between depression symptoms, HIV disease progression and mortality; and mental illness and substance abuse are barriers to optimal adherence to combination antiretroviral regimens.

One study of U.S. veterans found that survival was associated with greater number of mental health visits.Yet few studies have examined survival patterns for HIV-infected individuals who use alcohol or illicit drugs, but are generally not injection drug users, and have been diagnosed with psychiatric or SU disorders from a private health plan; nor have studies examined both psychiatric and SU disorders in relation to mortality. Previous research has shown that access to psychiatric and SU disorder care among HIV-infected patients varies based on sociodemographic factors and HIV illness severity.The current study compares mortality in HIV-infected patients diagnosed with psychiatric disorders and/or SU disorders to patients without either diagnosis receiving medical care from a private, fully integrated health plan where access to care andability to pay for care are not significant factors. We also examine the effects of accessing psychiatric or SU treatment services. Improvement in depression has been associated with better adherence to combination antiretroviral therapy and increased CD4 cell counts.Therefore, we hypothesize that accessing services is associated with decreased mortality among patients with HIV infection.We conducted a retrospective observational cohort study for years 1996 to 2007 among HIV-infected patients who were members of the Kaiser Permanente Northern California health plan. The KPNC is an integrated health care system with a membership of 3.5 million individuals, representing 34% of the insured population in Northern California. The membership is representative of the northern California population with respect to race/ethnicity, gender, and socioeconomic status, except for some under representation of both extremes of the economic spectrum.HIV infected patients are seen at medical centers throughout the KPNC 17-county catchment region. The study population consisted of 11,132 HIV-infected patients who received health care at KPNC at some time between January 1, 1996 and December 31, 2006. The study sample included all HIV-infected patients who were 14 years of age or older on or after January 1, 1996 and had at least 6 months membership during the first year of study observation .

This minimum age was chosen because the KPNC membership has very few HIV patients under age 14, children are likely to receive different psychiatric diagnoses than adolescents and adults , diagnosis of SU problems generally occurs later than age 13, and children are likely to receive services for these disorders in pediatrics departments rather than in the health plan’s specialty psychiatry and SU treatment programs. Patients could enter the study until December 31, 2006. In the data analyses, we also excluded 83 patients whose SU disorder diagnosis status was unclear . This resulted in a study analysis sample of 9751 patients.Since 1988, the KPNC Division of Research has maintained a surveillance system of patients who are HIV-1– seropositive,horticulture products ascertained through monitoring electronic inpatient, outpatient, laboratory testing, and pharmacy dispensing databases for sentinel indicators of probable HIV infection. HIV-1 seropositivity is then confirmed through review of patient medical records. Ascertainment of HIV infected patients by this registry has been shown to be at least 95% complete. The HIV registry contains information on patient demographics , HIV transmission risk group , dates of known HIV infection, and AIDS diagnoses. KPNC also maintains complete and historical electronic databases on hospital admission/discharge/transfer data, prescription dispensing, outpatient visits, and laboratory tests results, including CD4 T-cell counts and HIV-1 RNA levels. Mortality information including date and cause of death are obtained from hospitalization records, membership files, California death certificates, and Social Security Administration databases. Mortality data were complete through December 31, 2007. Antiretroviral medication prescription data were obtained from KPNC pharmacy databases. Approximately 97% of members fill their prescriptions at KPNC pharmacies, including patients whose prescriptions are obtained through the Ryan White AIDS Drug Assistance Program. ARV medication data included date of first fill, dosage, and days supply, as well as data on all refills. Patients were classified as: currently receiving combination-ARV , current dual NNRTI/NRTI ARV use, past ARV use, or never users .Psychiatric diagnoses were assigned by providers. One or more diagnoses can be coded by ICD-9 in the KPNC administrative databases.Psychiatric diagnoses selected for this study were the most common and serious psychiatric disorders diagnosed among health plan members including schizophrenic disorders , major depressive disorder, bipolar affective disorder, neurotic disorders , hysteria, phobic disorders, obsessive-compulsive disorder, anorexia nervosa, and bulimia. We examined the impact of having one or more of these psychiatric disorders in aggregate, as in prior HIV studies.31 Within the health plan, psychiatry can be accessed directly by patients. Mild cases of depression and anxiety may be addressed in primary care with medication but moderate to severe cases are referred to psychiatry. Treatment in psychiatry includes assessment, psychotherapy and medication management. Patients diagnosed with a psychiatric disorder generally return to psychiatry for individual and/or group psychotherapy and/or medication evaluations. Our measure of psychiatric treatment was whether or not a patient had visits to a psychiatric clinic after a psychiatric diagnosis,obtained from automated databases.A diagnosis of ICD-9 substance dependence or abuse can be made by the patient’s clinician in primary care, SU disorder treatment, or psychiatry as a primary or secondary diagnosis.Diagnostic categories include all alcoholic psychoses, drug psychoses, alcohol dependence syndrome, drug dependence , alcohol abuse, cannabis abuse, hallucinogen abuse, barbiturate abuse, sedative/tranquilizer abuse, opioid abuse, cocaine abuse, and amphetamine abuse; as well as multiple substance abuse and unspecified substance abuse. In our analyses we classified patients as having one or more diagnoses of substance abuse and/or dependence versus no diagnosis.KPNC provides comprehensive outpatient SU treatment available to all members of the health plan. Services include both day hospital and traditional outpatient programs,both of which include eight weeks of individual and group therapy, education, relapse prevention, family therapy, with aftercare visits once a week for ten months. In addition to these primary services, ambulatory detoxification and residential services are available, as needed. A small proportion of patients engage in residential SU treatment, conducted by contractual agreement with outside institutions. These data are available in the KPNC referrals and claims databases. As with psychiatric treatment, in the current study SU treatment initiation was measured as having one or more visits to an outpatient program or a stay in a residential SU treatment unit following diagnosis.Analyses focused on diagnoses of psychiatric disorders with and without co-occurring SU diagnoses as the primary predictors of interest. The distribution of demographic, clinical and behavioral characteristics was compared between patients with and without a major psychiatric diagnosis; statistical significance was assessed using the w2 test. The distribution of cause of death was examined by psychiatric diagnostic status ; statistical significance was assessed using the w2 test or Fisher’s exact test where table cells were sparsely populated. Cox proportional hazards regression was used to obtain point and interval estimates of mortality relative hazards associated with psychiatric diagnosis/treatment status and SU problems diagnosis/treatment status, with each of these two time dependent covariates measured at three levels: no diagnosis, diagnosis with treatment, diagnosis without treatment. With the goal of examining the joint effects of these two covariates on mortality, results are expressed as hazard ratios for combinations of psychiatric diagnosis/treatment and SU diagnosis/treatment levels, with no diagnosis of either comorbidity as the referent. These estimates were adjusted for an a priori chosen set of available covariates, including age at entry into study, race/ethnicity, gender, HIV transmission risk group, CD4 T-cell counts and HIV RNA levels and ARV treatment modeled as time-dependent covariates, year of known HIV infection, AIDS diagnosis prior to entry into study, and evidence of hepatitis C viral infection. Initial modeling results demonstrated a significant interaction between psychiatric and SU diagnosis/treatment status in Cox regression models . Therefore, relative hazard estimates of interest were obtained via appropriate linear combinations of parameter estimates from a fully saturated model .

Anatomical studies of endocannabinoid transport are greatly limited by the lack of transporter-specific markers. Nevertheless, biochemical experiments have documented the existence of [3 H]anandamide uptake in primary cultures of rat cortical neurons and astrocytes , rat cerebellar granule cells , human neuroblastoma cells , and human astrocytoma cells . The CNS distribution of endocannabinoid transport was investigated by exposing metabolically active rat brain slices to [14C]anandamide and analyzing the distribution of radioactivity in the tissue by autoradiography . A receptor antagonist was included in the incubations to prevent the binding of [14C]anandamide to CB1 receptors, which are very numerous in certain brain regions , and AM404 was used to differentiate transportmediated [14C]anandamide reuptake from nonspecific binding . Substantial levels of AM404-sensitive [14C]anandamide reuptake were observed in the somatosensory, motor, and limbic areas of the cortex and in the striatum. Additional brain regions showing detectable [14C]anandamide accumulation included the hippocampus, thalamus, septum, substantia nigra, amygdala, and hypothalamus . Thus, endocannabinoid transport may be present in discrete regions of the rat brain that also express CB1 receptors . Distribution of Endocannabinoid Transport Outside the CNS. The endocannabinoid system is not confined to the brain, and it is reasonable to anticipate that mechanisms of endocannabinoid inactivation may also exist in peripheral tissues. In keeping with this expectation,industrial rolling racks carrier-mediated [ 3 H]anandamide transport was demonstrated in J774 macrophages , RBL-2H3 cells , and human endothelial cells .

Although the kinetic and pharmacological properties of endocannabinoid uptake in peripheral cells appear to be generally similar to those reported in the CNS, some important difference have been observed. For example, in contrast to neurons, [3 H]anandamide uptake in RBL-2H3 cells is inhibited by arachidonic acid . Such disparities might reflect the existence in non-neural tissues of mechanisms of endocannabinoid internalization that are distinct from those found in the CNS. Inhibition of Endocannabinoid Transport: Molecular Tools. A variety of compounds have been tested for their ability to interfere with [3 H]anandamide internalization . Amongthem, the anandamide analog AM404 stands out for its relatively high potency and its ability to block endocannabinoid transport both in vitro and in vivo. AM404 inhibits [ 3 H]anandamide uptake in rat brain neurons and astrocytes , human astrocytoma cells , rat brain slices , and RBL-2H3 cells . AM404 does not directly activate cannabinoid receptors in vitro , but it augments several CB1 receptor-mediated effects of anandamide. For example, AM404 enhances anandamideevoked inhibition of adenylyl cyclase activity in cortical neurons, an effect that is reversed by the CB1 antagonist SR141716A . Likewise, AM404 potentiates the inhibitory actions of anandamide on GABA-ergic neurotransmission in the periaqueductal gray matter . These findings are consistent with the hypothesis that AM404 protects anandamide from inactivation and, by doing so, magnifies the biological effects of this short-lived lipid mediator. It is important to point out, however, that AM404 is readily transported inside cells , where it can reach concentrations that may be sufficient to inhibit anandamide hydrolysis . To what extent this effect contributes to the ability of AM404 to prolong anandamide’s life span is at present unclear. An initial screening found that AM404 has no affinity for a panel of 36 different pharmacological targets, including G protein-coupled receptors and ligand-gated ion channels .

However, additional studies revealed that AM404 activates capsaicin receptor channels at concentrations similar to those necessary to inhibit endocannabinoid transport . The fact that AM404 can produce undesired effects underscores the need to introduce appropriate controls in the design of in vivo experiments with this compound. In particular, the effects of a cannabinoid receptor antagonist should be routinely tested to verify that endogenously produced anandamide and 2-AG are involved in the response to AM404 . Inhibition of Endocannabinoid Transport: Functional Studies. AM404 does not display a typical cannabimimetic profile when administered in vivo; this is consistent with its poor affinity for cannabinoid receptors. For example, AM404 has no antinociceptive effect in mice or rats and causes no hypotension in guinea pigs . Nevertheless, in the same models, AM404 increases the responses elicited by exogenous anandamide, and this potentiation is reversed by the CB1 antagonist SR141716A . Despite the absence of overt cannabimimetic properties, AM404 resembles anandamide and other cannabinoid receptor agonists in certain respects. For example, when administered alone, AM404 causes a reduction in motor activity, which is prevented by the CB1 antagonist SR141716A . Furthermore, AM404 reduces the yawning evoked by low doses of the mixed D1/D2 dopamine agonist apomorphine and inhibits the hyperactivity elicited by the selective D2 agonist quinpirole . AM404 also decreases the levels of circulating prolactin, but the role of CB1 receptors in this response is unknown . Can the effects of AM404 be explained by its in vitro affinity for vanilloid receptors ? The fact that SR141716A, a selective CB1 antagonist, blocks the motor inhibitory effects produced by AM404 argues against this possibility. Furthermore, vanilloid agonists such as capsaicin have very different, in some cases even opposite, effects. For example, capsaicin causes hyperkinesia and pain , whereas AM404 elicits hypokinesia and enhances anandamide’s analgesic properties .

Therefore, a more plausible interpretation of the available data is that, by inhibiting anandamide clearance, AM404 may cause this lipid to accumulate outside cells and activate local cannabinoid receptors. In further support of this possibility, the systemic administration of AM404 in rats was found to cause a time-dependent increase in circulating anandamide levels . Finally, it is important to point out that several anandamide responses are not affected by AM404. One example is the inhibition of intestinal motility, which anandamide may produce in rodents by activating CB1 receptors on the surface of enteric neurons . This effect is not enhanced by AM404, suggesting that the predominant pathway of endocannabinoid inactivation in the intestine may be through enzymatic hydrolysis, not transport . The fact that rat intestinal tissue contains high AAH levels is in agreement with this possibility . Alternatively, anandamide transport may occur in the intestine through transport mechanisms that are insensitive to AM404.Mechanisms and Kinetics. Long before the discovery of anandamide, Schmid and coworkers identified in rat liver an amidohydrolase activity, which catalyzes the hydrolysis of fatty acid ethanolamides to free fatty acid and ethanolamine . That anandamide may serve as a substrate for this activity was first suggested on the basis of biochemical evidence and then demonstrated by molecular cloning and heterologous expression of the enzyme involved . AAH is an intracellular membrane-bound protein whose primary structure displays significant similarities with a group of enzymes known as “amidase signature family” . AAH may act as a general hydrolytic enzyme not only for fatty acid ethanolamides but also primary amides  and even esters . Site-directed mutagenesis experiments indicate that this unusually wide substrate preference may be underpinned by a novel catalytic mechanism involving the amino acid residue lysine 142. This residue may act as a general acid catalyst, favoring the protonation and consequent detachment of reaction products from the enzyme’s active site . Three serine residues that are conserved in all amidase signature enzymes may also be essential for enzymatic activity: serine 241 may serve as the enzyme’s catalytic nucleophile, while serine 217 and 218 may modulate catalysis through an as-yet-unidentified mechanism . Like other hydrolase enzymes, AAH may act in reverse, catalyzing the synthesis of anandamide from free arachidonate and ethanolamine . The high KM values reported for anandamide synthase activity suggest, however, that under normal circumstances AAH acts predominantly as a hydrolase. One exception is represented by the rat uterus, where substrate concentrations in the micromolar range are required for the synthase reaction to occur, implying that in this tissue AAH could contribute to anandamide biosynthesis . In addition to AAH, other ill-characterized enzyme activities may participate in the breakdown of anandamide and 2-AG. A fatty acid ethanolamide-hydrolyzing activity catalytically distinct from AAH was described in rat brain membranes and human megakaryoblastic cells . Furthermore, evidence indicates that 2-AG degradation may be predominantly catalyzed by an enzyme different from AAH,marijuana drying rack possibly a monoacylglycerol lipase . Structure-Activity Relationship Studies. Modifications in three potential pharmacophores have helped define several general requisites for endocannabinoid hydrolysis by AAH. First, reducing the number of double bonds in the hydrophobic carbon chain causes a gradual increase in metabolic stability .

Thus, [3 H]anandamide hydrolysis is inhibited by fatty acid ethanolamides in the 20 carbon atom series with the following rank order of potency: 20:4  20:3 20:2 20:1 20:0  no effect . Second, replacing the ethanolamine moiety with a primary amide leads to good AAH substrates. For example, the rate of hydrolysis of arachidonylamide is approximately twice that of anandamide . Third, anandamide congeners containing a tertiary nitrogen in the ethanolamine moiety are poor AAH substrates . Fourth, introduction of a methyl group at the C2, C1, or C2 positions of anandamide yields analogs that are resistant to hydrolysis, likely as a result of increased steric hindrance around the carbonyl group . Fifth, substrate recognition at the AAH active site is stereoselective, at least with fatty acid ethanolamide congeners containing a methyl group in the C1_x0007_or C2 positions . Finally, as a result of AAH’s remarkable “directed nonspecificity” , fatty acid esters also serve as substrates for this enzyme. Thus, 2-AG is hydrolyzed by AAH at a rate that is about 4 times faster than anandamide is . AAH Distribution in the CNS. AAH is widely distributed in the brain, with particularly high levels in cortex, hippocampus, cerebellum, amygdala, thalamus, and pontine nuclei . Immunohistochemical studies suggest that neurons, not glia, are the predominant cell type expressing AAH , although astrocytes in primary culture have been shown to contain AHH activity . CB1 cannabinoid receptors are present in various brain regions that also express AAH, but there appears to be no direct correlation between the concentrations of these two proteins . This discrepancy may reflect the participation of AAH in the degradation of non-cannabinoid lipid amides, such as oleamide and OEA. AAH Distribution outside the CNS. AAH mRNA and enzyme activity have been measured in a variety of nonneural cells lines, including lung carcinoma , human breast carcinoma , leukemia basophils , human monocytic leukemia , rat renal endothelial and mesangial cells , rat macrophages , human platelets , and human lymphocytes . Furthermore, high AAH levels have been found in rat liver, testis, kidney, lung, spleen, uterus, small intestine, and stomach; whereas lower levels were observed in heart and skeletal muscle . The distribution of AAH in human tissues is somewhat different from the rat, with expression levels that are reportedly higher in pancreas, brain, kidney, and skeletal muscle than in liver . Inhibition of AAH Activity: Molecular Tools. The armamentarium of AAH inhibitors available to the experimentalist has been recently enriched by two important groups of molecules. The first are fatty acid sulfonyl fluorides, such as the compound AM374 . AM374 irreversibly inhibits AAH activity with an IC50 value in the low nanomolar range and displays a 50-fold preference for AAH inhibition versus CB1 cannabinoid receptor binding . In superfused hippocampal slices, AM374 augments anandamide’s ability to inhibit [3 H]acetylcholine release, although it does not affect release when it is applied alone . The second group of AAH inhibitors is represented by a series of substituted  -keto-oxazolopyridines , which are reversible and extremely potent . Little information is as yet available on the pharmacological selectivity and in vivo properties of these interesting compounds. AAH Inhibition: Functional Studies. Systemic administration of the potent AAH inhibitor AM374 does not produce clear cannabimimetic effects in rats but enhances the operant leverpressing response evoked by anandamide administration . These results suggest that AM374 protects exogenous anandamide from degradation but does not cause a significant accumulation of endogenously generated anandamide. This idea is consistent with the finding that, in contrast to the transport inhibitor AM404 , AM374 does not increase circulating anandamide levels in rats . Further studies will be required to fully evaluate the behavioral impact of AAH inhibitors and to assess the biological availability and pharmacokinetics of these molecules.In Search of a Role. What place will inhibitors of endocannabinoid clearance occupy in medicine, if any, will largely depend on the answers to two key questions.

A quiz competition with questions on various aspects of mental illness also took place between four Junior High Schools in Tamale and was broadcast on the radio. In addition, BasicNeeds Ghana conducted research on mental health financing, lobbied Ghana’s Parliament to promote a speedy passage of the Mental Health Bill, and helped build a multipurpose psychiatric facility in the Upper West regional capital, Wa, with the help of Ghana Health Services and three other charities. The past ten years have seen the most significant increase in awareness of mental illnesses, which MindFreedom attributes to the birth of mental health NGOs. The first street march MindFreedom organized in 2006 presented neatly dressed, seemingly normal mentally ill patients and survivors, which subsequently shocked citizens and helped bring media attention to the plight of the mentally ill. When the executives were younger, mental illness was not talked about and one of the executives mentioned that he fearfully walked on the other side of the street when passing by the psychiatric hospital to avoid the mad people and the evils associated with them. Anyone seen walking into the psychiatric hospital also became the talk of the town in a negative way. MindFreedom dreams that Ghana will have mental health care as reliable as in the West in regards to human rights, access to treatment, and access to medication. They want everyone to know that anybody can be stricken by a mental illness, and they kept mentioning a proverb: “You shouldn’t wash your dirty linens outdoors, but if you keep them inside,clone rack the room will stink. By this they meant that families should not keep their disabled ones hidden in a room but should bring them out and not be ashamed of them.

Like in most developing countries, access to mental health in Ghana, where schizophrenia, depression, alcohol and cannabis abuse, and epilepsy are the most common diagnoses, remains low because of the limited number of treatment centres and the high mental patient to mental doctor ratio. Due to the discriminatory stigma, the low fatality of mental illness, and the alleged significance or discrepancy of physical health over mental health, the government in Ghana holds mental illness as a very low priority even though it is a leading component of the global burden of disease. The lack of priority lead to insufficient funding and outdated mental health policies which in turn caused a severe lack of mental health personnel and incentives to gain personnel, low employee morale, shortages of psychotropic medicine, human rights violations, congestion of institutionalized hospitals, poor condition of decaying facilities and inadequate equipment, lack of community care, lack of preventative and rehabilitative services, absence of research-based evidence, and the lack of an aggressive education and awareness campaign. All of these challenges need to be addressed in order to decrease the number of relapses and increase prevention and the rate of recover but unfortunately mental health professionals are often too busy to lobby for the implementation of change. Most importantly the psychiatric hospitals need to be decongested, the mental health staff strength needs to increase, community care and rehabilitation needs to be emphasized, and the Mental Health Bill needs to be passed. Despite Ghana’s challenges, much progress has been displayed through MindFreedom and BasicNeeds’ community and awareness work, Dr. Dzadey’s implementation of therapy and creation of the Drug Rehabilitation Unit, and Dr. Osei’s repatriation of the Accra Psychiatric Hospital. Though MindFreedom commended the repatriation of patients, BasicNeeds is arguing that there should have been a half-way home or reintegration centre set up to prepare the patients, who might have spent 20 or more years at the hospital, to live an independent life before being returned home. That would have been ideal; however, it is unrealistic because it would have taken a long time to create the rehabilitation centre and the hospital needed to be decongested as quickly as possible. The Castle Road Special School, built in 1968 and directed by Isaac Ben Roosevelt Gadoter, is the only special needs school in Ghana that is located in a Psychiatric Hospital.

The school provides hands-on therapy, art, reading, music, outdoor activities for the mentally ill or disabled in the Children’s Ward at the Accra Psychiatric Hospital. The teachers there represented one of the very few instances when I saw true compassion for the mentally ill/disabled during my time in Ghana and one of the even rarer instances when I heard that someone loved their occupation at the psychiatric hospital. After volunteering at another special needs school for children with autism, learning delays, hearing and speech problems, SENCDRAC, I luckily witnessed even more sympathy and care for the unique children in Ghana. There are 14 other registered special needs schools in Ghana, and they are at the forefront of displaying empathy for the mentally ill and disabled in the country. Hopefully, this sympathy will spread to mainstream schools and then to the entire public. The infrastructure of mental health services is reliant on satisfactory funding and allotting sufficient finances to allow for the delivery of notable mental health services, the effectual training of staff, and the development of collaborations and consultations which will make mental health service much more accessible. Though the health sector in general is underfunded, it is imperative that the Ministry of Health allocates funding to community mental health care and that the financing of the psychiatric hospitals becomes based on need, rather than unjustified ceilings, due to the vulnerable nature of the mentally ill. The Mental Health Bill will guarantee that at least eight percent of the total health budget will be apportioned to mental healthcare. The government is responsible for addressing the needs of its citizens by formulating suitable legislations and the Mental Health Bill offers the government a chance to enhance the delivery and accessibility of mental health services. The World Health Organization is calling the bill one of the best mental health laws in the developing world and believes that when it is passed it can serve as a model for other countries. The bill needs to be passed in order to avoid the collapse of a currently unstable mental health care system. The Mental Health Bill, Dr. Osei, MindFreedom, and BasicNeeds all promote the extension of psychiatric services into community district and regional hospitals.

This integration will also help improve access to mental health services in remote areas where patients presently travel a great number of miles for psychiatric treatment. Currently, care is mainly restricted to the institutional administration of psychotropic drugs instead of preventative or rehabilitative psychosocial interventions, due to the dearth of allied mental health personnel and the limited number of community psychiatric nurses. An accelerated, specialist training program should be locally established in order to increase the number of allied mental health personnel. The problematic brain drain of staff could be alleviated by providing satisfactory remuneration and incentives to encourage trained personnel to stay in Ghana or to return home from overseas. If a mental illness goes untreated, there are three possible consequences for the victim. The first is living with the sickness and underachieving or having low productivity because the person is not performing properly or to their highest potential. Secondly, the untreated person could engage in social vices such as drugs, armed robbery, and paedophilia. The third possibility is to die from complications of the illness, i.e. committing suicide due to depression, engaging in risky activities due to bi-polar disorder, not eating because of schizophrenia, or dying from a tumour that initially caused the illness. Each day that the bill remains before Parliament, Ghana is officially allowing the rights of the vulnerable to be abused by placing patients in overly congested institutions with little doctor-patient contact. A society of acceptance makes a much more favourable environment for recovery from mental illnesses, with stigma representing a large barrier to recovery [8]. Even in developed countries,4×8 tray grow people who are misinformed about mental illnesses can respond negatively to a friend or relative’s mental illness. Mental illness is not caused by poor decisions or by offending the gods, but can affect anyone no matter what ethnicity, background, age, or gender. The mentally ill can benefit from psychotherapy, group therapy, medication, self therapy, rehabilitation, and the acceptance and understanding from friends and family. Programs that encourage understanding and awareness of mental health issues and demystify mental illness should be forcefully undertaken for communities to further tolerate and acknowledge the mentally ill. Overcoming these widely prevalent traditional myths on mental illness will help lead more patients to seek professional treatment early on. Public health officers and the health promotion unit should integrate mental health into their awareness and advocacy programs. Mental health needs to be recognized and integrated into both primary and secondary care, social and health policy, and health system organization. The delivery of mental health care can also be improved by concentrating on currently active programs dealing with the prevention and treatment of tuberculosis, malaria, HIV, domestic violence, and maternal care.

This should spark the interest of the government because advancing the mental health system could help the country reach the Millennium Development Goals which address HIV/AIDs, malaria, tuberculosis, child mortality, maternal health, and the empowerment of women. It has been consistently reported that HIV is associated with poor mental health due to psychological trauma and the causing of neuropsychiatric complications such as depression, cognitive disorder, mania, and dementia due to effects on the central nervous system. Strong evidence from developed countries also shows that depression, alcohol and substance abuse disorders, and cognitive impairment negatively affect adherence to antiretrovirals. In the US, those treated for depression for six months showed improvement in HAART adherence compared to those who did not take antidepressants. Some studies have also shown that the incidence of tuberculosis infection is high in people with serious mental illnesses or substance use disorders. Heavy drinkers had double the risk of being infected with tuberculosis compared to non-drinkers, according to a study in the US. Though there is little evidence, depression might also cause low adherence to anti-tuberculosis medication, which makes it very difficult for a country to control the disease. With gynaecological health being greatly affected by depression, anxiety, sexual and domestic abuse, and substance and alcohol use, many studies have also linked reproductive morbidity with mental illnesses. Depression is more common among women, especially poor women, due to domestic violence and lack of autonomy. Maternal psychosis increases the risk of infant mortality while maternal schizophrenia can result in low birth weight or premature delivery. Postpartum depression also leads to poor mother-infant interaction and little devotion to the health of the child. Mental disorders increase the risk for transmission of infectious disease and the development of non-communicable diseases and communicable diseases, while other sicknesses increase the risk for mental illnesses. Because of this co-morbidity, mental health policies should be integrated into different levels of care, with primary care physicians trained in treating mental disorders. Current community and public health programs or campaigns should become familiar with mental disorders in order to help improve both the physical and mental health of their targeted patients, which will lead to lead to quicker recoveries. If general physicians and prominent health-related NGOs start to increase awareness and encourage or participate in the treatment of mental disorders, a great deal of pressure will be taken off of the limited mental health staff in Ghana.It is estimated that there were 35 million people worldwide living with HIV/AIDS by the end of 2013, of whom 16 million were women and 19 million were men. Among men, people who inject drugs and men who have sex with men were recognized as high-risk groups in many countries. MSM bear a disproportionately higher burden of HIV infection than the general population. In Asia, MSM are as much as 18.7 times more likely to be infected with HIV than the general adult population. Adult men who report having sex with men account for 3–5 % of male cases in East Asia, 6–12 % in South and Southeast Asia, 6–15 % in Eastern Europe, and 6–20 % in Latin America. By the end of 2012, there were approximately 209,000 people living with HIV in Vietnam.

The official language is English but there are about 100 linguistic and cultural groups in Ghana, and English only accounts for 36.1% of the population’s primary language. The 2010 GDP, purchasing power parity, was $38.24 billion dollars, with one-third produced agriculturally. Gold, cocoa, and timber are the country’s main exports and recent oil production is expected to heighten economic growth. Twenty-eight and one half percent of Ghanaians live below the poverty line and 11% are unemployed . Ghana’s health expenditure is roughly 4.5% of the Gross National Product, compared to 15.2% in the US . Ghana is divided 10 regions and 170districts. Due to the proximity to the University of Ghana, Legon Campus, interviews were conducted in the metropolitan capital city, Accra , and in the surrounding Greater Accra Region, which lies on the south-east coast. In order to gain first-hand information and opinions on the current mental health situation in Ghana, 1.5-3 hour interviews were conducted with prodigious psychiatrists and a mental health NGO during spring of 2011. The first two interviews were with Dr. Akwasi Osei, the acting Chief Psychiatrist of the Ghana Health Service and Administrative Head of the Accra Psychiatric Hospital, the oldest and main psychiatric hospital in Ghana. In addition to holding these positions for the past six years, Dr. Osei is also a senior lecturer, researcher, and spokesperson for Ghana’s mental health care. The first interview dealt with matters based on Ghana’s mental health system and the stigma of mental illness, while the second interview addressed the logistics and condition of the Accra Psychiatric Hospital. Dr. Anna Dzadey, a psychiatrist from Poland, was the second interviewee. She has been the Medical Director and Psychiatric Specialist in charge of the Pantang Mental Hospital since 2005. Dr. Dzadey provided ample amounts of information on the Pantang Hospital, one of the three psychiatric hospitals in Ghana.

One of the most prominent mental health NGOs in Ghana, MindFreedom, was also interviewed to learn how they are helping to improve the care available to the mentally ill, and to see if they are noticing signs of advancement. The interview with MindFreedom involved Janet Amegatcher, Nii Lartey Adico, and Dan Taylor,plant growing trays the executives and founders of the NGO.In all of Ghana, there are only three public psychiatric hospitals and four private psychiatric hospitals. The three public hospitals, Accra Psychiatric Hospital, Pantang Hospital, and Ankaful Psychiatric Hospital, are all located in the South, with two in the Greater Accra Region and one about three hours away in Cape Coast in Ghana’s central region. Treatment for mental health care in government hospitals is free and is funded by the Ghana Health Service, which allocates a mere, debatable 0.5–3.4% of the health budget to the mental health sector. There are also four private psychiatric hospitals, two in Kumasi, one in Accra, and one in Tema . Although Kumasi is not along the coast, it is still in the southern half of Ghana. The private hospitals are criticized for being too expensive, and it is said that their patients usually end up at a public hospital once their resources are drained. It is uncertain whether the quality of care at a private psychiatric hospital is superior to that of a public hospital, but there are most likely better accommodation, less congestion, and more doctor-patient contact time. The Accra Psychiatric Hospital offers in-patient and outpatient services, limited counselling and therapy, and clinical training for doctors, psychologists, and psychiatric nurses. Technically, all services are free to the Ghanaian public, but some small fees are charged in order to help keep the hospital running. New patients are obliged to pay four Ghana cedis for a hospital records folder, ID card, and some forms. Patients are also asked to pay about 80 pese was for their medication, which can cost up to 400 Ghana cedis. In turn, this helps the patient to value the medicine on top of providing money for the hospital.

Typically two psychiatric nurses and two aids work in each ward on a daily basis, taking care of an unbelievable amount of patients by dispensing medication, noting observations, feeding, washing, and offering group therapy if there is any time or motivation left. The nurses write down the progress of each patient almost every day, but when asked how often the doctors review these notes, the nurses laughed and encouraged me to ask the medical director of the Accra Psychiatric Hospital. Although doctors should be checking in on their inpatients every day, in actuality, it happens about every two weeks due to the overload of outpatients and inpatients. A nurse will usually only report to a doctor if the condition of the patient has become very poor or if they believe the patient is well enough to be discharged. The Pantang Hospital, the largest of the three psychiatric hospitals, was commissioned in the rural Pantang Village in the Greater Accra Region in 1975 in order to reduce the congestion at the Accra Psychiatric Hospital. It was planned to be a regional psychiatric hospital with a 500 bed capacity, but in addition to the original psychiatric services, the hospital now offers primary health care, reproductive and child health services, and, under the National Health Insurance Scheme, HIV counselling, screening, and ART service. The psychiatric services are free by description, but similar to the Accra Psychiatric Hospital, Pantang asks patients to pay a small fee for their folders and medication if they can afford it. Nurses, nursing students, Health Assistant Training School students, and Community Health Mental Officers also gain clinical psychiatric experience at the Pantang Hospital. Community mental health care exists in Ghana, however, it is not well developed. A Community Psychiatry Nursing Programme began in 1975, and there are currently 120 Community Psychiatric Nurses working in all ten regions, but some regions may have just one or two CPNs. The nurses are not distributed evenly throughout the country, and only 70 districts out 170 are covered by at least one CPN. To become a CPN, a psychiatric nurse only has to train for three to six weeks after their completion of the mental nursing program but soon there will be an official degree program that spans over one or two years. Dr. Osei believes that there should be at least 2,000 CPNs working in the country in order to provide adequate community based psychiatric care.

CPNs are responsible for identifying and managing cases, referring cases to the next level of care, counselling, providing after-care services , and creating awareness and promoting mental health in the community. In addition to institutional care and community mental health, another key component of treatment is traditional healing. Due to the nation-wide presence of unorthodox healthcare and the Ghanaian belief that mental illness is caused by spiritual forces, traditional and spiritual healers tend to the largest sum of mentally ill sufferers in the country. Even urban people who live near the three psychiatric hospitals frequently visit spiritualists. Dr. Osei believes that traditional or faith healing, which uses herbal preparations and/or spiritual incantations/invocations, could be valuable if the administrators recognized their limits. Minor disorders like anxiety, minor depression, neurosis, phobias, or OCD, which might not require medication for treatment, can sometimes benefit from the therapy provided by healers. A healer is typically well trusted and has considerable influence over one’s emotions, so a patient might subsequently change their way of thinking after treatment, or receive reassurance that whatever provoked the problem has been removed in a spiritual manner. However, except for the occasional use of anti-psychotic herbs prescribed by herbalists,rolling grow tables traditional healers generally cannot help a person suffering from a severe mental disorder. It is well reported that abuse of the mentally ill occurs at prayer camps. In a documentary released by Mind Freedom Ghana, the mentally ill are chained to trees, exposed to the sun and rain, deprived of food and/or water, and even chained or flogged in an attempt to exorcise the supposed demons. The violations of a mentally ill person’s human rights have yet to be curbed because there are no laws governing mental health care outside of the psychiatric hospitals. Nonetheless, seeing a faith healer is seemingly less stigmatizing than visiting a psychiatric hospital. A mentally ill person is usually shown some sympathy from the community if they attend therapy from a traditional healer while no empathy is given to one who visits a mental hospital. The executives of Mind Freedom encourage a balance between faith healing and physical treatment when necessary, agreeing that seeing a traditional or faith healer brings fewer stigmas and is more convenient transport wise. Because of this, the normal pattern for Ghanaians involves utilizing traditional care first and then going to a psychiatric hospital if the problem was not cured. Twenty to thirty percent of the Accra Psychiatric Hospital’s patients try spiritual or traditional healing before a family member or the court brings them to the psychiatric hospital. About 20% of patients use faith healing after leaving the hospital for spiritual reinforcement. Patients at the Accra Psychiatric Hospital and Pantang Hospital travel from all over the country and surrounding countries such as Togo, Cˆote d’Ivoire, Benin, Burkina Faso, and Nigeria. On an ordinary day at the Accra Psychiatric Hospital, around 100 to 400 outpatients are seen, ten patients are admitted, and nine patients are discharged from the hospital wards. Dr. Osei extrapolates that about 40,000 outpatients were seen in 2010, but this number might not be very accurate due to faulty forms. Outpatient attendance has reportedly shown an increasing trend since 1995. The number of inpatient admissions is no longer increasing because the hospital’s psychiatrists are now more stringent on their criteria for admittance. Patients are admitted into a ward if they are a danger to themselves or others, if they require medication that cannot be administered on an outpatient basis , or if they are ordered into a psychiatric hospital by the court. The maximum occupancy of the hospital is 600 but there are currently 1,000 inpatients living in the wards, and there were 1,200 inpatients in January 2011. Table 1 and Table 2 reveal the numbers and ages of patients admitted and discharged in the year 2010. In 2010, Pantang Hospital assessed 18,503 psychological outpatients; 9,143 were male and 9,360 were female.

There was a 4.9% increase in outpatients from 2009, when only 17,636 patients were seen. According to data collected from 2004 to 2010, the hospital sees on average a total of 33,410 outpatients per year for both general and psychological causes, with just 15,894 of that number owing to psychological purposes. A range of 20 to 100 psychological outpatients can be seen a day. One thousand five hundred and thirty-nine patients were admitted into the Pantang Hospital in 2010, which reveals a 5.9% decrease in the number of inpatients from 2009. Usually, the number of patients admitted increases between 2.2% to 33% from year to year, though a decrease in attendance was also observed between 2006 and 2007. Over the past seven years, the hospital on average admits 1,371 patients per year, and about ten to twelve patients a day. Table 3 shows the number of patients who were admitted, discharged, and died according to each year. The dashes symbolize a lack of information. It is hard to tell whether there has been an increase in the number of diagnoses of a certain mental disorder within the past decade. The rise in numbers could be a result of increased awareness or a larger population. In addition, it is difficult for Ghanaian psychiatrists to ensure uniformity in diagnosis because of different backgrounds in training and cultural perspectives. Several years ago, the Pantang Hospital, along with the other two psychiatric hospitals, began using the International Classification of Mental and Behavioural Disorders— Tenth Revision , which groups mental disorders into categories and subcategories and assigns each disorder a code number. Even though the ICD- 10 helps systemize and standardize diagnosis, speeds up the digitalization of record, and simplifies comparisons between years, hospitals, and countries, many Ghanaian medical professionals have not been consistent in their usage of the classification system. Old patients should also be re-diagnosed using ICD-10 but because of the additional time this takes, it rarely happens.

Ibudilast did not improve negative mood on drinking or non-drinking days, indicating that its mechanism of action may be non-mood dependent in non-treatment-seeking individuals. Ibudilast reduced the probability of HDDs over 2 weeks for non-treatment-seeking individuals relative to placebo. Ibudilast also attenuated alcohol cue-elicited activation in the VS, potentially through a dopaminergic-related mechanism. This is a critical proof-of-mechanism whereby modulation of neuroimmune signaling via ibudilast reduced the incentive salience of alcohol cues in the brain. Exploratory analyses indicated that ventral striatal activation to alcohol cues was predictive of subsequent drinking in the ibudilast group, such that individuals who had attenuated ventral striatal activation and were treated with ibudilast had the fewest number of drinks per drinking day in the week following the scan. Overall, these findings extend preclinical and human laboratory demonstrations of the efficacy of ibudilast for the treatment of AUD and suggest a potential bio-behavioral mechanism through which ibudilast acts. This study also demonstrates that ibudilast has a favorable side effect profile, even when combined with alcohol. These findings also provide novel insights into the role of neuroimmune modulation in AUD, including its effects on neural and behavioral outcomes of high clinical significance.Imagine, in the near future, you walk into a supermarket with a list of things to buy that you usually keep around the house. You walk in and go straight for the cereal aisle, because you are out of your favorite sugary “fruit loops” cereal. You approach the cereal only to double-take, because all the boxes now look the same. Instead of the colorful box you are used to, there is a plain white box with a large photo of rotting teeth that says, “Fruit Loops” in the same plain font as every other cereal box on the aisle. It just doesn’t feel right to buy the fruit loops without the normal packaging,gardening rack so you move to the next item on your list. Now imagine you decide to buy some beer for an upcoming dinner party. You walk to the beer aisle to pick out the most appealing brand. But as you approach the aisle, you realize that, like the cereal, every type of beer looks the same.

All the beer is packaged in a dark brown color with photos of failed livers and cars wrapped around telephone poles. The beers have different names, but the font and text size are identical. Instead of gravitating to the beers that look interesting, you must try to find a brand name that sounds like something your friend may like. After fifteen minutes, you get frustrated and give up. Finally, you decide to leave the store, but not before grabbing a carton of your favorite cigarettes. You approach the register and notice that again, all the tobacco products look similar. The cigarettes are packaged in an olive-green box with photos of black lungs and large warnings that say, “smoking causes cancer.” This is the last straw. You storm out of the supermarket, having spent twenty minutes shopping and coming away empty handed. The packaging was part of the fun, and it has been taken away from you. You enjoyed playing the games on the back of the fruit loops box. You loved the artistic beer packages that had the added value of convenience. Given the World Trade Organization’s recent decision to uphold plain packaging laws in Australia, this dystopian hypothetical could be a reality.Australia was the first country in the world to implement plain packaging laws for tobacco products with the Tobacco Plain Packaging Act of 20112 , and others have followed suit. Countries like Britain, France, and Hungary have already passed plain packaging laws, while others like Ireland, Canada, South Africa, New Zealand and Belgium are considering the idea.Countries that export tobacco, like Indonesia, are angered by the measures and the negative economic impact it will have. In 2013, Indonesia launched an attack on Australia’s new laws by requesting a consultation from the WTO.A five year legal battle ensued, ending in a landmark decision by the WTO that was a major blow to big tobacco.This Paper will discuss the WTO’s decision and the potential impact, whether good or bad, this decision could have moving forward. Indonesia claims that Australia’s laws contradict their obligations under three major agreements recognized by the WTO: the Agreement on Technical Barriers to Trade , the Agreement on Trade-Related Aspects of Intellectual Property Rights , and the General Agreement on Tariffs and Trade.

The following Parts will discuss the claims made under the TBT Agreement, TRIPS Agreement, and the GATT, as well as provide a prediction of the panel’s legal analysis and debate the possible impact it may have on the future of packaging and product advertising.It seeks to discourage its citizens from smoking, prevent relapse for those who have quit, and reduce overall exposure to tobacco products.In this spirit, the TPPA regulates “the retail packaging and appearance of tobacco products”, and therefore can “reduce the appeal of tobacco products . . . increase the effectiveness of health warnings . . . and reduce the ability of the retail packaging of tobacco products to mislead consumers about the harmful effects of smoking.”The TPPA enforces stringent requirements for the packaging of all tobacco products and establishes penalties and sanctions for violations.The Act regulates all tobacco products but includes specific regulations for cigarettes as well.For example, cigarette packaging must be rigid, have a matte finish, be made of cardboard, and must not be “embellished in any way, [unless] permitted by the regulations.”The color of the packaging must be a drab brown color , with the only exceptions being health warnings and brand names.The TPPA also states that no trademarks can appear on packaging except for the company name, relevant legislative materials, and any trademarks permitted by the TPPR.Further, the brand or company name must comply with specific provisions set out in the TPPR and may only appear once on the packaging.The TPPR establishes requirements for specific colors, dimensions, and features of the packaging.These regulations not only give the packaging a uniform and unattractive appearance, they also help prevent tobacco companies from misleading consumers and maximize the effectiveness of the health warnings.The color of the packaging must be “Pantone 448C,” a dull olive green and brown mixture like the color mentioned in the above hypothetical.These regulations also state that writings, other than health warnings, must be “in the typeface known as Lucida Sans . . . no larger than 10 points in size . . . in a normal weighted regular font . . . and in the colour known as Pantone Cool Gray 2C.”Indonesia cites to Articles 2.1 and 2.2 of the TBT, which fall under the “Preparation, Adoption and Application of Technical Regulations by Central Government Bodies” section of the agreement.Article 2.1 of the TBT Agreement declares that member states “shall ensure that in respect of technical regulations, products imported from the territory of any Member shall be accorded treatment no less favourable than that accorded to like products of national origin and to like products originating in any other country.”

In an earlier case, US-Clove Cigarettes , Indonesia complained that the United States violated,vertical farming equipment among other things, Article 2.1 of the TBT Agreement.28 Similar to its later complaint in Australia-Plain Packaging, Indonesia challenged U.S. regulations that were created to promote public health by dissuading tobacco use.Specifically, Indonesia challenged measures that banned flavored tobacco and clove cigarettes but not menthol cigarettes.Because Indonesia is a large producer of clove cigarettes, and the United States is a large producer of menthol cigarettes, Indonesia claimed the regulations “accorded to imported clove cigarettes less favourable treatment than that accorded to like menthol cigarettes of national origin.”This vital Appellate Body decision articulated the proper test for determining a violation of Article 2.1.According to the Appellate Body, to establish a violation of Article 2.1, “three elements must be satisfied: the measure at issue must be a technical regulation; the imported and domestic products at issue must be like products; and the treatment accorded to imported products must be less favourable than that accorded to like domestic products.”Regarding the first element, Annex 1.1 of the TBT Agreement defines the term “technical regulation” as a “[d]ocument which lays down product characteristics or their related processes and production methods, including the applicable administrative provisions, with which compliance is mandatory. It may also include or deal exclusively with terminology, symbols, packaging, marking or labelling requirements as they apply to a product, process or production method.”Because regulations in question are likely to be agreed upon as technical regulations, this element of the test need not be further discussed. The second element of the test requires that the imported and domestic products be “like.”In Clove Cigarettes, the Appellate Body addressed the meaning of like products in the context of Article 2.1.Although it agreed that menthol cigarettes and clove cigarettes were like products, it disagreed with the way the Panel came to that conclusion.According to the Appellate Body, the Panel erred in focusing on “the purposes of the technical regulation at issue, as separate from the competitive relationship between and among the products.”The proper analysis of like products must take into consideration the context of “Article 2.1 itself . . . other provisions of the TBT Agreement . . . the TBT Agreement as a whole, and . . . Article III:4 of the GATT 1994, as well as the object and purpose of the TBT Agreement . . . ”When viewed in this context, the test for likeness should be “based on the competitive relationship between and among the products . . . ”The third element, that “the treatment accorded to imported products must be less favourable than that accorded to like domestic products”, was also addressed by the Appellate Body in Clove Ciga-rettes.The Appellate Body first noted that, in the context of the TBT Agreement, Article 2.1’s “treatment no less favorable” requirement prohibits both de jure and de facto discrimination.However, to analyze Article 2.1 in the context of the similarly worded Article III:4 of the GATT, the Appellate Body noted that any examination of an Article 2.1 violation “should seek to ascertain whether the technical regulation at issue modifies the conditions of competition in the market of the regulating Member to the detriment of the group of imported products vis-à-vis the group of like domestic products.”In light of these conflicting ideas, the Appellate Body concluded that where measures do not “de jure discriminate against imports, the existence of a detrimental impact on competitive opportunities for the group of imported vis-à-vis the group of domestic like products is not dispositive of less favourable treatment under Article 2.1.”Instead, the correct approach is to “analyze whether the detrimental impact on imports stems exclusively from a legitimate regulatory distinction rather than reflecting discrimination against the group of imported products.”A detrimental impact stemming from a legitimate distinction is determined by careful scrutiny of the particular circumstances of the case.After careful scrutiny, the Appellate Body determined that the U.S. measure did not stem exclusively from a legitimate regulatory distinction.Specifically, the Appellate Body cited the purpose behind the measure as a reason why it was not in compliance with Article 2.1.Because the measure was enacted to deter youth smoking by banning flavored cigarettes, and menthol cigarettes are flavored, there was no reason for menthol cigarettes to be exempted.The TRIPS Agreement was also enacted as a part of the establishment of the WTO in 1995.Its purpose is to “reduce distortions and impediments to international trade . . . and to ensure that measures and procedures to enforce intellectual property rights do not themselves become barriers to legitimate trade . . . ”Indonesia cites to, inter alia, Article 3.1 in its Request for Consultations.This Part will examine Article 3.1 and its WTO jurisprudence. Article 3.1 is the “National Treatment” provision of the TRIPS Agreement, much like Article 2.1 of the TBT Agreement and Article III:4 of the GATT. Article 3.1 states, in pertinent part, that “[e]ach Member shall accord to the nationals of other Members treatment no less favourable than that it accords to its own nationals with regard to the protection of intellectual property . . . ”WTO jurisprudence on Article 3.1 is scant, but one dispute heard by the Panel, EC-Trademarks and Geographical Indications, discusses the application of Article 3.1 in detail.

Complete results are available upon request. Two sets of temperament by monitoring interactions replicated across both substance use and intention variables – those involving effortful control and depressive mood. Results suggested that parental monitoring had very little association with substance use intentions and substance use in 9th grade for adolescents with high levels of effortful control in 5th grade. However, parental monitoring was a significant predictor of these variables when adolescents were low in effortful control. Likewise, monitoring was primarily a protective factor when depressed mood was relatively high in 5th grade. These interactions are illustrated in Figures 1 and Figure 2. In short, there were indications that parental monitoring might be most relevant for youth with dispositional tendencies associated with substance use. We then evaluated concurrent relations using 9th grade data. Selected results are presented in Table 6. Significant results were restricted to the substance use intention variable, but the effortful control and depressive mood pattern was replicated. In general, the significant patterns were consistent with the prospective analyses and indicated that monitoring was a stronger predictor for youth with temperamental dispositions that placed them at risk for greater substance use . However, these interactions were restricted to only one substance use variable, and thus should be viewed with caution. We investigated the prospective influence of temperament and parental monitoring on substance use using data from a longitudinal study of Mexican-origin youth and their families. We focused on willingness to use substances , expectations for positive outcomes , and lifetime use of alcohol, cigarettes, and other drugs. The rates of substance use in this sample were similar to what has been reported for Hispanic adolescents in nationally representative surveys . Specifically, around 40% of participants had tried a substance at least once by 9th grade , and furthermore, considerably more participants had tried a substance by 9th grade compared to 5th grade. These rates are thus also similar to what has been reported for European American and African American adolescents,pruning cannabis and higher than what has been reported for Asian American adolescents .

As expected, low effortful control and high aggressive tendencies assessed in 5th grade were the most robust predictors of substance use variables in 9th grade. These findings fit with previous research indicating that temperamental traits related to impulsivity are associated with substance use . Moreover, these associations held while controlling for previous levels of the substance use variables in 5th grade . This finding is consistent with White and colleagues’ suggestion that aggression serves as a risk factor for future substance use irrespective of previous use. These longitudinal findings are particularly noteworthy because Mexican Americans are the largest and fastest growing ethnic minority group in the United States, yet this population has received relatively little attention in research on the temperamental correlates of substance use. Beyond finding evidence that temperament prospectively predicts substance use, we also examined the main and interactive effects of parenting monitoring. Consistent with previous research , child-reported parental monitoring in 5th grade was associated with 9th grade substance use variables, even after controlling for prior levels. In contrast, parent reports of monitoring had only concurrent associations with substance use variables. Although the greater predictive power of child reports could simply reflect shared method biases, we believe that a pure methodological explanation is unlikely to fully account for the findings. Instead, we suspect that youth perceptions of parental behaviors are especially salient developmental considerations when attempting to understand risk for substance use. Youth who believe their behavior is being monitored will likely behave differently than youth who do not believe there is surveillance of their behaviors. Indeed, beliefs about parental behaviors and values might be more consequential than actual parental behaviors and values for understanding adolescent substance use. This is consistent with Voisine and colleagues’ suggestion that parental injunctive norms are more effective in preventing substance use than parental monitoring per se.

Nonetheless, further research is needed to better understand the relative importance of child vs. parent reported monitoring for substance use outcomes. We found a number of significant interactions between temperament and child-reported parental monitoring. Most notably, both effortful control and depressive mood interacted with monitoring in 5th grade to predict intentions and use in 9th grade. These interaction effects suggest that parental monitoring is a protective factor for youth with the temperamental tendencies associated with risk for substance use. Considered from another perspective, the interaction effects suggest that certain temperamental traits are risk factors for substance use when parental monitoring is low, but not when it is high. Either interpretation is consistent with the findings and points to a similar conclusion about how temperament and parenting work together to increase risk for early substance use. Being raised in a home with a perception of minimal monitoring by parents may be a more salient risk factor for substance use for those adolescents with dispositional proclivities toward substance use, and possessing a disposition toward substance use may be a stronger risk factor when youth do not believe they are closely monitored by their parents. The broader developmental consideration is that temperamental factors and family variables should be considered jointly in models that attempt to understand early risk for substance use. Although the current study was notable for its multi-informant longitudinal design, and for the size and ethnic composition of the sample, there are limitations that merit consideration. For instance, our ability to detect effects for surgency was hampered by the low reliability of the scale in the 5th grade; thus, results involving surgency should be interpreted with caution. Also, we relied exclusively on youth reports of their substance use, intentions, and expectancies. However, intentions and expectancies are inherently subjective variables and are thus best assessed via self-report. Likewise, focal youth might be in the best position to report on their actual use given understandable motivations to hide substance use from parents, teachers, and other potential informants. In closing, we found evidence from a longitudinal study of Mexican-origin youth that temperament and parental monitoring assessed in 5th grade are prospectively related to substances use outcomes in 9th grade.

These findings are important because they suggest that theoretical models concerning the influence of temperament on substance use can be applied to adolescents of Mexican origin. Indeed, we suspect that factors like temperament and parental monitoring have transcontextual validity to the extent that they are risk factors for early substance use for a diverse range of youth. Of particular importance, we also found that relatively high levels of perceived monitoring might attenuate some of the risks associated with dispositional tendencies toward substance use. Although the current results should be replicated, we suggest that future intervention and prevention efforts could be enhanced by attending to individual differences in temperament. Such attention might be especially important when considering efforts to increase parental monitoring. Alcohol remains the most commonly used substance of abuse during adolescence and young adulthood. The act of binge drinking, often defined as the consumption of greater than either 4 or 5 drinks in a given drinking episode,dry room is of particular concern in youth given the host of associated negative consequences and potential for neurological alterations to the developing adolescent brain . Approximately 17% of 12th graders and 33% of college-aged young adults reported recent binge drinking, defined as the consumption of 5 or more drinks in a row at least once in the two weeks prior to assessment . Notably, almost 1% of adolescents aged 12 to 17 and 10% of young adults aged 18 to 25 engage in binge drinking episodes frequently, averaging more than once per week over the previous 30 days . Frequent binge drinking during adolescence is associated with elevations in multiple risk factors, including adolescent drug use, antisociality, and parent alcoholism , as well as a number of negative consequences in adulthood such as alcohol use disorder diagnosis, drug use, psychiatric morbidity, homelessness, legal problems, accidents, and lower social class . Importantly, many of these elevated risks are greater for those who frequently binge drink during adolescence, as opposed to those who are infrequent/moderate binge drinkers , suggesting that the frequency with which one binges during adolescence is an important factor in future alcohol-related outcomes. Thus, given the known neurotoxicity of alcohol at higher doses , efforts to predict who is at risk of drinking at these frequent high levels during the critical period of neurodevelopment are warranted.In line with this, diminished inhibitory control during adolescence is consistently implicated as a risk factor for future alcohol and substance use . Successful inhibitory control likely involves the ventral attention, fronto-parietal and fronto-striatal networks, including regions such as the inferior frontal gyrus extending to the insula, cingulate and paracingulate gyri, superior parietal gyrus, and basal ganglia structures , suggesting deficiencies in these networks may serve as correlates of alcohol-related risk prior to binge drinking onset . Longitudinal functional magnetic resonance imaging studies of adolescents have identified several neural aberrations during inhibition, as measured on the Go/No-go task, as significant predictors of greater alcohol and substance use, even in the absence of behavioral differences on the tasks . Specifically, greater left angular gyrus and less ventromedial prefrontal blood-oxygen-leveldependent activation during no-go correct rejection vs. go trials in 16 to 19 yearolds was found to predict higher levels of alcohol and substance use and dependence symptoms over an 18-month follow-up.

This effect was especially pronounced for adolescents who were high frequency substance users at baseline . In an analysis of 12–14 year-olds scanned prior to the onset of alcohol use and followed up about 4.2 years later, less BOLD response in regions including the right inferior frontal gyrus, left dorsal and medial frontal areas during no-go correct rejection vs. baseline trials was found to differentiate between those who transitioned to alcohol use from those who remained continuous controls ; however, the activation in those regions was found to be associated with attention problems at follow-up, and not substance use outcomes per se, suggesting the groups may have differed on multiple related factors. In an additional longitudinal analysis of 11–16 year-olds, with follow-up approximately 3 years later, adolescents who transitioned into drinking by follow-up exhibited less BOLD response during no-go correct rejection vs. go trials at baseline in bilateral middle frontal gyri, left putamen, right inferior parietal lobule, and left cerebellar regions. Yet increased activation was observed after the onset of heavy drinking in all regions except the putamen, as compared to matched continuous non-drinkers who displayed decreased activation in these regions at follow-up . These results suggest alcohol-exposure may increase engagement of these neural networks in order to successfully inhibit prepotent responses; however, the degree of alcohol exposure required to produce this change has yet to be investigated. Taken together, the current literature implies the presence of a pre-existing neural inhibition risk profile for future alcohol and substance use, along with a potential for additional alcohol and substance-related disturbances in normal neural inhibitory maturation processes. However, the neural underpinnings subserving the transition from moderate, arguably even “normative”, alcohol use behavior in adolescence to the extremely high-risk pattern of frequent binge drinking have not been determined. Thus, the present study seeks to prospectively predict the time to transition to high-risk frequent binge drinking from the neural patterns of successful inhibitory control in a single sample of adolescents who were already engaged in moderate alcohol use. Given the broad set of inhibitory-related regions identified in the earlier literature, a whole-brain exploratory approach was used for the present analysis, with a general hypothesis of alcohol risk-related activation to fall within the fronto-parietal and fronto-striatal networks. No directionality was hypothesized for the present analyses given the mixed results of the literature and the novelty of the current inquiry. Current study data was culled from a larger, ongoing longitudinal substance use and neuroimaging project . Participants at baseline were healthy 12–14 year-olds, recruited through schools in the San Diego area, with very minimal to no experience with alcohol or drugs. Exclusionary criteria for the parent study at baseline included: premature birth prior to the 35th gestational week; report of prenatal alcohol or illicit drug exposure; history of any DSM-IV Axis I or neurological disorder; psychoactive medication use; loss of consciousness or head trauma; learning disability or mental retardation; chronic medical illness; history of alcohol use ; history of drug use ; non-correctable sensory problems; and inadequate English comprehension.

The public-use NSDUH provides estimates of the prevalence of past-month use and past-year initiation of marijuana, available separately for age groups of 12-17, 18-25, and 26 years of age and older. Representative state-level data broken down by two-year averages is available from. Table 2.3 provides summary statistics for the marijuana use measures and state level covariates used in the NSDUH analysis. Comparing mean differences, MML states with a positive number of registered medical marijuana patients have higher levels of past-month cannabis users for all age groups than states without MMLs. However, MML states on average are more likely to have decriminalized marijuana,have higher cigarette taxes, and consist of populations that are on average younger and more male. As such characteristics are potentially correlated with prevalence of recreational cannabis use, all regressions control for the state covariates listed in Table 2.3. There are some limitations to this dataset. Firstly, the public-use NSDUH data is only available in two-year averages; thus the registration rate data may not correspond exactly with the marijuana outcome data, leading to a loss of precision for these estimates.22 Secondly, the NSDUH measures of substance use are self-reported. If individuals are more likely to report marijuana consumption truthfully based on legality, analysis of the effects of legal market size compared to MML enactment should be less subject to reporting bias. However, if reporting is driven by perceived changes in social approval, growth in the legal market size may induce changes in reporting behavior. Section 2.6 and Appendix D- provide supporting evidence that the self-reported marijuana use measure captures true changes in consumption. Despite these problems, the NSDUH is the only publicly available dataset that provides representative state-level estimates of marijuana consumption for all individuals aged 12 and older.

Additionally, the NSDUH Restricted-use Data Analysis System provides state-level estimates for perceptions about marijuana,heavy duty propagation trays which are used in section 2.6 to examine the mechanisms by which changes in the legal market affect adolescent marijuana use.Figure 2.2 presents descriptive evidence of changes in marijuana consumption over time. Trends in past-month use and past-year initiation are plotted by age groups and by strictness of state MML supply regulation. All trends are normalized such that the prevalence measure is zero for 2007-2008, the years just prior to the Ogden Memo. For all age groups, marijuana consumption increases in MML states after the Ogden Memo. For youths and young adults, these increases are largest in MML states with loose supply regulations, while loose and strict MML states saw similar growth rates for older adults. For adolescents aged 12-17, there is a sharp drop in consumption in MML states with loose regulations following the Cole Memo; for adults, consumption does not decrease after the Cole Memo but trends in use flatten. To examine whether these patterns in marijuana consumption are driven by growth in medical marijuana availability, Table 2.4 reports the first-stage and reduced form estimates of the differential effects of the Ogden and Cole Memos in MML states with lax supply restrictions on registration rates and the prevalence of marijuana consumption. The first-stage results of Table 2.4 are replicated from Column of Table 2.2 and are discussed in section 2.2.4. The F-test for excluded instruments takes a value of 52.3, mitigating any concerns of finite sample bias due to weak instruments . The reduced form results for past-month use and past-year initiation by age group have the expected signs, though the instruments have less predictive power for past-year marijuana initiation. Since this approach identifies effects off of changes in a monthly time series, ex-ante the results for past-month use are expected to perform better than the results for past-year initiation. Table 2.5 reports the estimated effects of growth in the legal medical marijuana market on marijuana consumption, showing results separately by age group for preva-lence of past-month marijuana use and past-year initiation.

To test whether these effects are driven by omitted variables influencing both legal and illegal use, the second-stage results of the instrumental variables analysis are compared to the OLS estimates. The results indicate that growth in medical marijuana registration rates significantly increases marijuana consumption for all age groups, with the largest effects for older adults. An additional one percentage point of the adult population registering as medical marijuana patients predicts a significant 6% increase in the share of 12-17 year olds reporting past-month marijuana use, a 7-8% increase for 18-25 year olds, and a 20% increase for older adults. The effects on past-year initiation are similar but smaller in magnitude, indicating a 1-5% increase in the share of 12-17 year-olds reporting past-year initiation, a 6% increase for 18-25 year olds, and a 12-18% increase for adults over age 25. Additionally, these estimates support that using registration rates as an exogenous measure of the size of the legal marijuana market does not produce biased estimates. The IV estimates are neither qualitatively nor statistically different than those from OLS, suggesting that changes in registration rates and recreational use are not being driven by some unobserved factor correlated with both recreational and medical demand. This conclusion will hold if the instruments are indeed excludable, supporting evidence of which is presented next. The exclusion restriction will be violated if changes in federal enforcement due to the Ogden and Cole Memos had differential effects on demand in states with lax compared to strict production restrictions through any channel other than supply. For example, the exclusion restriction would be violated if, when federal enforcement was removed and registration rates increased, local governments in strictly regulated states devoted more resources toward prosecuting users than state governments in states with loose regulations. I provide evidence that this did not occur in Figure 2.3, which plots changes in per user state marijuana possession arrest rates against changes in registration rates. Results are shown separately for juveniles and adults. There is no apparent correlation between legal market growth and state enforcement for either strict or loose regulatory regimes.

Another potential violation of the exclusion restriction would occur if, prior to the Ogden Memo, the expected user risks of federal prosecution were higher in states with loose compared to strict supply regulations. To address this, I first show that the actual risk of a marijuana user facing federal enforcement is very low. The federal government has never devoted substantial resources toward prosecuting individuals for simple marijuana possession. Figure 2.4 shows from fiscal year 1996 through 2012, less than 4% of federal prosecutions for marijuana-related offenses have been for simple possession.24 Between 1996 and 2012, the annual average of federal prosecutions for marijuana possession was 224 compared to 6,259 for sales. Focusing on enforcement against medical marijuana specifically, reports suggest there were fewer than 20 federal prosecutions of medical marijuana users or growers from 1996-2005 and about the same number from 2005-2009; this enforcement was almost exclusively directed toward large-scale producers in California. While the actual probability of federal prosecution was low, uncertainty among potential medical marijuana users about whether the federal government could access registry data may still have stifled demand. This deterrent was likely far greater in California than in other states,vertical cannabis as federal prosecution against suppliers was concentrated in California. Vickovic ’s analysis of news article mentions of medical marijuana showed that almost all articles about federal enforcement prior to the Ogden Memo were about dispensary raids in California, and the majority of these articles were published by local sources. Thus, it may be the case that the Ogden Memo led to a relatively larger shift in demand in California compared to other MML states.25 To address these concerns, Table 2.6 reports the results of the instrumental variable specification excluding California. The results for past-month use are unchanged, but the effect of legal market growth on past-year initiation for adolescents becomes small and insignificant and shows evidence of endogeneity. These results are consistent with past-month use serving as a better measure to detect short-run changes in marijuana access, while past-year initiation may better reflect longer-run changes in social approval or risk perceptions. In the regressions without state-specific trends, both registration rates and the categorical variable for MML enactment have positive effects on marijuana consumption, though the effects of the categorical MML variable are only significant for adults over age 25. However, after including state-specific linear trends to account for state differences in preexisting paths of marijuana use, the estimates for MML passage become small and insignificant and switch sign. In contrast, estimates of the effects of registration rates remain positive and significant for all age groups. The registration rate estimates are less sensitive to trend inclusion than those of the categorical variable. This could be due to the non-monotonicity of trends in registered patient counts or the categorical MML measure confounding preexisting trends with the dynamic effects of the policy .

Additional robustness checks of sample selection and model specification in Appendix D- support that the binary MML measure misses heterogeneous effects across states and the dynamics of these policies. There are a number of mechanisms through which MML policy, promoted as legislation to protect cannabis use for a relatively small number of individuals with chronic health conditions, might affect marijuana consumption by adolescents. If registered adult users are more visible to adolescents, youths may increase consumption due to lower perceived risks associated with social disapproval, formal sanctions, or health consequences. If growth in the legal market increases total availability, increased adolescent use may be driven by lower search costs, increased product variety, or declines in the quality-adjusted price of marijuana following the shift in supply . Sections 2.2 and 2.5 suggest that supply channels are particularly important indetermining MMLs’ effects on adolescent use. Spillover of medical marijuana supply to the illegal market serving adolescents could occur through resale or sharing of medical marijuana by legal users.27 Recent national surveys of high-school seniors show that almost 18% of past-year users report receiving some marijuana from another’s medical marijuana “prescription” ; focusing only on high-school seniors in states with MMLs, 34% of past-year users report one of their sources as another person’s medical marijuana “prescription” . This indicates substantial diversion from the legal market supplying medical marijuana patients to the illegal market supplying youths. Table 2.8 provides evidence of the mechanisms by which growth in the legal market influences cannabis consumption by youths aged 12-17 using state-level data from the NSDUH R-DAS. Columns – report effects on risk perceptions, and columns – report effects on measures of adolescent access. The outcome variable for each column is the share of youths aged 12-17 who report that: using marijuana monthly poses a “great risk,” their friends “somewhat” or “strongly” disapprove of monthly marijuana use, the maximum penalty for possession of one ounce of marijuana in their state is prison time, marijuana is “somewhat” or “very” easy to obtain, most students their age use marijuana, and they purchased marijuana in the past year. Since these measures are likely determined endogenously, these results are intended only to provide suggestive evidence. While growth in the legal market affects adolescent perceptions of both risk and availability, the results of Table 2.8 suggest that the legal market primarily affects adolescent use through changing access. A one percentage-point rise in registration rates significantly increases the share of 12-17 year-olds who believe marijuana is easy to obtain , who believe most students their age use marijuana , and who report buying marijuana in the past year ; these estimates are jointly significant with a p-value of 0.04. In contrast, estimates of the effects on risk perceptions are smaller and jointly insignificant with a p-value of 0.13. These results thus provide supporting evidence that the increases in adolescent marijuana use following medical marijuana market growth are due to supply spillovers rather than decreased risks of legal penalties or social disapproval. According to Department of Justice National Drug Threat Assessment reports, there is substantial internal movement of domestically produced marijuana, and Figure E.1 clearly illustrates that the sources of much of the marijuana trafficked domestically are the western MML states of Washington, Oregon, California, and Arizona. As marijuana markets are not isolated , supply shocks in legal medical marijuana state markets likely have spillover effects on price and availability in states without MMLs or in MML states with high production costs. For the empirical results, this should bias the estimates of the effects of legal market size toward zero. Tables E.1 and E.2 use Montana as a case study to assess whether spillover of marijuana supply from states with large legal markets to other states is biasing the estimates from the primary results downward.