To help address this we did include substance use disorder in estimating substance use among adults with chronic diseases.College-going individuals in the United States may have unique attitudes toward substance use behavior and tobacco use, including shifts in attitudes and behaviors that are associated with the constantly changing product landscape of alternative tobacco products , such as electronic-cigarettes . Psychosocial behaviors and campus culture, including class attendance, peer socializing, campus policies, and residential environments, may also facilitate these unique attitudes toward favorability of smoking among college subgroups, while also introducing a unique risk environments for tobacco initiation, uptake, transition, and use . In addition, part of the variation explaining these health behaviors may be influenced by the specific demographic and socioeconomic characteristics of a college campus population and community. Data from social media platforms are often used to self-report and publicly communicate health-related attitudes and behaviors . Young adults [ages 18–25 ] in the United States are much more likely than older populations to actively use social media, including popular platforms Twitter, Snapchat, and Instagram . Infoveillance research, which uses online information sources to detect trends about the distribution and determinants of disease, including health knowledge and behaviors, has been used to develop insights on numerous public health issues including infectious diseases, vaccination sentiment, opioid use disorder, mental health issues, and, relevant to the exploratory aims of this study, tobacco and alternative tobacco use attitudes and behavior . However, smoking-related discussions on social media tied to specific colleges with geographic specificity has not been widely investigated. Existing studies using social media to examine tobacco-related attitudes and behaviors in college aged populations have primarily focused on evaluating the impact of social media health promotion anti-tobacco campaigns,commercial greenhouse supplies recruiting hard-to-reach college populations using social media platforms, and examining the influence of exposure to tobacco-related social media content and marketing on current and future behavior and use .

Other research on college-aged populations has focused on assessing tobacco initiation and transition of use patterns, particularly as new alternative and emerging tobacco products become available . Accelerating research using social media to assess tobacco-related attitudes/influences among youth has also been supported by U.S. Federal initiatives, including projects funded by the National Cancer Institute and U.S. Food and Drug Administration Tobacco Centers of Regulatory Science, which for have identified and characterized e-cigarette advertisements on image-focused social media sites and tobacco user experiences with little cigars and e-cigarettes as discussed on Twitter . Changes in local, state, and national health policy related to tobacco and other products smoked or used concurrently with tobacco and electronic cigarettes can also have an impact on attitudes and behaviors of these populations. For example, recent debate in the United States regarding the legalization of marijuana/cannabis may positively influence marijuana-related attitudes for college populations, who tend to skew toward more liberal policies regarding decriminalization, legalization, and increased access . Similarly, the 2019 outbreak of e-cigarette and vaping-related lung injury associated with products containing tetrahydro cannabinol may dissuade tobacco or THC use in certain young adult populations, particularly since they were most heavily impacted by the disease . Examining the changing public attitudes and behaviors of college-aged smokers is particularly salient for the State of California, USA. As of January 2014, all campuses in the statewide University of California system became tobacco free , and the California State University system followed suit in 2017 . In addition, voters in California approved Proposition 56 in late 2016, which added a $2.00 increase to the cigarette tax effective April 2017, with an equivalent increase on other tobacco products and electronic cigarettes . Voters in 2016 also approved Proposition 64, which legalized the use of recreational cannabis in November 2016 . During this time, the popularity of e-cigarettes in the United States was increasing .

These changes in policy and preferences underscore the interconnected nature of the Triangulum of tobacco products , including potential for dual-use, transition between products, and challenges associated with conducting surveillance and implementing cessation programs . This changing policy landscape supporting tobacco control measures, as reflected in the shift of California’s public university systems to become smoke-free, is a key impetus for this study. The ability of these colleges to eliminate on-campus smoking relies in large part on understanding past and existing knowledge and attitudes held by the campus smoking populations, along with their perceptions and behaviors that may be associated with compliance or non-compliance to smoke free campus policies. In response, this study conducted exploratory research on the popular micro-blogging platform Twitter. specifically, we used big data, data mining, and geospatial approaches to identify and characterize tweets originating from Twitter users specifically geolocated at California 4-year university campuses. Our primary objective was to assess types of tobacco and ATP products mentioned by users, the distribution of user sentiment toward tobacco and smoking behavior, and to assess the feasibility of detecting self-reported smoking behavior that may represent a violation of campus smoke free policies. Secondarily, we also sought to conduct a cross-campus assessment to determine how these factors vary across different university and college communities and over time. The objective of the study’s data collection approach was to obtain a highly refined subset of tweets, which were both posted from college campus’ geolocated coordinates in California and also included user discussions about smoking, in preparation for manual review to more purposefully identify tweets that specifically discussed different types of tobacco and smoking products, sentiment of users toward smoking behavior, and self-reported smoking behavior on campus.

Data were collected from the Twitter public streaming Application Programming Interface using the cloud-computing service Amazon Web Services . The public streaming API was set with fifilters to collect all tweets that included metadata containing latitude and longitude coordinates, initially with no filter for keywords. Tweets were collected continuously from 2015 to 2019. All tweets collected included the text of the tweet and associated metadata, including the date and time of tweets. The use of the public Twitter streaming API to collect data pre-filtered only for tweets including latitude and longitude coordinates represent a subset of all tweets posted during the time frame of the study. There exists the potential for sampling bias associated with different Twitter APIs that are not representative of all Twitter data , and data filtered only for geocoded data may omit many conversations from college aged populations about topics, such as smoking, which may be linked to college-related user groups . Though resulting in a much smaller volume of data, our approach nevertheless allows for detection of tweets in specific geospatial bounds at the high resolution of latitude and longitude coordinates in the state of California. Therefore, by using this data collection approach, we were able to isolate tweets originating from geospatial coordinates within the formal spatial boundaries of all 4-year universities in California. To enable this geolocation, a basemap of California 4-year universities from the Stanford Prevention Research Center was obtained and cross-referenced. Tweet geolocated points were spatially joined to campus polygons using ArcGIS software.College areas were comprised of multiple polygons for different campuses and associated properties,cannabis dry rack though aggregation was conducted at the overall college level to enable comparison across different colleges. Tweets were then filtered for 37 keywords which were broadly related to tobacco-related topics, including the names and brands of different tobacco and ATPs and descriptive terms associated with smoking and vaping as expanded upon from those used in prior studies . specifically, the following keywords were used: bidis, cigarette, cigarettes, cigarillos, cigars, cigie, class, dip, e-cig, hookah, huqqa, joint, JUUl, kereteks, Marlboro, Newport, njoy, pipe, roll-up, shag, smoke, smoking, snuff, snus, tobacco, vape, vaped, vapejuice, vaper, vapes, vaping, vapor, water pipe, waxpen, and weed. The purpose of this keyword filtering was to better isolate smoking-related conversations from all other Twitter discussions occurring on college campuses. After tweets were manually reviewed to positively identify smoking-related conversations originating in these college campuses, a snowball sampling design was employed which compared the frequency of all non-keyword terms in “signal” tweets with the frequency of these words in “noise” tweets .

This methodology resulted in the identification and querying for ten additional keywords: 420, 818, blunt, bong, cigs, kush, marijuana, roll, smell, and stoge. Based on our use of tweets specifically geolocated for CA 4- year universities combined with a data filtering process to isolate tweets containing smoking-related keywords, 7,342 tweets were obtained for analysis that discussed smoking and also originated from California universities between 2015 and 2019. Within this corpus of social media messages, rates for use of the term “weed” decreased over time, changing from 28% in 2015 to 7% in 2019. Other commonly used smoking-related terms did not exhibit a percentage drop of this magnitude. The mechanisms underscoring the observed decrease in social media messages with this keyword are not clear but may result from evolving word choices to describe marijuana, decreased use of marijuana on CA college campuses, social inhibition of posting marijuana related public messages on Twitter, or some combination thereof. Further, it is unclear how passage of legalized adult-use cannabis Proposition 64 may have impacted these conversations, attitudes, and behaviors, particularly as despite state legalization, some college-aged students may not be of legal age and campus smoke free policies still restrict their use. Manual review uncovered 1,089 tweets explicitly related to smoking behavior and posted within the boundaries of California 4-year universities, with the majority of tweets expressing positive sentiment about smoking products and behavior. Five-hundred and-two of these tweets reported first-person use or secondhand observation of another person’s smoking behavior, with 146 tweets reporting possible violations of smoke- or tobacco free campus policies that were clearly in place from 2015 but were also in the process of being fully implemented. These tweets indicate early lack of compliance to smoke-free campus policy implementation as self-reported by social media users. For campuses where policies were not in place, tweets also reflect general positive sentiment about smoking and reports of smoking behavior, indicating possible barriers to enacting campus smoke free policies that would occur in 2017, when more smoke free campus policies across the California State University system were enacted. These results provide early indications that smoke free campus policy implementation requires continued attention and sufficient resources to ensure appropriate health promotion, education on policy requirements, and policy enforcement measures in college communities. Overall, our analysis found a higher number of tweets in our corpus identified for tobacco and marijuana products, with comparatively fewer for vaping products geolocated for California university campuses. The majority of geolocated data collected during this study originated in 2015, which may explain the overemphasis on tobacco and marijuana Twitter conversations as vaping products were rising in popularity. Additionally, national debate about marijuana legalization occurred during this time frame, though was not legalized in California for adult recreational use until 2016 and licensure of cannabis retailers was permitted in 2018. As previously stated, national and state discussions relating to marijuana legalization may have influenced the relative social acceptability and volume of marijuana-related Twitter conversations among campus populations. Tweets about vaping had the highest proportion containing first-hand accounts of use or other persons engaged in product use and behavior. The increasing popularity of vaping products throughout the study time period, especially among the college aged population, may partly explain why college students posted about themselves or other people using vaping products in this context, despite having an overall lower volume than other smoking products . The increasing use of more discreet forms of vaping, particularly JUUL , may also have had an impact on social media engagement about vaping behavior, though more research is needed. Also, the associated health risks of vaping were relatively unknown during the study period, though the outbreak of EVALI in 2019 may have generated more attention and possible concern among users about potential health risks of vaping, though these conversations were not detected in this study . Importantly, most tweets that included conversations about tobacco products and behavior expressed positive sentiment. Though unclear from these preliminary results, the influence of “party culture” on college campuses, the opportunities to experiment and initiate with forms of substance abuse behavior, and the immediacy of pleasure from substance use may outweigh concerns, including those relating to long-term health risks, among college students in the United States as observed in this user sentiment .

Of those gauges that are still in operation, most are located on rivers that are highly modified by human activities and gauge records prior to impacts are limited. These limitations can be partially overcome with modeling approaches to predict the attributes of natural stream flow expected in the absence of human influence. The predictions can then be compared to measured stream flow at gauging locations, or they can be used to estimate natural flow conditions in ungauged streams. In 2010, Carlisle et al. developed a modeling technique to predict natural attributes of stream flow and assessed stream flow alteration at gauges throughout the United States . Soon after, UC and TNC scientists began using the approach to expand and further refine the technique for applications in California . The models have evolved over time, but all rely on stream flow monitoring data from USGS gauges located on streams with minimal influence from upstream human activities. These are referred to as reference gauges. Some reference gauge data come from historical measurements made before significant modification of flows occurred, such as the years prior to the building of a dam. The remaining data are from reference gauges located in California watersheds that remain minimally altered by human influence. Once reference gauges were identified and flow records obtained from the USGS web-based retrieval system, we used geographic information systems to characterize the watersheds above each reference gauge based on their physical attributes, such as topography, geology and soils . We also assembled monthly precipitation and temperature climate data for the past 65 years for each watershed. The watershed variables and climate data were then compiled and statistically evaluated in relation to observed flow conditions at the reference sites using a machine-learning approach that uses the power of modern computers to search for predictive relationships in large data sets. An advantage of machine-learning techniques is the ability to make predictions from multiple model iterations ,vertical hydroponic garden which tends to increase accuracy.

Once we had developed and evaluated models using observed stream flow data from reference gauges, we could predict stream flow attributes for any portion of a stream or river in California for which the climate and watershed characteristics were known . Additional technical details of the modeling approach are provided in Carlisle et al. 2016 and Zimmerman et al. 2018.In a study led by Zimmerman et al. , we applied the machine-learning technique to assess patterns of stream flow modification in California. We did this by predicting natural monthly flows at 540 streams throughout California with long-term USGS gauging stations and comparing those predictions with observed conditions. We then assessed how observed flow conditions at the gauges deviated from predictions and recorded the frequency and degree to which flows were either higher or lower than natural expected levels, while considering the uncertainty of model predictions. We found evidence of widespread stream flow modification in California . The vast majority of sites experienced at least 1 month of modified flows over the past 20 years and many sites were modified most of the time . When stream flows were modified, the magnitude of modification tended to be high. On average, inflated stream flows were 10 times higher than natural expected levels, whereas depleted stream flows were 20% of natural expected levels. Overall, stream flow modification in California reflects a loss of natural seasonal variability by shifting water from the wet season to the dry season and from wet areas of the state to the drier south.Conversely, flow depletion was most common in winter and spring months and for annual maximum flows. Unaltered sites tended to occur in places with relatively low population density and water management infrastructure, such as the North Coast, whereas greater magnitude and frequency of alteration was seen in rivers that feed the massive water infrastructure in the Central Valley and the populated Central Coast and South Coast regions. A key water management goal in California is to manage river flows to support native freshwater biodiversity. By estimating natural river flows and the degree to which they are modified, our work provides a foundation for assessing “ecological flow” needs, or the river flows necessary to sustain ecological functions, species and habitats.

Assessments of ecological flow needs are generally performed at stream reach to regional scales , but rarely for an area as large and geographically complex as California. In 2017, a technical team that includes scientists from UC, TNC, USGS, California Trout, Southern California Coastal Water Research Project and Utah State University began developing a statewide approach for assessing ecological flows. The team has identified a set of ecologically relevant stream flow attributes for California streams that reflect knowledge of specific flow requirements for key freshwater species and habitats . Our modeling technique is now being extended to predict natural expectations for these new stream flow attributes. Model predictions of the natural range of variability for these ecologically relevant stream flow attributes will provide the basis for setting initial ecological flow criteria for all streams and rivers in California by the State Water Resources Control Board and other natural resource agencies. These ecological flow criteria will be based on unimpaired hydrologic conditions, but they can be refined in locations where management and ecological objectives require a more detailed approach. For example, refined approaches would likely be required in rivers that must be managed for species listed under the Endangered Species Act or in rivers where substantial flow and physical habitat alteration makes reference hydrology less relevant for setting ecological flow criteria, such as in the Central Valley or in populated watersheds of coastal California. Our technical team also was involved in establishing the California Environmental Flows Work group of the California Water Quality Monitoring Council . The mission of the Work group is to advance the science of ecological flows assessment and to provide guidance to natural resource management agencies charged with balancing environmental water needs with consumptive uses. The Work group is comprised of representatives from state and federal agencies, tribes, and nongovernmental organizations involved in the management of ecological flows. It serves as a forum to facilitate communication between science and policy development and to provide a common vision for the use of tools and science-based information to support decision-making in the evaluation of ecological flow needs and allocation of water for the environment.

The modeling technique described above has also been used to evaluate statewide water allocations. Grantham and Viers analyzed California’s water rights database to evaluate where and to what extent water has been allocated to human uses relative to natural supplies. They calculated the maximum annual volume of water that could be legally diverted according to the face value of all appropriative water rights in the SWRCB’s water rights database. Water rights were distributed according to their location of diversion, and the permitted diversion volumes were aggregated at the watershed scale to estimate a maximum water demand for each of the state’s watersheds. These permitted water diversion volumes were compared with modeled predictions of average annual supplies to estimate the degree of appropriation of surface water resources throughout the state . The study found that appropriative water rights exceed average supplies in more than half of the state’s large river basins, including most of the major watersheds draining to the Central Valley, such as the Sacramento, Feather, Yuba, American, Mokelumne, Tuolumne, Merced and Kern rivers. In the San Joaquin River,plant bench indoor appropriative water rights were eight times the volume of estimated natural water supplies . The volume of water rights allocations would be much higher if pre-1914 and riparian water rights had been included, but these data were not available at the time. The analysis also revealed that water rights allocations poorly represent actual water use by water rights holders. For example, comparisons of allocations with water use suggest that in most of California only a fraction of claimed water is being used. In a well-functioning water rights system where allocations are closely tracked and verified, an excess of water rights relative to supplies is not necessarily a problem. During water shortages, holders of junior appropriative rights would be required to curtail their water use. When water is abundant, most water rights holders should be able to fully exercise their claims. Uncertainty in when, how and where water is being used, however, threatens the security of water rights — particularly when water is substantially over allocated relative to natural supplies. During the 2012–2016 drought, for example, the SWRCB issued notices of curtailment to water rights holders to protect endangered fish species within priority watersheds. Less controversial targeted cutbacks to individuals might have been sufficient if the agency had more accurate information on how water rights were being exercised. As the 2012–2016 drought progressed, flaws in the state’s accounting system for tracking water rights became more apparent. This study, together with other policy reports , articulated the need for water accounting reforms, raised public awareness and helped to mobilize support for new legislation in 2015 , which significantly increased water-use monitoring and reporting requirements for water rights holders. The new regulations also extended reporting requirements to senior water rights holders , which are among the largest individual water users in the state.

The legalization of recreational cannabis in 2016 with passage of State Proposition 64 prompted state agencies to develop new policies to regulate the production, distribution and use of the plant. For example, California Senate Bill 837 directed the SWRCB to establish a new regulatory program to address potential water quality and quantity issues related to cannabis cultivation. The subsequently enacted California Water Code Section 13149 in 2016 obliged the SWRCB, in consultation with the California Department of Fish and Wildlife, to develop both interim and long-term principles and guidelines for water diversion and water quality in cannabis cultivation. As a result, in 2017, the SWRCB adopted the Cannabis Cultivation Policy: Principles and Guidelines for Cannabis Cultivation . The Cannabis Cultivation Policy’s goal is to provide a framework to regulate the diversion of water and waste discharge associated with cannabis cultivation such that it does not negatively affect freshwater habitats and water quality. A key element of the Cannabis Cultivation Policy is the establishment of environmental flow thresholds, below which diversions for cannabis irrigation are prohibited . During the dry season , no surface water diversions are permitted for cannabis cultivation. Diversions from surface water sources to off-stream storage are allowed between Nov. 1 and March 31. However, water may only be extracted from streams when flow exceeds the amount needed to maintain adult salmon passage and spawning and winter rearing conditions for juvenile salmon. Environmental flow requirements for the winter diversion season were determined by an approach known as the Tessmann Method , which uses proportions of historical mean annual and mean monthly natural flows to set protective thresholds. Because flows are not measured continuously in most streams in California , including at most points of diversion, the Cannabis Cultivation Policy instead relies on using the predictions of natural flows from the models described above. Predicted natural mean monthly and annual flows are used by the SWRCB at compliance gauge points to calculate the Tessmann thresholds. Cannabis cultivators seeking a Cannabis Small Irrigation Use Registration permit from the SWRCB are assigned a compliance gauge near their operation and can legally divert water only when flows recorded at the gauge meet or exceed the Tessmann thresholds during the diversion season . The motivation for developing natural stream flow models and data rests on the premise that rivers and streams can be managed to preserve features of natural stream flow patterns critical to biological systems while still providing benefits to human society . For any stream of interest, balancing the needs of humans and nature requires an understanding of its natural flows, whether observed conditions are modified relative to natural patterns and what degree of modification harms its health. As noted in the examples above, this work has both direct and indirect implications for policy and decision-making. A database of natural stream flows developed by machine-learning models was used to help define cannabis policy to set minimum flow targets — a direct application of the technique. However, this work also influenced policy and decision-making in more subtle ways, including building awareness of shortcomings in the state’s water rights accounting system.

Citing evidence that a high percentage of arrestees test positive for alcohol and various illegal drugs, advocates of continued criminalization frequently imply, contrary to the implications of the ONDCP cost study, that toxicologically induced crimes are more common or costly than those whose origins are systemic to drug prohibition. Data do show a correlation between crime and illicit drug use that is, upon first consideration, quite distressing: the 2008 Annual Report of the Arrestee Drug Abuse Monitoring Program found that in 2008, among ten major metropolitan areas across the country, the percentage of arrestees testing positive for the presence of some illicit substance ranged from 49 percent in Washington, D.C. to 87 percent in Chicago. However, as we will reiterate in the sections that follow, extrapolating from the ADAM II results to a belief that drug criminalization decreases crime or violence conflicts with a number of theoretical considerations as well as considerable empirical evidence concerning the relatively greater importance of systemic offenses. Three theoretical points should be highlighted. First, as previously noted, the approximately 1.8 million annual arrests for drug abuse violations are more than for any other category of offense . It is neither surprising,grow rack systems nor indicative of a causal relationship between drug use and crime that individuals in this subcategory of arrestees frequently test positive for illegal drugs.

Second, any causal extrapolation from the correlation between drug use and crime runs up against the intractable problem of omitted variables bias: it is quite likely that factors which predispose individuals to frequent use of drugs also push them toward both crime and greater likelihood of apprehension by authorities. This is especially true for marijuana: detectable traces may remain in one’s system for extended periods of time, so one may test positive upon arrest even if the last instance of use occurred days or even weeks before the arrest, and before or after the commission of the offense . Third, the important question is not whether crime systemic to prohibition substantially outweighs toxicologically-induced crime—although, the best evidence supports this hypothesis. Rather, the appropriate inquiry should be into how the marginal decreases in systemic crime would compare to the marginal increases in toxicologically-driven crime given a regime change. Even if lesser penalties, depenalization or legalization would increase use, the new class of users—individuals formerly deterred by criminalization—would constitute a class much less predisposed to commit other crimes than the group of people already using under criminalization. Return to the ONDCP’s aggregate cost study and three of its key insights: roughly forty percent of the current costs of illegal drugs in the United States are crime costs borne by offenders via incarceration and the government via administration of the criminal justice system; these costs dominate the victim-borne costs of drug-related crime and health-related costs of abuse; and the greatest driver of these costs is crime systemic to criminalization, rather than crime motivated by toxicology.

Together, these propositions suggest that a substantial portion of America’s current drug problem is its drug control policy. Since government policies create some of the costliest of all the burdens associated with illegal drugs, a substantial reduction in the social costs of illegal drugs would seem to require a reduction in the costs imposed by the current criminalization regime, not just a restraint of the costs of abuse. While many advocates of legalization and continued criminalization of illegal drugs see sufficient similarities across drug classes to paint with broad strokes, we perceive the nature and extent of the harms associated with each drug to call for careful, individualized analysis.That is not to say that recreational drugs do not share certain similarities or that society’s experience with legal drugs cannot provide insight into the likely impact of legalizing a currently proscribed drug. The gaping disjunction between the law and policy toward cigarettes and alcohol on the one hand, and toward marijuana, cocaine and other currently illegal drugs on the other, appears less the result of thoughtful distinction than of inertia and a self-perpetuating myth that drugs accorded legal status are qualitatively similar to each other and different from drugs that are criminalized.But if a unified approach across certain drugs might be desirable for a variety of reasons, only by meticulously examining each drug’s unique psychopharmacological effects and social attributes can we begin to group together the different drugs that should be treated similarly.In this section, we consider potential changes to America’s policy toward marijuana and cocaine. To oversimplify somewhat, marijuana is the most widely used illegal drug, one of the least dangerous for users across various dimensions, and the frequent subject of debate over policy reform.

Likewise, any decrease in social costs stemming from a change to marijuana policy is likely to be far smaller than would result from a comparable policy change concerning a “harder” drug such as cocaine. On the other hand, because the social costs under America’s current drug regime are highest for cocaine,changes to policy toward cocaine would change the social cost mitigation calculus in a way that would countenance potential risks and rewards of the greatest magnitude. Marijuana use has intruded into mainstream America to a greater degree than any other illegal drug.Moreover, Room et al. observe that because marijuana’s global prevalence so exceeds that of other illegal recreational drugs, the bureaucracies of drug control within individual countries and at the global level depend upon the criminalization of marijuana to broaden the scope of their mission. They note the World Drug Report 2008 estimates that 65 percent of global seizures and 67 percent of “doses” seized were for cannabis and argue, using global use figures, that without cannabis illegal drug use would not be a global population-level issue . Finally, the therapeutic potential of marijuana has given rise to a debate over whether doctors should be allowed to prescribe the drug for medicinal purposes. Perhaps for all these reasons, marijuana has proven an attractive target for advocates of legalization, though many prominent opponents endorse a continued hard-line stand. Growing numbers of commentators in the popular press have advocated the legalization of marijuana , and assessed the revenue boost legalization might provide states facing cash strapped budgets . The debate has been further stimulated in recent months as states have begun reacting to Attorney General Eric Holder’s announcement that the DEA will no longer raid state-approved medical marijuana distributors . Willingness to consider—if not outright endorse—legalization of marijuana has also grown among academics. Over 500 economists,rolling flood tables including three Nobel Laureates,signed an open letter to the President, Congress, Governors, and State Legislatures expressing skepticism about current marijuana policy and calling for open debate over a shift from prohibition to taxation and regulation. The letter highlights Harvard economist Jeffrey Miron’s 2005 report The Budgetary Implications of Marijuana Prohibition, which estimates that legalization would save the federal and state governments a combined $7.7 billion in prohibition enforcement expenditures and yield approximately $2.4 billion in tax revenues if taxed like an ordinary good or as much as $6.2 billion if taxed similarly to alcohol or tobacco .In the wake of the recent economic downturn, old and new reformers have latched on to the “lost revenues” argument for legalization. This section first considers the case for reforming marijuana policy, specifically weighing the costs of depenalization and legalization against those of the current system of prohibition.First, a completely unregulated market for marijuana would lead to undesirably high levels of consumption—either because of negative externalities or internalities .

Second, regulation and taxation will not adequately correct for these market failures. Third, severe criminal sanctions for users and sellers are cost-justified deterrence mechanisms for reducing use. A more sophisticated version of this third argument would make explicit an important hypothesis frequently left implicit but nevertheless underlying much thought about drug policy: criminalization may not only raise the price for the user but also, through the normgenerating or socializing effect of the law, actually alter individuals’ preferences such that for any given price, use and distribution hold less appeal.54 Though some libertarians argue that the value of individual autonomy dictates allowing marijuana use and simply sanctioning user behavior when it directly infringes upon the liberty of others, a cost-minimization approach demands consideration of the magnitude of social costs of use before accepting the notion that autonomy can trump all such social costs not generated directly from physical force or fraud. Few dispute that marijuana creates at least some externalities and also internalities—certainly at least in the case of minors not yet capable of adequately processing the risks but also perhaps for the 1 in 11 who becomes dependent on the drug merely from trying it. The great contention is over which policies can most efficiently mitigate the total costs associated with marijuana use—in other words, which policies will yield the lowest total social costs, combining the costs of use and control. The crux of the argument in favor of retaining the prohibitions on use, possession, and sale of marijuana is that eliminating any of these sanctions would increase marijuana use by reducing the cost and decreasing the risk. Full legalization might also stimulate demand by enabling advertisement and brand development. Increased use—either in terms of intensity and frequency or number of users—would in turn increase the costs of use borne by users themselves and society. There are also two related, subsidiary arguments, worth addressing. First, it is often contended that marijuana is a “gateway drug” that renders its users more likely to begin using other, more dangerous drugs, and, therefore, an increase in marijuana users as a result of depenalization or legalization would in turn increase the number of users of other illegal drugs.55 Second, it is sometimes argued that marijuana use induces crime. Before turning in subsequent sections to the evidence regarding expected increases in marijuana use under depenalization and legalization, it is helpful to consider briefly the insightful analysis of the gateway issues offered by MacCoun and Reuter. Though they believe that “there is little evidence that expanding marijuana use does increase the use of other, more harmful drugs,” MacCoun and Reuter present a taxonomy of seven possible meanings of the gateway concept: the first step; the spurious correlation; the early warning; the trap; the tantalizer; the toe in the water; and the foot in the door . The basic problems for an econometrician attempting to identify whether—and if so which—gateway hypotheses reflect actual experience are omitted variables bias and endogeneity. At the level of the individual, it is difficult to pinpoint a gateway mechanism because it is quite likely that underlying characteristics that predispose individuals to use marijuana also increase the likelihood of using other drugs. At the population level, it is difficult to assess the effect of marijuana use on the use of other drugs for an additional reason: causality likely runs in both directions. However, even without precisely estimating the impact of marijuana use on the likelihood of trying other drugs, one may place a rough upper bound on the extent of such an effect by noting how commonly individuals use marijuana without going on to other, more harmful drugs. In their recent cannabis report, Room et al. write: “Few [marijuana users] go on to use more dangerous illicit drugs; the 1995 US National Household Survey on Drug Abuse found that only 23 percent of 26-34 year olds who had used marijuana at some time had also used cocaine during their lives.” Similarly, the 2007 NSDUH found that those who used marijuana exclusively constituted 53.3 percent of illegal drug users and 73.2 percent of marijuana users . As MacCoun and Reuter remind us, it is also important to understand the mechanism of any gateway effect, assuming one exists at all. If the “gateway” is a matter of individuals becoming comfortable with illegal behavior and black market consumption, then legalization could undermine this gateway effect, even as it increased consumption directly via lower prices to users. The most-cited evidence in support of the hypothesis that marijuana users are driven to crime while under the influence is undoubtedly the ADAM II data indicating that in 8 of 10major metropolitan areas studied in 2008, over 40 percent of arrestees tested positive for marijuana at the time of arrest .

One in five young men report being a gang member in the townships of Cape Town and over half of all young men report committing at least one violent act. These findings are not surprising in these post-apartheid neighborhoods characterized by widespread poverty and limited educational and employment opportunities. Young men who report being involved in a gang are more than twice as likely to report ever being arrested. These findings extend previous research on the widespread culture of violence in the townships by examining the association between reports of different types of violence and being arrested in different neighborhoods. Further, SA young men who report being stressed are more likely to have a history of arrests. Prisoners and arrestees in SA, as with many other countries, experience higher rates of neuropsychiatric disorders than the general population. A large-scale longitudinal analysis in the United States reports that individuals with severe mental illness are only more violent if they also experience substance abuse. Mental health symptoms are rarely studied among men,drying cannabis especially in LMIC, and need more investigation. Although rates of food insecurity and unemployment are high in this study, young men living in communities with more formal housing and in-home water sources are more likely to report ever being arrested compared to those in less advantaged communities. Two of the 18 communities with the highest rates of arrests are located in a relatively new township.

Prior to any migrants arriving, the government provided paved roads, access to electricity, housing, and in-home water sources. Because this township has the most immigrants, residents are likely to have fewer ties to the community. Although households may have more infrastructure, the lack of long-standing family ties, along with the difficulty in obtaining employment, may contribute to a high risk of arrests. Research in rural areas of the United States suggests that communities characterized by high ethnic heterogeneity and less local engagement among juveniles are consistently linked to higher rates of arrests. Although all of the young men in this study are Black-African, many migrate from the Eastern Cape in SA, limiting their bonds to the township communities. These findings support the extension of the social disorganization theory to the township neighborhoods if SA. Housing and access to municipal services are disproportionally distributed across three police precincts in Khayelitsha and one police precinct in Mfuleni. For instance, the precinct in Lingelethu West PP includes a much higher proportion of formal housing , compared to those in Khayelitsha and Harare. In contrast, the precinct in Khayelitsha includes 56% informal settlements, compared to 46% in Harare and 25% in Lingelethu West. As certain police precincts include more informal settlements, service delivery and policing become a challenge due to the lack of infrastructure. For the present study, the precincts in Harare covers three of our neighborhoods, of which two are informal settlements. Informal settlements often do not have formal roads and corresponding municipal-issued physical addresses. This may account for the surprisingly higher number of arrests in formal areas in the current study. That is, policing, and subsequent arrests, may be more challenging in informal neighborhoods due to the lack of infrastructure and the police’s ability to detect and detain the accused.

The examination of risk associated with being arrested must consider clusters of individual and community-level factors that can interact to propagate violence, substance use, and potential criminal behavior. This approach helps inform community interventions to create new pathways for young men. There is some evidence that engaging people in community interventions can be an effective way to address public health problems, such as unwanted pregnancy, substance abuse, violence, and delinquency. However, it is notoriously difficult to engage young men in these types of interventions. As recently mentioned by Brooks , “human behavior happens in contagious, networked ways”. Community-level interventions are needed for community-level challenges in South Africa to combat substance use and gang activity. These findings support the need for pathways out of risk that engage young men in prosocial ways and support their access to education. As a first test of this idea, we examined the effects of a well-characterized FAAH inhibitor, the compound URB597, in two established mouse models of ASD: BTBR mice, an inbred strain discovered through the Mouse Phenotype Project, which shows pronounced deficits in social approach, reciprocal social interactions, and juvenile play, and fmr1 / mutant mice—a model of Fragile X Syndrome, the most common monogenetic cause of ASD, which features persistent social deficits.We show that FAAH inhibition substantially improves social behavior in BTBR and fmr1 / mice and that this effect is independent of anxiety modulation.Previously established methods were followed.Test mice were habituated to an empty three-chambered acrylic box . Habituation included a 10-min session in the center chamber with doors closed and then a 10-min session in all chambers with doors open.

Test mice were then tested in a 10-min session. Subjects were offered a choice between a novel object and a novel mouse in opposing side chambers. The novel object was an empty inverted pencil cup and the novel social stimulus mouse was a sex, age, and weight-matched 129/SvImJ mouse. These mice were selected because they are relatively inert, and they were trained to prevent abnormal behaviors, such as biting the cup. Weighted cups were placed on top of the pencil cups to prevent climbing. Low lighting was used—all chambers were measured to be 5 lux before testing. The apparatus was thoroughly cleaned with SCOE 10X odor eliminator between trials to preclude olfactory confounders. Object/mouse side placement was counterbalanced between trials. Chamber time scoring was automated using image analysis in ImageJ. Sniffing time was scored by trained assistants who were unaware of treatment conditions. Excluded were subjects with outlying inactivity.The procedure was based on previously published methods.The maze was made of black Plexiglas and consisted of two open arms and closed arms . The arms extended from a center square . The maze was mounted on a Plexiglas base and raised 39 cm above the ground. Lighting consisted of two 40W incandescent bulbs, each hanging at a height of 1 m above the open arms of the test apparatus. The floor of the apparatus was cleaned with a SCOE 10X odor eliminator between trials. The animals were placed in the center square and allowed to freely explore for 5 min. The amount of time spent in each arm and the number of entries into each arm were quantified by EthoVision 3.1 video tracking system .We used the CB1-receptor inverse agonist, AM251, or the FAAH inhibitor, URB597,to probe the role of anandamide in social behavior of young adult mice. Social activity was evaluated in the widely used social approach test.The mice were placed in a dimly lit three-chambered apparatus and given a choice between a novel inert mouse restrained by an inverted pencil cup in one chamber or a novel object in the opposite chamber.We first evaluated maximally effective doses of AM251 29 or URB597 25 in socially normal C57Bl6J mice and found that neither drug altered the two outcome measures of the test,greenhouse benches namely the time spent in the social chamber and the time spent sniffing the target mouse . In contrast to C57Bl6J mice, BTBR mice show no social preference in the test .However, administration of URB597 significantly increased the time BTBR mice spent in the social chamber and sniffing, to levels that were comparable to those displayed by control, socially normal C57Bl6J mice . The effect of FAAH inhibition on social approach depended on CB1 receptors and, thus, presumably on anandamide accumulation, because it was prevented by concomitant administration of AM251.

The results on time spent in the social chamber are summarized as an index . Using an enzymatic activity assay and LC/MS, we confirmed that URB597 inhibited FAAH and substantially increased the levels of anandamide in the fore brain of BTBR mice , without affecting levels of the other endocannabinoid 2-arachidonoylsn-glycerol . Together, the results suggest that elevated anandamide activity at CB1 receptors corrects social approach behavior in BTBR mice, whereas it does not alter social approach in control C57Bl6J mice.Interpretation of data obtained with BTBR mice is limited by the possibly polygenetic contributions to the phenotype of this inbred strain. Therefore, we asked whether the prosocial effect of anandamide istranslatable to a monogenetic model of ASD-related social impairment. Fmr1 / mutant mice bred on an FVB/NJ background have been reported to exhibit a deficit in social approach.In our hands, however, this deficit was not statistically significant . Nevertheless, we found that acute administration of URB597 , which did not alter the time spent in the social chamber or sniffing in wild type fmr1+/ + mice , increased the time spent by fmr1 / mice in the social chamber and the time spent sniffing to levels to those displayed by control mice . These results suggest that the prosocial action of increased anandamide activity is generalizable across at least two distinct models of ASD-related social impairment, without affecting socially normal animals. We did not test fmr / mice in the elevated plus maze test because these mice display an innate preference for the open arms of the elevated plus maze,which might confound data interpretation.For better or worse, desperate parents are treating their autistic children with various forms of marijuana. Successes have been reported in high-profile anecdotes publicized by social media. This societal experiment highlights the lack of scientific knowledge regarding the therapeutic utility and safety of cannabinoid agents in ASDs. The present study provides an initial test of the idea that enhancing anandamide-mediated endocannabinoid signaling might help to alleviate social impairment in ASD. We show that inhibition of the anandamide-deactivating enzyme FAAH corrects social impairment in two distinct ASD-related models—BTBR and fmr1 / mice. We confirm that FAAH inhibition is an appropriate strategy to elevate levels of anandamide, and thus, anandamide signaling, in BTBR mice. Furthermore, we show that the prosocial action of FAAH inhibition is independent of reducing anxiety in BTBR mice. Together, the results put forth FAAH as a novel therapeutic target for ASD-related social impairment.

Separate lines of previous research suggest the general notion that abnormal endocannabinoid signaling might contribute to ASD. First, endocannabinoids play important roles in neurodevelopment, which is also affected by exogenous cannabinoids.Second, ASD-related alterations in synaptic signaling have been linked to the endocannabinoid system. For example, mutations in neuroligins, a family of ASD-linked synaptic adhesion proteins, impair tonic endocannabinoid signaling.In a related example, we found that deletion of FMRP, the mRNA-trafficking protein missing in Fragile X Syndrome, impairs the formation of a key signaling complex that links metabotropic glutamate receptor-5 and the 2-AG-synthesizing enzyme diacylglycerol lipase-a .Third, ASD-related insults disturb resting endocannabinoid levels or endocannabinoid system components. For instance, we found that chronic isolation increases 2-AG in the prefrontal cortex, without affecting anandamide, and increases both 2-AG and anandamide in the piriform cortex.Furthermore, developmental treatment with valproic acid reduces cerebellar mRNA levels of DGL-a and reduces hippocampal mRNA levels of the 2-AG-hydrolyzing enzyme monoacylglycerol lipase.Importantly, however, these lines of research have not addressed whether deficient endocannabinoid signaling contributes to the core component of ASD—social impairment. A limited literature has hinted at this possibility indirectly by suggesting a role for endocannabinoid signaling in normal social behaviors. Genetic removal of CB1 receptors alters social interactions in mice in a context dependent manner,which may be related to social anxiety and/or cognition.CB1 agonists impair social play in rats.In contrast, genetic removal of FAAH in mice increases social interactions,and FAAH inhibition promotes social play in rats.Thus, the bidirectional modulation of social behavior likely depends on the dose and the identity of the affected circuits. We recently identified a signaling mechanism in male mice by which oxytocin drives anandamide-mediated endocannabinoid signaling to control social reward.In addition, human studies have found that marijuana may enhance sociability and a polymorphism in the CB1 cannabinoid receptor gene modulates social gaze.Given that endocannabinoid signaling has been linked to ASD and might play a role in normal social behavior, we focused the present investigation on the possible role of endocannabinoid signaling in the social impairment component of ASD.

Moreover, we know that a significant proportion of patients with behavioral disorders do not receive treatment. Therefore, the BHD prevalence data in our study likely underestimate the actual prevalence. Future studies could address whether the addition of pharmacy-based prescription data improves the prevalence estimates. Another possible limitation of our method is that we only required a single mention of a diagnosis to link the patient with that diagnosis. This could result in an overestimation of the true prevalence if diagnoses only mentioned one time are more likely to be inaccurate. However, we do not suspect this. The single-mention methodology is well established. And even if this methodology resulted in an overestimation, it would affect both arms of the case control and, therefore, would likely not affect our finding of a difference between the two arms. In addition, this study also does not examine whether there are specific diagnostic dyads and/or triads that are especially common — a possible focus for future studies. Finally, it is unclear whether the impact of these comorbidities on health care costs and outcomes is attenuated in an integrated health system like the one studied in which care is already highly managed, especially in comparison to study populations that are treated in largely a fee-for-service environment. This knowledge gap will be important for future studies to address. Regardless of how these results compare to other patient populations and health systems, the finding is striking — BHDs are highly prevalent, and even more concerning, these patients have a significantly higher medical comorbidity burden and associated risk of 10-year mortality rate. Given how the co-occurrence of behavioral and medical conditions leads to elevated symptom burden, functional impairment,pot for growing marijuana decreased length and quality of life, and increased costs, these findings highlight the importance of developing and implementing collaborative models of care in employment-based health systems that are effective at treating patients with comorbid BHD and medical conditions.

Many models have emerged ranging from enhanced coordination to colocation of services to full integration. All of these efforts share the concept of organizing care in a medical home in which a health care team provides stepped care with disease and population health management protocols. The high prevalence of multiple psychiatric disorders also argues for lifestyle interventions that focus on behavioral issues in general rather than specific diagnoses, a focus that would be greatly welcomed by primary care physicians. In the employment-based insurance population captured in this study, it is important to focus on depression and anxiety disorders. Important questions include whether outcome measures and even treatment protocols can be developed that are transdiagnostic , the role of Internet-based cognitive behavioral therapy, the relative mix of individual versus group-based treatments and the extent to which the medical record is fully open.AT THE TURN OF THE 21ST CENTURY, scientific gains in the pursuit of more effective treatments for alcohol and other drug use disorders had plateaued, and very little was known about the underlying processes that mobilize and sustain positive behavior change . In response to calls to better understand these underlying processes , the National Institute on Alcohol Abuse and Alcoholism invested in research on the social, behavioral, psychological, and biological mechanisms that support reductions in alcohol use and other addictive behaviors. As a result, the first Mechanisms of Behavior Change meeting was held in 2004 as a satellite session to the annual meeting of the Research Society on Alcoholism. The MOBC satellite session has been held annually for the past 13 years, growing from 30 attendees in 2004 to more than 100 attendees in 2017. NIAAA formalized its commitment to MOBC research via several key initiatives: the publication of a special issue monograph in Alcoholism: Clinical and Experimental Research ; the development of an NIAAA MOBC statement within the Strategic Research Plan; the formation of a transdisciplinary MOBC team within NIAAA leadership; the inclusion of a call for MOBC research in the main program announcement for Treatment, Services, and Recovery Research; the issuing of program announcements, requests for applications, and a research funding announcement with MOBC aims; and the funding of two MOBC-focused conference grants .

NIAAA was not alone in its efforts to improve behavior change interventions. Concurrently, the National Institutes of Health Institute directors identified research on crosscutting processes or mechanisms of change as a top scientific priority, and Science of Behavior Change became a program within the National Institutes of Health Common Fund, with its first funding opportunity announced in 2010. MOBC initiatives within NIAAA and the National Institutes of Health Common Fund represented a shift away from the then-prevailing efficacy paradigm as the exclusive means for building knowledge to improve alcohol and other drug treatment outcomes. The efficacy paradigm often resulted in evidence-based modalities producing near-equivalent reductions in alcohol and other drug use . That distinct treatment programs with unique behavior targets were producing near-equivalent effects made it impossible for a test of treatment efficacy to determine exactly how change was occurring . Although equivalent outcomes across different treatments could suggest uniform processes of behavior change, behavior change outcomes often vary by person and contextual factors. If we do not know how individuals change addictive behaviors or who is most likely to benefit from addictive behavior treatment, then we do not know how to improve treatment effectiveness. This recognition has resulted in an increased focus on MOBCs, a sixfold increase in citations using mediation models to assess MOBCs within alcohol research studies, and the dissemination of conceptual frameworks and statistical tools to promote research on MOBCs. The scientific imperative included a call for multidisciplinary research teams, multilevel change process considerations, and increasingly sophisticated analytic methodologies . Combined, these efforts represent an attempt to “peel the onion” of human behavior change initiation, maintenance, and relapse. This Special Section in the Journal of Studies on Alcohol and Drugs is aimed at promoting the next phase in examining state-of-the-science approaches to studying MOBCs in addictive behaviors. We hope to highlight advances in this evolving literature and to guide researchers in developing new studies in MOBC science. Further, we offer a selection of empirically supported mechanisms, both established and novel. The Special Section begins with two articles that consider issues related to study design and data analysis in MOBC research.

Topics include approaches to improving causal inference in MOBC research and the development and testing of behavioral intervention theories through tests of statistical mediation. These articles provide timely reviews that address key methodological questions and issues of debate in MOBC research. First, Finney explores limitations inherent to observational mediation design because of the inability to manipulate the purported mediator of interest. For example, it is often not feasible to randomly assign persons to different levels of hypothesized mechanisms . Because of this and other challenges, he raises the question of whether brief experimental manipulations could reasonably be expected to have enduring effects in the face of over-learned drinking behaviors. Finney provides recommendations for future MOBC research that may increase our confidence in causal attributions and includes examples of earlier experiments designed to directly manipulate mechanistic effects. Second, O’Rourke and MacKinnon examine an ever-present question related to mediation tests in behavioral intervention research. specifically, they consider conditions under which mediation may or may not be present in the absence of a main effect for the experimental condition. A core argument in this article is that even when intervention efficacy is not observed,container for growing weed there may be significant and meaningful mediation. Here, we have a central question for mediation design—when should mediation tests be pursued? The authors’ work highlights conditions for the use of mediation tests to develop and refine behavioral intervention theories and underscores that studying MOBCs despite a non-significant main effect can advance understanding of how a given treatment is effective and for whom. The next set of articles present advanced analytic approaches for testing MOBCs. First, Hallgren and colleagues consider greater levels of nuance in mediation questions, such as optimal methods for handling time when examining mechanisms of intervention effects. As the authors note, timing is everything and greater temporal resolution will be important in refining understanding of MOBCs. Moreover, it is important to recognize that alcohol and other drug treatments mobilize long-acting processes that will vary in strength over time. Statistical models should take these factors into account. Many of the recommendations from Hallgren and colleagues are demonstrated in the next two empirical studies, both of which used variants of structural equation modeling to test for mediator effects. The study by Treloar Padovano and Miranda applies multilevel SEM to the analysis of data from ecological momentary assessment among adolescents who use cannabis and who were enrolled in a randomized clinical trial examining the efficacy of topiramate for cannabis misuse. In this way, Treloar Padovano and colleagues take MOBC research into the natural environment and capitalize on analytic techniques that allow for disaggregating within- and between-person mechanisms of change in cannabis use.

Results indicated that topiramate was more effective than placebo in reducing subjective high from cannabis, which resulted in less cannabis use at the daily level. Next, Witkiewitz and colleagues present a novel application of latent class analysis in an SEM framework to examine coping skills as a mediator of outcomes for adults who received combined behavioral intervention and/ or pharmacotherapy for alcohol use disorder. Results indicated that individuals who received the combined behavioral intervention were more likely to have a broader coping repertoire at the end of treatment and that coping repertoire significantly mediated the effect of treatment on drinking outcomes. Latent class mediation holds promise as a method for examining heterogeneity in the mechanisms through which individuals change. Together, these articles represent significant advances in theory and applied MOBC data analysis, present novel findings on mechanisms in two pharmacotherapy trials, and have clear implications for future MOBC research. The sixth and seventh articles, by Eaton and colleagues and Houck and colleagues , respectively, present recent findings on processes of change in motivational interviewing . They focus on different populations , but both studies found that what clients say in MI sessions mediates the effects of MI-based intervention on alcohol-related outcomes, with different effects depending on the follow-up period that is evaluated. As such, both studies provided support for the notion that MI therapist skills can influence client statements about change and that those statements are associated with changes in behavior . These congruent results are notable given that the two designs varied on the type of MI providers . Given that the effects of client change and sustain talk have been found in other therapeutic approaches , these studies support the generalizability of client speech as a mechanism of action.Noyes and colleagues address pretreatment changes in drinking as they relate to process and outcomes among treatment-seeking adults with alcohol use disorder. specifically, they examined change in drinking days and heavy drinking days during the month before initiating cognitive–behavioral treatment. Noyes and colleagues found that pretreatment drinking moderated the relationship between self-efficacy measured during treatment and drinking days after treatment. This study suggests that the role of self-efficacy as a potential change mechanism may vary as a function of whether patients have already initiated behavior change before treatment begins. Noyes and colleagues indicate that baseline matters and that we need to further develop methods to study pretreatment behavior change. In the final article, Buckman and colleagues provide an overview of the baroreflex, a novel mechanism involving a heart–brain feedback loop that affects physiological reactivity. Consideration of the baroreflex as an MOBC provides an important translational linkage between emotion regulation and behavioral outcomes. This linkage has direct application to intervening with addictive behaviors, and there may be fewer roadblocks to experimental manipulation when biological or physiological mediators are the mechanisms of interest. The work of Buckman and colleagues brings the MOBC science closer to multilevel assessment and intervention with alcohol or other drug use disorders. Overall, the Special Section provides a snapshot of current efforts to advance the state of MOBC science.

Associations of the MRI outcome measures with measures of neurocognitive test performance used Pearson’s correlations.In this cross-sectional volumetric MRI study, one-monthabstinent alcohol dependent individuals without current psychostimulant dependence , ALC individuals with current dependence on at least one psychostimulant ,and drug-free LD differed significantly on regional GM and WM volumes normalized to ICV: PSU had significantly larger lobar WM volumes than LD and ALC, whereas ALC showed no regional WM volume differences compared to LD. GM volumes in PSU were lower only in the temporal lobe, thalami and lenticular nuclei compared to LD. In ALC however, most lobar cortical GM volumes, thalamic GM, and total cerebellar volume were significantly smaller than in LD. Consistent with these tissue volume differences, sulcal CSF volumes of the frontal and temporal lobes in PSU were smaller than in both ALC and LD. All effect sizes for the significant WM differences between PSU and LD or ALC were greater than 0.50, indicating moderate to-large magnitude group differences. Parietal WM volume in PSU correlated positively with prior year cocaine use, suggesting a substance-relatedparietal WM volume expansion. Frontal,parietal,mobile vertical rack and total cortical GM volumes were associated with some critical neurocognitive domain measures in both PSU and ALC, but not in LD. These neuroimaging abnormalities may serve as poly substance abuse biomarkers and as potential targets for pharmacological and behavioral PSU-specific treatment aimed at decreasing the high relapse rates in PSU.

MR-based structural neuroimaging of individuals with different substance use disorders have yielded mixed findings regarding brain tissue volume alterations. Smaller WM volumes , particularly of the frontal, temporal and cerebellar regions relative to drug-free controls were reported in middle-aged active and abstinent users of cocaine and cannabis . A few reports showed similar WM volumes in active or abstinent users of these substances compared to controls . However, enlarged volumes or density of frontal, temporal, and sub-cortical WM were reported in active amphetamine users and in amphetamine users in both early and long-term abstinence . Here, we found larger WM volumes in one-month abstinent PSU compared to both LD and one-month abstinent ALC. Our PSU cohort was dependent on alcohol , cocaine , and methamphetamine . When the four PSU individuals with methamphetamine dependence were removed from the entire PSU sample, all WM volumes remained significantly larger compared to LD or ALC. This observation, together with the positive correlation of parietal WM volume with cocaine use quantities in the PSU suggests that, the larger WM volumes in our PSU cohort were not driven simply by methamphetamine dependence in the PSU group. Larger WM volumes in recently abstinent methamphetamine users were postulated to be a result of tissue inflammation and/or reactive astrogliosis as a response to tissue injury sustained from the chronic substance abuse . A dose-related enhancement of neurological and histological signs of acute encephalomyelitis following in vivo administration of amphetamine or cocaine in rats was described . Also, in rats administered with cocaine daily for 7 days, increases in glial fibrillary acidic protein and vimentin expressions, the hallmarks of reactive astrocytes and reactive gliosis , were observed in the prefrontal cortex and nucleus accumbens at 3 weeks after substance administration . These findings support the theory of brain tissue enlargement due to reactive astrogliosis. Therefore, it is not out of context to interpret the observed larger lobar WM volumes in our PSU cohort as inflammation and/or glial scarring associated with reactive astrogliosis observed at one month after withdrawal from chronic consumption of both alcohol and illicit substances.

Results of quantitative MRI-based regional GM volume/density in individuals, who purportedly depended on or abused primarily a single drug, have been inconsistent. Some cross-sectional studies reported smaller regional GM volumes/densities in both active and abstinent users of cocaine , cannabis , methamphetamine and heroin compared to controls. Others reported larger GM volumes/densities in cocaine dependent individuals , cannabis abusers and methamphetamine abusers compared to controls; and yet others found no effects of chronic cannabis misuse on brain morphology . On the other hand, while previous reports on the effects of PSUD on brain GM volumes are sparse, they are at least consistent: GM volumes were reduced compared to age-matched drug-free controls in prefrontal and temporo-parietal cortices of active cocaine dependent individuals, many of whom were dependent also on other drugs , in the orbitofrontal cortex of poly-substance abusers abstinent for at least 15 days , and in prefrontal cortex of poly-substance dependent individuals abstinent for more than 2 years . This suggests GM atrophy in active, short-term and long-term abstinent poly-substance users. We found appreciable GM volume loss in our one-month-abstinent PSU only in the temporal cortex, lenticular and thalamic GM. The apparent “normal” frontal and parietal cortical GM volume in our PSU sample could be the result of reactive astrogliosis described above , or where GM loss is offset by a neuroadaptive response to the need for greater cognitive control over substance use . The discrepancies between regional GM volume findings from our PSU participants and those of the previous studies could relate to the differences in age , the duration and type of drugs used, and/or the duration of abstinence: i.e., the younger cohorts in the previous studies could have been less prone to brain inflammation from chronic substance use, brain inflammation may not be present in active users or in poly-substance abusers abstinent for a few weeks , or brain inflammation could have subsided after 2 years of abstinence .

However, this is speculative and can only be tested in longitudinal studies of abstinent poly-substance users: if our speculation/interpretation were correct, the observed GM differences – and particularly the larger WM volumes – should diminish with duration of abstinence as the substance withdrawal-related inflammation subsides over time. Such a dynamic change has been suggested in abstinent methamphetamine users . Methodological issues in studying brain effects of poly-substance dependence with relevance to the above discussion were recently reviewed . Larger ventricular and lobar CSF volumes have been reported consistently in short-term abstinent and active AUD individuals compared to controls . However, our findings showed smaller CSF spaces in PSU compared to ALC with similar drinking severities or controls, possibly compensating for the larger lobar WM volumes within the physical confines of the skull. Whereas both Ersche papers showed larger sub-cortical GM volumes in currently using PSUD individuals, our abstinent PSU patients had smaller lenticular and thalamic GM as well as normal caudate, cerebellar and brainstem volumes. As the authors speculate that some of these increases may reflect a compensatory response to reduced dopamine neurotransmission, this may have normalized in our abstinent PSU sample. Our study has limitations: the substance dependent cohort was treatment-seeking and abstinent at time of study, and it included only a few female participants. Our findings may therefore not generalize to female or treatment-naïve substance dependent individuals. The variance of the sub-cortical volume measures obtained with our automated segmentation method is larger than that shown in manually outlined structures of cocaine dependent individuals , which might have made it impossible to detect small group differences.Thus, our lobar outcome measures lack functional specificity, which likely contributed to the few correlations with neurocognitive measures. Finally, we did not screen participants for DSM-IV Axis II disorders, such as antisocial personality disorders , nor did we measure potential group differences in nutrition,vertical grow rack exercise and genetic predispositions. All these conditions may also influence brain morphometry and should ideally be considered in future studies of both treatment-naïve and treatment-seeking individuals with well defined dependence on alcohol and illicit substances. To address the issue of regional specificity of volume changes within the relatively large lobes and to increase the functional relevance of such measures, reliable segmentation and examination of small brain regions or of the cortical ribbon may be needed, such as provided by whole-brain voxel-based morphometry and cortical thickness measures . These limitations notwithstanding, our neuroimaging study reveals gross brain structural differences between PSU and ALC that may have implications for different treatment approaches of poly-substance dependence and alcohol dependence. The findings complement previous neuronal and glial differences we detected in the frontal lobe of these substance dependent groups . Here, we confirmed commonly reported smaller lobar GM and cerebellar volumes and more sulcal CSF in one-month-abstinent middle-aged ALC compared to age-matched LD. However, these volume measures were largely unaffected in one-month-abstinent alcohol dependent PSU. Furthermore, PSU had larger lobar WM volumes than both ALC and LD. The larger WM and the lack of apparent GM volume loss in PSU, despite a very long drinking history similar to that of ALC who showed marked cortical GM volume loss, suggest hypertrophic processes in short-term abstinent PSU, perhaps astrogliosis associated with neuro-inflammation. These processes may mask underlying cortical GM tissue loss associated with chronic poly-substance misuse.Many meta-analyses and reviews have been published in recent years.

Studies of cannabinoid efficacy vary greatly: some have tested whole-leaf marijuana ; others assess isolated compounds such as THC, or known/controlled combinations of plant-derived products , and some study only synthesized products like nabilone. These differences make comparisons difficult. A recent Cochrane-style review looked at the quality of evidence supporting the use of cannabinoids in CINV, as appetite stimulant in HIV/AIDS, in chronic pain, spasticity from MS or paraplegia, depression, anxiety, sleep problems, psychosis, glaucoma, or Tourette’s syndrome. Seventy-nine randomized trials involving 6462 patients were identified. Moderate quality evidence supports the use of cannabinoids for chronic pain and spasticity. Low quality evidence supports the use of cannabinoids for CINV, wasting, sleep problems, and Tourette’s syndrome. Many other uses of cannabinoids are rationalized based on cultural traditions, small case series, open label trials, anecdote, or opinion. The American Academy of Neurology completed its own recent review and concluded that cannabinoids, particularly nabiximols, provide small benefits for patients with MSrelated spasticity, central pain, and urinary symptoms but shows little evidence of efficacy for other neurologic conditions.Orrin Devinsky, a leading U.S. investigator in the useof CBD for treatment-refractory pediatric epilepsy, has published an open-label trial showing some efficacy that warrants randomized controlled trials. The already-mentioned National Academies monograph draws nearly identical conclusions to those above. Readers are referred to it for a comprehensive review of the evidence. There is also interesting preclinical data suggesting that cannabinoids may have a role in reversing opioid-associated hyperalgesia,may reduce craving and relapse risk in opioid dependence,and could help prevent or treat chemotherapy induced peripheral neuropathic pain.There is emerging, equivocal data regarding whether cannabinoids improve quality-of-life and reduce symptom burden or disease activity in inflammatory bowel disease.In a recent review of the common indications for use listed in state cannabis regulations, Alzheimer’s disease, amyotrophic lateral sclerosis , cachexia, cancer, Crohn’s/ inflammatory bowel disease , epilepsy, severe/chronic pain, glaucoma, hepatitis C, HIV/AIDS, MS, and post-traumatic stress disorder appear regularly. This listing suggests the degree to which state guidelines depart from, and generally exceed, evidence-based uses, and in turn the degree to which lawmaking may be influenced by popular beliefs or political processes. For the palliative care practitioner, these efficacy data are complicated not just by the generally low volume of only moderate quality evidence, and by state regulations that regularly depart from that evidence, but also increasingly by the growing reach of our field beyond cancer and HIV into the realms of adult degenerative diseases of the central nervous system, heart, lung, liver, digestive tract, and to serious non-cancer childhood disorders.As the National Academies monograph and other recent excellent reviews suggest, recreational use of cannabinoids is particularly concerning in young people with still-developing brains, persons with preexisting mental illness, and those with existing substance abuse problems. In these populations regular cannabis use can unmask or hasten the onset of psychotic illness, is associated with reduced IQ, addiction/dependence, and a withdrawal syndrome. Other widely recognized sequela of regular/chronic use include dropping out of school, decreased motivation, socialization, and life-satisfaction, and chronic bronchitis. Other than bronchitis, the data regarding respiratory consequences of cannabis consumption are equivocal. Inhaled cannabis does NOT appear to confer increased risk for lung cancer or head and neck cancer. The data on marijuana use and cardiac disease have not shown compelling evidence for concern.

Cigarettes and alcohol can have combined pharmacological effects that can result in a heightened reward , and may contribute to their co-use. Previous research found that young adults reported increased pleasure from smoking cigarettes under the influence of alcohol , which could be an important factor underlying their co-use. The relationship between frequency of binge drinking and pleasure from smoking remains unclear. We previously reported differences in tobacco use characteristics among young adults who all drank alcohol but differed in binge drinking frequency . Compared to alcohol use with no binge drinking, frequent binge drinking was associated with smoking more cigarettes per day, and greater temptations to smoke in positive affective/social situations. Other smoking characteristics, such as being a social smoker, were associated with any past month binge drinking. We also reported a high rate of cigarette smoking on days participants binge drank alcohol , suggesting that cigarettes could have greater rewarding effects when larger amounts of alcohol are consumed. For the current study, we examined the hypothesis that greater pleasure from smoking cigarettes would be found among individuals who binge drink alcohol more frequently, e.g. engage in cigarette smoking when larger amounts of alcohol are consumed.Similar to alcohol, grow cannabis use and dependence are more common among cigarette smokers compared to nonsmokers , and marijuana use is associated with greater nicotine dependence and heavier patterns of cigarette smoking among young adults .

The literature on combined effects of tobacco and marijuana suggest that shared genetic risk factors and neurobiological pathways may explain some overlap in addictive processes for the two substances . There is evidence that cannabinoid receptors may be involved in the rewarding effects of nicotine and that cannabinoid receptor agonists may increase the rewarding and reinforcing effects of nicotine . Subthreshold doses of Delta 9-tetrahydrocannabinol and nicotine in combination were found to induce a conditioned place preference in mice , suggesting possible synergistic enhancement on reward processes. Differences between cigarette smokers and nonsmokers in response to endocannabinoid modulation of reward processing in the nucleus accumbens have also been reported . Behavioral studies have pointed to additional reasons for co-using tobacco and marijuana, including to enhance the high from marijuana or to counteract certain effects of marijuana . However, to date, limited research has examined rewarding effects of marijuana and tobacco co-use. Using cross-sectional survey data, we examined extent of cigarette smoking under the influence of alcohol or marijuana and differences in perceived pleasure from cigarette smoking when drinking alcohol compared to using marijuana among cigarette smokers who used marijuana and alcohol. Hypotheses were: a similar proportion of smoking episodes would occur under the influence of alcohol and marijuana; perceived pleasure would increase from smoking when drinking alcohol and using marijuana, and not differ across substance; and perceived pleasure from alcohol would be greater with more frequent binge drinking. Perceived pleasure from smoking when drinking alcohol or when using marijuana was also compared between the cigarette smokers who used both marijuana and alcohol in the past month and cigarette smokers who only drank alcohol or only used marijuana.

Perceived pleasure experienced from smoking cigarettes when drinking alcohol or using marijuana could underlie the persistence of use over time and problems with cutting down or quitting . Given the high prevalence of co-use of cigarettes with either alcohol or marijuana and previous research suggesting that co-use is associated with greater nicotine dependence potentially undermining smoking cessation , results of this study could inform the design of specific intervention components addressing substance co-use in smoking cessation interventions for young adults.The study analyzed baseline survey data from a randomized controlled trial of English literate young adults, age 18-25, residing in the United States, who reported smoking at least 100 cigarettes in their lifetime and currently smoked at least 3 days per week. A full description of the study design and protocol is described in Ramo et al. . Because the study was designed to examine the efficacy of a Facebook smoking cessation intervention, participants also had to use Facebook at least 4 days per week. Recruitment occurred between October 2014 and August 2015 through a paid advertising campaign on Facebook. Participants were screened for eligibility online, and, if eligible, signed an online University of California Institutional Review Board approved informed consent, and sent proof of identity. Verified participants were sent the baseline survey online, assessing demographics, smoking, and other health risk behaviors, including alcohol and marijuana use. Of the 7540 respondents who passed online eligibility screening, 1039 signed online consent; 739 sent verification of identity online; and 500 completed a baseline assessment. Enrollment rates were consistent with those reported in online smoking studies . The primary analyzes for the present study used baseline data from a sub-sample of participants who reported past 30-day use of both alcohol and marijuana in addition to tobacco.

Results were also compared to cigarette smokers who only used marijuana or only drank alcohol in the past month.Demographic and substance use measures used here have previously demonstrated good reliability and validity with young adults . Sociodemographics assessed were gender, age, ethnicity, years of education, and annual household income. Participants were asked “Have you smoked at least 100 cigarettes in your life” , followed by “What is the usual number of cigarettes you smoke in a day,” and “On average, how many days in a week do you smoke cigarettes” . Participants were asked if they had consumed alcohol in the past 30 days, if “yes,” they were also asked to report how often they drank alcohol, how many standard drinks they consumed on a typical day, and on how many of the past 30 days they binge drank alcohol. Binge drinking was defined as having 4 or more alcoholic drinks for women, 5 or more alcoholic drinks for men . Marijuana use was assessed as any use in the past 30-day .Participants were asked to report “what percentage of your cigarette smoking episodes occurred under the influence of alcohol” and “does your pleasure from smoking cigarettes change when you are drinking alcohol” based on McKee et al. . These questions were adapted for marijuana.Among cigarette smokers who used marijuana and alcohol, extent of co-use and perceived pleasure from smoking cigarettes when drinking alcohol or using marijuana were compared using paired samples t-tests. Perceived pleasure from smoking cigarettes when drinking alcohol or using marijuana were each tested against the null hypothesis . Participants were also grouped based on frequency of binge drinking in the past month based on Gubner et al. . Perceived pleasure from smoking cigarettes when drinking alcohol was compared across the binge drinking groups using ANOVAs. To validate findings in the current study among cigarette smokers who used both marijuana and alcohol, results from these individuals were compared to cigarette smokers in the parent study who used only marijuana or only alcohol . Statistical analyzes were performed using SPSS22 .Among a sample of young adult cigarette smokers who used both alcohol and marijuana in the past month, a similar proportion of cigarette smoking episodes were reported under the influence of alcohol and indoor cannabis grow system. In contrast, perceived pleasure from smoking cigarettes was only reported to increase when drinking alcohol but not when using marijuana. There were no differences between smokers who used alcohol þ marijuana compared to smokers who used only marijuana or only alcohol on these measures, increasing the validity of the findings. Tobacco and alcohol have been found to have combined pharmacological effects that result in greater reward . In contrast, marijuana and cigarettes may be coused primarily for reasons other than increased pleasure. For example, nicotine may attenuate some of the cognitive impairments induced by acute or chronic marijuana use and it has been suggested that nicotine may attenuate the sedative effects of marijuana . A recent qualitative study examining the effects of cigarette smoking on the perceived effects of marijuana use found certain individuals reported smoking cigarettes to intensify the marijuana high, while others reported not liking the combined effects as it made them feel dizzy or nauseous . Combined effects of marijuana use and cigarette smoking seem to vary by user, and may not be as uniform as the combined effects of alcohol and cigarettes. Since the main route of administration for marijuana is smoking, some aspects of marijuana use may serve as cues that increase urges to smoke cigarettes . In addition certain individuals may enjoy aspects of smoking in general, regardless of substance . Previous studies have found that urges to use marijuana and tobacco were correlated among young adults and that using tobacco subsequent to marijuana is a common pattern of use . The primary route of marijuana administration is smoking, often mixed with tobacco . Route of marijuana administration could play a role in differences in perceived pleasurable effects of smoking cigarettes when using marijuana. Research is needed to compare reasons for use and effects of cigarette smoking between different routes of marijuana administration .

Both the non-binge drinkers and all binge drinking frequency groups reported an increase in perceived pleasure from smoking cigarettes when drinking alcohol, suggesting that frequency of binge drinking and binge drinking itself may not be essential to the relationship between enhanced pleasure from smoking during alcohol consumption. Greater pleasurable effects of smoking cigarettes when drinking alcohol may occur with lower levels of alcohol consumption. Alcohol has biphasic stimulant and sedative effects, and nicotine has been found to attenuate the sedative/hypnotic effects of heavy alcohol consumption . Attenuation of sedative effects may be a motivation for the co-use of tobacco and alcohol most relevant to binge drinking.There are several limitations of this work. We used retrospective self-reported data which may be biased and cannot establish a causal inference between alcohol and marijuana use and perceived pleasure from smoking cigarettes. Laboratory-based human pharmacology studies or intensive longitudinal event-level designs , are needed to replicate our findings and advance this area of research. We did not assess the overlap between cigarettes smoked when both drinking alcohol and using marijuana, mode of marijuana use , or marijuana use frequency. This last limitation is especially important, since the relationships between marijuana and tobacco use and reasons for co-use may vary as a function of frequency of use . We also focused exclusively on the enhancement of perceived pleasure of smoking cigarettes by alcohol or marijuana rather than the ability of cigarettes to enhance the pleasurable effects of other substances. Previous work by McKee et al. suggests the direction we assessed was likely to be more affected, with individuals deriving more pleasure from smoking cigarettes while drinking compared to pleasure from drinking alcohol when smoking cigarettes . It should be noted that we asked participants to distinguish pleasurable effects of smoking cigarettes from effects of other psychoactive substances they co-used and we do not know how well participants were able to reliably do this. However differences in the reported pleasurable effects of alcohol on cigarettes compared to cigarettes on alcohol suggest that individuals are able to differentiate the effects of one substance on another . Future studies might also investigate reasons for and expectancies of substance co-use in addition to perceived pleasure . Lastly, our sample comprised young adult smokers participating in a Facebook smoking cessation intervention, which may limit the generalizability of the results; however given that 90% of all US young adults use social media , this concern is limited.The United States faces a dynamic landscape regarding marijuana, opioids, and alcohol. Concerns about these substances center around opioid misuse,an ongoing high prevalence of alcohol-related harms,and the liberalization of marijuana use policies.Not surprisingly, excessive use of alcohol, marijuana, and prescription opioids increases risk of addiction and developing associated substance use disorders .In 2014, 17.0 million people 12 years of age or older were diagnosed with alcohol use disorder, 4.2 million had a marijuana use disorder, and 1.9 million had a disorder related to the non-medical use of prescription pain relievers.In recent years, heroin and other potent opioids such as fentanyl have made increasing contributions to rising opioid overdoses.In addition, persons with alcohol, marijuana, or opioid use disorder are more likely to have comorbid conditions, which worsen prognosis, contribute to poor health,and can lead to inappropriate health service use.

The available evidence indicates that PLWH may have a heightened risk of poor COVID-19 outcomes, in part due to social determinants of health and multi-morbidity . Historically, PLWH have been disproportionately affected by mental health problems, including substance misuse and dependence, compared to the general population and HIV-uninfected peers . On one hand, psychiatric illnesses can contribute to HIV infections . On the other hand, psychiatric disorders can develop or worsen in PLWH due to neurologic manifestations of HIV , antiretroviral therapy -related toxicity , and psychosocial stressors, such as HIV-related stigma and loss of social capital . That said, PLWH may benefit from psychological resilience developed through the process of adapting to and overcoming the adversities brought on by living with HIV . Resilience, in general terms, is the process of coping with stress or trauma . In other words, it is a positive adaptation to adverse events, and may act as a buffer against adverse mental health outcomes. In PLWH, high resilience has been associated with lower depression and anxiety , improved health behaviors leading to higher ART adherence and viral suppression , safer sexual practices , and higher health-related quality of life . In the Miami Adult Studies on HIV cohort, PLWH exhibited higher resilience than their HIV-uninfected peers during the early months of the pandemic . Additionally,vertical grow system higher resilience in part accounted for lower anxiety and stress in PLWH. Based on these findings and the theory of HIV resilience , we hypothesized that higher resilience in PLWH would predict lower risk of substance misuse. The study of resilience in the context of HIV infection and substance misuse may offer unique insights regarding public health emergencies related to infectious diseases, such as the COVID-19 pandemic. In this study, we conducted a multi-cohort investigation on the relationships between psychological resilience, anxiety, and substance misuse in people living with and without HIV.

Descriptive statistics are reported as percentages for categorical data, as means ± standard deviations for continuous variables with a normal distribution, and as medians with 25th and 75th percentiles for data with a non-normal distribution. The normality of the data’s distributions was first determined using the Kolmogorov Smirnov test, and the equality of variances was confirmed using Levene’s test. Between-group differences were tested with Chisquare test, T test, or Mann-Whitney U test as adequate. Primary analyses consisted of multivariate generalized linear mixed models with separate random intercepts using binary logistic regression. The random intercepts used were C3PNO cohort , survey wave, and month of survey. This model generates a flexible marginal correlation among the repeated binary outcomes, including a declining association with increasing time separation, while retaining the property that the marginal probabilities follow a logistic regression model. The fixed effects include HIV status, age, sex, race/ethnicity, employment, homelessness, mental health care prior to pandemic, and treatment for SUD prior to pandemic. Due to substantial losses to follow-up, we performed an additional cross sectional analysis using data from all participants during the 1st wave of the survey. Logistic regression parameters were summarized as odds ratios or relative risk with 95% confidence intervals and P-value. We conducted a multi-cohort study of the Collaborating Consortium of Cohorts Producing NIDA Opportunities to assess psychological resilience, anxiety, and substance misuse in people living with and without HIV during the COVID-19 pandemic. Resilience in this study refers to an individual’s “ability to bounce back or recover from stress” . In this analysis of the combined C3PNO cohorts, data collected during the COVD-19 pandemic indicated that PLWH had higher odds for high resilience than HIV-uninfected participants after controlling for important factors such as sociodemographic characteristics and cohorts within C3PNO. In turn, high resilience was associated with lower risk of anxiety and substance misuse during the same period of time. These findings suggest that strategies to identify and strengthen resilience resources may help mitigate mental health problems and substance misuse in vulnerable populations.

Further, learning from HIV resilience and the public health response to HIV may provide valuable insights for individual- and community-level resilience that could help increase preparedness for public health crises, such as the COVID-19 pandemic, potentially reducing the burden on the mental health and well being of marginalized populations. Among those disproportionately affected by the pandemic are PWUD, who are often highly vulnerable, underserved, and understudied . Distress directly related to COVID-19, as well as the unintended social and economic consequences of lock downs contributed to increased patterns of substance misuse, along with alcohol- and drug-related overdoses . This was foreseen by many, as stress has long been linked to substance abuse and risk of relapse . Alarmingly, a prevailing concern is that the pandemic will have long-lasting impacts on mental and behavioral health. For example, people who initiated misuse of substances during lock downs may develop an SUD that may persist long after pandemic recovery. Disruptions to health systems may also make it more difficult for people with psychiatric disorders to seek and obtain adequate care and treatment. Moreover, bidirectional associations between COVID-19 and psychiatric conditions have been noted . The data presented in this study was collected between May 2020 and March 2021, and is likely not representative of usual patterns of substance misuse among C3PNO participants. Changes to the drug supply, such as decreased availability and quality along with increased costs have been reported by PWUD . For instance, cocaine use in the MASH cohort declined by more than half during the early months of the pandemic . Therefore, some substances may have been less frequently used during the study period. Also, changes in the availability of some drugs may lead some individuals to shift towards more easily accessible substances, such as alcohol and prescription drugs. As such, changes in substance misuse may be due to changes in drug supply rather than personal choices. On the other hand, the United Nation’s World Drug Report 2021 found that, despite initial disruptions, the global drug trade was largely unaffected throughout 2020.

This may explain why patterns of reported substance misuse among the C3PNO participants who completed both surveys remained stable throughout the study period, besides a slight decline in hazardous drinking among HIV-uninfected participants. Nevertheless, losses to follow-up must be taken into consideration, as participants who were lost to follow-up were more likely to smoke cigarettes , use cannabis and heroin/fentanyl than those who completed both surveys. Given the rise in incidence of substance-related overdoses during the pandemic, it is possible that some of the attrition in this study may be related to overdoses. Continued monitoring of substance use patterns in the C3PNO cohorts and other at-risk groups is warranted. While there are several important distinctions between the HIV epidemic and the current COVID-19 pandemic, this study illustrates that lessons from HIV may extend to resilience and its impact on mental and behavioral health. Resilience has been conceptualized most commonly as the process of overcoming adversity, but it has also been used in reference to a trait and the outcome of such process . What is common in all conceptualizations of resilience is that adversity is an antecedent and usually consists of traumatic events, disease processes, and daily stressors . With the advent of highly effective ART, HIV infection has become a manageable, chronic illness rather than a deadly disease. PLWH develop resilience as they learn to manage the infection, which includes engaging with health care providers and adhering to treatment. de Santis et al. described the process of resilience in HIV as one that entails intrinsic and extrinsic motivation, management of the disease, and mastering of the disease. On the other hand, the circumstances that led to acquiring HIV, the unique trauma of an HIV diagnosis, along with the wide array of adversities brought on by it,mobile grow systems may make it more difficult for PLWH to build resilience when compared to other conditions . Our findings show that PLWH had higher resilience and were less likely to report anxiety and substance misuse during the pandemic as compared to HIV-uninfected peers. Methamphetamine use was more frequent among PLWH than HIV-uninfected participants, and the use of other substances was either similar or lower among PLWH. However, resilience consistently showed a protective effect against substance misuse, including methamphetamine use. Notably, the higher resilience among PLWH seen in this study may be in part susceptible to survivor ship bias, as those who build resilience by engaging in treatment and managing the disease are more likely to survive and participate in research studies. Nevertheless, since high resilience demonstrated a protective effect against anxiety and substance misuse, higher resilience may partly explain the lower risk of these among PLWH. Similarly, a study of PLWH in Argentina showed that resilience mitigated the impact of economic disruptions on mental health during the COVID-19 pandemic . Others have also shown that higher levels of resilience are associated with less perceived stress and higher life satisfaction in PWUD, two critical factors involved in SUDs . These results support the notion that psychological resilience serves as a buffer against poor mental health that may directly and indirectly protect from substance misuse. Similar to PLWH, PWUD may develop resilience as they overcome SUDs, yet the circumstances surrounding substance misuse may also pose a barrier for resilience. As such, the relationship between resilience and substance misuse can be reciprocal and bidirectional. However, in the substance use literature, resilience is most commonly conceptualized as an outcome determined based on the presence or absence of substance use.

An excessive focus on resilience as an outcome fails to recognize the impact of resilience on substance use, as well as its malleability over time depending on circumstances. Further research is needed to understand the complex pathways between resilience and substance misuse. For instance, the effect of resilience on substance misuse may be in part mediated by anxiety, with higher resilience acting as a safeguard against anxiety, thereby reducing the risk of substance misuse. The potential complexity of these pathways is exemplified in a study by Yang et al. , which found that positive affect, self-esteem, and social support partially mediated the effects of resilience on perceived stress and life satisfaction among PWUD. On the other hand, resilience may directly reduce the risk of substance misuse by enhancing cognitive control and mindfulness over urges to use and to avoid impulsive and social behaviors conducive to substance use . Efforts to foster resilience within marginalized communities may help reduce the burden of mental health problems and increase preparedness for future public health threats. An advantage of studying resilience in the context of substance misuse is its strength-based approach. Rather than emphasizing the vulnerabilities of PWUD, resilience focuses on facilitators of well-being and other protective factors that can help PWUD overcome their adversities. Particularly in marginalized populations, understanding social and cultural contexts may reveal hidden sources of resilience . Nevertheless, resilience in the context of substance use has received relatively little attention and research on resilience-focused interventions is greatly limited . Interventions must consider the multi-factorial nature of resilience. In the context of substance use, an array of internal resilience resources are cited, including self-esteem, self-efficacy, personal skills, intellectual ability, religiosity/spirituality, and personality traits . External resilience resources are often considered at the family, school, and community levels, while environmental and structural factors are often overlooked . Efforts to enhance community resilience, which is fundamental for preparedness and recovery from public health crises, must address social and health inequities. Indeed, a key aspect of community resilience is health promotion, as the level of physical and psychological health of a population impacts their needs and ability to recover after crisis events . Public health advocates and policymakers may foster community resilience by addressing social determinants of health and other sources of social, economic, and health disparities. These strategies will require the integration and involvement of governmental and non-governmental agencies. Several strengths and limitations of the study must be considered. The data presented was self-reported, collected from convenience samples across C3PNO cohorts via in-person and telephone-administered surveys. As such, it is possible that the use of substances was under reported.

Natural aeration refers to the replenishment of O2 to the root zone from the atmosphere during the drainage period.It depends on the drainage class of the soil because O2 supply to the root zone is possible only after some critical air contenThis reached.Note that the critical air content represents the connectivity between the root zone and the atmosphere by air-filled pores.In the context of Ag-MAR, natural reaeration of the soil after flooding can be controlled by considering the soil parameters, the water application duration, and the crop tolerance to saturation.Forced aeration refers to intentional oxygenation of the root zone by several methods such as air injection, air bubbles, H2O2 , and solid peroxides.These methods are currently not used in commercial agriculture, although some of them have shown positive results in previous studies.Among these methods, air injection through subsurface drip systems might have higher potential in terms of O2 delivery and implementation costs, because it uses the in situ subsurface drip system.Previous forced aeration studies with air injection have focused on its impact on improving crop yield, nutritional value, and water use efficiency , but it has not been studied in Ag-MAR applications as a method to protect yield lost due to prolonged flooding.Monitoring soil physical–biogeochemical processes during MAR has been extensively studied ; however, since Ag-MAR is a relatively new technique in the MAR toolbox, to date only a few studies have monitored these processes in actual agricultural fields during Ag-MAR.Most Ag-MAR studies have focused on developing soil suitability guidelines , regionalscale aquifer storage estimations ,vertical grow rack water availability analysis , hydro-economicanalysis , and benefits evaluation using numerical modeling.

Among the few Ag-MAR field studies that exist, the soil aeration status, which may impair the implementation of future Ag-MAR projects, has been largely neglected.Dahlke et al.estimated soil aeration status using Eh measurements during 3 d of Ag-MAR in an alfalfa field on a well-drained gravelly sandy loam.The Eh values were closely correlated to water content and Eh was quickly returned to preflooding aerobic conditions when water application ceased.The report of Bachand et al.is the only work that examined the impact of flooding on soil O2 during Ag-MAR, which was studied in three almond, walnut [Juglans regia L.], and pistachio [Pistacia vera L.] orchards all located on well-drained soils.Bachand et al.calculated O2 depletion and recovery rates based on soil O2 and water content measurements in the root zone and suggested a few best management guidelines for growers:avoid standing water for more than 3–4 d,reduce time with water saturation above 74%, and plan Ag-MAR flood duration based on past, soil-specific flood irrigation guidelines.The applied water amounts in these demonstrations were relatively conservative , and therefore in the current study, we sought to explore soil aeration during Ag-MAR with higher hydraulic loads.The goal of this study is to quantify the soil aeration status during Ag-MAR experiments and to test air injection as a technique for improving soil aeration during continuous flooding, thus reducing the risk of root and crop damage due to anoxia.For this purpose, three field experiments were conducted: one at a cover-crop field, and two at almond orchards, all located in the Central Valley, California, USA.The experiments were used to compare natural aeration and forced aeration by air injection through the subsurface drip system during Ag-MAR.In the following, we first explain the method we chose to quantify soil aeration and the methodology of the experiments.Next, we present the results of the Ag-MAR field experiments.Finally, we discuss the impact of forced aeration during flooding and implications for Ag-MAR projects.We used soil O2 concentration and Ehmeasurements to quantify soil aeration status during Ag-MAR.

Using these aeration quantifiers in combination allows assessing the soil aeration status during both aerobic and anaerobic conditions.We set a soil O2 threshold of 5% as a lower bound, since O2 concentrations below that are considered inadequate for root function.In all O2 measurements, we assume an equilibriumin the bulk soil between the gas and liquid phases.Redox potential is a useful soil aeration quantifier in waterlogged soils where O2 levels are low.Generally, Eh above and below 300 mV indicates aerobic and anaerobic conditions, respectively.The Eh values of 300 to −50 mV indicate moderately reducing conditions, which are dominated by facultative reducing microbes.In this range, O2 is the preferred electron acceptor in cellular respiration, followed by NO3 −, Mn4+, and Fe3+.The Eh below −50 mV indicates highly reducing conditions where SO4 2− and CO2 are the electron acceptors.Note that Eh is a qualitative aeration quantifier, as it measures the mixed potentials of the soil and therefore cannot be used for identifying a specific redox couple.As such, it is only useful for indicating trends over time of more reducing or oxidizing conditions.At each site three treatments were tested:flooding with air injection by subsurface drip irrigation ;flooding without air injection; and control.The treatments were divided by bermsto prevent flooding of adjacent plots.Each treatment comprised a row of 11–12 almond trees at KARE and NSL, or four beds of cover crop along 80 m, at CT.Plot area, including all three treatments, was 1,500, 940, and 1,440 m2 at KARE, NSL, and CT, respectively.In each treatment, one to four profiles were installed with soil sensors at 15-, 30-, and 50-cm depth.Soil sensors measured volumetric water content , temperature, gas-phase soil O2, and Eh.To complete the Eh measurements, a commercial Ag/AgCl reference electrode was placed in a salt bridge that was installed at a depth of 30 cm at each profile.Redox potential readings in the field were corrected to standard Eh by adding ∼210 mV.Soil O2 readings in the soil were temperature and pressure corrected as recommended by the manufacturer.Note that these galvanic-cell O2 sensors are diffusion based, and when its membrane is clogged , it will measure zero O2 concentration, although a pore water sample from the same location might show higher DO concentration.Still, these sensors are widely used in soil studies and our experience under flooded conditions shows that this issue is more prominent, as expected, in clayey soils.All sensors readings were taken every 1 min, and 10-min mean values were recorded with data loggers.

In addition to the continuous monitoring, following the method of Friedman and Naftaliev , air samples were extracted with a 100-ml syringe from perforated 100-ml plastic bottles that were buried inside the soilat depths of 15, 30, and 50 cm.Air samples were measured onsite with an O2 flow-through sensor.In several cases where the plastic bottles were filled with pore water, samples were extracted using a syringe and measured onsite for DO with an optic sensor.At CT, dedicated pore-water samplers were installed at depths of 15 and 30 cm and used for routine manual measurements of DO.The detailed setup of the three sites is shown in Figure 2.Both almond sites were regularly irrigated with surface micro-sprinklers, and therefore a dedicated SDI was installed for the air injection treatment as follows: holes were augured to 30-cm depth using a 5-cm-or 2.5-cm-diam.hand auger and then a 4-mm polyethylenetube was inserted inside, and the holes were back filled with a soil-bentonite slurry.This was done carefully using an outer rigid pipe as a guide, to prevent soil clogging of the tubes.The tubes were connected to drippers that were connected to an on-surface lateral line , which delivered the injected air.In order to mimic an SDI system of a commercial orchard, we used a configuration of two lateral lines, each at a distance of 90 cm from the tree trunks, with drippersat a depth of 30 cm, spaced 120 cm apart.Note that the horizontal distance between the buried emitters centerline and the soil sensors was in the range of 40–60 cm.The cover crop site was rainfed, and air injection was based on an SDI system that was already installed in the soil for several years.The horizontal distance between the buried emitters centerline and the soil sensors was in the range of 0–15 cm.Each experiment started by flooding the plots with ground wateror surface water using flood-irrigation-gated pipesor sprinklers.Applied water volumes were measured by water meter and doppler flow meter.At NSL, the continuous discharge was not measured but applied water volume was estimated manually several times during the experiment using a graduated measuring bucket.Water was applied continuously for a few hours and up to1 d,cannabis grow racks depending on the infiltration rate of each site.When O2 concentrations started to decline, air was injected through the SDI with a pressure-regulated air compressor , which kept the absolute pressure at the range of 160–200 kPa.Air injection was ceased a few hours and up to 2 d after water application ceased.At the end of the experiment at NSL, we conducted a preliminary test of aeration using CaO2 powder, which reacts with water to produce O2 and H2O2.A 600 g of CaO2 powder was scattered on the soil surface, covering an area of 9 m2 around one tree only , and a small amount of water was sprayed over it.Gross almond yield was collected per tree for all varieties at KARE and for the Nonpareil variety at NSL at the end of August after the recharge season.At CT, plant height, dry root length, and dry root weight of bell beans were measured before and after the flooding experiment.Plant sampling included careful excavation of the roots using a shovel, measurement of stem height in the field, washing roots in the laboratory, and measuring dry root weight and vertical root length.From each treatment 12 bell beans plants were sampled before and after the flooding experiment, and a total of 68 plants were analyzed.Root weight was normalized to root vertical length and plant height, to reduce the sampling error due to natural variability in root and plant morphology, and averages values were calculated for each treatment.Data were analyzed using ANOVA performed with the software R.A one-way ANOVA was applied to the manually collected data and differences between means were determined with Tukey’s test.Continuous data collected with sensors were not analyzed with ANOVA due to heteroscedasticity and lack of independence of the high-resolution continuous measurements.For these measurements, we report the summary staThistics and compare the distribution of differences of the soil aeration quantifiers between the treatments with and without air injection.Water was applied continuously at all sites according to the site-specific infiltration rate, in order to maintain a ponding depth of few centimeters.

To avoid flooding of adjacent plots, the water supply was decreased or stopped occasionally during the experiment.Although maintaining even flooding within the flooded treatments was a difficult task at all sites , it was practically impossible at the NSL site due to a combined effect of poor soil drainage and plot slope.Nevertheless, an estimated total water amount per area of 0.76, 0.065, and 2.9 m, was applied at KARE, NSL, and CT, respectively.Note that these estimations are averages that are based on the total plot area.Although at KARE flooded area and total plot area were almost identical, at NSL and CT, it represents lower and upper bounds for the total applied water, due to smaller and larger effective flooding area, respectively.Flooding of the plots led to the expected trend of increasing soil water content and decreasing O2 and redoxlevels, whereas at the control treatments, high soil aeration status was observed at relatively low θw.An example of the soil aeration status is shown in Figure 3, where for each site one profile from each treatment at 30-cm depth is presented.For the air injection treatments, the impact of air injection on soil aeration status can be detected as an increase in O2 and Eh levels during air-injection periods; it is limited at KARE and NSL, but consistent at CT.The distribution of the continuous measurements of all sensors at all depths is summarized in Figure 4, where results are grouped according to treatment and period.The period before air injection was defined as the time before the first air injection started, the period during air injection includes active air injection and the times between air injection cycles, and the period after air injection starts when the last injection ends.Accordingly, in all flooded treatments , aeration status decreased below the soil-aeration lower bounds for few hours at CT, a few days at KARE, and up to several days at NSL.At NSL, hypoxic to anoxic, and anaerobic conditions were mainly observed in the air-injection treatment, likely as a compounding effect of plot slope and specific poor-drainage conditions where the soil sensors were located.