Cannabis Grow

Such a project could provide land managers and law enforcement with the support they need to adequately monitor areas and respond accordingly. It could also encourage individuals to write to governmental officials and create pressure for policy makers to act. Mexican DTOs are the foremost cultivator group and have the single largest impact on the marijuana industry. The same organizations responsible for the majority of marijuana production on California public lands are the heart of the bloody Mexican drug war. President Obama met with officials in Mexico City and augmented “ongoing US aid to Mexico under the Merida initiative: a three-year, $1.4 billion package aimed at helping Mexico fight the drug cartels with law enforcement training, military equipment and improved intelligence cooperation.”However, this money is yet to incur any noticeable effect on drug cartels.In order to disrupt DTOs, the United States needs to halt the flow of money and weapons from the US to Mexico. By upholding current regulations, we empower cartels to continue their destructive, violent practices. Marijuana cultivation on public lands is a significant problem with viable solutions, but without essential changes in law enforcement strategies and nationwide public policy, it is a problem we can expect to continue,vertical grow rack system putting the future of our lands and our people at risk. The US war against marijuana has increasingly escalated since its conception because it is not a war that can be won.

Drug production has become increasingly destructive and dangerous despite an estimated $7.7 billion spent annually by the US Government to enforce marijuana laws.Such regulation inflates the steady revenue flowing to criminal organizations that in turn generate widespread crime and violence. Regardless of the legal status of marijuana, as long as it remains in high demand there will be a market to supply it, regulated or unregulated. Government-imposed prohibition gives rise to black market systems that are dominated by major criminal organizations that control production and distribution. This system of perpetual crime and punishment is sustained at the cost of all parties involved, and requires a fundamental change in the system itself. Public policy plays the most crucial role in dictating the status of marijuana markets and their effects on governance and fiscal resources. The most powerful mechanism for opposing cultivation trends is to change the role of marijuana in California and the United States through legalization. California legislator Tom Ammiano proposed the Marijuana Control, Regulation, and Education Act in 2009 in an effort to take marijuana cultivation out of cultivator control and put it to use for the government through tax revenues. It was estimated that marijuana taxes could generate over a billion dollars in tax revenues while saving the state of California hundreds of millions more in enforcement, legal, and incarceration costs. The Regulate, Control & Tax Cannabis Act, Proposition 19, was put on the California ballot in November, 2010, to legalize marijuana and control it like alcohol. Though Prop 19 failed by a narrow margin, widespread legalization could bring marijuana out of the black market and into the mainstream, enabling governmental controls that are impossible under the current system, such as barriers to marijuana access for youth.

On a national scale, such a system would de-incentivize DTO operations by reducing their profit margins, and removing black market demand. Legalization would create a legitimate marijuana industry through which cultivators can be regulated, resulting in more efficient and less damaging practices. Consumers could then buy less harmfully produced marijuana because it would be available through established institutions. Finally, alternative uses of hemp including fibers, oil, and protein could be re-established within legitimate and competitive industries. Decarbonization of the U.S. and global economies requires a transition away from fossil fuels to renewables, especially in the transportation sector – the largest contributor to U.S. greenhouse gas emissions.The environmental costs associated with the production and combustion of petroleum fuels have not been internalized by producers and consumers, respectively, prompting government intervention. Federal and state governments have increasingly looked to market-based environmental policies to reach their decarbonization goals, often by enacting credit trading schemes for markets to meet an annual standard. This dissertation studies the most prominent of such U.S. public policies that incentivize displacement of petroleum fuels with renewable and low carbon transportation fuels. The Renewable Fuel Standard is the largest program to support renewable fuels in the U.S., requiring a variety of bio-fuels to be blended in the national fuel supply. The RFS is criticized for being technology biased, as it specifies how much of which biofuels must be used to reach its emissions reduction goals. State and other federal governments now increasingly look to carbon intensity standards in the transportation sector, which provide a technologyneutral policy option.

The largest of such policies is California’s Low Carbon Fuel Standard , which sets a carbon intensity standard for the state’s transportation fuel supply. This dissertation explores the past, present, and future of low-carbon fuel incentive programs. Chapter 1 begins with the present, addressing an important ongoing challenge associated with these policies – namely incomplete pass-through of incentives and costs to fuel prices. Chapter 2 looks ahead a decade, forecasting a range of compliance outcomes for California’s LCFSthrough 2030. Finally, lessons from the last decade are drawn in Chapter 3, exploring trends in the three standing carbon intensity policies worldwide using publicly available historical data. Chapter 1 provides an empirical analysis of credit revenue pass-through. Specifically, time series techniques are used to estimate the extent to which implicit taxes and subsidies generated from the RFS, LCFS, and CFP are passed through to a variety of diesel fuel prices. In a second best policy framework, an efficient RFS and LCFS achieve their respective GHG targets while minimizing compliance costs. If fuel blenders have market power, they have the incentive to drive up compliance costs, leading to an inefficient outcome. The findings from Chapter 3 suggest that obligated parties completely pass through their implicit taxes from the RFS, LCFS, and CFP to wholesale diesel prices. They suggest incomplete pass through, on the other hand, of bio-diesel subsidies to rack blended diesel prices. The RFS, LCFS, and other carbon intensity standards all tout an attractive feature: revenue neutrality. These policies are revenue neutral to the transportation system because the implicit tax revenue generated from obligated parties purchasing compliance credits is used to lower the price of alternative fuels, effectively subsidizing them. Market imperfections, however, may restrict how much of the credit revenue is being fully passed through to consumers in the form of lower prices for alternative fuels. Chapter 2 assesses if and how California is likely to achieve the 20 percent CI reduction target by 2030 set forth by their LCFS. Using a Vector Error Correction model, LCFS credit demand is projected through 2030 under business-as-usual uncertainty. The model is trained using 30 years of historical trends in gasoline and diesel demand, vehicle miles travelled, oil prices, and other economic indicators. Several policy scenarios are simulated and evaluated against a baseline scenario, which extrapolates current trends. Biomass-based diesel, the marginal fuel for LCFS compliance, makes up between about 60 and 80 percent of finished diesel in 2030 in the baseline scenario, reflecting a substantial increase from current levels. Under most alternative policy scenarios,vertical grow system and especially in the case of rapid electric vehicle deployment, compliance is met with significantly less biomass-based diesel. The first two chapters analyze the LCFS and CFP, which are a relatively new policy instruments used to reduce transportation emissions reductions. As more and more states continue to adopt similar carbon intensity standards, it is imperative to understand similar existing programs have performed, however comprehensive analyses on them are relatively scant.

Aiming to fill that gap, the final chapter, Chapter 3, reviews the three standing carbon intensity standards in California, Oregon, and British Columbia using publicly available data and information. British Columbia was the first jurisdiction to implement a CI standard in 2010, followed shortly after by California in 2011, and later followed by Oregon in 2016. California’s program is the largest given the state’s voluminous population and fuel demand. Low CI scores associated with avoided emissions have brought about staggering growth in the use diesel alternatives such as bio-diesel, renewable diesel, and biogas in the three jurisdictions. In California, diesel alternatives generated the majority of LCFS credits, generating nearly two billion dollars in revenue in 2020 alone, a third of the total. Since diesel are so critical to compliance, this dissertation pays special attention to that side of the transportation sector and seeks to impart an understanding of how diesel markets and alternative fuel policies interact.Renewable and low carbon fuels are becoming an important part of decarbonization strategies worldwide. Several policies have been, or are being planned to be, implemented in the United States. There are three policies, one federal and two state, that lead this effort. The U.S. Renewable Fuel Standard requires certain percentages of gasoline and diesel be displaced by renewable fuels each year. California’s Low Carbon Fuel Standard and Oregon’s Clean Fuels Program set targets to reduce the CI of transportation energy in their states. The RFS, LCFS, and CFP all rely on systems of tradeable credits for compliance which prompt implicit tax-subsidy schemes in fuel markets. Firms pay a penalty on their petroleum products and the revenue is transferred to alternative fuel producers effectively in the form of a subsidy. The efficacy and efficiency of these policies hinge on the implicit taxes and subsidies propagating through fuel supply chains. This paper studies pass through across two dimensions in the diesel sector: implicit taxes placed on petroleum diesel and implicit subsidies awarded to bio-diesel. Implicit taxes and subsidies from the RFS stack with those from the LCFS and CFP in California and Oregon, respectively, and therefore are evaluated both separately and together. There are three points in fuel supply chains where pass through is relevant, this paper studies two of them: the wholesale market to blenders and blenders to retailers. This paper does not investigate pass through from retailers to consumers, which must also be complete to achieve efficacy of the policies. The pass through of bio-diesel subsidies to retail prices of blended diesel is an important area for future research, especially given evidence of incomplete pass through of ethanol RIN subsidies to E85 retail prices in the literature . U.S. crude oil refiners and petroleum importers are required to purchase Renewable Identification Numbers , the compliance credits in the RFS, for each gallon of gasolineand diesel supplied, which act as an implicit tax. California and Oregon refiners and importers face a similar obligation under the LCFS and CFP, respectively, namely deficits that are generated for each gallon of gasoline and diesel consumed in-state. There are robust markets for RINs, LCFS, and CFP credits and the market price, along with the stringency of the policies, determine the level of the taxes and therefore the cost of compliance. Fuel blenders purchase bio-fuels with a RIN attached to it. Once the fuel is blended, the RIN is separated from the fuel and can be sold on the RIN market. The value of the RIN then, acts as an implicit subsidy on the bio-fuel. If blenders have market power in selling RINs, they have the incentive to drive up RIN prices, which in turn, raises compliance costs for refiners and consumers. How much of the RIN tax that is passed through by refiners will determine the incidence of the increased RIN prices resulting from the incomplete pass through of the RIN subsidy. The same relationship between the tax and subsidy is present in the LCFS and CFP. This paper is the first to analyze RIN pass through on both sides of the tax-subsidy mechanism, the first to examine pass through of bio-diesel subsidies, and the first to consider either the LCFS or CFP. Indeed, most studies to date on pass-through for implicit taxes and subsidies for fuels have focused on the federal RFS and the gasoline industry, with much less focus on state policies and the diesel industry. Diesel fuels accounted for 27 percent of total transportation energy in 2020.3 Biomass-based diesel earns the lion’s share of credits in California’s LCFS and a growing proportion in Oregon’s CFP, making diesel an important piece of the transition to lower carbon fuels. Furthermore, pass-through results from the gasoline industry may not hold for the diesel industry because of differences in costs, production, storage, and blending constraints, demand and supply elasticities, and market structure.

Marijuana cultivation on state and federal lands became a major law enforcement priority and the US Forest Service, National Guard, CAMP and other cooperative task forces have taken on primary roles in conducting counter-cultivation efforts.New law enforcement objectives were established in the “Strategic Plan” which identified short-term and long-term goals, as well as the methodology “to eliminate, disrupt and dismantle the leadership, command, control, and financial infrastructure of Drug Trafficking Organizations.”The key developments within the agencies regulating marijuana cultivation were year round operations and investigations that targeted whole organizations. However, sustained operations required benchmarks for progress. Enforcement agencies would use short term results to measure progress on long term goals. Previous measures of short-term success persisted, including site location, plant eradication and cultivator arrests. However, law enforcement agencies created divisions strictly dedicated to opposing DTOs by assigning patrol officers exclusively to the issue, reassigning alternative workloads, and removing extraneous administrative duties of those in charge in order to focus the necessary resources to impact DTOs. In addition, increased funding allowed agencies around the state to begin a training and recruitment process to significantly increase staffing. In the Pacific Southwest Region of the Forest Service, the additional staff would include 1 supervisory special agent, 3 patrol captains, 18 special agents, 50 law enforcement officers, pipp drying racks and 6 administrative assistants, all of whom will be dedicated almost exclusively to marijuana control.

This will allow for long-term engagement in year round counter-cultivation efforts that utilize preventative measures as an advantage. Instead of waiting for a site to be found in July or August, agents will be able to look for and follow up on leads throughout the year. Equally important, they can identify priority cases for full investigation so they may be completed to a “reasonable conclusion.”Investigations will be prioritized based on existing intelligence, site logistics, available resources, and special public interest. The process of site review involves a methodical documentation of evidence such as cell phone contacts and the origin of supplies, which is entered into records and scrutinized for pursuable leads. Previously, useful evidence would have remained untouched at the site, or on rare occasions, kept in police storage. The potentially useful information left at sites was lost to neglect. Now, a significant portion of the evidence left behind is subjected to intelligence analysis. Increased utilization of intelligence analysis centers has made this process much more efficient and effective, which enables preventative tactics and helps governmental agencies learn about and infiltrate tight drug trafficking institutions. Governmental agencies have also changed investigation and detection strategies. While some authorities claim that there is nothing better than a helicopter and a well-trained eye, enforcement agencies are developing the use of more sophisticated techniques. These include, but are not limited to, ultraviolet, infrared, and electronic detection systems. Other techniques include night time patrols in high risk areas when cultivators may be less attentive, year-round patrols, and new detection methods such as monitoring for irrigation and cultivation supplies, comparing watershed precipitation with surveys of water flow quantities, and testing for chemical nutrient imbalances in bodies of water.

The more time that is dedicated to research and detect sites early, the less time is required to raid and eradicate each site. Raids are carefully planned efforts, designed to reach set goals while minimizing the risk to agents. First, team leaders develop a raid plan and develop logistics such as funding sources, equipment requirements and invasion methods. Agents in charge then gather a team that they brief, supply and prepare. New agents and officers are required to complete a thorough training program to learn remote raid techniques. Teams sometimes hike into sites for covert operations, but more often, they rappel down from a helicopter into the nearby area. Officers face major disadvantages when raiding sites because cultivators have been living at the location for months. Covert operations involve the most risk because hiking conditions and landscape characteristics can subject officers to ambush and provide cultivators with vantage points for armed engagement. While no officers have been fatally wounded during remote operations, there have been various cases involving gunshot wounds. During helicopter raids, cultivators generally flee from the scene while law enforcement officers are lowered into the area. While living on-site for months, cultivators develop elaborate escape routes and hiding spots. Hiding places can be as close as one hundred feet from a grow site, and are rarely found without K-9 assistance. The cultivators that are obtained are generally low-level employees with minimal knowledge about the larger organization that employs them. To complement tactical operations, government agencies have developed another significant long-term goal to develop an understanding of commercial scale, remote marijuana cultivation, within the broader public.

Regional leadership conducts public education programs by presenting PowerPoint demonstrations about DTOs at meetings, forums, and presentations for politicians, government employees, and the general public. Law enforcement organizations facilitate information sharing with the media and local contacts, and have developed “bi-lingual material to be distributed in high risk areas seeking information and offering rewards.”These programs aim to increase the awareness in an effort to increase reports of suspicious activities. When marijuana related activities are reported early, enforcement agencies gain a strategic advantage in combating individual sites. In addition, early detection allows more sites to be discovered and raided throughout the year because enforcement efforts are spread over a longer period of time. Public education creates an understanding of the consequences of marijuana production on various scales. This can provide political support for the prevention of DTO related activities in California, as well as alter patterns of marijuana acquisition and consumption within the general public. The production of potent marijuana requires intensive resource inputs to achieve high yield. This means that carefully planned and executed cultivation systems are crucial to developing quality marijuana harvests, and that cultivators manipulate the environment to optimize conditions for Cannabis plants. The widespread influence of Mexican cartels on outdoor cultivation in California causes similar processes to be performed at separate sites dispersed across large geographic distances. DTO operated grow sites have developed systematic patterns of behavior that occur with regularity and make their efforts distinct. Cultivators inhabit remote sites over long periods of time to develop plantations, and create a multitude of adverse effects in the process. Site selection is a crucial aspect of the cultivation process. DTOs often choose prospective locations long before they enter into a site. Some key elements that they look for on maps and aerial photographs are isolated water sources, slight canopy cover and adequate sunlight exposure. Sites are created in areas such as logged landscapes, conservation reserves, remote areas of national parks,pipp horticulture and other places with difficult access and visually indistinct features from a birds-eye view. These are often areas where people rarely go because entry is made difficult by physical barriers such as cliff faces, steep talus slopes, dense clusters of vegetation such as poison oak, and even man-made berms. Due to the rugged and highly vegetated condition of most prospective sites, preparing land for marijuana planting is both labor intensive and time-consuming. Laborers work long hours to provide Cannabis plants a monopolistic domination of the landscape. The dynamics of landscape alteration depend on site-specific characteristics, but many similar practices occur throughout DTO operations. During the site supply process, cultivators cut or wear trails into the landscape that weave back and forth making site access for material transport easier. In order to avoid detection, laborers try to avoid leaving evidence of their presence up to a certain point, such as a major physical barrier, after which distinct paths are worn into the ground. The sheer weight of laborers’ equipment loads combined with regular use of the trails is enough to trample and kill small vegetation.

The paths connect site entry routes to the food preparation area, sleeping area, latrine, and various marijuana plantations. One site may contain 30,000 plants, but within that site the plants are often divided up between multiple smaller plots. Laborers’ movement along the paths is responsible for the introduction and distribution of non-native plant species to new areas. Laborers accumulate and transport seeds or spores on their bodies, clothing, shoes and equipment. In the California central coast region, cultivator movement along self-created paths is cited for the spread of Sudden Oak Death syndrome in Tan Oak, Black Oak, and Coastal Live Oak trees.Studies conducted by the Santa Lucia Conservancy show that the occurrence of SOD is facilitated by remote inhabitance through transmission of the plant pathogen responsible for SOD, Phytophora ramorum. Marijuana cultivators contribute to the spread of Phytophora ramorum to uninfected oak trees and exacerbate the effects of Sudden Oak Death syndrome by moving throughout affected landscapes that are part of their widespread system of sites. Movement by any person or animal can effectively transmit this pathogen to uninfected oak trees, but cultivators navigate through these areas more frequently than other people who may pass through. Their movements are also responsible for the spread of a variety of harmful invasive species including thistles, Vinca, Periwinkle, English Ivy Yard, and others.Invasive organisms often out-compete native species because they possess adaptive characteristics and lack natural competitors when introduced in new areas, which results in widespread alterations to the food-web, nutrient cycling, fire regimes, and hydrology of otherwise well preserved ecosystems. Many attributes of remote ecosystems are not ideal for agriculture, so laborers invest much time and energy in altering land to make it suitable for Cannabis cultivation. Workers clear understory vegetation to eliminate potential competition and prepare the soil for Cannabis plantations. The cleared vegetation, referred to as “slash piles,” are discarded in stream beds, causing impediments to hydrologic flows, or used to create berms up to 8 feet tall in order to bar site access.Throughout the growing season, cultivators use chemical techniques to maximize THC content and bud production. These intensive methods change soil dynamics, nutrient levels and chemical makeup, thus creating the opportunity for a new composition of vegetation to emerge. Landscape alteration may awaken seed banks in the soil that have sat dormant for up to hundreds of years, alter the ability for some plants to re-grow because of changes in soil chemistry, destroy habitat for a variety of organisms, and have many other adverse affects on otherwise preserved ecosystems. In short, remote Cannabis cultivation forever changes the ecosystems in which it takes place. In highly mountainous areas, growers dig out terraces on hill slopes to create planting beds. In the process, soil is displaced leading to accelerated rates of hill-slope erosion. Some terrace beds are stabilized by falling trees, trimming them into logs, and inserting the logs into the terrace walls to hold the dirt in place. This is an important step to provide somewhat stable access to individual plants on steep slopes, and to prevent landslides that could destroy entire plantations. However, when these are removed, the stock of topsoil is greatly diminished. On slight grades or flat surfaces, cultivators mound soil around Cannabis stems to optimize nutrient uptake. For plantations with high percentages of gravel or sand, growers will bring in loamy soil to provide proper soil composition and nutrients. The affects of these changes on the natural environment can vary. For instance, fallen trees naturally promote the growth of under story species; however, the cutting of trees can disturb soil and impact the ecosystem services that they once provided such as habitat, nutrient cycling and moisture retention. Many land alterations remove perennial root structures that stabilize sediment causing the hillsides to lose stability and become more susceptible to small landslides and sedimentation of water sources during precipitation. Sedimentation alters water flow, reduces the capacity of water stocks, degrades the habitats of various species, and makes waters turbid – reducing the capacity for organisms to photosynthesize. Further, chemical toxins and metals bind to clay particles in fluvial sediment, are consumed by bottom feeding organisms, and bio-accumulate in higher order predators throughout the food chain. Cultivators approach land alterations with utter disregard; falling old growth trees, discarding of brush in stream beds, and littering the ground indiscriminately with waste. In sites intended for continued cultivation, laborers dig deep holes that are used to dispose of trash at the end of the harvest season in order to reduce the chances of detection between one season and the next.

There are many possible explanations for why deer and gray fox space use might be more influenced by cannabis farms than lagomorphs. These generally have to do with characteristics on the farms themselves. Wildlife may be interacting with the increased presence of domestic cats and dogs on cannabis farms , for instance, for deer as potential or perceived prey, or gray foxes as competitors . Alternatively, deer and gray foxes may be responding to behavioral cues from increased human presence and activity on cannabis farms . It is possible that lagomorphs are more behaviorally flexible than deer and gray foxes and can avoid altering their spatial patterns by instead shifting their temporal activity patterns, for instance, becoming more nocturnal . More research is needed to disentangle these potential mechanisms. Both detection rate summaries and model results suggest that cannabis farms appeared to disproportionately influence the space use of larger wildlife species. Black bears had a higher detection rate on comparison sites compared to cannabis farms and the model results indicate that larger black-tailed deer and gray foxes might avoid cannabis farms, while smaller animals such as lagomorphs appear to be unaffected. This result is expected, as large bodied animals such as deer may be unable to access space on the farms if they are physically blocked by fencing,vertical grow system while smaller species are still able to move through these barriers .

Despite variation in which species responded to cannabis farms, we did not find evidence from either detection rate summaries or model results to suggest that predators were attracted to these sites. Other studies have shown predators tend to avoid agricultural development, and our results seem to support the same trend . By contrast, there has been recent suggestion that cannabis production on public lands may serve as an “ecological trap” by attracting carnivores to production areas that then expose individuals to deadly toxicants . Our results, at least in the short-term, suggest that this dynamic may be less likely to occur on small-scale private land cannabis farms. This highlights the different potential ecological threats and processes playing out on public versus private land cannabis production sites. Not only do private land cannabis farms seem to use fewer toxicants , but they may also have higher human activity levels on site compared to public land production located in more remote areas. Wildlife may in turn tend to avoid this human presence rather than being attracted . This study begins the discussion regarding a glaring shortage of data on animal space use on cannabis sites, but there are many further avenues for future research. For example, the relative importance of cannabis farms in their influence on animal space use should be analyzed in the surrounding landscape context. The influence of roads on the modeled detection results implies that cannabis cultivation, despite occurring in a rural area in this case, was not the only form of human disturbance to which animals were responding. It may therefore be useful to compare cannabis and other forms of rural land use.

In addition, it is necessary to conduct further study at broader spatial and temporal scales in order to examine long term wildlife community response to cannabis and unravel the complicated set of potential contributing factors.Wildlife are likely to have species-specific responses to small-scale outdoor cannabis farms, and, thus, the specific land use practices occurring at a site may be influential for biodiversity conservation in these communities. Future studies should examine the role of fencing, timing of human activity, presence of domestic dogs and cats, and other site level practices that may influence wildlife use. Many small-scale cannabis farms are not part of a licensed production system , and therefore cannot be regulated for their production practices . For these producers, a mix of educational resources on wildlife friendly growing practices, grower enforced community standards or expectations, and law enforcement efforts to reduce noncompliance, may play an important role in increasing or maintaining biodiversity. For species deterred from cannabis farms, such as was implied by our deer and gray fox results, further research is needed to understand the mechanism for this avoidance. If, for example, fencing, artificial lighting, or sound are identified as major causes of this deterrence, then careful consideration should be given to the regulations on these practices at cannabis farms and their relation to critical habitat features such as water sources or animal migration routes.There is a national trend toward statewide legalization of medical marijuana despite federal classification of marijuana as a Schedule I illicit drug. There are compelling arguments for and against medical marijuana legalization and its potential impact on an array of complex social issues .

Residents in states where medical marijuana is legal are more likely to have tried marijuana, report current marijuana use, and be diagnosed with marijuana abuse or dependence . Additionally, there is preliminary evidence to suggest that there is likely a dose-response relationship between the number of years since legalization and marijuana prevalence rates . A key question regarding more liberal marijuana policies is whether and how they affect use of other drugs including addictive and harmful substances like tobacco. Previous studies have found a strong positive association between cigarette and marijuana use . Epidemiologic data indicate that the prevalence of tobacco and marijuana co-use has increased from 2003 to 2012 . Moreover, the increase in co-use occurred specifically among those ages 26–34 years, and the greatest percent increase, in those ages 50 years and older . It is unknown, however, if this national increase in co-use is directly associated with statewide legalization of medical marijuana. If marijuana policies are indeed associated with co-use, the current trend toward legalization of medical and/or recreational marijuana, without any regulatory action, has the potential to influence patterns of cigarette and marijuana use/co-use over time. An increase in cigarette and marijuana co-use has the potential to create challenges for cigarette smokers who want to quit. There is evidence to suggest that cigarette and marijuana co-use is associated with greater nicotine dependence . Possible explanations for this link include the role of the endocannoboid system in nicotine metabolism , genetic predisposition for co-use , and various environmental and cultural influences . The relationship between co-use and nicotine dependence, however, is understudied in adults, particularly among those ages 50 years and older. Since nicotine dependence is influenced by both nicotinic receptors and nicotine associated metablism that change with age ,pipp racking we can expect nicotinedependence among cigarette and marijuana co-users will also vary over the lifespan. Few studies have examined cigarette and marijuana co-use and nicotine dependence from adolescence through adulthood. As the nation is well-past the tipping point on medical marijuana legalization, studies are needed to take a closer look into whether marijuana policies have the potential to influence tobacco control efforts at the population level. For example, over time, it is likely that greater access to legal marijuana will increase the absolute number of co-users who have greater nicotine dependence and difficulty quitting cigarettes. Such data can help to identify subset populations at higher risk of nicotine dependence and could have both policy and treatment implications in tobacco control. In this study, we sought to examine relationships between medical marijuana laws and cigarette and marijuana co-use. Additionally, we examined the likelihood of nicotine dependence in co-users. We analyzed data from the 2013 National Survey on Drug Use and Health and stratified the analysis by age categories. Results from this study can inform the direction of future medical marijuana policies that may inadvertently affect tobacco control efforts.We analyzed cross-sectional data from the 2013 NSDUH conducted by the Substance Abuse Mental Health Services Administration . The primary purpose of NSDUH is to measure prevalence and correlates of drug use in the civilian, non-institutionalized U.S. population aged 12 years and older. Since 1991, NSDUH has consisted of an independent multistage area probability sampling design for each state and the District of Columbia and uses a combination of the Computer-Assisted Interviewing and Automated Computer Assisted Interviewing instruments in selected individuals and households . The survey offered $30 in cash to participants and was conducted in 2013 by Research Triangle Institute . The final survey consisted of 67,838 CAI interviews with a weighted screening response rate of 84% and an interview response rate of 72%. The public use file consisted of 55,160 records due to a sub-sampling step which included a minimum item response requirement for weighting and further analysis.

A detailed description of the questionnaire items, sampling methodology, data collection/ response rates, and sample weights is published elsewhere . The present study was exempt from the University of California San Francisco’s Human Research Protections Program approval since data were publically available and subjects cannot be identified. In this analysis, only those with complete responses for all measures were included. Additionally, while the analysis included participants aged 50–64 years, those 65 years of age and over were excluded due to a small sample size . The final sample included 51,993 participants. The item “How long has it been since you last used marijuana or hashish?” was used to classify respondents into three categories: “Within the past 30 days” ; “more than 30 days” ; and “never used marijuana” . Current marijuana users reported frequency of past 30-day use [Range = 1–30 days]. Cigarette use was assessed with an item asking whether and how recently participants had smoked “part or all of a cigarette.” Past 30 day users were categorized as current cigarette smokers, other than “within the past 30 days” as former smokers, and “never used cigarettes” as never smokers. Participants were coded as co-users if they had smoked at least one cigarette in the past 30 days and used marijuana in the past 30 days. Respondents who indicated blunt use were not included in our analysis since our analysis includes comparison of nicotine dependence in cigarette smokers who use marijuana vs. those who do not marijuana .Nicotine dependence was measured in two ways: the 17-item Nicotine Dependence Syndrome Scale and the single “time to first cigarette” item from the Fagerstrom Test of Nicotine Dependence . Respondents’ average NDSS scores were calculated over 17 items across five aspects of dependence and current smokers with a cutoff score of 2.75 or above were categorized as nicotine dependent. Those who responded smoking cigarettes in the past month and having their first cigarette of the day within 30 minutes of waking on the TTFC were categorized as nicotine dependent. Additional information on NDSS and TTFC questionnaire items, scoring procedure, and methods used for cutoff scores are published elsewhere . We examine both NDSS and TTFC scores to potentially increase the reliability of our findings. Descriptive statistics are reported for demographics, cigarette and marijuana use, and lifetime depression as well as chi-square tests of differences by statewide medical marijuana legalization status . One-way ANCOVA models tested for differences in marijuana use and cigarette and marijuana co-use in the overall sample, and separately for each age category, between states where medical marijuana was legal vs. illegal, adjusting for age , gender, race/ethnicity, education, age at first cigarette initiation, age at first marijuana initiation, and lifetime depression. Additionally, we calculated mean NDSS and frequency of TTFC scores by statewide legalization categories across age groups. In the overall sample and within each age category, two logistic regression models examined nicotine dependence, as measured by NDSS and TTFC scores, in cigarette and marijuana co-users . Models were adjusted for age , gender, race/ethnicity, education, lifetime depression, and statewide medical marijuana legalization status. Bonferroni adjustments were applied to all models with over five independent variables . In this analysis, we used the Taylor series method for replication methods to estimate sampling errors of estimators based on complex sample designs. The regression coefficient estimators were computed by generalized least squares estimation using element-wise regression. The procedure assumes that the regression coefficients are the same across strata and primarily sampling units . All models were run in SAS 9.4 using the SURVEY procedures to obtain weighted estimates to increase the generalizability of the findings . The study sample was approximately half male, majority non-Hispanic White , and more than a quarter was college-educated .

Data were analyzed by a t-test, one-way or two-way ANOVA with Prism 9 software , as appropriate. Significant main or interaction effects were followed by Bonferroni post-hoc comparison with correction for multiple comparisons. The criterion for significance was set at α = 0.05 two-tailed.In these studies, we sought to examine how adolescent exposure to nicotine, THC, or co-exposure may alter later reward- and relapse-related behaviors. For translational relevance to youth, THC was administered orally as related to edible consumption, and nicotine was administered via e-cigarette aerosol exposure. However, for the nicotine treatment, we aimed to compare to our prior findings with subcutaneous injections, so this additional group was included. Given the different routes of nicotine administration, we desired to first validate the respective level of nicotine’s metabolite, cotinine, for both methods. Moreover, given other findings in our lab suggesting that THC may alter nicotine metabolism [unpublished data], we also examined cotinine levels in the THC and nicotine coexposure groups. Higher blood cotinine levels were found across all nicotine-treated groups compared to the vehicle , thereby validating the measure. When comparing among drug-treated groups,vertical grow rack system co-exposure to nicotine vapor and the higher dose of THC led to lower cotinine levels as compared to nicotine vapor alone or co-exposure to nicotine vapor and the lower dose of THC .

This indicates that the high dose of THC did alter nicotine metabolism. Importantly, males exposed to only nicotine, whether via injections or vapor, did not differ in blood cotinine levels, indicating that both of these administration methods resulted in similar levels of nicotine exposure.Next, since adolescent drug exposure could possibly alter general growth, body weight was examined across the adolescent treatment days and in adulthood. Body weight was measured throughout the treatment period and in adulthood .The post-hoc analysis revealed that males exposed to either the lower or higher dose of THC, as well as those co-exposed to nicotine and the higher dose of THC , gained less weight from PND 38 to 49, as compared to control subjects. The post-hoc analysis revealed that adolescent exposure to the higher dose of THC led to lower body weight than vehicle exposure . Thus, these data indicate that adolescent exposure to a higher dose of THC, but not when co-administered with nicotine, induced persistent changes in body growth into adulthood.To examine whether adolescent drug exposure altered the subjects’ ability to learn an operant task, groups were examined for their ability to press a lever to earn food reward. Post-hoc analysis revealed that co-exposure of nicotine and lower dose of THC in adolescence led to a higher level of active lever pressing than the control group in adulthood, but only in session 3 . In session 7, males exposed to nicotine vape alone exhibited a lower level of active lever presses than the control .

With regard to subjects co-exposed to nicotine and the higher dose of THC, a higher level of active lever pressing was found for sessions 6 , 7 and 8 .Thus, to further investigate if the active lever differences are reflected in the number of food pellets obtained across sessions 6-8, we next compared the mean pellets earned. with the exception of the co-exposure nicotine and higher dose THC group that earned significantly more food pellets compared to the control. Therefore, these findings indicate that higher dose THC and nicotine co-exposure during adolescence in males induces more persistent effects on the drive to obtain food in the operant paradigm in adulthood.Next, to determine whether adolescent nicotine and/or THC exposure alters the reinforcing properties of nicotine in adulthood, mice were assessed for intravenous nicotine self-administration. Specifically, compared to control subjects, significantly more nicotine infusions were earned following adolescent exposure to the lower and higher dose of THC , and co-exposure to nicotine and the lower dose of THC . Given these findings with THC altering later nicotine intake, it is surprising to note that differences were not found with co-exposure to nicotine and the higher dose of THC, even though this group exhibited a greater drive to obtain food reward. Taken together, these results indicate that adolescent use of cannabinoids have a persistent effect on reward consumption, which is dependent on THC dose, nicotine co-exposure, and type of reward.Since drugs of abuse may differentially alter development dependent on sex, we next examined whether adolescent nicotine, THC, or co-exposure in females results in similar physiological and behavioral outcomes in adulthood.As above, all of the nicotine treatment groups resulted in a significant level of detectable cotinine .

When comparing among treatment conditions, injections of nicotine resulted in lower cotinine levels than nicotine vapor and co-exposure of nicotine and low dose THC , although it is important to note that all of these groups exhibited levels of cotinine >50 ng/ml which is in the range of that found with human e-cigarette and tobacco smokers. Interestingly, similar to that observed in males, females exhibited significantly lower cotinine levels with nicotine vapor and the higher dose of THC as compared to nicotine vapor alone or co-exposure to nicotine vapor and the lower dose of THC , suggesting that the high dose of THC interacts with nicotine metabolism. Posthoc analyses revealed that the females gained less weight from PND 38 to 49 if exposed to either the lower or higher dose of THC or coexposed to nicotine and the higher dose of THC , compared to vehicle. The posthoc test revealed that the high dose of THC, either in the absence or presence of nicotine , led to decreased body weight differences that were maintained into adulthood, compared to vehicle. Even so, a trend was noted with higher dose of THC potentially resulting in a lower body weight than vehicle . Together, these data indicate that a higher dose of THC during adolescence may have persistent developmental effects on body growth.We next focused our investigations of operant food training in the female mice. The post-hoc analysis revealed that females exposed to the higher dose of THC exhibited a higher level of active lever pressing for sessions 7 and 8 compared to control. Further, co-exposure to nicotine and the lower dose of THC resulted in greater active lever pressing across sessions 6 and 7 , but no difference on the final session 8 compared to the control. Thus, these findings indicate that regardless of adolescent exposure, females were able to acquire the food training task,grow rack with lights although high dose THC may have led to increased responding to obtain food pellets in later sessions, an effect not found with nicotine co-exposure. We then examined intravenous nicotine self-administration during adulthood in female subjects with a history of drug exposure.The post-hoc analysis revealed that a higher dose of THC during adolescence led to increased nicotine intake in adulthood compared to vehicle . While not statistically significant, we also noted a trend with the co-exposure nicotine and lower dose of THC group having higher intake compared to control . Taken together, these findings reveal that a high dose of THC during adolescence increases the drive to consume both food and nicotine in adulthood, an effect which appears to have been counteracted by the co-exposure of nicotine.Re-exposure to the auditory, visual, and/or olfactory cues associated with drug taking has been shown to enhance relapse-related behaviors. Thus, after intravenous nicotine self-administration acquisition, we examined lever pressing behavior for a visual and auditory cue in the absence of nicotine infusions. Since this procedure has been mainly used in rats, it was important to first demonstrate that control subjects could exhibit a robust incubation of nicotine craving effect, as validation of this protocol in mice. For our analysis, we also included comparisons of active lever pressing that correspond to the nicotine self-administration data presented in Figures 1E and 2D .

These data were important to include to determine whether the mice exhibited an extinction burst on the first day of incubation testing , which could have implications for interpretation of the later incubation effect on Day 24. Therefore, the post-hoc analysis compared incubation day 1 to the other sessions . In the post-hoc analysis, there was a significant increase in active lever pressing comparing incubation Day 1 to Day 24 for both males and females . However, active lever pressing did not differ when comparing responding for nicotine infusions to incubation Day 1 . Thus, these findings demonstrate that incubation of nicotine craving can be readily detected in mice. For the nicotine vapor group, the post-hoc analysis revealed an increase in active lever pressing on Day 24, as compared to Day 1, of incubation , but no differences were found comparing Nicotine to Day 1. This effect was interesting given that these groups did not differ in the level of cotinine, suggesting that the differences in duration of daily adolescent exposure may be relevant. While both of the ANOVAs indicated a statistically significant effect, post-hoc analyses did not reveal significant differences among sessions, although with nicotine vapor exposure a trend was noted between the Nicotine and Day 1 sessions suggesting a potential burst in responding. Given the differences found in body weight and food training with some of the THC exposure groups, we predicted that significant differences would also be found for incubation of craving. These findings suggest that the higher dose of THC during adolescence may have led to overall increased active lever pressing, suggesting either overall increased general activity , or alternatively, a premature incubation effect with higher immediate and persistent drug seeking behavior.Finally, we sought to determine whether nicotine and THC together would have unique effects on relapse-related behaviors. Surprisingly, co-exposure elicited differential outcomes compared to what we previously reported for single drug exposure.For all of the above co-exposure comparisons, statistically significant differences were not found between baseline Nicotine and incubation Day 1. Together, these findings indicate that nicotine and THC can interact to induce a differential effect than either substance alone during development, thereby sustaining a heightened response to drug associated cues to propagate increased nicotine seeking behavior and potential risk of relapse.This study sought to determine whether prior nicotine and/or THC exposure during adolescence would alter operant learning, drug reinforcement, and nicotine seeking behaviors. Importantly, we found that nicotine exposure in adolescence regardless of route of administration resulted in significantly high levels of cotinine in both sexes; but coexposure with the higher dose of THC altered the metabolism of nicotine as evidenced by significantly lower cotinine levels in these subjects than those exposed to nicotine alone. Males that were co-exposed to nicotine and the higher dose of THC in adolescence also exhibited increased food self-administration in adulthood. In contrast, none of the female groups differed in food self-administration. Furthermore, males that were exposed to either dose of THC alone in adolescence or co-exposed to nicotine and the lower dose of THC had increased nicotine intake in adulthood. Whereas females with adolescent exposure to only the higher dose of THC exhibited increased nicotine intake in adulthood. Following nicotine self-administration, both male and female control mice exhibited increased nicotine-seeking behaviors following a 24-day abstinence period. Males exposed to nicotine vapor or either dose of THC alone also demonstrated this increased cue-induced nicotine seeking. However, adolescent exposure to nicotine via injections in either sex or to nicotine vapor in females did not result in this later enhanced nicotine seeking behavior. Interestingly, for both sexes, co-exposure to nicotine and THC at either dose in adolescence does result in this incubation of nicotine craving effect in adulthood, even when single drug exposure does not. Nicotine and cannabis use during adolescence has been shown to have lasting implications on later learning and memory. However, our findings did not reveal any differences in the subjects’ abilities to learn the operant food training task in either sex. All groups were able to sufficiently dissociate between the active and inactive levers during training and further achieved the lever pressing criteria within a similar number of sessions. Rather, differences in lever pressing behavior were only found in later sessions once the learning already occurred. Males co-exposed to the higher dose THC and nicotine during adolescence as well as females exposed to the higher dose of THC alone demonstrated a higher level of responding for this task and maintained a more persistent drive to obtain food, which may be indicative of greater hedonic value of food for these subjects.

Building on and expanding the scope of the international obligations enshrined in the Vienna Convention and the INCB recommendations, the US has made extensive use of bilateral treaties to create an issue-linkage between states’ willingness to adopt zero-tolerance models of drug policy and their eligibility for foreign aid. Over the next decades, such bilateral agreements provided a basis for the operation of extensive cooperation and capacity-building projects in countries as diverse as Afghanistan, Colombia, Mexico, Nigeria, Peru, Ghana, Thailand, and many others. Along with these multilateral and bilateral instruments used to influence the drug policies of other countries, the US government has had an extensive reliance on unilateral tools of imposing economic and reputational sanctions on non-compliant states. In 1986, Congress introduced the Omnibus Drug Enforcement, Education, and Control Act, which created a certification process for drug-producing and drug-transit countries.The certification process requires the president to withdraw financial assistance and support in multilateral lending institutions from countries that fail to comply with requisite benchmarks of anti-drug policy. To enable congressional deliberations over such sanctions, the US Department of State submits an annual International Narcotic Control Strategy Report that identifies the major illicit drug-producing and drug-transit countries and evaluates the extent to which their domestic policies are in compliance with the US counter narcotic agenda. The INCSR narrative explores a wide range of countries . The certification process is applied to countries included in what came to be known as the Majors List .

The success of the US to coerce and to induce dozens of countries to adopt its preferred models of implementing cannabis prohibitions promoted convergence of drug laws across jurisdictions and thus increased the degree of concordance between the transnational and the national levels of this TLO. However,rolling grow tables the global diffusion of tougher cannabis laws cannot be sufficiently explained by focusing on the coercive mechanisms employed by the US alone. This diffusion was also a product of broader social transformations stimulating increasing political mobilization around law and order issues during the final decades of the twentieth century.41 Illustrating Durkheim’s observation that societies have a functional need to construct categories of deviance,the instigation of moral panics concerning drug abuse epidemics provide a useful tool of identifying “suitable enemies” and scoring political points.In an era during which a broader shift from welfare oriented to punitive-focused approaches to governing social marginality took place,strengthening state capacities to condemn and to penalize drug dealers and users proved to be a far more attractive project for politicians than undertaking to address the public health implications of drug use. As the primary international organization responsible for monitoring the implementation of the UN drug conventions, the INCB played an important role in facilitating the concordance between the transnational and national levels of the cannabis prohibition TLO. In its annual reports, the INCB has repeatedly supported the “gateway drug thesis,” according to which the use of cannabis serves as a risk factor in increasing the user’s probability of using harder illicit substances, such as amphetamine, cocaine, or heroin. Based on this thesis ,the Board’s 1983 Report criticized those “circles in certain countries” that “apparently assume that to permit unrestricted use of some drug, regarded by them as less harmful, would permit better control of other drugs which they deem more perilous to health.”

This criticism was leveled at supporters of the separation of markets strategy, which came to be endorsed by Dutch policymakers at the time.In its later reports throughout the 1980s and 90s, the Board adopted an increasingly critical stance toward the Dutch attempts to depenalize cannabis usage. In its 1997 Report, the selling of cannabis in coffee shops was depicted as “an activity that might be described as indirect incitement.”The focus on the Netherlands and its singling out for disapprobation reflects the rarity of open contestations of the prohibitionist imperatives enforced by the Board during that period. The extensive institutionalization of the cannabis prohibition TLO throughout the 1980s and 1990s facilitated the international spread of tougher laws, severer penalties, and more aggressive policing strategies. However, the very success of this TLO to propagate its policy models highlighted its failure to deliver on its own promise to reduce the prevalence of cannabis use and to eliminate its illicit supply chains. The intensification of enforcement activities also brought into focus the adverse human rights impacts of implementing the prohibitionist cannabis policies. The increasing criticisms of the failures and boomerang effects of the cannabis prohibition TLO prompted both internal and external processes that eroded its legitimacy and compromised its ability to continue guiding the practices of legal actors at the national and local levels. From the early stages of the institutionalization of the cannabis prohibition TLO, it became vulnerable to criticism of its inherent input legitimacy deficiencies. As discussed earlier, the central role played by the US in shaping the goals and strategies of this TLO has largely depended on the exercise of unilateral measures of coercion and inducement. The degree to which the certification process has realized basic standards of transparency, inclusiveness, and accountability is obviously limited. The procedures by which the INCB defines and applies its compliance criteria seem conspicuously insulated from ongoing public debates regarding the impact of cannabis prohibition laws on marginalized populations.

These legitimacy deficits are conveniently set aside by proponents of the war on drugs, who tend to focus more on the ability of these measures to promote global public goods than on the quality of the processes through which these measures are created. As Niko Krisch observes, such tendency to prioritize output legitimacy considerations is pronounced in various contexts of global governance and often produces pressure to move toward more informal and hierarchical modes of transnational governance in these issue-areas.However, this view is becoming increasingly difficult to maintain in the issue-area of cannabis policy given the mounting evidence on the failure of this TLO to achieve its regulatory goals. Despite billions of dollars of investment and extensive law enforcement resources, a sizable body of scholarship has documented the growing availability of the drug during the 1990s, the widespread prevalence of its usage among adolescents, and the increasingly tolerant attitudes toward cannabis consumption among both users and non-users.Drawing analogies to the failure of the “Noble Experiment” of the alcohol prohibition period,criminologists developed thorough critiques of the underlying assumptions of the cannabis prohibition TLO. The assumption that the availability of cannabis can be meaningfully reduced by the deployment of militarized policing strategies has been criticized for overlooking the resilience of cannabis markets and their high levels of adaptability to changes in their regulatory environments. Studies have shown that rather than eliminating supply chains, such interventions served to disperse, displace, and fragment supply sources and distribution routes.In turn, such interventions precipitated a spillover of armed violence to new geographical areas and exposed otherwise uninvolved indigenous populations to new risks and insecurities. The inherent flaws of this dimension of the cannabis prohibition TLO are often illustrated by referencing the “balloon effect” metaphor, depicting the ways in which efforts to suppress the cultivation of cannabis in one geographical area causes a convenient shift of its production elsewhere. The legitimacy of the cannabis prohibition TLO has also been damaged by evidence regarding the immense human rights violations that the implementation of war on drugs policies has entailed. Advocacy networks led by prominent transnational NGOs,flood drain table such as Amnesty International and Human Rights Watch, have exposed the disproportionate punishments imposed under the banner of the war on drugs in various countries. In the US, such criticism focused on the contribution of marijuana prohibitions to the nation’s internationally unparalleled incarceration rates and its distinctive patterns of racially-skewed law enforcement.A recent ACLU report using data extracted from the FBI’s Uniform Crime Reporting Program indicates that between 2001 and 2010, there were over eight million marijuana arrests in the US, of which 88% were for marijuana possession.In 2010, there were more than 20,000 people incarcerated for the sole charge of cannabis possession. Outside of the US, human rights activists focused on the increasing use of capital punishments for drug offenses from the late 1980s onward, as part of the broader escalation of enforcement efforts during the war on drugs era.The exportation and importation of illegal drugs constitute capital offenses in more than 30 countries. In China, Saudi Arabia, and the Philippines, the death penalty is exercised regularly for cannabis trafficking offenses. By the mid-1990s, the criticism leveled at the cannabis prohibition TLO began to stimulate increasing advocacy activity in favor of reform.

These activities failed to change the direction of drug policy making at the international level. Indeed, the “outcome document” issued in the wake of the 2016 UN General Assembly Special Session on drugs kept in place the existing framework of cannabis prohibition and did not endorse the calls to reclassify cannabis as a less dangerous drug. However, the criticism of the prohibitionist approach had a considerable transformative impact on the development of drug policies at the national and subnational levels. Before long, the diffusion of liberal cannabis policies across national borders began to jeopardize the normative settlements institutionalized by the cannabis prohibition TLO in previous decades. The efforts to liberalize cannabis regulations have focused on three distinct models of reform: depenalization, decriminalization, and legalization. Under formal depenalization regimes, the possession of cannabis is still formally prohibited; however, such prohibitions are enforced through intermediate justice measures rather than through conventional penal sanctions such as incarceration. The Netherlands pioneered the experimentation with depenalization strategies in 1976 when it formalized the use of the expediency principle to guide the enforcement of drug prohibitions. Based on this principle, Dutch prosecutors are instructed not to bring charges when cannabis use offenses take place within the user’s home or within the so-called coffee shops, where cannabis can be openly consumed and purchased.From the 1990s onward, many national and subnational jurisdictions introduced cautioning and diversion schemes to deal with drug use offenses.Cautioning schemes authorize police officers to avoid arresting suspected drug offenders under certain circumstances. Instead, the cautioning schemes require them to issue a written warning of the possible consequences of the illegal behavior. Diversion schemes, which may operate at the pre-trial, pre-sentence, or post-conviction stages of the legal process, are intended to shift offenders from the criminal justice system and its carceral institutions to other channels of legal intervention. When applied before the sentencing stage, such measures may require the offender to participate in certain treatment and education programs as part of the bail conditions. After the sentencing stage, diversion measures may subject a convicted offender to community-based or rehabilitative measures . The widespread transnational diffusion of depenalization regimes is enabled by the structural mismatch between the actors shaping the formal rules of the international drug control system and those implementing these rules in national and local contexts.The diffusion of these regimes was not initiated by international organizations or powerful countries. Rather, it has evolved through uncoordinated processes of institutional isomorphism, reflecting converging professional concerns regarding the complexities of implementing criminal prohibitions that are extensively violated by ordinary citizens and that do not reflect widespread social disapprobation of the targeted activity. From the perspectives of ground-level enforcement officials and more senior bureaucratic elites, the implementation of cannabis prohibitions raised pragmatic concerns regarding the limited effectiveness of conventional penal measures and the immense costs that such efforts entailed. In democratic systems committed to the principle of legalism, it seems natural to expect that schemes of depenalization would translate into de jure changes in the statutory definitions governing processes of criminalization. The international drug conventions place constraints on the ability of national legislatures to introduce such reforms. However, the treaties also contain textual ambiguities that provide leeway for negotiating the scope and ambit of such prohibitions. The movement began to gain ground in the early 1990s, focusing its efforts on promoting ballot initiatives at the municipal and state levels in the US.Within the next two decades, it effectively initiated the enactment of laws decriminalizing the medical use of marijuana in thirty-one states across the US and inspired norm entrepreneurs in dozens of other countries to campaign for the adoption of similar models.

These are just a couple of examples on how we had to conceptualize the plasmid making process differently on the LAS than how we typically do on the benchtop.After the construction of mutation plasmids both manually and utilizing the Living Biofoundry, we heterologously expressed the mutated Ma_OvA plasmids with Ma_OvaB and Ma_OvaC in Aspergillus nidulans. Out of the many mutation plasmids we constructed, we identified two that produced olivetolic acid analogs. Heterologous expression of first plasmid, containing the F418A and Y420A mutations, with Ma_OvaB and Ma_OvaC produced the nonyl and undecyl variants of olivetolic acid, both previously mentioned as having antibacterial activity. Heterologous expression of the second plasmid, containing the T318W and S347W mutations, with Ma_OvaB and Ma_OvaC produced orsellinic acid and divarinic acid which were confirmed by analytical standard and heterologous expression also produced what we propose to be ethyl variant based on mass and UV, although at low quantities so NMR was not taken. We also further utilized genome mining to elucidate new clusters producing olivetolic acid analogs. As previously detailed, we had identified three clusters homologous to the Metarhizium anisopliae cluster containing the Ma_OvaA, Ma_OvaB, and Ma_OvaC genes. As described, we identified the Tolypocladium inflatum and Metarhizium rileyi clusters in which heterologous expression produced the same product profile as Metarhizium anisopliae albeit at lower titers and the Talaromyces islandicus cluster which selectively produced olivetolic acid.

From the percent identity comparisons between the enzymes,2×4 flood tray we determined that clusters harboring close to 50% or less homology to the Metarhizium rileyi cluster would produce the greatest variety in products different from the product profile of the Metarhizium anisopliae cluster. Equipped with this knowledge, we utilized the Targeted Genome Mining Information Finder program, a MATLAB based program develop by Dr. Nicholas Liu, an alumnus of the Tang lab. Employing MATLAB’s Bioinformatics Toolbox which includes the ability to use Basic Local Alignment Search Tool to analyze FASTA formatted sequences, Dr. Liu developed a program to elucidate possible bio-synthetic gene clusters based on a target queried for. Although this program was developed to query for target resistance gene clusters, it can be used for a variety of different purposes. We employed the program to query for tandem polyketide synthases and used the Tang lab’s in-house fungal strain list as the database. We elucidated a cluster in Penicillium thomii containing 48%, 41%, and 36% homology to Ma_OvaA, Ma_OvaB, and Ma_OvaC, respectively. We heterologously expressed this cluster in Aspergillus nidulans and produced the nonyl olivetolic acid variant with a diene at the C1 and C3 positions of the alkyl chain as well as the heptyl variant unsaturated at the C3 position of the alkyl chain and a hydroxy group at the C2 position, both of which are non-native to the Cannabis sativa plant and therefore can be further processed to new to nature cannabinoids.We have detailed ways in which we were able to be diversify our product profile to produce rare olivetolic acid analogs. There are still more mutations near the active site of the KS domain as well as the AT domain that can be made to produce even more olivetolic acid analogs with different alkyl chain lengths.

With regards to homologous cluster expression, we only searched through the100+ sequenced fungal strains that we have. Therefore, there is a large number of fungal strains that can be queried to search for homologous clusters that can producer are olivetolic acid analogs. Testing of these variants and the ones produced utilizing the Living Biofoundry can lead to potentially promising results with regards to biological activities. As previously detailed, microbial production of naturally occurring and novel cannabinoids has potential to be a disruptive technology to the ~$10 billion global cannabis industry. From olivetolic acid, the next step in the cannabinoid bio-synthetic pathway is the geranylation of olivetolic acid to produce cannabigerolic acid , known as “the mother of all cannabinoids”CBGA can be decarboxylated to form cannabigerol , a cannabinoid with intriguing therapeutic potential. In the Cannabis sativa plant, CBG is produced in larger quantities in the early stage of the plant but in minute quantities in the mature stage of the plant. Preliminary research has indicated that CBG is non-psychoactive but has anti-oxidant, antimicrobial, anti-inflammatory, anticancer, photoprotective, and appetite-enhancing properties.Studies on the effect of CBG on the cannabinoid receptors have shown that CBG is a partial agonist for the CB2 receptor but cannot bind to the CB1 receptor, hence its nonpsychoactive properties.As previously described, the CB2 receptors are primarily located in the nervous system and agonists of the receptors provide anti-inflammatory and anti-oxidant effects. CBG was first isolated in 1970 and was fully characterized shortly after.We therefore sought to produce this cannabinoid microbially. To do so, we had to identify the prenyltransferase responsibly for geranylating the C2 carbon position of olivetolic acid.

This prenyltransferase activity was first demonstrated in the Cannabis plant and was proposed to beattributed to cannabis sativa prenyltransferase 1 and was soon patented. However, when Luo et al heterologously expressed CsPT1 in Saccharomyces cerevisiae, they observed no activity. Therefore, they mined for prenyltransferases with predicted activity similar to CsPT1 and heterologously expressed those candidate prenyltransferases. They demonstrated that the Cannabis sativa prenyltransferase 4 was able to successfully prenylate olivetolic acid to produce CBGA. CsPT4 was found in the Cannabis sativa plant and is part of the UbiAmembrane bound family of prenyltransferases, predicted to contain eight transmembrane helices. When expressed in Saccharomyces cerevisiae, and with the plastid targeting amino acid sequence removed, the CsPT4 enzyme was found to be located in the microsomal fractions of the yeast strain. Luo et al performed in vitro assays with the microsomal fraction harboring CsPT4 and demonstrated that the enzyme displayed Michaelis Menten behavior when olivetolic acid concentration varied whilst GPP concentration stayed constant but deviated from Michaelis Menten behavior when olivetolic acid concentration was held constant while GPP concentration varied.Aromatic prenyltransferases capable of geranylating olivetolic acid to produce CBGA outside of the Cannabis sativa plant have also been discovered. There are three classes of aromatic prenyltransferases: ABBA-type prenyltransferases, UbiA-type prenyltransferases, and dimethylallyl tryptophan synthase -type prenyltransferases. ABBA-type and DMATStype prenyltransferases are found in bacteria and fungi and UbiA-type prenyltransferases are found in fungi, plants, and bacteria. These aromatic prenyltransferases catalyze formation of carbon nitrogen, carbon oxygen, and carbon-carbon bonds between the prenyl donor’s carbonand the aromatic substrate.ABBA-type and DMATS-type have been elucidated as soluble aromatic prenyltransferases while UbiA prenyltransferases are membrane bound aromatic prenyltransferases. UbiA-type prenyltransferases are membrane bound prenyltransferases found in a variety of organisms such as bacteria, fungi, plant, human, etc. These prenyltransferases have been observed to be involved in menaquinone and ubiquinone biosynthesis as well as fungal meroterpenoid biosynthesis, archaeal membrane lipid biosynthesis, and prenylated aromatic secondary metabolites biosynthesis in plants, among other biosynthesis reactions. These UbiAtype prenyltransferases typically contain eight to nine transmembrane helices. Regarding their structure, enzymes in the family contain two conserved aspartate rich motifs with the first used for Mg2+ binding in order to catalyze the reaction; therefore, these prenyltransferases are metal dependent.DMATS-type prenyltransferases have been elucidated in fungal and bacterial species. These aromatic prenyltransferases are metal independent although addition of metal ions like Ca2+ and Mg2+ have been reported to have enhanced the catalytic activities of several of these prenyltransferases.DMATS-type prenyltransferases primarily act upon indole derivatives such as tryptophan,food and drain table indole terpenoids, and cyclic dipeptides that contain tryptophan by prenylating these compounds. Reports have demonstrated that DMATS-type prenyltransferases have the ability to prenylate all positions of the indole ring and characterization of its structure have revealed that these prenyltransferase also have the α-β-β-α prenyltransferase folds that ABBA-type prenyltransferases have.Similarly to ABBA-type prenyltransferases, DMATS prenyltransferases show selectivity in prenyl donor, with most enzymes in the family utilizing dimethylallyl pyrophosphate for prenylation, but have great flexibility with regards to prenyl acceptor, capable of prenylating not only those indole derivative previously mentioned but also xanthones, tricyclic and tetracyclic aromatic compounds, and tyrosine.ABBA-type prenyltransferases are found in both fungi and bacteria. They primarily utilize DMAPP and geranyl pyrophosphate as the prenyl donor. All the members of the ABBA-type family of prenyltransferases, except for NphB, do not need metal to assist in catalyzing the reaction.

Although CloQ from Streptomyces roseochromogenes var. oscitans was the first member of the ABBA family of prenyltransferases to be discovered, NphB was the first in the family to have its crystal structure. The crystal structure revealed a structure containing an unique three dimensional α-β-β-α prenyltransferase fold, hence the name ABBA.156 NphB, a member of the ABBA family of prenyltransferases, from the bacteria Streptomyces sp. CL190 was discovered to have non-specific prenylation activity for the formation of CBGA.These prenyltransferases are soluble and are capable of catalyzing the transfer of dimethylallyl , geranyl , or farnesyl prenyl groups onto a diverse set of electron-rich aromatic acceptors. Genome mining for analogs to CloQ, the first gene identified as part of the ABBA family of prenyltransferases, led to the discovery of NphB in Streptomyces sp. CL190.Wildtype NphB is specific in prenyl donor, preferring the geranyl group but is promiscuous with regards to aromatic acceptor although the major substrate is 1,6- dihydroxynapthalene.Wildtype NphB was shown capable of prenylating olivetolic acid toCBGA although at low catalytic efficiencies .Wildtype Nphb was also non-specific in prenylation of OA, capable of producing not only CBGA when reacted with GPP but also 2-O-geranyl olivetolate.Therefore Valliere et al. preformed mutations on NphB to increase specificity for the production of CBGA. They docked the olivetolic acid structure to the NphB crystal structure and then utilizing Rosetta, developed a 22-construct library, constructed the library, and screened for CBGA production. They identified two amino acid mutations that greatly increased specificity to CBGA. From the initial library, then they constructed a focused library and discovered that all but one of the mutations in the focused library had 100-fold higher activity than wildtype NphB with regards to kcat value. Ultimately, they determined that their two best mutations were Y288AG266S and Y288VA232S. Both mutations selectively produced CBGA and both had kcat values 1000-fold higher than the wildtype. Valliere et al. demonstrated that they were capable of producing 1.25g/L of CBGA in a cell free manner utilizing their mutated NphB enzyme.Based on the Tang’s lab collaboration with the Bowie lab, from where Valliere et al developed the mutated NphB enzyme, and the company that he helped found, Invizyne, we were given the mutated NphB enzyme which we used in order to test its ability to prenylate the olivetolic acid analogs in vitro as well as test for functional expression in vivo. We purified the enzyme and performed in vitro assays with our olivetolic acid analogs and GPP. Based on LCMS/HPLC data, NphB was able to prenylate olivetolic acid analogs that we produced as well as other analogs bought commercially, although the final prenylated products were not confirmed by NMR. However, the CBGA product produced by the NphB reaction with olivetolic acid and GPP was confirmed by an analytical standard. Additionally, based on the masses of the in vitro assays, we observed an interesting trend: the shorter alkyl chain variants reacted with NphB and GPP generated not only the C3 geranylated product but also the C3 geranylated product with an O-geranylation. As the alkyl chain length increased, the less appearance of this double geranylated product, with the C3 geranylated product being the major product. We then tested for the functional expression of NphB in vivo in Aspergillus nidulans. We heterologously expressed NphB and the GPP synthase enzyme vrtD from Penicillium aethiopicum , along with Ma_OvaA, Ma_OvaB, and Ma_OvaC in Aspergillus nidulans, expecting to observe the CBGA and CBGA analog products. However, we did not observe any of the geranylated products. We also heterologously expressed Nphb and vrtD with Ti_OvaA, Ti_OvaB, and Ti_OvaC in Aspergillus nidulans and did observe production of CBGA but it was very minute. We additionally expressed CsPT4 as well as an aromatic prenyltransferase from Aspergillus terreus recorded to have prenylation activity in vitro with our platform. However similar to NphB, we observed no production of CBGA. These results led us to postulate that the enzymes are not being properly expressed in A. nidulans, especially engineered NphB, after all a bacterial gene; therefore, we sought to look at its transcription.

They demonstrated that ∆9 -THC synthetic mimics were able to bind to a specific site in the membranes of the brain, inhibiting synthesis of cyclic adenosine monophosphate through a G-protein mediated mechanism. Furthermore, molecular cloning of the first cannabinoid receptor gene as well as brain mapping of the cannabinoid binding sites in rats confirmed the existence of the cannabinoid receptor in the brain, known as the CB1 receptor. The cannabinoid receptors are part of a larger family of receptors known as G-protein coupled receptors . G-protein coupled receptors total about 800 in number and are divided into five major families: secretin, frizzled/taste 2, adhesion, glutamate, and rhodopsin. Majority of GCPRs including CB1 and CB2 belong to the rhodopsin like family. Rhodopsin is a pigment found in the rod photoreceptor cells of the retina and its role is to change photons into chemical signals, allowing vertebrate animals and humans to sense light by stimulating cellular biological processes in these organism’s central nervous systems. With regards to structure, GCPRs contain a transmembrane unit harboring seven alpha-helices conjoined with a G-protein that itself has three subunit proteins: Gα, β, and γ. Once an agonist binds to the GCPR transmembrane domain, the G-protein subunits conjoin with another cellular protein such as a protein kinase or adenyl cyclase to catalyze downstream functions. GCPRs role in regulating functions in the cells is so important that drugs targeting GCPRs make up 30- 40% of all the drugs in the market. 20 The CB1 receptor’s discovery was in 1984 through the observation that cannabinoid binding to the receptors reduced cyclic adenine monophosphate concentrations in neuroblastoma cells.

Two years later,seedling starter trays work was done to demonstrate that the cAMP concentration reduction by cannabinoid binding could be reversed through the exposing of the cells to the pertussis toxin, a Gαi protein inhibitor. However, it wasn’t until 1990 that the CB1 receptor was cloned and elucidated from a cDNA library of cerebral cortex tissues with studies that same year demonstrating that CB1 receptors in the brain were nearly as prevalent as gammaaminobutyric acid receptors and glutamate receptors. The prevalence of CB1 receptors and their localization in the brain allowed researchers to correlate their expression to the subsequent pharmacological effects. For example, localization and expression of CB1 in the hippocampus and cerebral cortex correlated to memory and cognition effects whereas localization and expression of CB1 in the cerebellum and basal ganglia was correlated to stride or gait effects. Therefore, binding of the CB1 receptors in the brain correlates to the psychoactive effects of cannabis. Although CB1 receptors are prevalent in the brain, they also have been found to be located in the uterus, prostrate, adrenal glands, tonsils, gastrointestinal tract, spleen, and vascular smooth muscle cells. The discovery of the CB2 receptor answered the question of why cannabis was reported to have immunomodulatory effects. The CB2 receptor was discovered three years after the CB1 receptor and was found in a human promyelocytic leukemia cell line. Unlike the well characterized CB1 receptor, CB2 has not been as well as characterized due to numerous conflicting reports about the effects of its expression but one thing is known for sure: the CB2 receptor plays a strong role in immunomodulatory effects with great implication for example, in Alzheimer’s and Huntington’s disease. The CB2 receptor is known as the peripheral receptor for cannabinoids and is primarily found and expressed in immune tissues.

When these cannabinoid receptors are activated, as previously mentioned with regards to CB1, there is a decrease in cAMP levels and there is also modulation of potassium and calcium levels in the cells. When these receptors are stimulated, p38 mitogen activated protein kinases , c-Jun N-terminal kinases, and p42 and p44 MAPKs are activated. The p42/44 MAPKS are also referred to as extracellular signal regulated kinases 1 and 2 and they are involved in transcription regulation, cell differentiation, downstream regulation of genes, and cytokine synthesis regulation.Both cannabinoid receptors utilize the transducing G proteins, G1 and Go, responsible for a wide range of cellular functions such as response to environmental stimuli and responses to hormonal signals. ∆ 9 -THC binding to these receptors causes the opening of potassium channels, inhibition of adenylyl cyclase activity, closing of voltage gated calcium channels, and stimulation of mitogen-activated protein kinases, among other responses. The characterization of these cannabinoid receptors in human signaled to researchers that there are likely some endogenous ligands capable of binding to these receptors. These ligands are part of the endocannabinoid system and include anandamide which was found to produce similar effects as the cannabinoids from Cannabis sativa, O-arachidonoyl ethanolamine, and 2- arachidonoylglycerol , and 2-arachidonoyl glycerol ether. Additionally, reports have been made indicating that cannabinoids have been able to bind to other receptors in the body outside of CB1 and CB2. Cannabinoids have been found to be capable of binding to the transient receptor potential cation channel vanilloid type 1 , 5- hydroxytryptamine -3A ligand-gated ion channel, G-protein-coupled receptor 55 , 5-hydroxytryptamine -3A ligand-gated ion channel, and transient receptor potential cation channel Ankyrin type 1 . Both ∆ 9 -THC and CBD were isolated from the hemp oil plant in the 1940s. Unlike ∆ 9 -THC, CBD has no psychoactive properties and has low affinity to both CB1 and CB2 receptors, whereas ∆9 -THC binds effectively to the CB1 receptor.

Although CBD has low binding affinity to the endocannabinoid receptors, there is some data that indicates that CBD has some beneficial properties in the treatment of seizures and epilepsy, movement disorder, psychosis, anxiety, multiple sclerosis, and Huntington’s disease, once again highlighting the therapeutic potential of cannabinoids. The therapeutic potential of cannabinoids has led to the development of cannabinoidbased medicines . Currently, in the United States, there are 3 licensed CBMs approved by the Food and Drug Administration: nabilone , a synthetic analog of ∆9 -THC, used as an antiemetic, preventing vomiting and nausea caused by cancer medications, dronabinol, synthetic ∆9 -THC , used to treat lack of appetite leading to weight loss in AIDS victims as well as treat nausea and vomiting like nabilone, and a liquid formulation of dronabinol. The FDA has also placed on the fast track a few more CBMs and has also approved investigational drug studies of CBD due to its ability to treat chronic pain and help prevent seizures in childhood epilepsy cases. All in all, the global pharma cannabinoid industry is projected to exceed $102 billion by 2030 indicating a significant interest in the development of CBMs; therefore, methods for the efficient large-scale production of cannabinoids are necessary.In recent years, there has been significant interest from the synthetic biology community to produce cannabinoids using microbial and cell-free strategies because of the flexibilities in engineering the pathway to access rare or unnatural cannabinoids, the challenges associated with chemical synthesis, and the inconsistent and relatively low production of cannabinoids from plants.Owing to the identification of important enzymes in the cannabinoid biosynthesis pathway such as olivetolic acid synthase and olivetolic acid cyclase , which converts hexanoyl-CoA to olivetolic acid, microbial hosts have been utilized to produce cannabinoids.Another key finding was the discovery of the prenyltransferase responsible for prenylating olivetolic acid with geranyl to form cannabigerolic acid . With these key enzymes identified, botanicare trays different groups have attempted to microbial produce cannabinoids and their precursors. Tan et al., employing olivetolic acid synthase and olivetolic acid cyclase from the Cannabis sativa plant in addition to further engineering, were able to produce 80 mg/L of olivetolic acid from E. coli. To date, that is the highest literature recordedamount of olivetolic acid produced in vivo in any wild type or engineered organism. Additionally, Luo et al. were able to express the entire cannabinoid pathway in Saccharomyces cerevisiae and produce 8 mg/L of tetrahydrocannabinolic acid , the direct ∆9 -THC precursor, and 4.3 ug/L of cannabidiolic acid, the direct CBD precursor; this was the first time that ∆9 -THC and CBD were produced by yeast. Furthermore, Valliere et al., utilizing commercial olivetolic acid and the synthetic biochemistry approach of cell-free systems, showed that they were able to produce 1.25 g/L of cannabigerolic acid , by engineering an aromatic prenyltransferase from Streptomyces sp. CL190 to efficiently prenylate olivetolic acid, another important intermediate in the cannabinoid biosynthesis platform. 42 Additionally, Jimbo Ma et al engineered the yeast Yarrowia lipolytica to improve the biosynthesis of olivetolic acid and achieved an 83 fold titer increase giving a final titer of .11 mg/L. 43 E.coli and yeast strains have not been the only microbial organisms utilized to produce olivetolic acid and cannabinoids. Two groups have demonstrated that amoeba can also be engineered for the production of olivetolic acid. Reimer et al. engineered Dictyostelium discoideum, due to its ability to produce polyketides and terpenoids, to ultimately produce olivetolic acid. By fusing the OLS to the C-terminal of the D. discoideum StII gene , they were able to engineer an amoeba/plant hybrid gene for the production of olivetolic acid. The group utilized the StII gene, an enzyme consisting of a type III PKS and FAS and swapped the type III PKS domain with OLS and overexpressed this fused hybrid gene to produce olivetolic acid.

Kufs et al also utilized Dictyostelium discoideum to produce olivetolic acid , developing a scaled approach in bioreactors able to achieve a titer of 4.8 µg/L. Although novel with the use of Dictoystelium discoideum to produce this cannabinoid intermediate, such a result underscores the need to increase production of olivetolic acid. To date, these approaches for the production of olivetolic acid and cannabinoids all rely on the plant pathway with the enzymes olivetolic acid synthase and olivetolic acid cyclase catalyzing the formation of olivetolic acid from hexanoic acid and have heavy intellectual property surrounding them so a novel way of producing olivetolic acid is preferred. We were able to discover a novel pathway to olivetolic acid by focusing on fungal natural product bio-synthetic pathways, a vast field with promising capabilities. Natural products from fungi have demonstrated great therapeutic and agricultural potential with two of the currently used anti-fungal drugs being the natural products echinocandins and amphotericin. Echinocandins, referred to as the “penicillin of antifungals”, and amphotericin are also included in the World Health Organization’s List of Essential Medicines, showcasing the powerful potential of fungal natural products. Natural products, also referred to as secondary metabolites, are most times not essential for the organism’s life but do still have important roles such as acting as metal-transporting agents, symbiosis facilitators, sexual and differentiation effectors, and metal-transporting agents, among other functions. Fungi produce a vast variety of natural products that can be classified as terpenes, polyketides, sugars, and alkaloids. There are 100,000 known fungal species, although upwards of one million fungal species are expected to be in existence. Of the known 100,000 fungal species, only a fraction of their natural products and bio-synthetic pathways have been elucidated. Therefore, there is great potential to search for more fungal natural products with interesting bio-activities, underscoring the importance of genome mining. These bio-synthetic pathways encode secondary metabolite genes that produce natural compounds. Genome mining has been used to search for bio-synthetic pathways for known products as well as undiscovered bio-synthetic pathways that can produce novel natural products. Genome mining answers the question of how natural products are formed. It describes the utilization of genomic information to search for bio-synthetic gene clusters responsible for producing natural products. Over the years many different methods of genome mining have been developed. Among them include classical genome mining, comparative genome mining, phylogeny-based genome mining, and resistance gene/target directed genome mining. Classical genome mining involves the search for genes involved in a bio-synthetic pathway. Typically, the process consists of querying for a desired gene across many genomes and then querying for that gene in the context of a bio-synthetic gene cluster. NCBI Basic Local Alignment Search Tool is widely utilized for classical genome mining. Comparative genome mining involves comparing multiple genomes in different organisms to identify similar clusters. It differs from classical genome mining in that instead of searching for single genes, one is searching for partial or whole gene clusters across various genomes. Gene clusters in a genome are then prioritized based on their homology to other clusters in other organisms’ genomes.

The models that have been used in previous studies are simple steady state models for the fuel cell and liquid desiccant systems. In this study, I investigate the integration of rack and row level fuel cell powered servers with Liquid Desiccant Dehumidifier technology that can be dynamically dispatched to produce electricity and cooling in various amounts to meet power and air conditioning demands of data centers. In addition, the storage capacity to meet the demand of data center for the entire year is evaluated. The objectives of this phase of the study focus on theoretically evaluating the integrated system concept and to assess the achievable air conditioning from SOFC waste heat. To explore the feasibility of thermally integrating SOFC with LDD, a spatially resolved physical model developed in MATLAB is used to simulate the operating characteristics of this SOFC system. A corresponding physical model is developed to simulate the liquid desiccant air conditioner for dehumidification. This study considers SOFC systems capable of powering single server rack and row of servers and the operation of an LDD for cooling and dehumidification of that same configuration. The small-scale LDD operation is based on distributed waste heat from each individual SOFC at the rack level. The analysis will indicate whether waste-heat based cooling and dehumidification can power the servers and maintaining server operating temperatures and humidity in the safe range for different weather conditions.A spatially and temporally resolved fuel cell stack model has been developed based on the developed model in NFCRC using the MATLAB software. The model is developed for one unit cell that describes the response of the entire stack. 51 unitary anode-supported planar rectangular cells are assembled into one-unit SOFC stack.

Figure 18 presents one crossflow cell geometry with its components as well as a depiction of two repeated cells in series. The planar rectangular cells are flexible, compact,how to cure cannabis easy to produce, and have lower manufacturing cost compared to tubular cells. The unit cell consists of five layers i.e., cathode flow, anode flow, Positive electrode, Electrolyte, Negative electrode , fuel bipolar plate and air bipolar plate. The spatially and temporally resolved model uses different states to calculate parameters at different nodes of a cell. These nodal states are calculated at each time step among set of points in the time vector using the MATLAB Ordinary Differential Equation solver. These nodal states are composed of nodal temperatures of fuel and air separator plates , temperature of fuel and air flows, nodal temperature of the PEN, nodal concentration of different species in both cathode and anode flow sides , nodal current and cathode/anode flow inlet pressure. The evaluated parameters based on the mentioned states are nodal Nernst voltage, nodal voltage losses, nodal operating voltage , nodal molar flow rate of ions crossing the PEN, nodal heat generation in the PEN, nodal heat and mass transfers and many other parameters. A two-dimensional multi-layer approach is accomplished for both the electrochemical modeling and heat transfer modeling resulting in a quasi-3-D representation of an electrochemical cell. As an assumption, instantaneous electrochemical reactions are assumed, due to relatively fast electrochemical reactions compared to cell and stack thermal response dynamics. Using Faraday’s law, the rate of electrochemical reactions is directly proportional to the cell current. Furthermore, it is considered that electrical current flows only in one direction from one electrode to the other one along the PEN, as the electrical potential is assumed constant on the electrode surfaces.

In the developed model, gases behave as ideal gas due to high operating temperature of the SOFC. In this study a 5×5 spatial resolution is accomplished for all 5 layers . The solid oxide fuel cell has an active surface area of 139.24cm2 . Fuel cell module material properties are presented in Table 2 and geometry parameters are presented in Table 3. Figure 19 depicts schematically the geometric parameters of the fuel cell.The developed model takes into account the conservation of energy within each node and energy transfer between control volumes to calculate the nodal temperature changes during dynamic operating conditions for all 5 layers which are fuel plate, air plate, cathode flow, anode flow and the PEN. Nodal energy balance equation for the cathode/anode stream includes convective heat transferred to the solid walls , enthalpy flux due to the electrochemical reaction, mass transfer of oxygen ions from/to the PEN, and inlet/outlet enthalpy flux of the bulk flow from/to adjacent nodes. It is assumed that temperature in each control volume decreases/increases linearly along the control volume of each node . A nodal energy balance for the PEN includes convective heat transferred to the PEN from streams, conductive heat transferred to the PEN from bipolar plate, conductive heat transferred to adjacent nodes in PEN and heat generation due to the electrochemical reactions and electrical resistances. Radiation heat transfer between PEN and bipolar plate is negligible. A nodal energy balance equation for the bipolar plate includes convective heat transferred to bipolar plate from streams, conductive heat transferred to bipolar plate from PEN and conductive heat transferred to adjacent nodes in bipolar plate. Adiabatic boundary condition is considered for all the nodes located at the beginning and at the end of the cell on PEN and bipolar plate, as the cell height is relatively thin compared to its length. Also, it is considered that the stack is well insulated such that heat loss to the environment is negligible. The nodal energy balance equation for cathode and anode flows, PEN and bipolar plate are presented below.

Note that all nodal specific heat capacities are calculated at the node temperature. Also, for each cathode/anode node, inlet flow enthalpy is the outlet flow enthalpy of the previous node in the flow direction as follows. As flows move from inlets to the cathode and anode outlets, the composition of fuel in anode side and the composition of oxygen/nitrogen at cathode side will be changed. The developed model takes into account the conservation of mass within each node and mass transfer between control volumes to calculate the nodal species’ concentration’s changes . Mass balance in cathode/anode flow side includes inlet/outlet molar flow rates from/to adjacent nodes and variation due to the existing electrochemical reaction. The nodal dynamic mass balance equations for steam, hydrogen, carbon monoxide, carbon dioxide, methane, oxygen and nitrogen species are presented below. Note that for each node, the inlet molar flow rate is the outlet molar flow rate of the previous node in the flow direction as follows. Figure 20 to Figure 24 show the spatial distribution of temperature, Nernst voltage, losses, voltage, and current density in a unit SOFC. The temperature changes between 1000K- 1040K. The temperature has its lowest amount at the corner close to the cathode and anode streams inlet where the air which is cooling stream has its lowest temperature and the reformation which is endothermic is still occurring at the beginning of the cell. Temperature has the highest amount at the corner close to the cathode and anode streams outlet where air has its highest temperature and electrochemical reaction which is dominant at the end of cell generates heat due to its exothermicity. The Nernst voltages are among 0.9V-0.98V. The Nernst voltage is highest at the corner close to the cathode and anode inlet streams where both fuel and oxidant partial pressures are high leading to high thermodynamic potential with the lowest Nernst potentials realized at the corner close to the cathode and anode streams outlet. The lowest amount of losses is 0.065V captured where the temperature is highest. High temperature increases the thermal energy available in the system,trimming cannabis generally resulting in the fact that all the particles in the system now move and vibrate with increased intensity. This higher level of thermal activity will possess sufficient energy to overcome activation polarization and most importantly increases electrolyte ionic conductivity, which decreases the ohmic loss. Figure 22 shows the spatial distribution of cell operating voltage which is uniform along the cell as expected due to the equipotential surface that is established by the good electronic conductivity of the electrodes and bipolar plates. The current density along the direction of fuel flow decreases as the fuel gets consumed and has less potential to produce current.The SOFC system model contains a fuel cell stack, an anode off-gas oxidizer, air preheating heat exchangers, recirculate valve, mixer, blower, and reformer. A system diagram is provided in Figure 25. The oxidizer outlet preheats air and fuel first, and then, the leftover heat from the SOFC exhaust is recovered for regenerating desiccant liquid in the LDD system.Cell temperature control is one of the key issues involved in the dynamic operation of high temperature SOFC systems. In this study, the stack is thermally managed by manipulating one actuator, which controls the blower power. A variable speed blower enables control of blower dynamics that consider the inertia of the blower as described above. Increasing the blower power ultimately increases the blower speed, which in-turn increases the air flow rate introduced to the stack. The air flow rate has two functions in the proposed system, i.e., providing the oxygen for the electrochemical reactions and providing cooling or heating to the stack. The temperature control strategy consists of two parts. Stack temperature gradient is controlled with blower power. If the temperature gradient goes higher than the set point, the blower power increases which increases the air flow rate which cools the stack. To control stack average temperature, the valve position changes to increase or decrease the air flow to oxidizer which affects the cell inlet air flow temperature. To decrease the cell average temperature, the valve opens more, to decrease the hot flow temperature in the air heat exchanger. In this study, the controller set-point temperature difference constraint is 50K. Also, the inlet temperature of both anode and cathode temperature are controlled to the set point of 1023K. The system model is based on a commercially available SOFC systems called BlueGEN. BlueGEN CHP unit, originally manufactured by Ceramic Fuel Cells Ltd . BlueGEN is a commercially available SOFC CHP system, now built and sold by SOLIDpower, designed for small- to medium-scale building applications. Operating on natural gas, the unit can produce power modulated from 500We to 2kWe ; however, it achieves its highest net electrical efficiency of 60% at a 1.5kWe output. The BlueGEN SOFC unit consists of 51 planar type Yttria Stabilized Zirconia electrolyte-supported cell layer sets and operates at around 750℃. Hydrogen is produced from natural gas by external and internal steam reforming. The polarization curve data from the BlueGEN SOFC system tested at the NFCRC and the developed model results are presented in Figure 26. Note that the V-j curve obtained from the test covers only the operating envelope of the SOFC system. The steady state performance of the system was calculated under the standard operating conditions of the BlueGEN at 85% fuel utilization and cathode outlet temperature of 750˚C. The SOFC system is controlled to keep the stack temperature difference at 50˚C. The SOFC parameter and standard operating conditions are presented in Table 4. The electrical efficiency of the stack is over 61% under standard operating conditions. The steady state performance parameters of the model for 1.5kW SOFC system and experiment values are compared in Table 5. Note that experimental values well match those of the model. Note also that the exhaust gas temperature and flow rate were not measured during the experiment. The particular SOFC system that was evaluated in this study was designed for CHP, and thus produces more heat than would be used for preheating the SOFC inlet air and fuel. The heat produced from the SOFC system in the current case is then used for producing hot water for LiCl regeneration purposes. This model indicates that a nominal 1.5kW system would produce 0.0104kg/s of exhaust gas and that the temperature of the exhaust would be 100˚C. Electricity demand for a single residential unit is used as a desired demand applied to the spatially resolved dynamic SOFC model. SOFC model results that generated output power follows the desired demand quite closely except for very short periods of high ramp rate operating conditions. Figure 28 shows the electrical efficiency of the system during the dynamic operation. The average efficiency during dynamic operation is 71%. The high efficiency is due to high fuel utilization and part load operation of the system which also lead to a lower exhaust temperature.

The vast majority of adult smokers began smoking during adolescence. Each day, approximately 2,000 youth smoke their first cigarette and over 300 become daily smokers. Previous studies have shown that the younger people are when they begin using tobacco products, the more likely they are to develop nicotine dependence and other substance use disorders. It has also been shown that adolescents can become nicot inedependent very quickly, even after occasional intermittent use. Furthermore, a meta analysis of longitudinal studies confirms that ENDS use is associated with an increased likelihood of future cigarette smoking. Although the percentage of teen ENDS use had been consistently increasing over the years, the percentage of high school seniors vaping nicotine actually decreased from 34.5% in 2020 to 26.6% in 2021 during the COVID-19 pandemic in the US. This decrease in adolescent drug use was surprisingly consistent across many substances, including alcohol and opioids. This phenomenon could possibly be attributed to limited access to drugs during government ‘stay at home’ orders, reduced in person peer pressure, increased messaging of the harmful effects of drug products targeted at youth, and/or potential survey response biases as adolescents are likely responding in the presence of a parent or guardian at home. According to the World Health Organization, cannabis, also known as weed or marijuana, is the most abused illicit drug. As of 2021,air racking only eight countries have at least partially legalized cannabis for recreational use, but approximately 200 million people report using cannabis worldwide.

Cannabis is derived from the Cannabis plant which contain over 100 compounds called phytocannabinoids, with Δ9-tetrahydrocannabinol and cannabidiol being the most well-characterized. Cannabis use may induce sensations of euphoria, altered sense of time, distorted sensory/body perception, and mood changes. THC is the main psychoactive component in cannabis and can result in feeling ‘high’, along with increased anxiety and paranoia, altered perception, impaired working memory, slower movements, and cognitive deficits, depending on the dose. Among youth, smoking cannabis appears to be becoming somewhat less prevalent, but this downward trend has been paralleled by a general upward trend in consumption of edibles and use of THC vapes. Of concern, high frequency adolescent cannabis use has been linked to deficits in attention, learning, and memory, as well as mental health issues including increased depression, anxiety, suicidal ideation and schizophrenia. Similar to nicotine, however, in correlation to the COVID-19 pandemic, there was a decrease in the percentage of adolescents who report using cannabis in 2021. Interestingly, there is evidence that low doses of THC in older mice may help restore cognitive function. Similarly, in older humans , short-term low-dose cannabis consumption does not seem to have adverse effects on cognition and can aid in pain management. THC can be also used to help counteract weight loss in HIV/AIDS patients and to alleviate nausea for patients undergoing chemotherapy. Synthetic cannabinoids are those created in a laboratory and fall under the drug classification ‘New Psychoactive Drugs’. Examples include WIN 55,212-2 and CP- 55,940 – which are compounds that can be used in the street drug termed ‘spice’.

Some forms of spice are created by spraying synthetic cannabinoids onto shredded plant material, with users smoking the resulting combination like a joint. However, it has more intense psychoactive and physiological effects than THC. Synthetic cannabinoids were initially created for pharmaceutical research and were not intended for human consumption. However, because synthetic cannabinoids have similar physiological effects as THC and were not federally illegal, they have been sold in US and European street drug markets since the early 2000s. Further, these synthetic cannabinoids are not typically tested for during routine drug screens and often remain undetected when law enforcement or hospitalization is involved. Synthetic cannabinoids induce many more intense effects than merely altering one’s mood and perceptions, such as tachycardia, psychosis, hallucinations, respiratory distress, and in some cases, death. In 2012, 26 different formulations of spice were banned with the Synthetic Drug Abuse Prevention Act in the US, classifying them as Schedule I drugs. Nevertheless, as different versions of these synthetic compounds become illegal, new modified versions created by underground chemists consistently reappear in the market. They have not yet been classified as illegal, but still can be quite harmful. Drug co-use is also of concern, given the potential synergistic effects on the user. For instance, a study in youth aged 12-17 found that those who used cannabis were more likely to use nicotine products at the same time, or initiate nicotine consumption within one year. Daily cannabis use has also been associated with co-use of opiates, cocaine, and/or inhalants, and approximately half of young cannabis users report simultaneously consuming alcohol and cannabis. Moreover, young adults co-using tobacco and cannabis were more likely to use nicotine ENDS, cocaine, and greater amounts of cannabis than those that just consumed cannabis alone. In older adults, using cannabis is associated with an increased likelihood of being diagnosed with a substance use disorder for either nicotine, alcohol, or cannabis.

Thus, the drug co-use condition represents a significant health concern among various age groups. When inhaled, nicotine readily enters the bloodstream through the alveoli in the lungs and becomes absorbed into the brain within seconds. Nicotine selectively binds to nicotinic acetylcholine receptors , which are pentameric ligand-gated ion channels located on either the presynaptic or postsynaptic membrane. The nAChR subtype may be heteromeric or homomeric, containing a combination of a and b subunits or containing all the same subunit, respectively. The a subunits present in nine different types, a2 – a10; whereas the b subunits present in three different types, b2 – b4. Various combinations of these subunits result in diverse effects on the pharmacokinetics of the receptor with ligand binding. The a7, a4 and b2 subunits are the most prevalent in the central nervous system. The homomeric a7 nAChR has a relatively lower affinity for nicotine and is important for modulating inflammation. The a4 and b2 subunits combine to form a functional heteromeric receptor with a high affinity for nicotine; the a4b2 nAChR is involved in mediating nicotine’s reinforcing and rewarding properties through receptor localization in the mesolimbic circuit. Further, receptors containing the a5, a3 and b4 subunits have been shown to modulate aversive signaling that limits nicotine intake and aspects of the withdrawal syndrome via receptor localization in the habenulo-interpeduncular circuit. Like nicotine, when cannabis smoke is inhaled, active phytocannabinoids pass from the lungs into the bloodstream and are carried throughout the brain and body. THC acts on the cannabinoid 1 receptor and cannabinoid 2 receptor. In the brain, CB1Rs are mainly localized in neurons and astrocytes, whereas CB2Rs are primarily found on immune cells. In humans and rodents, CB1Rs are highly expressed on neurons in the neocortex, hippocampus, amygdala, cerebellum, and basal ganglia. Since endogenous cannabinoids engage in retrograde signaling from the cell body to the presynaptic axon terminal, activation of CB1Rs results in inhibition of presynaptic neurotransmitter release. CB1Rs are also located on postsynaptic membranes and astrocytes. Of note, THC is a partial agonist of the CB1Rs and CB2Rs, whereas synthetic cannabinoids are typically full agonists. Cannabinoids can also act on other receptors, including GPR55 and TRPV1, although the functional role of these receptors is lesser known. When individuals co-use nicotine and cannabinoids, one would expect activity at both the nAChRs and CB1Rs. Both of these receptor types exhibit overlapping expression patterns in drug addiction-associated brain regions, such as the prefrontal cortex, nucleus accumbens ,drying weed ventral tegmental area , and amygdala. In particular, the mesolimbic dopamine pathway, a circuit from the VTA to the NAc, controls reward processing and the reinforcement of natural rewards and most drugs of abuse. Mechanistically, as nicotine and cannabinoids bind to nAChRs and CB1Rs in the VTA, they increase the firing rate of dopamine neurons and trigger the release of dopamine to the NAc which subsequently reinforces the drug-taking behavior. Nicotine acts on the a4b2-containing nAChRs to mediate dopamine signaling via their locations on both dopaminergic and GABAergic neurons in the VTA and neuron terminals in the NAc . Due to a lack of CB1R expression on VTA dopamine neurons, cannabinoids likely act on this circuit indirectly. Through retrograde mechanisms, cannabinoid binding to presynaptic CB1Rs expressed on GABAergic presynaptic terminals decrease GABAergic inhibition, thereby increasing dopamine release in the NAc.

In addition, it is important to acknowledge the involvement of other neurotransmitters, such acetylcholine, glutamate, and serotonin in consideration of the intricate complexity of the projections among brain regions. Thus, nicotinic and cannabinoid signaling within reward-related brain regions may lead to interactions among signaling mechanisms that modulate various aspects of drug-taking behaviors.Approximately 20-30% of people who experiment with cigarettes will meet criteria for nicotine use disorder during their lifetime. Around 30% of cannabis users are anticipated to develop some degree of cannabis use disorder. Individuals who begin using cannabis prior to 18 years of age have a four to seven times increased likelihood of developing the use disorder. Moreover, as noted above, the co-use of both substances is quite frequent. Around 60% of cigarette smokers reported ever using cannabis, and 90% of cannabis users reported ever smoking cigarettes in their lifetime. While individual drug use has its own potential to develop into a substance use disorder, co-users of both substances are at an increased risk of developing both nicotine dependence and cannabis dependence. This increased risk is of further concern because adults with cooccurring cannabis use disorder and nicotine dependence are more likely to have bipolar, anxiety, and personality disorders than those with only nicotine dependence. Among youth and young adults, the concern of these co-occurring substance use disorders is also prevalent. Teens who vape nicotine or smoke hookah are four times more likely to start smoking cannabis within two years, and current adolescent tobacco smokers who frequently use cannabis are more likely to report nicotine dependence. Likewise, adolescents who use cannabis are more likely to become daily cigarette smokers and develop nicotine dependence. Additionally, a longitudinal study looking at the trajectories of nicotine and cannabis vaping from adolescence into early adulthood revealed that those who frequently vape were also very likely to be users of both substances. Adolescent and young adult cannabis and tobacco cigarette co-users exhibit increased cannabis use disorder symptoms including continued use despite negative consequences, developing a tolerance, and inability to reduce cannabis use, in comparison to those who only use cannabis. Moreover, young adults who co-use cannabis and nicotine together report consuming more cannabis and nicotine in the past year than those who only use one of the drugs. In sum, across age ranges, nicotine and cannabis co-use conditions increase the risk of individual drug use and the development of substance use disorders. Furthermore, sex differences have emerged with the prevalence and patterns of substance use disorders in the population. Adult men are more likely to initiate drug use, but adult women develop substance use disorders more rapidly. Interestingly, during adolescence, drug use is initiated at similar rates between sexes, but boys appear to escalate their drug use faster than girls. According to a recent report, men are more likely to smoke cigarettes, vape nicotine, use smokeless tobacco, and be daily cannabis users. Women with a history of cannabis use are four times more likely to become regular cigarette smokers and almost three times as likely to develop nicotine dependence. However, women report experiencing more intense nicotine withdrawal symptoms.While the above findings suggest an important role of age or sex in nicotine and cannabis co-use, many individual, societal, and familial factors also influence drug taking behaviors in humans, and as such, animal models are important to delineate the precise effects of such factors on drug taking behaviors. Findings from rodent models have established that cannabinoids and nicotine exert unique effects on drug-related behaviors based on the duration and timing of exposure, in addition to the animal’s sex. Interestingly, adolescent male and female rats will self administer greater amounts of nicotine than adults, and nicotine exposure during adolescence can lead to increased self-administration of other drugs of abuse, including alcohol, methamphetamine, and cocaine. Drug exposure during adolescence can also induce long-lasting effects on the animal into adulthood. Adolescent male rats exposed to THC were found to self-administer higher levels of the synthetic cannabinoid WIN or heroin in adulthood.

Taylor and colleagues report that between 34% and 61% of adult males used cannabis at least once in the year 2000, including between 17% and 63% of violent criminal offenders and between 34% and 74% of offenders in property crimes . These findings, while far from definitive, do not suggest a clear and direct link between cannabis use and crime. Many arrestees who test positive for cannabis also test positive for alcohol or other drugs . This makes it difficult for researchers to infer the extent to which certain behaviors can be attributed to specific substances. Furthermore, because of the way that the human body metabolizes marijuana, positive tests for marijuana only indicate use within the past month, and therefore do not necessarily signify that a particular crime was committed while under the drug’s influence . In fact, in some studies cannabis has been shown to inhibit aggression and violence . Thus, although it may appear that marijuana use is associated with criminal arrests, there are many reasons to be skeptical about that correlation. The drug-crime link, in psychopharmacological terms, is stronger for alcohol than it is for illicit drugs . “In the case of marijuana,” Resignato concludes, “the assumed psychopharmacological connection between use and violent crime has been almost completely disproved in the research” . Research on economic compulsive drug related crime tends to focus on drugs with higher addictive potentials than cannabis,how to cure cannabis most notably heroin and cocaine .

Perhaps the most compelling mechanism through which drugs might lead to crime is through the occurrence of systemic violence . The violence associated with markets for illegal drugs is at least indirectly caused by drug prohibition and enforcement, “a relationship that may be underestimated by many policy officials” . It is plausible that this would apply to retail vendors of medical marijuana—although arguably less so than the illicit dealers of the drug, who are displaced by legal or quasi-legal cannabis businesses . I conclude from the available literature that cannabis has no significant relationship with crime via its psychopharmacological effects or its capacity to bring about economic-compulsive criminal behavior in its users . I argue that the only plausible link between cannabis and crime lies in the extent to which the drug attracts “systemic violence”, due to its illicit status and high market value. The following chapter presents a conceptual model that can be used to test empirically whether or not medical cannabis dispensaries are associated with crime in city neighborhoods. In the remaining sections of this chapter, I discuss potential linkages between MCDs and crime and present two theoretical approaches to urban criminology: routine activities theory and social disorganization theory.Do medical cannabis dispensaries increase crime? It depends who you ask. Empirical evidence is scant and is almost entirely overshadowed by anecdotal reports. For example, a 2009 report compiled by the Coalition for a Drug-Free California alleges that “marijuana escalates the level of mental illness, crime and all related problems” . But the report offers little empirical evidence in support of these claims.

The California Police Chiefs Association —an organization representing California’s municipal law enforcement agencies—has also been a vocal critic of dispensaries. Its 2009 White Paper on Medical Marijuana Dispensaries concludes that the presence of dispensaries “poses a clear violation of federal and state law; they invite more crime; and they compromise the health and welfare of law-abiding citizens” . The underlying evidence is entirely anecdotal: the CPCA presents no statistical analysis supporting the conclusion that medical cannabis dispensaries cause crime at a higher rate than any other business. The CPCA’s assertion that dispensaries increase crime stands in conflict with an analysis conducted by the Police Department of Denver, Colorado, which in 2010 projected that dispensaries attract crime at a similar rate as pharmacies and a lower rate than banks or liquor stores.A recent study conducted by researchers at the UCLA Luskin School of Public Affairs examined crime data in 95 census tracts in Sacramento . No clear link was found between the density of marijuana dispensaries and the rate of violent or property crime, suggesting that dispensaries do not increase crime and that some security steps taken by dispensaries may actually reduce local crime. Despite the insistence of organizations such as the Coalition for a Drug-Free California and the California Police Chiefs Association, there does not appear to be an obvious link between medical cannabis dispensaries and criminal behavior in surrounding areas. Limited reports from California and Colorado suggest a neutral or negative correlation between MCDs and crime, but more empirical research is needed to substantiate a generalized claim to that effect. This study aims to extend current knowledge about the relationship between MCDs and crime by conducting a spatial analysis of crime data from San Francisco.Thus routine activities theory attempts to explain crime by looking at the ecological circumstances in which it occurs, while other criminological approaches tend to focus on the characteristics of criminal offenders.

Both are useful to the present study, which analyzes whether crime is related to MCD presence in city neighborhoods but is also interested in controlling for demographic characteristics related to crime across those neighborhoods. Regarding the number and concentration of motivated offenders in an area, MCDs could have a positive, negative, or neutral effect on crime. If cannabis use directly or indirectly leads to criminal behavior, then MCDs might increase crime in a neighborhood by concentrating a large number of cannabis users in one place. It is also possible that MCDs could reduce criminal behavior in a neighborhood by displacing illicit dealers of the drug. And it is of course possible that MCDs have no effect whatsoever on the number or concentration of motivated criminal offenders in an area. From a routine activities perspective, the most likely link between MCDs and crime is probably in the extent to which MCDs present suitable targets for crime. Components of target suitability include value, visibility, and accessibility . With respect to value, MCDs tend to possess large amounts of cash and cannabis, which are high-value targets for theft. As Felson notes, “lions look for deer near their watering hole” .Patients, vendors, and especially staff are potential targets of crime: “Employees of the dispensaries can be at-risk for violent crimes, such as robbery or assault, as they are gatekeepers to both the marijuana products and the cash at the site” . In California it is estimated that MCDs conduct roughly $1.9 billion in gross sales annually.Beyond the fairly obvious point that criminals like to steal things of value—which is just as true for MCDs as it is for banks, pharmacies, and other retail businesses—there are other valid reasons to believe that criminals would perceive MCDs as suitable targets. Most MCDs are open systems that are constantly seeking new members through advertising and other means. Thus they present, in many cases, highly visible targets for crime. Although few empirical studies have examined the relationship between MCDs and crime, existing research has explored the criminogenic effects of other land uses. A study by Roncek and Lobosco reported that high schools elevate local crime rates, probably through the concentration of likely offenders . Brantingham and Brantingham found an inverse relationship between crime rates and distance from the nearest McDonald’s. As Felson explains, the restaurants themselves may be safe—but they attract customers who are “in prime offending and victim ages,indoor grow methods producing high crime risk for nearby properties” . There is strong evidence to suggest that bars and other establishments that serve alcohol meet the criteria for target suitability .

This provides an interesting point of comparison for medical cannabis dispensaries and other retail businesses. A criminal might reasonably perceive that a patron entering or leaving such businesses would be in possession of some amount of cash and therefore be an attractive target for theft . The establishments themselves operate largely in cash and are accessible to the public, in many cases advertising themselves in an effort to increase their accessibility. The perception that these would be easy targets is compounded by the perception that patrons and staff might be medically ill or intoxicated . Thus, as Roncek and Maier conclude in the case of bars, “the patrons and the businesses have all the components of target suitability” . The degree to which MCDs present suitable targets for crime—a notion that is subject to considerable debate—is largely dependent on the effectiveness of MCD security measures. Here we see an inverse relationship between target suitability and the third core component of routine activities theory, capable guardianship. As guardianship increases, a potential target becomes less and less accessible to predatory crime. By definition, members of MCDs suffer from medical conditions that qualify for medical cannabis treatment. This could create a perception of vulnerability that is attractive to criminals seeking to obtain cannabis and/or cash without a fight. It is also possible that criminals perceive MCD operators to be less likely to report crime due to their precarious legal existence and a resulting incentive not to attract attention from law enforcement. Thus it is plausible that the presence of MCDs might increase crime in a neighborhood by presenting, in the terms of routine activities theory, accessible targets for crime. But it is also possible that criminals do not perceive MCDs to be suitable targets for crime, or that they consider them no more attractive than other retail businesses with high-value inventories and large amounts of cash. Furthermore, it is possible that—compared to other potential targets in the neighborhood—criminals actually perceive MCDs to be unsuitable targets. This largely depends on the effectiveness of guardianship in a neighborhood to prevent crime. Compared to other businesses, MCDs might represent superior guardianship in a neighborhood and thereby serve to reduce the frequency of crime. Security protocols are one way in which an MCD might do this.Many dispensaries implement security protocols—in order to comply with local mandates or simply to protect their patients, vendors, and staff—that might serve to increase the level of guardianship in a community and thereby reduce crime in a neighborhood, as routine activities theory suggests. These range from I.D. verification to external lighting and alarms; some dispensaries even conduct external patrols in order to demonstrate guardianship over their property and improve the surrounding community. 23 Unlike pharmacies and liquor stores, MCDs verify their customers’ qualifications before they can enter the premises and make a purchase. It is plausible that these and other security protocols have a deterring effect on crime. If these outweigh the criminogenic aspects of MCDs—that is, the potential for MCDs to attract likely offenders to suitable targets—then it is likely that the net effect of MCDs on crime is neutral. I examine this possibility in the present study. Social disorganization researchers have identified several neighborhood characteristics that are positively associated with crime. This study borrows from their work in selecting control variables to address the fact that social and demographic characteristics vary widely across city neighborhoods, with significant implications for social and economic activity, public health and safety, and other outcomes. Whereas routine activities theory focuses on the circumstances in which crime occurs, social disorganization theorists point to the social and demographic characteristics of surrounding communities in explaining outcomes of high crime and violence. Social disorganization has been concisely summarized by Sampson and Groves: “The general hypothesis is that low economic status, ethnic heterogeneity, residential mobility, and family disruption lead to community social disorganization, which, in turn, increases crime and delinquency rates” . This approach is summarized in Figure 2.2. According to this theory, crime is associated with what Sampson and Groves call “exogenous sources of social disorganization” . This study controls for three such categories of neighborhood characteristics: economic deprivation, residential instability, and family disruption. Low socioeconomic status translates to lower levels of formal and informal social control. Higher rates of family disruption, i.e. a higher proportion of single-parent versus married-couple households, results in decreased parental supervision and a relative lack of guardianship . These conceptual links to crime, expounded originally by Shaw and McKay , have received more nuanced theoretical attention from Kornhauser , Sampson and Groves , and Veysey and Messner . The explanatory power of their empirical correlates is discussed in the following section, which describes the measures to be analyzed in the present study.