These prior studies suggested that MI can improve MH treatment initiation in veterans

We included measures of employment indicating whether respondents were employed, temporarily unemployed or seeking work, or part of a residual category that included retirees, students, and stay-at-home spouses or partners. The study was approved as exempt by the UCSF institutional review board on July 16, 2016. The 2016 survey contained 3,058 respondents. Weighted probabilities of use in each category, by sociodemographic characteristics, are shown in Table 1. Overall prevalence rates were 14.5% for cigarette smoking, 5.6% for ENDS use, and 9.5% for cannabis use. Prevalence of separate use for tobacco and cannabis, for all modalities, was 6.1% and prevalence of simultaneous tobacco and cannabis use was 3.4%. As shown in Table 1, rates of cigarette smoking, ENDS use, and cannabis use were higher for men than women. Rates of cigarette smoking and combined cannabis and tobacco use decreased with higher levels of education, but were not associated with higher education levels for ENDS use, cannabis use, or combined use. Rates of cigarette smoking, ENDS use, cannabis use, and combined use were highest among those unemployed and seeking work and persons with disabilities, relative to those who were employed or retired. Over half of cigarette smokers who initiated smoking over the age of 18 reported smoking in the past 30 days.For cigarette smoking, there was a lower odds ratio among those with at least a bachelor’s degree and those with household incomes greater than $100,000, as shown in Table 2. There was a significantly greater odds ratio among persons with disabilities and those who had begun smoking at 15 or older. For ENDS use, grow tables 4×8 there was a significantly lower odds ratio among those aged 55 or older. For all cannabis use, women were approximately half as likely to use as men .

Additionally, those with household incomes from $25,000–$49,999 were half as likely to use cannabis as those who had incomes of less than $25,000 . For combined tobacco and cannabis use, there was a significantly lower odds ratio among some lower-income groups. There was a significantly greater odds ratio for those who were unemployed and seeking work. For using tobacco and cannabis simultaneously, there was a significantly lower odds ratio for those with incomes $25,000–$49,999 and greater than$75,000. There was a significantly higher odds ratio for those who were unemployed and seeking work or and persons with disabilities. Past research has identified the practice and consequences of simultaneous tobacco and cannabis use among adolescents, however there has been limited data on the prevalence of this practice in different population subgroups or relative to other consumption, such as use of individual substances or separate use . Existing research suggests that young adults may be more likely to engage in simultaneous use, particularly given the increase in new modalities of use , however surveillance data has not yet verified this expectation . Our findings suggest that in contrast to findings from previous research, rates of simultaneous use may be highest among those who were involuntarily unemployed and persons with disabilities rather than among youth. We also found that more people used either cannabis or ENDS than smoked cigarettes, despite the relative novelty of these products. These results suggest a transition toward modalities that allow simultaneous use, a trend that could continue or accelerate as these novel products become increasingly normalized. Research on simultaneous use suggests that such a transition would lead to more dependence and reduced quit attempts , a concern given that these sub-populations are likely to have lower income and co-occurring conditions . Our findings have limitations. The data are based solely on California residents and responses reflect a policy environment that for 20 years has focused on reducing tobacco use and increasing access to medical marijuana.

These policy changes preceded similar changes made in many other states, suggesting that these data , primarily provide insight into how use patterns may change over time in those states that also legalized medical marijuana prior to recreational cannabis. Survey responses were based on self-report and did not biochemically validate responses; previous research suggests that respondents may under report use . As a result, our findings may have failed to identify other groups at risk of simultaneous use. As states continue to legalize medical marijuana and recreational cannabis, it is critical to monitor shifts in patterns of tobacco and cannabis use. Adolescents and young adults have been a focus of prior research, particularly in light of their susceptibility to uptake of novel delivery devices such as JUUL . However our findings suggest that young adults are not necessarily the population with the highest prevalence or highest risk of simultaneous use. Simultaneous use is linked with more severe consequences than using tobacco or cannabis alone, or with separate use of these products. Our findings that simultaneous users in California were not disproportionately young adults are relevant for developing targeted prevention and cessation interventions for individuals at high risk. In addition to emphasizing risks faced by adolescents and young adults, our findings suggest that public health interventions should expand their focus to address other vulnerable populations, including persons who are involuntarily unemployed and those with disabilities. Disproportionately more rural veterans are enrolled in Department of Veterans Affairs healthcare than their urban counterparts . Most rural veterans receive care from smaller VA community based outpatient clinics established by VA expressly to improve access to care, including mental health care. Rural veterans who utilize VA community-based clinics are typically older, sicker and poorer, and experience significantly greater MH burden and poorer clinical outcomes than their urban counterparts receiving care at VA medical centers. 

VA mandates that all veterans, including those receiving care at VA community-based clinics, have access to evidence-based MH treatments. Minimally adequate MH treatment has been defined as ≥ 8 MH treatment sessions or receiving ≥ 2 months of psychiatric medication plus > 4 visits within 1 year. Nevertheless, despite access to VA community-based clinics, rurality remains one of the strongest predictors of poorMH treatment engagement. Roughly, only 20% of rural veterans with MH conditions initiate any MH treatment and even fewer complete a full course of evidence-based MH treatment. Rural veterans’ lack of engagement in MH treatment reflects a myriad of logistical barriers, paramount among them geographical distance, and lack of access to consistently available MH services. Other barriers are cultural norms in rural communities, including negative beliefs surrounding MH treatment, stigma against needing or seeking MH treatment, and stoicism, with rural veterans preferring to address MH and emotional problems within their own communities, families, and religious organizations. Motivational interviewing is an evidence-based approach to facilitating behavioral change, and multiple studies over decades have demonstrated MI’s effectiveness for MH treatment engagement among veterans. One pilot trial of 73 younger Iraq and Afghanistan veterans who screened positive for MH symptoms demonstrated that 4 brief sessions of telephone MI conducted by trained research staff resulted in 62% initiating MH treatment versus 26% assigned to receive 4 brief neutral telephone sessions . Of note, this trial was conducted in younger, urban veterans by research staff with backgrounds in psychology. However, none of these trials were conducted among rural veterans who might experience greater barriers to MH treatment engagement. In addition, ebb flow tray most prior trials have used MH clinicians to deliver MI. There is emerging evidence that peers who may have shared experiences and “speak the same language” as the populations they serve may encounter less resistance and be more effective in promoting positive change, including engagement in MH care, especially in rural populations. Here, we describe the results of a multisite pragmatic randomized controlled trial , “Motivational Coaching to Enhance Mental Health Engagement in Rural Veterans,” hereafter abbreviated as “COACH.” The trial tested a veteran peer-delivered telephone motivational coaching intervention for veterans receiving care atpredominantly rural VA community-based clinics in either Northern California or Louisiana who had screened positive for ≥1 MH symptoms but were not engaged in MH treatment. We hypothesized that veterans who received MI-consistent feedback about MH screen results and MH referrals plus several sessions of veteran peer delivered telephone motivational coaching would be more likely to engage in clinician-directed MH treatment than veterans who received MH screen results and a referral without motivational coaching . Secondarily, we hypothesized that veterans assigned to veteran peer-delivered telephone motivational coaching would experience improvements in MH symptoms, quality of life indicators, and self-care as a direct effect of peer coaching itself compared to those randomized to the control condition. Qualitative exit interviews of participants in the intervention arm were conducted to better understand trial results.VA administrative databases were used to identify veterans with the following criteria: had received primary care within 1 year of study enrollment at 1 of 8 participating VA community-based outpatient clinics: 4 facilities in Northern California and 4 in Louisiana ; and had screened positive on ≥ 1 VA MH screens or had received ≥ 1 MH diagnosis, but had never attended an MH visit , or had attended up to 2 MH visits , but without follow-up within 90 days of recruitment.

Veterans identified through VA administrative data were mailed a study information sheet and a postcard they could mail back to indicate interest in study participation. If participants indicated interest or if no postcard was received after 2 weeks, study staff attempted to contact veterans by phone. In addition, VA community-based outpatient clinic providers were encouraged to refer patients to the study and flyers were posted in their clinics. Veterans deemed eligible and interested on initial telephone screening underwent informed consent prior to enrollment. Participants were enrolled from October 29, 2015, to October 19, 2017, and the study concluded June 1, 2018. The study protocol was approved by the VA Central Institutional Review Board and the local Research and Development Committees at the participating VA enrollment sites.60-min baseline assessment by telephone to collect baseline data and verify trial eligibility. Information was collected on sociodemographics, VA service connection/disability status, and prior VA and non-VA mental health treatment experiences in the past 5 years and past 60 days. Psychometrically valid assessment instruments with published cut points were used to determine participants’ symptom status for 5 target MH disorders: posttraumatic stress disorder , depression , anxiety , panic disorder , and alcohol and illicit substance use . Additional instruments were used to assess: quality of life across 4 domains: physical health, psychological health, social relationships, and environment ; importance, confidence, and readiness for MH treatment; and logistical, stigma- and beliefs-related barriers to MH treatment . Results from the telephone baseline assessment were entered directly into a web-based data collection system and scored in real time to verify non-MH treatment-engaged participants who screened positive for ≥ 1 MH problems, thereby confirming trial eligibility. This was defined as: scoring in the “mild” range on at least 2 MH screening instruments ; or scoring in the “moderate” range on at least 1 MH screening; or scoring in the “mild” range for at least 1 substance and in the “mild” range on at least 1 MH screen.The study was a single-blind, 2-arm pragmatic effectiveness RCT comparing MI-styled veteran peer-delivered feedback on MH screen results and referrals plus 4 sessions of telephone motivation alcoaching versus veteran peer-delivered MH results and referrals without motivational coaching . The study was designed as a Hybrid Type 2 pragmatic implementation effectiveness study, in which the implementation of the trial intervention was tailored to meet the needs, resources, and preferences of stakeholders at each VA community-based clinic study site. Thus, prior to trial implementation, a formative evaluation was conducted at each of the 8 VA community-based clinic sites, beginning with qualitative interviews with study stakeholders—veterans and VA staff—to understand barriers and facilitators of MH treatment for veterans at the clinic and in the local communities. Subsequently, the study team convened lunchtime meetings with study stakeholders at each of the VA community-based clinics to review evidence for the motivational coaching intervention, provide feedback from the qualitative interviews, and to engage study stakeholders in decision making about flexible components of the trial. For instance, some clinic stakeholders preferred to be more involved with recruitment efforts than others. Also, in this formative stage, the study outcomes related to MH treatment engagement were broadened to reflect rural veterans’ preferences for self-care activities based on input from VA stakeholders at the 8 participating VA community-based outpatient clinic sites.

It is important to highlight that the network traffic in these systems is typically nonuniform

The ECP also helps the missions of other agencies like the National Institutes of Health , National Science Foundation , National Oceanic and Atmospheric Administration , and the National Aeronautics and Space Administration. Such large-scale systems require interconnections between thousands of computing nodes. Traditional networks offer fixed links where optical fibers connect electronic packet switches with high-speed point-to-point optical links. Standard topologies to interconnect computing nodes include 3D and 4D Torus and fat-trees. where the network architecture is hierarchical. At the bottom in the edge layer, hosts are connected to Top-of-rack switches. Spots in the network can be barely or heavily loaded, and throughput bottlenecks may occur. Hence, the necessity of reconfigurable networks for bandwidth steering arises, to allocate higher bandwidth resources in hotspots on demand. To enable these flexible networks, we combine traditional electronic packet switches with optical switching technologies. In that way, we get the benefits of both fabrics to develop a reconfigurable optical network. The topology can be dynamically modified with an optical switch. Finally, routing and forwarding is managed with flow updates, so we can orchestrate the traffic to go through the newly configured physical links. We do not use traditional routing protocols, but a Software Defined Networking control plane that allows more flexibility in the definition of the routing schemes and forwarding rules. In the following subsections we briefly introduce the related work and enabling technologies relevant to different modules of the test bed that was implemented in this research. Finally, we discuss the purpose and contribution of our investigation.All-optical switches, hydroponic flood table such as optical micro electro mechanical systems, MachZehnder switches, microresonator ring and wavelength routing are alternatives to electronic switches.

They offer lower power consumption, scalability, fast reconfiguration, low latency and cost savings with silicon photonics integration. However, optical switching technologies have not been commercially deployed in datacenters and HPC systems due to several challenges, including the lack of optical buffers, the scalability limitation posed by physical layer technology , and the design of a scalable control plane that can orchestrate fast reconfiguration operations at large scale to follow the bursty nature of the traffic. Therefore, it is necessary to investigate hybrid switching systems that combine the benefits of traditional electronic devices and optical technologies.Our test bed combines aMEMS optical switch and SDN-enabled electronic packet switches, as described later in Chapter 3.In the Software Defined Networking approach, the control plane is decoupled from the hardware. It leaves only the data plane in the chassis, while the controller is software-based and uses Application Programming Interfaces to send instructions to the hardware to handle network traffic. A centralized control plane is useful to manage complex networks. Google’s Software Defined Wide Area Network , B4, which connects their data centers globally, is an example of a successful deployment of a commercial Software Defined Network . B4 maximizes the average bandwidth, and gives complete management across all network. It also enables traffic engineering, which derives in other benefits. One is multi-path routing, that leverages resources based on application priority, and assigns bandwidth on demand. Google reports an improvement of 3× in link utilization efficiency compared to previous standard practices . On average, links run at 70% of their capacity in the long term.

In addition, Google adopted SDN in their data centers when they realized that traditional decentralized routing protocols were not the solution to challenges such as creating routes through a broad, fixed and multi-path network. Management in such systems is easier to achieve if the network is modeled as a single device with multiple ports instead of a collection of several individual switches running routing protocols. LIGHTNESS is one example of research project that explored and demonstrated the integration of SDN control plane, virtualization of network resources, and an all-optical dynamic data center network. With a modified version of OpenFlow, a customized controller and the abstraction of the Optical Packet Switch node, which was implemented with an FPGA, they achieved optical packet switching . Furthermore, by assigning priority to flows of different applications, Quality of Service can be guaranteed. Real-time monitoring is another feature that was implemented by collecting statistics from the network agents through OpenFlow . From these case studies we can conclude that SDN is the key to control and to use resources efficiently in complex networks. TCP/IP is the name commonly used to refer to the set of network protocols behind the internet. TCP stands for Transmission Control Protocol and Internet Protocol. This is a practical implementation of the theoretical reference model, OSI . Due to the complexity of computer networks, organizing the protocols in independent layers with specific purposes makes it easier to implement, provision and debug communication links all around the world. The OSI reference model has seven layers, while TCP/IP condenses all in fewer layers. So far we have introduced research projects in technologies for reconfigurable optical networks, with applications in data centers and High Performance Computing . Specifically in the physical layer. Now we will cover the impact of link reconfiguration in upper layers. We focus on transport layer, following the TCP congestion control mechanism and the reliable data transfer between hosts when there is an event in the optical paths in the middle. A retransmission timer is used to guarantee data delivery when the receiver does not confirm reception of packets. It is defined as Retransmission Timeout, RTO, in internet standards.

We discuss this timer in our results in Chapter 4. Network traffic in our testbed is generated with iPerf, a tool that can be configured with TCP or UDP. The first one is known for reliable communication among hosts, thus we choose that protocol in our experiments. Nevertheless, it was originally designed for WANs, where the data Round-Trip Time is in the order of hundreds of millisecond due to large geographic distances between nodes, but 2-3 orders of magnitude higher than RTT in datacenters. Such a large RTO in this context impacts in latency and throughput. Reducing the RTO might be a solution, but the challenge is that most systems do not have high resolution timers. Furthermore, varying the RTO helps to act fast against packet loss, but it yields to spurious retransmissions. Researchers have found that optical reconfigurations raise RTO events. RTT in datacenters is generally in the sub-millisecond scale, while optical switching can reach tens of milliseconds if using MEMS technologies. TCP waits for a certain time , ebb and flood table then it attempts to send data again. The default RTO varies across operating systems. It is set to 200 ms in Linux, 300ms in Windows . A new trend in transport protocols points towards programmable NICs and FPGAs, to leverage the optimized latency that state of the art distributed datacenter applications require. The High Precision Congestion Control and NanoTransport projects present transport protocols and congestion control schemes in dedicated programmable hardware. This topic is out of the scope of this thesis, and is left as future work to test novel transport protocol schemes in reconfigurable optical networks.An optical reconfiguration operation consists of the following steps: decide when to make the reconfiguration, select a new topology based on specific optimization goals, and finally migrate the traffic to the new path. Service halts arise amid topology migrations, in particular when a new light path is provisioned dynamically. That is, when the old link is removed and the new one is configured afterwards. To reduce the outage impact, which depends on the link setup time, a make-before-break approach is advised. If the optical channels are placed in the network prior to the reconfiguration, they will be ready to carry traffic instantly. However, this technique involves using additional resources, because more links must be operational simultaneously. Quality-of-Service and network performance in general are improved if bandwidth is reserved before the traffic transition, since the length of disturbance is minimized. Hitless reconfiguration in optical networks was defined in 1996 as the reconfiguration process where not even a single ATM cell is lost. ATM stands for Asynchronous Transfer Mode, a standard in telecommunications for data transfer between user-network or network-network nodes, prior to the wide adoption of IP based networks. Bit Error Rate and Forward Error Correction are useful metrics to monitor the quality of a link in an Optical Transport Network . Specific thresholds must be specified for minimizing or preventing packet loss. As long as these metrics are within the desired range, the link is considered optimal .

Research in hitless optical reconfiguration have demonstrated a switching of less than 1µs, without deteriorating the real-time BER, using fast tunable lasers. Other studies implemented a testbed as well, with commercial transceivers and a channel spacing of a minimum frequency step of 0.5GHz to keep BER in a desired range. By adding SDN elements to manage reconfiguration in an AWGR-based optical network via wavelength tuning, the total switching time reached only millisecond scale, and the packet loss was reduced by 50%. For the rest of this thesis, we consider hitless reconfiguration as the update in the topology that generates 0% packet loss, end-to-end. Reconfigurable optical networks have been studied in recent years, in both simulations and testbeds. On the experimental side, we find that SDN-controlled systems are practical to prevent packet loss and throughput drop due to light path updates. With SDN in hybrid networks, we can perform the reconfiguration in different steps: take the traffic from the ports to be updated, reconfigure the topology with the optical switch, synchronizing the transceivers in the new physical routes, and finally route the traffic through the new paths. In terms of reconfiguration latency, we find systems with delays of different orders of magnitude.ProjecTor is another testbed with a similar architecture, with a reconfiguration latency of 12µs. In the nanosecond level we find Sirius. These projects are mainly prototypes that integrate several blocks to build a reconfigurable optical network. Our testbed was built with commercial solutions such as an EdgeCore electronic packet switch, DWDM transceivers, a Polatis MEMS optical switch, along with Linux and a python-based SDN controller . If the reader is interested in the state of the art of optical technologies for datacenters and future trends, I recommend the paper ”Prospects and Challenges of Photonic Switching in Data Centers and Computing Systems”. Simulators are tools that researchers use to demonstrate models, algorithms, devices and other elements of networking and computing systems to improve their performance for large scale and high performance applications. To validate the simulation studies, it becomes essential to execute testbed experiments, which is the main focus of this thesis. We describe the testbed in terms of architecture, infrastructure and software tools. First, we will discuss the general design of the system, the purpose of each block and how they interact with others. Second, we will discuss how the system is implemented with servers, switches, wires, fibers, racks and any other physical device. Third, we will explain the software tools we used to orchestrate our experiments. We cover virtualization, network monitoring and traffic generators that we used in our investigation. In this chapter we start with the architecture of our testbed. Similar to Emulab, we connected physical and virtual hosts to different networks on top of a single infrastructure. The first is the management network, which helps to connect remotely to our testbed elements from anywhere. It is practical as it allows researchers from our team to handle experiments through the UC Davis VPN and an internet access point without being connected with a wire to the hosts nor restricted to UC Davis LAN . The second is the control network, which orchestrates our experiments and collect statistics from our computing hosts and network nodes. The control and application planes are encompassed here. The third is the experimental network data plane, a reconfigurable optical network composed of electronic and optical switches with 10 Gbps transceivers and optical fibers connecting our computing nodes and carrying data with rates up to 10 Gbps. Figure 2.1 illustrates the general architecture of our testbed. The data plane incorporates four electronic packet switches , an optical switch and optical fibers that interconnect four computing nodes .

Crime and criminals are subjective, spatially delineated and historically contingent categories

They are not, nor ever have been, pre-determined or natural classifications. As laws, land use regulations, as well as national and local power relations shift, so do the definitions of crimes and criminals . Thus, remote sensing cannot detect crime as it might detect a stand of a certain tree species: crimes, their perpetrators and their forms are defined by the dominant forces in society rather than spectral signatures or texture patterns. Because remotely sensed images are collected remotely , they lack detailed or nuanced definitions of crime drawn from the context of the landscapes they seek to analyze; they do not tell us why certain things happened or by whom, specifically. They leave understandings of causality and attribution to their interpreters. Despite the serious imbalances and problems that may arise from the remote sensing of crime, it continues apace, as we have seen from increasing discussions in the popular press and academic journals about the use of unmanned aircraft systems , increasing availability of micro-satellites and Google Earth images in the detection of crime . The continued and increasing use of remote sensing for these purposes brings us to the third limitation that we will mention here: the issue of validation. As remote sensing scholars, such as Jensen, Congalton and Foody note, validation is a critical part of any remote sensing exercise, and these scholars and others have laid forth strict protocols for validation exercises. Validating that crimes are actually occurring in the places that remote sensing algorithms say they are is not a simple task, however. On the ground, verification of potential illicit drug production, arms and drug smuggling or even illegal logging, flood table activities which are often protected by, or associated with, armed guards or agents, is often dangerous.

The lack of validation in the remote sensing of crime is troubling, however, because drastic military or police actions are often used to intervene where crimes are detected with lasting ecological, economic and social impacts: lives, security and livelihoods can be at stake, not to mention law enforcement credibility and resources. In short, classifying an action as a crime or a person as a criminal may have much higher costs than other classification mistakes. Thus, we must be doubly sure of what we classify as crime using remotely sensed images before we act. Further, such validation may add nuance and greater contextual understanding of the images used for analysis, which may allow for a more fair and balanced law enforcement response. Although all three of the above limitations are important to consider, this paper will take a methodological approach to engage with the issue of the validation of remotely sensed crime. We believe a focus on validation is critical, because as remotely sensed products become increasingly available to our desktops and smartphones, a rising trend of validation-free analysis is emerging. In these circumstances, products, like Google Earth, are used with the assumption that their images portray “the truth”, which should be acted upon. Despite the ease with which these data now flow to us, validation of our findings based on these images remains critical; competing sensors, processing methodologies and the familiarity of analysts with the limitations of the data they are using can present very real challenges to the ethical and accurate use of remote sensing in law enforcement and/or litigation. In this paper, we will first analyze how remote sensing technologies have been used to aid in the detection of crimes that might otherwise go undetected. As other authors have shown, “satellite imagery highlights the spatial footprint of human actors in very real and compelling ways” . Here, we review the literature that discusses how satellite and airborne technologies have been used in the active detection of felony cases of drug production, smuggling and extra-legal migrations.

We use the term “extra-legal” here, rather than “illegal,” in order to highlight the fact that though these acts are prohibited by USA or international law, the prohibition of these actions is often highly political and may not be deemed illegal in all cultures or by all groups. Forensic remote sensing has also been critical in the detection of environmental crimes, such as extra-legal mining and timber extraction, as well as in detecting oil spills and hazardous waste dumping. While the use of remote sensing in environmental forensics of this kind are important, many of the articles on these topics are embedded in larger land-clearance, deforestation and oceanographic literatures that deal with licit, illicit and accidental extraction or pollution, making the attribution of legality associated with the event difficult. Forensic remote sensing can also be used to identify the location of single and mass grave sites, but because most of these studies are experimental or historically oriented, we excluded them from our review. Remote sensing has also been used to find bodies, munitions and toxic waste that may have drifted based on water-current analysis. While our scope is narrower than that of forensic remote sensing, we do draw upon the advances in crime detection and validation that these studies have advanced in our analysis. Second, building on this literature review, we consider what kinds of validation protocols for the remote sensing of crime have been attempted and what the limitations to these protocols are, geographically, financially, as well as in terms of personnel and time. Third, we seek to generate a discussion on new and less traditional ways that crime may be sensed remotely or validated. While “first order” validation protocols, such as the collection of ground reference data, over flights and the use of higher spectral or spatial resolution images, are critical to assessing the accuracy of remotely sensed processes, they may not always be useful, possible or sufficient in the context of criminal investigations. Here, we propose going beyond the “first order” validation protocols that are standard in remote sensing to ensure accurate assessments of remotely sensed crime are occurring in ethical and contextually-situated ways. Here, we define the remote sensing of crime as the use of airborne and satellite remote imagery to detect crimes that have heretofore gone unreported or undetected. Lein describes forensic remote sensing as considering “the investigative use of image processing technology to support policy decisions regarding the environment and the regulation of human activities that interact with environmental process and amenities.” In this definition the term “forensic” refers to detailed investigation rather than a criminological one . As Lien points out, forensic remote sensing seeks to generate information pertaining to a specific event rather than “provide a broad thematic explanation”. As we note above, not all crimes are well suited to detection by remote sensing, however. Those crimes that have been most successfully detected using remote sensing technologies generally have the following three characteristics: first, they occur over relatively large geographic areas, so that their patterns may be easily detected, even with moderate or low spatial resolution imagery, like Landsat or MODIS ; second, the crimes or their evidence are generally visible for extended periods of time, allowing for their detection by satellites or airborne sensors over the length of a day, week or month; and third, they generally have characteristic spatial or spectral patterns that can be recognized from above using object-based analysis or spectral analysis.

This paper focuses on the utility of remote sensing in detecting crimes that are deemed a felony offense under U.S. federal law and are recognized as crimes internationally: arms, drug and human trafficking, 4×8 flood tray repeat extra-legal migration and drug production/possession . While there exists a plethora of academic papers that test methods that could theoretically be used for the remote sensing of crime—testing algorithms, detection techniques or spectral reflectances of illicit crops and smuggling trails—there are relatively few studies that document the use of remote sensing in the active reconnaissance of criminal activities. In this section, we review studies of active reconnaissance that exist in peer reviewed journals, as well as in gray literature in relationship to drug production, smuggling and extra-legal migrations. The characteristics of these activities fit those described above: they often occur in large geographic and temporal scales and may be uniquely identifiable from the surrounding landscape using aerial images. Because of these attributes, they represent the most common examples in papers regarding remote sensing used in the active detection of crimes. We reviewed 61 papers, reports from the United Nations Office on Drugs and Crime and master’s theses on these topics that were found through searches in the Google Scholar, Web of Science and Jstor search databases using a number of combined words and phrases . Some of these reports involved multiple case studies. Though, as Figure 1 shows, there were thousands of results that came from these combinations of search terms, very few of these results dealt with the active reconnaissance of crimes using remote sensing. We do acknowledge that there are probably many more reports and papers available on this topic in the law enforcement literature that are not available to the public. Government agencies, like Homeland Security, the Federal Bureau of Investigation and the Central Intelligence Agency, as well as international law enforcement agencies, like Interpol, may have extensive documentation on these topics that we were unable to access. Most prevalent in literature involving remote sensing of crime were studies on the detection of the cultivation of illicit substances. While the criminalization of each of these plants and their use is fraught with important political, cultural, economic and militaristic implications, an in-depth discussion of the reasoning behind these criminalizations and their ethics is beyond the purview of this article. Rather, we narrow our focus to the application of remote sensing products to actively detect “crime”, as it is construed by international or national governing powers. The use of remote sensing to detect the cultivation of illicit crops is a trend that has increased over time, perhaps because of the opening of the Landsat archives in 2008, and perhaps because of interest in opium growing in Afghanistan and South East Asia . We gathered the publicly available literature on the remote sensing of drug production in Afghanistan, Myanmar, Thailand, Laos, Bolivia, Colombia and Peru, countries targeted for drug production monitoring both by the UN’s Office of Drugs and Crime and academic researchers, due to these countries’ historically high exports of illicit substances . Using remote sensing to detect the growth of illicit drugs can be extremely helpful to those seeking to eradicate these plants, apprehend their cultivators, and limit the trade of the substances they produce. Unlike in-person surveys actually does conduct in some areas, which are labor intensive, time consuming, expensive, and potentially life threatening, remote sensing allows a small number of analysts to survey vast stretches of land to locate scattered sites of illicit crop production. Further, illicit crop detection methods that utilize remote sensing enable more frequent and complete surveys of the landscape than in-person surveys would. These techniques can focus the efforts of law enforcement officers, defoliant missions, and outreach programs. Remote sensing techniques may also allow governments and international groups to target drug production sites without putting their agents in harm’s way, or tipping off producers that some kind of action may be taken against them . Although the war on drugs began in the 1970s, the first publicly available papers we found on the active detection of illicit crop growth using remote sensing technologies were Sadler’s discussion of opium in Afghanistan and Chuinsiri and others’ detection of opium growth in Thailand. It was not until 1999 that groups like the UNODC’s Illicit Crop Monitoring Program began using remote sensing techniques to detect the growing of drug crops, particularly coca and opium poppies. The first UNODC cannabis survey was carried out in collaboration with the Afghan Ministry of Counter Narcotics and was not carried out until 2009. Like the criminalization of drug production, the criminalization of human movements across national borders either for migration or trade is also fraught with problematic social, political, economic, and militaristic issues and implications. Here, again, in-depth discussion of the reasoning behind these criminalizations and their ethics is beyond the purview of this article and we narrow our focus to the application of remote sensing products to actively detect “crime”, as it is construed by international or national governing powers.

Many arrestees who test positive for cannabis also test positive for alcohol or other drugs

These findings, while far from definitive, do not suggest a clear and direct link between cannabis use and crime. This makes it difficult for researchers to infer the extent to which a certain behaviors can be attributed to specific substances. Furthermore, because of the way that marijuana is metabolized by the human body, 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 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, 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 .

This is the dynamic explored by the present study. I conclude from the available literature that cannabis drying rack 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. Do medical cannabis dispensaries increase crime? It depends who you ask. Empirical evidence is scant and is almost entirely overshadowed by anecdotal reports and sensationalized hearsay. 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 CaliforniaPolice 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 through a geospatial 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, 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, vertical grow system 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. In a recent working paper for the California Center for Population Research at UCLA, Nancy Williams and colleagues present a routine activities approach for examining the link between MCDs and crime. They examined 95 census tracts in Sacramento and found that tracts containing dispensaries were not significantly associated with higher rates of crime when controlling for other neighborhood characteristics . This study borrows from their work in applying a routine activities approach to MCDs in San Francisco.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 below. 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. High residential turnover disrupts social relations and erodes collective efficacy. 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. In the original test of social disorganization theory by Sampson and Groves , low SES was found to be significantly associated with crime. The link between economic deprivation and crime may be more complex than the simplistic explanation that poor people have higher incentives to commit crime and suffer lower opportunity costs for doing so. For example, Sampson reports in an earlier work that low SES neighborhoods have higher levels of police supervision, independent of actual law violate behavior .

A prenylated product like CBGA can be converted into a variety of cannabinoids

Shoyoma et al published the chemical shifts of CBGVA in CD3OD, so by direct comparison of our NMR spectra to the published chemical shifts we conclude that we produced CBGVA. This is further supported by the work conducted by Bohlmann, which suggests that if the prenylation occurred at the C5 site, we would observe a proton with a chemical shift around 5.8 ppm, which we did not observe, Figure 2-15. We placed olivetolate in the active site of NphB in six different starting positions denoted as Olivetolate P1-6 in Table 2-2. We ran ROSETTA 5 times for each olivetolate position for a total of 30 designs. The mutations predicted in each design are listed in Table 2-2. For each olivetolate position we chose a consensus set of mutations to evaluate further: Consensus Group A through F . We then sought to evaluate the relative importance of each ROSSETTA suggested mutation. For each Consensus Group, we set the mutations back to WT residue, one at a time, and used ROSETTA to calculate the change in energy score . Those that caused the largest change in energy were deemed to be the most important mutants to include in the library for experimental testing. To model the olivetolic acid, we took the 4MX.sdf 3-D structure of olivetolate from the 5B09 crystal structure and added hydrogen atoms to the structure assuming pH 7 using Open Babel 2.3.1.39 A rotamer library was generated for olivetolic acid using the Bio Chemical Library molecule: Conformer Generator 3.5 using the PDB library.The olivetolic acid molecule was then manually placed into the co-crystal structure of NphB with GST and DHN with the DHN and crystallographic waters removed using pymol. The olivetolic acid was placed in 6 different positions in the active site with the plane of the olivetolate aromatic ring parallel to the GST alkyl tail and the desired prenylation site 3.7 angstroms away from the eventual carbocation mirroring the placement of DHN in the 1ZB6 crystal structure.

Residues 49, 162, 213, 224, 232, 233, 234, 271, 286, and 288 were allowed to be any amino acid during the Rosetta design with other sidechains held in a fixed position and the backbone fixed. The designed residues were in direct contact with the olivetolate and not in direct contact with GST. The reactions were incubated for 12 hours at room temperature, vertical grow systems then extracted 3 times with 100 µL of ethyl acetate. The organic extract was pooled for each reaction and the solvent was removed using a vacuum centrifuge. The samples were redissolved in 100 µL of methanol and subjected to HPLC analysis. The initial rate was plotted vs the concentration of substrate, and fit with the Michaelis-Menten equation to determine the kinetic parameters kcat and KM . Each Michaelis-Menten curve was performed in triplicate. The average and standard deviation of the kinetic parameters are reported. The time courses with olivetolate as the substrate were as follows: for WT, M1, M10 and M30 the time course was 3, 6, 9, and 12 minutes. For M25 the reactions were quenched at 1, 2, 4 and 8 minutes, and for M31 the reactions were quenched at 1, 2, 4 and 6 minutes. The conditions were altered slightly to characterize the constructs with divarinic acid as the substrate. For M31, the time course was 0.5, 1, 1.5 and 2 minutes. For M23, the time course was 5, 10, 15 and 20 minutes, and for WT NphB the time course was 8, 16, 24 and 32 minutes. The enzyme concentration for the mutants was ~27 µM, and the concentration of WT NphB was ~ 35 µM.Samples were dissolved in 200 µL of ethyl acetate. GC-MS measurements were carried out using an Agilent Model 7693 Autosampler, 7890B Gas Chromatograph, and 7250 Q-TOF Mass Selective Detector in the Electron Ionization mode. Sample injection was carried out in split mode with inlet temperature set to 280o C. Separation was carried out on an Agilent HP5-MS column with dimensions 30m x 250 µm x 0.25 µm. Ultra High Purity Grade He was used as carrier gas with the flow set to 1.1 mL/min in constant flow mode. The initial oven temperature was set to 120o C for 1 min followed by a 20o C/min ramp to a final temperature of 300o C which was maintained for 4 min. A 3.0 min solvent delay was used. EI energy was set to 15 eV.

The MSD was set to scan the 50 – 500 m/z range. Data collection and analysis were performed using Mass Hunter Acquisition and Qualitative Analysis software . Due to the increased temperature of the GC inlet, CBGA undergoes spontaneous decarboxylation as described by Radwan et al, resulting in an M+ ion at 316 m/z. The retention time corresponding to the 316 m/z ion for the CBGA standard was 10.48 minutes.A PyOx/PTA reaction was set up as detailed above. A 500 µL nonane overlay was added to the reaction in a 2 ml glass vial which was covered with 2 layers of breathable cell culture film. 2 18-gauge needles were inserted into a 15 mL falcon tube at the ~750 µL mark and the 3.5 mL mark. Luer locks to tubing connectors were connected to the needles and Viton tubing was connected to the other end of the luer lock. 18-gauge needles were connected to the other end of the tubing via a luer lock connector and inserted through the mesh covering so they were only touching the nonane layer and not the reaction. 2 mL of Tris buffer [pH 8.5] was added to the 15 mL conical tube, and 6 mL of nonane was added. The nonane was pumped through the system using a peristaltic pump such that the nonane flowed from the top of the reaction, through the buffered solution . The nonane pumped into the reservoir separated into the top layer of the 15 mL conical tube. The nonane from the top of the 15 mL conical tube was pumped into the top of the reaction vial . This essentially diluted the CBGA throughout the system driving the diffusion of CBGA into the nonane layer and out of the reaction. A gene block of CBDAS with the signaling peptide was ordered from IDT codon optimized for Pichia pastoris. The signal sequence was removed by PCR amplifying from the 28th residue of the protein sequence through the end of the protein, with overhangs compatible with the pPICZα vector. The PCR product was cloned into the pPICZα vector digested with EcoRI and XbaI using the Gibson cloning method. The product of the assembly reaction wastransformed into BL21 Gold cells a clone with the correct sequence isolated. The plasmid was digested with PmeI for 2 hours, and then purified using the Qiagen PCR purification protocol. The plasmid was transformed into Pichia pastoris X33 using electroporation. Immediately following electroporation, the cells were incubated in 1 mL of cold 1 M sorbitol and 1 mL of YPD media without shaking for 2 hours. The cells were plated on YPDS plates with 500 µg/mL of zeocin.

Colonies were screened using PCR for the presence of the CBDAS gene between the AOX1 promoter and terminator. For screening, pruning cannabis the colonies were re-suspended in 15 µL of sterile water and 5 µL of the resuspended colony was transferred into a PCR tube with 0.2% SDS. The samples were heated for 10 minutes at 99ºC, and then 1 µL was used as the template for PCR. Six colonies with positive colony PCR hits were screened for the expression of CBDAS. The six colonies were grown overnight at 30ºC in 25 mL of BMGY to obtain a saturated culture. The overnight cultures were used to inoculate a 25 mL culture in BMGY media and grown to an OD of ~2. The cells were harvested by centrifugation at 2,000 x g for 10 minutes. The cell pellet was re-suspended in 90 mL of BMMY media, and incubated at 30ºC for 5 days. Each day, 1 mL of the culture was removed for SDS-PAGE analysis, and 500 µL of methanol was added to the remaining culture. On day 3 the cultures were screened for CBDAS activity. The 1 mL culture samples were centrifuged to pellet the cells . 50 µL of the media was used in a subsequent activity assay, and the remainder of the media was stored at -80ºC in addition to the cell pellet. The assay conditions were as follows: 100 µL of 200 mM citrate buffer, 100 µM CBGA, 5 mM MgCl2, 5 mM KCl, 1 mM FAD and 50 µL of the expression media. in a final volume of 200 µL. The reactions were incubated overnight at room temperature and then extracted 3 times with 200 µL of ethyl acetate. The ethyl acetate extractions were pooled for each sample, and removed using a vacuum centrifuge. The samples were re-suspended in 200 µL of methanol and analyzed by HPLC. All clones produced active CBDAS. To convert the precursors CBGA and CBGVA into CBDA and CBGVA respectively, a secondary reaction was set up with cannabidiolic acid synthase . To produce CBDA, a PyOx/PTA enzymatic system was set up as detailed above to produce CBGA. After 24 hours 200 µL of the nonane overlay from the CBGA reaction was transferred to a CBDAS reaction vessel. In the aqueous layer: 50 mM Hepes [pH 7.0], 5 mM MgCl2, 5 mM KCl, 25 µM FAD, 0.1 mg/mL CBDAS concentrate. The reaction was incubated at 30ºC with gentle shaking. Reactions were quenched at 12, 24, 48, 72 and 96 hours. To produce CBDVA, HPLC purified CBGVA was converted to CBDVA using CBDAS. The final reaction volume was 200 µL, with 50 mM Hepes [pH 7.0], 5 mM MgCl2, 5 mM KCl, 25 µM FAD and 0.1 mg/mL of CBDAS concentrate. A 200 µL nonane overlay was added, and the reactions were incubated at 30 ºC with gentle shaking. The reactions were quenched at ~ 24, 48, 72 and 96 hours.Glucose is broken down to pyruvate through a modified glycolysis pathway that includes a purge valve system. The purge valve allows carbon flux to continue through the glycolysis pathway without building up excess NADPH. Pyruvate is converted to acetyl-CoA through the PDH bypass outlined in light blue. Acetyl-CoA is then converted into GPP via the mevalonate pathway . Finally, the GPP from the mevalonate pathway is used to prenylate aromaticpolyketide. Shown here is the prenylation of olivetolate to produce CBGA; however, olivetolate could be replaced with a wide range of aromatic substrates to generate various prenylated products. An example of the conversion of CBGA into CBD by the action of CBDAS and a spontaneous decarboxylation is shown.This brief review will cover potential benefits of cannabis in reducing persistent in- flammation and immune activation in virally suppressed people with HIV and the possible resulting clinical benefits. While no randomized clinical trials have been performed, both pre-clinical and clinical evidence supports these potential benefits. We discuss sources of inflammation in HIV, their clinical impact, the endocannabinoid system , effects of exogenous cannabinoids on the ECS and inflammation, particularly neuroinflammation, and potential treatment implications. This review attempts to weave together research threads from multiple areas: clinical, pre-clinical, in vivo and in vitro. The goal is to be integrative, not exhaustive. Overall, the observations reviewed here suggest a program of future basic and clinical research to explore the potential benefits of cannabinoids for the treatment of inflammation-related disorders in PWH. Additional work in this area is reviewed by Yadav-Samudrala and Fitting.The proportion of PWH who use cannabis is 2–3 times higher than in the general population < 10%, in part because many PWH use cannabis to manage symptoms such as nausea, sleep disorders, musculoskeletal and neuropathic pain, anxiety, and depression. There is, however, great heterogeneity in findings on therapeutic benefits of cannabis, likely due in part to extensive variation in the formulations being used. Components of cannabis, present in varying degrees depending on the formulation, include the principal psychoactive component,tetrahydrocannabinol , identified in the 1960s, cannabidiol , cannabinol , cannabigerol , cannabidivarin , and other compounds, such as terpenes. Each of these exerts unique pharmacological actions, with considerable evidence suggesting that the whole is greater than the sum of its parts , reflecting therapeutic synergies between all of the phytocannabinoids and phytoterpenoids.

Resveratrol is an aromatic polyketide first isolated from the skin of red grapes

Terpene synthases catalyze the cyclization of the hydrocarbon moiety of isoprenoids to yield cyclized hydrocarbons. While terpene synthases generally have one major product, they are fairly promiscuous and can produce several different terpenes with one enzyme. For example, the humulene synthase from Abies grandis species mainly produces humulene, but also produces 51 additional sesquiterpenes at lower levels. The benefit of producing 52 different compounds with one enzyme is to maximize the diversity of secondary metabolites made from one bio-synthetic pathway, or better yet one enzyme. Due to the myriad of beneficial properties of terpenes, a great deal of research has been dedicated to engineering microbial strains to produce terpenes. Limonene is a rather simple, well characterized monoterpene that is commonly used in the fragrance industry and as a food additive. While limonene has a relatively high natural abundance in the rind of citrus fruit, several groups have engineered E. coli to produce this molecule as proof of concept. Additionally, a derivative of limonene, perillyl alcohol, is reported to have anticancer properties, and a low natural abundance making it an interesting target for an engineered microbe. Alonso-Gutierrez et al engineered E. coli to produce limonene at 435 mg/L from glucose, and then introduced a cytochrome P450 to hydroxylate limonene to produce perillyl alcohol at 100 mg/L.However, this level of limonene production still falls short of the theoretical maximum, 3.2 g/L, cannabis dryer indicating the system is not an efficient producer of limonene. Willrodt et al improved on the E. coli production system by introducing different mevalonate pathway enzymes, and reached a titer of 2.7 g/L of limonene.

While the authors were not able to determine the limiting factor in their system, they identify high acetate levels in the high limonene producing strain. While the authors determine this to mean there was sufficient levels of acetyl-CoA, they do not discuss how a competing pathway, like phosphotransacetylase and acetate kinase, could limit the flux of acetyl-CoA into the desired mevalonate pathway. Engineering microbes to produce monoterpenes is further complicated due to the effects monoterpene toxicity. To address this issue both studies utilized an organic overlay to extract the secreted product. Amorphadiene is a sesquiterpene and a precursor to the essential anti-malarial drug artemisinin. The highest titer of amorphadiene was achieved by Westfall et al. They reached a titer of 40 g/L of amorphadiene in yeast by overexpressing enzymes in the mevalonate pathway and the amorphadiene synthase, and limiting competing pathways. In an attempt to produce artemisinic acid in an engineered microbe, the strain developed by Westfall et al was further engineered to express a cytochrome P450 to produce artemisinic acid. However, despite the high titers of amorphadiene, the artemisinic acid levels remained significantly lower at ~150 mg/L. Amyris improved the titer substantially to 25 g/L of artemisinic acid. The improvement in artemisinic acid was due to the discovery of an aldehyde dehydrogenase from A. annua that improved the conversion of artemisinic aldehyde into artemisinin. Additionally they increased the viability of the strains by introducing an organic overlay, isopropyl myristate, which helped solubilize the product.

While amorphadiene is a precursor in the biosynthesis of artemisinin, artemisinic acid is not. Therefore, Amyris designed a four step synthetic approach to convert artemisinic acid into artemisinin. The combination of synthetic and bio-based approaches is known as semi-synthesis, and is another approach for the production of natural products. This approach can reduce the difficulty of chemical synthesis, and lead to a more cost effective option. Amyris demonstrated this by chemically converting artemisinic acid derived from microbial fermentation into artemisinin in a 4 step chemical synthesis with an overall yield of 40%. This semi-synthetic process is currently being used by Sanofi to supplement the world’s supply of artemisinin. Taxadiene is a diterpene and the first intermediate in the biosynthesis of paclitaxel. Several groups have engineered microbes to produce taxadiene and one study produced taxadien-5a-ol, the second intermediate in the pathway. While taxadiene has been produced at moderate titers in E. coli , the production in other organisms, such as S. cerevisiae, B. subtilis and the fungi A. alternata TPF6 remains low . The E. coli system that generated 1 g/L taxadiene was also engineered to produce taxadien-5a-ol, but the titers of taxadiene remain significantly higher indicating inefficiencies with the hydroxylation of taxadiene. This is most likely because cytochrome P450s are challenging to express in E. coli. Biggs et al were able to improve hydroxylation of taxanes by optimizing for P450 expression, reductase partner interactions and modifications of the N-terminus of the P450.  While it may be possible to complete the paclitaxel biosynthetic pathway in a microbe, it would be extremely challenging. Therefore, plant cell culture is still the best route for paclitaxel production. While there are some success stories of engineering microbes to produce terpenes and terpene derived molecules , several challenges still remain. Monoterpenes are toxic to both E. coli and yeast at relatively low concentrations . While cell viability can be improved by using an organic solvent to extract the product, slow diffusion out of the cell can still have an impact. There are also issues with precursor availability. The data from Willrodt et al indicates that competing pathways reduce the availability of the precursor acetyl-CoA. 

Additional challenges, like functional enzyme expression create issues with the production of complex natural products like artemisinin and paclitaxel. While yeast and E. coli are relatively easy to engineer, they do not always possess the cellular machinery needed for the functional expression of necessary enzymes.Alkaloids are a broad group of natural products that are produced by plants, fungi and bacteria, they are loosely classified as molecules that include one or more nitrogen atoms. Some examples of alkaloids are caffeine , opiods and psilocybin . Due to the broad classification of alkaloids, their biosynthesis is rather diverse . For example, the molecules listed above are derived from different precursors, caffeine is derived from xanthosine, opioids are derived from tyrosine and is derived from tryptophan. Several alkaloids found in plants have been produced in engineered microbes. Although caffeine is naturally abundant, Jin et al engineered S. cerevisiae to produce the stimulant. The conversion of xanthosine to caffeine is four enzymatic steps requiring three enzymes, however the nucleosidase is naturally present in yeast, so they only introduced two genes into the strain, a caffeine synthase and a methyl transferase. The strain produced 0.38 mg/L of caffeine, when supplemented with xanthosine. The authors hypothesized the low titer could be due to low nucleosidase activity and screened several non-native nucleosidases, however this did not increase titers. Additionally, Jin et al demonstrate that substrate consumption is not correlated with caffeine production, and that no caffeine is produced if the culture is not supplemented with xanthosine. Because xanthosine is required for primary metabolism of yeast, it is likely that the added xanthosine is being diverted into primary metabolic pathways instead of caffeine biosynthesis, limiting the titers of caffeine. As mentioned previously, vertical farming systems many opioids are still isolated from their natural source. In attempt to find a better production method yeast was engineered to produce the opioid, hydrocodone. It required introducing over twenty genes into the yeast genome . The resulting strain produced 0.3 µg/L of hydrocodone. At this titer it would require nearly 17,000 L of yeast to produce one dose of hydrocodone. The low titer is likely due to the length and complexity of the biosynthetic pathway, but it is a proof of concept suggesting that long, complex exogenous pathways can be functional in yeast. The remaining challenge is identifying the bottlenecks and adjusting flux accordingly. Aspergillus nidulans was engineered to produce psilocybin, a psychotropic molecule under FDA investigation as a treatment for anxiety, depression and substance abuse. Because psilocybin is naturally produced by fungi, it is logical to use the fungal model organism A. nidulans to produce this molecule. The four step pathway, shown in Figure 1-4, was transformed into A. nidulans, which resulted in a final titer of 110 mg/L, or 1.5% of mycelium dry weight, similar to the amount naturally produced in mushrooms. However, besides using a fluorescence based assay to identify positive transformants, the authors did not make any additional changes to the fungi. Therefore, by engineering the fungi to limit competing pathways and direct flux into the desired pathway it is possible to reach higher titers. The microbial production of alkaloids has similar challenges to that of terpenes. It is a challenging to balance competing pathways with a target pathway, like for the production of caffeine. Xanthosine is required for primary metabolism, and so most of the added substrate is diverted into primary metabolism instead of caffeine production. A similar challenge is presented for opioids with tyrosine being an essential metabolite that is required for opioid biosynthesis as well. In addition, longer more complex pathways are generally extremely difficult to engineer into a heterologous host. First, over expressing twenty enzymes can create a metabolic burden, and it can be difficult to express the enzymes at appropriate levels. Additionally, the enzymes used in the study were sourced from mammals, plants, bacteria in addition to yeast enzymes, which means there could be issues with functional expression.

The opioid pathway also produces several non-native intermediates which could have an impact on cellular metabolism. Interestingly, the baseline production of psilocybin in Aspergillus nidulans was 110 mg/L, however it may be possible to reach significantly higher titers by engineering the organism further. Previous studies have indicated that altering central metabolism to increase precursor pools can have a dramatic improvement on overall titer. Polyketides are produced by all kingdoms of life, and are a rich source of medicinal compounds. In fact, several are FDA approved antibiotics, immunosupressants, anticancer and cholesterol reducing medications. The biosynthesis of polyketides is similar to fatty acid biosynthesis, where small extender units are added to a growing acyl chain; however the subsequent steps are less uniform than FA biosynthesis allowing for more diversity in the final polyketide product. While the chemistry for the biosynthesis of polyketides is highly conserved, the types of polyketide synthases involved are very different. There are three general types of PKS reviewed previously by Hertweck in 2009. While several bacteria have been engineered to increase natural production of FDA approved antibiotics, herein the focus will be on producing plant polyketides in microbial hosts. Stilbenoids and flavonoids are a classes of aromatic polyketides produced by plants, and they have an array of useful bio-activities. These molecules can further modified to yield prenylflavonoids and prenyl-stilbenoids , which has been shown to increase the potency of flavonoids and resveratrol. Due to the low natural abundance of flavonoids, stilbenoids and their prenyl derivatives, they are an interesting target for microbial engineering. The molecule is potent antioxidant cited to have neuroprotective, cardioprotective and anti-aging properties. The molecule is sold as a supplement, and is also used as an additive in food products and cosmetics. The market for resveratrol in 2017 was valued at $69.1 million based on a report published by Coherent Market Insights. Several groups have engineered microbes to produce this molecule . The most successful was Lim et al, reaching a titer of 2.3 g/L. They attribute the high titer to directing carbon flux into the malonyl-CoA precursor, and limiting pathways, like fatty acid biosynthesis that would compete with the resveratrol pathway. Naringenin is a flavonoid produced by an array of plants. It is a fairly potent estrogen mimic, and is sold as a supplement to ease the symptoms of menopause. In addition it is a potent antioxidant with potential antimicrobial and antiviral properties. There are numerous studies dedicated to engineering E. coli and S. cerevisiae to produce naringenin, however the best titer of 474 mg/L was reported by Xu et al in 2011. Unlike the number of other studies, Xu et al did more than simply transform the biosynthetic pathway for naringenin into E. coli. They sought to increase carbon flux into the pathway by increasing the precursor, malonylCoA. To do this they overexpressed key enzymes in the native glycolysis pathway to increase the available pool of acetyl-CoA. Then they introduced acetyl-CoA carboxylase from Photorhabdus luminescens to convert the acetyl-CoA into the precursor malonyl-CoA. Additionally, they downregulated genes that would direct carbon into the citric acid cycle. Although Xu et al were able to increase the pool of malonyl-CoA, they did not address the issue of native E. coli pathways that siphon off the available malonyl-CoA. This data along with data for resveratrol production would indicate that one of the limiting factors in the production of polyketides in E. coli is the availability of the precursor malonyl-CoA, and that increasing malonyl-CoA levels increases product titers. However, there is potential for other issues that may not be as clear. For example, it is possible that some of intermediates or the product of the target pathway could negatively impact cellular metabolism. 

Cannabis smoking may also lead to increased rates of pneumonia and upper respiratory infections

The NASEM, CDPHE, and WHO reports state there is substantial evidence of a statistical association between marijuana smoking and worse respiratory symptoms and more frequent chronic bronchitis episodes. These data were based primarily on a systematic review by Tetrault et al. from 14 studies that assessed the association between long-term cannabis smoking respiratory symptoms including chronic cough , increased sputum production , and wheezing . There is also evidence of a statistical association between the cessation of cannabis smoking and improvements in respiratory symptoms. On histology, this is associated with a reduction in ciliated cells and increase in mucus secretion from the larger number of mucus-secreting cells. Reported exposures to children less than age 10 have sharply increased in Colorado following recreational marijuana legalization. A retrospective cohort study of hospital admissions and regional poison control center cases between January 1, 2009–December 31, 2015 at a tertiary-care children’s hospital found that the mean rate of marijuana-related visits to the children’s hospital increased from 1.2 per 100,000 population in the two years prior to legalization to 2.3 per 100,000 after . The median age of exposure was 2.4 years. The majority were exposure to an infused edible product ; 65% were observed in the ED or UC; 21% were admitted to an inpatient ward; and 15% were admitted to the intensive care unit. Two of these children required respiratory support. The median length of stay for all patients was 11 hours, ebb and flow rolling benches and the median length of stay for admitted patients was 26 hours. Annual RPC pediatric marijuana cases increased more than five-fold from 2009 to 2015 . 

Colorado had an average increase in RPC cases of 34% per year while the remainder of the United States had an increase of 19% . In a follow-up study in October 2018, the same author found that despite multiple public health interventions in legislation after 2014 , the incidence of children’s hospital visits and RPC calls has continued to rise in Colorado with an observed doubling of children’s hospital visits in 2017 compared to 2016. Edibles are sold as cookies, candies, and sodas with advertising that appeals to children. Varying cultivation techniques and end-product alterations further complicate the understanding of the physiological effects of cannabis. Cannabis plants can be altered to achieve higher growth rates, changes in potency, and increased bud production. These techniques can include use of varying soil types, fertilizers, and pesticides that can result in physiological effects. These changes may also result in exposures to possible fungal agents such as powdery mildew and botrytis; budworm or mite infestations have been reported in the literature. Historically, there have been reports of bacterial contamination with salmonella, enterobacter, streptococcus, and klebsiella, as well as case reports of fungal spore contaminants, including mycotoxin‐ producing strains of aspergillus. There are three pathways through which cannabis may be contaminated with heavy metal substances. Firstly, cannabis is able to remove heavy metals from substrate soils and deposit these in its tissues by virtue of its bio-accumulative capacity. Secondly, cross‐contamination may occur during processing . Thirdly, post‐processing adulteration may occur, whereby metals may be added to the preparation to increase weight and thereby appreciate its street value. There are case reports of lead and arsenic poisoning from cannabis. Pesticides are also commonly used in cannabis cultivation. In a report from Washington State, laboratory analysis revealed that 84.6% of legalized cannabis products contained significant quantities of pesticides including insecticides, fungicides, miticides, and herbicides.

These comprised a wide array of different substances and encompassed proven carcinogens , endocrine disruptors, as well as a variety of developmental, reproductive, and neurological toxins. There are also changes in end-product concentrations through post-processing of the plant. These changes include creation of oils, waxes/shatter, and dabs. Oils are created by removing the hydrophobic components such as THC with a heated butane solvent. THC concentrations may reach up to 55.7%. Waxes and shatter are concentrated and solidified oil with THC concentration reaching up to 90% THC. Dabs are composed of heated wax and are inhaled off of an object such as a nail, which even further concentrates THC content over 90%. Preparation of these concentrated products has also led to fires and explosion injuries in amateur production attempts in garages, tool sheds, and vacant homes. In Colorado 29 patients with butane hash-oil burns were admitted to the University of Colorado Burn Center from 2008-2014. Zero cases presented prior to medical liberalization, 19 during medical liberalization , and 12 from January–June 2014 at the study’s conclusion. The median total body surface area burn size was 10% . Median length of hospital admission was 10 days. Six required intubation for airway protection while 19 required skin grafting. Marijuana shop employees not trained in medicine or pharmacology are giving medical advice that may be harmful to patients. A recent study in Colorado found that employees are giving medical advice 70% of the time to use cannabis for treatment of nausea and vomiting in pregnancy and few dispensaries encouraged discussion with a healthcare provider without prompting. The author has personally had patients bring in products recommended by dispensary workers with a recommended potency and frequency of use and report being advised to stop their usual medications and use the cannabis product instead. Cannabis dispensaries provide medical advice and offer treatment without medical training even when this may harm the patient.

There are potential therapeutic intervention targets for cannabinoids. In general, these therapeutic targets require a high ratio of cannabidiol compounds , and are from products that significantly differ from those found in commercial dispensaries. The NASEM report found substantial evidence that cannabis or cannabinoids are effective for the treatment of chronic pain in adults, as an antiemetic for chemotherapy-induced nausea and vomiting, and for improving patient-reported multiple sclerosis spasticity symptoms. They also found moderate evidence that cannabis or cannabinoids are effective for improving short-term sleep outcomes associated with obstructive sleep apnea, fibromyalgia, chronic pain, and multiple sclerosis. Studies have also demonstrated that cannabinoids may improve cardiovascular outcomes. Likely the most significant treatment implication has been in patients with refractory epilepsy, most commonly in patients with Dravet’s syndrome and Lennox-Gestault syndrome, but also in other patients. This has led to the U.S. Food and Drug Administration approving Epidiolex in June 2018 for the treatment of Dravet’s syndrome and Lennox-Gestault syndrome. Despite these potential medicinal uses, current Colorado legal distribution of cannabis products goes through an intermediary bud tender before making it to the patient which may not consistently promote therapeutic benefit; there is insufficient training of dispensary staff to serve this purpose.The potential positive health effects of cannabis rest on which of the multiple species and hybrids are studied and their specific chemical composition. One of the difficulties in determining the physiological effects of cannabis is that “marijuana,” or “cannabis,” can refer to multiple species of plants with widely varying chemical compounds and corresponding variable physiological effects. The cannabis genus includes multiple species, most commonly Cannabis sativa and Cannabis indica, and within those are hybrids specifically developed by growers to achieve a specific effect. For example, the commonly used term, hemp, refers to a variety of Cannabis sativa that is fast growing and can be spun into usable fiber for paper, textiles, clothing, bio-fuel, animal feed, and other industrial uses. Hemp has low concentrations of THC and higher concentrations of CBD. The differences in composition offer different potential treatment effects. For example, rolling grow benches the effect for pain control cited in the NASEM review was primarily found with nabiximols , a cannabis extract mouth spray that delivers a dose of 2.7 mg of THC and 2.5 mg of CBD. For comparison, a typical marijuana cigarette or joint contains 0.5 g of marijuana and THC content ranges from 12-23%; therefore, a typical joint contains 60-115 mg of THC, 20-40 times the medicinal dose. The NASEM cautioned that many of the cannabis products sold in state regulated markets bear little resemblance to those available for research at the federal level in the U.S. This is further complicated in that commonly sold cannabis products are often mislabeled for CBD and THC content. One study showed only 17% of dispensary products were accurately labeled. Scientific studies, particularly for treatment of pain, have been limited by a substantial bias, and results have varied. Some demonstrate improvement in pain with coinciding decreases in opiate abuse, while others show the opposite.

The conflict between federal and state laws on the medical use of cannabis products, the lack of consistency among state laws, and the availability of artisanal products in dispensaries, with high variability between composition of products, have caused significant confusion for researchers and limited the ability to fully and accurately research the true effects of commonly available dispensary cannabis products. This was not a systematic review of the literature but rather a summary of selected research including several large reviews from the NASEM, the WHO, and the CDPHE. There is undoubtedly much literature, some of it conflicting, not cited here. However, as other states and countries wrestle with decriminalization and legalization of cannabis for personal use and sale, it is crucial to report the Colorado experience as a cautionary tale. This review summarizes a large body of research for practicing emergency physicians who are increasingly confronted with questions and patients who use cannabis. Although the author practices in Colorado, the information is likely generalizable. This review clearly reflects the author’s biases, yet its composition was motivated by alarming experience in everyday practice. Discussions of cannabis’ effects are relevant not only to the healthcare system, but to legal, business, environmental, legislative, and other branches within a public health framework. This article does not address those other facets. Neither have numerous other physiological effects of cannabis been reviewed here. Many of the previous research studies have focused on cannabis with a much lower THC level limiting applicability to cannabis sold at dispensaries today. Finally, the words “marijuana” and “cannabis” were used interchangeably throughout the article. This was done to maintain the wording from the studies cited consistent with their original language. No difference should be implied with the alternating use of these terms. Cannabis legalization has led to significant health consequences, particularly to EDs and hospitals in Colorado. The most concerning include psychosis, suicide, and other substance abuse. There are deleterious effects on the brain and some of these may not be reversible with abstinence. Other significant health effects include increases in fatal motor vehicle collisions, adverse effects on cardiovascular and pulmonary systems, inadvertent pediatric exposures, cannabis contaminants exposing users to infectious agents, heavy metals, and pesticides, and hash-oil burn injuries due to preparation of concentrates. Finally, cannabis dispensary workers not trained in medicine are giving medical advice that could be harmful to patients. Cannabis research may offer opportunities for novel treatment of seizures, spasticity from multiple sclerosis, nausea and vomiting from chemotherapy, chronic pain, improvements in cardiovascular outcomes, and sleep disorders. However, progress has been difficult due to absent standardization of the chemical composition of cannabis products and limitations on research secondary to federal classification of cannabis. Given these factors and the Colorado experience, other states should carefully evaluate whether and how to decriminalize or legalize non-medical cannabis use. Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia. Some cannabinoids, the hallmark constituents of Cannabis, as well as analogues thereof have been investigated extensively for their potential medical applications. Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a variety of human ailments. However, greater study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis, low abundances of nearly all of the several dozens of known cannabinoids in planta, and their structural complexity, which limits bulk chemical synthesis. Here, we report the complete biosynthesis of the major cannabinoids cannabigerolic acid , Δ9 -tetrahydrocannabinolic acid , cannabidiolic acid , Δ9 -tetrahydrocannabivarinic acid , and cannabidivarinic acid in Saccharomyces cerevisiae from the simple sugar galactose. To accomplish this, we engineered the native mevalonate pathway to provide high flux of geranyl pyrophosphate and introduced a heterologous, multi-organism-derived hexanoyl-CoA biosynthetic pathway as well as the Cannabis genes encoding the enzymes involved in olivetolic acid biosynthesis, a previously undiscovered enzyme with geranylpyrophosphate:olivetolate geranyltransferase activity, and corresponding cannabinoid synthases. Furthermore, we established a biosynthetic approach, harnessing the promiscuity of several pathway genes, for the production of cannabinoid analogues.

Cannabis use may result in dependence and cessation may result in withdrawal symptoms

Suicides with marijuana toxicology by year and overall suicide by year data are displayed in Figure 5.Cannabis has been associated with adverse social outcomes which may impact EDs and patient health. The large cohort study of Swedish men drafted at age 18-20 and followed to age 40 showed increased risk of unemployment and need for welfare assistance in those using cannabis greater than 50 times . These results were repeated in a longitudinal birth cohort study in New Zealand to 25 years old, which found high levels of cannabis use correlated with statistical significance to poorer educational outcomes, lower income, greater welfare dependence and unemployment, and lower relationship and life satisfaction. This cohort was classified into six levels of cannabis use, and found that as cannabis use increased, the odds ratio of adverse outcome increased. Both of these studies adjusted for confounding factors including socioeconomic background of the family, family functioning and exposure to adversity, exposure to child sexual and physical abuse, childhood and adolescent adjustment, academic achievement in early adolescence, comorbid mental health disorders, and other substance use. A prospective cohort study from upstate New York found that, compared with cannabis nonusers or minimal users , chronic users and users who began use in early adulthood and then tapered off use into later adulthood, had a significantly higher likelihood of unemployment at mean age 43 , even after controlling for covariates. The NASEM review stated that there was a limited level of evidence of impaired academic achievement and education outcomes, cannabis grow systems increased rates of unemployment and/ or low income, and impaired social functioning or engagement in developmentally appropriate social roles. 

The report stated that although there was evidence to suggest these outcomes, it was difficult to document a direct link between cannabis use and these outcomes because other variables played a role. Social outcome data for cannabis users specifically in Colorado are currently unavailable and could be an area for further research.A number of review articles on cannabis have described adverse effects on brain imaging. These findings may help establish a mechanistic link between the epidemiological studies on the adverse effects of cannabis. Structural, functional, and chemical changes to the brain have been established. These include both the gray matter and white matter . Structural changes to the brain include reductions in the hippocampus and amygdala volumes in cannabis users. Several studies also identified reductions in volume of specific areas of the prefrontal cortex, as well as functional magnetic resonance imaging studies demonstrating reduced functional connectivity in the prefrontal networks responsible for executive function and the subcortical networks, which process habits and routines. Other fMRI studies show reduced connectivity in the fimbriae of the hippocampus and commissural fibers extending to the precuneus, and suggest that this disturbed brain connectivity in cannabis users may underlie cognitive impairment and vulnerability to psychosis, depression, and anxiety disorders. Multiple other areas of the brain have also been shown to demonstrate changes on fMRI studies in response to cannabis and include the orbitofrontal cortex, anterior cingulate cortex, striatum, amygdala, hippocampus, and cerebellum. In general, these changes on both structural and functional MRI studies corresponded with frequency of use and earlier age of onset of use. Changes to neurotransmitters in the brain have also been well described in systematic reviews and include disruptions in glutamate, dopamine, N-acetylaspartate, myo-inositol, choline, and γ-aminobutyric acid.

Taken together, these changes may underlie the clinical features being observed in observational and epidemiological studies demonstrating increases in psychosis, impulsivity, depression, anxiety, suicidality, decreases in cognition, IQ, and executive function, abnormalities in habits, routines, decision making capacity, and deficits in learning, memory, attention, and social interaction. Cannabis use has also been associated with abuse of other illicit substances. According to the NASEM report, there is a moderate level of evidence of a statistical association between cannabis use and the development of substance dependence and/or substance abuse disorder for alcohol, tobacco, and illicit drugs. Multiple cohort studies have demonstrated these results. Four separate discordant twin studies have found that the twin who used marijuana was more likely to use other substances even after controlling for environmental and genetic influences.53-56 Although some studies reported that medical cannabis has resulted in improvements in opiate-related deaths, Colorado has had an increase in poisoning and deaths from opiates and methamphetamines since 2010, with the highest in 2017. These rates have increased nationwide as well and the influence of cannabis in Colorado is difficult to discern. Nevertheless, the increase in overdose deaths in Colorado is alarming. These data are shown in Figure 6.25 Although animal studies do not consistently translate to human effects, rat studies can provide some mechanistic clues. After exposure to tetrahydrocannabinol , rats have an increased behavioral sensitization response to not only THC but also opiates and nicotine. Studies also demonstrate that these behavioral changes in rats correspond to neuronal activity changes in mesolimbic dopamine neurons in the ventral tegmental area and nucleus accumbens and that cross tolerance results with exposure to morphine, amphetamines, and cocaine. Repeat morphine self-administration has been shown to be significantly lower in CB1 knockout mice and opiate withdrawal symptoms significantly less when the knockout mice are administered naloxone. 

Dependence rates are reported at one in 10 among those who ever use cannabis, one in six among adolescent users, and one in three among daily users. Withdrawal symptoms may include anxiety, insomnia, appetite disturbance, and depression. These symptoms are sufficient to impair everyday functioning and are markedly attenuated by doses of an oral cannabis extract. Cannabinoid hyperemesis syndrome has been well described in the literature. The symptoms of CHS include significant nausea, violent vomiting, and abdominal pain in the setting of chronic cannabis use. Cardinal diagnostic characteristics include regular cannabis use, cyclic nausea and vomiting, and compulsive hot baths or showers with resolution of symptoms after cessation of cannabis use. CHS patients present similarly to cyclic vomiting syndrome patients with the exception that cannabis use is required to make the diagnosis. Following legalization, the prevalence of cyclic vomiting presentations to Denver Health and the University of Colorado Hospital increased 1.92-fold from 41 per 113,262 ED visits from a year prior to marijuana liberalization to 87 per 125,095 ED visits a year following marijuana liberalization . Patients with cyclic vomiting in the post-liberalization period were more likely to have marijuana use documented than patients in the pre-liberalization period . These patients often are evaluated with multiple imaging studies, lab work, endoscopies, and admissions to the hospital as well as antiemetic treatment. These studies are often non-diagnostic and treatment is often ineffective. This may also influence ED crowding. Traffic fatalities with blood or urine drug screens positive for cannabinoids have sharply risen across Colorado. Total fatal motor vehicle collisions in Colorado had been decreasing from a high of 677 in 2002 to a low of 407 in 2011 but then began increasing each year since then to 600 in 2017. Total MVCs mirror this trend. The NASEM review found substantial evidence of a statistical association between cannabis use and increased risk of MVCs. CDPHE found substantial evidence that recent marijuana use by a driver increases his or her risk of a MVC and that the higher the blood THC level, the higher the risk of MVC. The use of alcohol and marijuana together increases risk of impairment and MVC more than either substance alone. For less-than-weekly marijuana users, using marijuana containing 10 milligrams of THC is likely to impair the ability to safely drive, bike, or perform other safety-sensitive activities. A typical marijuana cigarette, or joint, contains 60-115 mg of THC. A systematic review of observational studies and meta analysis for acute cannabis consumption and MVC risk found that driving under the influence of cannabis was associated with a significantly increased risk of MVCs compared with unimpaired driving , ebb and flow tables especially for fatal collisions . However, a recent study of crash fatality rates after recreational marijuana legalization in Washington and Colorado found changes in motor vehicle crash fatality rates were not statistically different from those in similar states without recreational marijuana legalization. This was, however, only after further statistical regression analysis . Initial data demonstrated that after legalization, motor vehicle crash fatality rates increased by a mean of +0.1 fatalities per billion vehicle miles traveled in Washington and Colorado, and decreased by a mean of -0.5 fatalities per billion vehicle miles traveled in the control states each year. The effect of cannabinoids on the cardiovascular system is complex and an area of ongoing research. Of concern to practicing emergency physicians is ST-segment elevation myocardial infarctions and acute stroke presentations with a close temporal relationship with cannabis use, which have been documented in multiple case reports in otherwise young, healthy, male patients. The NASEM summary found there was a limited level of evidence of a statistical association between acute cannabis use and triggering an acute myocardial infarction , ischemic stroke, or subarachnoid hemorrhage. The WHO review states: “There is evidence that cannabis use can trigger coronary events. Recent case reports and case series suggest that cannabis smoking may increase cardiovascular disease risk in younger cannabis smokers who are otherwise at relatively low risk.” CDPHE found moderate evidence that marijuana use increases risk of ischemic stroke in individuals younger than 55 years of age and limited evidence that acute marijuana use increases risk of myocardial infarction. The main case crossover study cited for the AMI findings demonstrated that the risk for AMI associated with cannabis use during the hour preceding symptoms of AMI was elevated 4.8 times over baseline .

This risk was substantially reduced following that hour. A review of nationwide inpatient sample data from 2010 to 2014 demonstrated a 32% increase in inpatient admissions for primary diagnosis of myocardial infarction and secondary diagnosis of cannabis use disorder . The overall mean age of patients was 41 years old. These patients also had longer lengths of stay, higher hospitalization costs, and higher levels of morbidity due to AMI following hospitalization than non-cannabis users. In a study reviewing secondhand marijuana smoke exposure, the authors found that one minute of exposure substantially impaired endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco secondhand smoke. The pathophysiological basis of these events is not fully understood and a full discussion is beyond the scope of this review. In short summary, it may encompass a complex interaction between exogenous cannabinoids and the endocannabinoid system, autonomic nervous system, oxidative stress, direct cellular effects on the endothelium, and pro-coagulant effects. Exposure to THC causes activation of the sympathetic nervous system and inhibition of the parasympathetic nervous system. These effects include elevated heart rate, serum norepinephrine levels, elevated supine blood pressure, and increases in left ventricular systolic function. Smoking results in decreasing oxygen delivery to the heart and other vital organs and may be further compromised by increasing carboxyhemoglobin levels. The impaired myocardial oxygen demand-to-supply ratio following cannabis smoking has been shown to reduce the time to onset of symptoms during exercise in patients with stable angina. Direct effects of cannabis on blood vessels are complex due to the differing compounds in cannabis and the functional properties of the blood vessels examined. Studies are inconsistent regarding the effects on vasoconstriction and dilation. Cannabis has been consistently shown to produce vasodilation with resultant orthostatic hypotension, but it has also been implicated in vasoconstrictive arteritis mechanisms. A large review article suggested that there are three phases in cardiovascular parameters affected by the endocannabinoid system and that different chemical constituents of the cannabis plant have varying effects at different target organs, which may account for the differences. Transient vasospasm and reduction in cerebral blood flow are well described and may underlie changes in coronary, cerebral, and peripheral arterial systems leading to end organ ischemia. Myocardial blood flow has been shown to correlate inversely with circulating plasma levels of endocannabinoids. Cannabis has also been shown to be a potent source of cellular oxidative stress through formation of reactive oxygen species, and this may contribute to endothelial dysfunction and promote regional arterial vasospasm. THC has also recently shown a dose-dependent procoagulant effect. This ex vivo observation has been supported by reports of thrombotic coronary artery occlusion in young individuals without underlying atherosclerosis. There are also cannabinoid receptors on the surface of platelets and THC has been shown to increase the surface expression of glycoprotein IIb–IIIa and P selectin in a concentration-dependent manner resulting in platelet activation. Figure 7 summarizes these effects.Marijuana smoking leads to adverse pulmonary outcomes.

Gang violence usually arises out of the desire to control a particular market area

The route of administration also affects motivation. As discussed earlier, edible forms of cannabis typically tend to be much stronger and last much longer than smokable forms . Many edible users experience extreme body and mental highs that leads to extreme lethargy. High-C, after I asked him why she smoked so much instead of just eating an edible that would last much longer told me that edibles were too strong and that he would be completely out of commission if he consumed cannabis too often. On the exact opposite spectrum, other users experience a jolt of energy when smoking cannabis. These users frequently use cannabis sativa. In a study conducted by Carlini and Kramer, rats performed better on maze trials after being injected with cannabis sativa. Depending on the type of strain and strength of the strain, sativa can be either mildly or extremely stimulating. Dorian took me on hikes with him. I never would have thought about using cannabis and exercising before his suggestion. It always seemed antithetical to the goal and practicality of exercise. After seeing Dorian smoke, I noticed an upbeat mentality and a somewhat jittery disposition. I am used to seeing users smoke, taking 30 or 40 minutes to smoke, and then getting so tired after smoking that they do not want to do anything. Dorian on the other hand, commercial racks suggested that this strain of cannabis made him want to get outside and gave him an extreme amount of energy. He told me about a website/podcast called the StonedHiker.com. This website discusses different forms of cannabis strains that are mentally stimulating and are useful for exercise.

Sativa and hiking is particularly effective, according to Dorian, because it stimulates the mind and body while allowing for an upbeat, unique and pleasurable outlook on the surrounding landscape. Dorian was not the only user that uses cannabis sativa for stimulation. Natty told me about a patient in his early 40s who used cannabis as a way to deal with back pain while working. He previously used cannabis at home after work, but he needed pain relief while at work but I couldn’t deal with the draining effects of opiates or most cannabis. Sativa was a godsend when he found it. It kept his mood and energy elevated the entire day. Unfortunately, there is no way to completely predict the effect of a particular cannabis strain, and many users find that sativa and indica are not mutually exclusive and the effects are not as simplistic as one would hope. Cannabis growth is still an unregulated industry in the U.S. and the quality and potency of cannabis is inconsistent at best. Moreover, the prohibition of cannabis has produced a system where scientific study of cannabis is still underdeveloped. One user, a 25-year-old female patient Dorian told me about had to take Xanax mixed with indica at night sometimes because the indica was too stimulating for her and she would stay up until 4am some nights after smoking stimulating indica. Likewise, many sativa users claim they need to be careful and test their sativa because of the risk that it may put them to sleep, or make them drowsy when they have something to do during the day. Nico Escondido , a High Times journalist suggests that our common understandings of the distinction between Sativas and Indicas are wrong. He suggest that terpenoids, which are organic chemical compounds produced by plants, may be responsible for the variations in effects from onestrain to another. Terpenes such as Myrcene are found in strains of cannabis that produce the stoned “couch lock” effect. Myrcene is also present in hops and is often credited with the sedated feeling that comes from drinking hoppy beers.

Other factors such as setting can affect motivation and user experience in general. Some people use cannabis during parties to calm social anxiety, others use cannabis to provide a jolt of energy when partying, while others like to sit and watch TV and go to sleep while under the influence. The effect of cannabis is not always what the user expects or hopes for sometimes, but experienced users know how to alter their consumption to fit their individual needs. Thus, cannabis is used in a variety of settings for a variety of reasons, and the expectations and settings are many times just as relevant as the cannabis itself. Back to the original question, is the anti-motivation syndrome real? The answer is not a simple yes or no. It is certainly the case that cannabis has the ability to affect a user’s motivation to succeed at work, take care of themselves and thrive. However, the negative perception of such an act is more indicative of a workaholic, consumerist, conformist and irrationally rational bureaucratic society than an indication about anything negative about the cannabis plant itself. Yes, cannabis can lead to less motivation to work and make money, but since when did work and money become the ultimate goal? This is perhaps most indicative in my opinion of the anti-cannabis camp. The uncritical acceptance of social conformity to the logics of capitalism, consumerism, materialism and work blinds individuals to the reality of cannabis as a unique plant that has the ability to change one’s perspective on the world in contradiction to the logic of a workaholic capitalist model. Thus, cannabis opponents typically point to the dangers of cannabis to society, such as demotivation without critically examining the direction society is going. This is characteristic of the conservative ethnocentric views of the world that the way things are is the way things should be. Cannabis has the ability to change minds and this in my opinion is the real threat that conservatives, politicians, and capitalist fear that people will not blindly follow the logic of the system set up to exploit and oppress them. Furthermore, it must also be noted that cannabis can have the exact opposite effect of anti-motivation.

Many users have told me that cannabis, and particular cannabis sativa, has a stimulating effect on par with coffee and tea. Likewise, many users state that cannabis increases their motivation to succeed at work, and leads to a type of near paranoia about one’s life and ones direction in life. Cannabis may occasionally lead to lack of work, but it also leads to less crime and less violence. Researchers found that for couples, marijuana use is inversely related to intimate partner violence . Similarly, researchers studying the effect of medical marijuana laws found that crime was not exacerbated by reforming medical marijuana and pointed to the fact that medical marijuana laws may be correlated with a reduction in homicide and assault rates . Goldstein found that, early studies that sought to attribute violent behavior to the use of opiates and marijuana have been largely discredited. Indeed, cannabis has been historically recognized as a peaceful substance as Indian’s refer to it as “Sattvik Nasha” translated as “the peaceful intoxicant” . Furthermore, Goldstein suggest some drug may have reverse psychopharmacological effect and may ameliorate violent tendencies . In my own study, I cannot think of a single instance in which I saw any act of violence out of the group or their associates and customers. In fact, my interviews with TBC and Natty suggest that cannabis was used to control violent impulses. TBC explained, “I’m kinda an asshole without weed. I would have fought these guys already if it wasn’t for weed.” In a similar vein, Natty confided that he did not like to drink with High-C because he was a violent drunk. Smoking helped them to maintain group interaction without conflict. However, in TBC’s case, it was never truly clear if cannabis mellowed him out, or if the addiction he developed from cannabis made him agitated and restless when not smoking. Although they participate in a semi-illegal activity, greenhouse rolling benches violence is relatively nonexistent, but always possible in their lives. What is particularly striking is the relative banality of the Kings’ behaviors and lives. When interviewing the Kings I was expecting to hear a bottom to top Scarface type story. What I got was a story of stoner hippies that seem eccentric yet ordinary in practically every way. In fact, other than the fact that cannabis and other drugs are illegal, and the occasional driving under the influence, I cannot think of a single criminal act these individuals participated in while the study was ongoing. The main proponents of “problem-prone behavior theory,” Jessor and Jessor , indicate that drug users, in comparison with those that do not partake in drug use, tend to be rebellious, hold unconventional attitudes, and are much more willing to take risks. Although these personality characteristics can frequently manifest themselves as artistic and creative in nature, Jessor and Jessor contend that these characteristics, more often than not, manifest themselves in ways that become problematic for both the individual and society. Examples of this could be deviant sexual behavior, underachievement in school and the likelihood of delinquent and criminal behavior. Jessor and Jessor explain the drug user’s personality as, “concerned with personal autonomy, a lack of interest in the goals of conventional society, and a more tolerant view of transgression” . As Jessor and Jessor explain marijuana use, “the differences between users and non-users might be termed conventionality unconventionality” .

Consistent with this theory, the group I seek to studied fit the mold of a counterculture in that they reject the norms of mainstream society and believe they are actively undermining “the system” through the sale and use of pot. Yet Jessor and Jessor consider behavior such as deviant sexual practices and underachievement in school or at the job injurious to society. This view is emblematic of the extremely conservative and conformist nature of most criminological theories. In contrast, I argue that what are termed by Jessor and Jessor as problematic behaviors such as deviant sexual practices and underachievement in school or jobs are themselves, a form of social expression. Deviant sexual practices are more of a cultural prescription that any inherent moral right or wrong. Likewise, schooling, in particular K-12 is in my opinion, more of a mechanism designed to promote conformity, obedience and docility to the capitalist system than it is a mechanism to enlighten minds and engender creative expression. Moreover, the Eurocentric curriculum does as much to reproduce race class and gender inequality than it does to change the structure.Another theory relevant to my dissertation is Robert Merton’s anomie theory. Without drawing out the various dimensions of Merton’s anomie theory, the two elements that have been considered particularly useful for an understanding of substance use are, “retreatism” and “innovation.” Cloward and Ohlin utilize retreatism when explaining drug addicts. From Cloward and Ohlin’s standpoint, the drug addict represents the double failure in Merton’s taxonomies. The drug addict failed to achieve the American dream through both legitimate and illegal means, and consequently, has retreated into a life of resignation and addiction. The other aspect of Merton’s theory, innovation, appears to at least partially explain the decision to sell, produce, or transport drugs. The ability to cut different forms of drugs, disguise the transportation of drugs, and sell without getting caught is certainly an innovative process. William Julius Wilson , in When Work Disappears, agrees with this line of reasoning. He argues that high levels of drug selling activity within poor inner-city neighborhood is related to a lack of social organization within those areas. Social disorganization theory posits that as neighborhoods loose resources and the positive social organizations and role models the society becomes disorganized. As neighborhoods become disorganized, the traditional mechanisms of social control, schools, families, police lose their effectiveness in maintaining social order. In addition to the lack of resources to maintain social cohesion in the community, a profound loss of trust in traditional mechanisms of social control arises and a breakdown occurs. This was documented in Anderson’s The Code of the Street, where a violent street culture arose to govern interpersonal communication on the streets of Philadelphia. High rates of joblessness and closed economic opportunities due to racism feed drug trafficking crime and other types of gang violence. Attempts to lock up drug dealers usually fail to stem the violence as the structure that gave rise to the problem remains in tact. Dohan’s study of a Mexican barrio also illustrates how many individuals cut out of the formal economy, view drug dealing as a path towards upward mobility. Particularly in the barrio of Chávez drug dealing, stripping cars and peddling stolen merchandise was common.

Every member of the group brought a bag of their best weed to share with the group

Prior to these new laws, finding high quality marijuana was difficult. Now, with store front dispensaries with delivery services, high quality potent cannabis is available with the THC content listed on the bag. Moreover, as was discussed earlier, new and stronger routes of administration are being developed daily. Even the most fanatical drug dealer would never dream of operating a marijuana shop the way the Kings did prior to the establishment to the medical marijuana laws. A modern cannabis dispensary, as was outlined in this chapter, is far beyond anything on the illegal market today, and far beyond what drug dealers sold prior to these changes. Recent shifts in cannabis laws have led to an increase in delivery services and a decrease in dispensaries. While medical marijuana is legal in the state of CA, it is illegal federally and the DEA has consistently targeted large-scale dispensaries for raids. Cease and-desist letters has led to many dispensaries closing shop one place and opening up under another name another place; others have given up on storefronts all together and switched over to strictly delivery services. Delivery services are much more dangerous than dispensaries and many female bud tenders consider it to be a dangerous a line of work. Delivery services are dangerous because of the lack of security guards, security precautions and the inability to control the environment. The Kings told me many stories of delivery drivers being robbed for their cannabis.The Kings established a functional, vertical grow rack competent growing operation that led to a functional, safe and profitable medical marijuana dispensary.

Unlike common perceptions of drug users and sellers as indolent potheads, crazy meth addicts’ urban gangbangers, my researcher has shown that cannabis users and sellers are normal in practically every way. During my ethnographic observations with the Kings, I did not see any shootouts, never saw instances of white slavery,14 and never saw a stickup kid attempt a jacking, I never even saw the police. Unlike the images perpetuated in the media of gang violence and drug fueled beefs , this market was relatively subdued plain and quite normal. Instead of black and Latino gang members shooting at each other over a bad drug deal, there were pasty white people buying cannabis in sanitary shop from a cordial, happy and inviting bud tender. The overemphasis on drug markets that reside in broken down inner-cities that lack social control and police trust has led to a mental blinder on the rampant drug use present within upper-middle class white communities. Moreover, this type of narrow research by criminologist has furthermore led to a pathologizing of the communities within which these studies take place. In a type of voyeuristic gaze, white Americans love stories of street violence in communities of color and seek to attribute them to drugs while dismissing the real social structural and economic barriers that give rise to this type of violence. Truly, what this chapter shows is that drug markets are neither inherently violent, dangerous, nor pathological, especially when they are legal, taxed and regulated.Occasionally their girlfriends would attend the meetings and smoke along, other times they would just hangout and not partake of the rituals. Having known their girlfriends quite well I found it surprising that they never brought their kids along. All of the members seemed to believe the experience gained from marijuana is sacred knowledge for which children are not ready.

It was never clear when they believed the appropriate age to start smoking, as they themselves started at a young age. But what is clear, is that they take various steps to keep their children away from Ganj until they reach the appropriate age. Friends, acquaintances, and old smoking buddies would frequently be called to these sessions. They would tickle in slowly; however, the four members were usually present. There was a set series of practices that were strictly adhered to and deviations were sanctioned. The sessions always began after 10pm. By that time, their children were in bed, the collective was closed and everybody could meet. Although some would consider it nothing more than a smoke out session, the group took it seriously and used it as a time to discuss business and other important matters. The first time I was invited to a board meeting, I showed up to Dorian’s house at 10pm on the dot. Dorian answered the door and said, “You’re early.” I told him, “You said 10pm.” He replied, “We’re stoners, everybody is gonna be late. Let’s chill.” He explained that he recreated the holy drink Soma. I did not know what he meant, or what he was talking about so he told me to wait. He explained to me that it is like a chai tea milk cannabis infused drink. As stated earlier, the Kings were vegetarians and were strong raw foodist. He told me he recreated the famous drink Soma from the Rig Veda. He called it Holy Soma and used it as a way to keep the smoking high going for long periods of time. He stated, “It also helps with cotton mouth.” Cottonmouth is a common side effect of cannabis consumption. The ingredient list he used was raw milk, raw honey, cinnamon stick, cannabis and peppermint. He put the cannabis in a pot of milk and boiled it for 30 minutes. The cannabinoids found in the plant are fat-soluble so when one wishes to make a liquid drink, they must decarboxalate the drink in a fat substance. Milk fit this bill. He told me holy soma is frequently consumed when they smoke together. He said it would be sacrilege to drink Soma without the other group members present. The living room was cut off from the kitchen with hanging beads. His music was blaring form the speakers and his living room was decked out in black light Bob Marley and Shiva posters and beanbag chairs. The self-produced music was an infusion of reggae and futuristic beats.

There were no words in the song, just a trippy rhythm that was meant to be heard while high. However, as I entered the most noticeable thing was the centerpiece of the entire room, The Shiva. The Shiva, as the group calls it, is a five-foot green glass on glass bong with an ash catcher, arm percolator and down stem15. The Shiva was all green except red and gold ribs every foot marking the bongs height. Dorian told me his friend made it for him as a gift. They originally had it at the dispensary as a decorative piece but moved it out of fear a patient might break it. I asked him why they called it the Shiva and he told me because it is the “Destroyer of Worlds.” In the Hindu tradition, Shiva is a God that is responsible for the destruction of the world. The Kings play off this metaphor by claiming the bong, combined with cannabis destroys and transforms their conception of the world. In the Hindu tradition, destruction opens the path for a new creation of the universe. Moreover, many Sadhus believe a chilam is a representation of Shiva himself. The bowl piece is Shiva’s head the stem is his torso and limbs. Natty was the first to show up. TBC and High-C showed up shortly after together.In addition to discussing cannabis and its revelatory properties, hydroponic shelf system the Kings would occasionally use the meetings as corporate board meetings. They discussed their own business, legalization, and general market dynamics and trends. Monthly meetings were held by the Kings to discuss various issues related to the operation of the dispensary. The Kings, Lucy and another recommending physician who was an early investor with the Kings sit in on the meetings. They physician would always skype into the meeting, he never attended in person. The meetings typically proceed with Natty giving a report on important issues relevant to the operation of the dispensary. New types of sample buds and other types of products that could be sold at the collective, changes in ordinances that effect the dispensary and occasionally employee compensation was brought up in the executive report. Natty would frequently distribute the various forms of sample provided by vendors to the rest of the Kings to try. It may be the first and only corporate board meeting where the drugs were openly passed around as samples and used. The board would vote on whether or not the dispensary would carry the product based on the strength and potency of the product. However, the Kings were willing to give any product a shot to see how it would sell before they dismissed it. Different shelf heights let patients know about differences in the potency so potency, or lack thereof, was not a deal breaker. Lucy would give the financial report on the dispensary. Everybody had access to the finances of the collective because of the MMJmenu system the Kings employed. However, the expenses of the dispensary frequently went beyond the accounting of product. Some of these other expenses included security for the dispensary, banking needs, employee , rent, electricity and other incidentals.As discussed prior, Dorian, Lucy and Natty and a handful of volunteer bud tenders are primarily left to run the dispensary.

However, the other Kings and other investors not named and unbeknownst to me invested in the collective and enjoy periodic updates on the functioning of the dispensary. As loosely illustrated in the previous chapter, cash is the only source of currency accepted at cannabis dispensaries. As a result of this, the money collected at the end of each day must be handled by a private security guard and deposited to a bank from which it is dispersed to the Kings and investors. A video monitor feed of the dispensary is accessible by all of the Kings and investors through an internet connection and the dispensaries accounting is kept and tracked on the MMJmenu website which is also accessible by the investor group. One interesting feature about the operation of the dispensary is that despite the high markup on the price of cannabis, the dispensary does not make a huge profit. After factoring in the cost of running the collective such as rent, advertising, employee compensation, security and the like, the dispensary hardly makes a profit. As Lucy explained to me, “The money has to go to a lot of places before we can turn a profit. The dispensary always makes a profit, but when considering all the competition and the cost of running a legal dispensary, it is not the green rush I think people may think it is.” It is intriguing that the Kings engaged in this risky business when their profit margins are so small. However, the Kings motivations are not as much financial as social and spiritual as will be explained below. Notwithstanding, the investors main objective was to make money and the keep tabs on the operation of the dispensary.Each member grew their own side stash at their house. And although they ran a grow-op together, they used the grow-op for the collective, and they smoked their own personal stashes during smoking sessions. Each member of the group is expected to chip in equally, similar to an offering. They all gathered around the Shiva and one by one took their sack out and placed it in the community smoking pot. It was expected that members bring their best weed and share their weed freely. Reciprocation was a vital part of the session and signs of stinginess were heavily frowned upon. It was also crucial that the Kings brought their best product as individual members were judged on the strength of their grow. Much of the interaction was symbolic and did not serve a purpose other than the meaning the group members created for themselves. But the symbolic purpose was important to the group. And any indication that a member brought swag weed to the session, or was stingy with his weed, would cause a demotion in one’s status and prestige within the group. Having weak weed would indicate the member did not know how to grow or no longer prided himself on the grow, and being stingy would be a hint that the member could not yield the same level of bud as other members. Smoking status is an important component of the Kings identity, and thus, the Kings employ various mechanisms to maintain that status.