Trial interventionists were 2 veterans of the armed forces with some prior exposure to counseling, hereafter referred to as “veteran peers.” Of note, in this study, veteran peers were different from VA-employed Veteran Peer Specialists, who are also considered peers, not only because of their prior military service, but also because they are in MH recovery themselves. Veteran peers for this study were trained by psychologists at their respective study sites to use MI techniques, such as open-ended questions, affirmations, reflections, and summary statements, as well as key MI principles, such as expressing empathy and rolling with resistance with the goal of having veteran peers conduct MI-informed coaching rather than formal MI. Veteran peers were encouraged to relate to study participants as veteran peers and potentially disclose more personal information than is typical when using manualized MI. Psychologist supervisors also trained the veteran peers in how to address potential suicidal and homicidal ideation and race/ethnic and sexual orientation and identity issues. During the trial, with participant consent, motivational coaching sessions were audio recorded for fidelity monitoring . Psychologist supervisors reviewed the audio-recordings and provided feedback to veteran peers at weekly group supervision meetings. For participants assigned to the intervention arm, veteran peers started by providing participants feedback on each of their baseline MH screens and used MI-informed, open-ended questions to elicit participants’ reactions to their MH screen results. For example, a veteran peer coach would inform a veteran participant of their PHQ-9 score and explain the meaning of a positive score for depression as either mild, moderate, or severe, flood drain tray asking veterans to share their thoughts or feelings on hearing this information, using psychoeducation and normalizing data as appropriate.

Veteran peers then explored participants’ readiness for MH treatment, reminded veterans that they themselves were not licensed practitioners and, based on their location and preferences, asked permission to provide a customized list of MH treatment and self-care options. Subsequently, participants received up to 3 additional 20- to 30-min motivational coaching calls at 2, 4, and 8 weeks to encourage MH treatment initiation using MI principles as described above. For example, a veteran peer coach attempting to elicit change talk and motivation for MH treatment might use the Readiness Ruler to ask a participant how ready they were to receive MH treatment and would reflect back to them, “You gave yourself a 4 out of 10, why not a lower number? What would need to happen to move you up one or two numbers?” Because veteran peers were trained in coaching in addition to MI, they might add additional coaching language, such as: “If you decided to start receiving outside help, what kind of help do you think would work the best for you?” and, “If we take a step back and think about the big picture, what really matters in your life?” During the 8-week motivational coaching intervention, if a participant scheduled or engaged in clinician-directed MH treatment , the peer-delivered coaching intervention shifted to treatment retention. Treatment retention calls consisted of 20- to 30-min calls at 2 and 6 weeks after MH treatment initiation. During retention calls, veteran peers focused on eliciting the benefits of sustained MH treatment engagement, that is, “Now that you are receiving outside help, how do you see your life getting better?”VA and non-VA community MH services in Northern California and Louisiana were identified and vetted to create a comprehensive annotated list of MH treatment referrals for veterans. As described above, MH treatment referrals were provided to veterans with positive MH screens in both study arms following the baseline assessment and were grouped as follows: clinician-directed MH treatment either within VA or in the community reimbursed by VA, or through a non-VA community MH facility; non-clinician-directed MH care either through VA or in the community ; and self care .

For participants in both arms, veteran peers provided contact information for referrals by phone and letter but did not schedule referrals for veterans.All primary and secondary study outcomes were assessed by blinded research staff at 8 and 16 weeks using the same battery of items administered at baseline and only MH treatment engagement was assessed at 32 weeks. The primary outcome was initiation of clinician-directed MH treatment, and among participants who initiated treatment, retention in MH treatment for ≥ 2 visit, as determined by self-report, VA administrative data, or both . Any new VA or non-VA MH appointment during follow-up between participants’ baseline assessment to 60 days after the final 32-week time point was counted as MH treatment engagement. An MH treatment experiences self-report questionnaire was used to identify categories of clinician-directed VA or non-VA MH treatment. Only MH treatment encounters at VA or in non-VA community settings reimbursed by VA are included in VA administrative data. Secondary outcomes included: non-clinician-directed MH care at VA or in the community and engagement in self-care activities , defined as activities that reduce stress and promote well-being, which can be particularly important for rural veterans and influenced by location. Other secondary outcomes included MH symptoms and quality of life domains .At baseline , following randomization, the 135 controls and 137 telephone motivational coaching participants did not differ in terms of sociodemographics. Overall, the majority was male and middle-aged . Although most participants were White, racial minorities were over represented compared to the US population. The majority earned < $50,000/year; 72% had a military service-connected disability ; 14%- 26% enrolled in VA health care had used private insurance or Medicaid/Medicare within the past 6 months; and the majority received care at rural VA health care facilities. As shown in Table 2, the 2 groups also did not differ at baseline in terms of quality of life measures, MH symptoms , as well as most substance use scores .

Overall, most participants screened positive for MH symptoms, including depression and anxiety , followed by PTSD , and roughly one-quarter screened positive for high-risk drinking. Controls demonstrated significantly higher baseline opioid and amphetamine use than intervention participants , although use of both was extremely low. The 2 groups did not differ in terms of barriers to MH care, but at baseline, controls were significantly more ready than intervention participants to obtain MH treatment. At baseline, the 2 arms did not differ regarding past 5-year MH treatment or self-care activities . In the intervention arm, of 4 possible motivational coaching sessions for MH treatment initiation, participants competed a mean of 2.6 sessions, and of 2 possible MH treatment retention sessions , a mean of 1.72 sessions were completed. As shown in Table 4, a similar number of controls and intervention participants initiated clinician-directed MH treatment during follow-up . Of those initiating MH treatment, a similar proportion reported ≥ 2 MH visits: 41% of controls reported a mean of 6.6 visits, SD = 9.6, and 37% of intervention participants reported a mean of 4.4 visits, SD = 4.6. While there were no between-group differences in type of clinician-directedMH treatment, in this largely rural veteran sample, most MH care was within primary care, followed by MH clinics and receiving “psychiatric medication.” Adjusted Cox proportional hazards regression confirmed no independent differences between the 2 arms with regard to MH treatment initiation , after adjusting for site, MH treatment history, baseline MH symptom severity, baseline opioid and amphetamine scores, and readiness for MH treatment. Of note, the only positive independent association with MH treatment initiation was greater MH symptom severity. Table 6 shows that there were also no significant between group differences regarding engagement in nonclinician-directed MH treatment. Figure 3 summarizes the proportion of participants in each arm initiating self-care activities during follow-up. Compared with controls, more participants in the intervention arm engaged in MH-related Internet or mobile self-help applications and MH-focused community classes . Self-reported MH screen scores and quality of life domain scores were captured at 8 and 16 weeks . Varying numbers of participants did not complete assessments at these 2 time points, resulting in missing values. Nevertheless, as shown in Table 7, compared with controls, intervention participants had significantly lower depression scores and cannabis scores . The COACH trial tested a veteran peer-delivered telephone motivational coaching intervention to improve MH treatment initiation among veterans who primarily used rural VA health care facilities and screened positive for MH symptoms but were not in MH care; which, to our knowledge, is the only study of its kind. No significant differences were found between groups in clinician-directed MH treatment initiation , nor in MH treatment retention. Notably, however, veterans randomized to the intervention were significantly more likely than controls to demonstrate modest improvements in several secondary outcomes, flood and drain tray including MH symptoms, quality of life indicators, and self-care. Qualitative findings may explain how achieving these secondary MH and quality of life outcomes in the intervention arm may have paradoxically obviated veterans’ need to engage in more formal MH treatment. Both participant- and intervention-related factors may explain the lack of difference observed between the 2 groups regarding MH treatment engagement. First, rural veterans prefer to address MH concerns on their own terms , largely influenced by geography and culture, as opposed to engaging in traditional MH treatment. 

In addition, stoicism, self-reliance, and preference for community, family, and peers may have presented barriers to MH treatment engagement among rural veterans not observed in prior similar studies of urband welling veterans. Regarding the intervention, while other studies have employed MH professionals to deliver MI, this study trained peer veterans to conduct motivational coaching. MITI scores demonstrated fair fidelity to MI, raising the question of whether the primary outcome may have been enhanced by stronger adherence to MI principles. Additionally, intervention participants received a mean of 2.6 of 4 motivational coaching sessions, suggesting that dose may have been attenuated, although other studies with fewer doses of MI have achieved treatment engagement. Nevertheless, this study achieved overall enhanced MH treatment engagement in all participants, likely through components common across both study arms, for example, multiple MH assessments, feedback of MH results, and personalized treatment referrals by veteran peers. These findings align with studies which have demonstrated that assessment of substance use alone is associated with significant reductions in use, known as “assessment reactivity.” Similar to our study, Walker et al found that repeated assessment for alcohol abuse followed by a single session of telephone-delivered MI versus psychoeducation were both associated with increased treatment seeking in soldiers with untreated alcohol abuse, pinpointing repeated assessment as a key ingredient. The between-group descriptive analyses for the secondary outcomes demonstrated that veteran peer motivational coaching resulted in improved MH symptoms, reduced cannabis use, improved quality of life scores, and encouraged self-care activities compared to controls as observed in another study. This finding may be explained by the fact that “partnership” was the highest of the peers’ MITI global ratings. Self-disclosure about their experiences may have explained the higher partnership scores, although self disclosure is not measured by the MITI.Non-clinician peers were specifically selected as study interventionists for this trial because rural veterans are known to prefer and trust insiders over “outside experts.” Qualitative exit interviews did suggest that the veteran peers achieved a therapeutic effect themselves, possibly through partnership and relatability, in their delivery of the motivational coaching intervention. For example, one study participant explained, “When she opened up that she was a veteran, I think it made me -. I let my guard down a lot more. It gave me more freedom to express myself and actually talk.” Another consideration is that greater MH symptom severity , and hence perceived need for MH treatment, is a major driver of MH treatment engagement. Thus, as veteran peers achieved secondary outcomes of improved MH symptoms, quality of life, and increased self-care through motivational coaching, they may have paradoxically reduced veterans’ need for formal MH treatment engagement, perhaps explaining our findings in this trial. For example, one participant described the veteran peer coach as helping them, “catch it quickly, without it getting so out of hand that I have to call somebody for mental health. That was—to me—the highlight of all this.” This trial had several limitations that should be considered in interpreting results. First, as evidenced by the CONSORT diagram , veterans enrolling in the trial were likely a biased sample as roughly half who were assessed for eligibility declined to participate. However, this attrition is not wholly unexpected because administrative data were used for recruitment. Second, the sample was largely White, male, and VA service-connected , so findings may not generalize to veterans of color and non-veteran populations. Third, there was large loss to follow-up among rural veterans , but reasons for drop-out are not known. Fourth, fidelity to the MI component of the intervention, intended to enhance MH treatment engagement, may have been supplanted by veteran peers’ “peerness” or relatability, which may have favored the study’s secondary outcomes.

The control plane runs on the controller server, with the purpose of sending instructions to the network to update routes. Our orchestrator server set up applications in the computing nodes and collects statistics to measure performance. The northbound and southbound interfaces enable the communication from the SDN controller to the control plane and the orchestrator. We configured SNMP and SCPI as well, for coarse-grain statistics and to send instructions to the optical switch. To differentiate between host and guest machines for both servers and switches, we use the terms host or physical when not referring to the virtualized elements. The purpose of the control network is to create out-of-band links that facilitate experiment orchestration and collecting data from the testbed, without sending instructions through UC Davis network. In such manner, we have full control over the infrastructure, the network design and we keep dedicated links without worrying for bandwidth availability nor external outages. The individual clouds in Figure 2.3 illustrate different networks, with their own IP addressing. Orchestrator, EPS chassis, controller, node1, and node2 are connected with physical 1 Gbps ethernet links through an electronic switch. The Opticalswitch is also connected with a 1 Gbps ethernet cable to the orchestrator. Our computing nodes vm1, vm2, vm3 and vm4 are hosted in node1 and node2, interconnected with virtual links. As we mentioned at the beginning of the chapter, our data plane is a reconfigurable optical network driven by an optical switch and four electronic packet switches. Br1, br2, br3 and br4 are hosted in an EPS chassis configured for running in OVS mode, which means that they are optimized for OpenFlow applications and receive instructions from a centralized SDN controller. Each individual link can forward data at rates up to 10 Gbps. Figure 2.4 represent the general topology of our data plane. Nevertheless, grow racks the physical links can be attached or removed with software to or from different bridges as a consequence of the flexibility that OVS yields. We use the terms bridge, EPS and ToR as synonyms.

SDN-enabled devices communicate with a controller through a channel, using OpenFlow protocol. In our testbed, the SDN controller is the built-in application OFCTL OpenFlow switches use flow tables to route packets by matching one or more fields. to achieve dynamic routing in a software defined network. Pica8 PICOS is the Network Operating System that runs in our physical EPS. It allows the chassis to run in two modes: Traditional L2/L3 mode and OVS. We use the latter, as it fits in our SDN design. In our testbed, we handle the traffic as needed without traditional routing protocols like OSPF. If there is any overlap in the flow tables, the forwarding action will be random and this behavior is not desired. To avoid that, the priority field is varied in our experiments. We use a single flow table for each bridge, and the addressing is done with IPv4. The relevant fields for our testbed are described in Table 2.1. An alternative to run tests with SDN is to use the L2/L3 mode in PICOS with cross flow enabled. This hybrid approach allows a combination of both networking paradigms. Network operators interact with the switch with Linux commands or a CLI similar to Juniper Junos interface. The flexibility of having two consoles is useful for researchers with different backgrounds. Some may be experienced with Linux servers, others with enterprise or service provider networking. However, throughout our experiments we found issues while performing optical reconfiguration in hybrid operation. We observed that the ports where we connect the transceivers remained in down state after we execute the optical reconfiguration. We had to reboot the Picos service and reinstall the flows to get the ports up, adding at least one minute to the reconfiguration. Hence we decided to run OVS mode. So far, we have discussed the pertinence of flows in our testbed and how we use the SDN controller to update routes from the orchestrator using a REST API. Now we will introduce the concept of flow in computer networks. RFCs are technical documents published by the IETF after being written and reviewed by interested parties.

They cover foundations for computer networks, namely transport, addressing and routing. From RFCs 2722 and 3697, a flow is defined as the packets sent from a source to a destination that may be unicast, multicast or anycast, with specific attributes . An alternate definition for flow refers to the packets in a single physical media or stream of data. In the context of our testbed, a flow is an entry in a table that is attached to a specific bridge, with different fields that will be matched to follow the desired route towards their destination.Two EXXACT chassis , node1 and node2, host the virtual machines, vm1, vm2, vm3 and vm4. Each physical server has an Intel X710 dual NIC which supports up to 10 Gbps per port. The main issue with this card was the transceiver compatibility, because it does not read generic devices but only products listed in the Intel compatibility tool. Every virtual server has its own 10 Gbps dedicated port that connects to the data plane, as illustrated in Figure 2.4. Additionally, we connected the virtual machines to the orchestrator with dedicated 1 Gbps NICs apart from the 10 Gbps cards. Figure 3.2 represents the wired and virtual links between the orchestrator, host servers and virtual machines. Virtual bridges inside node1 and node2 map the traffic from the guest servers to the exterior. These interconnections enable the orchestration of applications in our experiments from a principal server. In the rest of the thesis, we use virtual machines, virtual server, computing nodes, computing servers as synonyms.Technologies for optical switches were introduced in chapter 1. In our testbed, optical reconfigurations were performed with a Polatis optical switch tray , a single-mode MEMS device that takes up to 25 ms to steer the light beam to the new port. Instructions for switching were sent from the orchestrator with SCPI commands through a TCP socket. The ethernet interface of the switch speeds up the deployment and integration with our testbed control network. The lack of an openflow agent in the OST does not allow to seamlessly integrate the optical switch with an SDN controller. Nevertheless, most recent chassis such as the Polatis 6000 and 7000 series come with open flow agents to enable centralized management with SDN.

These products offer flexibility for theindustry. However, they are built on top of the same MEMS-based technology and the switching latency is still in the order of tens of millisecond.Small Form-factor Pluggable are defined by Cisco as compact optical transceivers. They create an interface between optical and electrical communications, with a transmitter and a receiver in both sides of the link, and support several communication standards like Ethernet, SONET and PON . They are manufactured for different purposes: single mode, multimode, for short and long distances, fiber and copper. It is important to choose the appropriate SFP for the application, otherwise the deployments could not work properly or the devices could get damaged. We installed two types of 10 Gbps transceivers. The first works with multi mode fiber in the 850 nm band, grow table and allow us to connect the computing nodes with the electronic packet switches, as observed in Figure 2.4. The second kind is 10 Gbps DWDM SFP, operating in the C band. By using Single Mode Fiber patch cords connecting our electronic packet switches and optical switch, we created a reconfigurable optical network which supports multiple wavelengths. Various tools are available to generate packets between hosts. Some are packeth, ostinato, D-ITG, MGEN iperf and TRex. The latest is developed and maintained by Cisco, and it offers scalability up to 200 Gbps per server. However, this tool is made for a single server, that is, the transmitter and receiver are hosted in the same physical machine, which must have at least two NICs from the supported models. The Device Under Test can be an external element or virtualized. Codilime, a company that specializes in software and computer networks, customized TRex to allow testing a network from different start and end points. We tested this traffic generator, but the installation, configuration and integration with our testbed was not straightforward. In contrast, iPerf installation and execution is quick, it does not show issues with drivers and the integration with our experiments was successful. This tool has been widely used in research and generates synthetic packets to emulate traffic between servers. Several studies have shown different approaches to gather statistics to analyze network performance. Platforms like Netseer, Jetstream, Planck have demonstrated improvements in the detection of network performance anomalies, including packet drops, decrease in throughput and increased latency, at different scales like data center and cloud. Zhang et al. [99] compare two ways of gathering data from computer networks, fine and coarse sampling. To analyze testbed latencies and network performance metrics,we used tcpdump as we need end-to-end per-packet resolution. On the other hand, SNMP counters work well to confirm that the data stream is going through the desired route when we design the reconfiguration paths. Zabbix is a popular tool in enterprises for monitoring systems, including SNMP statistics, and there are docker versions for agile implementation. With this software we observed how the traffic flows through the EPSs interfaces. To monitor traffic per flow, we deployed an sflow collector and sflow agents in the virtual bridges. Recalling the first chapter, the goals for this research comprehend building a networking and computing testbed with SDN capabilities to demonstrate the benefit of make before break approach combining optical and electronic packet switches to achieve hitless reconfiguration. In Figure 2.1 we show the architecture of the testbed and the meaning of each element in the network diagram. The data plane encompasses an optical switch and four electronic packet switches , connected to an SDN control plane. The topology can be modified as needed with Open vSwitch commands. Additionally, an orchestrator sends the route updates to the controller and optical switch. In the first subsection we analyze the hardware and software switching latency introduced by our control plane. Next, we compare the throughput, round-trip time and packet loss of a single data stream between a pair of servers . We show the benefit of our make before break approach for updating the route, compared to a plain optical reconfiguration. Finally, similar to the single data stream experiments, we show the metrics of doing a route update with two data streams to demonstrate the benefit of make before break. We refer to the last subsection as bandwidth steering experiments. Five main switching latencies were found in our testbed. A summary is shown in Table 4.1. We discuss each one in the following subsections. Overall, the dominant latency of 605ms is introduced by the transceivers and the operating system of the host electronic packet switch. In later sections, we show how to avoid interrupting the data stream due to a link unavailability caused by a path reconfiguration, by using our MBB approach. We define the optical switching latency as the time it takes from the beginning of the reconfiguration performed by the optical switch, which leads the ports to go down, until all the transceivers report operativity in the ToR chassis. The topology in Figure 4.1 shows a single data stream between servers vm2 and vm3. At the beginning, the data transfer goes through EPS br2, br1, br4, and br3 . Then we perform the path reconfiguration with the optical switch ost1, and the new route between servers passes through switches br2 and br3 . A summary of steps performed in our experiment is shown in Table 4.2. Server 2 and server 3 run iperf in server and client mode, respectively. The data rate on the sender side is set at values from 5 Gbps to 10 Gbps, with a duration of 20s. After 485 experiments, we obtained the logs from the physical electronic packet switch, which hosts the virtual switches br1, br2, br3, br4. Then we identify all the interface flapping events of the ports in the topology shown in Figure 4.1. Finally, we calculate the time difference between these events, port down and port up, to obtain the summary of statistics in Table 4.3 and Figure 4.2 as well.

Though border concerns have existed since the conception of the United States, post September 11, 2001, these concerns grew markedly. Fences, walls and guard posts along the U.S. Mexico border were established or fortified. More regular patrols of the borderline by Homeland Security agents were initiated. These infrastructure and personnel investments are expensive to initiate and maintain and are still ineffective at complete surveillance of the 3145-km border; approximately 250,000 people try to cross the border illegally each year who have stepped into action. Aside from the human rights violations that such forms of surveillance pose to groups seeking to cross the border, these homeland security activities are also threats to the environment. Environmentalists worry that the new roads, fences and facilities created to accommodate these new forms of surveillance are degrading fragile desert landscapes, ripping up vegetation, compacting soil and threatening wildlife movements . Finally, these operations seriously threaten precious and irreplaceable archeological sites located along the nations’ borders. Although the use of remote sensing cannot address the human rights violations, geopolitical tensions or cultural and ethical problems posed by current forms of border surveillance, it does offer ways to make homeland security efforts more efficient at recognizing extra-legal migrations, while also potentially lessening the impact of current efforts on the environment and cultural heritage sites. Using aerial and satellite images, remote sensing can allow Homeland Security officers to target their surveillance and enforcement efforts by revealing where smuggling or migrations are taking place by displaying habitual paths through the desert. They may also allow law enforcement agents to stay out of harms’ way during reconnaissance missions. Further, with increasingly advanced technology, 4×4 flood tray remote sensors affixed to light aircraft provide almost real-time detection of human movement across the landscape. Targeted efforts and fewer law enforcement vehicles and patrols for surveillance may lessen the impact of border security on local ecologies.

Remotely detecting smuggling or extra-legal migrations is more difficult than detecting the growth of drug crops, because these illicit activities are not static; people and goods can move across a landscape in a matter of hours. Thus, the adoption of these techniques is still in progress. To try to detect where drug, human and arms smugglers were traveling through the landscape, Kaiser and others used ADAR 5500 mounted on a helicopter to try to detect trails crossing the desert border along the southern limit of the United States. Cao and others conducted a similar study in 2007 [87]. Coulter and others used a Canon EOS 5D Mark II camera system fixed on a light aircraft to detect the active movement of people through the landscape in near-real time. In all of the terrestrial cases we reviewed , it is assumed that the movement of any people through this landscape is linked with smuggling or extra-legal migrations, since remote sensors are unable to detect the intentions or identities of these people. This, in and of itself, is a problematic assumption given that these areas have traditionally been used by indigenous groups, homesteaders and cattlemen for generations. In situ interactions with people in these areas would facilitate the detection of various people’s identities and intentions. Problematic at a different level, remote sensing would be unable to detect smuggling operations that occur via trucks or through tunnels under the U.S.-Mexico border, which may be equipped with electricity and rail systems . The U.S.-Mexico border is not the only place where remotely sensed surveillance for crimes and criminals is taking place, however. As Zhao shows, many countries in Europe, Asia and North America are working to develop ship surveillance systems to detect ships that may be used for extra-legal migration, illegal fishing, piracy and smuggling along maritime borders . These surveillance systems integrate Synthetic Aperture Radar satellite data with automatic identification systems that are ship, land and space-based. Although we did not find any studies that chronicled the active detection of crime , there exists a plethora of studies that present theoretical or retrospective case studies of how this might take place.

These studies tested the use of TerraSAR-X, TanDEM-X, RapidEye, RADARSAT, Envisat-ASAR, Cosmo-Skymed, MODIS and ALOS images to detect the presence of ships in the Mediterranean, the North Sea, the Gulf of Aden, the Campos Basin, the English Channel, the Port of Halifax, the Bosporus, the Ionian Sea, the Southern Ocean and the Strait of Italy. There also exists a fairly extensive literature that deals with the active detection of oil spills , as well as illicit drift-net fishing . Both of these topics fall outside the realm of our analysis, however. While these studies differ from terrestrial studies of human and drug trafficking in that they acknowledge that ships may have many uses that are not nefarious, these studies do seek to survey some of the most vast and unmanned areas on the planet. Differentiating between legitimate ship users and potential pirates or smugglers presents a challenge. Some scholars have proposed methods of differentiating “abnormal behavior” from standard shipping procedures to identify piracy in action. These studies consistently must deal with false alarms in their detection algorithms caused by oceanographic or meteorological phenomena and bathymetry—underwater banks and azimuth ambiguity. Any credible remote sensing project should assess the accuracy of its results, and particularly those used in the active detection of crime. In these projects, accuracy or validity can be thought of as the “correctness” of the resulting map or classification product . The means by which accuracy assessments have been carried out have changed over time, starting as an afterthought and progressing to a well-defined and necessary component of remote sensing analyses . These “first order” accuracy assessment protocols ideally include well-distributed independent samples from the ground or a data source of higher accuracy , development of error matrix reporting of the overall error, errors of omission and commission per land cover class and the kappa statistic. Although remote sensing analysts attempting to detect crimes acknowledge that ground-referenced data is the gold standard for accuracy assessment, publicly available gray literature and peer reviewed papers agree that this method is not always feasible, due to security concerns, rugged and remote terrain and funding limitations. Eleven of the 58 studies on drug production that we reviewed reported that their accuracy assessments were limited due to insecurity issues on the ground. Of the same group, eight reported that no accuracy assessments were possible because of insecurity . The security concerns addressed in these reports are very serious. For example, a member of a ground survey crew in Afghanistan was killed while collecting data on cannabis production in 2009. Ground validation of extra-legal migrations in U.S. borderlands was also limited by security concerns and dense vegetation. In order to avoid the issues presented by potentially dangerous and/or expensive field missions for ground reference data collection, analysts seeking to assess the accuracy of their illicit drug identification have come up with alternative methods . For example, Chuinsiri et al. used large-scale aerial photographs collected at the same time as the satellite data for accuracy assessment instead of gathering ground reference data. Unfortunately, these aerial surveys may not be as effective as ground surveys. For example, in a similar study, aerial surveys were often unable to detect shade-grown coca. In other cases, bad weather delayed the collection of data from aircraft, putting the utility of the data collected for accuracy assessment into question. Further, one UNODC report notes that even over-flights were too dangerous in certain regions, thus limiting the accuracy assessment within those areas. In cases where ground or aerial validations proved unfeasible, analysts sought other means of performing accuracy assessments of their detection of illicit crops. In some cases , “surrogate” ground-reference data were produced using the visual interpretation of two satellite images using poppy reflectance, disappearance of the vegetation in the second image , apparent fields surrounded by natural vegetation, distance to populated spaces and accessibility. UNODC used a quality control mechanism that involved each analyst’s work being checked by two other experts and then cross-validating first and second dated photographs rather than using ground validation data.

Wang used UNODC and the Islamic Republic of Afghanistan Ministry of Counter Narcotics’ surveys from the same time period as satellite data were collected to calculate the accuracy of his classification of opium crops. Where no survey data were available, Wang used coarsely constructed opium maps. Surprisingly, hydroponic tray over thirty-six percent of the drug production studies reviewed did not mention accuracy assessments in any way . Those that did discuss validation often did so in limited ways. In one study, analysts did not update the previous years’ accuracy assessment, assuming that a similar level of accuracy could be considered for the year at hand. Similarly, in all three of the studies of illicit human movements in the landscape that we reviewed, accuracy assessments either were not performed, or the methods for assessment were not mentioned or clearly discussed. For example, despite the fact that Coulter and others have a table assessing the accuracy of their detections of trails, they do not describe how they calculated these percentages. The lack of discussion of accuracy assessments in drug and human-movement studies is surprising given the potentially serious impacts these reports may have on local communities and ecologies. Because this is a review paper, we were unable to independently research the potentially harmful ecological and social impacts that a lack of validation may have had, but we believe it is important to raise the point that studies with such important real-world implications should be validated; and many are not. Most of the retrospective and theoretical marine case studies relied on ship-specific automatic identification systems data to validate the remote sensing of ships. Posada and others point out three problems with AIS to validate remote sensing. First, AIS equipment is often misused by its operators, resulting in the wrong ship ID numbers being attached to a given vessel, potentially misrepresenting the type of ship that is on the water. Second, AIS messages “regularly contain errors ”, leading to confusion in ship tracking. Third, AIS do not report ship position rapidly, thus, if there is a significant time gap between when SAR data were collected and when AIS data were reported, the ship may have moved a significant distance, making validation very difficult. Beyond these three limitations, Lehner and others point out that smaller vessels may not have AIS and may also be more difficult to differentiate from false-alarms, like breaking waves. We posit that few ships intent on criminal activity would have AIS either. Finally, Paes and others note that the Earth’s curvature and meteorological influences on data transmission leads to instances where vessels far from the coast are not present in the AIS databases. To get around some of these issues, some scholars used maritime patrol aircraft to survey blank areas, had analysts do manual inspection of images or did on-the-ground validations of ships. All of these techniques are difficult, time consuming and expensive to enact, thus making it likely that validation of actively identified marine crimes will follow similar trends as terrestrial drug production or smuggling. Aside from the more refined remote sensing techniques we mention above, law enforcement and government officials have leveraged the power of freely available remotely sensed products, like Google Earth, to detect crime. Although, to date, there is a limited discussion of the use of Google Earth to detect crime in the academic literature, it is widely discussed in the popular press . These discussions note that Google Earth is being deployed by law enforcement officers, government employees, scientists and even private citizens to actively detect crimes in progress around the world. For example, a Swiss police department “stumbled across a large marijuana plantation while using Google Earth”. Aside from international agencies and law enforcement departments, researchers, like Anthony Silvaggio, an environmental sociologist at Humboldt State University, have sought to point out where large-scale, unregulated industrial marijuana grow sites are occurring in Humboldt county, California, including in national forests. Amateur searchers have also started seeking out and identifying marijuana growing using Google Earth . Google Earth’s use for crime investigation does not stop at drug production, however. In Greece, Italy, Argentina, India and the United States, Google Earth has been used by government officials to identify homes that have violated building codes, built swimming pools without permits and to compare declared home values with actual existing structures.

Sampson concludes that “the influence of SES on police contacts is contextual in nature, and stems from an ecological bias with regard to police control” . Whether economic deprivation has a direct relationship with crime through individuals’ behavioral mechanisms , or an indirect effect on crime rates through the operation of police bias, there is a strong theoretical basis for the finding that poor neighborhoods report higher crime rates than rich ones. The measures of economic deprivation that are controlled for in this study are poverty and unemployment. Mollie Orshansky developed the original poverty thresholds in 1963-64 when she was an economist working for the Social Security Administration, shortly before the declaration of a “War On Poverty” by President Johnson . An individual or household is in poverty when its total cash income falls below the applicable threshold, determined by family size and composition . The 2010 poverty thresholds range from $11,139 for a single individual living alone to $42,156 for a family of eight or more people living in the same household. Indicators of socioeconomic disadvantage, including poverty and unemployment, have been associated with higher crime rates in Miami, Florida and Columbus, Ohio . Other studies show that rates of crime and violence are extremely high in neighborhoods containing public housing developments, which are areas of extremely concentrated socioeconomic disadvantage . In their study of medical marijuana dispensaries in Sacramento, Williams and colleagues found that violent crimes were significantly associated with “concentrated disadvantage”, a variable constructed from 2008 poverty guidelines. Property and violent crimes were not associated with density of marijuana dispensaries, indoor weed growing accessories but both categories were significantly related to unemployment rate . Further evidence of the link between crime and unemployment is found in crime data from across the United States in the 1990’s, a decade of incredible crime reduction.

Raphael and Winter-Ebmer found that a substantial amount of the reduction in property crimes could be explained by the corresponding decline in unemployment rate. A weaker relationship existed between unemployment and violent crime, according to the researchers. Freeman presents similar findings and concludes that as much as one-third of the drop in crime in the 1990’s can be explained by the expanding job market. Theorizing from earlier empirical work by Sampson , which found that macrolevel indicators of family disruption were related to rates of juvenile crime, Sampson and Groves include family disruption among their “exogenous sources of social disorganization” . The theoretical basis for this lies in the notion that “traditional” families provide their communities with greater parental supervisory resources, compared to single-parent families. Additional supervision results in greater social control and more effective prevention against crime . This theoretical link is supported by empirical evidence. In their reassessment of Sampson and Groves’s original analysis, Veysey and Messner report that family disruption has significant relationship with crime even independently of other social disorganization processes. Indeed, percent of single person households was significantly related with crime in the Sacramento dispensary studies conducted by Williams and colleagues .According to social disorganization theory, communities with higher levels of residential turnover suffer from correspondingly lower levels of social control and are therefore likely to report higher rates of crime . The present study conceptualizes “residential instability” as an index of the percent of housing units in a given census tract that are vacant and the percent of individuals living within the tract who are between the ages of 18 and 29. These variables are also used by Martínez and colleagues in their study of crime and drug use in Miami neighborhoods. Williams and colleagues found that property crimes—but not violent crimes— were significantly associated with percent of owner-occupied households, which is a measure of residential stability. Hipp and colleagues examined residential turnover in an ethnic context and found it to be significantly associated with crime. They conceptualized “residential stability” as the average length of residence of households in the relevant census tract .

Although it is not included in the forthcoming analysis, there is one final measure of social disorganization that appears in the theoretical literature which is relevant to the present discussion of crime in city neighborhoods: population heterogeneity . The argument here is that segregated communities suffer from lower rates of communication and interaction, which prevent them from organizing collectively to reduce crime and delinquency—even when the different population groups have a shared interest in law and order. A number of studies have found that population heterogeneity is associated with higher crime rates . Conclusion In this chapter I have reviewed the literature on cannabis, MCDs, and crime that is relevant to the present study. Particular attention has been given to routine activities theory as well as social disorganization theory . In the next chapter I extrapolate from these theories in developing a conceptual model of crime to test for the criminogenic effect of MCDs.Empirical testing is needed in order to assess the strength of these claims. I develop the model that will be used to test these claims in the first section of this chapter. In the latter sections I describe the various measures that comprise this model, which are tested in the following chapter. In comparing crime rates across city neighborhoods, it is important to control for neighborhood characteristics that are related to crime independently of MCDs. In the present study I consider three vectors of social and demographic variables, drawn from social disorganization theory, that will be used as control variables in my model: economic deprivation, family disruption, and residential instability . “Social disorganization” is a concept used to describe communities in which there is a lack of sufficient social cohesion among members—characterized by low socioeconomic status, fewer stable families, and high residential turnover—that would otherwise serve as a deterrent against crime. Higher levels of these social disorganization indicators are associated with higher crime rates at the citywide and neighborhood level . Controlling for these variables across city neighborhoods will help determine whether, and to what extent, MCDs have an independent effect on crime. Current debates about the relationship between MCDs and crime tend to revolve around politicized rhetoric and anecdotal claims .

The only scholarly discussion of this question known by this author at the time of this writing consists of a pair of studies out of UCLA that examined crime data from 95 census tracts in Sacramento for the year 2009 . Nancy J. Williams and colleagues found that crime rates were not significantly associated with neighborhood density of medical marijuana dispensaries. The researchers identified several other variables with higher explanatory power with respect to crime, including unemployment, percent of the population that is young, and percent of one-person households. These findings correspond with the assertion made by social disorganization researchers that low levels of SES, high residential instability, and high rates of family disruption correspond with relatively higher rates of crime. In the following sections of this chapter, I will discuss these and other measures that comprise the empirical model developed by this study. First, I will briefly review the two criminological theories that I draw upon: routine activities theory and social disorganization theory.Stemming from human ecology, routine activities theory attempts to explain crime on the basis of three conjoining factors: suitable targets, likely offenders, and absence of capable guardians . This approach suggests that MCDs could potentially lead to crime by increasing the concentration of likely offenders in the local neighborhood, or, more directly, by themselves presenting suitable targets for crime. These are precisely the sorts of claims that are made by critics of MCDs . Conversely, it is conceivable that MCDs might decrease crime in a neighborhood by introducing increased guardianship, rolling benches which could serve as a deterrent against crime. Proponents of MCDs make arguments of this type when asserting that dispensaries—especially those in compliance with local regulatory schemes requiring stringent security protocols—actually reduce crime in their neighborhoods . Routine activities theory is an appropriate and compelling lens through which to analyze these competing claims. It is appropriate because it presents direct causal mechanisms through which MCDs might affect crime, and it is compelling because those mechanisms plausibly run in either direction . Another useful approach found in the criminological literature is social disorganization theory, first developed by Shaw and McKay, which links urban crime to the concept of “social disorganization” . Studies have identified several measures of social disorganization that are positively associated with crime . In the present study I examine three “exogenous sources of social disorganization”: socioeconomic deprivation, residential instability, and family disruption. If these neighborhood characteristics predict crime, as social disorganization theory suggests, then they ought to be incorporated into more specific models of urban crime—including the present attempt to explain the relationship between MCDs and crime. I do not argue that there is a direct relationship between MCDs and social disorganization. Rather, I look to social disorganization theory to identify neighborhood characteristics, independent of cannabis, which might confound the real relationship between MCDs and crime. Variables from each of the three categories of social disorganization variables used in the present model are summarized in Table 3.1 below. For a more thorough review of the underlying theories and concepts, see the previous chapter.This study examines the spatial relationship between medical cannabis dispensaries and crime across 189 census tracts in San Francisco in the year 2010. I test two hypotheses drawn from the theoretical literature on routine activities theory , controlling for neighborhood characteristics drawn from social disorganization theory . The first is that MCDs increase crime by attracting likely offenders and presenting them with suitable targets; the second is that MCDs actually decrease crime by protecting their surrounding community with adequate security measures and thereby providing capable guardianship.

The theoretical bases for these claims are discussed in greater length in the previous two chapters. In this chapter I present the research methodology employed by this study and discuss their implications. Data are collected from the San Francisco Police Department, Planning Department, and Department of Public health; the California Department of Finance; the American Community Survey ; and the United States Census Bureau. Linear regression models are tested using four dependent variables at the census tract level: total property crimes, property crimes per 1,000 residents, total violent crimes, and violent crimes per 1,000 residents. Findings are largely but not perfectly consistent across these different models with respect to the spatial relationships between crime, MCD density, and the seven other neighborhood characteristics analyzed: poverty, unemployment, family stability, vacancy rate, percent of the population ages 18-29, percent of the population that is male, total population size, and percent of land commercially zoned. Findings indicate a consistently weak but statistically significant relationship between MCDs and crime. MCD-containing tracts have slightly higher rates of both property crime and violent crime than tracts that do not contain MCDs. The link is stronger for violent crime than property crime . I am careful not to infer too much from this finding, due to the limited number of cases under review—26 dispensaries across 16 census tracts, compared to 173 non-MCD-containing tracts. Crime is more strongly predicted by the social disorganization variables examined by this study: socioeconomic disadvantage, family disruption, and residential instability. Consistent with social disorganization theory, socioeconomic disadvantage and family disruption are found to be strong predictors of high crime rates. By “stronger” I mean that it has a larger correlation coefficient and a higher degree of statistical significance . “Family stability” is negatively associated with crime across all four models. Again, this link is stronger than the link between MCD density and crime. The third category of variables drawn from Sampson and Groves’ “exogenous sources of social disorganization” , residential instability, was not as strongly predictive of crime as socioeconomic disadvantage or family disruption. In the following sections I explore these findings more deeply and discuss their implications for research as well as policy making. 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 examine 95 census tracts in Sacramento using data for the year 2009. Their findings indicate that tracts containing dispensaries are not significantly associated with higher rates of crime when controlling for neighborhood characteristics associated with crime . This study borrows from their work in conducting a cross-sectional analysis of the spatial relationship between MCDs and crime in 189 San Francisco census tracts for the year 2010. All measures are aggregated to the level of census tracts.

This phenomenon may explain why isolated compounds derived from cannabis appear only capable of exerting a limited effect as seen in drugs such as with the synthetic ∆-9 THC drug, dronabinol. To what extent each of these components confers anti-inflammatory benefits is a current focus of research. To what extent each of these components confers anti-inflammatory benefits is a current focus of research.An extensive literature beyond the scope of this review demonstrates persistently elevated levels of inflammatory and immune activation biomarkers even in PWH on antiretroviral therapy who have achieved plasma HIV RNA levels less than 50 copies/mL, designated “virally suppressed”. These include interleukin-6 , C-reactive protein and tumor necrosis factor alpha, CD4+ T cell depletion in gut lymphoid tissue persist, activated T cells are increased, and many immune cells are senescent. PWH also have a dysfunctional gut epithelial barrier , an increase in the permeability of the intestinal barrier accompanied by gut dysbiosis and immune dysregulation from loss of T cells in the GALT, resulting in activation of pro-inflammatory soluble CD14 , a response to circulating bacterial products, or microbial translocation . The central nervous system is an important site of inflammation in HIV, as demonstrated by measuring inflammatory biomarkers in cerebrospinal fluid, by brain magnetic resonance spectroscopy, and by positron emission tomography using microglial activation markers. Several mechanisms contribute to the persistence of inflammation in virally suppressed PWH. These include coinfections and gut dysbiosis. Cytomegalovirus co-infection is highly prevalent in PWH; CMV replication is frequently reactivated, triggering an inflammatory response. As mentioned above, gut microbial dysbiosis, which promotes dysfunction of the gut epithelial barrier, drying room resulting in a positive feedback loop sustained by increased microbial translocation of pro-inflammatory antigens such as lipopolysaccharide and subsequent immune activation and chronic inflammation.

Whereas normal commensal flora contribute to tolerance and balance between T helper subsets, loss or replacement of these beneficial flora leads to loss of T-helper type 1 function, amplifying GALT dysfunction in HIV infection. Depletion of Th17 cells in the GALT leads to reduced IL-22 production, diminishing epithelium repair processes and maintenance of tight gap junctions. Such barrier defects create a pathway for microbial products to escape the gut lumen and enter the systemic circulation. The entry of microbial products into the blood, known as microbial antigen translocation triggers the innate immune response and release of pro-inflammatory cytokines, such as interleukin -1β, TNF-α and others. Abundant data show activation of the NLRP3 inflammasome in virally suppressed PWH. Hepatitis C virus co-infection is common in PWH and may be another source of microbial translocation that drives inflammation. Plasma levels indicative of microbial translocation in HIV-HCV co-infection were higher than in monoinfected PWH virally suppressed on ART. PWH co-infected with HCV had a marked increase in markers of microbial translocation than uninfected healthy controls, whereas the plasma 16S rDNA was relatively similar, suggesting that it is the immune activation that persists as opposed to the circulating bacterial products. Tudesq and colleagues demonstrated for the first time that the plasma 16S rDNA levels increased with the duration of HIV infection in HIV-HCV co-infection, independent of HCV progression.Increased inflammation in virally suppressed PWH as described above is associated with adverse health outcomes such as myocardial infarction and even death. Persistent inflammation also affects the central nervous system , where microglia and astrocytes are chronically activated , ddimer, IL-6, CRP, monocyte chemoattractant protein 1 , soluble CD14 and sCD40L. Adjusting for age, comorbidity status, sex, ethnicity, AIDS status, current and nadir CD4, and virologic suppression on ART, factor analyses reduced the dimensionality of the biomarkers, yielding three factors, one of which was loaded on d-dimer, IL-6 and CRP and was correlated with worse depressed mood. We also reported that poorer social support was associated with higher levels of plasma MCP-1, IL-8 and VEGF, as well as CSF MCP-1 and IL-6 , suggesting that that enhancing social support might be an intervention to reduce inflammation and its associated adverse outcomes among PWH.The ECS comprises a network of receptors, endogenous ligands and enzymes expressed in diverse cell types.

Among the many functions of the ECS is regulation of energy use and substrate metabolism to maintain homeostasis. Components of exogenously administered cannabis bind to EC receptors, thereby modulating the function of the ECS. ECS signaling pathways have been pursued as a target for future pharmacotherapy to reduce inflammation and provide therapy in pathological conditions. The cannabinoid receptors type-1 and -2 are expressed in most tissues. CB2Rs are densely expressed in immune tissue and organs in diverse cell types including macrophages, splenocytes, microglia, monocytes, and T-cells resident in the thymus, spleen, and bone marrow and tonsils, providing a mechanism by which cannabinoids can exert anti-inflammatory effects. CB1Rs are most abundant in the brain, where they serve to modulate neurotransmitter activities, thereby mediating effects of phytocannabinoids on neurobehavior. They are particularly highly expressed in nociceptive areas of the CNS, as well as in the cerebellum, hippocampus, limbic system, and basal ganglia. They are not found in the medullary respiratory centers and thus, unlike opioids, do not cause respiratory depression. CB1Rs are also expressed on immune, cardiac, and testicular cells. In the GI tract, CB1Rs are involved in feeding, gastrointestinal motility, satiety signaling and energy balance. CB1R peripheral activity includes lipogenesis and inhibition of adiponectin, found at elevated levels in obese and diabetic individuals . CB1R signaling has been linked to increased levels of free fatty acids, low HDL, high triglycerides and insulin resistance. The two main endocannabinoids are arachidonoyl ethanolamide, or anadamide , and 2-arachidonoylglycerol , both derived from lipid precursors and synthesized on demand. Endocannabinoids in the postsynaptic neuron are released into the synaptic cleft, and travel retrograde to the presynaptic neuron, where they inhibit neurotransmitter release. The principal enzymes for degradation of ECs are fatty acid amide hydrolase and monoacylglycerol lipase . Additional EC-degrading enzymes include cyclooxygenase-2 , lipoxygenase , serine esterases and cytochrome P450.The anti-inflammatory effects of exogenous cannabinoids are mediated by the ECS , likely through CB2Rs in the periphery that have immunomodulatory functions.

Both preclinical and clinical evidence support theseanti-inflammatory effects of exogenous cannabinoids, particularly THC and CBD. This may be particularly important in the context of HIV, which is characterized by persistent inflammation as described above. For example, PWH heavy cannabis users had decreased frequencies of T-cells bearing the activation marker HLA-DR+ CD38+ CD4+ compared to non-cannabis-using individuals. Heavy cannabis users also showed reduced frequencies of antigen-presenting cells that produced pro-inflammatory interleukin-23 and tumor necrosis factor-α. In another study, HIV-infected cannabis users had lower IFN-γ-inducible protein 10 levels in plasma. In an experimental study examining the interaction between the ECS and cytokine networks in humans, CB1 and CB2 expression were significantly induced by TNF-α, IL-β, and IL-6. CBD may be a particularly potent anti-inflammatory component of cannabis. CBD reduces pro-inflammatory cytokines, inhibits T cell proliferation and reduces migration and adhesion of immune cells. These effects translate to improved outcomes in disease models. Thus, CBD protected against the deleterious effects of inflammation in a viral model of multiple sclerosis. Cannabidivarin , structurally similar to CBD, is a non-psychoactive cannabinoid found in cannabis. Very little work has been conducted on CBDV in PWH. In one study, CBDV was safe but failed to reduce neuropathic pain in patients with HIV. In the laboratory, it has been shown that CBDV decreases fat formation and inflammation in human skin cells. Many anti-inflammatory actions of cannabinoids may be mediated through the gut, particularly through stabilization of the gut barrier. The gut barrier is composed of epithelial cells, tight junctions, and a mucus layer. It controls beneficial nutrient absorption and protects against the deleterious invasion of pathogenic bacteria and toxins from the gut lumen into the blood. The ECS, how to trim cannabis together with the gut microbiota, regulates epithelial barrier permeability. In an animal model of HIV, macaques infected with simian immunodeficiency virus showed increased markers of inflammation and immune activation in epithelial crypt cells; these markers were reduced after chronic THC administration. Exposure to phytocannabinoids may reduce neural injury by decreasing excitotoxicity and neuroinflammation. In a large cohort of PWH, we recently reported that neurocognitive impairment was less frequent in cannabis users than non-users, regardless of viral suppression. In comparison, cannabis exposure was not related to NCI among PWoH. Unlike many prior reports, this analysis carefully controlled for any non-cannabis substance use disorders, positive urine toxicology for other illicit drugs and any past methamphetamine use disorder, positive breathalyzer test for alcohol, major depressive disorder and HIV disease characteristics. A possible mechanism of the specificity of the benefits of cannabis only for PWH is the anti-inflammatory effect of cannabis, which may be particularly important for PWH who have persistent inflammation despite good antiretroviral treatment. In contrast to cannabis’s beneficial actions in PWH, research on PWoH typically reports adverse effects on brain development and neurocognition. Examples include attentional and memory deficits, behavioral problems and structural and functional brain changes. The data are particularly concerning for adolescents. It is possible that PWH are less likely to suffer these adverse consequences than PWoH because of the counterbalancing effects of cannabis in reducing neuroinflammation, as we discussed when considering stroke. In an animal study, euroinflammation, measured as levels of TNFα, IL-1β, IL-6 and MCP-1, was reduced in the striatum of SIV-infected animals treated with THC.

Enteroendocrine signaling and the vagus nerve may provide a mechanism through which the gut microbiota may influence the central nervous system. Additionally, signaling through CB1Rs is influenced by Akkermansia muciniphila and administration of this organism to obese and type 2 diabetic mice increased intestinal levels of ECs that control gut inflammation and the gut barrier. These relationships between the gutmicrobiota and the ECS may be therapeutically useful. Thus, in zebrafish treated with a probiotic formulation for 30 days, gene expression of FAAH and MAGL, the enzymes responsible for degradation of the endocannabinoids AEA and 2-AG, decreased. Thus, probiotic treatment enhanced endocannabinoid signaling and improved gut integrity. Gut bacteria control the differentiation and function of immune cells in the intestine, periphery, and brain. There is increasing evidence that gut microbiota and the immune system are critical factors in the pathogenesis of neurodevelopmental, psychiatric and neurodegenerative disease as microbiota immunomodulation orchestrates communication between the gut and brain. Some cognitive domains are subject to immune-mediated CNS injury from HIV-induced microglial activation and contribute to HIV-related cognitive dysfunction. Furthermore, microglia are exquisitely responsive to the gut microbiome and commensal bacteria support the maintenance of microglia in normal homeostasis conditions. When microbiota is absent, microglia lose the ability to mature, becoming defected in differentiation, and function. In a study with germ-free mice, severely defected microglia led to impaired innate immune responses. LPS activates microglial cells leading to neuroinflammation and when chronic, is a likely contributor to CNS pathologies, via a leaky gut–brain barrier. Microbial antigen translocation refers to the entry of bacterial, fungal and viral components, such as LPS, and metabolites, such as short-chain fatty acids , cross from the gut lumen into the bloodstream. The endogenous cannabinoid, AEA, contributes to the process by which the gut immune system actively tolerates such microbial antigens. In HIV, MAT is associated with monocyte activation and inflammation. Thus, β-D-glucan is a microbially derived antigen that serves as one index of MAT. The anti-inflammatory effects of cannabinoids may be beneficial with respect to HIV reservoirs, which are the principal barrier to HIV cure. We analyzed HIV DNA in blood as a marker of reservoir size in men who had sex with men and initiated ART within a median of 4 months of estimated date of HIV infection. All achieved suppressed HIV RNA within a median of 5 months. Exclusive use of cannabis, as compared to no substance use or use of other drugs, was associated with a faster decay of HIV DNA during suppressive ART. These results are in line with prior reports of reduced HIV replication and cellular infection rate in the presence of cannabinoids in vitro. Thus, the potential anti-inflammatory effects of cannabis could translate to a beneficial impact in reducing HIV persistence. However, there is no consistent evidence that cannabis use affects levels of plasma HIV RNA. In addition to their expression in the peripheral immune system, CB2Rs are also expressed in the CNS . In humans, the bulk of CB2R expression is by microglia and astrocytes, consistent with a role in neuroinflammation.

In addition to the various classes of natural products described above, there are some hybrid natural products that span two classes. Cannabinoids for example are derived from the terpenoid pathway and the polyketide pathway . Prenyl-flavonoids and prenylstilbenoids would also fall under this category. Cannabinoids are a very interesting class of natural products, with some pretty remarkable medicinal properties. For the past 83 years cannabis or marijuana was considered a schedule one drug by the United States, which stunted the research into the molecules that cannabis makes. Although it is still classified as a schedule one drug by the federal government, the perception of the plant and the molecules it makes is starting to change. Thirty-three states now permit the use of medical marijuana and 10 states and Washington DC have legalized it for recreational use. The shift in perception may be due to recent clinical studies. A non-psychoactive component of cannabis, cannabidiol or CBD was FDA approved to treat severe childhood epilepsy, and has been suggested as a possible treatment for the spasticity associated with diseases like Parkinson’s Disease and Multiple Sclerosis . THC or D9 -tetrahydrocannabinol, the psychoactive component of marijuana is FDA approved as an appetite stimulant for patients going through chemotherapy.54 In addition to the conditions these cannabinoids are already approved for, both THC and CBD are cited to have antiemetic, antianxiety, anti-inflammatory, antidepressant and anticonvulsant properties. While THC and CBD are produced abundantly by cannabis plants, several groups have attempted to engineer microbes to produce cannabinoids and their intermediates in order to create a more sustainable source of these pharmaceutical compounds. As shown in Figure 1-7 the biosynthesis of cannabinoids can be broken down into three parts, cannabis grow room the polyketide biosynthesis , the terpenoid biosynthesis and the cannabinoid biosynthesis .

Gagne et al were the first group to transform the olivetolic acid biosynthetic pathway into yeast. Previous work by Taura et al had identified an olivetol synthase, capable of making the decarboxylated form of OA. Gagne et al posited that there was an additional enzyme in the biosynthetic pathway that would cyclize the polyketide chain to form OA instead of olivetol. In this work they identified olivetolic acid cyclase, which cyclizes tetraketide intermediate to form OA instead of olivetol. Gagne et al transformed the genes necessary to produce OA in S. cerevisiae, and reported a titer of 0.5 mg/L; however this titer is not optimized. Six years later Tan et al engineered the same pathway into E. coli. They added additional enzymes to increase the malonyl-CoA and hexanoyl-CoA precursors, and were able to obtain 80 mg/L of OA. At the other end of the biosynthesis , Zirpel et al have engineered several yeast strains to catalyze the final two steps in the biosynthetic pathway. First in 2017, Zirpel engineered P. pastoris to express a promiscuous prenyltransferase, NphB, and THCA synthase to convert OA into THC. While the yeast expressed both enzymes, they did not detect any THC until they lysed the cells and supplemented with two precursors, OA and geranyl pyrophosphate . Even then, the production of THC was slow at ~ 10 nmol/L/hr, which was attributed to an inefficient prenylation step, and low levels of the cannabinoid synthase. In later studies, Zirpel et al focused on engineering the yeast strains to improve the expression of the cannabinoid synthases THCAS and CBDAS. They identified five proteins that aid in the expression of the cannabinoid synthases. When they supplemented the yeast over expressing the cannabinoid synthases with CBGA, they were able to produce over 3 g/L of THCA and 400 mg/L of CBDA, a significant improvement to their first study.60 Only one group has reported the entire biosynthesis of cannabinoids in yeast, however the titers are low.

They produced the precursor cannabigerolic acid at 8 mg/L, THCA at 1.1 mg/L and CBDA at 4.2 µg/L, when the cultures were supplemented with 1 mM hexanoic acid. These low titers indicate the difficulty associated with engineering a microbe to produce a complex natural product. When the authors supplemented cultures with 1 mM of the precursor OA, they were able to produce higher levels of the CBGA intermediate 200 mg/L a 55% conversion of the OA added. This may indicate that OA biosynthesis is limiting in their strain, probably due to the low malonyl-CoA concentrations. Similarly to other engineered microbes for opioid, paclitaxel and artemisinic acid production, the cannabinoid pathway is very complex. The root of the pathway is the essential precursor acetyl-CoA, which is required to make both the aromatic polyketide component, and the isoprenoid component of the cannabinoid. Additionally there is always the possibility of product or intermediate toxicity, which can limit titers. Further, expression of the cannabinoid synthases can be challenging. Zirpel et al observed low titers of THC until they co-expressed the synthase with several chaperones, and an enzyme to improve cofactor biosynthesis. Listed above are 15 examples of microbes that have been engineered to produce various natural products , and it’s evident that microbial engineering allows for the production of vastly different natural products. Microbial fermentation is an important tool for the production of natural products, and is used in several industrial processes. However, the cases presented above demonstrate the highly variable nature of titers, ranging from µg/L to g/L, and its apparent that some studies are more successful than others. The studies that are more successful tend to be shorter metabolic pathways, and they do more than simply add an exogenous bio-synthetic pathway, they try to drive carbon flux into the target pathway. This highlights one inherent problem with engineering microbes.

The target pathway engineered into the microbe is always competing with native metabolic pathways for cofactors and metabolites. Therefore, essential pathways will always deplete resources from the target pathway. Additionally, metabolites from the background metabolism have the potential to inhibit the target pathway. These interactions are extremely challenging if not impossible to identify in vivo, and can limit the overall titers of any pathway. The final product can also decrease cell viability, like in the case of monoterpenes and alcohols, and limit product titers. Finally, while engineering microbes is fairly simple and efficient compared to other organisms, it still takes a significant amount of time to develop strains, approximately “150 person-years” of work were required to engineer yeast to produce artemisinic acid at 25 g/L.62 There are two alternatives to metabolic engineering, cell-free biosynthesis and synthetic biochemistry. They are built on the same principles, using enzymes to produce a target molecule, but instead of engineering a microbe, the biocatalysts are reconstituted either in a cell lysate or in vitro. The difference between cell-free and synthetic biochemistry is small, with cell-free relying on the cellular machinery in a lysate to recycle essential co-factors, whereas synthetic biochemistry relies on pathways with the ability to recycle the necessary co-factors. Cell-free systems are most commonly used to power protein expression, however there are some cases where lysates have powered the production of a biosynthetic pathway. There’s. lot of flexibility within this set up. Kay et al produced 2,3 butanediol at 84 g/L using a lysate derived from an E. coli strain expressing all three enzymes in the pathway, but Dudley et al expressed the desired proteins individually, lysed the cells and mixed the various lysates together to produce mevalonate at 17.5 g/L. Interestingly, when Dudley applied the same concept to the production of limonene , the titers were significantly lower at approximately 100 mg/L.This type of system shares some of the challenges with metabolic engineering. Even though the cells are lysed, metabolic enzymes still remain active; therefore its possible for carbon flux to be diverted from the target pathway. Dudley et al cite this as a major challenge for the cell-free production of limonene. The native E. coli farnesyl pyrophosphate synthase remains active, grow trays and siphons flux away from the monoterpene pathway to produce a sesquiterpene alcohol. Additionally, metabolites present in the lysate can inhibit the pathway of interest and limit titers. However, cell viability is no longer limiting, products can be extracted in real time limiting product inhibition and the target pathway protein levels are easily manipulated.Synthetic biochemistry provides several advantages over metabolic engineering. Many of the successful studies mentioned above required altering central metabolism to account for the target pathway, but in every instance it was a balancing act between essential pathways and the target pathway. A synthetic biochemistry approach also allows for rapid design, build, test cycles, which makes it easier and faster to identify pathway bottlenecks. Once bottlenecks are identified, it is very easy to tailor the enzyme activity to alleviate the problem, something that is very challenging to do in vivo. Additionally, because enzymes can be expressed and purified from a range of expression platforms , it increases the pool of potential enzymes that can be used.

Finally, like the cell-free approach the products can be easily extracted, limiting problems associated with product toxicity. However there is a challenge with this approach. Without the cell, the in vitro pathways need to incorporate components that will balance and regenerate co-factors. In their simplest form, in vitro enzymatic systems can be broken down into two modules, the sugar breakdown module and the build module. The sugar breakdown module catabolizes the sugar into 2-3 carbon building blocks and generates high energy co-factors like ATP and reducing equivalents in the process. Those components are then assembled in the build phase to generate the final product. The challenge is the high energy cofactors produced in the sugar breakdown module are not always balanced with the build module. This is the case for the in vitro biosynthesis of monoterpenes and isobutanol. Korman et al engineered a system with 27 enzymes to biosynthesize monoterpenes. To produce a monoterpene, the feedstock, glucose, was converted into pyruvate via glycolysis, pyruvate was converted into acetyl-CoA with pyruvate dehydrogenase , acetyl-CoA fed into the mevalonate pathway to yield geranyl pyrophosphate , which was converted into a monoterpene via a monoterpene synthase. The pathway originally was not stoichiometrically balanced for the reducing equivalents, NADH. The sugar breakdown module originally produced 6 moles of NADH, and the build module required 2 moles of NADPH. Not only were the reducing equivalents stoichiometrically unbalanced, they were not the type the build module needed. To counteract this imbalance Korman et al employed a molecular purge valve. The purge valve consists of three components. First, an NAD+ specific glyceraldehyde-3-phosphate dehydrogenase is responsible for maintaining carbon flux through glycolysis. An NADH oxidase was used to burn excess reducing equivalents, and an NADP+ specific GAPDH was used to generate the reducing equivalents required for the mevalonate pathway. All three components were required for the in vitro system to run efficiently. Using the NADP+ specific GAPDH alone leads to a buildup of NADPH, which prevents the conversion of glyceradehyde-3-phosphate into 1,3-bisphosphoglycerate . This would eliminate ATP regeneration via the glycolysis pathway and eventually stop the system. The pathway yielded 12.5 g/L of limonene and 14.9 g/L of pinene, which is significantly higher than titers achieved in microbes. Opgenorth et al engineered an in vitro enzymatic system to produce isobutanol. As previously mentioned alcohols are fairly toxic to microorganisms. Therefore, an in vitro, cell-free approach might lead to higher titers. For isobutanol, the sugar breakdown module is glycolysis which nets 2 reducing equivalents and 2 ATP per cycle. The isobutanol build module requires 2 moles of NADPH, but 0 ATP. Therefore, in order to balance the system Opgenorth et al utilized GapN, an enzyme that converts G3P and NADP+ into 3-phosphoglycerate and NADPH, thereby eliminating a step that regenerates an ATP. This leads to a system that is stoichiometrically balanced, however, this may not be optimal in a cell-free system. Opgenorth et al found that ATPase activity from purified enzymes or spontaneous ATP hydrolysis can deplete ATP stores and limit product titers. So, they engineered a component to generate excess ATP under high phosphate conditions , called the molecular rheostat. The rheostat is a branchpoint in glycolysis providing two paths that convert G3P into 3PG, with one path produces ATP and the other does not. The GapN path directly converts G3P into 3PG yielding no ATP. The phosphorylation path converts G3P into BPG with an NADP+ specific GAPDH, and BPG is converted into 3PG using phosphoglycerate kinase, which regenerates an ADP into ATP. Because the activity of the GAPDH enzyme is dependent on the phosphate concentration, the rheostat ATP production is also dependent on the phosphate concentration.

The Hangzhou Public Bicycle System has surpassed Vélib as the largest bike sharing program in the world. Not surprisingly, it has sparked great interest in bike sharing in Mainland China. Indeed, Beijing, Tianjin, Hainan, and Suzhou have already launched pilot programs in 2008 and 2009.Nature plays a crucial role in medicine. Natural products, or molecules produced by living organisms, are a rich source of novel molecules that have a myriad of beneficial properties. The idea of using natural products as medicines is not a new concept. In fact, it dates back to ancient civilizations where various plant products were used to manage, treat and prevent disease. Mesopotamia relied on cedar and cypress oils to cure ailments, Egypt had a collection of about 700 plant based medicines detailed in “Ebers Papyrus.” Chinese civilizations also cultivated their own list of natural medicines with the first record dating back to 1100 BC.1 Over time the lists of natural remedies evolved; however, it was not until the 19th century AD when scientists began to identify the actual molecules that had the medicinal effects. Morphine was the first natural product to be isolated from its natural source and sold in 1826.Since, scientists have continued to identify novel natural products with amazing properties, and while the list of natural product medicines is long, some of the most notable are: penicillin , paclitaxel , lovastatin , quinine and cannabidiol .Beyond medicinal natural products, scientists have also identified natural products that can be used as fuels, fragrances and dyes. Nature continues to be a rich source for novel molecules, with some predicting only 10% of the biodiversity that exists on the planet has been discovered. Despite the importance of natural products in everyday life, drying cannabis there has been a paradigm shift from the use of unmodified natural products to semi-synthetic modified natural products, and synthetic compounds. 

This is in part due to the expense associated with identifying and characterizing natural products, and the decision of the Supreme court in Association for Molecular Pathology v. Myriad Genetics, 569 U.S.  which decided that natural products cannot be patented, thereby limiting economic motivation for identifying new natural products. However, it is imperative to realize the myriad of applications for natural products in human health and other industries, and continue to develop methodologies to identify and synthesize this class of molecules. Herein, we focus on methods to produce natural products. Chemical synthesis is the most common method used to produce a molecule, and while this technique can be used to produce almost any molecule, the process is not always economically feasible on an industrial scale. This is often the case for natural products; the chemical synthesis is possible , but the cost of the synthesis process is greater than the cost of extracting the target molecule from a natural source. As a result, the world’s supply of morphine, paclitaxel and cannabinoids as well as an array of other molecules is still dependent on natural sources. However, there are many challenges associated with relying on natural sources to produce these crucial medicines. Plants are slow growing, susceptible to environmental conditions, inconsistent in secondary metabolite production, and secondary metabolites are often present at very low concentrations. A great example is paclitaxel, produced by the pacific yew tree. It requires 3 to 6, 100-year old, pacific yew trees to treat one cancer patient.1 This is simply not sustainable. Additionally, there can also be political implications. The world’s supply of morphine is predominantly produced in Turkey, India and Afghanistan, and shifts in the political climate could lead to shortages or high prices of the essential drug. So while chemical synthesis and natural product extraction are sufficient for now, in order to capitalize on the properties of natural products, we need new cost-effective, consistent and efficient methods to produce natural products.

Several ideas have been proposed to address these challenges outlined in Figure 1-1, such as engineering plants to improve natural abundance, plant cell culture, engineering microbes, cell-free biosynthesis and synthetic biochemistry. Herein, each method listed above is reviewed for the pros and cons. It is important to realize that natural products are unique and different methods will be suitable for different molecules. First, some effort has been dedicated to engineering plants to either improve the abundance of a target molecule, or engineer a plant to make a natural product it would not make normally. Zhang et al were able to engineer tomatoes to improve the production of genestein, a flavonoid with an array of important medicinal properties. Naturally tomatoes produce very low levels of genistein , but Zhang et al improved the amount of genistein to 78 mg/g of dry weight, nearly 0.8% of the tomato DW. Additionally, you could engineer a plant to produce a molecule it would not have produced naturally. In addition to boosting genistein levels, Zhang et al were able to engineer tomatoes to produce resveratrol a compound not naturally produced by tomatoes at levels 100-fold higher than grapes .However genetically engineering plants can be challenging. There are only a few species that have been extensively studied, which limits the number of model systems. Additionally, plant metabolism is complex and it can be difficult to identify molecular components, like transcription factors, that are necessary to boost biosynthesis of the target molecule. This also does not address some of the inherent issues with plant sources, such as cultivation time and susceptibility to mold, pests and environmental conditions. Plant cell culture is an exciting alternative to extracting the compound from the natural source. They can be generated from a variety of plant species by first isolating plant tissue sterilizing the tissue, and plating the sterilized tissue on solid media supplemented with plant hormones and nutrients. The explants proliferate to form a callus . Calluses can then be used to initiate plant cell suspension cultures, which have the ability to produce secondary metabolites. This method has many advantages over extraction from the natural source such as improved sustainability, shorter incubation times, increased production level through metabolic engineering, consistent environmental conditions, and protection from insects and mold. 

Cell culture has been particularly fruitful for the production of paclitaxel, a powerful anticancer drug. As previously stated it would take 6, 100 year old trees to produce enough paclitaxel to treat one patient, however the plant cell cultures are able to produce 150 mg/L in 6 weeks, a dramatic improvement. Plant cell culture is well suited for the production of paclitaxel due to the complexity of the bio-synthetic pathway, so generating cell lines from cells that naturally produce paclitaxel is a relatively simple process. Some additional examples natural products produced by plant cell culture include: scopolamine , protoberberines rosmarinic acid , shikonin and geraniol .Despite the benefits of plant cell cultures there are still several challenges. The cultivation time is still 2-3 weeks, which is rather long compared to microbial cultivation times. Further genetic instability and physiological heterogeneity leads to variability and unpredictability in secondary metabolite production. The secondary metabolites also remain intracellular which can make it difficult to reach high titers. As this technology develops further it may be possible to address some of these issues. For example, Wilson et al are working to reduce genetic instability and rescue necrotic calluses in order to improve production of paclitaxel in plant cell cultures. However, some challenges are more difficult to address such as improving the titer of toxic compounds. While plant cell culture is an important method for natural product biosynthesis, specifically paclitaxel biosynthesis, the method is not broadly applicable to other natural products due to the complexity of plant metabolism. In addition to plants, microbes are a rich source of natural products. Both fungi and bacteria naturally produce an array of useful molecules. In fact, several FDA approved antibiotics are produced via microbial fermentation. However, it is also possible to engineer microbes to produce natural products from other organisms such as plants. Microbes are easy to manipulate, they have relatively short cultivation times , curing cannabis and are easier to culture than plant cells. As a result, there is an entire field of research dedicated to engineering microbes to produce nonnative natural products. Due to the vast number of studies conducted in this field, this review will only focus on several examples of microbial production of bio-fuels, terpenes, alkaloids and polyketides. In addition to being a rich source of medicines, nature also produces molecules that play an important role in everyday life. Due to the need for energy security and limits on the world’s petroleum supply there is a need for sustainable liquid fuels for transportation. Microbes naturally produce alcohols, isoprenoids, and fatty acids, which can be used as fuels or easily converted into fuels. 

As a result, a great deal of research has focused on engineering microbes to improve the natural production of bio-fuels. Microbial production of isobutanol and farnesene are reviewed below. Alcohol-derived bio-fuels are the ideal candidate to replace gasoline used in cars. Isobutanol has a high energy density low vapor pressure, and a high octane rating . Therefore, it can either be blended into gasoline or replace petrochemicals altogether. There have been several studies published that discuss the microbial production of isobutanol in various organisms, such as: E. coli, C. glutamicum, S. cerevisiae, C. acetobutylicum, R. eutropha, and S. elongatus. The highest titer achieved was an engineered strain of E. coli. Atsumi et al engineered E. coli to produce 22 g/L of isobutanol. First, they over expressed the enzymes in the isobutanol pathway shown in Figure 1-2. Then, they deleted non-essential genes that would divert precursors and intermediates out of the isobutanol pathway. Finally, they improved the flux of pyruvate into the isobutanol pathway by using a non-native enzyme with better kinetic parameters. A later study by Baez et al using a similar E. coli strain obtained titers of 50 g/L by continuously removing isobutanol from the culture, demonstrating the effects of isobutanol toxicity on E. coli cultures. While alcohol based bio-fuels are a possible alternative, they are too expensive to compete with the low cost of gasoline. Iftiters could be improved further, the cost of the bio-fuels would decrease, however this is unlikely due to the toxicity of alcohols at high concentrations. The highest microbial production of a bio-fuel reported thus far is a sesquiterpene derived bio-fuel, which can be converted into diesel fuel and jet fuel. Amyris was able to engineer yeast to produce the sesquiterpene farnesene at titers that exceed 130 g/L by re-engineering yeast central metabolism to direct sugar into the isoprenoid pathway. However, these production levels are still relatively low, when considering the energy demand of US transportation. At this titer, it would require 23.5 L of yeast culture to produce 1 gallon of farnesene. To replace the amount of jet fuel used in the US airlines in 2018 with farnesene, 1.2 billion liters of yeast would need to be cultivated and processed per day a total of 420 billion liters of yeast per year. In addition, while this titer is significantly higher than most reported, the cost of producing farnesene via microbial production is still more expensive than petrochemicals . The real challenge with bio-fuels is not engineering the microbes, but competing with the very low prices of petrochemical products. While bio-fuel production in microbes is generally too expensive to compete with fossil fuels, this is not the case with all natural products. Due to the challenges associated with chemical synthesis, a low natural abundance and the variability with plant based production of complex natural products, microbial fermentation is a plausible alternative for the production of high value natural products. Microbes have been engineered to produce an array of compounds, spanning three of the major classes of natural products: terpenoids, alkaloids and polyketides. Terpenes and terpenoids are a large diverse class of natural products derived from the mevalonate or methylerythritol phosphate pathway . The products of the MEP and MVA pathways are isopentyl pyrophosphate and dimethyallyl pyrophosphate , which serve as the core building blocks for terpene biosynthesis . For example, the condensation of DMAPP and IPP produces geranyl pyrophosphate , the precursor to monoterpenes. Condensation of GPP with IPP produces farnesyl pyrophosphate , which is the precursor to sesquiterpenes, like farnesene mentioned above. The condensation of two FPP molecules yields squalene , which is the precursor to cholesterol. Terpenes are classified by the number of isoprene units which range from monoterpenes to polyterpenes . 

Because of this closed network of potential buyers and smoking their own product, they only have enough money to purchase cannabis in small increments. This puts them in a situation where they don’t make much, if any, money at all. Thus, many cannabis sellers quickly resign themselves to the status of “helper,” part-time dealer, or simply a user that sells to smoke for free.Another facet that I found unique about the group is that none of them considered themselves drug dealers. Some referred to themselves as “herbalists,” some called themselves “helpers,” but none would call themselves drug dealers or refer to cannabis as a drug. They refused to use the term drug dealer or drug because of the negative connotations associated with them. They would frequently refer to their clients or customers as “patients” even though they admitted that only some of the visitors to the dispensary were actual medical patients. Moreover, they considered the act of selling to be helping. The Kings, as discussed prior, believed that cannabis could cure all the evils of the world so any instance of selling to an individual would be an instance of helping them or helping the world. This is in direct contrast to the more economic motivations discussed by the various criminological theories of drug selling . Back to the original questions of this dissertation, why do these users smoke sell and sell and how do they understand those processes. What I found was mostly inconsistent with the criminological theories prominent within the discipline. I found no instances of structural and social strain that lead to innovation. Nor did I find evidence of social disorganization among the Kings or their neighborhood. Rather, industrical drying racks what I found was a group of individuals who had an understanding of what cannabis is, does, and can be that was radically different than mainstream social conceptions of this plant.

Although many will be quick to dismiss the act of smoking cannabis as nothing more than a juvenile stoner act practiced by a group pot smoking hippies, mainstream culture heavily influences our outsider perception of this substance. In order to truly understand the practice of drug using and selling, it is important to take an interactionist and culturally relativistic understanding to this practice. Thus, we can see that meaning, interpretation and action is not a simple universal understanding. Instead, interpretation and meaning is socially constructed just as the Kings would suggest our social world is. Given the large and significant number of cannabis users in the United States today , the fact that more research on cannabis users motivations is not so scant is astounding. Moreover given the radical social and legislative changes going on in the U.S. today, the lack of research that examines the motivations of cannabis use and cannabis dealers is even more flabbergasting. Given the social significance that hallucinogens have held throughout history and the significance and social impact of the war on drugs, I would assume that researchers would seek to move beyond the old moralistic criminal control and pathological medical theories. Considering the overwhelming evidence of the effectiveness of cannabis for treating a myriad of diseases, and the fact that many states, four as of this writing, and the District of Columbia, have legalized recreational use of cannabis it is perplexing that within the field of criminology we still hold onto theories of drug use that are clearly no longer suitable in our modern era. Moreover, it is even more perplexing that much of the drug literature has stayed focused on problematic drug use to the detriment of cultural and social interpretations. Indeed, the majority of drug use in the U.S. is recreational and non-problematic. The majority of drug users are recreational users. Only a small percentage of the drug sing population uses the heavy drugs such as cocaine, methamphetamine and heroine. Moreover, only a small percentage of the hard drug using population develops serious addiction patterns. Likewise, by conceptualizing drug use as a criminal problem in need of control, and by conceptualizing users as deviants, criminals and delinquents, we as researchers, criminologists and sociologists have unwittingly, or wittingly, been complacent in the very type of thinking that produces systematic racist and classist systems of inequality. It was the goal of this dissertation to counter our moralistic and criminological assumptions about drugs, drug users and drug sellers by focusing on the life history, practices and motivations of a unique group of cannabis users, growers and sellers.

Through ethnographic and interview methodology, I sought to illustrate an understudied yet culturally and socially relevant context of cannabis use. From the viewpoint of users, growers and sellers of these substances, the criminal justice system is but an intruder on the lives of people. One, it seeks to create a paradigm shift in our understanding of drug use and drug users. Two, it contributes to the interactionist and cultural understanding of drug use by examining the social and spiritual motivations of users instead of imposing moralistic judgements. And three, it investigates an under examined and understudied phenomenon of suburban semi-legal drug markets. The findings from this study counter many of the common misconceptions about drug users and sellers. They contradict Merton’s anomie theory as at no point did the Kings indicate that they perceived that legitimate economic opportunities were blocked to them. Likewise, when asked about their motivations to start selling their answers were more altruistic and cultural than economic. The neighborhood I studied did not resemble a ghetto and none of the members discussed depression or anything of that nature that would make me believe that their use was a coping mechanism to deal with the drudgery of life. This study contributed to sociological theories of money making in the sense that some of the members, High-C and TBC in particular, saw cannabis as a way to ball and make money. Like Dohan’s study, they saw cannabis as a means of upward mobility and a way to increase their status. Unfortunately, much like the individuals in Dohan’s study, the Kings are not rich and it is questionable whether or not selling cannabis is a more effective method of making money than a good paying nine-to-five job. Rather, what I found was a complex system of beliefs and rituals that related to cannabis that rival any cultural belief system. The Kings, influenced by the Rastafarian religion and the hippy movement of the sixties, hold a set of beliefs about the healing and spiritual power of cannabis that made it appear that they believed God created the plant for humans to use. They believe the hallucinogenic power of the plant was not merely coincidental.

They believe there was a co-evolutionary symbiotic relationship that humans held with marijuana; marijuana shows humans reality, spurs human creativity, intelligence, and consciousness and cures physical and social ills, and in return, humans spread the genes of the cannabis species throughout the world. By documenting the actual motivations and perceptions of the Kings, I seek to shift our understanding that portrays it as a public health or criminal activity to a more social, spiritual and cultural understanding. Lastly, this study contributed to our understanding of suburban drug markets and the effect of legalization and regulation of drug markets. Unfortunately, the few studies that examine the operation of drug markets in the United States tend to focus on banal characteristics such as whether or not the market is indoor or outdoor and whether or not it is an open or closed market. This dissertation advances our understanding of the cannabis networks that grow, transport and distribute this plant. Moreover, commercial greenhouse benches it illuminates what occurs to markets that are in the precarious situation of being semi-legal, which has been previously under-studied by scholars. By looking at the operation of semi-legal drug markets it shows that legalization has had and overwhelmingly positive impact in reducing drug related crimes. Likewise, it illustrates the unique and ingenious mechanism dealers use to skirt around the laws. The dissertation looked at prices, markups, potency and new types of routes of administration . Likewise, it looks at the various mechanisms used to stay compliant the new laws that regulate the use and distribution of cannabis. This contributes to our understanding of drug markets and how bureaucratic organizations operate by structuring a division of labor designed to stay compliant with the ever changing laws. Additionally, this dissertation looks at the various mechanisms used by county and cities to curb the legality of the cannabis industry.Although not the original goal of this dissertation, one would be remiss to not discuss the racial, classist and gendered implications of the shift in cannabis laws in the United States. As it was not germane to my main research questions, I only breifly touched upon the racialized and gendered nature of the dispensary. I discussed how the female bud tenders emotional and sexual labor is exploited to draw in and maintain the loyalty of young male customers. I also touched upon how the dispensary itself is broken down in a racialized manner with a black security workhorse and a white male running the dispensary. The Kings themselves do not openly exhibit racial bias, to my knowledge, and they do not maliciously sexualize women, to my knowledge. Rather, their behavior mirrors trends that have been occurring in the marijuana industry since its inception. In an attempt to keep up with competition, the Kings employ physically attractive female bud tenders to work at their dispensary. This is common as most job ads for bud tenders request a photo to be sent with the application. This allows potential employers to filter out men and unattractive women. Because the job is technically “volunteer work,” anti-discrimination laws typically do not apply to this industry.One recent study on the recreational cannabis industry in the state of Washington found that the marijuana industry is mostly controlled by white males. An analysis showed that in the state of Washington, about 60% of individuals that work in Seattle dispensaries are white. However, it is important to note that this approximately reflects the racial demographics of the city. The proportion of business owners to regular employees is actually much more relevant to whether and how racial inequalities shape the industry. While the study conducted by the pot blog found that approximately forty percent of individuals that work in Washington’s dispensaries are people of color, only about nine percent of those working in production and processing are non-white . Going beyond simple statistics, when looking at business ownership in the state of Washington, one can see a clear racial hierarchy emerging. When the state of Washington did the lottery for recreational licenses , there was not a single African-American winner . Thus, as we see in the corporate world and practically every other American social institution, racial hierarchy is emerging in the legal cannabis industry. For this reason many observers suggest that the legalization of marijuana has led to a whitening of the cannabis industry. It is important to note that although recreational cannabis use is legal in some states, there are still various barriers to entry into the market in these states and selling cannabis on the street corner is still very much illegal. Thus, while black and brown Americans are being locked up across the country for selling drugs, a select group of rich white Americans are raking in profits and becoming millionaires for the exact same act.Considering the fact that many states have ballot propositions to legalize the recreational use of cannabis , and the decreasing social stigma of the cannabis industry, it is important to critically analyze the racial, class and gendered dynamics of this industry. It is furthermore important that we do not reproduce the same inequality that legalization seeks to dismantle and afford former criminals prosecuted for non-violent marijuana-related crimes the same rights as other American citizens. For it is those disenfranchised and dispossessed that have the most to gain if legalization was truly an open market. Those disenfranchised and dispossessed can pull their years of experience together and compete with big cannabusiness.I think another interesting future direction for cannabis research would be to examine the motivation of cannabis users both before and after its legalization.

One aspects of Dohan’s work is revealing about drug trades in general, he mentions how while many who deal aspire for upward mobility, he points out how few climb the ladder. Much like Venkatesh’s documented in Gang Leader for a Day, few low level dealers make any significant money. Rather, drug dealing enterprises typically operate in a pyramidal structure with middle men and those at the tope holding out the allure of making it big while exploiting labor of the low level dealers. Yet, Dohan also points to how gang’s in the Barrio serve as a form of social organization and control where traditional mechanism have disintegrated. In a similar vein, Anderson suggest the code of the street is a new form of organization and control when previous systems of control break down. Yet, Wilson’s , Anderson’s , Venkatesh’s and Dohan’s studies assumes that blocked opportunities and economic survival is what drives the sale of drugs. Consistent with this theory, many of the members of the group have been effectively barred from the mainstream economy as a result of stints in juvenile hall and jail. However, unlike drug markets dealing with harder drugs, the marijuana market is partially legal and overly saturated. In some cities, it is possible to find 30 or 40 delivery services. Much like the cannabis market in general, many delivery drivers view cannabis selling as an effective path towards economic viability and social mobility. The financial incentive for cannabis selling is only one component. Moreover, the high cost of running dispensaries and the extensive risk creates barriers other businesses do not face. For example, bank loans, credit card transactions, leasing units and security are all prohibitive costs for dispensaries. Moreover, greenhouse bench top in the middle class area of Orange County, one cannot claim the type of destitute and blocked economic opportunities that Wilson observed. Wilson’s study was conducted primarily in the innercity Chicago area, conditions far different from middle-class suburban white Orange County.

Although Wilson’s theories related to upward social mobility and economic motivations are partially correct, the Kings motivations are not inherently financial. Rather, they view selling and smoking as a symbol of prestige and disconformity to the system. Culture, ideology and counter cultural belief systems play a significant role in their motivations. As Natty explained, “We’re burning down Babylon.” In a similar light, social disorganization theories posit that conditions within urban lower class environments affect crime rates. Criminologists working within this paradigm, a perspective popularized by Chicago school criminologist McKay and Shaw , point to factors such as high-unemployment, large high-school dropout rates, deteriorated housing, poverty and large number of single parent households as contributing to despair and anti-social behavior and lack of resources to sustain social organizations and community institutions. Anti-social behavior manifests itself in ways that leads to higher crime rates in poor socially disorganized communities. Again, while it is commendable for criminologist to see delinquency, crime and drug use as emanating from social structure instead of individual pathology, an overemphasis by criminologist on focusing on poor communities has lead to a type of virtual blinders of crime and delinquent behavior elsewhere. In the middle class area of Orange County, drug use, both cannabis and other drugs, are fairly normalized. A focus on inner-city neighborhoods ignores the extensive drug use that occurs in middle class and affluent neighborhoods. Self-report surveys indicate the drug use and selling is, and has always been a phenomenon in every race and social class. As is illustrated in both surveys and my dissertation, middle-class white Americans are just as likely to use drugs as any other racial group. It appears that the main difference between the two groups drug selling and usage is the attention paid to each group by academics, researcher, the media and police.Elliot’s integrated delinquency model is a synthesis of various social process and strain theories into one comprehensive theory of drug use.

Elliot et al. argue that drug use is the result of bonding with deviant peer groups. As the social structure becomes more disorganized and the individual loses his/her pro-social ties to society, deviant peer groups fill the void for social interaction. This is a step above the rest as it synthesizes various approaches from the macro and micro level, yet its overemphasis on peer bonding downplays the fact that non-users report bonding with deviant peers . Harton and Latane note the importance of social approval in the process of using drugs. Consequently, Anderson suggests that meaning systems and new definitions of the self may be the more important explanatory factors that distinguish users from non-users. Accordingly, I suggest, that when viewing the group I am studying that it is relevant to understand the meaning and symbols to this particular culture when understanding their substance use and selling. The groups cultural beliefs will be briefly recapped later in this chapter. Theorists working in the labeling tradition typically point to two features. One, the social construction of crime and deviance; and two, the development of a criminal identity. As has been discussed throughout this dissertation, drugs historically have not had the same type of reaction that they elicit today. Many cultures consider mind-altering substances of all types gifts from Gods. Today, because of political and social forces, drugs are perceived as inherently dangerous and immoral. The second line of tradition labeling theorists operate within is the development of a deviant identity. Edwin Lemert first proposed this in 1951 when discussing why certain individuals persist in their criminal career trajectory. Lemert’s thesis is that, once labeled, the deviant undertakes an intellectual process that works to justify the behavior through the adoption of a deviant identity. One can clearly see this manifest itself with the Kings. Both Natty and Dorian were arrested and sent to Juvenile Hall at a relatively early age . Having thus been labeled by the society as deviants, they undertook an identity as deviants, took that identity, and turned it into a career trajectory.

Although many theorists working within a pro criminal justice paradigm believe juvenile hall serves as a means of rehabilitation for young kids, my research suggest the opposite. Instead of rehabilitating Natty, juvenile hall actually brought him into contact with Dorian, who would become his life-long friend and life-long cannabis business partner. In 1973, Edwin Schur wrote his seminal text Radical Non-Intervention in which he claimed that the delinquent label can actually increase delinquency. Natty was sent to juvie for a relatively minor offense that today is common place . Moreover, juvenile hall and the process of delinquent labeling has a tendency to reproduce race and class inequality. When deciding whether or not to proceed with a juvenile trial an intake officer takes a record of the juveniles’ history of mental health, history of substance use and other factors. Natty, being the child of a single mother that was addicted to drugs certainly influenced the intake officer to detain Natty. Again, juvenile hall many times has the opposite effect of rehabilitation. The fact that juvenile hall takes into account social demographics of the child into consideration when making decisions inherently reproduces racial and class inequality. This type of experience led to a strong and profound anti-systemic feeling within Natty and Dorian. In fact, The Kings Self-conception is so heavily influenced their identity as rebels and smokers that they nickname themselves off of cannabis substances. High-C is a reference to being high and TBC is a reference to THC . Natty is a reference to Dread locks. I changed the names of these individuals for confidentiality purposes, however, botanicare rolling benches their nicknames in real life are somewhat similar. Indeed, being shunned by society may have led to their radical anti-American, anti-capitalist stance. Much of their behavior is counter cultural in nature. Differential Association Differential association is highly applicable to the Kings. This theory posits that through interaction with other deviants, individuals learn the motivations, techniques, values and ideas conducive to criminal behavior . In fact, every one of the Kings mentioned peer influence when discussing their own motivations to use and sell cannabis. For both Natty and Dorian, their parents were drug addicts or at the very least, appeared to use drugs on a relatively consistent basis. Dorian’s father, before he was locked up, taught Dorian how to set up and run a growing operation and taught him a lot about the culture and some of the techniques on how to not be caught with cannabis. Natty’s mother was so permissive of drug use that she would buy alcohol for the Kings while they were still in high school. TBC and High-C were both experienced smokers before they decided to get in the medical marijuana business. Yet, they did not have the same family situation as Natty and Dorian. I personally doubt whether their parents or close family members were aware of their activities. However, their interactions with Natty and Dorian influenced them to fund the grow-op and collective. Moreover, it was particularly interesting how all of them seemed to have perceived cannabis as positive for society. This type of uniformity in thought may have been influenced by the fact that they discussed the nature of cannabis with each other and it is a social status symbol within the group to know about cannabis culture and history. Bruce Johnson’s subcultural model is a form of deviant subcultural theory. Johnson focused on a college setting in which users were separated from their parents and influenced by their teenage peers. Johnson argued that the more isolated an individual was from his parents and the more attached they were to the teenage subculture, the greater likelihood they would participate in drug use.

The relevance of Johnson’s articles is dual in that it focuses on the meanings ascribed to drug use, and the social and cultural context in which the use existed. Johnson acknowledges that there is a competition for prestige and status within peer groups and that status and prestige are attained by engaging in activities that depart from the normative demands of mainstream society. Another relevant aspect of Johnson’s study is his use of college students. Although he noted these individuals were more likely to drop out of school, it is relevant to note that the use of drugs is a product of all social and economic classes, and is not a product of a culture mired in pathology. However, although Johnson notes the inherently social nature of drug use, he digresses into moralistic judgments about how the use increases the likelihood of dropping out and participating in deviant sexual behavior, further illustrating the fact that criminology has yet to shake the conservative view of drugs as a problem in society in need of remedy. All of these previous theories and studies pointed to the fact that substance use is correlated with various other anti-social, deviant, or occasionally criminal acts. I suggest two reasons for these findings. For one, as a result of various laws and moral entrepreneurs that create anti-drug campaigns, drugs are demonized as illegal, harmful and injurious to society. Consequently, the more likely one is to hold unconventional views on society, the more likely they are to participate in unconventional behavior, of which drug use may be one. Secondly, these studies tended to focus on adolescents, who, while they experience a gap between biological and social maturity, undertake rebellious and anti-social attitudes to break out of the juvenile roles they existed in when children . Johnson’s subcultural, Elliot’s integrated delinquent, and Jessor and Jessor’s problem-prone behavior theories all focused onadolescents or teens. My study on the other hand, focused on young adults that ran a competent business. All of these studies tended to focus on adolescents that were experiencing a gap between biological and social maturity and therefore undertook rebellious attitudes and anti-social attitudes to break out of the juvenile roles they existed in when children . Moffit claims that there are two types of offenders, adolescent limited , and life course persisters . As adolescents transition into adulthood and take on more prosocial roles, the propensity for engaging in criminal offenses dissipates . This is relevant to understand why we see such high correlations between drug use and other types of anti-social behavior. It has less to do with the drugs as it does with particular life stages in American culture and the age of the group studied.

All members said underground in unison as if they knew what TBC was going to say . I am assuming they had discussions about mainstream versus underground music prior to me asking about it. For the group, conformity to the establishment, whether that be music, dress, drugs, or any other lifestyle sets one apart as a poser or a conformist. Thus, a dramaturgical hierarchy developed within the group as each member tried to conform the least to common norms and practices such as listening to mainstream music or participating in mainstream culture.One goal of this dissertation was to use a unique group of cannabis users and sellers to examine the commonly held assumptions and scholarly theories about drug use and drug users. The goal was to create a shift in our understanding of drug use, which today is still trapped in overly moralistic and pejorative assumptions about the lives, perceptions, histories and motivations of drug users. Our understanding of substance use is still largely informed by models that seek to pathologize drugs and their users and to either rehabilitate or incarcerate them. As Geoffrey Hunt explains, “In contemporary Western industrialized societies, our current approach to drugs is influenced by both a medical and a criminal vision that emerged a little more than a century ago. The concepts of addiction and ‘drug control’ have imposed themselves as the unquestionable truths of drug issues.” . Hunt goes on to explain how these two perspectives create a type of mental blinder that make it difficult to comprehend or frame the issue of drug usage in any way other than a medical or criminal problem in need of regulation and/or extermination. Moreover, cannabis drying racks commercial this has led to a pathologizing of the individual user and the social environment that the individual exists within while simultaneously ignoring social, cultural and spiritual functions the consciousness altering substance may serve.

In contrast, substance use scholars recognize that consciousness-altering substances are used and enjoyed by every known society, including our own, in some form or another. Paleontologist believe that humans may have cultivated opium and cannabis with the rise of agriculture over 10,000 years ago . And, new theories suggest that the production and cultivation of cereals, specifically rye in ancient Mesopotamia was for the purpose of manufacturing beer, and not bread, as previously theorized . Others speculate that animals used drugs before humans , and thus, substance use predates human history. Likewise, Andrew Weil argues that the desire to induce altered states of consciousness is an innate biological human drive, on par with sex and hunger. Considering the widespread use of consciousness altering substances throughout human history and perhaps even prehuman history, it is necessary to understand such uses from a more culturally relativistic perspective and to understand why these substances have such universal appeal. Despite this, the belief that drug use serves particular cultural and social functions for groups is conspicuously absent from the sociological and criminology literature. Reviewing the literature on drug use, except for a few notable cases , I found it difficult to find criminological or sociological literature on drug usage that did not entrap the issue within the medical or crime control perspective. I frequently found myself rummaging through cultural anthropologic literature in order to find literature that considers substance use from a cultural perspective. This dissertation sought to fill in this gap in the literature on substance use. Instead of taking a criminologic and/or medical perspective on drug use, I sought to understand the behavior from a cultural and socially relativistic standpoint. However, much to my chagrin, the use of these individuals neither completely refuted nor completely confirmed either the criminologic and/or medical literature or my own assumptions. This chapter will discuss the major medical and criminologic theories of drugs to see how they fit, or do not fit this group of cannabis users. The end of the chapter will discuss my observations of the group and propose a new theory to create a cultural and social understanding of drug use.

The classical or medical model of substance use frames the issue as defined by the appearance of withdrawal symptoms. One of the first sociological attempts to explain drug use was proposed by Lindesmith , although today it is regarded as belonging to the addiction model. Lindesmith countered popular notions of drug abuse at the time by suggesting that drug addiction was not the product of psychopaths’ desire to escape life, but resulted from the desire to avoid the pain of withdrawal symptoms. This perspective of drug abuse dominated up until the 1970’s . Although his theory helped to counter the more pejorative psychopath label ascribed to drug addicts by many psychologists, it did not explain why individuals used the drugs in the first place. Lindesmith discussed it as prescribed by doctors yet did not adequately address other factors that lead one person and not another, to use opiates. Likewise, his theory failed to explain the high proportion of users that took drugs on a regular enough basis for some to label that use “abuse.” Furthermore, the substance I am studying, marijuana, has relatively mild physical-withdrawal symptoms, and only for chronic long-time users. These mild withdrawal symptoms include restlessness, irritability, mild agitation and insomnia . Yet, the withdrawal symptoms are usually too miniscule and irrelevant to be termed addiction in the classical sense as proposed by Lindesmith, likewise, the theory fails to explain onset and the process that accompanies it. Lindesmith’s classical addiction model proposed that addiction was defined as withdrawal symptoms when drug using behavior, primarily opiates were removed. This failure led to the idea of psychological or behavioral dependence. This led to a psychological explanation of drug use termed the reinforcement model. Two types of reinforcement model explain drug use: positive and negative. As Bejerot explains, “The pleasure mechanism may…give rise to a strong fixation on repetitive behavior.” . In its most simplistic form, this perspective states that getting high is pleasurable and consequently, gets repeated by the user. The negative reinforcement, similar to the addiction model suggests users take substances for the purpose of avoiding physical or emotional pain. In the classic model, this pain is associated with withdrawal, in the negative reinforcement model, any type of pain can lead someone to seek out substances, such as the desire to drink if one is depressed.

As indicated earlier, both of these models fail to explain onset. And although the positive reinforcement model is particularly useful for understanding the substance I am studying, marijuana, it is telling that positive reinforcement is framed in medical jargon that seeks to situate use within an existing medical or mentally pathological framework instead of conceptualizing use as a desire for pleasure in itself. Many theories abound about cannabis’ addicting properties. Some suggest it has little to no physically addicting properties, while others suggest it has the ability to create dependence and affect an individual’s life . Most users are recreational users that use in a social context with friends. However, heavy users have the ability to develop mild physical and strong mental dependence. Researchers believe that over stimulation of the endocannabinoid system leads to changes in the structure of the brain that can lead to addiction. Similar to the Kings explanation of a balance to the world, researchers believe that the more cannabis one uses the more cannabis they will need to feel the same effect. Physical addiction is typically associated with withdrawal symptoms. The typical withdrawal symptoms of a cannabis user is irritability, mood and sleep difficulties, decreased appetite, cravings, vertical grow racks restlessness and other types of physical discomfort . My own personal experience with cannabis prior to starting the study lead me to believe that claims of marijuana addiction were exaggerated at best and a downright propagandist lie at worst. It was not until I saw addiction first hand did I see how powerful it could be for some people. The Kings for example, would smoke on average about once every hour. Likewise, Dorian explained to me that he frequently had to wake in the middle of the night to smoke cannabis because if he did not smoke he would be too restless to go back to sleep. High-C and TBC, would frequently smoke on their way to do drop offs for the collective and the other volunteers at the collective would frequently go out back and smoke every couple of hours despite ordinances preventing on-site use at many collectives. Indeed, Dorian once told me he could never work the typical nine-to-five because he smoked too much and the one job he had at Kmart he always showed up lit and would go to his car on his breaks to smoke cannabis. Furthermore, he claimed working a nine to-five kept him trapped in the system as nothing more than a corporate minion.One of the biggest concerns of marijuana opponents is the question of motivation, or lack thereof amongst cannabis smokers. As the American Council for Drug Education suggest, cannabis leads to, “A loss of ambition and initiation, a withdrawal from customary activity, and a regression to a simpler kind of life.” . Many consider cannabis as leading to a life of indolence, free from the cares of the world, and that cannabis users typically stop caring about their appearances.

The question of anti-motivation is relevant for many reasons. For one, it is a common conservative talking point that seeks to demonize a plant that has little to no dangers associated with it besides possible mild addiction. Two, the idea is promulgated through popular culture and seems to be blindly accepted as fact by both cannabis opponents and users alike. And three, it is indicative of the conservative in the box thinking indicative of society today. The common image perpetuated in the media of cannabis users, particularly espoused by groups such as the Partnership for a Drug Free America, is one where a productive, intelligent and highly motivated teenager uses cannabis, rebels, and retreats to a life of indolence and sloth. The user typically becomes a school dropout, working for minimum wage if working at all, all the while, living in their parents’ basement playing video games and eating junk food. Ironically, this is neither entirely truthful nor a complete lie. In order to understand the effect cannabis can have on and individual and his or her motivation one must understand the nature of drugs and drug usage. There are a variety of factors that can and does affect the high an individual user may experience, things such as route of administration, cannabis type and strength, an individual’s expectations and predispositions and the set and setting. Perhaps the most significant of these is the type of cannabis and the type of strain and the differing chemicals coumpounds within each strain. Based upon the type of strain, a veteran user typically wants a certain feeling and experience. Users typically use this to help them calm down, ease nervousness and restlessness, manage physical pain and help them to sleep. In this context, many cannabis users who consume indica dominant strains during the day can experience fatigue and anti-motivation. I know many users who consume indica dominant cannabis throughout the day and these individual typically resort to a life of idleness and apathy. Dorian told me a story about Jenna, a cannabis user he met at a collective. He told me the cannabis helped to relax her when she is around other people. Unfortunately, he also told me it makes her extremely tired and she ends up sleeping a lot. He told me she slept until 4pm each day. He said, she looked like she had slept all day, she didn’t wear makeup and seemed to have shown up to the collective in the exact same clothes she wore to sleep. Natty told me he ran in to many users at the Corner that fit this description, many people did not shave and looked unkempt. This is perhaps one of the worst aspects of cannabis use, especially for medical cannabis patients. Many patients need the pain relief and anti-nausea effect cannabis provides, but experience the cannabis as working during, and temporarily after the hallucination. Many wish they could get the relief without the high associated with the plant. Cannabis plants high in CBD and low in the psychoactive THC may help with this. CBD is a cannabinoid that mellows the mood and calms nerves while curbing the hallucinogenic effects of THC .