Cannabis Grow

Fourty-four percent of twelfth-graders have used marijuana in their lifetime, 20% used in the past month, and 5% use daily , representing a large increase from the 16% of 8th graders who have tried marijuana. Furthermore, 40% of high school students who used marijuana in the past year met criteria for marijuana abuse or dependence . Marijuana use in adolescence causes significant concern since marijuana use may impact the brain, which is still developing throughout adolescence. Though overall brain size stabilizes around age five , important progressive and regressive developmental processes continue throughout adolescence, including myelination , synaptic refinement , reductions of grey matter volumes and improved cognitive and functional efficiency . It is unclear how heavy marijuana use at this time could influence neural development. The long-term effects of marijuana have not yet been determined, but could potentially have major implications on social, academic, and occupational functioning. Although a good deal of research has been done on the effects of marijuana in chronic adult users, very little is known about adolescent users. Studies have shown that chronic marijuana has an influence on the neuropsychological performance of adults within a week of use. Specifically differences have been found in attention and executive functioning , memory , psychomotor speed and manual dexterity . One study demonstrated verbal learning deficits among cannabis flood table users compared to controls 0, 1, and 7 days following use, but that these impairments subsided after a 28-day abstinence period .

However, others have identified impairments in memory, executive functioning, psychomotor speed, and manual dexterity after 28 days of verified abstinence compared to published norms . Furthermore, adults who began use early in adolescence demonstrated greater decrements on verbal IQ after a 28-day abstinence period those who began late in adolescence and non-using controls, suggesting an adolescent vulnerability . Due to its high safety profile and good spatial resolution, functional magnetic resonance imaging has become a powerful method for visualizing neural activation. Research on adult marijuana users has shown alterations in brain response via fMRI scanning. More specifically, these studies have demonstrated an increase in spatial working memory brain response in marijuana users compared to normal age-matched controls in the pre-frontal cortex, anterior cingulate, and the basal ganglia . This suggests a compensatory neural response as well as recruitment of additional brain areas to achieve necessary task requirements, as seen in a recent study of task performance and brain functioning in marijuana users . However, because this study was done on adults who were abstinent for only 6-36 hours prior to the scan, it may be that these effects reflect recent use and not persisting effects . Others have characterized visuospatial attention among 12 recent marijuana users who had used 2 – 24 hours earlier, 12 abstinent users who not used for an average of 38 months, and 19 non-using controls . Both active and abstinent users showed decreased brain response in prefrontal, parietal, and cerebellar regions that normally subserve visual attention, and increased activation in alternate regions, suggesting brain response alterations even after extended abstinence. These adult fMRI studies point to altered neural functioning among marijuana using adults during visuospatial tasks, particularly in frontal and parietal regions. Less is known about neurocognitive functioning in adolescent marijuana users. A longitudinal study of ten adolescent marijuana users showed incomplete recovery of learning and memory impairments even after six weeks of abstinence . Recent fMRI studies of SWM involving alcohol-abusing adolescents and marijuana and alcohol-abusing adolescents have found that marijuana and alcohol were associated with greater changes than alcohol alone. Specifically, after an average of 8 days of abstinence, adolescent marijuana users showed an increase in dorsolateral prefrontal activation and reduced inferior frontal response compared to alcohol users and non-using controls, suggesting compensatory working memory and attention activity associated with heavy marijuana use during youth.

Adolescent marijuana users demonstrated increased right hippo campal activity and poorer attention and verbal working memory performance compared to demographically similar tobacco smokers and non-using controls, suggesting compensatory neural recruitment, even after a month of abstinence . In a follow-up study, marijuanausing youths who were abstinent at least two weeks performed similarly as non-users on verbal working memory during ad libitum smoking and again during nicotine withdrawal, but exhibited increased parietal activation and poorer verbal delayed recall during nicotine withdrawal compared to non-marijuana users . Together, these studies suggest altered working memory functioning among adolescent marijuana users that may persist after a month of abstinence. Yet it is unclear how variability in task performance might contribute to brain activation patterns. Among normal adolescents, spatial working memory task performance is associated with activation in bilateral prefrontal and posterior parietal brain regions . Adult studies have suggested increased frontal and parietal activity associated with greater spatial working memory task difficulty . FMRI studies of adolescent and adult marijuana users have suggested that increased neural responding associated with marijuana use may be evidence of compensatory neural recruitment to maintain task performance . Therefore, the relationship between task performance and neural response may differ between marijuana users and controls, with a stronger positive relationship among marijuana users. The interaction between task performance and fMRI response to SWM has not yet been studied in adolescent marijuana users. The goal of the present study was to understand how task performance patterns contribute to neural activation in abstinent adolescent marijuana users. We studied blood oxygen level dependent fMRI neural activation during a SWM task which typically activates bilateral prefrontal and posterior parietal networks in adolescents and adults .

This SWM task has been shown to be sensitive to brain response abnormalities in adolescent alcohol and marijuana users. In this study, both adolescent users and controls were required to abstain from all drugs and alcohol for 28 days prior to their fMRI scan, and all were free from psychiatric disorders and learning disabilities. Based on our previous work we predicted that after 28 days of abstinence, marijuana users as a group would perform as well as controls; however, the task performance would vary within each group resulting in a group by task performance interaction that would be associated with brain response. Specifically, we hypothesized that there would be interactions between task performance and fMRI response in the bilateral dorsolateral prefrontal and posterior parietal cortices, such that marijuana users show a stronger positive association between performance and brain response than controls in these regions. This study examined the association between behavioral performance and brain response during a SWM task among 16- to 18-year-old marijuana users and controls after 28 days of abstinence. Results suggest that, in general, marijuana-using teens performed similarly on SWM than controls, perhaps due to the low difficulty level of the task , which approached ceiling effects. This has been observed in fMRI studies of SWM in adult cannabis grow supplier users . However, specific localization and intensity of response varied between the MJ users and controls, with MJ users showing more performance-related activation in certain regions and less in others. These differential patterns emerged despite similar overall task performance across groups, suggesting an alternate relationship between task performance and brain activity among marijuana users. MJ users showed significantly more activation than controls in the right basal ganglia, an area associated with skill learning . Since the subjects were only allowed to practice the task once before entering the scanner, it is possible that the MJ users were still in the skill learning process during imaging. The other two clusters, which were significantly more activated in marijuana users than controls, were the right and left parietal lobes. Bilateral parietal regions have been implicated in attention, spatial perception, imagery, working memory, special encoding, episodic retrieval, skill learning monitoring, organization, and planning during working memory . It is possible that there is compensatory neural effort in these areas, as observed in SWM studies of adult marijuana users . The performance data positively related to activation in several areas, and did not negatively associate with brain response in any region. Performance was positively associated with activation in the left and right temporal regions, which are associated with verbal mechanisms and episodic, nonverbal working memory and retrieval, respectively . This suggests that good task performance may be related to using multiple memory modalities. High-scorers showed more activation in the bilateral prefrontal and bilateral parietal regions that have been shown to activate during SWM tasks in youths . The performance by group interactions were the focus of this study and yielded the most interesting results. In particular, an interaction in the left superior temporal gyrus suggested a positive association in the users and a negative association in the controls. This may imply that the MJ users used more of a verbal strategy to achieve high task performance scores than the controls. This is interesting when considering the previous findings of deficits in verbal learning and IQ in marijuana using adolescents compared to controls . Furthermore, the right superior temporal gyrus showed an interaction where users had a negative association and controls had a positive association. Previous studies have shown this area to be involved in poorer recognition of previously seen words . This would support the notion that users are relying on a verbal strategy so that better performance linked to a decrease in activation in the right superior temporal gyrus. Moreover, an interaction in the right thalamus and pulvinar showed a negative association in the users and a positive association in the controls. These subcortical structures have shown an association with spatial neglect when damaged.

It is interesting that these areas have a negative association in users and a positive association in controls, and may suggest that marijuana users utilize less spatial strategies than controls. The nature of the interaction revealed a positive association in marijuana users and a negative association in controls in the left anterior cingulate. This region has been linked to attention, decision-making, cue response, and response monitoring . It may be that good performing marijuana users are making a more conscious decision to react to task cues than controls, who may be reacting more automatically. The left parahippocampal gyrus demonstrated an interaction of negative association in marijuana users and positive association for controls. This region is involved in working memory and is recruited when the temporal lobe is not in use . Since marijuana users are using more energy in the left temporal lobe as their performance increases, higher scoring subjects may rely less on the parahippocampal gyrus. The distinct interactions viewed in these different areas of the brain can mean that different systems are at work, and as one part of a system decreases in action, the other area of the system increases in activation. Previous studies suggest that subjects who do not use traditional strategies for specific tasks showed an increased extent of activation and recruitment of additional areas, specifically verbal areas, to accomplish the task . More specifically, the pattern of results suggests that marijuana users may apply a verbal strategy to the task when achieving higher scores. It is possible that this alternative way of using the brain may be less efficient; this would explain the greater overall activation in users versus controls and recruitment of other brain regions as a compensation method. A recent review also found that multiple neuroimaging studies of marijuana users pointed toward recruitment of compensatory regions as well as task-related regions to achieve task demands . A possible limitation to this study is the interpretation of a difference in fMRI activation between experimental groups. It is possible that alternative neural pathway use is more dynamic and versatile. It is unclear whether the results are an adverse effect of the marijuana use or merely a benign difference. Further studies that more carefully describe the relationships between task performance and brain response will clarify this question. Another limitation of thecurrent study is that most marijuana users were also moderately heavy alcohol drinkers. While these participants are representative of the population of adolescent marijuana users, most of whom also consume alcohol , it is nonetheless difficult to disentangle the effects that may be related to alcohol use.

While multiple complex processes are involved in the pathogenesis of ischemic AKI, tubular cell injury, increased oxidant stress, and inflammation are common denominators.IR-induced renal tubular injury results in increased expression of adhesion molecules, such as vascular and intercellular adhesion molecule1 , and selectins, such as Pselectin and E-selectin.This is followed by the attachment, activation, and transmigration of immune cells into renal tissue, which results in inflammation. Subsequent production of reactive oxygen species and disruption of the nitric oxide pathways lead to further tubular damage, inflammation, and oxidative stress.7 These abnormalities trigger a pathologic cascade of events that ultimately lead to propagation of renal injury and manifest clinically as kidney failure. The endocannabinoids are endogenous, bio-active lipid mediators that exert their effects mainly through specific G protein-coupled receptors: type-1 cannabinoid receptor and type-2 cannabinoid receptor . The most extensively studied ECs are arachidonoyl ethanolamide and 2-arachidonoylglycerol . They are synthesized on demand through distinct cellular pathways and are released in the local micro-environment, leading to autocrine or paracrine downstream effects. Given the abundance of CB1 receptors found in the central nervous system and CB2 receptors on immune cells, the ECs were initially thought to be active only in these systems. However, CB1 and CB2 receptors have been discovered in a multitude of peripheral tissue, including the kidneys.Although not fully understood,heavy duty propagation trays the activation of CB1 receptors in the periphery has been shown to be associated with increased oxidative stress and inflammation, whereas activation of CB2 receptor has been known to have the opposite effect.Furthermore, the ECs and their metabolites can also exert hemodynamic and other effects through CB receptor dependent and -independent pathways.

Given the major role that inflammation and oxidative stress play in IRI and the known involvement of the EC system in these pathways, there has been extensive evaluation of the EC system in pathophysiology of IRI of several organ systems, including the brain, heart, and the liver. Several reports indicate that both the blockade of CB1 receptors and the activation of CB2 receptors protect against IRI in the tissues mentioned.Interestingly, these findings have also been confirmed in nephrotoxic AKI using a murine cisplatin renal tubular injury model.In addition, there are now numerous reports that highlight the involvement of the EC system in renal injury and fibrosis in a variety of settings, including diabetic nephropathy.Despite the preponderance of evidence implicating the EC system and ECs in nonrenal IRI, data on the role of ECs in renal IRI remain sparse.In addition, most of the studies examining the role of the EC system in renal injury focus on the effects of the activation or inhibition of the CB receptors and do not provide data on the tissue level of the endogenous ligands for these receptors, 2-AG and AEA. In this study, we show for the first time that renal IRI leads to a significant increase in renal level of 2-AG, one of the major activators of the EC system. Furthermore, enhancement of renal 2-AG levels using pharmacologic tools improved indices of renal function without changing markers of inflammation or oxidative stress. These results indicate that renal ECs are involved in the pathogenesis of IR-induced AKI, and how modulation of the EC system may impact renal injury and function will need to be studied in further detail.All animals were handled and procedures were performed in adherence to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and all protocols were approved by the University of California, Irvine Institutional Animal Care and Use Committee. Male C57BL/6 mice 8–12 weeks old were obtained from Jackson Laboratories . They were housed in the UC Irvine facility under specific pathogen-free conditions, were allowed free access to standard chow and water, and were kept in a 12-h light:12-h dark cycle. In the first set of experiments, 20 mice were divided into two groups: one was sham operated and the other underwent 30 min of bilateral ischemia . For the second set of experiments, 20 animals were divided into two groups: one received the monoacylglycerol lipase inhibitor JZL184 and the other received the correspondent vehicle 2 h before I/R .We used an established mouse model of ‘‘warm’’ renal I/R injury.27 Briefly, mice were anesthetized with ketamine/xylazine and kept on a homoeothermic station to maintain body temperature at 37 C. A warming blanket was used throughout the procedure and for 30 min post procedure . The body temperature of each animal was monitored closely throughout the procedure and afterward using a noninvasive infrared digital temperature device. A midline incision was made and bilateral renal pedicles were exposed.

Using atraumatic Micro Serrefne straight clamps , both renal pedicles were cross-clamped. To maintain fluid balance, mice received 0.7 mL of sterile 0.9% saline by intraperitoneal injection. After 30 min of warm ischemia, clamps were removed initiating renal reperfusion. Sham control animals were subjected to identical operation without clamping. Mice were sacri- fificed at 24 h after reperfusion for serum/kidney sampling under terminal general anesthesia using isoflurane. Blood was taken by intracardiac puncture after accessing the chest cavity from underneath the diaphragm. Briefly, before the opening of the chest for blood collection through cardiac puncture, anesthesia was induced in a chamber with 4–5% isoflurane in 100% O2 and then maintained by continuous administration of 1– 2% isoflurane through nose cone. We made certain that all animals were fully anesthetized prior and during surgery. This method is approved by the University of California Irvine Institutional Animal Care and Use Committee and consistent with the AVMA Guidelines for Euthanasia. Approximately 100 lL of serum was isolated and stored at 80 C. The kidneys were harvested after euthanasia/cardiac puncture. Both kidneys were cut in half along the renal pelvis. One and half kidney was immediately snap-frozen in liquid nitrogen while half of the kidney was fixed immediately. To avoid inter tissue variability and avoid comparing different regions of the kidney, we fixed the same half of the kidney for all animals and compared the same region of the fixed kidney for histopathology evaluation.This is the first study that examines the effect of kidney IRI on renal EC levels and their potential impact on pathophysiology of AKI. We have found that kidney IRI is associated with a significant increase in renal2-AG content. Kidney 2-AG levels correlated positively and significantly with serum BUN and creatinine. Furthermore, enhancement of renal 2-AG levels using the selective MGL inhibitor, JZL184, caused a modest but significant improvement in renal function. Interestingly, the latter findings were not associated with improvement in renal markers of inflammation and oxidative stress, indicating that the improvement in renal function induced by 2-AG may be independent of proinflammatory and oxidative processes.

The findings of our study are unique in several respects. First, while the role of the EC system in AKI has been examined through modulation of CB receptors in animal models of nephrotoxic tubular injury, this is the first investigation examining EC levels and the role of the EC system in ischemic AKI and renal IRI.Therefore, the current findings shed light on how the EC system as a whole may be involved in the changes observed in renal IRI. Furthermore, our study demonstrates that renal IRI is associated with increased kidney 2-AG content. The latter findings are significant because understanding how ECs are mobilized in renal IRI is crucial to their potential exploitation as a therapeutic strategy. It is also intriguing to note that increased tissue 2-AG content has also been reported in IRI in other organ systems such as the liver,vertical cannabis and, just as in the kidney, enhancement of tissue 2-AG levels was associated with improvement of IRI.Therefore, it is noteworthy that the findings described in this study are not exclusive to the kidney, thus reflecting a potential physiopathological role of 2-AG and the EC system in IRI, which needs to be further explored. While increased 2-AG levels have mostly been reported to be associated with reduced tissue injury in IR, the mechanisms through which 2-AG affords protection in IRI remain unclear. Several possibilities have been examined, one of them being a potential anti-inflammatory action of 2-AG mediated by CB2 receptors. However, available data on the impact of 2-AG on inflammation are contradictory, with some studies reporting anti-inflammatory properties, while others noting proinflammatory effects.In our study, we did not find significant changes in the expression of proinflammatory cytokines or adhesion molecules following pharmacological enhancement of renal 2-AG levels. In fact, we observed a trend toward an increased expression of these markers. Indeed, there are recent studies that link increased 2-AG levels with worsening of inflammation.It is possible that increased tissue levels of 2-AG may lead to activation of CB1 receptor, hence causing a trend toward worsening inflammation; however, this mechanism has not been established in renal IRI. Given that indices of renal inflammation and oxidative stress remain unchanged, our findings support the notion that the modest improvement in renal function observed with enhanced 2-AG levels may be related to effects independent of its role in in- flammation and oxidative stress. In this regard, there are several studies indicating that 2-AG has vasodilatory properties through CB1-dependent and -independent mechanisms.For instance, Awumey et al. have demonstrated that 2-AG can cause relaxation of arterial smooth muscle through its metabolite glycerated epoxyeicosatrienoic acid, which can activate potassiumgated calcium channels on vascular smooth muscle cells resulting in hyperpolarization of these cells and vascular relaxation.One possibility is that increased kidney 2- AG levels in renal IRI could cause arterial vasodilatation, which would lead to improved renal perfusion and enhanced glomerular filtration rate, thereby explaining the improvement observed in renal function.

It should also be noted that since we administered JZL184 systemically and most likely increased 2-AG levels in other parts of the body, it is possible that the renoprotective effect observed in our study may be emanating from outside of the kidneys . These possibilities will need to be examined in future studies.First, there is emerging evidence that dysregulation of this system may be involved in diabetic nephropathy, proteinuria, renal fibrosis, and AKI.Second, pharmacological agents are available, which can modulate EC levels and CB receptor activity, thereby providing potential therapeutic strategies. Finally, considering recent reports pointing at synthetic cannabinoid use as a cause of AKI,investigation of the EC system in renal disease may shed light on the mechanism by which these recreational drugs can potentially cause renal injury and help formulate preventive plans in risk population. Several limitations of our study need to be mentioned. The potential role of 2-AG as a mediator of vasodilation and its impact on renal blood flow rate will need to be thoroughly explored in future studies. Furthermore, in our mouse model of AKI, we had a limited supply of plasma, and therefore, systemic levels of ECs in IR AKI remain to be determined. Moreover, given that JZL184 was administered systemically, we cannot rule out inhibition of MGL in other organs that could have had a downstream effect on the kidneys. In addition, despite its specificity for MGL, it is possible that JZL184 may have an impact on other serine hydrolase enzymes that may explain some of the results we are observing in our studies. Furthermore, our evaluation of renal markers of inflammation and oxidative stress pathways was limited to mRNA analysis, and therefore, renal abundance of each protein will need to be determined to complement the mRNA findings. Finally, our study does not address the mechanism/s responsible for increased renal 2-AG levels. We have recently reported that oxidative stress can cause the reversible sulfenylation of MGL and inhibition of its activity, hence leading to decreased 2-AG breakdown and increased 2-AG levels.42 Given that kidney injury is associated with significant oxidative stress, it is possible that MGL inhibition is the mechanism responsible for increased 2-AG levels in renal IRI, however, this possibility will need to be confirmed in future studies. In conclusion, renal IRI is associated with a significant increase in kidney 2-AG content. Further enhancement of renal 2-AG levels using a pharmacologic tool, which inhibits its breakdown, improves indices of renal function and kidney injury, without affecting expression of markers of inflammation and oxidative stress.

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,cannabis equipment 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. Though in North Carolina, U.S. government officials only used Google Earth to verify code violation complaints, in places like India, New York, Argentina and Greece, Google Earth was used in the active reconnaissance of committed crimes. Marine researchers have also used analyses of Google Earth to evaluate the veracity of fish-catch reports made to the UN. Spain’s Green Party has reported illegal bottom trawling of beaches for fish using Google Earth images, as well. Google Earth has also been used to detect illegal dumping. For example, in Florida, a sheriff’s deputy used Google Earth to apprehend an individual who dumped a large boat; in Mississippi, a landowner identified a stolen and illegally dumped truck on his property using Google Earth; while in Bangalore, Google Earth was used to identify unauthorized and illegal waste dumping sites. Illegal logging is also actively identified using Google Earth by such groups as local police departments in the Philippines, the Finnish Association for Nature Conservation and their associated NGOs in Russia, the Amazon Conservation Team and associated indigenous groups. Amateur Google Earth users have reported potential body-dumping based on the imagery available, as well. Some of the issues associated with Google Earth arise from the fact that its images are made available by a privately-owned corporation and are technology driven. Thus, as Sheppard and Cizek note, the visualizations of the Earth made available by this interface are more geared towards “efficiency, convenience…entertainment value, popular demand, and profit” than they are towards “truth, deeper understanding, improved civil discourse, safer and more informed decisions, and other ethical considerations”. As these and other authors point out, realism in landscape visualization is not the same as accuracy or validity.

Virtual globes, like Google Earth, may suffer from low data resolution, interfering with image clarity and accuracy, missing data or inaccurately displayed data. Further, it is often impossible to know the exact date of the imagery available on Google Earth and whether all images in a scene are from the same date . Thus, a potential crime sighted on Google Earth may be months or even years old or may be exaggerated by differing image dates. Finally, these data may be manipulated by the producers of these virtual globes for various privacy reasons; some areas are intentionally blurred or objects are not displayed. More significant than spatial and temporal accuracy is the consumption and use of these images by untrained or informal interpreters. These informal interpreters may not understand the temporal or spatial inaccuracies inherent in these data. Goodchild points out that users of Google Earth may be misled to think it is more accurate than it is in reality. Despite the fact that Google Earth images’ absolute positional accuracy is sufficient for assessing remote sensing products of moderate resolution, errors and positional inaccuracies are still a problem. Trained remote sensing analysts understand these limitations and may be able to account for them, whereas casual users may not. Untrained remote sensing analysts may also misinterpret the images available to them. For example, in the case mentioned above, where amateur Google Earth users reported a dumped body, their interpretation of the image was flawed. In this case, the “dumped body” turned out to be a swimming dog. The dog’s watery trail on the cedar wood dock and the dog lying on that dock appeared to be a bloodied body rather than a picture of a sunny day at a lake.Un-validated identifications of “crimes” using Google Earth images by amateur analysts unfamiliar with the inaccuracies of these images or the nuances of image interpretation may be problematic for several reasons. First, they may cause law enforcement officers to seek places or things that are not where they are purported to be, are no longer present or never existed in the first place. This may result in a waste of funds, resources and personnel hours. Second, the mis identification of a site as a place where a crime is or has occurred opens that place and its residents up to potentially needless intrusion, intimidation, surveillance or violence.

Despite the increasing ease with which satellite images and other spatially explicit data flow to us, ethical and scientific rigor should not be laid aside. Finally, as Purdy and Leung note, Earth Observation data like those used in products like Google Earth may have their evidential weight in a court of law seriously reduced if un-validated, because the medium by which it was taken, the data management systems used or even the date the image was taken may be unknown. Given the potential for amateur misinterpretation or overconfidence in Google Earth images, it is obvious that crimes detected in this manner must be validated to ensure appropriate, timely and safe responses by government of law enforcement officers. While there have been a few cases where crimes detected using Google Earth were validated, either by fly-overs or personal ground validation missions , in the majority of cases, there is no discussion of accuracy assessment or validation. This dangerous trend toward trained and untrained analysts taking Google Earth images as “truth” with no validation may have broad reaching potential impacts on law enforcement efforts and personal security. Despite the fact that cutting-edge technologies are being used to remotely detect crime, the accuracy assessments of those analyses lag well behind current remote sensing standards. Indeed, as we have shown above, some studies that attempt to remotely sense crime do not perform accuracy assessments at all, depend on the opinions of “experts” or “surrogate ground truth data”, all of which are deemed to be substandard by today’s remote sensing community. Many of the studies noted above performed no accuracy assessment at all; they did not even use Google Earth or Digital Globes to validate their data. Particularly, in situations that may have life-and-death implications or serious environmental effects ,vertical grow shelf law enforcement officers must strive to be as accurate as possible in their targeting of crimes and criminals. Although drones or unmanned aerial vehicles/systems may present excellent options for accuracy assessment, offering up quiet, real-time, high resolution imagery of remote or distant areas without threat to human life, they are not ideal solutions in every situation. The equipment, licensing, training and maintenance required to acquire and safely maintain a UAV may be well beyond the means of many local police departments or underfunded government agencies. In the United States, the Federal Aviation Administration has seriously restricted the use of unmanned aircraft in national airspace . Further, there are serious questions about the constitutionality of using UAVs for law enforcement. Critics of UAV use by law enforcement argue that these vehicles impede an individual’s reasonable expectation of privacy as protected by the fourth amendment Despite these concerns, law enforcement is increasingly using UAVs to detect crimes and facilitate law enforcement . In the following section, we propose some alternate or additional means of validating remotely sensed crime. We hope that this initial thought experiment may help spark a conversation about the methods and ethics of remote sensing in law enforcement. We define “first order” accuracy assessments as those described in the accepted remote sensing protocol , which include ground-based validation or the use of imagery of higher resolutions than the imagery to be validated. Since these first order assessments can be limited by security, funding and terrain issues and drone use presents funding and legal issues, we propose a “second order” level of accuracy assessment. This second order accuracy assessment analyzes the larger geographical and social context in which remotely sensed crimes are detected by remote sensors. Such assessments could utilize crowd sourcing, big data mining, landscape-scale ecological data and anonymous surveys to determine whether and how crimes are occurring and where remote sensing analysts think they are. Second order accuracy assessments may allow remote sensors and law enforcement officers to confirm that crimes are taking place where analysts say they are without facing rugged terrain, insecure conditions or using costly overflight methods. Further, second order validation may enable analysts to gain better contextual understandings of those crimes, allowing for more ethical and proportionate responses by law enforcement. While these second order validation techniques may not be as reliable as first order techniques, they are better than no validation at all.

Alternatively, these second order techniques could be incorporated into interdisciplinary crime detection techniques that may increase detection accuracy. Urban areas are well suited to second order accuracy assessments because of the amount of available social data produced and available at any given moment. For example, Oakland’s Domain Awareness Center plans to link public and private cameras and sensors within the city limits into a single hub for law enforcement use . While highly controversial, these centers present numerous opportunities to validate remotely sensed crimes with closed-circuit television , as well as readily available on-the-ground policing. Rural or more remote areas present more of a challenge, however. These places typically lack surveillance cameras and mounted sensors. It is also in these places that large-scale drug production, human and drug smuggling frequently occur. Thus, here, we use illicit cannabis production as a case study to think through three potential second order accuracy assessment techniques in non-urban zones. Though we acknowledge that each of these methods would require further development and thought and that methods may exist beyond those we propose here, it is our hope that this will be the first effort in a larger conversation as to second order validation techniques in the remote sensing of crime. Social media: Location-based social network analysis may be helpful in validating crimes remotely sensed in other ways through geolocated self-reporting or observations by others. LBSN has been shown to provide reliable spatio-temporal information about incidents occurring in a broad landscape. For example, researchers from the Institute of Environment and Sustainability in Italy used a Twitter application programming interface to retrieve tweets and related metadata for a specific topic, the 2009 Marseille forest fire. These tweets were then organized into meaningful summary statistics using data mining and web crawling scripts. These researchers found that the LBSN data collected were temporally synchronized with actual events and provided some geographically accurate reporting. They note that Twitter “could offer promising seeds for crawlers to collect event-related data where time and location matter”.

Methods exist for extraction of cannabinoids from oral fluid using the Quantisal device. However, the goal of this manuscript is to combine previous methods into a single extraction procedure without a hydrolysis step that would allow for the quantification of the following compounds by one method: THC, cannabidiol , cannabinol , cannabigerol , Δ9 -tetrahydrocannabinolic acid , tetrahydrocannabiverin , 11-hydroxy-Δ9 -THC , 11- nor-9-carboxy-Δ9 -THC , 11-nor-9-carboxy-Δ9 -THC-glucuronide , and Δ9 -THC-glucuronide . This assay will be useful for OF cannabinoid analysis in the establishment of a cannabinoid concentration associated with driving impairment.Oasis prime HLB 96-well extraction plates were purchased from Waters . Mass spectrometry grade methanol , acetonitrile , and formic acid were purchased from Fisher scientific . Blank synthetic OF matrix used to prepare calibrators and quality control specimens was purchased from Immunalysis . OF was collected with the Quantisal™ device also from Immunalysis. Participants refrained from food or drink for 10 min, then the absorptive cellulose pad was placed under their tongue until the indicator turned blue or 5 min had passed. The collection pad was then placed into the plastic collection device containing 3 mL of extraction/stabilization buffer. The extraction buffer is supplied with the Quantisal™ device. The capped tube was placed at room temperature for at least 4 h but not > 24 h. The pad was then removed from the stem using fisher brand standard serum filters and decanted into nunc 3 mL cryovials from Wheaton.The samples were then stored at 4 °C. Each sample was weighed in attempt to derive a short sample correction factor before being analyzed within 2 months of collection.

Positive QC standard solutions of 300, 60, and 12 ng/mL were prepared by parallel dilutions from a 1000 ng/mL stock in methanol made the same as described for the calibrator solution except using stock solutions from a different lot than the calibrators. Each solution was aliquoted into amber glass auto sampler vials,garden racks wholesale sealed with parafilm and stored at −20 °C. The solutions correspond to three levels of QC at 60, 12, and 2.4 ng/mL when processed in synthetic OF. The lower level of QC was chosen to reflect a low concentration that was closer to per se cut off values adapted by several states. QC results were reviewed according to an absolute criteria of ± 20% of target values.All calibrators and QCs were prepared by adding 50 μL of calibrator, 50 μL of working IS, followed by one mL of blank matrix to corresponding borosilicate tubes. Subject specimens were treated in a similar manner except methanol was substituted for the calibrator. Samples were then acidified with 400 μL of 4% phosphoric acid. Samples were vortexed briefly then contents were transferred to a well of a 96 well Oasis Prime HLB C18 SPE plate. Samples were forced through the wells using a positive pressure manifold on low pressure until all liquid was pushed through. This took approximately five minutes to drip through. Each well was washed with 500 μL of SPE wash buffer twice under low pressure. The pressure was switched to max flow for one minute following the second wash to push any excess liquid through the well. Compounds of interest were eluted into 750 μL glass inserts with three successive 100 μL aliquots of 98% ACN with 2% formic acid for a total of 300 μL eluant. Extracts were evaporated under nitrogen at 40 °C with gas flow set to 70 psi for 30 min. Dried extracts were reconstituted with 200 μL of 50% ACN containing 0.1% formic acid. Plates were covered with a silicone/PTFE treated, pre-slit cap mat and vortexed using the Fisher scientific Ana Multi-tube vortexer on speed setting of 4 for 5 min.

Plates were centrifuged at 1962 x g for 10 min in Sorvall legend XFR centrifuge and then transferred to the sample organizer for LC-MS/MS analysis.Chromatography was performed using a Waters Aquity i-class UPLC system equipped with sample organizer, binary solvent manager, auto sampler, and a column oven . Separation of analytes was achieved using a Waters 2.1 × 50 mm Acquity UPLC BEH C18 column packed with 1.7 μm sized particles. The analytical column was attached to a 2.1 mm × 5 mm ACQUITY UPLC BEH C18 VanGuard Pre-column packed with 1.7 μm particle size to prevent column degradation due to sample buildup. Guard columns were replaced after every 1000 injections. The auto sampler was set to 10 °C. The column heater was set to 40 °C. A full-loop 10 μL injection was made for each sample. Gradient elution was performed using a mobile phase A of 5 mM ammonium formate buffer with 0.1% formic acid and a mobile phase B of acetonitrile with 0.1% formic acid at a constant flow rate of 400 μL/min. The initial gradient conditions were 50% MPB, held for 30 s, and then linearly increased to 90% MPB over 3.5 min. The final MPB concentration was maintained for 15 s, before returning to initial conditions and holding for 45 s. The maximum pressure was set to 15,000 psi.The LC system was coupled to a Waters TQ-S-micro triple quadrupole mass spectrometer interfaced with an electrospray ionization probe. Negative ionization was used for THC-COOH-gluc. All other compounds used positive ionization. The mass spectrometry transition ions were collected using a scheduled multiple reaction monitoring mode with four separate time windows. The first time window was collected in negative ion mode from 1.00 to 1.50 min. The subsequent windows were collected in positive ion mode from 1.51 to 2.59 min for TW-2, 2.60 to 3.22 min for TW-3, and 3.23 to 4.20 min for TW-4. The selected precursor and product ions, collision energy, retention times and associated windows are displayed in Table 1. The source temperature was set to 550 °C for both modes.

The instrument was controlled with Masslynx V4.1 SCN945 SCN960 software and peaks were processed using TargetLynxs XS. A representative reconstructed chromatogram of all quantifier ions from a 20 ng/mL calibrator is displayed in Fig. 1.To demonstrate that the synthetic OF was a valid substitute for OF specimens from humans, OF from 10 drug free volunteers was collected and processed such that a one mL aliquot was fortified with low QC and IS, while another one mL aliquot was processed unaltered . The percent bias was calculated by dividing the difference between the averaged concentration of the low QC in human OF samples from the average concentration of low QC in blank matrix by the averaged concentration of low QC in blank matrix. A qualitative assessment of matrix interference was also performed by injecting each of the unspiked OF samples while simultaneously infusing a calibrator solution containing 10 ng/mL of each analyte. See Fig. 2 for total ion chromatograms of the blank OF samples. Potential drug interferences were assessed by generating 5 pools of 10 different drugs belonging to opiates, benzodiazepines, and other common drugs of abuse that could be present in a suspected DUI subject . Superphysiological concentrations of the pools of drugs were added to blank OF samples fortified with low QC. Recovery of the QC within ± 20% of expected concentration in the presence of super physiological concentrations of drug pools was required to demonstrate lack of interference.Auto-sampler stability was assessed by comparing the average area counts from the low QC to the area counts of an injection at 24 and 48 h post-extraction. Acceptable stability was set at ± 20% CV in area of a 1.25 ng/mL stock compared to the initial injection. Lack of carryover was established by injecting a blank matrix fortified with IS immediately after the highest calibrator and then comparing the area counts to the same blank matrix with IS injected prior to the calibration curve. The acceptable level of carryover was a set to < 20% increase in area counts of the blank matrix following reinjection after the highest calibrator.Proof of applicability is demonstrated by evaluating the concentrations of cannabinoids in three participants enrolled in an Institutional Review Board-approved study evaluating the effects of inhaled cannabis containing either placebo , 5.9% or 13.4% THC by weight. Inclusion criteria for participation were individuals had to be at a minimum an occasional user ,hydroponic racks abstain from marijuana use 48 h prior to testing, and have a valid drivers license. Oral fluid samples were collected upon arrival to the laboratory which was tested to demonstrate THC < 5 ng/mL using the Alere OF point of care instrument. Individuals whose OF screened negative on the Alere device then smoked a joint containing either placebo, 5.9%, or 13.4% THC. Oral fluid was then collected 15, 90, 210, and 280 min after smoking and processed as described above.

The complete study design and detailed methods will be published after the target enrollment of 180 subjects is complete.A qualitative matrix effect study was performed by infusing a 10 ng/ mL calibrator solution during an injection of an extracted oral fluid specimen from drug-free volunteers . There was no observable ion suppression or enhancement across any of the analytes peaks in the human oral fluid specimens . Quantitative assessment of matrix effects was performed by fortifying the human drug-free oral fluid specimens with low QC and calculating the percent recovery to expected values established in the inter-day validation . Acceptable critera were set as a percent difference < 20% from expected. No matrix effect exceeding this criteria was observed in the human oral fluid specimens when compared with the synthetic oral fluid used for calibrators and controls. Extraction efficiency was determined by comparing average peak areas of extracted blank matrix samples fortified with low, mid, or high QC divided by peak areas of blank matrix samples fortified post-extraction with QC. All analytes had less than a 9% difference in extraction efficiency between any level of QC with a range of efficiencies from 26.0–98.8% . Percent matrix bias were determined by comparing average peak areas of blank matrix samples fortified post-extraction with low, mid, or high QC divided by neat solutions of QC. The range of percent matrix bias was −37.6–23.7%. THCA-A observed the worst ion suppression followed by THC-V . THC-COOH observed the greatest ion enhancement due to matrix effects observed to be > 20% in the mid QC, whereas all other analytes had percent differences < 20%. The THC-COOH internal standard compensated for the matrix enhancement providing results within ± 20% of target values. Interferences were assessed from five pools of ten drugs in blank OF fortified with low QC. The percent bias for all cannabinoids ranged from −17.4–12.7% . Thus, no drugs that were tested caused any interference in calculating the low QC concentration.The areas for all the compounds were within ± 20% upon reinjection at 24 h in the auto-sampler. The 48 h injection of samples had a percent difference within 20% for CBN, CBD, THC, 11-OH-THC, THCCOOH, and CBG, but a percent difference < 28% for THC-gluc, THCCOOH-gluc, THC-V, and THCA-A. In the 48 h reinjections, the internal standards compensated for changes in area counts so quantitative results were within 20% of the initial values. Dilution integrity was acceptable within ± 20% of target concentrations for THC after diluting 1:10 with blank matrix. THC quantified within 3.1% of expected concentrations. There was no evidence of carry-over for any of the cannabinoids following injection of a sample containing 2000 ng/mL.Quantification of THC and related metabolites is part of a research project that aims to establish the concentration of cannabinoids associated with driving impairment following consumption of a low does , high dose , or placebo . Participants have their OF samples collected prior to and immediately after smoking one of the randomly assigned joints. The study is a double-blinded approach, thus the laboratory is blinded to which participants have smoked which kind of joint until the conclusion of the study. To demonstrate proof of applicability, the laboratory was unblinded to identify the first three participants in this study that smoked either the placebo, low or high dose joint. The purpose of including data from three subjects who smoked marijuana is to demonstrate the analytical method is capable of measuring these compounds in specimens obtained from human volunteers, and not to draw any conclusions regarding pharmacokinetics or determining severity of impairment. One participant from each group had their oral fluid samples assessed by this method with concentrations of each cannabinoid listed in Table 7.

Mixed evidence for the combined impact of alcohol use and HIV infection on memory functioning may be attributable to different stratifications of alcohol use , presence of co-occurring substance use and mental health conditions, as well as assessment method. For example, standardized laboratory-based neuropsychological testing tends to assess performance at a single time point and in a highly specific contextual setting. Indeed, the ecological validity of using neuropsychological tests to assess cognitive function having been questioned due to the nature of laboratory settings for neuropsychological testing, the potential for interactive effects of increased demands on cognition in everyday settings and cognitive deficits, and compensatory strategies that may be effective for a laboratory-based task but are not reflected in self-reported memory skills. Although neuropsychological tests provide objective data for specific cognitive deficits, it has been argued that subjective cognitive measures are more sensitive indices for everyday memory functioning [see], such as patients’ experience of everyday memory failures or milder, more variable cognitive struggles that fluctuate over time [e.g., ]. Use of self-report measures may therefore provide a complimentary lens through which to examine the effects of problematic alcohol use on memory functioning among individuals with HIV. For instance,grow rack self-reported memory functioning has been shown to explain variance in self-reported medication management over and beyond that accounted for by neuropsychological test measures. At present there is a general dearth of empirical investigation of the impact of varying levels of alcohol use on self-reported and everyday memory functioning among those with HIV.

This is unfortunate given the well-established associations between memory dysfunction and poor HIV-related outcomes and lower perceived quality of life among individuals with HIV. Further, because even moderate alcohol use may be harmful in this vulnerable population, such questions are relevant for the effective implementation of interventions that heavily tax memory, learning and attention. It is also important to examine these relations in the context of cooccurring substance use and mood disorders, which are common in this population. Accordingly, the primary objective of the current study is to examine the extent to which problematic patterns of alcohol use impact different facets of self-reported everyday memory functioning among a sample of HIV-infected individuals. We hypothesize that problematic alcohol use will be associated with greater perceived memory dysfunction among individuals with HIV, even after controlling for medication adherence, depression, and co-occurring substance use. Given that problematic alcohol use and memory functioning are known to independently influence HIV outcomes, our secondary aim is to assess the extent to which poor perceived memory functioning may serve as an indirect pathway between problematic alcohol use and HIV symptom severity. specifically, we hypothesize that self-reported memory functioning will mediate the association between problematic alcohol use and HIV symptom severity.The Alcohol Use Disorder Identification Test is a 10-item self-report measure developed by the World Health Organization to identify individuals with alcohol problems. The AUDIT assesses three domains: alcohol dependence, harmful drinking , and hazardous drinking . Most items are rated on a 5-point Likert scale ranging from never to daily or almost daily. In the present study, items were summed to generate an index of total alcohol problems. A wealth of literature attests to the strong psychometric properties of the AUDIT [see], in addition to its use for the detection of problematic drinking in HIV-infected samples. Alcohol abuse and dependence were determined by the Structured Clinical Interview-Non-Patient Version for DSM-IV .

Criteria for cannabis dependence were consistent with DSM-IV criteria with the addition of withdrawal as proposed for DSM-5. Participants were classified as non-dependent cannabis users if they reported any cannabis use in the past 30 days, but did not meet criteria for cannabis dependence. Participants with no cannabis use in the past 6 months were classified as nonusers. The Marijuana Smoking History Questionnaire is a 21-item measure that assesses the frequency, patterns, and history of cannabis use. Participants who reported any cannabis use in the past 6 months were asked to provide additional information indicating the number of times they had used cannabis during the month prior to assessment. In the present study, cannabis use status was included as a covariate in all analyses and the MSHQ was used to describe frequency of cannabis use.Participants were recruited via informational flyers posted throughout a VA Medical Center and in numerous San Francisco Bay Area outpatient HIV clinics. Upon contacting the research team, individuals were provided with a detailed description of the study. Interested individuals were screened on the phone for eligibility and, if eligible, scheduled for a study appointment where they provided written consent to participate in the research study. The SCID-I–N/P was administered by trained research assistants and all interviews were audio-recorded and diagnoses were confirmed by the last author following a review of recorded interviews. Participants then completed the above-described measures. All study procedures were approved by a university Institutional Review Board .Descriptive statistics and alpha reliability coefficients were calculated for all measures. Number of cigarettes smoked per day, problematic alcohol use and memory functioning were log-transformed to correct for positive skew. A valueof 1 was added to variables including zero prior to their transformation. Bivariate Pearson correlations were conducted to examine relations between the EMQ total score and sub-scale scores, problematic alcohol use, and HIV symptom severity. Bivariate spearman and pears on correlations were then performed to assess associations between memory functioning, HIV symptom severity and potential covariates .

Based on these analyses, level of education, cannabis dependence and current depression diagnosis were included as covariates in all regression models. Self-reported adherence, although unrelated to memory functioning or HIV symptom severity, was included in the model to ensure that we accounted for variance in outcomes that could be explained by poor medication adherence. Six hierarchical linear regressions were performed to determine the impact of problematic alcohol use on total memory functioning as well as each individual facet of memory functioning. For the five individual memory facets we used a Bonferroni correction with alpha set at 0.01 for an overall rejection level of 0.05. Self-reported medication adherence was entered as a covariate on step 1. Level of education was entered as a covariate in Step 2. In step 3, two dummy coded variables were entered for cannabis use status . In step 4, current depression diagnosis was entered. Finally in step 5, problematic alcohol use was entered to determine how much additional variance in memory functioning was explained by problematic alcohol use after controlling for all covariates.Previous research has implicated memory functioning as a potential pathway through which problematic alcohol use may be related to HIV symptom severity [e.g., ]. Given that both alcohol problems and self-reported memory functioning correlated with HIV symptom severity in the present sample, a series of regression models were performed to determine whether memory functioning mediated the relation between problematic alcohol use and HIV symptom severity. Self-reported medication adherence, highest level of education, cannabis dependence and current depression diagnosis were entered as covariates at steps 1, 2, 3 and 4 respectively, in all models to ensure any relations observed were not accounted for by these variables. First, to test for mediation, problematic alcohol use was regressed on HIV symptom severity . Second, to reduce redundancy, results from the primary analyses were used to determine pathway A, the relation between problematic alcohol use and self-reported total memory functioning . Third, total self-reported memory functioning was regressed on the outcome variable , after controlling for problematic alcohol use . Last,microgreens shelving both bootstrapping and Sobel tests [see] were used to confirm findings from the Baron and Kenny mediational tests. Finally, as the mediational analyses were conducted among cross-sectional data, an additional model was tested to comprehensively assess directionality of the observed effect whereby the proposed mediator and criterion variable were reversed. To account for potential overlap of cognitive symptoms on the HIV symptom severity measure and the EMQ, mediation analyses were also conducted using a HIV symptom severity score that excluded cognitive symptoms. No differences emerged between models using the different scoring systems and thus the results presented represent all HIV symptoms.The present study sought to determine the influence of problematic alcohol use on self-reported memory functioning, and to assess relations with HIV symptom severity among a sample of HIV-infected individuals. Consistent with hypotheses and previous research, problematic alcohol use was associated with lower ratings of overall everyday memory functioning as well as increased difficulty with retrieval and memory for activities. Importantly, this pattern of results suggests that problematic alcohol use tended to specifically impact retrieval-based over processing-based aspects of memory functioning. Also of note, problematic alcohol use exhibited a direct and potent effect on these aspects of perceived memory functioning even after accounting for co-occurring substance use and depression . Finally, perceived memory functioning mediated the relation between problematic alcohol use and HIV symptom severity, though the direction of this relation was unclear and possibly reciprocal.

Findings from the present study lend support to clinical researchers’ call for initiatives to tailor substance abuse treatment and HIV risk-reduction programs to better address impediments posed by cognitive impairment. For instance, techniques to improve multi-modal encoding of clinical information may be particularly beneficial in helping to reduce retrieval-failures observed in the current study. External cueing systems and environmental supports in treatment clinics can also be employed. In addition, although the cross-sectional nature of these data does not permit us to draw conclusions about causality, interventions to remediate cognitive functioning may also improve outcomes in this particularly vulnerable population. For instance, computerized neuroscience-based cognitive remediation programs that target attention, memory and executive functioning could help augment existing treatments by enhancing patients’ cognitive reserve and mental flexibility to adhere to complex treatment regimens and encode, retrieve and employ HIV transmission-prevention skills. As hypothesized, perceived memory functioning provided an indirect pathway for the relation between problematic alcohol use and HIV symptom severity. Thus, one possibility is that the deleterious effects of problematic alcohol use on memory functioning explain the relation between problematic alcohol use and HIV symptom severity. For instance, problematic alcohol use may negatively impact memory for events and retrieval that may increase HIV-risk behaviors and reduce adherence and general self-care and ultimately, increase HIV symptom severity. Importantly though, reversal of the mediational model indicated that HIV symptom severity explained the relation between problematic alcohol use and self-reported memory functioning. As such, HIV symptom severity and memory functioning were interrelated and the extent to which memory functioning offers a distinct mediational pathway between problematic alcohol use and HIV symptom severity is unclear. The blurred directionality observed in our mediation models is believed to highlight the complexity associated with comorbid health conditions that commonly characterize this population, and their impact on HIV health outcomes. More likely, and as articulated in previous work, the relations between memory functioning, HIV outcomes and alcohol use are reciprocal. Among HIV infected individuals, problematic alcohol use is associated with worse HIV health outcomes which ostensibly result in increased HIV symptom severity and lower overall quality of life. Adding to the clinical profile, HIV disease progression is commonly associated with neurocognitive impairment. Given the high prevalence of alcohol problems among HIV-infected individuals coupled with its observed negative impact on memory functioning, routine screening for problematic alcohol use in HIV care settings is thus imperative. In the current sample, problematic alcohol use and all domains of self-reported memory functioning were associated with higher HIV symptom severity. Accordingly, this research combines with previous work to suggest that HIV symptom severity is intricately related to both alcohol consumption and memory functioning and that they should be considered collectively in clinical settings. Results from the current study are consistent with the literature in several respects. Previous research indicates that alcohol and drug use exert greater effects on neurocognitive function in HIV-infected versus non-infected individuals and, thus, HIV is posited to potentiate and exacerbate the impact of alcohol and drug use on neurocognitive functioning. Although no comparison group was available, our findings appear to support this notion and indicate that both problematic alcohol use and HIV symptom severity are associated with lower everyday memory functioning among individuals with HIV. In addition, HIV-infected individuals with a current depression diagnosis were at increased risk for reduced memory functioning and heightened HIV symptom severity, which is also consistent with previous research. Findings here also broadly align with research employing animal models of HIV infection which have shown that HIV can cause neuroplastic changes that impair cellular learning process implicated in memory.

Our use of provider-assigned diagnoses restricted our sample to ICD-9 codes assigned during health plan visits. This method is vulnerable to diagnostic under-estimation; and thus, the rates of bipolar and schizophrenia may be somewhat higher than we report. Another potential limitation with the methods used to select the sample is that we required a single mention of an ICD-9 code for SMI during the study period to link the patient with that diagnosis and included all current and existing diagnoses . While this single mention methodology is well established, it could result in overestimation if diagnoses only mentioned one time in the EHR are more likely to be inaccurate. Since patients with bipolar or schizophrenia could have multiple behavioral diagnoses. Thus, our results should be interpreted with caution until confirmatory studies are conducted in mutually exclusive SMI groups. All data are cross-sectional; and thus, no directionality can be assumed in associations between conditions, and associations do not imply cause-and-effect relationships. Long-term follow-up studies will be required to capture the full impact medical comorbidities have on the course and outcome of individuals with SMI. The reasons why having SMI is associated with disproportionately high odds of having medical comorbidities are complex and multi-factorial and future studies will need to continue to monitor medical comorbidity in this population as health policies evolve. We found having a SMI was associated with higher odds of having several medical comorbidities as well as chronic and severe medical conditions,rolling grow table even in an integrated health care system where patients have insurance coverage and broad access to care.

Our results suggest that that SMI patients have high medical needs, and implementing enhanced outreach efforts focused on prevention, early diagnosis, and treatment of medical comorbidities may help reduce associated morbidity and mortality and improve overall prognosis in this population.In November 1996, California became the first state to legalize the use of medical marijuana. Since then, a total of 23 states have passed medical marijuana laws , along with 4 states and Washington D.C. legalizing the recreational use of marijuana. With marijuana legislation continuously being seen on state ballots, it is important to research and understand the effects it brings to society. To conduct our research, we will be looking specifically at the effect of medical marijuana use in California. The goal of this paper is to observe the effects that medical marijuana has on crime rates and other drug and alcohol use. A specific question to be answered is whether or not marijuana can be a substitute, rather than a complement, for other illegal drugs and alcohol, resulting in a decrease in crime and drug and alcohol-induced deaths. To discover an answer, we will look at medical marijuana, crime, arrest, unemployment, and mortality rates in California counties from 2005-2014. The arrest and mortality rates will be used specifically to examine the possibility of marijuana being a substitute drug. Today, there are approximately 572,762 medical marijuana patients in California, which is equivalent to 1.49% of California’s population.While recreational use of marijuana has not been legalized in California, it is estimated that 9% of Californians use marijuana.If recreational marijuana use is legalized in California, it is possible that the percentage of marijuana users will increase. Given that California already has numerous marijuana farms and is predicted to provide 60-70% of the United States’ crop if legalized within the state, according to the International Business Times, it is pertinent to analyze the outcomes marijuana has on California’s society today. In 2010, the number one cause of death among 25-64 year olds in California was drug overdose.Many individuals have grown up with the notion that marijuana is a gateway drug to other illicit “hard” drugs. These other substances could include cocaine, heroin, methamphetamines, and prescription drugs, all of which can be extremely addicting and fatal. Since 1999, deaths from painkiller drug overdoses have increased 400% for women and 237% for men.This causes us to think of potential solutions for fatal substance abuse. If medical marijuana can be offered as a substitute drug, will it decrease drug-poisoning deaths? According to a survey implemented by the U.S. Department of Health and Human Services from 2005 to 2011, illegal drug use percentages were much higher in unemployed individuals than individuals with some sort of employment.Specifically, it was shown that 18% of the unemployed were involved in illegal drug use, compared to 10% of part-time workers and 8% of full-time workers. This causes us to question whether or not there’s a relationship between drug use and unemployment. When California passed Proposition 215, referred to as the California Compassion Use Act, it allowed patients, along with their primary physicians, to possess and grow marijuana for medical use, once given a referral from a California-licensed doctor. In 2004, California passed SB 420 to supplement Prop 215. The SB 420 specified the amount of marijuana each patient could possess and cultivate and created a voluntary, statewide, ID database through California health departments. This database is run by the California Department of Public Health and will be used to estimate marijuana use for this report. While both Prop 215 and SB420 protect patients and physicians from arrest in California, marijuana continues to be a federal crime, where there is no differentiation between medical and recreational marijuana use. Currently, the Drug Enforcement Administration has marijuana listed as a Schedule I drug, defined as a drug with the highest potential for danger and abuse and is listed along with heroin, LSD, and ecstasy. Schedule I drugs are assumed worse in comparison to Schedule II drugs, which are recognized to be less abusive. Schedule II drugs include cocaine, methamphetamines, and other highly addictive prescriptions. According to the Office of National Drug Control Policy, the reason marijuana legalization is refused at the national level, is because marijuana use is believed to increase the use in other illicit drugs.This brings us back to the question of whether or not marijuana can act as a substitute, rather than a “gateway”, to other hard drugs. While there has been little to no research done in the area of recreational marijuana, there have been many articles published on the effects of medical marijuana legalization. In 2013, Anderson et al. published a paper that studied the effects of MMLs on traffic fatalities across the nation by using alcohol consumption as an instrument. The authors first used price data to observe the effects on the marijuana market after the MML took effect. They found that the supply of high-grade marijuana dramatically increased, while the lower quality cannabis was moderately impacted. Getting to the basis of their main goal, they used data on traffic fatalities within a 20-year period, across 14 states, to determine if marijuana was a substitute for alcohol. It was discovered that there was an 8-11% decrease in traffic fatalities within the first year of legalization with an even larger effect on traffic fatalities involving alcohol consumption. The authors then used individual behavioral data to examine the probability of consuming alcohol in the past month, binge drinking, and the number of drinks consumed after the MML took place. They found that these probabilities drastically decreased after the legalization occurred. When looking at alcohol sales, it was also discovered that there was a decline of 5% on beer consumption in the age range of 18-29. The MMLs were then used as an instrument of beer consumption to establish the amount of traffic fatalities. It was deduced that for every 10% increase in beer sales per capita, alcohol related traffic fatalities increased by 24%. The article goes on to conclude that marijuana does have a substitution effect on alcohol, especially among young adults, which inherently declined traffic fatalities.There is currently a working paper called “The Effect of Medical Marijuana Laws on Marijuana, Alcohol, and Hard Drug Use,” where Hefei Wen studied these effects using geographic identifiers and by estimating a state-specific time trend model that included two-way fixed effects. It was discovered that the relative probability of marijuana use among individuals over 21 increased by 16%, the frequency of marijuana use increased by 12-17%, and marijuana abuse and dependency increased by 15-27%. While there was an overall increase in marijuana use after MMLs went into effect,vertical grow rack there was no strong evidence that showed marijuana use increased in youth. While the authors predicted that there could be a spillover effect of marijuana on other substances, there was no significant evidence that marijuana caused increases in alcohol and other drug use. A more recent study done through the Drug and Alcohol Review examined medical marijuana as a substitute for alcohol, prescription drugs, and other illicit substances. The data was taken from a cross-sectional survey, completed online by 473 Canadian medical marijuana patients. This included an 80.3% substitution rate for prescription drugs, a 51.7% substitution rate for alcohol, and a 32.6% substitution rate for other illicit substances. These rates serve as evidence that marijuana can “play a harm reduction role in the context of use of these substances, and may have implications for abstinence-based substance use treatment approaches.”While these results show significant effects for marijuana substitution, there are an estimated 2.3 million users of cannabis in Canada alone, making it difficult to assume a survey of only medical marijuana patients represents the entire population of all marijuana users. An additional study was done through the University of Virginia in 2014 that examined how MMLs affect crime rates.The author, Catherine Alford, decided to use difference-in-differences estimations where she controlled for state specific crime trends by collecting data across states over time from 1995-2012. It was discovered that after the implementation of MMLs, overall property crime and robbery rates increased. However, if the MMLs allowed for home cultivation, robbery rates actually decreased by about 10%. While these results show a positive relationship between MMLs and the previously mentioned crime rates, there was no statistically significant effect on violent crime rates. However, a study done in 2012, by the Center on Juvenile and Criminal Justice, showed that after California passed the SB 1449 for the decriminalization of marijuana, youth crime rates were at an all-time low.The SB 1449 allowed for a small possession of marijuana to count as an infraction, instead of a misdemeanor. Within a one-year period from 2010-2011, youth arrests declined by 16% for violent crime, 26% for homicide, and 50% for drug arrests. The author, Mike Males, concluded that the only significant explanations for a dramatic decline in juvenile crime rates would be the passing of SB 1449 and the improvement of socio-economic programs in California’s poor neighborhoods. In the previous reports examined, crime rates, drug and alcohol use, and traffic fatalities were all studied after the passing of MMLs among multiple states to discover any significant effects. While my proposed project would like to examine both crime rates and drug use affected by marijuana, it will look purely at California county data across a 10-year period and will not focus on age-specific crimes. The following report will also include an analysis of how the issuance of medical marijuana identification cards affects other drug and alcohol use, controlling for unemployment. The methodology used to answer the research questions above will be a series of multiple regressions with county and year fixed effects. To begin the analysis, we will determine how MMIC issuance affects crime rates. This regression will include unemployment as a right hand side variable to control for variations in the workforce. A regression will be run for every type of crime rate, as well as for total crime, in order to discover if marijuana has individual effects on different types of crime. In addition to regressing crime rates on MMICs, drug and alcohol arrest rates will be regressed on MMICs to examine if there’s a substitution effect between marijuana and other drugs and alcohol. Because arrest and crime rates do not depend solely on MMICs, we will also include unemployment rates as a right hand variable. After analyzing the number of MMICs on crime and arrest rates, drug, alcohol, and other mortality rates will be regressed on the number of MMICs issued per county.

The curated GIS database compiled by the ABCD Study LED Environment Working Group includes both vector and raster data of multiple built and natural environmental contextual variables. As shown in Table 1 and outlined in greater detail below, various environmental datasets have been used to map environmental factors to the state-, census-, residential-level for ABCD Study participants to date. Youth grow up in overlapping circles of cultural and socio-political contexts, from their local family and neighborhoods to the states and countries in which they live. We typically focus on the experience of stigma and bias at a relatively local level . Critically, there are also important indicators of more systemic or structural bias reflected in social norms at the community or institutionalized laws, policies and practices that may either reflect the behavior of individuals or shape the behavior of individuals in youths’ local environment. However, we rarely directly examine the relationship between objective measures of systemic/structural bias and function in youth. The ABCD Study provides a novel opportunity to address such critical questions with empirical data, given the geographic variability of the sites involved in the ABCD Study,hydroponic flood table which affords significant divergence across youth in their exposure to such systemic biases. To address such questions, colleagues at Harvard University created state-level indicators of three types of structural stigma : gender , race , and ethnicity . This information was linked to each youth in the ABCD Study as a function of their baseline site of participation and does not yet include information about whether the child moved to a different state, which may have different state level indicators, at later visits.

To create these state-level measures, they used several types of data. First, they obtained data about implicit and explicit attitudes about each of these three identity groups aggregated at the state-level, derived from large-scale projects that spanned several years: Project Implicit , the General Social Survey , and the American National Election Survey . Second, for information on gender, they obtained state-level data of women’s economic and political statuses and information about reproductive policies, such as information about availability of abortion providers. Third, for information on attitudes towards Latinx individuals, they examined state-level policies on immigration, recognizing that many Latinx individuals are not immigrants but that such state-level policies likely influence the experience of all individuals in the community with that identity. These data can be used to examine how these state level biases interact with youth’s identities to predict a range of factors, such as educational experience, mental health, brain development, and substance use/abuse. In the United States, public acceptance of cannabis use has increased alongside increased access because of broader cannabis legalization. Currently, 36 states have legalized either recreational or medical cannabis use. Early research suggests that cannabis legalization does not lead to increases in adolescent cannabis use . However, among younger adolescents , greater exposure to cannabis advertisements was associated with greater use, intention to use, and positive expectancies . The difference in results as a function of age highlights the importance of understanding how cannabis regulations affect younger cohorts of children and adolescents who may have greater exposure to cannabis advertisement after living in an environment with legal access to cannabis for a longer period. Furthermore, the ABCD Study is an ideal dataset to examine the effects of cannabis legalization because there are 21 sites located in 17 states with various state cannabis policies. In addition, the ABCD Study is collecting detailed substance use data unlike other national surveys.

The four cannabis legalization categories are: 1. Recreational – allows adults to use cannabis for recreational purposes, 2. Medical – allows adults to use cannabis for medical conditions, 3. Low THC/CBD – allows adults to use cannabis that is low in THC and high in CBD for medical conditions, and 4. Urbanicity can provide information as to the impact of living in urban areas. Urbanicity indices may reflect the presence of environmental and social conditions that are more common in urban areas, such as pollution, congestion, and increased rates of social interactions. To date, various health factors have been linked to urbanicity, such as increases in overweight/obesity, increased calorie intake, decreased physical activity, increased drug and alcohol use, and mental health disorders, among many others . In the ABCD Study, we have linked five measures of urbanicity to residential addresses, including two density measures , census-tract derived metrics classifying the locations as urban or non-urban areas, walk ability, and motor vehicle information including distance to roadway and traffic volumes. Population density refers to the number of people living in a given unit of area . Differences in population density have been linked to psychological and environmental quality of life , and has been shown to moderate relationships between the built environment and health outcomes . Thus, information about variability of population density may be important for contextualizing relationships between the build environment and health outcomes in the ABCD Study. As such, the population density from the Gridded Population of the World , provided by the Socioeconomic Data and Applications Center , has been linked to ABCD individual participant address information. National-level population estimates from 2010 used in this metric have been adjusted to the United Nations World Population estimates, which can often be corrected for over- or under-reporting and mapped to an ~1-km grid. Population density values represent persons per km2 . Similarly, gross residential density is a measure of housing units per acre on unprotected land and is an alternative measure of crowding. This measure was obtained from the Smart Location Database created by the United States Environmental Protection Agency based on the 2010 Census Data and also linked to ABCD Study individual addresses. While many studies have documented the effects of increased urbanicity on child and adolescent health outcomes, few studies have focused on differential risk associated with living in a rural area relative to an urban area . Although the number of studies devoted to this topic are few, linking this information to the ABCD Study may provide an opportunity to further investigate both positive and negative impacts of living in an rural area. To classify individuals as living in a rural or urban area, urban-rural census tract variables from 2010 were mapped to each address.

Based on this external database, the Census Bureau identifies two types of urban areas, including Urbanized Areas of 50,000 or more people and Urban Clusters of at least 2500, but less than 50,000 people. Rural areas are those that encompass all population, housing, and territory not included within an urban area . In urban places, city planning designs have limited the walk ability between work, home,hydroponic stands and recreational spaces, with distances too great to walk . Such reduction in walk ability leads to fewer opportunities for physical activity and a risk for health. Understanding potential links between the walk ability of the built environment of the child and physical and mental health outcomes is important in the context of the ABCD Study . A measure of walk ability was linked to ABCD participant addresses using the National walk ability Index from the Smart Location Database created by the United States Environmental Protection Agency based on 2010 census data. walk ability scores were calculated at the census-tract level, ranking each census tract on a range from 1 to 20 according to relative walk ability. The walk ability score is based on a weighted formula that uses ranked indicators as related to the propensity of walk trips. The ranked-indicator scores used in the weighted formula include a combination of diversity of employment types plus the number of occupied housing, pedestrian-oriented intersections, and proportion of workers who carpool. Beyond population density and walk ability, epidemiological studies have also reported associations between road proximity and brain health. Various neurodevelopment, cognitive functioning, and mental health outcomes have been linked to living near major roadways . As such, the ABCD Study may be valuable to help understand how the distance of a child’s home to major roadways as well as the daily traffic patterns on nearby roadways impacts cognitive and neurodevelopmental trajectories over time. Therefore, we have mapped road proximity and traffic volume estimates to residential addresses of the child in the ABCD Study to provide insight into both the major roadways nearby and how many cars and trucks typically utilize these roads. the geospatial coordinates of the major roads were obtained through the North American Atlas for roads, as last updated July 2012 , and the shortest distance to a major roadway in meters was linked to participant’s residential addresses. In the field of developmental cognitive neuroscience, socioeconomic status has traditionally been treated as an individual-level variable, specific to each family or person. However, socioeconomic status can also be attributed to neighborhoods and communities, which may represent an independent construct from family-level socioeconomic status with considerable effects on child development . In the ABCD Study, detailed questions are asked about socioeconomic and social factors at the family-level. Thus, the ABCD Study is an ideal dataset to examine the independent and multiplicative associations of family- and neighborhood-level socioeconomic status on adolescent health. Investigations with these ABCD data can elucidate the underlying mechanisms by which various contexts uniquely influence development and potential emerging health disparities . Accordingly, the ABCD Study has incorporated the Area Deprivation Index measure of neighborhood-level socioeconomic status in past data releases, as well as information on crime and risk of lead exposure. Moving forward, three additional metrics, including the Social Vulnerability Index, Opportunity Atlas, and the Child Opportunity Index, have been linked in the 4.0 annual data release. The ADI represents a composite multi-variable metric of neighborhood disadvantage , with higher values representing greater disadvantage. Developed and popularized by Singh , the ADI was initially constructed to determine how area deprivation was associated with mortality. However, as more pertinent to ABCD, per studies of related measures of neighborhood disadvantage, increased disadvantage is indirectly associated with children’s developmental outcomes and adult health problems through other neighborhood- and/or family-level variables. The ABCD Study includes the composite ADI metrics, including the weighted ADI score and its national percentile, along with the 17 component variables used to create the composite scores at the census-tract level for participants’ primary, secondary, and tertiary addresses at baseline, all of which were derived from the 2011–2015 American Community Survery . A description of the 17 component variables is included in Supplemental Table 2. Like the ADI, the SVI incorporates 15 variables from the ACS, which are described in Supplemental Table 3. These 15 items are grouped into 4 themes: socioeconomic status , household composition and disability , minority status and language , and housing type and transportation . SVI is calculated by deriving percentiles of each variable , summing the percentiles within the theme, and summing these totals across themes, with higher values of SVI representing greater vulnerability to disaster and disease. Here, linking SVI to ABCD data provides the opportunity to better understand not only how environmental contexts are interrelated with adolescent development, but how environmental vulnerability to external stressors may invoke downstream effects on developmental outcomes. The 4.0 annual release for the ABCD Study includes the census-tract level SVI for participants’ primary, secondary, and tertiary addresses. The neighborhoods in which children in America grow up can influence outcomes in adulthood. As such, the Opportunity Atlas estimates measures of average outcomes across 20,000 people in adulthood according to the census tracts in which they grew up . The ABCD Study includes scores from the Opportunity Atlas that indicate the predicted 2014–2015 mean income earnings of adults aged 31–37 years that grew up in that census tract as children. Scores are provided based on the childhood census tracts of the Opportunity Atlas cohort, but we also provide the adult mean earnings disaggregated by parental household income percentiles based on the national income distribution during their childhood. For example, the mean income earnings at the 25th percentile rank correspond to the mean income earnings of adults whose parents were at the 25th percentile of the national income distribution.

In our experiments we presented the olfactory and visual stimuliCannabis sativa contains more than 140 terpene-like compounds, called cannabinoids, that share the cannabinoid chemical scaffold. The 2 main members of this chemical family are Δ9 -tetrahydrocannabinol and cannabidiol . Animal and human studies have demonstrated that THC is responsible for the majority of the intoxicating effects of cannabis; it acts by binding to G protein-coupled cannabinoid receptors in the brain and other tissues of the body. By contrast, CBD exhibits a distinct set of pharmacological properties, including anti-epileptic and anti-inflammatory effects that are mostly independent of CB receptor activation.Data obtained from the National Health and Nutrition Examination Survey indicate that frequent use of recreational cannabis is positively associated with severe periodontitis, which was observed both in a bivariate analysis and in a multi-variable analysis adjusted for demographics , alcohol and tobacco use, diabetes mellitus, and past periodontal treatment. Research has also found that cannabis may produce adverse effects on oral tissues including gingival enlargement, nicotinic stomatitis, and uvulitis. Remarkably, a number of beneficial effects have also been reported. Considerable evidence supports that pharmacological strengthening of the endogenous cannabinoid system may exert beneficial effects on periodontal inflammation and nerve pain. CBD was shown to exert anti-inflammatory and anti-oxidative effects resulting in a faster resolution of oral mucositis in a murine model. Additionally, enhancing endocannabinoid signaling in cells that initiate local immune responses in the periodontium, the periodontal ligament cells, greenhouse grow tables significantly dampened their proinflammatory responses to lipopolysaccharide produced by Porphyromonas gingivalis.

It has been also shown that selective agonists for type 2 CB receptors exert anti-inflammatory effects in human periodontal ligament fibroblasts. Finally, pharmacological activation of the endocannabinoid system in periodontal ligament cells exhibited hostprotective effects by both dampening inflammation and preserving cellular integrity, while palmitoylethanolamide, a bio-active lipid structurally related to endocannabinoids, exacerbated inflammation. All in all, these results suggest that targeting the endocannabinoid system, in particular by boosting local CB2 receptor signaling, may lead to novel therapeutics that improve current treatments for periodontal disease and other oral inflammatory pathologies.The coronavirus disease 2019 pandemic due to the worldwide spread of severe acute respiratory syndrome coronavirus 2 infection has significantly affected the use of cannabis in 2 particular human populations, among others. First, it was shown that those who engaged in self-isolation used 20% more cannabis during the pandemic than those who did not, which was associated with self-reported isolation and loneliness. In addition, people with mental health conditions reported increased use of medicinal cannabis by 91% during the COVID-19 pandemic, compared to those with no mental health conditions. Therefore, during the pandemic, health care providers should pay particular attention to oral diseases. Importantly, communication and cooperation between physicians and dental practitioners should be encouraged in managing and treating patients. In addition, the seemingly opposite contribution of the 2 main ingredients of cannabis, THC and CBD, to periodontitis should be kept in mind when addressing the effects of cannabinoids. Certainly, further research is required to evaluate the beneficial and harmful effects of various phytocannabinoids and pharmacological modulators of the endocannabinoid system.In 2000, the Surgeon General identified oral disease as a “silent epidemic” . Despite the availability of effective prevention and treatment methods, oral health has improved little over the past two decades. Among some sub-populations , oral health disparities remain . In the United States, nearly a quarter of adults aged 20-64 have untreated dental caries and more than half have lost a permanent tooth .

Oral pain and tooth loss have a significant negative impact on quality of life and employment by affecting the ability to eat, speak, and smile . Older adults have worse oral health than younger adults due to age-related physiological changes and a higher prevalence of chronic conditions . Despite their heightened need for dental care, older adults have less access to such care . The homeless population is aging, with a growing proportion of adults experiencing homelessness at ages 50 and over . Older homeless adults have a high prevalence of chronic disease and poor dental health . In California, most adult dental services were discontinued as a Medicaid benefit in 2009 , eliminating coverage for more than 8 million people . Enactment of the Affordable Care Act in 2014 expanded Med-Cal medical insurance coverage to 3.8 million people in California, and restored basic adult dental coverage . Unlike pediatric dental care, which is considered an essential health benefit under the ACA, adult dental care coverage is not mandatory. In California, after the enactment of the ACA, adults with Medi-Cal became eligible for dental services, including basic preventive and restorative treatments, complete dentures, and complete denture reline/repair services through the Denti-Cal program . Access to dental care is important because poor oral health is associated with poor nutrition, oral pain, and impairments in oral functioning . People experiencing homelessness have inadequate resources for regular dental hygiene and a higher prevalence of risk for tooth loss, including smoking and substance use . Tooth loss, or edentulism, is a key indicator of oral health; it is affected by both access to dental care and risk factors for poor oral health . Edentulism is a risk factor for coronary artery plaque formation, diabetes, and certain cancers . Prior research in a sample of homeless adults found homeless adults had a higher prevalence of poor oral health than the general population, with high prevalence of tooth loss, or untreated dental decay . In a national study of homeless adults, approximately half of homeless adults had an unmet need for dental care as assessed by tooth or gum problems in the past year . Little is known about oral health in the growing population of homeless adults aged 50 and older. We examined the prevalence of tooth loss, oral pain, denture fit, and impairments in eating or sleeping due to oral pain as well as factors associated with poor oral health, in a population-based cohort of older homeless adults in Oakland, CA. The HOPE HOME Study, is a longitudinal study of life course events, geriatric conditions, and their associations with health-related outcomes among older homeless adults.

From July 2013 to June 2014, we enrolled a population-based sample of 350 homeless adults aged 50 years and older from all 5 overnight homeless shelters in Oakland that served single adults over age 25, all 5 low-cost meal programs that served homeless individuals at least 3 meals per week, a recycling center, and homeless encampments. Study visits took place at St Mary’s Center, a non-profit that serves indigent older adults. Participants did not have to receive services at St Mary’s to be eligible. To be eligible, participants had to be English-speaking, aged 50 years and older, defined as homeless as outlined in the Homeless Emergency Assistance and Rapid Transition to Housing Act , and able to provide informed consent. After determining eligibility, study staff administered an in-depth structured enrollment interview and collected extensive contact information from participants. We gave participants a $25 gift card to a major retailer for their participation in the screening and enrollment interview. The University of California, San Francisco Institutional Review Board reviewed and approved all study protocols. This analysis uses data from the baseline interview. Participants self-reported age, sex, race/ethnicity, and highest level of education. We categorized race/ethnicity as African American, White, or Other. We categorized highest level of education as less than high school versus high school graduate/General Educational Development or greater. Participants reported their total lifetime years of homelessness after the age of 18. To assess the prevalence of depressive symptoms, we administered the Center for Epidemiologic Studies Depression Scale. Using a shortened time frame of the previous 6 months to correspond to study time intervals, we administered the World Health Organization’s Alcohol Use Disorders Identification Test . To assess illicit drug use, we administered the WHO’s Alcohol, Smoking, and Substance Involvement Screening Test to assess for amphetamines, cocaine, opioids and cannabis growing system, using a lengthened time frame of the previous 6 months. We dichotomized substance use risk for each substance as low vs. moderate-to-high severity . We used the California Tobacco Survey to assess tobacco use. We classified smokers who had smoked at least 100 cigarettes in their lifetime as “ever smokers.”We adapted oral health questions from the Oral Health Impact Profile – 14 . We asked participants about tooth loss . For our primary dependent variable, we dichotomized responses as missing less than half versus missing half or more. We asked participants who reported having any teeth if they were able to eat with their teeth. For participants who reported missing all of their teeth, we asked if they had dentures, and if so, whether they fit . We asked participants how often they had oral pain in the last six months . If participants noted oral pain, we asked if the pain kept them from eating or sleeping . To assess access to dental care, we asked participants about how long it had been since they last visited a dentist: <6 months, 6 months to 1 year, >1 year to <5 years, or ≥5 years. To assess unmet dental need, we asked participants if, during the past 6 months, there was a time when they needed dental care but could not obtain it. We described sample characteristics and reported oral health variables using medians for continuous variables and proportions for categorical variables.

We examined oral health status by evaluating bivariate associations between independent variables and our primary dependent variable using Wilcoxon rank sum tests for continuous variables and chi-squared tests for categorical variables. Using multivariate logistic regression, we examined factors associated with participants having lost half or more of their teeth. We included all covariates in the model and through stepwise removal eliminated variables failing to achieve a significance of less than 0.2. We conducted these analyses using Stata version 14 . In a population-based sample of older homeless adults with a median age of 58, we found evidence of poor oral health and poor access to dental care. Over half of participants reported oral pain, which is over three times greater than the prevalence of oral pain in the general population over age 65 and more than twice that of the general poverty population over age 65 . Despite oral health needs, older homeless adults had poor access to dental care. Only a quarter reported visiting a dentist in the prior year, compared with 62% of adults in the general population . We found that over half of older homeless adults had been unable to get dental care in the prior year, compared with fewer than ten percent of adults aged 65 and older in the general population . Whereas approximately 10% of edentulous adults in the general population lack dentures, we found that almost half of edentulous participants either lacked dentures or had ones that couldn’t be used due to poor fit . Over a quarter of our participants reported that mouth pain prevented them from eating. Edentulism and oral pain may limit homeless individuals’ ability to eat, worsening food insecurity . Dental care is ranked as one of the leading unmet needs among the general homeless population . Many of our participants lacked health insurance; in addition, prior to Medicaid expansion , Med-Cal in California did not include access to dental care. However, even with Medicaid-supported dental coverage, access to dental care remains limited. Only about 20% of the nation’s 179,000 practicing dentists accept Medicaid payment for dental services and more than 49 million people live in areas categorized as dental health shortage areas . In California, only 1 in 4 dentists provide services to Medi-Cal beneficiaries. On average, throughout California, there are only 7.3 dentists that accept Medi-Cal per 10,000 beneficiaries. As many dentists who accept Medi-Cal limit the number of Medi-Cal patients they are willing to provide services to, the shortage is worse than it appears. . Having lost half or more of teeth was strongly associated with increased age, consistent with previous studies in both the general and homeless populations . This could reflect the increased adoption of preventive measures such as improved fluoridation and dental sealants with later birth cohorts .

Galve-Roperh et al. found that cannabinoids cause a bi-phasic increase in ceramide levels in C6 glioma cells. The first phase of ceramide accumulation occurred within seconds or minutes after cannabinoid administration, which was likely to be a result of stimulus-dependent hydrolysis of sphingomyelin. Two days after the addition of the drug, a second increase in ceramide levels took place, which coincided with the onset of the apoptotic response—probably reflecting an increase in de novo ceramide biosynthesis through the ceramide synthase pathway8 . How these changes in intracellular ceramide intervene in apoptosis is unknown, but the fact that they are synchronized with increases in extracellular signal-regulated kinase and Raf-1 kinase indicates that these three factors may cooperate in mediating cannabinoid-induced glioma cell death. But how likely is it that the discovery of anti-tumor effects of cannabinoids will affect malignant glioma therapy? At present, glioma patients who are subjected to an aggressive, multimodal treatment consisting of surgery, radiation therapy and chemotherapy have a median survival rate of 40–50 weeks9 . This bleak scenario alone should provide sufficient motivation to continue the studies initiated by Galve-Roperh et al. The risk of typical cannabinoid side effects—euphoria, amnesia,rolling flood tables decreased psychomotor performance and hypotension—may be outweighed by therapeutic advantages, and eventually be overcome through the development of selective CB2-selective agonists.CM is a type of behavioral therapy in which individuals are “reinforced,” or rewarded, for evidence of positive behavioral change . CM typically consists of monetary-based rewards or vouchers to reinforce abstinence from the target drug or to encourage retention in pharmacological or psychosocial treatment .

As presented in the Benefit Coverage, Utilization, and Cost Impacts section, with the amount of funding that would be available unknown, CHBRP has purposefully modeled a limited expansion — for only 1,000 beneficiaries — intending to provide two examples that could be scaled larger, depending on the amount of available funds. These two examples, stimulant use disorder and cannabis use disorder, serve as case studies on what the cost and utilization implications would be of Medi-Cal enrollees getting treatment for SUD with and without CM. As presented in the Medical Effectiveness section, evidence varies by SUD regarding the impact of CM. While there is clear and convincing evidence that CM is effective for stimulant use disorder and a preponderance of evidence that CM is effective for cannabis use disorder, these findings are related to outcomes during treatment. For both stimulant use disorder and cannabis use disorder, it is not clear how this may impact results in post treatment abstinence, but there is evidence to suggest that achieving abstinence during treatment is the greatest predictor of long-term recovery. The public health implications of these two simulations are discussed below.This simulation projected that for every 1,000 Medi-Cal enrollees engaged in treatment for stimulant use disorder, there would be 14,400 group counseling appointments and urinalysis tests without CM increasing to 16,800 with treatment including CM. As shown in Table 2, CM would lead to an additional 2,400 group counseling sessions per 1,000 enrollees attended and urinalyses performed. In absence of CM, 40% of the 14,400 urinalyses would be negative for stimulants for a total of 5,760 stimulant-free samples. With the addition of CM, it is expected that 60% of the 16,800 urine samples would be negative for a total of 10,080 negative samples.

Therefore, for every 1,000 Medi-Cal enrollees engaged in treatment for stimulant use disorder using CM, CHBRP would expect to see an increase of 4,320 additional negative urine samples. Therefore, as each negative urine sample represents roughly three days of abstinence, this translates roughly into nearly 13,000 additional stimulant-free days. SUD often involves cycles of relapse and remission, can vary in severity, and often requires ongoing professional treatment, lifestyle changes, and case management . Therefore, although abstinence may not persist post treatment, achieving periods of abstinence is still one goal of treatment, especially considering the best predictor of long-term recovery is abstinence during treatment . In addition, as there is no FDA-approved medication to treat stimulant use disorder, CM to improve treatment engagement and abstinence may be the best treatment option available. Patients addicted to stimulants such as methamphetamine are at higher risk for a range of physical and psychological issues including mental illness, cognitive issues, antisocial behaviors, cardiovascular events, sexually transmitted diseases, and blood-borne infections including HIV and hepatitis B and C, and consequently are at increased risk of death . The rate of amphetamine-related overdose deaths was 5.8/100,000 Californians in 2018 . Methamphetamine has taken over as the leading cause of overdose deaths in California, followed by the rate of all opioid overdose deaths of 5.23/100,000 . In addition, impacts of methamphetamine use are exacerbated by its association with increased violence and crime . Other downstream effects of methamphetamine use include reduced work related productivity and increased family and housing instability. It is possible that the additional 13,000 stimulant-free days among the 1,000 Medi-Cal enrollees in this simulation would lead to reductions in many of these short-term outcomes.The California Opioid Overdose Surveillance Dashboard shows that Blacks had the highest rates of hospitalizations for amphetamine overdose , which were more than double rates of whites , Latinos , Native Americans , and Asians . Yet, Native Americans had the highest amphetamine overdose mortality rates in California in 2018 , followed by Blacks and whites .

Asians had the lowest amphetamine overdose mortality rate at 1.4/100,000 . Disparities by gender existed in the rates of ER visits for amphetamine overdoses and deaths with males being more than twice as likely to have an ER visit for an overdose and more than three times as likely to die from amphetamine overdose .This simulation projected that for every 1,000 Medi-Cal enrollees engaged in treatment for cannabis use disorder in absence of CM, 30% of the 7,200 urinalyses would be negative for cannabis for a total of 2,160 cannabis-free samples. With the addition of CM, it is expected that 45% of the 7,200 urine samples would be negative for a total of 3,240 negative samples. Therefore, for every 1,000 Medi-Cal enrollees engaged in treatment for cannabis use disorder using CM, CHBRP would expect to see an increase of 1,080 additional negative urine samples. Therefore, as each negative urine sample represents roughly seven days of abstinence, this translates roughly into more than 7,500 additional cannabis-free days. The impacts of 7,500 additional cannabis-free days include reductions in risks of psychiatric disorders, impairments in learning and coordination, and lung inflammation/chronic bronchitis, and potential opportunities for improvements in cognitive function and educational and workplace outcomes . There is also a potential for a reduction in ER visits and hospitalizations due to cannabis use disorder.Some interventions in proposed mandates provide immediate measurable impacts , while other interventions may take years to make a measurable impact . When possible, CHBRP estimates the long term effects to the public’s health that would be attributable to the mandate. As presented in the Medical Effectiveness section, there is no research that examines the long term impacts of CM for SUD treatment. For this analysis, CHBRP modeled a 12-week substance use disorder treatment program using contingency management , one for stimulant use disorder and one for cannabis use disorder. It is unclear how many providers would choose to offer CM as part of SUD treatment and how many patients would participate in the long term. In addition,flood and drain tray since there is no research that examines long-term impacts of CM for SUDs treatment on health care utilization, it is not possible to quantify the long-term utilization and cost impacts of SB 110. As with other chronic conditions, effective management of SUDs will require repeated, short-term treatments or longer-term treatment over time. Current practices involve short-term episodic treatments, which have limitations when treating long-term chronic conditions. Of those that achieve long-term recovery, it is estimated that nearly half are able to enter recovery on the first try, 14% have one recurrence, 19% have 2-5 recurrences, and 15% have 6 or more recurrences prior to achieving recovery stability . It is estimated that between 2-5 recovery attempts are made by persons with stimulant use disorder and cannabis use disorder prior to successfully resolving the SUD . Therefore, to the extent that participating in CM treatment programs produce better during treatment abstinence results, this may encourage patients to try to make another recovery attempt in the future, with each attempt making it more likely they will enter long-term recovery. As discussed previously, a key barrier to abstinence for any SUD is patient interest and readiness to abstain. It is possible that the availability of CM will attract more patients to participate in treatment in the first place. In addition, CHBRP anticipates that the demand for treatment of SUDs would continue as relapsed patients attempt abstinence again and first-time initiators would join the pool of patients seeking care. This in turn could contribute to long-term positive public health impacts, as programs become more available and patients become more aware of them over time. However, limited patient readiness for SUD treatment and limited number of providers may remain significant barriers to care. To the extent that SB 110 results in an increase in SUD treatment with CM, and the extent to which this leads to additional quit attempts and long-term abstinence, it is possible SB 110 would contribute to reductions in substance use–related morbidity and mortality.

Sleep disturbance is one of the most prevalent symptoms reported by HIV-infected individuals , with up to 73% reporting significant sleep disturbances . Unlike some other symptoms associated with HIV that typically present during the initial phase of illness , sleep disturbance has been shown to be present over the course of the disease . This is particularly concerning as disturbed sleep has been associated with poorer antiretroviral medication adherence , viral load , greater HIV symptom severity , and higher rates of negative psychological symptoms . While the prevalence and consequences of sleep disturbances among individuals with HIV have been established, relatively little work has investigated malleable factors that may confer greater risk of sleep disturbances for this population. One relevant factor in this area is anxiety sensitivity , a cognitive vulnerability defined as the fear of anxiety, its relevant bodily sensations, and its potential negative social, physical, and mental consequences . AS has unique relations to sleep disturbances and, among individuals with HIV, specifically, has been linked to greater physiological distress, anxiety, and depression symptoms , suicidality , as well as self-reported HIV symptom severity . Unfortunately, there has been little work in terms of understanding whether greater AS might relate to decrements in sleep quality among individuals with HIV. Drawing from the literature more broadly, Vincent and Walker found that, in a sample of adults with chronic insomnia, AS was related to sleep-related impairment, with a trend relation between AS and frequency of medication use, after accounting for general worry and presence of Axis I psychopathology. Babson, Trainor, Bunaciu, and Feldner found that AS interacted with sleep anticipatory anxiety to predict sleep onset latency, after accounting for negative affect, gender, age, cannabis use, nicotine dependence, and alcohol use. In a similar investigation conducted among individuals with panic disorder, Hoge et al. found that after accounting for relevant covariates including age, major depression, and panic disorder severity, individuals with elevated AS reported significantly greater latency to sleep. Taken together, these studies indicated that elevations in AS confer risk for greater sleep disturbances, although these associations appear nuanced in terms of particular aspects of sleep quality, with no research having sought to elucidate these relations for individuals with HIV. Our study sought to explore the incremental association between AS and global sleep quality, as well as to determine differential associations between AS and a variety of facets that comprise global sleep quality, including perceived sleep quality, latency, duration, efficiency, disturbance, medication use, and daytime dysfunction in HIV-infected individuals receiving treatment at community clinics. We sought to explore AS in relation to global sleep impairment and specific components in order to explicate which aspects of sleep interference might be most relevant to AS.

The 12-item Electronic Cigarette Attitudes Survey was administered to further examine attitudes toward the use of e-cigarettes versus combustible NTP. The Questionnaire of Smoking Urges and the Hooked on Nicotine Checklist were also given to NTP users to acquire information on NTP addiction severity, with total scores calculated. Neurocognition, NIH Toolbox: Participants completed the National Institutes of Health toolbox cognition battery, consisting of seven individual tasks. All tests were completed using the NIH Toolbox app on 3rd generation iPad Air devices . Research subjects were seated upright and used their dominant index finger to make each response. To prevent participants from inadvertently skipping through instructions, a one-second touch-and-hold button was required to advance to the next task. Tasks completed included the Picture Vocabulary Task, where participants identified the picture matching the meaning of a word they were read aloud; oral reading, where participants received a single word as visual stimuli written on screen and were asked to read each aloud; the Dimensional Change Card Sort Test, where participants had to respond to stimuli based on changing rules displayed on top of the screen; Flanker Inhibitory Control and Attention Test, where participants had to select a left or right arrow based on a displayed target stimulus arrow in the midst of a row of arrows; the List Sort Working Memory Test was administered to assess working memory and required participants to sort stimuli,planting racks presented both visually and auditorily, from smallest to largest in size; Picture Sequence Memory Test, a measure of episodic memory, where participants had to recall a sequence of displayed pictures; and Pattern Comparison Processing Speed Test, where participants had to quickly decide if two side-by-side images were the same or different.

Population-adjusted scores, which adjusted for age, gender, race, ethnicity, and education level, were used in the present analyses. For the Rey Auditory Verbal Learning Test, participants were read 15 words over five trials and asked to recall the list after each repetition. A new, second list was read, and then participants were asked to again recall the original list. After 30 min, they were again asked to recall the original list. Raw scores on initial recall, total score over all trials, and long-delay recall were collected. The Game of Dice Task assesses decision-making and risk-taking behaviors. Participants view a virtual single die shaking in a cup, guessing one single number or a combination of two, three, or four numbers . A correct prediction would add the specified monetary amount to their total earnings, while an incorrect guess would result in a loss of the same amount. Performance was measured by a net score, computed by subtracting the number of disadvantageous, high-risk choices from the number of advantageous, low-risk decisions. Participants also completed a variation of the Emotional Stroop Task as a measure of emotional processing and cognitive control. The presentation of an emotional word was overlaid on a picture of a face that is displaying an emotion either congruent or in congruent to the word presented. The stimuli appeared one at a time on screen, and participants worked to sort the words into two categories while ignoring the distractor image in the background.Selection of Covariates: Sociodemographic characteristics were considered for inclusion in all analyses. Inclusion of covariates was determined based on characteristics that differed by group. Models with measures that were corrected for sociodemographics did not include sociodemographic variables as covariates. For primary outcome analyses of mental health and neurocognition, ANCOVAs were run, controlling for the past six months of alcohol and cannabis use and sociodemographic factors, which differed by group . Primary analyses: SPSS 28.0 was used for all primary analyses, and and Rstudio were used for multiple comparison corrections using the “sjstats” package for false-discovery rate corrections.

Differences by group in sociodemographics, substance use attitudes, substance use history are first presented. The selection of covariates was determined by ANOVAs and chi-squares. ANCOVAs assessed differences in mental health and neurocognition by group, controlling for alcohol and cannabis use in the past 6 months, and relevant sociodemographic covariates . Benjamini and Hochberg’s false discovery rate method was used within models to correct for multiple comparisons in ANCOVA models. In models with significant differences by NTP group , Fisher’s post-hoc tests were run to identify specific group differences, and marginal means were reviewed to determine directionality. Given the age range of participants, post-hoc analyses were conducted with only participants 18–22 years old. All models were re-analyzed, with covariates again selected by sociodemographic differences between groups and including past six-month cannabis and alcohol use.Despite the sharp rise in emerging adult NTP use in recent years, little is known about mental health and neurocognitive differences of e-cigarette use relative to traditional combustible NTP use , in concert with attitude differences toward NTP use. Here, we delineate clear and significant differences in NTP users’ substance use habits and attitudes despite minimal mental health or cognitive differences by nicotine group status. There appear to be qualitative differences in motivations , and expectancies of smoking behavior among individuals who have recently used combustible versus noncombustible products. Combustible product users at this young age also reported greater dependency on nicotine and craving for nicotine products as compared to individuals who only use e-cigarettes. Of note, individuals in both NTP groups had more favorable views of e-cigarettes as compared to traditional tobacco products and largely reported using e-cigarettes for the taste. In addition, combustible product users tended to use substances more heavily overall, including more episodic NTP use. Finally, both nicotine use groups reported higher levels of depression and stress symptoms as compared to NTP naïve controls.Interestingly, when considering the moderating influence of gender, male combustible users reported more depression symptoms than the other groups, while females did not differ in depressive symptoms by group status. Though Combustible+ users were significantly older than the other groups, when restricting analyses to only those between 18 and 22 years old, results remained consistent, suggesting that it is not merely that Combustible+ users have had more time to transition into heavier substance use.

While there is a growing body of literature on susceptibility and predictors of NTP use, there is a paucity of knowledge about NTP attitudes in young adults who use combustible and non-combustible NTPs. Harm is often a focus, with e-cigarette users stating the belief that e-cigarettes are less harmful than combustible cigarettes. However, here, we did not find a difference in perceived harm that was moderated by nicotine product use type. Motivations to use e-cigarettes in our sample tended to be more about the consideration of others or alleviating dependence on combustible products, rather than about harm, cost, or other motivating factors. Combustible product users also reported combustible NTP use for its reinforcing properties, affect regulation, social facilitation, and relief of boredom. Results suggest NTP users, and combustible product users in particular, have higher levels of substance use and more severe nicotine dependence. While alcohol and cannabis use were present in each group, E-Cig reported more use than NTP Naïve, while combustible users reported the most use. The Combustible+ group also reported more ecigarette use than the E-Cig group and had higher levels of severity of nicotine dependence across measures. Here, it is not clear that the use of combustible NTPs are driving the attitude and/or behavioral differences, rather than other individual characteristics or preexisting factors which impact overall substance use. This finding is in line with other reports of increased dependence in dual users of combustible and non-combustible NTP and has similarly been found in younger adolescents, in adults, in those with higher levels of tobacco product use, and in populations with greater substance use in general. Therefore, it may be that tobacco cigarette or dual users are at increased risk of substance dependence in general and downstream negative sequelae. NTP users in the present study reported higher levels of BDI depression and DASS stress symptoms,sub irrigation cannabis including a higher prevalence of symptoms crossing the threshold of clinical depression than NTP-Naïve participants. Male Combustible+ had higher levels of depression symptoms than either E-Cig or NTP Naïve, while there was no significant difference by group for females. There was also no difference in their self-reported anxiety symptoms when considering all participants together, regardless of gender. This is a cross sectional analysis in which direction and causality cannot be determined, and therefore it is unclear if NTP use was a risk factor for depression and stress, or vice versa. Indeed, a longitudinal analysis of emerging adults found depression was an important risk factor for nicotine dependence, while another longitudinal study found NTP use was associated with later depression.

Others have found cigarette, but not e-cigarette use, linked to mental health functioning. Given preliminary evidence here of heightened risk for combustible use among males with elevated depression scores, gender and emotional functioning should continue to be monitored and examined as potential risk factors for combustible product use. Future research is necessary to disentangle modes of nicotine administration and mental health outcomes in adolescents and emerging adults. This investigation is the first known study of e-cigarette use that objectively measured neurocognitive performance, and no differences in cognition by nicotine group status were observed. Cognitive differences in adolescent and young adult NTP users have been noted previously, though not always. E-cigarettes specifically have been linked to poorer self-reported neurocognition, though subjective concerns may not relate to true performance deficits. Lower or more acute doses of nicotine are linked to cognitive enhancement, while chronic and/or high doses of nicotine are linked to desensitization of nicotine acetylcholine receptors , including alterations of the modulation of dopamine, serotonin, and other receptors, which potentially impact cognitive performance. While 12 h of abstinence from alcohol, cannabis, and all other drug use were required for the present study, participants were allowed to smoke/vape during their study session to prevent withdrawal effects and, therefore, potentially enhance neurocognitive performance. Our participants were also using NTPs at relatively low levels in the past six months, vaping three-to-four times a day on average and, in combustible users, smoking combustible products five-to-six days per month. The lack of differences may imply that relatively low level NTP use may not be as detrimental as previously thought, suggesting that there is still time for intervention before more of the negative sequelae of sustained nicotine use and dependence become apparent. Interestingly, while not a primary aim of the present study, past six-month cannabis use was related to poorer Emotional Stroop congruent emotion processing , with no difference on the non-congruent condition. Congruent processing accuracy is particularly relevant for processing speed and attention, deficits previously shown in cannabis users and in pre-adolescent youth with higher externalizing symptoms. Further, prior research indicates cannabis users may be particularly vulnerable to cognitive control and affective processing deficits, including when identifying emotional faces. Cannabis users may have to use more neural resources to achieve the same level of performance, though this may not happen as readily on a less demanding task, such as on a congruent processing task. Future research should continue to investigate socio-affective response in cannabis users. Limitations: All groups included alcohol and cannabis use which, while better generalizing to typical real-world use patterns, may limit ability to detect differences due to NTP use alone, despite attempts to statistically control for these substances in the analyses. In addition, both E-Cig and Combustible+ used e-cigarette products, which may also be a source of bias, and makes it difficult to disentangle findings that are unique to e-cig vs. combustible product use. As mentioned above, NTP users in this age range, and particularly combustible NTP users, may not yet be using at a level to meaningfully impact neurocognition or mental health. Alternatively, the lower level of use may have contributed to limited neurocognitive differences in this young adult sample. Though group differences in attitudes are noted, and data are descriptive, it is unclear what individual and environmental characteristics may contribute to the acquisition of these attitudes. Finally, the present analyses are cross sectional in nature; longitudinal studies designed for causal inference are needed to establish directionality of results. The present findings add to the field’s understanding of the unique and shared characteristics between adolescent and young adult combustible and non-combustible NTP users.