The COVID-19 pandemic caused increased drug use and a widespread decline in mental health throughout American society. Yet, despite the unprecedented pandemic, society as a whole has shown an impressive ability to adapt to new ways of living, suggesting that a dramatically different version of America is not only possible, but achievable. Domestic drug policy, which has needlessly prohibited and criminalized a vast array of drugs since the early 1900s, is an area ripe for a similar dramatic change. This paper explores how the pandemic, combined with concurrent events including a change in Federal Administration and nationwide protests against systemic racism, presents an opportunity for our country to rethink its long-standing drug prohibition on a national scale.

Adolescence is a period of rapid brain development when psychiatric symptoms often first emerge. Studying adolescents may therefore facilitate the identification of neural alterations early in the course of psychiatric conditions. Here, we sought to utilize new, high-quality brain parcellations and data-driven graph theory approaches to characterize associations between resting-state networks and the severity of depression, anxiety, and anhedonia symptoms—salient features across psychiatric conditions. As reward circuitry matures considerably during adolescence, we examined both Whole Brain and three task-derived reward networks. Subjects were 87 psychotropic-medication-free adolescents (age = 12–20) with diverse psychiatric conditions (n = 68) and healthy controls (n = 19). All completed diagnostic interviews, dimensional clinical assessments, and 3T resting-state fMRI (10 min/2.3 mm/TR = 1 s). Following high-quality Human Connectome Project-style preprocessing, multimodal surface matching (MSMAll) alignment, and parcellation via the Cole-Anticevic Brain-wide Network Partition, weighted graph theoretical metrics (Strength Centrality = CStr; Eigenvector Centrality = CEig; Local Efficiency = ELoc) were estimated within each network. Associations with symptom severity and clinical status were assessed non-parametrically (two-tailed pFWE < 0.05). Across subjects, depression scores correlated with ventral striatum CStr within the Reward Attainment network, while anticipatory anhedonia correlated with CStr and ELoc in the subgenual anterior cingulate, dorsal anterior cingulate, orbitofrontal cortex, caudate, and ventral striatum across multiple networks. Group differences and associations with anxiety were not detected. Using detailed functional and clinical measures, we found that adolescent depression and anhedonia involve increased influence and communication efficiency in prefrontal and limbic reward areas. Resting-state network properties thus reflect positive valence system anomalies related to discrete reward sub-systems and processing phases early in the course of illness.

As legal cannabis begins to infiltrate most American states and public support grows for federal legalization, the national discussion has shifted from if cannabis should be legalized to how it should be legalized. A significant part of this debate has centered around the need to use cannabis legalization to address the lasting harm done to communities of color through federal prohibition. A fair and just framework for the legal cannabis industry cannot be achieved without sufficient efforts to foster social equity within the industry and to right the wrongs done by decades of prohibition. While most states with legal cannabis have recognized this issue and have taken some steps to address it, state action as a whole has been mostly ineffective and does not adequately reflect the scale of the problem. This paper argues that broad federal action is needed to achieve true social equity in the cannabis industry, action that goes beyond recognizing the problems and works to change the stigma surrounding drug use and its historical relation to communities of color.

Despite the significant impact of laws and policies surrounding controlled substances, few classes in the typical law school curriculum focus on either basic legal doctrines or broader scholarship in this field. This gap in law school curricula is especially problematic given the shifts in the landscapes of legalized cannabis and hemp, as well as the range of legal and policy responses to the recent opioid crisis. To continue our efforts to better understand how law schools currently approach these issues and to identify how drug policy and law could be better incorporated into law school curricula, we conducted a third survey of all accredited law schools in the U.S. The 2020-21 survey followed two previous annual surveys and a workshop of legal scholars who work in this space. The surveys and 2019 workshop were designed to identify law school courses currently taught and the primary obstacles to teaching this subject matter. The results show that the vast majority of law schools do not teach courses touching on drugs or the evolving legal structures around cannabis, and this is true even for law schools located in states with legalized cannabis markets.

Objective Adolescence is a period of rapid brain development when symptoms of mood, anxiety, and other disorders often first emerge, suggesting disruptions in maturing reward circuitry may play a role in mental illness onset. Here, we characterized associations between resting-state network properties and psychiatric symptomatology in medication-free adolescents with a wide range of symptom severity. Methods Adolescents (age 12-20) with mood and/or anxiety symptoms (n=68) and healthy controls (n=19) completed diagnostic interviews, depression/anhedonia/anxiety questionnaires, and 3T resting-state fMRI (10min/2.3mm/TR=1s). Data were preprocessed (HCP Pipelines), aligned (MSMAll), and parcellated into 750 nodes encompassing the entire cortex/subcortex (Cole-Anticevic Brain-wide Network Partition). Weighted graph theoretical metrics (Strength Centrality=CStr; Eigenvector Centrality=CEig; Local Efficiency=ELoc) were estimated within Whole Brain and task-derived Reward Anticipation / Attainment / Prediction Error networks. Associations with clinical status and symptoms were assessed non-parametrically (two-tailed pFWE <0.05). Results Relative to controls, clinical adolescents had increased ventral striatum CEig within the Reward Attainment network. Across subjects, depression correlated with subgenual cingulate CStr and ELoc, anhedonia correlated with ventromedial prefrontal CStr and lateral amygdala ELoc, and anxiety negatively correlated with parietal operculum CEig and medial amygdala ELoc within the Whole Brain network. Conclusions Using a data-driven analysis approach, high-quality parcellation, and clinically diverse adolescent cohort, we found that symptoms within positive and negative valence system constructs differentially associated with resting-state network abnormalities: depression and anhedonia, as well as clinical status, involved greater influence and communication efficiency in prefrontal and limbic reward areas, whereas anxiety was linked to reduced influence/efficiency in amygdala and cortical regions involved in stimulus monitoring.

The COVID-19 pandemic, while detrimental to the American economy as a whole, positively impacted the cannabis industry in many ways. This paper examines how the pandemic changed the medical cannabis industries in three states where medical cannabis programs were recently implemented -- Ohio, Pennsylvania, and Maryland. In all three states, cannabis dispensaries were declared essential businesses and have remained in operation throughout the pandemic. Due to the necessities of social distancing and minimizing contact, the medical cannabis programs in these states implemented new, innovative measures such curbside pickup, online ordering technology, drive-thru windows, delivery systems, and telehealth consultations. Additionally, some states loosened restrictions on supply limits and caregiver registration, making medical cannabis more accessible to patients. This paper suggests that many of these changes should remain permanent after the pandemic ends because they have modernized and, in some cases, legitimized, the cannabis industries in these states.

Growing evidence suggests an association between dysregulation of γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, and the pathophysiology of MDD. Earlier results by the mentor’s laboratory showed that decreased anterior cingulate cortex (ACC) GABA is associated with anhedonia and more severe illness in a cross-sectional study. In this pilot study, we aimed to assess the clinical predictive value of baseline ACC GABA in adolescents with MDD and in healthy control (HC) subjects at long-term follow-up.

Background: The neuroimmunological kynurenine pathway (KP) has been hypothesized to play a role in depressive/ anhedonic symptoms and related CNS disturbances. Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme which leads to neurotrophic [kynurenic acid (KA)] and neurotoxic [Quinolinic acid (QUIN)] branches. In this pilot, we sought to examine associations between blood KP neuro-toxic/trophic measures and anhedonia/depression associated networks in youth with major depression (MDD) and healthy controls (HC). Methods: Subjects were 14 psychotropic-medication free adolescents with MDD and 7 HC, ages 12-19 yo. All underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxel-wise maps were generated indicating correlation strengths among 4 bilateral seeds [(dorsal anterior cingulate cortex (dACC), perigenual ACC (pgACC), subgenual ACC (sgACC) and nucleus accumbens (NAc)] and remaining brain regions. FMRI analyses were family-wise error corrected. KP metabolites were measured using liquid chromatography-tandem mass spectrometry. Results: Connectivity between the right dACC and the right precuneus was positively correlated with KA levels. This same cluster demonstrated an inverse correlation with IDO activity. Exploratory analysis at a more liberal clustering threshold showed the KA/QUIN ratio was positively correlated with connectivity between the pgACC and the right medial prefrontal cortex. Lastly, connectivity between the pgACC and the left inferior temporal gyrus was positively correlated with QUIN levels. Limitations: Findings are preliminary due to the small sample size. Conclusions: This pilot study is the first report in depressed adolescents demonstrating associations between the KP and anhedonia/depression-associated brain networks. This pilot adds evidence to the putative role of the KP in MDD.

Background: As the most commonly used illicit substance during early adolescence, long-term or latent effects of early adolescent marijuana use across adolescent developmental processes remain to be determined. Methods: We examined cortical thickness, gray/white matter border contrast (GWR) and local gyrification index (LGI) in 42 marijuana (MJ) users. Voxelwise regressions assessed early-onset (age <16) vs. late-onset (≥16 years-old) differences and relationships to continued use while controlling for current age and alcohol use. Results: Although groups did not differ by onset status, groups diverged in their correlations between cannabis use and cortical architecture. Among early-onset users, continued years of MJ use and current MJ consumption were associated with thicker cortex, increased GWR and decreased LGI. Late-onset users exhibited the opposite pattern. This divergence was observed in all three morphological measures in the anterior dorsolateral frontal cortex (p < .05, FWE-corrected). Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

Background: Exteroception involves processes related to the perception of environmental stimuli important for an organism's ability to adapt to its environment. As such, exteroception plays a critical role in conditioned response. In addiction, behavioral and neuroimaging studies show that the conditioned response to drug-related cues is often associated with alterations in brain regions including the precuneus/posterior cingulate cortex, an important node within the default mode network dedicated to processes such as self-monitoring. Objective: This review aimed to summarize the growing, but largely fragmented, literature that supports a central role of exteroceptive processes in addiction. Methods: We performed a systematic review of empirical research via Pub Med and Google Scholar with keywords including 'addiction', 'exteroception 'precuneus and 'self-awareness', to identify human behavioral and neuroimaging studies that report mechanisms of self-awareness in healthy populations, and altered self-awareness processes, specifically exteroception, in addicted populations. Results: Results demonstrate that exteroceptive processes play a critical role in conditioned cue response in addiction and serve as targets for interventions such as mindfulness training. Further, a hub of the default mode network, namely, the precuneus, is (i) consistently implicated in exteroceptive processes, and (ii) widely demonstrated to have increased activation and connectivity in addicted populations. Conclusion: Heightened exteroceptive processes may underlie cue-elicited craving, which in turn may lead to the maintenance and worsening of substance use disorders. An exteroception model of addiction provides a testable framework from which novel targets for interventions can be identified.

The existing literature on the role of emotion regulation circuits (amygdala-prefrontal cortex) in the adolescent brain yields mixed results, particularly on the role of these regions in the context of reward sensitivity and risk-taking behavior sensitivity and risk-taking behavior. Here, we examined functional connectivity in the resting state in 18 risk-taking (RT) adolescents compared with 18 non-risk-taking (NRT) adolescents as defined by the Youth Risk Behavior Surveillance Survey. Separate seed-based correlations with bilateral amygdala and bilateral nucleus accumbens used as the seed were performed to determine functional connectivity using functional magnetic resonance imaging (fMRI). The results showed greater connectivity between the amygdala (seed region) and the right middle frontal gyrus, left cingulate gyrus, left precuneus and right inferior parietal lobule in RT adolescents than in NRT adolescents. Likewise, there was greater connectivity between the nucleus accumbens (seed region) and the right middle frontal gyrus in RT adolescents compared with NRT adolescents. These findings suggest that risk-taking behavior in adolescents is associated with hyperconnectivity during the resting state in networks associated with emotion regulation, reward sensitivity, executive control, and the default mode.

Context: The rising rate of overweight and obese individuals among developing countries despite focused efforts on prevention and treatment underscores not only the need to better define the physiological factors that contribute to weight problems, but also the need to elucidate the neurobiological mechanisms of the self-regulatory failure over eating that leads to weight problems. Emergent findings suggest an overlapping model of addiction and compulsive overeating.Objective: Our goal was to examine whether neural hyper-responsivity to reward typically associated with substance abuse could also be seen in individuals exhibiting binge-eating behavior. Design: Participants completed self-assessments of demographic information and eating behavior. Neurofunctional data were collected via functional MRI (fMRI) scans while participants were exposed to personally relevant high-calorie cues.Setting: The participants were recruited from the general community.Participants: Twenty-six individuals with high body mass index (BMI)>25 and moderate binge-eating behavior as assessed by the Binge Eating Scale (BES) were recruited for this study.Main Outcome Measures: fMRI BOLD response during exposure to high-calorie taste cues.Results: The results showed that exposure to high-calorie taste cues elicited fMRI BOLD response in the reward system of individuals with high BMI, and, more importantly, that this hyper-responsivity increases with greater number of binge-eating symptoms (cluster-corrected p<.05, z=1.9).Conclusions: These findings support an overlapping neural model of addiction and self-regulatory failure over eating that may lead to problems with weight in humans. These findings offer insight into the prevention and treatment of disordered eating. (C) 2012 Elsevier Inc. All rights reserved.

Cue-elicited craving or the intense desire to consume a substance following exposure to a conditioned drug cue is one of the primary behavioral symptoms of substance use disorders (SUDs). While the concept of cue-elicited craving is well characterized in alcohol and other substances of abuse, only recently has it been described in cannabis. A review of the extant literature has established that cue-elicited craving is a powerful reinforcer that contributes to drug-seeking for cannabis. Further, emergent research has begun to identify the neurobiological systems and neural mechanisms associated with this behavior. What research shows is that while theories of THC's effects on the dopaminergic-reward system remain divergent, cannabis cues elicit neural activation in the brain's reward network.

Darwinian fitness reflects trade-offs between reproduction and survival. Mechanisms have evolved in small nontropical mammals and birds to maximize reproductive output during the summer when thermoregulatory demands are relatively low and food is abundant and to shunt energy to processes that presumably increase the odds of survival during the winter when thermoregulatory demands are high and food is scarce. In order to predict the onset of winter, many seasonally-breeding mammals use day length (photoperiod) information. Seasonal adjustments of immune responses may be one mechanism to enhance survival; short days enhance cell-mediated immune function in seasonally-breeding rodents. The goal of the present study was to determine whether delayed-type hypersensitivity in hamsters is constrained or if photoperiod merely establishes a baseline level of immune response that can then be fined tuned by other environmental conditions. To test this, we used environmental enrichment, a manipulation that enhances many aspects of immune function. Hamsters were assigned to either long or short photoperiods and further assigned into either singly-housed or environmentally-enriched cages. After 10 weeks of concurrent photoperiod and housing treatment, delayed-type hypersensitivity (DTH) was induced. Although short days enhanced DTH responses compared with long days, environmental enrichment enhanced swelling responses in both short days and long days, suggesting that even during potential energetic bottlenecks or during maximal reproductive investment, hamsters can modulate their investment in immune function.