Nalbuphine Potentiates Reversal of Fentanyl Overdose by Naloxone.

Developing an effective antidote for fentanyl-induced overdose to achieve timely reversal is an unmet public health need. Previously, we found that naloxone derivative NX90 with mild κ-opioid agonistic properties was three-fold more effective than the parent naloxone in reversing a fentanyl overdose in rats. To investigate whether κ-agonistic properties could indeed augment the robustness of overdose reversal, we evaluated a κ-agonist/µ-antagonist nalbuphine (NB) as well as its combinations with naloxone (NX) in a fentanyl overdose model in rodents. An administration of either NB or NX as single agents at 0.1 mg/kg doses produced a full recovery in 90 ± 9.9 min and 11.4 ± 2.7 min, respectively. A higher dose of NX at 0.2 mg/kg reversed an overdose within 4.8 ± 1.0 min. In contrast to that, the coadministration of NB and NX at 0.1 mg/kg each produced a synergistic effect, with overdose reversal in 3.4 ± 0.2 min. The coadministration of NX and NB at sub-therapeutic doses of 0.05 mg/kg each was also 1.2-fold more effective than NX at 0.2 mg/kg. We further found that co-administration of NB at different doses (0.025, 0.05, 0.1 mg/kg) and ratios (1:4 and 1:1) with NX had differential effects on overdose reversal, cardiorespiratory liabilities, and analgesia.

Medicinal cannabis use among young adults during California's transition from legalized medical use to adult-use: a longitudinal analysis.

Background: In 2016, California transitioned from legalized medical cannabis use to adult-use. Little is known about how this policy change affected medicinal cannabis use among young adults.Objectives: To identify longitudinal groups of medicinal cannabis users and concurrent changes in health- and cannabis use-related characteristics among young adults in Los Angeles between 2014 and 2021.Methods: Cannabis users (210 patients and 156 non-patients; 34% female; ages 18-26 at baseline) were surveyed annually across six waves. Longitudinal latent class analysis derived groups from two factors - cannabis patient status and self-reported medicinal use. Trajectories of health symptoms, cannabis use motives, and cannabis use (daily/near daily use, concentrate use, and problematic use) were estimated across groups.Results: Three longitudinal latent classes emerged: Recreational Users (39.3%) - low self-reported medicinal use and low-to-decreasing patient status; Recreational Patients (40.4%) - low self-reported medicinal use and high-to-decreasing patient status; Medicinal Patients (20.3%) - high self-reported medicinal use and high-to-decreasing patient status. At baseline, Medicinal Patients had higher levels of physical health symptoms and motives than recreational groups (p < .05); both patient groups reported higher level of daily/near daily and concentrate use (p < .01). Over time, mental health symptoms increased in recreational groups (p < .05) and problematic cannabis use increased among Recreational Patients (p < .01).Conclusions: During the transition to legalized adult-use, patterns of medicinal cannabis use varied among young adults. Clinicians should monitor increases in mental health symptoms and cannabis-related problems among young adults who report recreational - but not medicinal - cannabis use.

Mental and Physical Health-Related Cannabis Motives Mediate the Relationship between Childhood Trauma and Problematic Cannabis Use over Time among Emerging Adult Cannabis Users.

BACKGROUND: While growing evidence has identified mental and physical health-related cannabis use motives as significant mechanisms between childhood trauma and problematic cannabis use (PCU) for emerging adults (EA), there is a need to understand the longitudinal stability of these pathways and how they impact PCU as cannabis users age into later adulthood. METHODS: The current study extends an analysis examining the impact of childhood trauma (e.g., emotional abuse, sexual abuse) on multiple indicators of PCU through a range of cannabis use motives. 339 medical cannabis patient and non-patient EA users from the Los Angeles area were sampled at baseline (mean age = 21.23; SD = 2.48). The present analysis used four waves of follow-up data collected from 2016 to 2018 (W3, W4) and 2019-2020 (W5, W6). RESULTS: Use of cannabis to cope with nausea, sleep, pain, and emotional distress mediated the relationships between some types of childhood abuse and PCU at W4, though most associations attenuated by later adulthood (W6). Specifically, greater emotional distress and nausea motives were associated with greater PCU in models of emotional abuse and neglect and sexual abuse, with emotional distress continuing to mediate at W6. Conversely, sleep and pain motives were associated with lower PCU in models for emotional neglect. CONCLUSIONS: Mental and physical health-related motives reflect potential intervenable factors that predict PCU in emerging adulthood among EA cannabis users with histories of childhood trauma. Results highlight the importance of and value for assessing a wide range of motives and PCU outcomes to target and address areas for intervention.

Predictive Dispatch of Volunteer First Responders: Algorithm Development and Validation.

BACKGROUND: Smartphone-based emergency response apps are increasingly being used to identify and dispatch volunteer first responders (VFRs) to medical emergencies to provide faster first aid, which is associated with better prognoses. Volunteers' availability and willingness to respond are uncertain, leading in recent studies to response rates of 17% to 47%. Dispatch algorithms that select volunteers based on their estimated time of arrival (ETA) without considering the likelihood of response may be suboptimal due to a large percentage of alerts wasted on VFRs with shorter ETA but a low likelihood of response, resulting in delays until a volunteer who will actually respond can be dispatched. OBJECTIVE: This study aims to improve the decision-making process of human emergency medical services dispatchers and autonomous dispatch algorithms by presenting a novel approach for predicting whether a VFR will respond to or ignore a given alert. METHODS: We developed and compared 4 analytical models to predict VFRs' response behaviors based on emergency event characteristics, volunteers' demographic data and previous experience, and condition-specific parameters. We tested these 4 models using 4 different algorithms applied on actual demographic and response data from a 12-month study of 112 VFRs who received 993 alerts to respond to 188 opioid overdose emergencies. Model 4 used an additional dynamically updated synthetic dichotomous variable, frequent responder, which reflects the responder's previous behavior. RESULTS: The highest accuracy (260/329, 79.1%) of prediction that a VFR will ignore an alert was achieved by 2 models that used events data, VFRs' demographic data, and their previous response experience, with slightly better overall accuracy (248/329, 75.4%) for model 4, which used the frequent responder indicator. Another model that used events data and VFRs' previous experience but did not use demographic data provided a high-accuracy prediction (277/329, 84.2%) of ignored alerts but a low-accuracy prediction (153/329, 46.5%) of responded alerts. The accuracy of the model that used events data only was unacceptably low. The J48 decision tree algorithm provided the best accuracy. CONCLUSIONS: VFR dispatch has evolved in the last decades, thanks to technological advances and a better understanding of VFR management. The dispatch of substitute responders is a common approach in VFR systems. Predicting the response behavior of candidate responders in advance of dispatch can allow any VFR system to choose the best possible response candidates based not only on ETA but also on the probability of actual response. The integration of the probability to respond into the dispatch algorithm constitutes a new generation of individual dispatch, making this one of the first studies to harness the power of predictive analytics for VFR dispatch. Our findings can help VFR network administrators in their continual efforts to improve the response times of their networks and to save lives.

Pre-Post Cannabis Legalization for Adult Use: A Trend Study of Two Cohorts of Young Adult Cannabis Users in Los Angeles.

Cannabis was legalized for adult use in California in 2016 for individuals 21 and older. Among 18-20-years-olds, who can possess cannabis legally as medical cannabis patients (MCP) but not as non-patient cannabis users (NPU), the impact of adult use legalization (AUL) on cannabis and other substance use is unknown. Two cohorts of 18-20-year-old cannabis users (MCP and NPU) were surveyed, one in 2014-15 (n = 172 "pre-AUL") and another in 2019-20 (n = 139 "post-AUL"), using similar data collection methods in Los Angeles, California. Logistic and negative binomial regressions estimated cohort and MCP differences for cannabis and other drug use outcomes based on past 90-day use. In both pre- and post-AUL cohorts, MCP were more likely to self-report medical cannabis use (p < .001) while the post-AUL cohort reported greater use of edibles (p < .01), but fewer mean days of alcohol (p < .05) and cigarette (p < .01) use in multivariate models. Notably, frequency of cannabis use (days or hits per day) did not significantly differ between the pre- and post-AUL cohorts, except for greater use of edibles, despite potentially greater access to cannabis.

Understanding Changes in Social Cannabis Use among Young Adults During the COVID-19 Pandemic: A Social Network Analysis.

Introduction: As the COVID-19 pandemic has caused historic morbidity and mortality and disrupted young people's social relationships, little is known regarding change in young adults' social cannabis use following social distancing orders, or other factors associated with such changes before and during the pandemic. Methods: 108 young adult cannabis users in Los Angeles reported on their personal (egocentric) social network characteristics, cannabis use, and pandemic-related variables before (July 2019 - March 2020) and during the COVID-19 pandemic (August 2020 - August 2021). Multinomial logistic regression identified factors associated with increasing or maintaining the number of network members (alters) participants used cannabis with before and during the pandemic. Multilevel modeling identified ego- and alter-level factors associated with dyadic cannabis use between each ego and alter during the pandemic. Results: Most participants (61%) decreased the number of alters they used cannabis with, 14% maintained, and 25% increased. Larger networks were associated with a lower risk of increasing (vs. decreasing); more supportive cannabis-using alters was associated with a lower risk of maintaining (vs. decreasing); relationship duration was associated with a greater risk of maintaining and increasing (vs. decreasing). During the COVID-19 pandemic (August 2020 - August 2021), participants were more likely to use cannabis with alters they also used alcohol with and alters who were perceived to have more positive attitudes towards cannabis. Conclusions: The present study identifies significant factors associated with changes in young adults' social cannabis use following pandemic-related social distancing. These findings may inform social network interventions for young adults who use cannabis with their network members amid such social restrictions.

COVID-19 Vaccine Uptake and Attitudes Within Two Cohorts of Younger Adult Cannabis Users.

It is crucial to understand COVID-19 vaccine uptake and attitudes among young adult cannabis users given the lowest vaccination rates among young adults and negative association between cannabis use and willingness to get vaccinated. 18-21-year-old and 26-33-year-old cohorts of cannabis users, recruited in California, were surveyed about the COVID-19 vaccine uptake/attitudes between March-August 2021. Cannabis use/demographic differences were investigated by vaccination status. Vaccine attitudes data were categorized and presented descriptively. 44.4% of the older and 71.8% of the younger cohorts were vaccinated. Non-Hispanic Black/African American race/ethnicity, lack of health insurance, and medicinal orientation towards cannabis use were negatively associated with vaccine receipt within the older cohort. For both cohorts, top reasons for vaccine hesitancy and rejection were concerns about speed of development, potential side effects, natural immunity, and lack of trust of vaccines. Our results highlight greater vaccine hesitance/rejection and need for targeted interventions among mid-20's-early-30's cannabis users.

COVID-19's Impact on Substance Use and Well-Being of Younger Adult Cannabis Users in California: A Mixed Methods Inquiry.

Few qualitative studies have examined the impact of COVID-19 on cannabis and alcohol use, and overall well-being among cannabis users. Cannabis users (aged 26-32) were surveyed quantitatively (n=158) and interviewed qualitatively (n=29) in April 2020-May 2021 in Los Angeles. 63.3% of the quantitative sample reported increasing use of either cannabis (29.1%) or alcohol (15.2%) or both (19.0%) following the COVID-19 outbreak. Qualitative data revealed that increases in cannabis and alcohol use were largely attributed to changes in employment and staying at home resulting in fewer impediments and boredom. Themes of loneliness and utilization of various coping strategies were more pronounced among those who increased cannabis and/or alcohol use. For some, increases in cannabis/alcohol use were temporary until participants adjusted to "a new normal" or embraced more adaptive coping strategies. Results suggest monitoring cannabis/alcohol use trends and identifying coping strategies to reduce the pandemic's impact on substance use and mental health.

Miscarriage and Abortion Among Women Attending Harm Reduction Services in Philadelphia: Correlations With Individual, Interpersonal, and Structural Factors.

Background: Reproductive health research among women who use drugs has focused on pregnancy prevention and perinatal/neonatal outcomes, but there have been few investigations of miscarriage and abortion, including prevalence and associated factors. Methods: Using cross-sectional data from a sample of non-pregnant women receiving harm reduction services in Philadelphia in 2016-2017 we examined lifetime miscarriage and abortion (n = 187). Separately for both outcomes, we used modified Poisson regression to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for associations with each correlate. We also explored correlates of reporting both miscarriage and abortion. Results: Approximately 47% experienced miscarriage, 42% experienced abortion, and 18% experienced both. Miscarriage correlates included: prescription opioid misuse (e.g., OxyContin PR 1.82, 95% CI 1.23, 2.69); 40% increase in prevalence associated with housing instability, 50% increase with survival sex, and two-fold increase with arrest. Abortion correlates included: mental health (e.g., depression PR 2.09, 95% CI 1.18, 3.71), stimulant use (e.g., methamphetamine PR 1.83, 95% CI 1.22, 2.74), and drug injection (PR 1.76, 95% CI 1.03, 3.02); partner controlling access to people/possessions, physical and emotional violence; and a two-fold increase associated with survival sex and arrest. Experiencing both reproductive outcomes was correlated with mental health, opioid and simulant use, housing instability, survival sex, and arrest. Conclusion: Miscarriage and abortion was common among women with history of drug misuse suggesting a need for expanded access to family planning, medication-assisted therapy, and social support services, and for the integration of these with substance use services. Future research in longitudinal data is needed.

Multiple Victimizations and Overdose Among Women With a History of Illicit Drug Use.

The experiences of violence and overdose are highly prevalent among women who use illicit drugs. This study sought to ascertain whether multiple victimizations during adulthood increase the frequency of women's overdose. The sample comprised 218 women recruited at Philadelphia harm reduction sites during 2016-2017. Victimization was assessed as exposure to 16 types of adulthood violence. Three measures were constructed for multiple victimizations: continuous and categorical polyvictimization, and predominant violence domain. Negative binomial regression estimated the incidence rate ratio (IRR) of lifetime overdoses from multiple victimizations. Lifetime history of opioid use (88.6%) and drug injection (79.5%) were common. Among overdose survivors (68.5%), the median of lifetime overdoses was 3. The majority of participants (58.7%) were victims of predominantly sexual violence, 26.1% experienced predominantly physical abuse/assault, and 3.7% were victims of predominantly verbal aggression/coercive control. Participants reported a mean of seven violence types; the higher-score category of polyvictimization (9-16 violence types) comprised 41.7% of the total sample. In multivariable models, one-unit increase in continuous polyvictimization was associated with 4% higher overdose rates (IRR: 1.04, 95% confidence interval [CI]: [1.00, 1.08]). Compared to women who were not victimized (11.5%), those in the higher-score category of polyvictimization (IRR: 2.01; 95% CI: [1.06, 3.80]) and exposed to predominantly sexual violence (IRR: 2.10, 95% CI: [1.13, 3.91]) were expected to have higher overdose rates. Polyvictimization and sexual violence amplified the risk of repeated overdose among drug-involved women. Female overdose survivors need to be screened for exposure to multiple forms of violence, especially sexual violence. Findings underscore the need to scale-up victimization support and overdose prevention services for disenfranchised women.

Changes in Medical Cannabis Patient Status before and after Cannabis Legalization in California: Associations with Cannabis and Other Drug Use.

It is unknown how patterns of cannabis and other drug use changed among young adult cannabis users as they became, exited or stayed medical cannabis patients (MCPs) after California legalized cannabis for adult use in 2016. A cohort of 18-26 year-old cannabis users was recruited in Los Angeles in 2014-15 (64.8% male; 44.1% Hispanic/Latinx). Based on wave 1 (pre-legalization) and wave 4 (post-legalization) MCP status, four transition groups emerged: MCP, Into MCP, Out of MCP and NPU (non-patient user). Relationships between self-reported medical cannabis use, transition group membership, and cannabis/other drug use outcomes were examined. Changes in cannabis practices were consistent with changes in MCP status. Cannabis days, concentrate use, self-reported medical cannabis use and driving under influence of cannabis were highest among MCP, increased for Into MCP, and decreased for Out of MCP in wave 4. A majority of drug use outcomes decreased significantly by wave 4. Self-reported medical cannabis use was associated with more frequent cannabis use but less problematic cannabis and other drug use. Future studies should continue to monitor the impact of policies that legalize cannabis for medical or recreational use, and medical motivations for cannabis use on young adults' cannabis and other drug use.

Modifying naloxone to reverse fentanyl-induced overdose.

Developing an effective antidote for fentanyl-induced overdose (OD) is an unmet medical need that requires both lipophilicity comparable to fentanyl and fast onset of overdose reversal. We synthesized and evaluated a bioreversible derivative of naloxone (NX-90) in silico, in vitro and in vivo to yield a robust reversal of fentanyl-induced OD in rats. All monitored reflexes along with the heart rate (HR) and respiratory rate (RR) were fully restored faster in the NX-90 groups than in naloxone groups on equimolar bases when given intranasally. In NX-90 treated rats RR over the time of observation (RR AUC) was significantly higher at all respective doses with no re-narcotization observed. Apart from the enhanced pharmacodynamics profile, NX-90 was found to have lower circulating levels of naloxone, clean profile in in vitro selectivity panels, as well as Ames and CYP450 counter screens. Finally, we demonstrated a robust release of the parent naloxone in brain matrix, as well as lower peripheral naloxone levels after NX-90 iv administration. With the demonstrated pharmacological profile superior yet congruent to naloxone we nominated NX-90 for preclinical development as an effective intranasal fentanyl antidote.

Wearable biosensors have the potential to monitor physiological changes associated with opioid overdose among people who use drugs: A proof-of-concept study in a real-world setting.

INTRODUCTION: Wearable biosensors have the potential to monitor physiological change associated with opioid overdose among people who use drugs. METHODS: We enrolled 16 individuals who reported ≥ 4 daily opioid use events within the previous 30 day. Each was assigned a wearable biosensor that measured respiratory rate (RR) and actigraphy every 15 s for 5 days and also completed a daily interview assessing drug use. We describe the volume of RR data collected, how it varied by participant characteristics and drug use over time using repeated measures one-way ANOVA, episodes of acute respiratory depression (≤5 breaths/minute), and self-reported overdose experiences. RESULTS: We captured 1626.4 h of RR data, an average of 21.7 daily hours/participant over follow-up. Individuals with longer injection careers and those engaging in polydrug use captured significantly fewer total hours of respiratory data over follow-up compared to those with shorter injections careers (94.7 vs. 119.9 h, p = 0.04) and injecting fentanyl exclusively (98.7 vs. 119.5 h, p = 0.008), respectively. There were 385 drug use events reported over follow-up. There were no episodes of acute respiratory depression which corresponded with participant reports of overdose experiences. DISCUSSION: Our preliminary findings suggest that using a wearable biosensor to monitor physiological changes associated with opioid use was feasible. However, more sensitive biosensors that facilitate triangulation of multiple physiological data points and larger studies of longer duration are needed.

A vicious cycle of neuropathological, cognitive and behavioural sequelae of repeated opioid overdose.

In the midst of an escalating U.S. opioid crisis, the immediate focus of public health interventions is on fatal overdose prevention. Few studies, however, have sought to examine the long-term health consequences of exposure to repeated nonfatal opioid overdose. We reviewed recent literature to examine three corresponding downstream health outcomes of repeated overdose: a) neurodegenerative processes; b) cognition and memory; and c) overdose risk behaviours. We found a remarkable congruency among available biochemical and cognitive data on how nonfatal overdose precipitates various pathological feedforward and feedback loops that affect people who use opioids for years to come. We found however that downstream behavioural implications of neurodegenerative and cognitive sequelae are less studied despite being most proximal to an overdose. Findings point to a vicious cycle of nonfatal overdose leading to neurodegeneration - closely resembling Alzheimer Disease - that results in cognitive decline that in turn leads to potentially reduced adherence to safe drug use behaviours. The collected evidence not only brings into the focus the long-term health consequences of nonfatal overdose from the perspectives of biology, neuroscience, and public health, but also creates new cross-disciplinary context and awareness in the research and public health community that should benefit people at risk.

Overdose response among trained and untrained women with a history of illicit drug use: a mixed-methods examination.

Little is known about differences in bystander behavior among people who use drugs, trained and untrained in opioid overdose prevention. We examined three types of recommended overdose response - a 911 call, rescue breathing/CPR, and naloxone administration-among Philadelphia-based, predominantly street-involved women with a history of illicit drug use. The study utilized a convergent mixed methods approach integrating data from 186 quantitative survey responses and 38 semi-structured qualitative interviews. Quantitative findings revealed that compared to untrained women, trained women were more likely to administer naloxone (32.9% vs. 5.2%) and use two recommended responses (20.0% vs. 9.5%). No significant differences were found between the two groups in calling 911 or using rescue breathing/CPR. Qualitative findings indicated that barriers to enacting recommended overdose response were either structural or situational and included the avoidance of police, inability to carry naloxone or phone due to unstable housing, and perceived lack of safety on the streets and when interacting with strangers. Our study demonstrated that overdose training improved the frequency of naloxone administration among this sample of predominantly street-involved women. Future efforts need to focus on avoiding intrusive policing, scaling-up naloxone refill sites, and providing secondary naloxone distribution via drug user networks.

Pain Profiles among Young Adult Cannabis Users: An Analysis of Antecedent Factors and Distal Outcomes.

BACKGROUND: Pain is a primary reason for medical cannabis use among young adults, however little is known about the patterns of pain in this group. This study identified pain profiles among young adult cannabis users and examined related antecedents and distal outcomes. METHODS: Past 30-day cannabis users aged 18-26, both medical cannabis patients and non-patients, were enrolled in Los Angeles in 2014-2015. A latent class analysis was used to identify pain classes based on history of chronic pain conditions and recent non-minor pain. The study assessed the predictors of membership in pain classes and examined the association of classes with recent mental health characteristics, cannabis use motives and practices. RESULTS: Three classes were identified: Low pain (56.3%), Multiple pain (27.3%), and Nonspecific pain (16.4%). In adjusted models, lifetime insomnia was associated with membership in Multiple pain and Nonspecific pain classes versus the Low pain class. Medical cannabis patients and Hispanics/Latinos were more likely to belong to the Multiple pain class than the other classes. Regarding recent outcomes, the Multiple pain and Nonspecific pain classes were more likely than the Low pain class to use cannabis to relieve physical pain. Additionally, the Multiple pain class had a higher probability of psychological distress, self-reported medical cannabis use, consuming edibles, and using cannabis to sleep compared to one or both other classes. CONCLUSION: Findings suggest that young adult cannabis users can be separated into distinct groups with different pain profiles. The Multiple pain profile was associated with medically-oriented cannabis use motives and practices.

Decision-making by laypersons equipped with an emergency response smartphone app for opioid overdose.

BACKGROUND: Targeted naloxone distribution to potential lay responders increases the timeliness of overdose response and reduces mortality. Little is known, however, about the patterns of decision-making among overdose lay responders. This study explored heuristic decision-making among laypersons equipped with an emergency response smartphone app. METHODS: UnityPhilly, a smartphone app that connects lay responders equipped with naloxone to overdose victims, was piloted in Philadelphia from March 2019 to February 2020. Participants used the app to signal overdose alerts to peer app users and emergency medical services, or respond to alerts by arriving at overdose emergency sites. This study utilised in-depth interviews, background information, and app use data from a sample of 18 participants with varying histories of opioid use and levels of app use activity. RESULTS: The sample included 8 people who used opioids non-medically in the past 30 days and 10 people reporting no opioid misuse. Three prevailing, not mutually exclusive, heuristics were identified. The heuristic of unconditional signalling ("Always signal for help or backup") was used by 7 people who valued external assistance and used the app as a replacement for a 911 call; this group had the highest number of signalled alerts and on-scene appearances. Nine people, who expressed confidence in their ability to address an overdose themselves, followed a heuristic of conditional signalling ("Rescue, but only signal if necessary"); these participants had the highest frequency of prior naloxone administrations. Eleven participants used the heuristic of conditional responding ("Assess if I can make a difference"), addressing an alert if they carried naloxone, were nearby, or received a signal before dark hours. CONCLUSION: The deployment of specific heuristics was influenced by prior naloxone use and situational factors. Success of overdose prevention interventions assisted by digital technologies may depend on the involvement of people with diverse overdose rescue backgrounds.

Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles.

INTRODUCTION: Cannabidiol (CBD) is purportedly a promising therapeutic agent to provide relief for a variety of medical conditions with mild or no psychoactive effects. However, little is known about young adults who use cannabis and CBD-dominant products, and associations between CBD use and other drug use. METHODS: Young adults (aged 24-32) who currently used cannabis (n = 239) were surveyed in Los Angeles in March 2019 through March 2020. The sample was divided into CBD-dominant (at least 1:1 CBD:THC ratio) and THC-dominant product users. We described CBD forms, reasons and conditions for CBD use and examined between-group differences in sociodemographic characteristics, cannabis practices, health and other drug use. RESULTS: CBD-dominant users were more likely to be female, use cannabis at lower frequency and amount (except for edible/drinkable/oral products), self-report medical motivation for cannabis use, use cannabis for pain and report more health problems. Oil, flower, topicals and sprays/drops/tinctures were the most prevalent CBD forms. Psychological problems and pain were commonly reported conditions and medical reasons for CBD use. CBD-dominant users were more likely to report illicit drug use, where psilocybin use was markedly different between the two groups. CONCLUSIONS: CBD use was associated with health histories and motivations linked to pain and psychological problems. Positive association between CBD use and illicit drug use may indicate self-medication for psychological conditions. Future studies should evaluate the effectiveness of various CBD forms and dose regimens for treatment of pain and psychological problems, and as a potential intervention for decreasing other drug use and associated harms.

Layperson reversal of opioid overdose supported by smartphone alert: A prospective observational cohort study.

BACKGROUND: Rapid naloxone administration is crucial in reversing an opioid overdose. We investigated whether equipping community members, including people who use opioids (PWUO), with a smartphone application enabling them to signal and respond to suspected overdose would support naloxone administration in advance of Emrgency Medical Services (EMS). METHODS: This observational cohort study of opioid overdose intervention used a dedicated smartphone app, UnityPhilly, activated by volunteers witnessing an overdose to signal other nearby volunteers in Philadelphia (March 2019 - February 2020). Alerted volunteers chose to respond, or declined to respond, or ignored/missed the alert. Witnessing volunteer was connected to 9-1-1 through a semi-automated telephone call. The primary outcome was layperson-initiated overdose reversal before EMS arrival, and a secondary outcome was hospital transfer. This study is registered with ClinicalTrials.gov, NCT03305497. FINDINGS: 112 volunteers, including 57 PWUO and 55 community members, signaled 291 suspected opioid overdose alerts. 89 (30⸱6%) were false alarms. For 202 true alerts, the rate of layperson initiated naloxone use was 36⸱6% (74/202 cases). Most naloxone-use cases occurred in the street (58⸱11% (43/74)) and some in home settings (22⸱98% (17/74)). The first naloxone dose was provided by a nearby volunteer responding to the alert in 29⸱73% (22/74) of cases and by the signaling volunteer in 70⸱27% (52/74) of cases. Successful reversal was reported in 95⸱9% (71/74) of cases. Layperson intervention preceded EMS by 5 min or more in 59⸱5% of cases. Recovery without hospital transport was reported in 52⸱7% (39/74) of cases. INTERPRETATION: Our findings support the benefits of equipping community members, potentially witnessing suspected opioid overdose, with naloxone and an emergency response community smartphone app, alerting EMS and nearby laypersons to provide additional naloxone. FUNDING: Funding provided by NIH through NIDA, grant number: 5R34DA044758.

Sex Trafficking Victims at Their Junction with the Healthcare Setting-A Mixed-Methods Inquiry.

U.S.-born citizens are victims of human trafficking typically exploited through sex trafficking. At least some of them interact with healthcare providers during their trafficking experience; yet a majority goes unidentified. Although protocols and training guides exist, healthcare providers often do not have the necessary skills to identify and assist victims of sex trafficking. Understanding where victims seek care and barriers for disclosure are critical components for intervention. Thus, this study interviewed survivors of sex trafficking to ascertain: a) healthcare settings visited during trafficking, b) reasons for seeking care, and c) barriers to disclosing victimization. An exploratory concurrent mixed-methods approach was utilized. Data were collected between 2016-2017 in San Diego, CA and Philadelphia, PA (N = 21). Key findings: 1) Among healthcare settings, emergency departments (76.2%) and community clinics (71.4%) were the most frequently visited; 2) medical care was sought mainly for treatment of STIs (81%); and 3) main barriers inhibiting disclosure of victimization included feeling ashamed (84%) and a lack of inquiry into the trafficking status from healthcare providers (76.9%). Healthcare settings provide an opportunity to identify victims of sex trafficking, but interventions that are trauma-informed and victim-centered are essential. These may include training providers, ensuring privacy, and a compassionate-care approach.