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The author presents an investigation of patent-application filings made without external financial support, or "at-risk", based on inventions disclosed to the University of California from fiscal years 1991 to 2000. The success of the at-risk patent applications filed on these invention disclosures is examined from the perspective of agreements executed and income generated. He then puts forward recommendations for improving the overall process of at-risk patent-application filings. (Contains 13 notes and 4 figures.)

Introduction: Cannabis use to alleviate medical symptoms is increasing in middle-aged and older adults. Cognitive impairment associated with cannabis use may be especially detrimental to these understudied age groups. We hypothesized that among middle-aged and older adults who used cannabis for 12 months, frequent (≥3 days/week) compared with nonfrequent (≤2 days/week) use will be associated with cognitive impairment. Materials and Methods: We performed secondary analysis on data from a clinical trial of cannabis use for medical symptoms. Participants ( n =62) were ≥45 years, and completed a baseline and at least one postbaseline visit. Cognitive domains were assessed through the Cambridge Neuropsychological Test Automated Battery. Cannabis use was assessed prospectively through daily smartphone diaries. Frequency of cannabis use was a binary predictor in a mixed-effects logistic regression model predicting cognitive impairment adjusted for baseline cognitive functioning. Results: At baseline, participants were primarily nonfrequent cannabis users; however, in all other time periods, most participants were frequent users (range: 55-58%). Cognitive outcomes did not differ between frequent and nonfrequent cannabis users. However, in sensitivity analyses, respondents with problematic cannabis use scored significantly worse on one cognitive domain compared to those without problematic cannabis use. Conclusions: In a clinical sample of adults aged ≥45 years, no longitudinal associations were found between cannabis use and cognitive functioning. However, a few significant associations were observed between problematic use and cognitive functioning. Further research is needed to assess the impact of cannabis use on adults, particularly those aged ≥65 years, and to investigate potential subtler influences of cannabis use on cognition. ClinicalTrials.gov ID: NCT03224468.

Aim: Standardized survey measures that capture diverse cannabis consumption patterns are needed to inform public health and policy. Our team is developing a flexible, personalized, low-burden survey item inventory to measure cannabis use patterns and estimate milligrams of THC (mgTHC) consumption in large samples. This study aimed to identify measurement gaps and analysis implications associated with an initial pool of candidate items that assessed use of cannabis flower and concentrate products (smoked and/or vaporized). Methods: Adult cannabis consumers ( n =4247) completed an online survey assessing cannabis use frequency, quantity, product types, product potencies (%THC), and methods of administration. Participants chose to report their consumption quantities using one of three units: "hits per day," "grams per week," or "joints per week." Respondents also indicated whether their past 7-day consumption pattern represented their typical pattern. Results: Eighty-one percent had used cannabis daily in the past week. Thirty-two percent, 53%, and 15% chose to report flower and concentrate consumption quantity in hits, grams, and joints, respectively. Approximately 80-90% of responses for the number of hits, grams, and joints consumed were less than the maximum response option-suggesting that response options captured the full range of potential cannabis consumption behaviors. Those who chose grams or joints units were generally more likely to endorse higher risk cannabis use (e.g., morning use, high %THC products) in the past week than those who chose the hits unit (adjusted Odds Ratio range: 1.2-3.9). Among those who reported that the past week represented their typical behavior (83%), past 30-day and past 7-day frequencies were highly correlated (Spearman's Rho=0.77)-supporting the feasibility of using lower burden "typical week" items to extrapolate patterns beyond a 1-week time frame. Conclusion: Results from this online convenience sample of frequent cannabis consumers suggest that the current items yield coherent and expected response patterns. Although additional testing is required, a standardized, flexible survey instrument for large-scale assessment of cannabis patterns and calculation of mgTHC seems within reach.

Introduction: Quantification of consumption patterns of the primary psychoactive compounds in cannabis, which cause euphoria or intoxication, is sorely needed to identify potential risks and benefits of use and to provide meaningful safety information to the public. The diversity of products available, multiple methods of administration, and lack of labeling of products have made such quantification challenging. Our group is developing a survey instrument for estimating the quantity of delta 9-tetrahydrocannabinol (THC) consumed in population samples, which is flexible and incorporates individualized reports of patterns of consumption. This study provides an illustration of a procedure for translating self-reported consumption into milligrams of THC (mgTHC), which may serve as a working model for future quantification efforts. Methods: Social media advertising was leveraged to enroll 5627 adults who use cannabis into an online, anonymous survey study. Only those who used cannabis in the past 7 days, used flower or concentrate products, and who chose to report their quantity of use in hits per day or grams per week ( n =3211) were included in this report. Formulas were used to estimate mgTHC used per day, in hits per day or grams per week; potency (%THC); constants for estimating the amount of material consumed for each hit; and a method of administration efficiency constant to account for THC loss due to the administration method. Results: The estimate for mgTHC used per day was M =92.8 mg/day (SD=97.2 mg; 1st-3rd quartile range=25-132 mg). The estimated quantity of use was much lower for those reporting in hits ( M =43.7 mg, SD=43.8) than for those reporting in grams ( M =115.1 mg, SD=107.0). The estimated rate of binge use in the past week, arbitrarily defined as more than 50 mgTHC within any one daily time quadrant, was 6.8%, which increased to 29.3% if 25 mgTHC was used. Conclusions: The approach illustrated in this study goes beyond existing cannabis measures by asking participants to provide highly detailed estimates of their past 7-day use patterns and then applying a logical formula to translate this information into mgTHC. This initial procedure has limitations and lacks generalization; however, we hope this demonstration stimulates testing of similar approaches and relevant laboratory experiments that will enhance the validity of cannabis consumption estimation procedures.

Background: Cannabis use is increasing among middle-aged and older US adults, populations that are particularly vulnerable to the adverse effects of cannabis. Risks for adverse effects differ by cannabis use patterns, which have become increasingly heterogeneous. Nevertheless, little is known about age differences in such patterns. Objective: To investigate age differences in cannabis use patterns, comparing younger (age 18-49), middle-aged (age 50-64), and older adults (age ≥65). Methods: A total of 4,151 US adults with past 7-day cannabis consumption completed an online survey (35.1% male; 60.1% female; 4.8% identified as "other"). Regression models examined age differences in cannabis use patterns. Results: Compared to younger adults, middle-aged and older adults were more likely to consume cannabis during evening hours (50-64: adjusted odds ratio [aOR] = 2.98, 95% CI 2.24-3.96; ≥65: aOR = 4.23, 95 CI 2.82-6.35); by only one method (50-64: aOR = 1.67, 95% CI 1.34-2.09; ≥65: aOR = 3.38, 95 CI 2.24-5.09); primarily by smoking as the only method (50-64: aOR = 1.52, 95% CI 1.29-1.78; ≥65: aOR = 2.12, 95 CI 1.64-2.74); but less likely to consume concentrated cannabis products (concentrates) with extremely high %THC (50-64: aOR = 0.71, 95% CI 0.54-0.93; ≥65: aOR = 0.30, 95 CI 0.16-0.55). Age differences in cannabis use patterns were also observed between middle-aged and older adults. Conclusion: Findings suggest that middle-aged and older adults may engage in less risky cannabis use patterns compared to younger groups (e.g. lower likelihood of consuming highly potent concentrates). However, findings also underscore the importance of recognizing risks unique to these older demographics, such as smoking-related health events. Consequently, prevention strategies targeting such use patterns are needed.

Objective: Cannabis use disorder diagnoses are increasing among U.S. adults and are more prevalent among people with comorbid psychiatric disorders. Recent changes in cannabis laws, increasing cannabis availability, and higher-potency cannabis may have placed people with cannabis use and psychiatric disorders at disproportionately increasing risk for cannabis use disorder. The authors used Veterans Health Administration (VHA) data to examine whether trends in cannabis use disorder prevalence among VHA patients differ by whether they have psychiatric disorders., Methods: VHA electronic health records from 2005 to 2019 (N range, 4,332,165-5,657,277) were used to identify overall and age-group-specific (<35, 35-64, and ≥65 years) trends in prevalence of cannabis use disorder diagnoses among patients with depressive, anxiety, posttraumatic stress, bipolar, or psychotic spectrum disorders and to compare these to corresponding trends among patients without any of these disorders. Given transitions in ICD coding, differences in trends were tested within two periods: 2005-2014 (ICD-9-CM) and 2016-2019 (ICD-10-CM)., Results: Greater increases in prevalence of cannabis use disorder diagnoses were observed among patients with psychiatric disorders compared to those without (difference in prevalence change, 2005-2014: 1.91%, 95% CI=1.87-1.96; 2016-2019: 0.34%, 95% CI=0.29-0.38). Disproportionate increases in cannabis use disorder prevalence among patients with psychiatric disorders were greatest among those under age 35 between 2005 and 2014, and among those age 65 or older between 2016 and 2019. Among patients with psychiatric disorders, the greatest increases in cannabis use disorder prevalences were observed among those with bipolar and psychotic spectrum disorders., Conclusions: The findings highlight disproportionately increasing disparities in risk of cannabis use disorder among VHA patients with common psychiatric disorders. Greater public health and clinical efforts are needed to monitor, prevent, and treat cannabis use disorder in this population., Competing Interests: Dr. Saxon receives royalties from UpToDate. Dr. Hasin has received support from Syneos Health.The other authors report no financial relationships with commercial interests.

LGBT+ adults demonstrate greater cannabis-related problems (e.g., Cannabis Use Disorder [CUD]) compared to non-LGBT+ counterparts. No study has explored age-related disparities in cannabis problems across the adult lifespan, nor have studies identified specific CUD criteria that contribute to elevated CUD among LGBT+ adults. The purpose of this study was to examine associations between LGBT+ identity and age with endorsement of CUD criteria in a sample of regular cannabis consumers. An online sample of N = 4334 (25.1% LGBT+) adults aged 18-64 residing in the U.S. completed an online survey about cannabis use behaviors and CUD diagnostic criteria. Bivariate contrasts revealed significantly greater CUD criteria endorsement among LGBT+ respondents, largely driven by differences at younger ages. However, this effect disappeared in the majority of adjusted logistic regression models. LGBT+ identity was associated with greater probability of use in larger amounts (adjOR = 2.10, 95% CI: 1.22-3.60) and use despite physical/mental health problems (adjOR = 2.51, 95% CI:1.23-5.03). No age*LGBT+ identity interactions were detected. Plotted trends depict more pronounced disparities in outcomes among LGBT+ adults under 35 years. Several potential risk and protective factors including employment, education, and reasons for use were identified. There were age-related differences in these characteristics among LGBT+ and non-LGBT+ respondents. Initial findings highlight the need for LGBT+ research examining trends in health outcomes and sociodemographic and cannabis characteristics across the lifespan. The study also provides a substantive contribution regarding specific cannabis-related problems that young LGBT+ cannabis consumers may be more likely to endorse than their non-LGBT+ counterparts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In the U.S. non-medical use of prescription opioids (NMOU) is prevalent and often accompanied by opioid withdrawal syndrome (OWS). OWS has not been studied using nationally representative data. Objectives: We examined the prevalence and clinical correlates of OWS among U.S. adults with NMOU. Methods: We used data from 36,309 U.S. adult participants in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III, 1,527 of whom reported past 12-month NMOU. Adjusted linear and logistic regression models examined associations between OWS and its clinical correlates, including psychiatric disorders, opioid use disorder (OUD; excluding the withdrawal criterion), medical conditions, and healthcare utilization among people with regular (i.e. ≥3 days/week) NMOU ( n  = 534). Results: Over half (50.4%) of the sample was male. Approximately 9% of people with NMOU met criteria for DSM-5 OWS, with greater prevalence of OWS (∼20%) among people with regular NMOU. Individuals with bipolar disorder, dysthymia, panic disorder, and borderline personality disorder had greater odds of OWS (aOR range = 2.71-4.63). People with OWS had lower mental health-related quality of life (β=-8.32, p  < .001). Individuals with OUD also had greater odds of OWS (aOR range = 26.02-27.77), an association that increased with more severe OUD. People using substance use-related healthcare services also had greater odds of OWS (aOR range = 6.93-7.69). Conclusion: OWS was prevalent among people with OUD and some psychiatric disorders. These findings support screening for OWS in people with NMOU and suggest that providing medication- assisted treatments and behavioral interventions could help to reduce the burden of withdrawal in this patient population.

Background: Researchers need accurate measurements of cannabis consumption quantities to assess risks and benefits. Survey methods for measuring cannabis flower and concentrate quantities remain underdeveloped. Objective: We examined "grams" and "hits" units for measuring flower and concentrate quantities, and calculating milligrams of THC (mgTHC). Methods: Online survey participants ( n  = 2,381) reported preferred unit (hits or grams), past-week hits and grams for each product, and product %THC. Quantile regression compared mgTHC between unit-preference subgroups. Hits-based mgTHC calculations assumed a universal grams-per-hit ratio (GPHR). To examine individualized GPHRs, we tested a "two-item approach," which divided total grams by total hits, and "one-item approach," which divided 0.5 grams by responses to the question: "How many total hits would it take you to finish 1/2 g of your [product] by [administration method]?" Results: Participants were primarily daily consumers (77%), 50% female sex, mean age 39.0 (SD 16.4), 85% White, 49% employed full-time. Compared to those who preferred the hits unit, those who preferred the grams unit reported consuming more hits and grams, higher %THC products, and consequently, larger median mgTHC (flower-hits mgTHC: 32 vs. 91 (95%CI: 52-67); flower-grams mgTHC: 27 vs. 113 (95%CI: 73-95); concentrate-hits mgTHC: 29 vs. 59 (95%CI: 15-43); concentrate-grams mgTHC: 61 vs. 129 (95%CI: 43-94)). "Two-item" and "one-item" approach GPHRs were similar and frequently 50% larger or smaller than the universal GPHR. Conclusion: Allowing respondents to choose "hits" or "grams" when reporting cannabis quantities does not compromise mgTHC estimates. A low-burden, one-item approach yields individualized "hit sizes" that may improve mgTHC estimates.

Background: Cannabis use disorder is associated with considerable comorbidity and impairment in functioning, and prevalence is increasing among adults with chronic pain. We aimed to assess the effect of introduction of medical cannabis laws (MCL) and recreational cannabis laws (RCL) on the increase in cannabis use disorder among patients in the US Veterans Health Administration (VHA)., Methods: Data from patients with one or more primary care, emergency, or mental health visit to the VHA in 2005-19 were analysed using 15 repeated cross-sectional VHA electronic health record datasets (ie, one dataset per year). Patients in hospice or palliative care were excluded. Patients were stratified as having chronic pain or not using an American Pain Society taxonomy of painful medical conditions. We used staggered-adoption difference-in-difference analyses to estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed cannabis use disorder and associations with presence of chronic pain, accounting for the year that state laws were enacted. We did this by fitting a linear binomial regression model stratified by pain, with time-varying cannabis law status, fixed effects for state, categorical year, time-varying state-level sociodemographic covariates, and patient covariates (age group [18-34 years, 35-64 years, and 65-75 years], sex, and race and ethnicity)., Findings: Between 2005 and 2019, 3 234 382-4 579 994 patients were included per year. Among patients without pain in 2005, 5·1% were female, mean age was 58·3 (SD 12·6) years, and 75·7%, 15·6%, and 3·6% were White, Black, and Hispanic or Latino, respectively. In 2019, 9·3% were female, mean age was 56·7 (SD 15·2) years, and 68·1%, 18·2%, and 6·5% were White, Black, and Hispanic or Latino, respectively. Among patients with pain in 2005, 7·1% were female, mean age was 57·2 (SD 11·4) years, and 74·0%, 17·8%, and 3·9% were White, Black, and Hispanic or Latino, respectively. In 2019, 12·4% were female, mean age was 57·2 (SD 13·8) years, and 65·3%, 21·9%, and 7·0% were White, Black, and Hispanic or Latino, respectively. Among patients with chronic pain, enacting MCL led to a 0·135% (95% CI 0·118-0·153) absolute increase in cannabis use disorder prevalence, with 8·4% of the total increase in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·188% (0·160-0·217) absolute increase in cannabis use disorder prevalence, with 11·5% of the total increase in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in cannabis use disorder prevalence (MCL: 0·037% [0·027-0·048], 5·7% attributable to MCL; RCL: 0·042% [0·023-0·060], 6·0% attributable to RCL). Overall, associations of MCL and RCL with cannabis use disorder were greater in patients with chronic pain than in patients without chronic pain., Interpretation: Increasing cannabis use disorder prevalence among patients with chronic pain following state legalisation is a public health concern, especially among older age groups. Given cannabis commercialisation and widespread public beliefs about its efficacy, clinical monitoring of cannabis use and discussion of the risk of cannabis use disorder among patients with chronic pain is warranted., Funding: NIDA grant R01DA048860, New York State Psychiatric Institute, and the VA Centers of Excellence in Substance Addiction Treatment and Education., Competing Interests: Declaration of interests DSH receives support from Syneos Health for an unrelated project. JLG reports consulting fees from Hoffman-La Roche, a patent pending (use of glecaprevir and pibrentasvir for the treatment of post-traumatic stress disorder), and participation on a data safety monitoring board or advisory board for National Institute of Mental Health (using machine learning to optimise user engagement and clinical response to digital mental health interventions). SSM serves on the Board of Directors for the College on Problems of Drug Dependence. AJS has received consulting fees from Indivior, travel support from Alkermes, research support from MedicaSafe, and royalties from UpTo-Date. KMK has served as an expert witness in litigation. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to examine trends in cannabis-positive urine drug screens (UDSs) among emergency department (ED) patients from 2008 to 2019 using data from the Veterans Health Administration (VHA) health care system, and whether these trends differed by age group (18-34, 35-64, and 65-75 years), sex, and race, and ethnicity., Method: VHA electronic health records from 2008 to 2019 were used to identify the percentage of unique VHA patients seen each year at an ED, received a UDS, and screened positive for cannabis. Trends in cannabis-positive UDS were examined by age, race and ethnicity, and sex within age groups., Results: Of the VHA ED patients with a UDS, the annual prevalence positive for cannabis increased from 16.42% in 2008 to 27.2% in 2019. The largest increases in cannabis-positive UDS were observed in the younger age groups. Male and female ED patients tested positive for cannabis at similar levels. Although the prevalence of cannabis-positive UDS was consistently highest among non-Hispanic Black patients, cannabis-positive UDS increased in all race and ethnicity groups., Discussion: The increasing prevalence of cannabis-positive UDS supports the validity of previously observed population-level increases in cannabis use and cannabis use disorder from survey and administrative records. Time trends via UDS results provide additional support that previously documented increases in self-reported cannabis use and disorder from surveys and claims data are not spuriously due to changes in patient willingness to report use as it becomes more legalized, or due to greater clinical attention over time., (Copyright © 2023 American Society of Addiction Medicine.)

Purpose of Review: Veterans are a large population that is disproportionately affected by various physical and mental health conditions. The primary aim of this review is to provide a concise overview of recent literature on the prevalence of cannabis use and cannabis use disorder (CUD) among US Veterans, and associations with mental and physical health conditions. We also addressed gaps in the literature by investigating associations between CUD and mental and physical health conditions in 2019 data from the Veterans Health Administration (VHA; N=5,657,277)., Recent Findings: In total, 25 studies were reviewed. In 2019, the prevalence of Veteran cannabis use ranged from 11.9%-18.7%. Cannabis use and CUD were associated with bipolar disorders, psychotic disorders, suicidality, pain conditions, and other substance use, but less consistently associated with depressive disorders, anxiety disorders, and posttraumatic stress disorder. Analyses of 2019 VHA data indicated that CUD was strongly associated with a broad array of physical and mental health conditions and mortality., Summary: Cannabis use and CUD are prevalent and highly comorbid with other conditions among US Veterans. Harm reduction methods tailored to these populations are needed.

Abstract: In the United States, cannabis is increasingly used to manage chronic pain. Veterans Health Administration (VHA) patients are disproportionately affected by pain and may use cannabis for symptom management. Because cannabis use increases the risk of cannabis use disorders (CUDs), we examined time trends in CUD among VHA patients with and without chronic pain, and whether these trends differed by age. From VHA electronic health records from 2005 to 2019 (∼4.3-5.6 million patients yearly), we extracted diagnoses of CUD and chronic pain conditions ( International Classification of Diseases [ ICD ]- 9-CM , 2005-2014; ICD-10-CM , 2016-2019). Differential trends in CUD prevalence overall and age-stratified (<35, 35-64, or ≥65) were assessed by any chronic pain and number of pain conditions (0, 1, or ≥2). From 2005 to 2014, the prevalence of CUD among patients with any chronic pain increased significantly more (1.11%-2.56%) than those without pain (0.70%-1.26%). Cannabis use disorder prevalence increased significantly more among patients with chronic pain across all age groups and was highest among those with ≥2 pain conditions. From 2016 to 2019, CUD prevalence among patients age ≥65 with chronic pain increased significantly more (0.63%-1.01%) than those without chronic pain (0.28%-0.47%) and was highest among those with ≥2 pain conditions. Over time, CUD prevalence has increased more among VHA patients with chronic pain than other VHA patients, with the highest increase among those age ≥65. Clinicians should monitor symptoms of CUD among VHA patients and others with chronic pain who use cannabis, and consider noncannabis therapies, particularly because the effectiveness of cannabis for chronic pain management remains inconclusive., (Copyright © 2023 International Association for the Study of Pain.)

Background: Gender and sex can influence cannabis behaviors and consequences (Cannabis Use Disorder [CUD]). Research typically examines sex and gender independently. Gender analyses often exclude transgender and gender diverse (TGD) populations. The objectives of this study were to (a) replicate less frequent cannabis use among TGD young adults compared to cisgender counterparts (b) compare severity of CUD, and (c) examine the role of sex on cannabis outcomes. Method: Online survey participants between 18 and 34 ( N =1213) from the United States who reported past-week cannabis consumption provided information on cannabis practices and CUD from February to April 2022. Bivariate analyses explored gender differences across frequency (daily frequency across routes of administration [ROAs]; daily use of 2+ ROAs, use throughout the day) and CUD. Adjusted regression models provided model-estimated marginal probabilities and means to examine differences across four gender-by-sex categories (cisgender men: n =385; cisgender women: n =681; male-at-birth TGD: n =26; female-at-birth TGD: n =121). Benjamini-Hochberg adjustments (10% false discovery rate) were applied. Results: Among past-week consumers, female-at-birth TGD participants demonstrated lower probability of daily flower smoking compared to cisgender men (0.54 vs. 0.67). Cisgender men reported greater probability of daily concentrate vaping (0.55) compared to cisgender women (0.45) and female-at-birth TGD participants (0.27); they were also more likely to report daily use of 2+ ROAs (cisgender men: 0.51 vs. cisgender women: 0.39 and female at-birth TGD: 0.27). TGD participants reported greater CUD severity compared to cisgender counterparts, t (1096)=-3.69, p =0.002. Model-estimated means found lower severity among cisgender women compared to cisgender men and female-at-birth TGD participants. Stratified regression models support positive associations between daily cannabis use and CUD in both TGD in cisgender groups. Among cisgender participants, greater severity was predicted by male sex, younger age, and younger age of onset. Conclusions: The present study replicates and extends a prior finding that among past-week cannabis consumers, TGD young adults report less frequent use than cisgender counterparts. Despite this, TGD participants demonstrated greater severity of CUD. While analyses were limited by the small sample of male-at-birth TGD participants, the article highlights the importance of expanding sex- and gender-focused analyses. Future work is expanding efforts to target hard-to-reach consumers.

Background: Recreational cannabis laws (RCLs) may have spillover effects on binge drinking. Our aims were to investigate binge drinking time trends and the association between RCLs and changes in binge drinking in the United States (U.S.)., Methods: We used restricted National Survey on Drug Use and Health data (2008-2019). We examined trends in the prevalence of past-month binge drinking by age groups (12-20, 21-30, 31-40, 41-50, 51+). Then, we compared model-based prevalences of past-month binge drinking before and after RCL by age group, using multi-level logistic regression with state random intercepts, an RCL by age group interaction term, and controlling for state alcohol policies., Results: Binge drinking declined overall from 2008 to 2019 among people aged 12-20 (17.54% to 11.08%), and those aged 21-30 (43.66% to 40.22%). However, binge drinking increased among people aged 31+ (ages 31-40: 28.11% to 33.34%, ages 41-50: 25.48% to 28.32%, ages 51+: 13.28% to 16.75%). When investigating model-based prevalences after versus before RCL, binge drinking decreased among people aged 12-20 (prevalence difference=-4.8%; adjusted odds ratio (aOR)=0.77, [95% confidence interval (CI) 0.70-0.85]), and increased among participants aged 31-40 (+1.7%; 1.09[1.01-1.26]), 41-50 (+2.5; 1.15[1.05-1.26]) and 51+ (+1.8%; 1.17[1.06-1.30]). No RCL-related changes were noted in respondents ages 21-30., Conclusions: Implementation of RCLs was associated with increased past-month binge drinking in adults aged 31+ and decreased past-month binge drinking in those aged < 21. As the cannabis legislative landscape continues to change in the U.S., efforts to minimize harms related to binge drinking are critical., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The DSM-5 criteria for cannabis use disorder (CUD) combine DSM-IV dependence and abuse criteria (without legal problems) and new withdrawal and craving criteria. Information on dimensionality, internal reliability, and differential functioning of the DSM-5 CUD criteria is lacking. Additionally, dimensionality of the DSM-5 withdrawal items is unknown. This study examined the psychometric properties of the DSM-5 CUD criteria among adults who used cannabis in the past 7 days (N = 5,119). Adults with frequent cannabis use were recruited from the US general population through social media and filled in a web-based survey about demographics and cannabis use behaviors. Factor analysis was used to assess dimensionality, and item response theory analysis models were used to explore relationships between the criteria and the underlying latent trait (CUD), and whether each criterion and the criteria set functioned differently by demographic and clinical characteristics: sex, age, state-level cannabis laws, reasons for cannabis use, and frequency of use. The DSM-5 CUD criteria showed unidimensionality and provided information about the CUD latent trait across the severity spectrum. The cannabis withdrawal items indicated one underlying latent factor. While some CUD criteria functioned differently in specific subgroups, the criteria set as a whole functioned similarly across subgroups. In this online sample of adults with frequent cannabis use, evidence supports the reliability, validity, and utility of the DSM-5 CUD diagnostic criteria set, which can be used for determining a major risk of cannabis use, i.e., CUD, to inform cannabis policies and public health messaging, and for developing intervention strategies., Competing Interests: Declaration of competing interest Alan Budney has served as a scientific consultant for Canopy Growth, Inc. and Jazz Pharmaceuticals. All other authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Compared to plant/flower cannabis products, cannabis concentrates have higher average potency of delta-9-tetrahydrocannabinol (Δ9-THC), which may be associated with greater likelihood of cannabis-related harms. Information on factors associated with use of cannabis concentrates is needed., Methods: Respondents were 4,328 adult past-7-day cannabis users from all 50 U.S. states and Washington DC (DC) who participated in an online 2021 survey. Using logistic regression to generate adjusted odds ratios (aOR), we investigated whether participants in states that enacted recreational cannabis laws (RCL, 12 states plus DC [treated as a state], n = 1,236) or medical cannabis laws (MCL-only, 23 states, n = 2,030) by December 31, 2020 were more likely than those in states without cannabis laws (no-CL, 15 states, n = 1,062) to use cannabis concentrate products in the prior 7 days., Results: Most participants (92.4%) used plant material in the prior 7 days; 57.0% used cannabis concentrates. In RCL, MCL and no-CL states, concentrate use was reported by 61.5%, 56.6%, and 52.5%, respectively. Compared to participants in no-CL states, odds of using cannabis concentrate products were greater among those in RCL states (aOR = 1.47; CI = 1.17-1.84) and MCL-only states (aOR = 1.29; CI = 1.08-1.55). Whether states had legally-authorized dispensaries had little effect on results., Conclusion: Results suggest that individuals in MCL-only and RCL states are more likely to use cannabis concentrate products. Determining mechanisms underlying these results, e.g., commercialization, could provide important information for prevention. Clinicians should be alert to patient use of concentrates, especially in MCL-only and RCL states. Continued monitoring is warranted as additional states legalize cannabis use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The diversity in characteristics of cannabis products and behavior patterns make evaluation of cannabis exposure in population-based, self-report surveys challenging. Accurate identification of cannabis exposure and related outcomes necessitates a thorough understanding of participants' interpretations of survey questions assessing cannabis consumption behaviors., Objectives: The current study utilized cognitive interviewing to gain insight on participants' interpretation of items in a self-reported survey instrument used to estimate the quantity of THC consumed in population samples., Methods: Cognitive interviewing was used to evaluate survey items assessing cannabis use frequency, routes of administration, quantity, potency, and perceived "typical patterns" of use. Ten participants ≥18 years ( n  = 4 cisgender-men; n  = 3 cisgender-women; n  = 3 non-binary/transgender) who had used cannabis plant material or concentrates in the past week were recruited to take a self-administered questionnaire and subsequently answer a series of scripted probes regarding survey items., Results: While most items presented no issues with comprehension, participants identified several areas of ambiguity in question or response item wording or in visual cues included in the survey. Generally, participants with irregular use patterns (i.e., non-daily use) reported more difficulty recalling the time or quantity of cannabis use. Findings resulted in several changes to the updated survey, including updated reference images and new quantity/frequency of use items specific to the route of administration., Conclusion: Incorporating cognitive interviewing into cannabis measurement development among a sample of knowledgeable cannabis consumers led to improvements in assessing cannabis exposure in population surveys, which may otherwise have been missed., Competing Interests: Alan Budney has served as a scientific consultant for Canopy Growth, Inc. and Jazz Pharmaceuticals., (© 2023 Published by Elsevier B.V.)

Importance: Cannabis use disorder (CUD) is increasing among US adults. Few national studies have addressed the role of medical cannabis laws (MCLs) and recreational cannabis laws (RCLs) in these increases, particularly in patient populations with high rates of CUD risk factors., Objective: To quantify the role of MCL and RCL enactment in the increases in diagnosed CUD prevalence among Veterans Health Administration (VHA) patients from 2005 to 2019., Design, Setting, and Participants: Staggered-adoption difference-in-difference analyses were used to estimate the role of MCL and RCL in the increases in prevalence of CUD diagnoses, fitting a linear binomial regression model with fixed effects for state, categorical year, time-varying cannabis law status, state-level sociodemographic covariates, and patient age group, sex, and race and ethnicity. Patients aged 18 to 75 years with 1 or more VHA primary care, emergency department, or mental health visit and no hospice/palliative care within a given calendar year were included. Time-varying yearly state control covariates were state/year rates from American Community Survey data: percentage male, Black, Hispanic, White, 18 years or older, unemployed, income below poverty threshold, and yearly median household income. Analysis took place between February to December 2022., Main Outcomes and Measures: As preplanned, International Classification of Diseases, Clinical Modification, ninth and tenth revisions, CUD diagnoses from electronic health records were analyzed., Results: The number of individuals analyzed ranged from 3 234 382 in 2005 to 4 579 994 in 2019. Patients were largely male (94.1% in 2005 and 89.0% in 2019) and White (75.0% in 2005 and 66.6% in 2019), with a mean (SD) age of 57.0 [14.4] years. From 2005 to 2019, adjusted CUD prevalences increased from 1.38% to 2.25% in states with no cannabis laws (no CLs), 1.38% to 2.54% in MCL-only enacting states, and 1.39% to 2.56% in RCL-enacting states. Difference-in-difference results indicated that MCL-only enactment was associated with a 0.05% (0.05-0.06) absolute increase in CUD prevalence, ie, that 4.7% of the total increase in CUD prevalence in MCL-only enacting states could be attributed to MCLs, while RCL enactment was associated with a 1.12% (95% CI, 0.10-0.13) absolute increase in CUD prevalence, ie, that 9.8% of the total increase in CUD prevalence in RCL-enacting states could be attributed to RCLs. The role of RCL in the increases in CUD prevalence was greatest in patients aged 65 to 75 years, with an absolute increase of 0.15% (95% CI, 0.13-0.17) in CUD prevalence associated with RCLs, ie, 18.6% of the total increase in CUD prevalence in that age group., Conclusions and Relevance: In this study of VHA patients, MCL and RCL enactment played a significant role in the overall increases in CUD prevalence, particularly in older patients. However, consistent with general population studies, effect sizes were relatively small, suggesting that cumulatively, laws affected cannabis attitudes diffusely across the country or that other factors played a larger role in the overall increases in adult CUD. Results underscore the need to screen for cannabis use and CUD and to treat CUD when it is present.

Background: Gender is an important factor in understanding cannabis patterns, yet few studies have explored cannabis patterns among gender minority (GM) individuals - particularly among high-risk age groups including young adults. The evolving cannabis market is reshaping typical patterns of cannabis use in the U.S. The combination of these factors warrants increased efforts to examine cannabis practices in gender-diverse samples., Methods: Online survey participants between 18-34 years (N=2377) from the U.S. provided information on cannabis practices from May - July 2021. Gender differences across several cannabis outcomes (onset, methods of consumption, product potency, frequency, and quantity) were assessed. Bivariate tests and multiple regression models examined associations between gender (cisgender men: n =1020; cisgender women: n =1178; and GM: n =179) and cannabis outcomes adjusting for sociodemographic characteristics., Results: In regression models adjusted for sociodemographic characteristics, GM identity was associated with later age of onset and lower likelihood of daily use compared to cisgender men and women. Identifying as GM or cisgender woman was associated with fewer lifetime methods of consumption and lower plant and concentrate potency usage., Conclusions: Findings provide initial insights into potential gender differences in cannabis practices from a sample of heavy cannabis users. GM young adults report use patterns indicative of lower risk compared to cisgender men and women in our sample. Future investigations of gender differences in cannabis use that explore specific gender minority categories and that include alternative sampling strategies are needed to better understand differential risks associated with gender.

Background and Aims: Hallucinogen use is potentially harmful. Information on whether such use has increased in recent decades is lacking. This study assessed overall and age-specific time trends in the prevalence of 12-month hallucinogen use in the US general population., Design: Cross-sectional., Setting: Data from the US National Survey on Drug Use and Health, 2002-19., Participants: Respondents aged ≥ 12 years (n = 1 006 051)., Measurements: Predictors were continuous years. Outcome variables included any hallucinogen use and use of lysergic acid diethylamide (LSD), ecstasy and phencyclidine (PCP) in the past year. Socio-demographic variables (gender, age, race/ethnicity, educational level and family income) were covariates., Findings: Overall, hallucinogen use increased between 2015 and 2019 [prevalence difference (PD) = +0.44, P < 0.05]. Since 2002, hallucinogen use has increased in adults aged ≥ 26 years (PD, 2002-14 = +0.24, P < 0.05; PD, 2015-19 = +0.45, P < 0.001) and decreased in adolescents aged 12-17 years (PD, 2002-14 = -1.60, P < 0.0001; PD, 2015-19 = -0.73, P < 0.001). Ecstasy use has decreased in adolescents (PD, 2002-14 = -0.56, P < 0.001), adults aged 18-25 years (PD, 2015-19 = -0.96, P < 0.01) and ≥ 26 years (PD, 2015-19 = -0.13, P < 0.05). LSD use between 2002 and 2019 increased overall (PD = +0.71, P < 0.0001) and in all age groups (12-17: PD = +0.67, P < 0.001; 18-25: PD = +3.12, P < 0.0001; ≥ 26: PD = +0.36, P < 0.0001). Conversely, PCP use between 2002 and 2019 decreased overall (PD = -0.06, P < 0.001), in adolescents (PD = -0.24, P < 0.001) and young adults (PD = -0.32, P < 0.0001)., Conclusions: Since 2002, hallucinogen use in the United States has decreased among adolescents but increased in adults and is now estimated to affect more than 3 million adults aged 26+ years and more than 5.5 million adults aged 18+ years., (© 2022 Society for the Study of Addiction.)

Background: Consensus guidelines recommend multimodal chronic pain treatment with increased use of non-pharmacological treatment modalities (NPM), including as first-line therapies. However, with many barriers to NPM uptake in US healthcare systems, NPM use may vary across medical care settings. Military veterans are disproportionately affected by chronic pain. Many veterans receive treatment through the Veterans Health Administration (VHA), an integrated healthcare system in which specific policies promote NPM use., Objective: To examine whether veterans with chronic pain who utilize VHA healthcare were more likely to use NPM than veterans who do not utilize VHA healthcare., Design: Cross-sectional nationally representative study., Participants: US military veterans (N = 2,836)., Main Measures: In the 2019 National Health Interview Survey, veterans were assessed for VHA treatment, chronic pain (i.e., past 3-month daily or almost daily pain), symptoms of depression and anxiety, substance use, and NPM (i.e., physical therapy, chiropractic/spinal manipulation, massage, psychotherapy, educational class/workshop, peer support groups, or yoga/tai chi)., Key Results: Chronic pain (45.2% vs. 26.8%) and NPM use (49.8% vs. 39.4%) were more prevalent among VHA patients than non-VHA veterans. After adjusting for sociodemographic characteristics, psychiatric symptoms, physical health indicators, and use of cigarettes or prescription opioids, VHA patients were more likely than non-VHA veterans to use any NPM (adjusted odds ratio [aOR] = 1.52, 95% CI: 1.07-2.16) and multimodal NPM (aOR = 1.80, 95% CI: 1.12-2.87) than no NPM. Among veterans with chronic pain, VHA patients were more likely to use chiropractic care (aOR = 1.90, 95% CI = 1.12-3.22), educational class/workshop (aOR = 3.02, 95% CI = 1.35-6.73), or psychotherapy (aOR = 4.28, 95% CI = 1.69-10.87)., Conclusions: Among veterans with chronic pain, past-year VHA use was associated with greater likelihood of receiving NPM. These findings may suggest that the VHA is an important resource and possible facilitator of NPM. VHA policies may offer guidance for expanding use of NPM in other integrated US healthcare systems., (© 2022. The Author(s).)

The DSM-5 definition of cannabis use disorder (CUD) differs from DSM-IV by combining abuse and dependence criteria (without the legal criterion) and including withdrawal and craving criteria. Information on construct validity of the DSM-5 CUD diagnosis and severity levels is lacking. This study examines the associations between DSM-5 CUD and severity classification and a set of concurrent validators. Adults with problematic substance use were recruited from two settings: a research setting in an urban medical center and a suburban inpatient addiction treatment program. Participants who reported past-year cannabis use (n = 392) were included in this study and completed a semi-structured, clinician-administered diagnostic interview. Regression models estimated the associations between binary DSM-5 CUD and severity levels with a set of validators, including cannabis use variables, psychopathology, and functional impairment. DSM-5 CUD and all severity levels were associated with cannabis use validators, including number of days used, self-reporting that cannabis use was a major problem, and greater cannabis craving. DSM-5 CUD and severe CUD were associated with other psychiatric disorders and social impairment. Findings add information about the validity of DSM-5 CUD diagnosis and severity levels, with severe CUD receiving the strongest support from its association with validators across all domains, as distinct from the mild and moderate CUD measures that were associated with cannabis-specific validators alone. Severe CUD is likely to require more intensive treatment to bolster physical, psychiatric, and social functioning, whereas the mild and moderate severity thresholds provide useful information for identifying less severe disorders for prevention and brief intervention., Competing Interests: Declaration of competing interest Dr. Fink, Dr. Shmulewitz, Dr. Mannes, Ms. Stohl, Dr. Livne and Dr. Wall report no conflicts of interest. Dr. Hasin reports funding for an unrelated project from Syneos Health., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Use of novel cannabis products whose primary active compound is Delta-8 tetrahydrocannabinol (Delta-8 THC), an isomer of Delta-9 THC has recently surged. While Delta-8 THC has psychoactive effects and is potentially harmful, little is known about its use. We examined sociodemographic characteristics, motivations, and consumption patterns of Delta-8 THC in US adult cannabis users., Methods: Cannabis-using adult online survey participants (N = 4,348) provided information on Delta-8 use, and other characteristics. We assessed frequencies of sociodemographics, patterns, and correlates of Delta-8 THC use. Regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) of associations between past 30-day Delta-8 THC use, sociodemographic and other characteristics., Findings: Among past 30-day cannabis users, 16.7% reported Delta-8 THC use. The most common consumption method was vaping concentrated formulations of Delta-8 THC (41.2%). Primary motivations for use were its legal status and perceived therapeutic benefits. Males were more likely than females to report Delta-8 THC use (aOR = 1.4, 95% CI 1.2, 1.7). Respondents residing in states with restrictions on sales of Delta-8 THC products had lower odds of Delta-8 THC use (aOR = 0.7, 95% CI 0.57, 0.86)., Conclusions: Findings provide initial insight into the current state of Delta-8 THC use in the US. Given the limited knowledge on use of Delta-8 THC, and considering emergence of reports indicating its harmful effects, there is urgent need for nationally representative data to investigate correlates of Delta-8 THC use (e.g., effectiveness of state-specific restrictions on its products). Such information can guide public-health policy around Delta-8 THC use., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: In the United States, adult cannabis use has increased over time, but less information is available on time trends in cannabis use disorder. The authors used Veterans Health Administration (VHA) data to examine change over time in cannabis use disorder diagnoses among veterans, an important population subgroup, and whether such trends differ by age group (&lt;35 years, 35-64 years, ≥65 years), sex, or race/ethnicity., Methods: VHA electronic health records from 2005 to 2019 (range of Ns per year, 4,403,027-5,797,240) were used to identify the percentage of VHA patients seen each year with a cannabis use disorder diagnosis (ICD-9-CM, January 1, 2005-September 30, 2015; ICD-10-CM, October 1, 2015-December 31, 2019). Trends in cannabis use disorder diagnoses were examined by age and by race/ethnicity and sex within age groups. Given the transition in ICD coding, differences in trends were tested within two periods: 2005-2014 (ICD-9-CM) and 2016-2019 (ICD-10-CM)., Results: In 2005, the percentages of VHA patients diagnosed with cannabis use disorder in the &lt;35, 35-64, and ≥65 year age groups were 1.70%, 1.59%, and 0.03%, respectively; by 2019, the percentages had increased to 4.84%, 2.86%, and 0.74%, respectively. Although the prevalence of cannabis use disorder was consistently higher among males than females, between 2016 and 2019, the prevalence increased more among females than males in the &lt;35 year group. Black patients had a consistently higher prevalence of cannabis use disorder than other racial/ethnic groups, and increases were greater among Black than White patients in the &lt;35 year group in both periods., Conclusions: Since 2005, diagnoses of cannabis use disorder have increased substantially among VHA patients, as they have in the general population and other patient populations. Possible explanations warranting investigation include decreasing perception of risk, changing laws, increasing cannabis potency, stressors related to growing socioeconomic inequality, and use of cannabis to self-treat pain. Clinicians and the public should be educated about the increases in cannabis use disorder in general in the United States, including among patients treated at the VHA.

Aims: Information on time trends in use of different plant-based hallucinogens is lacking. The current study used nationally representative U.S. data to assess overall and age-specific time trends in the prevalence of lifetime and 12-month use of plant-based hallucinogens and dissociative agents., Methods: Participants were respondents aged ≥ 12 years (N = 1,006,051) from the National Survey on Drug Use and Health, 2002-2019. Predictors were continuous years. Outcomes included illicit use of peyote, mescaline, psilocybin, ketamine, salvia, and tryptamine. Sociodemographic variables (gender; age; race/ethnicity; educational level; family income) were modeled as covariates. Trends were estimated overall and by age (12-17, 18-25, 26+). Prevalence differences [PDs] were obtained for each category, along with 95 % confidence intervals [CI]., Results: Increases in lifetime use were observed for psilocybin (2002-2019 PD=+1.61), tryptamine (2006-2014 PD=+0.55; 2015-2019 PD=+0.44), and ketamine (2006-2014 PD=+0.27; 2015-2019 PD=+0.21). Mescaline use decreased (PD = -0.89). While overall lifetime salvia use increased between 2006 and 2014 (PD=+1.81), prevalence did not change between 2015 and 2019. Twelve-month use of tryptamine and ketamine increased between 2006 and 2014 (PD=+0.14; +0.03, respectively). Twelve-month ketamine use also increased from 2015 to 2019 (PD=+0.03). By age, participants aged 12-17 and 18-25 showed decreases in use of most types of hallucinogens, but those age 26+ generally showed increases., Conclusions: While use of plant-based hallucinogens and dissociative agents remains rare, lifetime use of ketamine, tryptamine, and psilocybin is increasing in adults. Considering these increases alongside concerns about unsupervised use of illicit products whose dose and composition is uncertain, clinicians and policymakers should remain mindful of the rising rates of illicit use in the general population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Objective: We examined the prevalence of risky alcohol and cannabis use among Brazilian varsity college athletes and whether this group had a greater likelihood of risky use than non-athletes., Methods: In 2009, Brazilian college students (n=12,711) were recruited for a national stratified random survey. Their sociodemographic characteristics, mental health, substance use, and participation in varsity sports were assessed. Binary logistic regression models were used to examine the association between varsity athlete status and moderate to high-risk alcohol and cannabis use., Results: Among varsity athletes, 67.6 and 10.7% reported risky alcohol and cannabis use, respectively. Varsity athletes had greater odds of risky alcohol consumption than non-athletes (aOR = 2.02, 95%CI 1.08-3.78). Varsity athletes also had greater odds of risky cannabis use than non-athletes in unadjusted analyses (OR = 2.57, 95%CI 1.05-6.28), although this relationship was attenuated after covariate adjustment., Conclusions: Among college students in Brazil, varsity athletes had a higher prevalence of risky alcohol and cannabis use than non-athletes. The rates were considerably higher than those observed among samples of U.S. college athletes. Future research should examine the use of these substances among varsity college athletes in other middle-income countries since these findings will likely guide prevention and treatment efforts.

Background: Substance use disorders (SUD) elevate the risk for COVID-19 hospitalization, but studies are inconsistent on the relationship of SUD to COVID-19 mortality., Methods: Veterans Health Administration (VHA) patients treated in 2019 and evaluated in 2020 for COVID-19 (n=5,556,315), of whom 62,303 (1.1%) tested positive for COVID-19 (COVID-19+). Outcomes were COVID-19+ by 11/01/20, hospitalization, ICU admission, or death within 60 days of a positive test. Main predictors were any ICD-10-CM SUDs, with substance-specific SUDs (cannabis, cocaine, opioid, stimulant, sedative) explored individually. Logistic regression produced unadjusted and covariate-adjusted odds ratios (OR; aOR)., Results: Among COVID-19+ patients, 19.25% were hospitalized, 7.71% admitted to ICU, and 5.84% died. In unadjusted models, any SUD and all substance-specific SUDs except cannabis use disorder were associated with COVID-19+(ORs=1.06-1.85); adjusted models produced similar results. Any SUD and all substance-specific SUDs were associated with hospitalization (aORs: 1.24-1.91). Any SUD, cocaine and opioid disorder were associated with ICU admission in unadjusted but not adjusted models. Any SUD, cannabis, cocaine, and stimulant disorders were inversely associated with mortality in unadjusted models (OR=0.27-0.46). After adjustment, associations with mortality were no longer significant. In ad hoc analyses, adjusted odds of mortality were lower among the 49.9% of COVID-19+ patients with SUD who had SUD treatment in 2019, but not among those without such treatment., Conclusions: In VHA patients, SUDs are associated with COVID-19 hospitalization but not COVID-19 mortality. SUD treatment may provide closer monitoring of care, ensuring that these patients received needed medical attention, enabling them to ultimately survive serious illness., (Copyright © 2022. Published by Elsevier B.V.)

Bipolar disorder (BD) is a serious chronic mood disorder associated with high rates of co-occurring substance use disorders. Shared psychotic disorder (SPD) is a rare clinical phenomenon and has been reported in only a few cases of individuals diagnosed with BD. Furthermore, reports concerning SPD being induced by substance use or withdrawal are lacking. We report the case of a married couple endorsing simultaneous psychosis, a form of SPD. The primary case (the wife) had a diagnosis of BD, without any history of psychotic episodes before the current episode, while the secondary case (the husband) had a diagnosis of posttraumatic stress disorder. Both individuals were misusing prescribed synthetic opioids, and their psychosis was most likely induced by a withdrawal state. Cases of SPD involving patients with BD have rarely been reported. Considering the high rates of dual diagnoses among patients with BD, clinicians should be aware of the risk of substance-induced psychosis among these individuals and the manifestation of these psychotic episodes. This case report strengthens previous reports suggesting that SPD is a clinical entity that can occur not only in situations where the primary case involves an individual diagnosed with delusional disorder or schizophrenia, but that it may also occur when the primary case has a diagnosis of BD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite its potential to produce serious adverse outcomes, DSM-5 alcohol withdrawal syndrome (AWS) has not been widely studied in the general population., Methods: We used cross-sectional data from 36,309 U.S. adults from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III to examine the past-year prevalence of AWS and its correlates. We focused on an important clinical population-past-year drinkers with unhealthy alcohol use-i.e., those with a positive score on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire. We also examined the association of AWS with sociodemographic measures, psychiatric disorders, alcohol-related measures, and healthcare utilization., Results: Approximately one-third (n = 12,634) of respondents reported unhealthy alcohol use (AUDIT-C+). Of these, 14.3% met criteria for a DSM-5 AWS diagnosis. The mean (SE) number of withdrawal symptoms among individuals with AWS was 2.83 (1.88), with the most common being nausea/vomiting and insomnia (19.8% and 11.6%, respectively). Among AUDIT-C+ respondents, the odds of AWS were significantly higher among males (adjusted odds ratio [aOR] = 1.17 [95% CI, 1.02-1.33]), unmarried participants (aOR = 1.55 [95% CI, 1.25-1.92]), and those at the lowest (vs. highest) income levels (aOR = 1.62 [95% CI, 1.37-1.92]). Among AUDIT-C+ respondents, AWS was also associated with psychiatric disorders (with aORs that ranged from 2.08 [95% CI, 1.79-2.41]) for major depressive disorder to 3.14 (95% CI, 1.79-2.41) for borderline personality disorder. AUDIT-C+ respondents with AWS also had higher odds of past-year alcohol use disorder (aOR = 11.2 [95% CI, 9.66-13.07]), other alcohol-related features (e.g., binge drinking), and healthcare utilization., Conclusions: Among individuals with unhealthy alcohol use, AWS is prevalent, highly comorbid, and disabling. Given the risk of AWS among unhealthy drinkers, a comparatively large segment of the general population, clinicians should seek to identify individuals with AWS and intervene with them to prevent serious adverse outcomes., (© 2022 by the Research Society on Alcoholism.)

Objective: The authors sought to determine the association of cannabis indicators with self-reported psychotic disorders in the U.S. general population., Methods: Participants were from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309). Logistic regression was used to estimate standardized prevalences of past-year self-reported psychotic disorders within each survey and to evaluate the association of past-year self-reported psychotic disorders with indicators of nonmedical cannabis use (any use; frequent use [at least three times/week], daily/near-daily use, and DSM-IV cannabis use disorder) compared with those with no past-year nonmedical cannabis use. Whether the strength of associations differed between surveys was indicated by difference-in-difference tests (between-survey contrasts) and ratios of odds ratios between surveys., Results: Self-reported psychotic disorders were significantly more prevalent among participants with any nonmedical cannabis use than those without (2001-2002: 1.65% compared with 0.27%; 2012-2013: 1.89% compared with 0.68%). In 2001-2002, self-reported psychotic disorders were unrelated to either frequent use or daily/near-daily use. However, in 2012 - 2013, compared with nonusers, self-reported psychotic disorders were more common among participants with frequent use and those with daily/near-daily nonmedical cannabis use (2012-2013: 2.79% and 2.52%, respectively, compared with 0.68% among nonusers). Self-reported psychotic disorders were significantly more prevalent among participants with cannabis use disorder than nonusers in both surveys (2001-2002: 2.55% compared with 0.27%; 2012 - 2013: 3.38% compared with 0.68%). The strength of these associations did not change over time., Conclusions: Data from the U.S. general population, especially more recent data, suggest associations between self-reported psychotic disorder and frequent nonmedical cannabis use and cannabis use disorder. Clinicians and policy makers should consider these relationships when monitoring patients and formulating programs.

Background: Highly-potent cannabis products, e.g., concentrates, entail greater risks of cannabis-related harms than lower-potency products such as plant or flower material. However, little information is available on whether individuals in U.S. states with recreational cannabis laws (RCL) or medical cannabis laws (MCL) are more likely than individuals in U.S. states without cannabis legalization (no-CL) to use highly-potent forms of cannabis., Methods: Cannabis-using adults in a 2017 online survey (N = 4064) provided information on state of residence and past-month cannabis use, including types of products used, categorized as low-potency (smoked or vaped plant cannabis) or high-potency (vaping or dabbing concentrates). Multivariable logistic regression models generated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for use of high-potency cannabis products by state cannabis legalization status (RCL, MCL, no-CL)., Results: Compared to participants in no-CL states, participants in RCL states had greater odds of using high-potency concentrate products (aOR=2.61;CI=1.77-3.86), as did participants in MCL-only states (aOR=1.55;CI=1.21-1.97). When participants in RCL states and MCL states were directly compared, those in RCL states had greater odds of using high-potency concentrate products (aOR=1.69;CI=1.27-2.42)., Discussion: Although the sample was not nationally representative and the cross-sectional data precluded determining the direction of effect, results suggest that use of high-potency cannabis concentrates is more likely among those in RCL states. Clinicians in RCL states should screen cannabis users for harmful patterns of use. Policymakers in states that do not yet have RCL should consider these findings when drafting new cannabis laws, including the specific products permitted and how best to regulate them., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The DSM-5 definition of alcohol use disorder (AUD) has been well validated, but information is lacking on the extent to which alcohol use, comorbidity, and impairment are associated with the 3 DSM-5-defined AUD severity levels: mild, moderate, and severe. This study examined clinical and functional characteristics as predictors (validators) of these severity levels., Methods: Participants aged ≥18 years reporting current problem substance use (N = 588) were recruited between 2016 and 2019 and assessed for DSM-5 AUD and a set of potential validators: indicators of alcohol use severity (i.e., craving, binge drinking frequency, problematic use, and harmful drinking), psychiatric disorders, and functional impairment. Multinomial logistic regression models examined the association between the predictors and the 3 AUD severity levels (mild, moderate, and severe) vs the reference group, no AUD, controlling for sociodemographic characteristics and other substance use., Results: All alcohol use validators were associated with a greater likelihood of all 3 AUD severity levels compared with the no-AUD group. However, psychiatric disorders were associated only with severe AUD and participants with major depression (aOR = 2.44), posttraumatic stress disorder (aOR = 1.65), borderline personality disorder (aOR = 1.99), and antisocial personality disorder (aOR = 1.78) had a greater likelihood of severe AUD than the no-AUD group. Functioning validators were also associated only with severe AUD and participants with social (aOR = 1.87), physical (aOR = 1.62), or mental (aOR = 1.84) impairment had a greater likelihood of severe AUD than the no-AUD group. Many alcohol-related, psychiatric, and functioning validators were associated with greater odds of severe AUD than mild or moderate AUD., Conclusion: This study supports the criterion validity of the DSM-5 tri-categorical measure of AUD. Specifically, results fully supported the validity of severe AUD by its associations with all predictors, whereas the validity of mild and moderate AUD was supported only by alcohol use predictor variables. Findings suggest the value of using severity-specific interventions utilizing the DSM-5 AUD., (© 2021 by the Research Society on Alcoholism.)

Background: In DSM-5, definitions of substance use disorders (SUD) were changed considerably from DSM-IV, yet little is known about how well DSM-IV and DSM-5 SUD diagnoses agree among substance users. Because data from many studies are based on DSM-IV diagnostic criteria, understanding the agreement between DSM-5 and DSM-IV SUD diagnoses and reasons for discordance between these diagnoses is crucial for comparing results across studies., Measurements: Prevalences and chance-corrected agreement of DSM-5 SUD and DSM-IV substance dependence were evaluated in 588 substance users in a suburban inpatient addiction program and an urban medical center, using a semi-structured interview (PRISM-5). Alcohol, tobacco, cannabis, cocaine, heroin, opioid, sedative, and stimulant use disorders were examined. Cohen's kappa was used to assess agreement between DSM-5 and DSM-IV SUD (abuse or dependence), DSM-5 SUD and DSM-IV dependence, and DSM-5 moderate/severe SUD and DSM-IV dependence., Results: Agreement between DSM-5 and DSM-IV SUD was excellent for all substances (κ = 0.84-0.99), except for cannabis and tobacco (κ = 0.75; 0.80, respectively). The most common reason for diagnostic discrepancies was a positive DSM-5 SUD diagnosis but no DSM-IV diagnosis, due to the lowered DSM-5 SUD threshold. Agreement between DSM-5 SUD and DSM-IV dependence was excellent for all substances (κ = 0.88-0.94), except for alcohol, tobacco, and cannabis (κ = 0.63-0.75). Agreement between moderate/severe DSM-5 SUD and DSM-IV dependence was excellent across all substances., Conclusion: While care should be used in interpreting results of studies using different methods, studies relying on DSM-IV or DSM-5 SUD diagnostic criteria offer similar information and thus can be compared when accumulating a body of evidence., (Copyright © 2021. Published by Elsevier B.V.)

Background: In recent decades, the US religious landscape has undergone considerable change such as a decline in religious service attendance. These changes may indicate that religious social support structures have deteriorated, possibly leading to a decrease in strengths of associations with substance use. Considering this, and given limitations of past studies (e.g., limited control for potential confounders), large-scale general population studies are needed to reexamine associations between religiosity domains and substance use., Methods: This cross-sectional study used data from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (N = 36,309). In unadjusted and adjusted models, controlling for religiosity domains and other covariates, we examined associations between three religiosity domains (importance of religiosity/spirituality, service attendance, and religious affiliation) and DSM-5 SUD. Focusing on service attendance, we also examined associations with other substance use-related outcomes., Results: Among religiosity domains, only frequency of service attendance was associated with SUD across most substances. Frequent service attendees had lower odds of alcohol use disorder (adjusted OR [aOR] = 0.4, 95 % CI 0.33,0.51), tobacco use disorder (aOR = 0.3, 95 % CI 0.22,0.33) and cannabis use disorder (aOR = 0.4, 95 % CI 0.24,0.68), compared to non-service attendees. For alcohol and tobacco, the protective effect of frequent service attendance was more robust for SUD than for respective substance use., Conclusions: Despite decreasing rates of religious belief and practice in the US, service attendance independently lowered the odds of substance use and SUD across multiple substances. Results may inform religious leaders and clinicians about the value of utilizing religious social support structures in the prevention and treatment of substance use and SUD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction and Aims: It has been previously reported that more than 34% of individuals who use cannabis may qualify for a diagnosis of DSM-IV cannabis abuse or dependence throughout their lifetime. The introduction of the DSM-5 cannabis use disorder (CUD) diagnostic criteria reflects several intrinsic changes in the perception of substance use disorders. However, little is known about the probability of transition from cannabis use to CUD over time nor about the sociodemographic and clinical correlates associated with this transition., Design and Methods: Participants were individuals ≥18 years interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions-III in 2012-2013. Measurements included univariable and multivariable discrete-time survival analyses performed to examine the association between previously reported cannabis dependence predictors and the hazards of transitioning from cannabis use to CUD. Survival plots assessed the probability of transition from cannabis use to CUD over time since age of first use and differences in probability between predictor levels., Results: Among lifetime cannabis users (N = 11 272), lifetime probability of transition to CUD was approximately 27%. A higher probability of transition from cannabis use to CUD was observed in the following: men, participants belonging to an ethnic minority group, early-onset cannabis users and individuals who reported experiencing three or more childhood adverse events., Discussion and Conclusions: This is the first study to explore transition from cannabis use to the DSM-5 CUD diagnosis. The current study identified specific predictors of this transition, which may assist in targeting at-risk populations., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

The global spread of bacterial resistance to antibiotics promotes a search for alternative approaches to eradication of pathogenic bacteria. One alternative is using photosensitizers for inhibition of Gram-positive and Gram-negative bacteria under illumination. Due to low penetration of visible light into tissues, applications of photosensitizers are currently limited to treatment of superficial local infections. Excitation of photosensitizers in the dark can be applied to overcome this problem. In the present work, dark antibacterial activity of the photosensitizer Rose Bengal alone and in combination with antibiotics was studied. The minimum inhibitory concentrations (MIC) value of Rose Bengal against S. aureus dropped in the presence of sub-MIC concentrations of ciprofloxacin, levofloxacin, methicillin, and gentamicin. Free Rose Bengal at sub-MIC concentrations can be excited in the dark by ultrasound at 38 kHz. Rose Bengal immobilized onto silicon showed good antibacterial activity in the dark under ultrasonic activation, probably because of Rose Bengal leaching from the polymer during the treatment. Exposure of bacteria to Rose Bengal in the dark under irradiation by electromagnetic radio frequency waves in the 9 to 12 GHz range caused a decrease in the bacterial concentration, presumably due to resonant absorption of electromagnetic energy, its transformation into heat and subsequent excitation of Rose Bengal.

Background: Cannabis withdrawal syndrome (CWS) was newly added to the Diagnostic and Statistical Manual of Mental Disorders in its most recent edition, DSM-5. With cannabis use increasing among U.S. adults, information is needed about the prevalence and correlates of DSM-5 CWS in the general population. This study presents nationally representative findings on the prevalence, sociodemographic and clinical correlates of DSM-5 CWS among U.S. adults., Method: Participants ≥18 years were interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) in 2012-2013. Among the sub-sample of frequent cannabis users in the prior 12 months (≥3 times a week; N = 1527), the prevalence and demographic and clinical correlates of DSM-5 CWS were examined., Results: In frequent cannabis users, the prevalence of CWS was 12.1%. The most common withdrawal symptoms among those with CWS were nervousness/anxiety (76.3%), hostility (71.9%), sleep difficulty (68.2%) and depressed mood (58.9%). CWS was associated with significant disability (p < 0.001), and with mood disorders (adjusted odds ratios [aOR] = 1.9-2.6), anxiety disorders (aOR = 2.4-2.5), personality disorders (aOR = 1.7-2.2) and family history of depression (aOR = 2.5) but not personal history of other substance use disorders or family history of substance use problems., Conclusions: CWS is highly comorbid and disabling. Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it to promote more effective treatment among frequent cannabis users., (Copyright © 2018. Published by Elsevier B.V.)

Background: Though high rates of co-occurring cannabis use and depression are well-documented, data regarding the association between cannabis use and dysthymia is scarce. The aim of this cross-sectional study was to explore clinical correlations of cannabis use among individuals with dysthymia, as well as the changes in the association between cannabis use and dysthymia across six decades of birth cohorts., Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III; 2012-2013; N = 36,309). Participants were divided into six birth cohorts (1940s-1990s), based on their decade of birth, and individuals with dysthymia were further categorized by 3 levels of lifetime cannabis use: non-users, non-CUD users, and CUD-users. We compared rates of co-occurring psychiatric and substance use disorders among cannabis users vs non-users and conducted logistic regression analyses in order to determine the odds of dysthymia among cannabis users across six decades., Results: Rates of several psychiatric disorders, such as personality disorders, and substance use disorders were higher among individuals with dysthymia who used cannabis compared to those who did not. The interaction between cannabis use (without a CUD) and birth cohort was associated with a decrease in the odds of dysthymia (OR=0.90, 95% CI 0.84-0.97) and remained significant after controlling for confounding variables. Similar changes over time were not demonstrated for CUD users., Limitations: Likelihood for recall bias and misclassification based on cross-sectional nature of the study and on respondents' self-reports of symptoms throughout their lifetime., Conclusions and Implications: Our study's findings demonstrate that the association between cannabis use (but not CUDs) and dysthymia has weakened over time. These findings highlight the need for further research examining changes over time in the relationship between cannabis use and associated psychiatric disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis -expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants., Competing Interests: Conflict of interest statement: S.E.L., J. Laramie, and R.G.T. were employees of Complete Genomics during this study. T.M.T. is an employee of Regeneron Pharmaceuticals. D.A. is an employee of Vertex Pharmaceuticals.

Objective: The aim of this study was to determine the utility of an intraoperative magnetic resonance imaging (i-MRI) system (Polestar N-10, 20, 30) in achieving maximal resection of intra-axial brain lesions., Methods: The subjects comprised 163 patients with intra-axial brain lesions who underwent resection at Sheba Medical Center using the Polestar from February 2000 through February 2012. Demographic and imaging data were obtained and analyzed retrospectively. The patients included 83 men (50.9%) and had a mean age of 43 years. High-grade gliomas were diagnosed in 72 patients, low-grade gliomas in 35, metastases in 22, and various pathologies (e.g., cavernous angiomas, juvenile pilocytic astrocytoma, pleomorphic xanthoastrocytoma, etc.) were diagnosed in 34. The majority of the lesions (84, 51.5%) were located in or near eloquent areas. Fifty-one patients had nonenhancing lesions., Results: We intended to achieve complete resection in 110 of 163 cases, based on preoperative imaging. Complete resection was achieved in 90 of these 110 (81.8%) cases. Intraoperative MRI led to additional resection in 42.3% of the total cases and to complete resection in 43.3% of all the cases in which a complete resection was achieved. In 76.8% of these cases, 2 intraoperative scans were sufficient to achieve complete resection. Sex, age, intent of resection, recurrence, affected side, and radiologic characteristics did not differ significantly between cases in which intraoperative MRI led to further resection and cases in which it did not. Nonenhancing lesions of all types were 3 times more likely to require additional resection after obtaining intraoperative MRIs (P = .02)., Conclusions: The Polestar (N-10, 20, 30) proved useful for evaluating residual intra-axial brain lesions and achieving the maximal extent of resection in 42.3% of the total cases and in 43.3% of cases in which complete resection was achieved. Intraoperative MRI led to extended resection in 46.9% of patients for whom the initial intent was to perform an incomplete resection. Nonenhancement was the only independent variable predicting the usefulness of intraoperative MRI for additional lesion resection., (Copyright © 2014 Elsevier Inc. All rights reserved.)