Open Label Pilot of Lorcaserin (a serotonin 2C-receptor agonist) for Cannabis Use Disorder.

Background And Objective: Cannabis Use Disorder (CUD) has no FDA approved treatment. Serotonin-2c (5HT2c) agonists have preclinical and human laboratory evidence for potential efficacy for CUD. We assessed the tolerability and effects of lorcaserin (5HT2c agonist) on CUD. Methods: In a 10-week, open label, uncontrolled trial, the tolerability of lorcaserin was tested in outpatients with CUD. Adverse events (AE) were assessed weekly. Cannabis use was assessed twice weekly by the Timeline follow-back and quantitative urine metabolites. Results: 17 participants enrolled, and 14 received medication. Participants' average age was 35 years; majority were male (N=12). The medication was well tolerated in males. There were no serious adverse events (SAE). The most common AE's were headache/migraine (N=4, all females), anorexia (N=3), and irritability (N=2). Participants decreased their frequency of cannabis use significantly (p < 0.001), adjusted for baseline use. By the end of the trial, participants decreased by 1.76 (SE=0.47) cannabis using days/week. Average daily amount of cannabis and urine THC metabolite levels did not change significantly. Conclusions: Lorcaserin was well tolerated in males but not females suggesting possible sex differences. Future trials of other 5HT2c agonists (lorcaserin was withdrawn at the request of the FDA) should consider longer dose titration phases. Trial Registration: NCT02932215.

Mixed amphetamine salts-extended release (MAS-ER) as a behavioral treatment augmentation strategy for cocaine use disorder: A randomized clinical trial.

Psychosocial interventions remain the primary strategy for addressing cocaine use disorder (CUD), although many individuals do not benefit from these approaches. Amphetamine-based interventions have shown significant promise and may improve outcomes among individuals continuing to use cocaine in the context of behavioral interventions. One hundred forty-five adults (122 males) who used cocaine a minimum of 4 days in the prior month and met the criteria for a CUD enrolled in a two-stage intervention. All participants received a computer-delivered skills intervention and contingency management for reinforcing abstinence for a 1-month period. Participants demonstrating less than 3 weeks of abstinence in the first month were randomized to receive mixed amphetamine salts-extended release (MAS-ER) or placebo (80 mg/day) for 10 weeks under double-blind conditions. All participants continued with the behavioral intervention. The primary outcome was the proportion of individuals who achieved 3 consecutive weeks of abstinence as measured by urine toxicology confirmed self-report at the study end. The proportion of participants demonstrating 3 consecutive weeks of abstinence at study end did not differ between the medication groups: MAS-ER = 15.6% (7/45) and placebo = 12.2% (5/41). Participants who received MAS-ER reported greater reductions in the magnitude of wanting cocaine, although no group differences were noted in either the perceived improvement or the frequency of wanting cocaine. Retention rates were greater for both medication groups compared to behavioral responders. Overall, augmenting a behavioral intervention with MAS-ER did not significantly increase the abstinence rate among individuals continuing to use cocaine following a month of behavioral therapy alone. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cocaine use disorder patients develop distinct patterns of regulation of acth secretion by a vasopressin agonist and oxytocin: Report on a laboratory study.

Background: : Oxytocin and Vasopressin systems in the brain sustain adaptation to stressors. Cocaine being a stressor, it may alter brain homeostatic function. This dysregulation may entrench cocaine use disorder. Method: : This is a human laboratory study of the effects of intranasal desmopressin (a Vasopressin 1b receptor agonist) and oxytocin on ACTH secretion in cocaine use disorder patients versus a control group. It consisted of two endocrine challenges performed on consecutive days. On day 1, the effect of intranasal desmopressin (80 IU) on ACTH secretion was measured. On day 2, a pre-treatment with intranasal oxytocin (24 IU) preceded intranasal desmopressin to monitor its effect on desmopressin-induced ACTH secretion. We hypothesized that the effect of intranasal oxytocin in controls would differ from the effect in cocaine use disorder patients. Results: : Forty-three patients were included in this study: 14 controls and 29 cocaine use disorder patients. Significant differences were noted in the direction of change of ACTH secretion between the two groups. In cocaine use disorder patients, overall ACTH secretion was on average 2.7 pg/ml/min higher after intranasal desmopressin than after intranasal oxytocin/desmopressin (t292 = 2.91, p = 0.004). The opposite was observed in controls: overall ACTH secretion averaged 3.3 pg/ml/min less after intranasal desmopressin than after intranasal oxytocin/desmopressin (t292 = -2.35, p = 0.02). Conclusion: : Intranasal oxytocin and desmopressin revealed a pattern of ACTH secretion in cocaine use disorder patients that is distinct from a non-addicted control group. (ClinicalTrial.gov00255357, 10/2014).

Anxiety and Depression Symptoms Among Young U.S. Essential Workers During the COVID-19 Pandemic.

OBJECTIVE: Emerging cross-sectional data indicate that essential workers in the COVID-19 era face increased mental health risks. This study longitudinally examined clinical symptoms of generalized anxiety disorder, depression, and posttraumatic stress disorder (PTSD) among U.S. essential workers, including health care workers and workers in indispensable occupations such as manufacturing, food industry, construction, transportation, hospitality, and emergency services, during the COVID-19 pandemic. The authors anticipated high symptom levels and greater symptom severity among women versus men and among younger adults compared with older adults. Analyses also explored the association between COVID-19 vaccination status and clinical symptoms. METHODS: This four-wave online survey study assessed clinical symptoms in a convenience sample of 4,136 essential workers at baseline and 14, 30, and 90 days between August and December 2021. Symptoms of anxiety, depression, and PTSD were measured with the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Primary Care PTSD Screen instruments, respectively. RESULTS: At every time point, 74%-78% of respondents reported symptoms of anxiety and depression, which were highest among younger adults (ages 18-22 years), females, and transgender respondents. Vaccinated participants had slightly higher symptom levels than unvaccinated respondents. Rates of clinical symptoms did not change significantly over time. CONCLUSIONS: Essential workers consistently reported symptoms of generalized anxiety, depression, or PTSD, especially younger adult, female, and transgender participants. The overwhelming and unprecedented nature of the COVID-19 pandemic underscores the need to offer mental health care to essential workers, especially those in these subgroups. Employers and administrators should support and proactively encourage employees to access care when needed.

State Cannabis Legalization and Cannabis Use Disorder in the US Veterans Health Administration, 2005 to 2019.

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.

Fentanyl withdrawal: Understanding symptom severity and exploring the role of body mass index on withdrawal symptoms and clearance.

BACKGROUND AND AIMS: Fentanyl is a highly lipophilic mu opioid receptor agonist, increasingly found in heroin and other drug supplies, that is contributing to marked increases in opioid-related overdose and may be complicating treatment of opioid use disorder (OUD). This study aimed to measure the influence of body mass index (BMI) on fentanyl withdrawal and clearance. DESIGN, SETTING, PARTICIPANTS: This secondary analysis, from a 10-day inpatient study on the safety and efficacy of sublingual dexmedetomidine for opioid withdrawal, includes participants with OUD (n = 150) recruited from three sites in New York, New Jersey and Florida, who were maintained on oral morphine (30 mg four times per day) for 5 days before starting study medication. Most participants (n = 118) tested positive for fentanyl on admission to the inpatient unit. MEASUREMENTS: Urine toxicology and opioid withdrawal symptoms [Clinical Opioid Withdrawal Scale (COWS) and Short Opiate Withdrawal Scale (SOWS)] were assessed daily. The present analysis includes data on opioid withdrawal from days 1-5 of stabilization and urine toxicology data from days 1-10. FINDINGS: Fentanyl status at admission was not significantly associated with COWS or SOWS scores after adjusting for sex, site and polysubstance use. Participants classified as overweight or obese (n = 66) had significantly higher odds of testing positive for fentanyl across days 1-10 [odds ratio (OR) = 1.65; P < 0.01] and higher SOWS maximum scores across morphine stabilization (P < 0.05) compared to those with a healthy BMI (n = 68). CONCLUSIONS: Among inpatients with opioid use disorder, fentanyl status does not appear to be statistically significantly associated with Clinical Opioid Withdrawal Scale and Short Opiate Withdrawal Scale mean and maximum scores. High body mass index status (overweight or obese) appears to be an important predictor of slower fentanyl clearance and higher Short Opiate Withdrawal Scale maximum scores across the inpatient period than lower body mass index status.

Medicaid Expansion and Racial-Ethnic Health Care Coverage Disparities Among Low-Income Adults With Substance Use Disorders.

OBJECTIVE: In light of historical racial-ethnic disparities in health care coverage, the authors assessed changes in coverage in nationally representative samples of Black, White, and Hispanic low-income adults with substance use disorders after the 2014 Affordable Care Act Medicaid expansion. METHODS: Data from 12 years of the annual National Survey on Drug Use and Health (2008-2019) identified low-income adults ages 18-64 years with alcohol, cannabis, cocaine, or heroin use disorder (N=749,033). Trends in coverage focused on non-Hispanic Black, non-Hispanic White, and Hispanic individuals. Age- and sex-adjusted difference-in-differences analysis assessed effects of expansion state residence on insurance coverage for the three groups. RESULTS: Before Medicaid expansion (2008-2013), 38.5% of Black, 37.6% of White, and 51.2% of Hispanic low-income adults with substance use disorders were uninsured. After expansion (2014-2019), these proportions significantly declined for Black (24.2%), White (22.0%), and Hispanic (34.5%) groups. Decreases in rates of individuals without insurance and increases in Medicaid coverage tended to be more pronounced for those in expansion states than for those in nonexpansion states. In nonexpansion states, the proportions of those without insurance significantly decreased among Black and White individuals but not among Hispanic individuals. Proportions receiving past-year substance use treatment did not significantly change and remained low postexpansion: Black, 10.7%; White, 14.6%; and Hispanic, 9.0%. CONCLUSIONS: After Medicaid expansion, coverage increased for low-income Black, White, and Hispanic adults with substance use disorders. For all three groups, Medicaid coverage disproportionately increased among those living in expansion states. However, coverage remained far from universal, especially for Hispanic adults with substance use disorders.

Healthcare coverage and service access for low-income adults with substance use disorders.

INTRODUCTION: Although health coverage facilitates service access to adults in the general population, uncertainty exists over the extent to which this relationship extends to low-income adults with substance use disorders. METHODS: The health status and service use patterns of low-income adults with substance use disorders who had continuous, discontinuous, and no past year health coverage were compared using data from the 2015-2019 National Survey on Drug Use and Health (NSDUH). The NSDUH is a nationally representative survey of the civilian non-institutionalized population. RESULTS: In the weighted sample (unweighted n = 9243), approximately 65.66% of low-income adults with substance use disorders had continuous coverage, 17.03% had discontinuous coverage, and 17.31% had no insurance coverage during the past year. Although few group differences were observed in self-reported health status, the uninsured group compared to the discontinously and continuously covered groups, respectively, was less likely to report a past year substance use treatment visit (11.03% vs. 14.83% vs. 15.61%), an outpatient care visit (53.39% vs. 71.27% vs. 79.04%), an emergency department visit (33.33% vs. 45.76% vs. 45.57%), or an inpatient admission (9.24% vs. 15.11% vs. 15.58%). CONCLUSIONS: Although the cross sectional design limits causal inferences, the correlations between lacking health insurance and low rates of substance use treatment and healthcare use raise the possibility that increasing healthcare coverage might increase access to substance use treatment and other needed healthcare services for low-income adults with substance use disorders.

Hearing Rehabilitative Treatment for Older Adults With Comorbid Hearing Loss and Depression: Effects on Depressive Symptoms and Executive Function.

OBJECTIVES: Recent research has revealed important neural and psychiatric consequences of hearing loss (HL) in older adults. This pilot study examined the neural effects of HL and the impact of hearing aids on neuropsychiatric outcomes in major depressive disorder (MDD). DESIGN: Twelve-week, double-blind, randomized controlled trial. PARTICIPANTS/INTERVENTION: N = 25 (≥60 years) with MDD and moderate-profound HL were randomized to receive hearing aids (100% gain targets) or sham hearing aids (flat 30 dB HL) in addition to psychiatric treatment-as-usual. MEASUREMENTS: Depressive symptoms (Hamilton Rating Scale for Depression [HRSD]), executive functioning (NIH Toolbox Flanker), integrity of auditory brain areas (structural MRI, diffusion tensor imaging). RESULTS: At baseline, worse speech discrimination was associated with auditory cortical thinning (Left anterior transverse temporal gyrus: r = 0.755, p = 0.012) and lower integrity of the superior longitudinal fasciculus (FA: Left r = 0.772, p = 0.025, Right r = 0.782, p = 0.022). After 12-weeks, hearing aids were effective at improving hearing functioning (Hearing Handicap for the Elderly: active -12.47 versus sham -4.19, t = -2.64, df = 18, p = 0.016) and immediate memory (active +14.9 versus sham +5.7, t = 2.28, df = 16, p = 0.037). Moderate improvement was observed for hearing aids on executive functioning but did not reach statistical significance (Flanker: active +4.8 versus sham -2.4, t = 1.95, df = 15, p = 0.071). No significant effect on depression was found (HRSD: active -5.50 versus sham -7.32, t = 0.75, df = 19, p = 0.46). CONCLUSIONS: HL can affect brain regions important for auditory and cognitive processing, and hearing remediation may have beneficial effects on executive functioning in MDD. Future studies may evaluate whether impairment in cognitive control consequent to HL may be an important risk mechanism for MDD.

Non-abstinent treatment outcomes for cannabis use disorder.

BACKGROUND: Abstinence remains a standard outcome for potential treatment interventions for Cannabis Use Disorder (CUD). However, there needs to be validation of non-abstinent outcomes. This study explores reductions in self-reported days of use as another viable outcome measure using data from three completed randomized placebo-controlled clinical trials of pharmacological interventions for CUD. METHODS: The three trials tested the effect of quetiapine (QTP, n = 113); dronabinol (DRO, n = 156); and lofexidine + dronabinol (LFD, n = 122). Self-reported cannabis use was categorized into three use-groups/week: heavy (5-7 days/week), moderate (2-4 days/week) and light use (0-1 days/week). Multinomial logistic regressions analyzed the treatment by time effect on the likelihood of light and moderate use compared to heavy use in each study. RESULTS: Across the three trials, there was no significant overall time-by-treatment interaction (QTP: p = .06; DRO: p = .15; LFD: p = .21). However, the odds of moderate compared to heavy use were significantly higher in treatment than in placebo groups starting around the midpoint of each trial. No treatment differences were found between the odds of light compared to heavy use. CONCLUSIONS: While study-end abstinence rates have been a standard treatment outcome for CUD trials, reduction from heavy to moderate use has not been standardly assessed. During the last several weeks of each trial, those on active medication were more likely to move from heavy to moderate use, which suggests that certain medications may be more impactful than previously assessed. Future studies should determine if this pattern is associated with less CUD severity and/or improved quality of life.

An open-label pilot study of pregabalin pharmacotherapy for alcohol use disorder.

Background: There is a need for alcohol use disorder (AUD) pharmacotherapy that can be administered to actively drinking outpatients. Pregabalin, a gabapentoid anticonvulsant, has preliminary evidence supporting effects on alcohol withdrawal and AUD.Objectives: To evaluate the safety, tolerability, and optimal dosing of pregabalin for treating AUD.Methods: In an open-label, 8-week, outpatient trial of eighteen adults (nine women) with AUD, participants were titrated to 600 mg/day (or the maximum tolerated dose) over 3 weeks and then maintained for 5 weeks.Results: The majority (11/14, 78.6%) of participants with at least one-week of medication exposure achieved a maximum dose of 600 mg/day. Mean retention was 6.8 weeks (SD = 2.6). Eighty percent (12/15) of participants with post-enrollment data reported any adverse effects during the trial; and for those reporting adverse effects the most common were drowsiness (33.3%, 4/12), and fogginess (25%, 3/12), dizziness (25%, 3/12), and insomnia (25%, 3/12). Two participants discontinued study medication due to adverse effects and one had a dose reduction. Mean Heavy Drinking Days (HDD)/week decreased significantly by 3.43 days (SD = 2.47; median (IQR) = 4.00 (1.00 to 5.50)); Wilcoxon signed rank test statistic ((S) = 49.5, p = .0006). Mean proportion of HDD significantly decreased on average by 48.7% (SD = 35.1%; median (IQR) = 57.1% (14.3% to 78.6%)). The proportion of abstinent days increased significantly on average by 36.1% (SD = 35.0%; median (IQR) = 17.9% (14.3% to 75.0%); S = 49.5, p = .0005).Conclusions: Pregabalin treatment of AUD appears to be safe and well tolerated in doses up to 600 mg per day.Trial Registration: clinicaltrials.gov identifier: NCT03256253.

Effects of the ACA on Health Care Coverage for Adults With Substance Use Disorders.

OBJECTIVE: The authors assessed changes in health care coverage in nationally representative samples of low- and middle-income adults with and without substance use disorders following the 2014 Affordable Care Act marketplace launch and Medicaid expansion. METHODS: Data from the 2012-2018 (N=407,985) National Survey on Drug Use and Health identified low- and middle-income nonelderly adults with alcohol, marijuana, cocaine, or heroin use disorders. A sociodemographically adjusted difference-in-differences analysis assessed the trends in Medicaid and individually purchased private insurance between adults with and without substance use disorders. RESULTS: Between 2012-2013 and 2015-2016, the percentages without health insurance significantly declined for adults with substance use disorders (from 27.8% to 18.7%) and for those without these disorders (from 22.6% to 14.6%). These trends were related to gains in Medicaid and in individually purchased private insurance but not to gains in employer-based private insurance coverage. Between 2015-2016 and 2017-2018, however, the percentages without health insurance among adults with substance use disorders (18.7% to 18.4%) and without these disorders (14.7% to 14.7%) was little changed. CONCLUSIONS: With insurance gains having stalled and the downturn of the U.S. economy, there is renewed urgency to extend health care coverage to middle- and low-income adults with substance use disorders that meets their substance use and general health needs.

Civil Commitment for Substance Use Disorders: A National Survey of Addiction Medicine Physicians.

BACKGROUND: Civil commitment (CC) for substance use disorders (SUDs) is a legal mechanism, initiated by family members, healthcare professionals, or others, that compels individuals with substance use problems into involuntary treatment. With the recent rise of US overdose deaths, more states are considering these laws. Yet little is known about physicians' perspectives regarding CC in treating patients with SUDs. METHODS: We conducted a web-based survey of American Society of Addiction Medicine (ASAM) physician members regarding their awareness of, attitudes towards, and experiences with CC for adults with SUDs. RESULTS: One hundred sixty-five addiction physicians completed the survey; 60.7% favored, 21.5% opposed, and 17.8% were unsure regarding CC for SUDs. More than a third (38.4%) were unfamiliar with these laws and more than a quarter (28.8%) were unsure if CC for SUDs was permitted in their state. Support for CC was strongest for SUDs involving heroin (79.0%), alcohol (74.7%), and nonheroin opioids (74.7%). Those opposing CC were more likely to believe it would jeopardize patient rapport (P < 0.001), would be ineffective for unmotivated individuals (P < 0.001), and should only be permitted for certain substances (P = 0.007). A majority of respondents endorsed the need for more clinician education (91.5%) and research (87.1%) on this topic. CONCLUSIONS: Although most addiction physicians in this study approve of CC for SUDs, enthusiasm for this compulsory intervention is mixed with strongest support for patients with opioid and alcohol use disorders. At the same time, many respondents are unfamiliar with these laws and most believe more education and research are needed.

Open-label pilot study of lisdexamfetamine for cocaine use disorder.

Background: Cocaine use disorder (CUD) is a substantial public health problem with no FDA-approved medication treatments. Psychostimulants have shown promise as pharmacotherapy for CUD. Lisdexamfetamine, a novel prodrug psychostimulant, is roughly 40-50% as potent as dextroamphetamine.Objectives: To evaluate the safety, tolerability, and optimal dosing of lisdexamfetamine for treating CUD.Methods: Open-label, 8-week trial of 17 CUD adults. Participants were titrated to the maximum tolerated dose of 140 mg over 2-week period and maintained for 4 weeks, followed by a two-week taper period. The primary outcome measures were the maximum daily dose achieved during the study period and tolerability as measured by medication-related study drop-out.Results: Among the 16 participants with post-enrollment data, the mean dose of lisdexamfetamine achieved was 118.1 mg (standard deviation (SD) = 40.4), mean retention was 6.5 weeks (SD = 2.0), and no participants discontinued study medication due to adverse effects. Four participants had dose reductions due to adverse effects and continued in the trial. Six participants (37.5%) were abstinent for the last 3 weeks of their study participation. Mean dollars of cocaine spent per day significantly decreased from $19.72 at baseline to $7.57 during the last 3 weeks of study participation (t15 = 3.60, p = .003). The mean percent of using days significantly decreased from 25% at baseline to 12% during the last 3 weeks of study participation (t15 = 3.33, p = .005).Conclusion: The use of lisdexamfetamine for CUD in doses ranging to 140 mg daily was safe and generally well tolerated.

Predicting response to cognitive training for schizophrenia using results from two studies with different outcomes.

BACKGROUND: Collaborative data sharing between research groups provides an opportunity to explore the basis for the heterogeneity in cognitive training outcomes reported in the schizophrenia literature. The current analyses focused on the contribution of site and participant characteristics to these heterogeneous outcomes. METHODS: Data from two independent studies, from New York (NY) and Los Angeles (LA), were combined to yield a sample of 132 outpatient adults with schizophrenia/schizoaffective disorder. While similar treatment doses, cognitive exercises and outcome measures were used, sites differed in use of coaching, group discussion and compensation. Between-site differences in participant demographic and baseline clinical characteristics were tested. Regression examined predictors of change in cognition (MCCB) and functional capacity (UPSA) which could explain site differences in treatment effects. RESULTS: Medium to large treatment effect size differences in MCCB and UPSA favored the NY site over LA. When the studies were combined, the effect of site was significant for both outcomes with a medium effect size difference. After controlling for background characteristics, the effect of site was reduced for both outcomes, but remained significant for cognition. Improvement in UPSA was associated with better baseline MCCB (p < 0.001), lower baseline UPSA (p < 0.001) and younger age (p = 0.019). The overall model with site, baseline scores, and participant background characteristics explained about 30% to 40% of the variance in outcomes. DISCUSSION: Participant and treatment characteristics are both predictive of outcomes, but treatment characteristics may be more consequential to cognitive gain, while participant characteristics may be more consequential to change in functional capacity.

Lorcaserin treatment for extended-release naltrexone induction and retention for opioid use disorder individuals: A pilot, placebo-controlled randomized trial.

BACKGROUND: Opioid Use Disorder (OUD) is a significant public health problem associated with severe morbidity and mortality. While effective pharmacotherapies are available, limitations exist with each. Induction onto extended-release naltrexone (XR-NTX) is more difficult than initiation of buprenorphine or methadone, even in inpatient settings, as it is recommended that patients remain abstinent for at least 7 days prior to initiating XR-NTX. The purpose of this trial was to determine if lorcaserin, a 5HT2c agonist, improves outpatient XR-NTX induction rates. METHODS: An 8-week trial beginning with a brief detoxification period and induction onto XR-NTX. Sixty participants with OUD were enrolled in the trial, with 49 participants at the initiation of detoxification randomized to lorcaserin or placebo for 39 days. Additionally, ancillary medications were provided. The primary outcome was the proportion of participants inducted onto the first XR-NTX injection. Secondary outcomes were withdrawal severity (measured by COWS and SOWS) prior to the first injection and the proportion of participants receiving the second XR-NTX injection. RESULTS: The proportion of participants inducted onto the first (lorcaserin: 36 %; placebo: 44 %; p = .67) and the second XR-NTX injection (lorcaserin: 27 %; placebo: 31 %; p = .77) was not significantly different between treatment arms. Prior to the first injection, withdrawal scores did not significantly differ between treatment arms over time (treatment*time interaction COWS: p = .11; SOWS: p = .39). CONCLUSIONS: Lorcaserin failed to improve outpatient XR-NTX induction rates. Although this study is small, the findings do not support the use of lorcaserin in promoting induction onto XR-NTX or in mitigating withdrawal symptoms.

Development, Psychopathology, and Ethnicity II: Psychiatric Disorders Among Young Adults.

OBJECTIVE: To estimate the prevalence of psychiatric disorders and their continuity since childhood among young adults from the same ethnic group living in 2 low-income contexts. METHOD: Young adults (N = 2,004; ages 15-29) were followed (82.8% retention) as part of the Boricua Youth Study, a study of Puerto Rican youths recruited at ages 5-13 in the South Bronx (SBx), New York, and Puerto Rico (PR). We estimated prevalence (lifetime; past year) of major depressive (MDD), mania, hypomania, generalized anxiety (GAD), tobacco dependence, and any other substance use disorders (SUD). RESULTS: The prevalence of every disorder was higher among young women from the SBx compared with those from PR (eg, 9.2% versus 4.1% past-year SUD; 14% versus 6.8% for MDD/GAD). Among SBx young men, tobacco dependence and illicit SUD were elevated. Across both contexts, men had higher adjusted odds of illicit SUD than women, while women had higher GAD than men. MDD did not differ by gender. Young adulthood disorders (except for alcohol use disorder and GAD) followed childhood disorders. For example, childhood externalizing disorders preceded both MDD (young men and women) and illicit SUD (young women only). CONCLUSION: Young women raised in a context where adversities like ethnic discrimination concentrate are at high risk for psychiatric disorders. In certain high-poverty contexts, young men may present with MDD as often as women. Interventions to prevent psychiatric disorders may need to address gender-specific processes and childhood disorders. However, SUD prevention among young men may need to address other factors.

Slowed Processing Speed Disrupts Patient Expectancy in Late Life Depression.

OBJECTIVE: Slowed processing speed and executive dysfunction are associated with poor outcomes in Late Life Depression (LLD), though it is unclear why. We investigated whether these variables interfere with the development of positive treatment expectancies in an antidepressant trial. METHODS: Depressed older subjects were randomized to Open (intended to increase patient expectancy) or Placebo-controlled (termed 'Hidden,' intended to decrease expectancy) administration of antidepressant medication for 8 weeks. Analysis of covariance analyzed the between-group difference on expectancy (Credibility and Expectancy Scale [CES]) and depression (Hamilton Rating Scale for Depression [HRSD], Clinical Global Impressions [CGI] Severity). Moderator analyses examined whether these Open versus Hidden differences varied based on higher versus lower processing speed and executive function. RESULTS: Among the 108 participants, a significant between-group difference was observed on expectancy (effect size [ES, Cohen's d] = 0.51 on CES Item 2; ES = 0.64 on Item 4), indicating the manipulation was effective. Processing speed as measured by the Stroop Color-Word Test (number color-words named in congruent condition) was a significant moderator of the Open versus Hidden effect on expectancy. Depressive symptom improvement was greater on average for Open versus Hidden participants who received active drug (CGI-severity ES = 1.25, HRSD ES = 0.41), but no neurocognitive moderators of the between-group difference reached statistical significance. CONCLUSIONS: Slowed processing speed impairs the development of expectancies in antidepressant trials for LLD, which may help explain lower antidepressant response among older adults. Future studies may address whether interventions to optimize treatment expectancies are capable of improving treatment outcomes.

The COVID-19 Pandemic as a Traumatic Stressor: Mental Health Responses of Older Adults With Chronic PTSD.

OBJECTIVE: Individuals with post-traumatic stress disorder (PTSD) who experience additional traumas or stressful life events may undergo symptomatic worsening, but no data exist on whether exposure to the COVID-19 pandemic in a high infection area worsens mental health among older adults with chronic PTSD. METHODS: Seventy-six older adults (N = 46 with PTSD and N = 30 trauma-exposed comparison subjects [TE]) for whom prepandemic data were available were interviewed between April 1 and May 8, 2020 to quantify depressive (Hamilton Rating Scale for Depression [HRSD]) and PTSD symptom (Post-traumatic Stress Disorder Checklist [PCL-5]) levels. Group differences in baseline characteristics as well as pre-post pandemic symptom levels were examined, and participant characteristics were assessed as moderators of symptom change. RESULTS: Compared to TEs, individuals with PTSD more often reported living alone and experiencing a physical illness (χ2 = 5.1, df = 1, p = 0.02). PCL-5 scores among individuals with PTSD decreased during the COVID-19 pandemic by 7.1 points (t(69) = -3.5, p = 0.0008), whereas the TE group did not change significantly. Overall no significant differences in HRSD were found between groups, but a race or ethnicity variable was found to moderate HRSD symptom change. Non-black or Hispanic individuals with PTSD experienced significantly increased HRSD scores during the pandemic compared to black or Hispanic PTSD participants. CONCLUSION: The findings are indicative of complexity in the responses of older individuals with PTSD to further stressful life events as well as possibly unique aspects to the COVID-19 pandemic as a stressor. Sources of resilience may exist based on experience with prior traumas as well as increasing age promoting more adaptive coping styles.

Impulsiveness as a moderator of amphetamine treatment response for cocaine use disorder among ADHD patients.

BACKGROUND: Amphetamines are a first-line treatment for ADHD and have shown promise for the treatment of cocaine use disorder (CUD), both alone and with comorbid ADHD. Impulsiveness is a key aspect of both ADHD and substance use disorders. We sought to understand the role of baseline impulsiveness in the treatment of comorbid CUD and ADHD. METHODS: In a post hoc analysis (N = 76) of a 14-week, double-blind, randomized, placebo-controlled trial of mixed amphetamine salts-extended release (MAS-ER) for comorbid ADHD and CUD, we examined the relationship between treatment response and participants' baseline Barratt Impulsiveness Scale (BIS-11) score by comparing those with scores below versus above the median. In the original trial, participants received daily 60 mg MAS-ER, 80 mg MAS-ER, or placebo, in conjunction with cognitive behavioral therapy. RESULTS: The odds of a cocaine-abstinent week over time were significantly greater in the high BIS group compared to the low BIS group, both when missing data was treated as missing (p = .0155; OR = 1.23, 95% CI: 1.13, 1.35 versus OR = 1.04, 95% CI: 0.95, 1.15) and when missing data was treated as cocaine-positive (p = .003; OR = 1.15, 95% CI: 1.06, 1.24 versus OR = 0.96, 95% CI: 0.88, 1.05). CONCLUSIONS: The results show an association between higher within-group trait impulsiveness, as measured by the BIS-11, and response to MAS-ER for CUD in a cohort with comorbid ADHD. This result further demonstrates that impulsiveness is an important factor when considering treatment options for patients with CUD and that higher baseline impulsiveness may predict response to treatment with psychostimulants for CUD.