COVID-19-Related Financial Hardship Is Associated With Depression and Anxiety in Substance Use Treatment Across Gender and Racial Groups.

ABSTRACT: Many individuals lost their employment during the COVID-19 pandemic and experienced financial hardship. These experiences may increase risk for co-occurring conditions, including substance use disorders (SUDs) and related symptoms of depression and anxiety. This study aimed to examine the associations between COVID-19-related financial hardship and/or job loss and co-occurring symptoms, across gender and racial groups. Respondents (N = 3493) included individuals entering SUD treatment in the United States in March-October of 2020. Results demonstrated that COVID-19-related financial hardship and unemployment in the household was associated with greater depression and anxiety severity among people in SUD treatment (p's < 0.05). Our findings highlight financial hardship and loss of employment as risk factors for co-occurring depression and anxiety. However, additive effects between marginalized identity status and COVID-19 economic hardship on co-occurring symptoms were not observed.

Intersectional Risk and the Significant Gap in Care for Persons with Co-occurring Chronic Pain and Opioid Withdrawal.

OBJECTIVES: Persons with chronic pain and women tend to enter treatment for opioid use disorder with greater opioid withdrawal severity than persons without chronic pain and men, respectively. This study examined characteristics of facilities with opioid withdrawal treatment, including gender-based services, as a function of whether they reported having a tailored pain management program. METHODS: The National Survey of Substance Abuse Treatment Services 2020 was used to examine 3942 facilities with opioid withdrawal treatment in the United States. Using a multivariable binary logistic regression model, facilities were examined for the presence of a tailored program for individuals with co-occurring pain. Regional location of the facility, ownership status, and availability of tailored gender programs, nonhospital residential services, and outpatient services served as independent variables in the analysis. RESULTS: A slight majority of the sample had a program for both adult men and adult women (n = 2010, 51.0%). Most facilities had outpatient services (n = 3289, 83.4%) and did not have a tailored program for addressing co-occurring pain (n = 2756, 69.9%). Binary logistic regression analysis showed that among opioid withdrawal facilities, programs with nonhospital residential services, government or private nonprofit funding, or tailored gender programming had higher odds of reporting having a tailored program for pain and substance use disorder. Facilities in the Western United States were most likely to have tailored programs for pain and substance use disorder. CONCLUSIONS: Future research should investigate what support patients may receive and how to better scale access to pain management during opioid withdrawal treatment.

Knowledge, Preference, and Adverse Effects of Xylazine Among Adults in Substance Use Treatment.

This cross-sectional study evaluates aspects of xylazine adulteration of opioids among individuals entering substance use disorder treatment.

The association of pain impact and sleep disruption with opioid withdrawal during opioid-use disorder treatment.

AIMS: Persons with opioid-use disorder (OUD) often experience opioid withdrawal and opioid craving, which can drive continued opioid use and treatment discontinuation. In addition, hyperalgesia is common among persons with OUD, yet few studies have examined the role of pain impact during OUD treatment. The purpose of the present study was to test whether opioid withdrawal and craving were elevated in the context of greater pain impact (i.e. greater pain intensity and interference), and whether these associations changed throughout treatment. METHODS: Participants in residential OUD treatment (n = 24) wore wrist actigraphy to measure sleep and completed daily measures of pain impact, opioid withdrawal and opioid craving for up to 28 days. Mixed effects models were used to examine whether daily elevations in pain impact and sleep continuity were associated with withdrawal severity and opioid craving. RESULTS: Elevations in withdrawal, but not craving, occurred on days when individuals reported higher scores on the pain impact scale. Associations between pain impact and withdrawal were present throughout treatment, but stronger during early treatment. In contrast, both withdrawal and opioid craving were elevated following nights of greater wake after sleep onset and awakenings, but these findings were often more pronounced in early treatment. CONCLUSIONS: Pain impact and sleep disturbance are 2 factors associated with opioid withdrawal and opioid craving. Novel pharmacotherapies and scalable adjunctive interventions targeting sleep and pain impact should be tested in future work to improve OUD treatment outcomes.

A brief measure of non-drug reinforcement: Association with treatment outcomes during initial substance use recovery.

BACKGROUND: Translational research demonstrates that drug use is inversely associated with availability and engagement with meaningful non-drug reinforcers. Evaluation of non-drug reinforcement in treatment-receiving clinical populations is limited, likely owing to the time intensive nature of existing measures. This study explores the association of non-drug reinforcers with treatment outcomes using a novel, brief measure of past month non-drug reinforcement quantifying three elements: relative frequency, access, and enjoyability. METHODS: Respondents enrolled in substance use treatment (residential, intensive outpatient, and medically managed withdrawal) in clinics across the United States (N = 5481) completed standardized assessments of non-drug reinforcement and treatment outcomes (i.e., return to use and life satisfaction) one-month after treatment discharge. Non-drug reinforcement measures (availability, engagement, enjoyability) were used as predictors of return to use and life satisfaction using generalized linear models. RESULTS: Non-drug reinforcement indices were associated with return to use and life satisfaction in unadjusted models (e.g., 12.4 % versus 58.3 % return to use for those with the highest and lowest availability, respectively). Consistent results were observed in models adjusted for sociodemographic variables and risk factors (i.e., sleep disturbance, anhedonia, stress). Comparisons by drug class generally showed lower non-drug reinforcement among patients reporting heroin or methamphetamine as their primary drug. CONCLUSIONS: Results highlight the importance of non-drug reinforcement during the first month following treatment. Rapid measurement of non-drug reinforcement in stepped care settings may illuminate critical deficits in early stages of behavior change, identify those at greatest risk for return to use, and provide targets for treatment to improve recovery trajectories.

Age moderates the association of optimism on craving during substance use disorder treatment.

BACKGROUND: Optimism, characterized by a positive expectancy toward future outcomes, has garnered attention for its potential role in influencing well-being and may be a protective factor in substance use disorder (SUD) treatment. This study evaluated the relationship of optimism and craving among those in substance use disorder SUD treatment. METHODS: Drawing from a cohort of 4201 individuals in residential SUD treatment programs, this study used both cross-sectional and longitudinal assessment to examine tonic (steady-state) and cue-induced (phasic) cravings across individuals primarily using eight classes of substances. Previous research established that optimism increases during adulthood and peaks during an individual's 50s. This study sought to establish if the association between optimism and craving is moderated by age during the first week of treatment and if that relationship changes over the course of treatment both within and between-person. RESULTS: This study found a negative correlation between optimism and craving intensity. Elevated optimism scores correlated with substantially reduced levels of both tonic (ß = -0.31, p < 0.001) and cue-induced (ß = -0.29, p < 0.001) cravings. Age was a significant moderator of the relationship between optimism and craving such that as individuals age, the potency of optimism in mitigating cravings gradually attenuates (interaction for tonic craving: ß = 0.06, p < 0.001; interaction for cue-induced craving: ß = 0.05, p < 0.001). Reflected in the fact that in older individuals' cravings tended to converge toward lower or moderate levels, regardless of their optimism scores. CONCLUSIONS: By delineating the contemporaneous association between high optimism and lower cravings, the study suggests that interventions aimed at fostering optimism may represent an avenue to improve the effectiveness of SUD treatment, especially in emerging adults.

Suvorexant alters dynamics of the sleep-electroencephalography-power spectrum and depressive-symptom trajectories during inpatient opioid withdrawal.

STUDY OBJECTIVES: Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine the effects of suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, and to examine their association with withdrawal severity and depressive symptoms. METHODS: Participants with opioid use disorder (N = 38: age-range:21-63, 87% male, 45% white) underwent an 11-day buprenorphine taper, in which they were randomly assigned to suvorexant (20 mg [n = 14] or 40 mg [n = 12]), or placebo [n = 12], while ambulatory sleep-EEG data was collected. Linear mixed-effect models were used to explore: (1) main and interactive effects of drug group, and time on sleep-EEG band power, and (2) associations between sleep-EEG band power change, depressive symptoms, and withdrawal severity. RESULTS: Oscillatory spectral power tended to be greater in the suvorexant groups. Over the course of the study, decreases in delta power were observed in all study groups (ß = -189.082, d = -0.522, p = <0.005), increases in beta power (20 mg: ß = 2.579, d = 0.413, p = 0.009 | 40 mg ß = 5.265, d = 0.847, p < 0.001) alpha power (20 mg: ß = 158.304, d = 0.397, p = 0.009 | 40 mg: ß = 250.212, d = 0.601, p = 0.001) and sigma power (20 mg: ß = 48.97, d = 0.410, p < 0.001 | 40 mg: ß = 71.54, d = 0.568, p < 0.001) were observed in the two suvorexant groups. During the four-night taper, decreases in delta power were associated with decreases in depressive symptoms (20 mg: ß = 190.90, d = 0.308, p = 0.99 | 40 mg: ß = 433.33, d = 0.889 p = <0.001), and withdrawal severity (20 mg: ß = 215.55, d = 0.034, p = 0.006 | 40 mg: ß = 192.64, d = -0.854, p = <0.001), in both suvorexant groups and increases in sigma power were associated with decreases in withdrawal severity (20 mg: ß = -357.84, d = -0.659, p = 0.004 | 40 mg: ß = -906.35, d = -1.053, p = <0.001). Post-taper decreases in delta (20 mg: ß = 740.58, d = 0.964 p = <0.001 | 40 mg: ß = 662.23, d = 0.882, p = <0.001) and sigma power (20 mg only: ß = 335.54, d = 0.560, p = 0.023) were associated with reduced depressive symptoms in the placebo group. CONCLUSIONS: Results highlight a complex and nuanced relationship between sleep-EEG power and symptoms of depression and withdrawal. Changes in delta power may represent a mechanism influencing depressive symptoms and withdrawal.

Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment.

Allelic variations in the A118G SNP of the OPRM1 gene change opioid signaling; however, evaluations of how allelic differences may influence opioid effects are lacking. This human laboratory paradigm examined whether the AA versus AG/GG genotypes determined opioid response profiles. Individuals with limited opioid exposure (N = 100) completed a five-day within-subject, double-blind, placebo-controlled, residential study. Participants were admitted (Day 1), received 4 mg hydromorphone (Day 2) and 0 mg, 2 mg and 8 mg hydromorphone in randomized order (Days 3-5) and completed self-reported visual analog scale (VAS) ratings and Likert scales, observed VAS, and physiological responses at baseline and for 6.5 h post-dose. Outcomes were analysed as peak/nadir effects over time as a function of genotype (available for N = 96 individuals; AG/GG = 13.5%, AA = 86.4%). Participants with AG/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA. Persons with AG/GG were less physiologically reactive as determined by diastolic blood pressure and heart rate, but had more changes in core temperature compared with those with AA. Persons with AA also demonstrated more prototypic agonist effects across doses; persons with AG/GG showed limited response to 2 mg and 4 mg. Data suggest persons with AG/GG genotype experienced more pleasant and fewer unpleasant responses to hydromorphone relative to persons with AA. Future studies should replicate these laboratory findings in clinical populations to support a precision medicine approach to opioid prescribing.

Fentanyl Absorption, Distribution, Metabolism, and Excretion: Narrative Review and Clinical Significance Related to Illicitly Manufactured Fentanyl.

OBJECTIVES: This narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly manufactured fentanyl (IMF). RESULTS: Fentanyl is highly lipophilic, lending itself to rapid absorption by highly perfused tissues (including the brain) before redistributing from these tissues to muscle and fat. Fentanyl is eliminated primarily by metabolism and urinary excretion of metabolites (norfentanyl and other minor metabolites). Fentanyl has a long terminal elimination, with a documented secondary peaking phenomenon that can manifest as "fentanyl rebound." Clinical implications in overdose (respiratory depression, muscle rigidity, and "wooden chest syndrome") and opioid use disorder treatment (subjective effects, withdrawal, and buprenorphine-precipitated withdrawal) are discussed. The authors highlight research gaps derived from differences in medicinal fentanyl studies and IMF use patterns, including that medicinal fentanyl studies are largely conducted with persons who were opioid-naive, anesthetized, or had severe chronic pain and that IMF use is characterized by supratherapeutic doses and frequent and sustained administration patterns, as well as adulteration with other substances and/or fentanyl analogs. CONCLUSIONS: This review reexamines information yielded from decades of medicinal fentanyl research and applies elements of the pharmacokinetic profile to persons with IMF exposure. In persons who use drugs, peripheral accumulation of fentanyl may be leading to prolonged exposure. More focused research on the pharmacology of fentanyl in persons using IMF is warranted.

Transgender individuals are at higher risk for suicidal ideation and preparation than cisgender individuals in substance use treatment.

Introduction: This study describes the differences and similarities in mental health, substance use, and substance use treatment outcomes between people presenting for SUD treatment who identified as transgender and those who identified as cisgender men or women. Methods: We compared 64 individuals who self-identified as transgender and presented for SUD treatment to samples of cisgender men and women (separately) matched based on propensity scores which were created based on sociodemographic factors known to influence both the nature of substance use and patterns of treatment engagement including age, education, race, stable housing, and employment status. Comparisons were made using χ2 tests and t-tests in over 150 variables collected at treatment intake regarding physical and mental health, substance use patterns, events that led to treatment, reasons for seeking treatment, and treatment outcomes. Results: The transgender sample endorsed six of the seven suicide-related items more often than at least one of the cisgender-matched samples. Furthermore, the transgender sample remained in treatment significantly longer (M = 32.3, SD = 22.2) than the cisgender male sample (M = 19.5, SD = 26.1, t = 2.17, p = 0.03). Discussion: This study is a first step into understanding gender minority population experiences during SUD treatment. While there was no significant difference between the cisgender and transgender samples on most variables, there was an elevated prevalence of suicidal ideation and behaviors in the transgender sample, which warrants further investigation.

Within subject, double blind, examination of opioid sensitivity in participant-reported, observed, physiologic, and analgesic outcomes.

Background: Inter-individual differences in opioid sensitivity may underlie different opioid risk profiles but have often been researched in persons who have current or past opioid use disorder or physical dependence. This study examined how opioid sensitivity manifests across various assessments of opioid effects in a primarily opioid-naïve population. Procedures: Data were harmonized from two within-subject, double-blind trials wherein healthy participants (N = 123) received placebo and 4 mg oral hydromorphone. Demographics, self-report ratings, observer ratings, physiological, and cold pressor measures were collected. Participants were categorized as being responsive or nonresponsive to the opioid dose tested and compared using mixed-models, Pearson product correlations, and paired t-tests. Findings: Participants were 49.6% female, mean 33.0 (SD=9.3) years old, and 44.7% Black/African American and 41.5% White, with 89.4% reporting no prior exposure to opioids. Within-subject sensitivity to opioids varied depending on the measure. One in five participants did not respond subjectively to the 4 mg hydromorphone dose based on their "Drug Effects" rating. Persons who were responsive showed more evidence of drug-dependent effects than did persons who were not responsive on ratings of Bad Effects (p= .03), feeling High (p= .01), Nausea (p= .03), pupil diameter (p< 0.01), and on the circular lights task (p< 0.001). Conclusions: This study provides initial evidence that the experience of opioids may be domain specific. Data suggest potentially clinically meaningful differences exist regarding opioid response patterns, evident following one dose among opioid inexperienced individuals.

The impact of opioid-stimulant co-use on tonic and cue-induced craving.

The twin opioid-stimulant epidemics have led to increased overdose deaths and present unique challenges for individuals entering treatment with opioid-stimulant polysubstance use. This study examined tonic and cue-induced craving as a primary outcome among persons in substance use treatment who reported primary substances of opioids, methamphetamine, or cocaine. The sample consisted of 1974 individuals in 55 residential substance-use treatment centers in the United States in 2021. Weekly surveys were delivered via a third-party outcomes tracking system, including measures of tonic and cue-induced craving. Initial comparisons on tonic and cue-induced craving were made among those who primarily used opioids, cocaine, or methamphetamine. Further, the effect of opioid/stimulant polysubstance use on tonic and cue-induced craving was evaluated using marginal effect regression models. Primary methamphetamine use was associated with decreased tonic craving compared to primary opioid use (ß = -5.63, p < 0.001) and primary cocaine use was also associate with decreased tonic craving compared to primary opioid use (ß = -6.14, p < 0.001). Primary cocaine use was also associated with lower cue-induced cravings compared to primary opioid use (ß = -0.53, p = 0.037). Opioid-methamphetamine polysubstance use was associated with higher tonic craving (ß = 3.81, p = <0.001) and higher cue-induced craving (ß = 1.55, p = 0.001); however, this was not the case for opioid-cocaine polysubstance use. The results of this study indicate that individuals who primarily use opioids and have secondary methamphetamine use experience higher cue-induced and tonic-induced craving, suggesting that these individuals may benefit from additional interventions that target craving and mitigate relapse risk and other negative sequelae.

Operational definition of precipitated opioid withdrawal.

Background: Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal. Methods: People (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA). Results: Within 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1-40, 41-80, and 81-100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal. Conclusion: Data suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal.

Latent patterns of sleep disturbance, pain impact, and depressive symptoms in residential substance use treatment.

AIM: Sleep disturbance, clinically significant pain, and depressive symptoms commonly occur together among individuals with substance use disorders. The purposes of the present study were to 1) identify subgroups of individuals with heterogenous patterns of pain, sleep disturbance, and depressive symptoms, and 2) identify demographic and clinical correlates of profile membership. MATERIAL AND METHODS: The present study assessed a sample (N = 8621) of individuals seeking residential substance use treatment in 2020 and 2021 in the United States. We examined whether unique sub-groups could be identified based on patterns of sleep disturbance, pain impact, and depressive symptoms during the first four weeks of treatment, using longitudinal latent profile analysis. Next, we explored demographic, substance use, and clinical correlates (i.e., distress intolerance) of profile membership, as well as whether profile membership was associated with treatment attrition. RESULTS: The identified classes were: 1) Low sleep disturbance, pain impact, and depressive symptoms, 2) High pain, remitting depressive symptoms, and mild sleep disturbance, 3) High depressive symptoms, low pain, and remitting sleep disturbance, and 4) High sleep disturbance, pain impact, and depressive symptoms. Individuals with high pain, depressive symptoms, and sleep disturbance were more likely to be older, use opioids as their primary substance, have high distress intolerance, and discontinue treatment. CONCLUSION: Results highlight the importance of comprehensive care and management of physical health conditions, particularly among older adults. Further, results highlight that distress intolerance may be a modifiable risk factor for co-occurring sleep disturbance, pain impact, and depressive symptoms.

Patterns of demoralization and anhedonia during early substance use disorder treatment and associations with treatment attrition.

BACKGROUND: Although depressive symptoms represent a promising therapeutic target to promote recovery from substance use disorders (SUD), heterogeneity in their diagnostic presentation often hinders the ability to effectively tailor treatment. We sought to identify subgroups of individuals varying in depressive symptom phenotypes (i.e., demoralization, anhedonia), and examined whether these subgroups were associated with patient demographics, psychosocial health, and treatment attrition. METHODS: Patients (N = 10,103, 69.2 % male) were drawn from a dataset of individuals who presented for admission to SUD treatment in the US. Participants reported on their demoralization and anhedonia approximately weekly for the first month of treatment, and on their demographics, psychosocial health, and primary substance at intake. Longitudinal latent profile analysis examined patterns of demoralization and anhedonia with treatment attrition as a distal outcome. RESULTS: Four subgroups of individuals emerged: (1) High demoralization and anhedonia, (2) Remitting demoralization and anhedonia, (3) High demoralization, low anhedonia, and (4) Low demoralization and anhedonia. Relative to the Low demoralization and anhedonia subgroup, all the other profiles were more likely to discontinue treatment. Numerous between-profile differences were observed with regard to demographics, psychosocial health, and primary substance. LIMITATIONS: The racial and ethnic background of the sample was skewed towards White individuals; future research is needed to determine the generalizability of our findings to minoritized racial and ethnic groups. CONCLUSIONS: We identified four clinical profiles that varied in the joint course of demoralization and anhedonia. Findings suggest specific subgroups might benefit from additional interventions and treatments that address their unique mental health needs during SUD recovery.

Predictors of Suicidal Ideation During Residential Substance Use Treatment.

Background: Individuals with substance use disorders (SUDs) and co-occurring chronic health and/or psychiatric conditions face unique challenges in treatment and may be at a greater risk for suicidal ideation relative to persons with SUD alone.Methods: In a sample of individuals entering residential SUD treatment in 2019 and 2020 (N = 10,242), we tested adjusted and unadjusted associations between suicidal ideation and (1) psychiatric symptoms and (2) chronic health conditions at treatment intake and during treatment using logistic and generalized logistic models.Results: Over a third of the sample endorsed suicidal ideation at intake, though the prevalence of suicidal ideation decreased during treatment. In both adjusted and unadjusted models, individuals who reported past-month self-harm, those who reported a lifetime suicide attempt, and individuals who screened positive for co-occurring anxiety, depression, and/or posttraumatic stress disorder were at elevated risk of endorsing suicidal ideation at intake and during treatment (P values < .001). In unadjusted models, chronic pain (odds ratio [OR] = 1.51, P < .001) and hepatitis C virus (OR = 1.65, P < .001) were associated with an elevated risk for suicidal ideation at intake, and chronic pain was associated with elevated risk for suicidal ideation during treatment (OR = 1.59, P < .001).Conclusions: Increasing accessibility to integrated treatments (ie, those that address psychiatric and chronic health conditions) for patients experiencing suicidal ideation may be beneficial in residential SUD treatment settings. Developing predictive models to identify those most at risk of suicidal ideation in real time remains a relevant direction for future work.

Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delta-9-tetrahydrocannabinol (dronabinol), as well as their effects on physical and cognitive functioning, and human abuse potential (HAP) outcomes among individuals with knee osteoarthritis (KOA). This was a within-subject, double-blind, randomized, placebo-controlled study. Participants (N = 37; 65% women; mean age = 62) diagnosed with knee osteoarthritis of ≥3/10 average pain intensity were included. Participants received (1) placebo-placebo, (2) hydromorphone (4 mg)-placebo; (3) dronabinol (10 mg)-placebo, and (4) hydromorphone (4 mg)-dronabinol (10 mg). Clinical and experimentally-induced pain, physical and cognitive function, subjective drug effects, HAP, adverse events, and pharmacokinetics were evaluated. No significant analgesic effects were observed for clinical pain severity or physical functioning across all drug conditions. Little enhancement of hydromorphone analgesia by dronabinol was observed on evoked pain indices. While subjective drug effects and some HAP ratings were increased in the combined drug condition, these were not significantly increased over the dronabinol alone condition. No serious adverse events were reported; hydromorphone produced more mild adverse events than placebo, but hydromorphone + dronabinol produced more moderate adverse events than both placebo and hydromorphone alone. Only hydromorphone impaired cognitive performance. Consistent with laboratory studies on healthy adults, the present study shows minimal benefit of combining dronabinol (10 mg) and hydromorphone (4 mg) for analgesia and improving physical functioning in adults with KOA.

Patterns of polysubstance use and clinical comorbidity among persons seeking substance use treatment: An observational study.

INTRODUCTION: Polysubstance use is common among individuals seeking treatment for substance use disorders (SUD). However, we know less about patterns and correlates of polysubstance use among treatment-seeking populations. The current study aimed to identify latent patterns of polysubstance use and associated risk factors in persons entering SUD treatment. METHODS: Patients (N = 28,526) being admitted for substance use treatment reported on their use of thirteen substances (e.g., alcohol, cannabis, cocaine, amphetamines, methamphetamines, other stimulants, heroin, other opioids, benzodiazepines, inhalants, synthetics, hallucinogens, and club drugs) in the month before treatment and prior to the month before treatment. Latent class analysis (LCA) determined the relationship between class membership and gender, age, employment status, unstable housing, self-harm, overdose, past treatment, depression, generalized anxiety disorder, and/or post-traumatic stress disorder (PTSD). RESULTS: Identified classes included: 1) Alcohol primary, 2) Moderate probability of past-month alcohol, cannabis, and/or opioid use; 3) Alcohol primary, Lifetime cannabis and cocaine use; 4) Opioid primary, Lifetime use of alcohol, cannabis, hallucinogens, club drugs, amphetamines, and cocaine; 5) Moderate probability of past-month alcohol, cannabis, and/or opioid use, Lifetime use of various substances; 6) Alcohol and cannabis primary, Lifetime use of various substances; and 7) High past-month polysubstance use. Individuals who engaged in past-month polysubstance use attended to face elevated risk of screening positive for recent unstable housing, unemployment, depression, anxiety, PTSD, self-harm, and overdose. CONCLUSIONS: Current polysubstance use is associated with significant clinical complexity. Tailored treatments that reduce harms resulting from polysubstance use and related psychiatric comorbidity may improve treatment outcomes in this population.

A double-blind, randomized, placebo-controlled, pilot clinical trial examining buspirone as an adjunctive medication during buprenorphine-assisted supervised opioid withdrawal.

Successful management of opioid withdrawal improves long-term treatment outcomes and reduces opioid use-related morbidity and mortality. Mechanistically supported pharmacotherapeutic approaches are needed to effectively manage acute and protracted opioid withdrawal. Buspirone is a D2 antagonist and 5-HT1a agonist that may decrease opioid withdrawal. Individuals (n = 15) admitted to a residential treatment center for opioid use disorder (OUD) were enrolled into a double-blind randomized clinical trial to assess the efficacy and acceptability of buspirone (45 mg/day) as an adjunctive medication to buprenorphine-assisted, supervised opioid withdrawal. Participants completed daily questionnaires which consisted of the Subjective Opiate Withdrawal Scale (SOWS) and a consensus sleep diary, which assessed total sleep time, time to sleep onset, and sleep quality. Total SOWS scores, individual opioid withdrawal symptoms and sleep outcomes were assessed between treatment groups (Placebo and Buspirone) and over time in a repeated measures linear mixed model. Total SOWS scores significantly decreased across study phases for both groups but decreased to a greater extent among individuals assigned to buspirone during both the first and second week of stable buspirone. Greater decreases in withdrawal were observed during Week 2 of stable buspirone relative to Week 1 of stable buspirone. Participants also reported significant increases in sleep duration and significant decreases in latency to sleep onset. This study provides further support that buspirone can help mitigate opioid withdrawal during a supervised opioid taper. Buspirone may confer unique benefits during protracted withdrawal periods. (PsycInfo Database Record (c) 2023 APA, all rights reserved).