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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.

Objective Minority stress may contribute to poor health by dysregulating stress response systems, including diurnal cortisol rhythms. However, few studies have examined the association between sexual and gender minority stress and diurnal cortisol in lesbian, gay, bisexual, and transgender (LGBT) individuals. The current investigation tested whether the daily experience of minority stressors is uniquely related to diurnal cortisol above and beyond general stressors. Method One hundred and 21 sexual and gender minority young adults (aged 18-35, 54.5% female) completed initial and daily evening questionnaires for 7 consecutive days to document daily general stressors and LGBT stressors. A randomly selected subset (n = 58) also provided salivary cortisol samples at wake, 45-min postwake, 12-hr postwake, and bedtime. Results Controlling for covariates (sex assigned at birth, wake time, bedtime, and day of the week) and general stressors, individuals who reported more LGBT stressors across the week displayed elevated cortisol levels at wake, t(491) = 9.68, p = .002 and 45-min postwake, t(492) = 6.41, p = .011, relative to individuals who reported fewer LGBT stressors. In contrast, after controlling for covariates, the frequency of general stressors only predicted cortisol 12 hr postwake, t(785) = 2.02, p = .043. Diurnal cortisol was unrelated to within-person fluctuations in LGBT and general stressors. Conclusions Results imply that the experience of everyday minority stressors is uniquely related to diurnal cortisol and may have implications for the mental and physical health of LGBT adults. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background Consistent with the dual-hormone hypothesis, the combination of high testosterone levels and low cortisol levels has been linked to increased dominant and aggressive behaviors. However, recent research indicates that this association is weaker or even reversed following provocation. It is also unclear whether the association between testosterone/cortisol and aggression is similar for men and women and for those with and without attention-deficit/hyperactivity disorder (ADHD). Methods Using data from a larger project examining ADHD in the context of romantic relationships, the current study tested the dual-hormone hypothesis in 32 heterosexual young adult couples who engaged in a conflict discussion and a competitive reaction time task in the laboratory. Aggressive behavior was indexed by greater noise blast intensity toward one’s partner during the competitive reaction time task. Two potential sources of provocation were examined: 1) affective responses to a conflict discussion task preceding the competitive reaction time task, and 2) whether participants received/did not receive a noise blast before the first two trials of the competitive reaction time task. Salivary testosterone and cortisol were assessed three times throughout the laboratory session, and the ratio of testosterone to cortisol output across the session (T/C AUCg ratio) was calculated. Results Consistent with the dual-hormone hypothesis, greater AUCg T/C ratios were associated with greater aggression. Further, T/C ratio–aggression associations were weaker under provoked conditions but did not differ as a function of sex or ADHD status. Conclusions Results provide support for the dual-hormone hypothesis and suggest that provocation may be an important moderator of the T/C–aggression relationship.

Meta-analyses suggest a small association between cardiovascular responses to acute stressors and cardiovascular disease, but a recent review suggests that this effect may be underestimated due to insufficient consideration of individual differences in habituation to repeated stressors. Objective The present article reports new analyses of a published randomized controlled trial comparing the effects of mindfulness-based stress reduction (MBSR), cognitive behavioral therapy (CBT), and a passive control condition on blood pressure habituation-a secondary outcome. Psychological mediators of intervention effects were examined. Method Participants (138 healthy adults reporting moderate/high stress) were randomly assigned to 6-week MBSR, CBT, or a waitlist control. Analyses were conducted on 86 participants who subsequently completed stressful speech and mental arithmetic tasks during two posttreatment visits scheduled 48 hr apart. Blood pressure was measured -15, +0, +5, +10, +25, +35, and +60 min poststressor onset. Results There were no between-condition differences in blood pressure habituation (all ps > .05). However, both MBSR and CBT led to increased perceived control over thoughts, F(2, 72) = 5.20, p = .008, and individuals who displayed a greater change in perceived control over thoughts also displayed greater habituation to the speech portion of the stressor, F(6, 799) = 2.32, p = .020. Results implied an indirect effect of stress reduction interventions on blood pressure habituation via change in perceived control over thoughts (b = -3.93, SE = 1.98, 95% CI: [-8.392, -0.701]). Conclusion Stress reduction interventions that increase perceived control over thoughts may benefit cardiovascular health by promoting blood pressure habituation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Masculine and feminine gender roles influence stressor appraisals and coping in everyday life, but their effect on stress response systems like the hypothalamic-pituitary-adrenocortical axis is unclear. Accordingly, the present study tested the association between gender roles and cortisol responses to repeated stress as part of secondary analyses of data from a randomized controlled trial examining the effects of stress management interventions on cortisol habituation. Participants (Nfinal = 86; 72% female) completed a baseline survey assessing gender role endorsement using the Bem Sex Role Inventory, from which 4 groups were derived: masculine (n = 20), feminine (n = 20), androgynous (high masculinity, high femininity; n = 22), and undifferentiated (low masculinity, low femininity; n = 24). Following the stress management intervention (mindfulness-based stress reduction or cognitive-behavioral skills training) or waitlist period control, participants completed the Trier Social Stress Test on two laboratory visits (48 h apart). Salivary cortisol was assessed 0, 25, 35, and 60 min post-stressor during both laboratory visits. Androgynous and undifferentiated individuals both exhibited a significant decrease in total cortisol from visit 1 to visit 2 (i.e. habituation) whereas feminine and masculine individuals did not. Undifferentiated individuals exhibited greater habituation than feminine and masculine individuals, whereas androgynous individuals only exhibited greater habituation than the feminine group. Controlling for study condition assignment did not alter these results. Results imply that gender roles may be implicated in stress-related disease because of their association with HPA axis functioning during episodes of acute stress.

Understanding the relationship between stress and telomere length (a marker of cellular aging) is of great interest for reducing aging-related disease and death. One important aspect of acute stress exposure that may underlie detrimental effects on health is physiological reactivity to the stressor.This study tested the relationship between buccal telomere length and physiological reactivity (salivary cortisol reactivity and total output, heart rate (HR) variability, blood pressure, and HR) to an acute psychosocial stressor in a sample of 77 (53% male) healthy young adults.Consistent with predictions, greater reductions in HR variability (HRV) in response to a stressor and greater cortisol output during the study session were associated with shorter relative buccal telomere length (i.e. greater cellular aging). However, the relationship between cortisol output and buccal telomere length became non-significant when adjusting for medication use. Contrary to past findings and study hypotheses, associations between cortisol, blood pressure, and HR reactivity and relative buccal telomere length were not significant. Overall, these findings may indicate there are limited and mixed associations between stress reactivity and telomere length across physiological systems.

Left censoring in salivary bioscience data occurs when salivary analyte determinations fall below the lower limit of an assay’s measurement range. Conventional statistical approaches for addressing censored values (i.e., recoding as missing, substituting or extrapolating values) may introduce systematic bias. While specialized censored data statistical approaches (i.e., Maximum Likelihood Estimation, Regression on Ordered Statistics, Kaplan-Meier, and general Tobit regression) are available, these methods are rarely implemented in biobehavioral studies that examine salivary biomeasures, and their application to salivary data analysis may be hindered by their sensitivity to skewed data distributions, outliers, and sample size. This study compares descriptive statistics, correlation coefficients, and regression parameter estimates generated via conventional and specialized censored data approaches using salivary C-reactive protein data. We assess differences in statistical estimates across approach and across two levels of censoring (9% and 15%) and examine the sensitivity of our results to sample size. Overall, findings were similar across conventional and censored data approaches, but the implementation of specialized censored data approaches was more efficient (i.e., required little manipulations to the raw analyte data) and appropriate. Based on our review of the findings, we outline preliminary recommendations to enable investigators to more efficiently and effectively reduce statistical bias when working with left-censored salivary biomeasure data.

Best practice standards for measuring analyte levels in saliva recommend that all biospecimens be tested in replicate with mean concentrations used in statistical analyses. This approach prioritizes minimizing laboratory-based measurement error but, in the process, expends considerable resources. We explore the possibility that, due to advances in salivary assay precision, the contribution of laboratory-based measurement error in salivary analyte data is very small relative to more important and meaningful variability in analyte levels across biological replicates (i.e., between different specimens). To evaluate this possibility, we examine the utility of the repeatability intra-class correlation (rICC) as an additional index of salivary analyte data precision. Using randomly selected subsamples (Ns=200 and 60) of salivary analyte data collected as part of a larger epidemiologic study, we compute the rICCs for seven commonly assayed salivary measures in biobehavioral research - cortisol, alpha-amylase, c-reactive protein, interlekin-6, uric acid, secretory immunoglobulin A, and testosterone. We assess the sensitivity of rICC estimates to assay type and the unique distributions of the underlying analyte data. We also use simulations to examine the bias, precision, and coverage probability of rICC estimates calculated for small to large sample sizes. For each analyte, the rICCs revealed that less than 5% of variation in analyte levels was attributable to laboratory-based measurement error. rICC estimates were similar across all analytes despite differences in analyte levels, average intra-assay coefficients of variation, and in the distributional properties of the data. Guidelines for calculating rICC are provided to enable investigators and laboratory staff to apply this metric and more accurately quantify, and communicate, the magnitude of laboratory-based measurement error in their data. By helping investigators scale measurement error relative to more scientifically meaningful variability between biological replicates, the application of the rICC has the potential to influence research strategies and tactics such that resources (e.g., finances, effort, number/volume of biospecimens) are allocated more efficiently and effectively.

Revealing one's sexual identity to others is a complex process marked by a shift in the types of stressors faced by sexual minority young adults. Such stressors influence the secretion of health-relevant hormones, including cortisol, yet how dimensions of disclosure (i.e., the degree and context) influence neuroendocrine functioning remains poorly understood. The current study examined the association between disclosure context (disclosure to family members, friends/co-workers/acquaintances, and members of religious groups) and diurnal cortisol while allowing disclosure to vary in degree (i.e., how much is disclosed).One hundred twenty-one sexual minority young adults (aged 18-35 years, 54.5% female, free of major psychiatric/endocrine disorders) completed an initial survey that assessed the degree and context of sexual minority identity disclosure. A randomly selected subset (n = 58) also provided salivary cortisol samples at wake, 45 minutes after wake, 12 hours after wake, and at bedtime for 1 week.Greater total disclosure and greater disclosure to family members were associated with reduced cortisol output, defined as Area Under the Curve relative to ground (AUCg; F(1,230) = 5.95, p = .015, and F(1,231) = 10.90, p = .001, respectively). Disclosure to co-workers, friends, acquaintances, or religious groups was unrelated to cortisol AUCg. All disclosure contexts tested were unrelated to the shape of diurnal cortisol slopes (including the cortisol awakening response).Disclosure to family members uniquely predicted cortisol AUCg. Therefore, these results suggest that effects of disclosure on diurnal cortisol and its associated health outcomes may occur in the context of familial relationships.