Objective and subjective measurement of sleep in people who use substances: Emerging evidence and recommendations from a systematic review.

People who use substances commonly experience sleep disruptions, affecting the regulation of physical and mental health, and presenting a significant barrier to treatment success. Sleep impairments are noted in all phases of substance use; however, differences between subjective versus objective methods used to measure sleep quality have been reported. While polysomnography is the gold-standard for sleep measurement, recent advances in actigraphy may help address the discordance between subjective and objective sleep reports. This systematic review examined emerging evidence (2016-present) for sleep impairment in people who use substances, with the twofold goal of: (1) identifying whether sleep outcomes vary across substance type (alcohol, nicotine, cannabis, cocaine, methamphetamine and opioids); and (2) contrasting results from subjective and objective measures. While some differences between subjective and objective sleep were noted, there was overwhelming evidence of clinically relevant sleep impairment in people who use alcohol, nicotine, cocaine, methamphetamine and opioids, with less consistent results for cannabis. Gaps in the literature are identified and future recommendations are presented, including utilization of common methodological frameworks, identification of mechanisms, and closer examination of sleep across stages of substance use and the interconnection between sleep and return to use.

A meta-analysis of electrophysiological biomarkers of reward and error monitoring in substance misuse.

Substance use disorders are characterized by marked changes in reward and error processing. The primary objective of this meta-analysis was to estimate effect sizes for the reward positivity (RewP) and error-related negativity (ERN), two event-related potential indicators of outcome monitoring, in substance users compared to controls. The secondary objective was to test for moderation by demographic, substance type, and EEG experiment parameters. Final PubMed searches were performed in August 2023. Inclusion criteria were substance use disorder/dependence or validated self-report of substance misuse, RewP/ERN means available, healthy control comparison group, non-acute drug study, peer-reviewed journal, English language, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. The RewP results (19 studies, 1641 participants) did not support an overall effect (Hedges' g = 0.07, 95% CI [-0.44, 0.58], p = .777) and nor effect of any moderators. The ERN results (20 studies, 1022 participants) indicated no significant overall effect (g = 0.41, 95%CI [-0.05, 0.88]). Subgroup analyses indicated that cocaine users had a blunted ERN compared to controls (g = 1.12, 95%CI [0.77, 1.47]). There was limited evidence for publication/small study bias. Although the results indicate a potential dissociation between substance types, this meta-analysis revealed the need for additional research on the RewP/ERN in substance using populations and for better designed experiments that adequately address research questions.

Distress tolerance: prospective associations with cognitive-behavioral therapy outcomes in adults with posttraumatic stress and substance use disorders.

74Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; Mage = 44.90, SD = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory Serial Addition Task. The Clinician-Administered PTSD Scale for DSM-5 severity scores and percent days of primary substance use, measured via Timeline Follow-back, were used as indicators of PTSD symptoms and substance use, respectively. Covariates included treatment condition, baseline PTSD symptom severity, and baseline substance use. Lower perceived DT at baseline (DTS total score) was associated with higher PTSD symptom severity at end-of-treatment. Lower behavioral DT at baseline (MTPT duration) was associated with higher substance use at the conclusion of treatment (i.e. proportion of number of use days to total number of days between two final treatment sessions).

Initial development of a brief assessment of cocaine demand.

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand.

Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial.

INTRODUCTION: Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome. METHODS: Eighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes. RESULTS: Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively. CONCLUSIONS: Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies. IMPLICATIONS: Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

A meta-analysis of tract-based spatial statistics studies examining white matter integrity in cocaine use disorder.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature.

Plasma pro- and anti-inflammatory cytokines may relate to cocaine use, cognitive functioning, and depressive symptoms in cocaine use disorder.

BACKGROUND: Inflammation is implicated in cocaine use and associated problems, including depression and cognitive impairment. OBJECTIVE: We assessed 18 cytokines, cocaine use, cognition, and depression in individuals with Cocaine Use Disorder. Our general hypothesis was that higher pro-inflammatory cytokines would relate to more cocaine use, poorer cognition, and more depression, while higher anti-inflammatory cytokines would relate to less cocaine use, better cognition, and less depression. METHODS: Data were collected from 85 individuals (76.5% male, 80% African American) aged 18-65. The ASI, Shipley-2, and BDI-II assessed frequency and duration of cocaine use, cognition, and depression. Cytokines were tested using Bio-Plex Pro™ assays. Elastic net regression identified which cytokines related to each measure, controlling for confounds. RESULTS: Lower IL-29 (B = -0.08, bootstrapped 95%CI = [-0.24,0.07]), scD163 (B = -0.11, bootstrapped 95%CI = [-0.27,0.04]), Eotaxin-1 CCL11 (B = -0.11, bootstrapped 95%CI = [-0.30,0.08]), and higher APRIL/TNFSF13 (B = 0.11, bootstrapped 95%CI = [-0.08,0.30]) related to more frequent cocaine use. Lower IL-29 (B = -0.24, bootstrapped 95% CI = [-2.26,1.79]) and IL-20 (B = -1.62, bootstrapped 95%CI = [-3.53,0.29]) related to longer duration of cocaine use. Higher Eotaxin-2 CCL24 (B = 2.79, bootstrapped 95%CI = [-0.59,6.17]) and TWEAK (B = 2.83, bootstrapped 95%CI = [-0.80,6.45]) related to better cognition. Finally, higher IL-20 (B = -1.83, bootstrapped 95%CI = [-3.70,0.04]) and Osteocalcin (B = -1.56, bootstrapped 95%CI = [-3.81,0.70]) related to lower depressive symptoms. However, none of these relationships survived bootstrapped analyses. CONCLUSION: Pro- and anti-inflammatory cytokines may relate to cocaine use, cognition, and depression, but inconsistent with our hypotheses, higher pro-inflammatory cytokines related to better functioning in several domains. Additionally, cytokines were selected at low frequencies and demonstrated weak relationships with outcomes. These preliminary findings suggest complex relationships between inflammation and cocaine use.

Equal response rates maintained by concurrent drug and nondrug reinforcers: a design for treatment evaluation.

During daily 3-h sessions, four rhesus monkeys had concurrent access to 16% alcohol (w/v) and saccharin. A response occurred when a monkey made mouth contact with the metal spout and thereby completed a drinkometer circuit. The liquids were available under concurrent nonindependent fixed-ratio 32 schedules. With these schedules, responses on the right spout decremented both the right and left fixed-ratio counters and vice versa. Responding was well maintained by both alcohol and saccharin. Increases in saccharin concentration produced increases in saccharin responding to the point that saccharin responding exceeded alcohol responding. Responses per saccharin delivery were also a direct function of the saccharin concentration. In contrast, responses per alcohol delivery generally decreased as the saccharin concentration became greater. Changeover or switching responses were also a direct function of the saccharin concentration. Relative reinforcing effects of each combination of liquid pairs were measured for each monkey. For all monkeys, it was possible to establish equal rates of responding for both reinforcers and frequent switching between reinforcers. The balanced responding can serve as a baseline for the evaluation of potential treatments that may alter relative reinforcing effects.

Resting Heart Rate Variability: Exploring Associations With Symptom Severity in Adults With Substance Use Disorders and Posttraumatic Stress.

Objective: Substance use disorders and posttraumatic stress symptoms are commonly comorbid. Previous studies have established that those with substance use disorders or posttraumatic stress disorder (PTSD) have lower high frequency-heart rate variability (HF-HRV) compared to controls, suggesting that low HF-HRV may be a biomarker of a common physiological mechanism underlying both disorders. We evaluated HF-HRV as a potential biomarker of a common underlying process by testing whether lower HF-HRV related to greater severity of substance use and PTSD symptoms in individuals with both substance use disorders and at least four symptoms of PTSD. Methods: HF-HRV was measured in 49 adults with substance use disorders and at least four symptoms of PTSD. We performed a series of regressions controlling for age to test whether low HF-HRV was associated with greater substance use disorder and PTSD symptom severity. Substance use disorder symptoms were measured by the Addiction Severity Index and PTSD symptoms were measured by the Clinician-Administered PTSD Scale and the PTSD Checklist. Results: After controlling for age, low resting HF-HRV was significantly associated with drug and alcohol symptom severity but not PTSD symptom severity. Conclusions: HF-HRV may be more sensitive to the severity of drug and alcohol use rather than PTSD. Findings may suggest that in PTSD populations, HF-HRV may primarily index comorbid substance use disorder symptoms. HF-HRV could serve as an objective measure of substance use severity and should be further investigated as a predictor of outcomes in treatment for substance use disorders.

The impact of substance use disorders on clinical outcomes in older-adult psychiatric inpatients.

OBJECTIVE: To examine associations among substance use disorder (SUD) and measures of length of stay (LOS) and non-psychiatric medical comorbidity (MEDCO) in older-adult inpatients with serious mental illness (SMI), hypothesizing SUD would be related to worse clinical outcomes. METHODS: A cross-sectional study analyzed medical records from 2010 to 2016 of 7258 inpatients with SMI ≥ age 50, obtained from a 274-bed psychiatric hospital. Descriptive analyses examined prevalence rates for SUD status (+/-), individual drug classes, and total number of SUDs (polysubstance use disorders). Regression models examined the influence of 2 independent variables of interest: (1) SUD status (+/-) and (2) type of SUD (ie, specific drug), controlling for demographic factors and additional (non-SUD) psychiatric disorders. Two dependent (outcome) variables were examined: LOS and MEDCO. RESULTS: The overall SUD rate was 26%; cocaine was the most common SUD (≈ 10%). SUD status and additional (non-SUD) psychiatric diagnoses were significantly associated with longer LOS (both P < 0.001). For individual SUDs, cocaine, marijuana, opiates, and alcohol were all significantly associated with LOS (all P < 0.01). SUD status, age, sex, admission status, and race were significantly associated with MEDCO (all P < 0.002). For individual SUDs, barbiturates, opiates, and alcohol were all significantly associated with MEDCO (P < 0.01). CONCLUSIONS: The prevalence of SUD in this sample underscores concerns related to treating older adults presenting providers with comorbid SUD and SMI. This combination may increase the burden and complexity of care, warranting further investigation into mechanisms and long-term consequences.