Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behaviour.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.

Reducing overdose deaths among persons with opioid use disorder in connecticut.

BACKGROUND: People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary. METHODS: We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons. RESULTS: Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime. CONCLUSIONS: Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.

Neuroimaging of opioid effects in humans across conditions of acute administration, chronic pain therapy, and opioid use disorder.

Evidence of central nervous system (CNS) exogenous opioid effects in humans has been primarily gained through neuroimaging of three participant populations: individuals after acute opioid administration, those with opioid use disorder (OUD), and those with chronic pain receiving opioid therapy. In both the brain and spinal cord, opioids alter processes of pain, cognition, and reward. Opioid-related CNS effects may persist and accumulate with longer opioid use duration. Meanwhile, opioid-induced benefits versus risks to brain health remain unclear. This review article highlights recent accumulating evidence for how exogenous opioids impact the CNS in humans. While investigation of CNS opioid effects has remained largely disparate across contexts of opioid acute administration, OUD, and chronic pain opioid therapy, integration across these contexts may enable advancement toward effective interventions.

Community-led approaches to making naloxone available in public settings: Implementation experiences in the HEALing communities study.

BACKGROUND: Expanding public naloxone access is a key strategy to reduce opioid overdose fatalities. We describe tailored community-engaged, data-driven approaches to install and maintain naloxone housing units (naloxone boxes) in New York State and estimate the cost of these approaches. METHODS: Guided by the Consolidated Framework for Implementation Research, we collected data from administrative records and key informant interviews that documented the unique processes employed by four counties enrolled in the HEALing Communities Study to install and maintain naloxone housing units. We conducted a prospective micro-costing analysis to estimate the cost of each naloxone housing unit strategy from the community perspective. RESULTS: While all counties used a coalition to guide action planning for naloxone distribution, we identified unique approaches to implementing naloxone housing units: 1) County-led with technology expansion; 2) County-led grassroots; 3) Small-scale rural opioid overdose prevention program (OOPP) contract and 4) Comprehensive OOPP contract including overdose education and naloxone distribution (OEND) to individuals. The first two county-led approaches had lower cost per naloxone dose disbursed ($28-$38) compared to outsourcing to an OOPP ($183-$266); costs depended on services added to installing and maintaining units, such as OEND. Barriers included competing demands on public health resources (i.e., COVID-19) and stigma toward naloxone and opioid use disorder. Geographic access was a barrier in rural areas whereas existing infrastructure was a facilitator in urban counties. The policy landscape in New York State, which provides free naloxone kits and financial support to OOPPs, facilitated implementation in all counties. CONCLUSIONS: If a community has the resources, installing and maintaining naloxone housing units in-house can be less expensive than contracting with an outside partner. However, contracts that include OEND may be more effective at reaching target populations. Financial support from health departments and legislative authorization are important facilitators to making naloxone available in public settings.

Simultaneous determination of methadone and tramadol in serum samples by ultrasonic-assisted micro solid phase extraction and gas chromatography-mass spectrometry.

Ultrasonic-assisted dispersive micro solid phase extraction (UA-DMSPE) is proposed as a fast and easy technique for the extraction and preconcentration of methadone and tramadol from serum samples. Different sorbents including carbon nanotubes, oxidized carbon nanotubes, and TiO2 nanoparticles were compared to extract methadone and tramadol. The best performance was obtained using oxidized carbon nanotubes due to the strong affinity between the drugs and carbon nanotube adsorbents. Final analysis of drugs performed by using gas chromatography-mass spectrometric detection. Different parameters affecting the extraction efficiency, such as the sample volume, amount of adsorbent, desorption solvent type and volume, centrifugation time, and speed were investigated and optimized. The striking features of this technique are correlated to its speed and the small volumes of sample (about 1 mL), desorption solvent (about 50 µL), and adsorbent (about 0.001 g) for analysis of drugs, and finally, milder centrifugation conditions relative to the previously reported adsorbent. The optimal parameters were achieved as follows: pH value was set at 9, the sample volume was adjusted to 1200 µL, the amount of adsorbent used was 1 mg, the extraction time was set at 5 min, and the volume of the desorption solvent was adjusted to 50 µL. The limits of detections (0.5 and 0.8 ng mL-1) and quantifications (1.5 and 2.5 ng mL-1) were obtained for methadone and tramadol, respectively. The developed method also showed good repeatability, relative standard deviation (RSD) of 9.49 % and 7.47 % (n = 5), for the spiked aqueous solution at the concentration level of 10, 50, and 100 ng mL-1 for analytes, and linearity, R ≥ 0.9809. The results showed that UA-DMSPE is a quick, relatively inexpensive, and environmentally friendly alternative technique for the extraction of opiate drugs from serum samples.

Unveiling the link between chronic pain and misuse of opioids and cannabis.

Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse. However, the causal effect between chronic pain and the development of SUDs has not been clearly established. In this review, we discuss evidence that affirms the proposition that chronic pain is a risk factor for the development of opioid and cannabis use disorders by outlining the clinical evidence and detailing neurobiological mechanisms that link pain and drug misuse. Central to the link between chronic pain and opioid and cannabis misuse is hypodopaminergic transmission and the modulation of dopamine signaling in the mesolimbic pathway by opioids and cannabis. Moreover, we discuss the role of kappa opioid receptor activation and neuroinflammation in the context of dopamine transmission, their contribution to opioid and cannabis withdrawal, along with potential new treatments.

Adverse Effects After Prehospital Administration of Naloxone by Bystanders: A Preliminary Study.

OBJECTIVE: Opioid use disorder is a cause of significant morbidity and mortality. In order to reverse opioid overdose as quickly as possible, many institutions and municipalities have encouraged people with no professional medical training to carry and administer naloxone. This study sought to provide preliminary data for research into the rates of adverse effects of naloxone when administered by bystanders compared to Emergency Medical Services (EMS) personnel, since this question has not been studied previously. METHODS: This was a retrospective cohort study performed at an urban, tertiary, academic medical center that operates its own EMS service. A consecutive sample of patients presenting to EMS with opioid overdose requiring naloxone was separated into two groups based on whether naloxone was administered by bystanders or by EMS personnel. Each group was analyzed to determine the incidence of four pre-specified adverse events. RESULTS: There was no significant difference in the rate of adverse events between the bystander (19%) and EMS (16%) groups (OR = 1.23; 95% CI, 0.63 - 2.32; P = .499) in this small sample. Based on these initial results, a study would need a sample size of 6,188 in order to reach this conclusion with 80% power. Similarly, there were no significant differences in the rates of any of the individual adverse events. Secondary analysis of patients' demographics showed differences between the two groups which generate hypotheses for further investigation of disparities in naloxone administration. CONCLUSIONS: This preliminary study provides foundational data for further investigation of naloxone administration by bystanders. Adverse events after the prehospital administration of naloxone are rare, and future studies will require large sample sizes. These preliminary data did not demonstrate a statistically significant difference in adverse event rates when comparing naloxone administration by bystanders and EMS clinicians. This study provides data that will be useful for conducting further research on multiple facets of this topic.

Effect of oral naloxone on opioid-induced constipation in methadone maintenance treatment patients, a double-blind, placebo-control, clinical trial.

BACKGROUND: Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. METHOD: Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. RESULTS: The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5 mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS. CONCLUSION: Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS.

Most dynorphin neurons in the zona incerta-perifornical area are active in waking relative to non-rapid-eye movement and rapid-eye movement sleep.

Dynorphin is an endogenous opiate localized in many brain regions and spinal cord, but the activity of dynorphin neurons during sleep is unknown. Dynorphin is an inhibitory neuropeptide that is coreleased with orexin, an excitatory neuropeptide. We used microendoscopy to test the hypothesis that, like orexin, the dynorphin neurons are wake-active. Dynorphin-cre mice (n = 3) were administered rAAV8-Ef1a-Con/Foff 2.0-GCaMP6M into the zona incerta-perifornical area, implanted with a GRIN lens (gradient reflective index), and electrodes to the skull that recorded sleep. One month later, a miniscope imaged calcium fluorescence in dynorphin neurons during multiple bouts of wake, non-rapid-eye movement (NREM), and rapid-eye movement (REM) sleep. Unbiased data analysis identified changes in calcium fluorescence in 64 dynorphin neurons. Most of the dynorphin neurons (72%) had the highest fluorescence during bouts of active and quiet waking compared to NREM or REM sleep; a subset (20%) were REM-max. Our results are consistent with the emerging evidence that the activity of orexin neurons can be classified as wake-max or REM-max. Since the two neuropeptides are coexpressed and coreleased, we suggest that dynorphin-cre-driven calcium sensors could increase understanding of the role of this endogenous opiate in pain and sleep.

Leveraging prescription monitoring program data to evaluate the implementation of buprenorphine telehealth flexibilities: An interrupted time series analysis in Texas.

Background: In March 2020, policy changes by the Substance Abuse and Mental Health Services Administration and the Drug Enforcement Administration aimed to maintain access to office-based opioid treatment services by easing telehealth buprenorphine prescribing restrictions. However, the effectiveness of these changes remains largely unmeasured. The objective of this study was to measure the effectiveness of COVID-19-related telehealth flexibilities in an all-payer cohort from the Texas Prescription Monitoring Program. Methods: Using Texas Prescription Monitoring Program data, we identified oral buprenorphine and buprenorphine/naloxone prescriptions dispensed in Texas between September 1, 2019, and September 26, 2020. Weekly counts of prescriptions, prescribing physicians, and dispensing pharmacies were analyzed. An autoregressive integrated moving average (ARIMA) model estimated changes in prescription volume between pre-implementation (September 1, 2019 - February 15, 2020) and post-implementation (April 12, 2020 - September 26, 2020) periods. Results: Pre-flexibility, an average of 8898 (SD: 342) buprenorphine prescriptions were dispensed to 7829 (SD: 326) patients weekly. This declined to 8360 (SD: 247) prescriptions and 7661 (SD: 229) patients post-flexibility. Adjusted for seasonality, this represented a statistically significant average decline of -257.27 (95% CI: -426.06, -88.49) patients and -647.01 (95% CI: -856.67, -437.36) prescriptions per week. Discussion: Our results suggest a modest decline in buprenorphine dispensing volume early in the COVID-19 pandemic. While difficult to assess its significance, it can be assumed that telehealth flexibilities mitigated a potentially larger decline. Future research should explore system and individual-level barriers to telehealth utilization.

Acute opioid overdose in pediatric patients.

Recent increases in pediatric and adolescent opioid fatalities mandate an urgent need for early consideration of possible opioid exposure and specific diagnostic and management strategies and interventions tailored to these unique populations. In contrast to adults, pediatric methods of exposure include accidental ingestions, prescription misuse, and household exposure. Early recognition, appropriate diagnostic evaluation, along with specialized treatment for opioid toxicity in this demographic are discussed. A key focus is on Naloxone, an essential medication for opioid intoxication, addressing its unique challenges in pediatric use. Unique pediatric considerations include recognition of accidental ingestions in our youngest population, critical social aspects including home safety and intentional exposure, and harm reduction strategies, mainly through Naloxone distribution and education on safe medication practices. It calls for a multifaceted approach, including creating pediatric-specific guidelines, to combat the opioid crisis among children and to work to lower morbidity and mortality from opioid overdoses.

The test-retest reliability of the Opiate Treatment Index in nyaope users in Johannesburg.

Background: Epidemiological studies suggest that nyaope, a heroin-based drug, is widely used in South Africa. Yet few reliable research tools are available to assess treatment outcomes of users. The Opiate Treatment Index (OTI), a tool developed in Australia, could potentially facilitate research on context-specific South African treatment outcomes. However, we know little of its test-retest reliability. Aim: This study aimed to assess the test-retest reliability of the OTI among a sample of nyaope users in Johannesburg. Setting: This study was conducted across three substance use treatment facilities in Johannesburg. Methods: The OTI was administered to 53 nyaope users at baseline and one week later. To determine the test-retest reliability of the OTI, the intra-class correlation coefficients (ICC) and the Brennan-Prediger coefficients of the two interviews were calculated. Results: The ICC of the Q-scores from the data sets along with the Brennan-Prediger coefficient for the substance use domain were calculated. The ICC for nyaope was 0.38. Brennan-Prediger coefficients were as follows: alcohol - 0.96, crack-cocaine - 0.89, cannabis - 0.92, methaqualone - 0.85 and crystal methamphetamine - 0.89. Conclusion: A significant positive finding was the excellent test-retest reliability of the injecting and sexual behaviour domains and moderate reliability of the criminality, general health and social functioning domains. Contribution: The results of this study provide insight into the reliability of this tool and for its use in future studies in the South African context.

Integrated exercise program in opioid agonist therapy clinics and effect on psychological distress: study protocol for a randomized controlled trial (BAReAktiv).

BACKGROUND: Substance use disorder is associated with unhealthy lifestyle choices, resulting in adverse social and health consequences. People with opioid use disorder receiving opioid agonist therapy, in particular, have high morbidity and reduced quality of life. Physical activity is recommended as an adjunctive treatment for people with substance use disorder, but there is minimal evidence from randomized controlled trials on the effects of this among people with substance use disorder receiving opioid agonist therapy. METHODS: BAReAktiv is a multicentre randomized controlled trial. The study aims to recruit 324 patients receiving opioid agonist therapy (parallel groups randomized 1:1 to integrated exercise intervention or control, superiority trial). A 16-week group-based integrated exercise intervention with workouts twice a week. The exercise program consists of endurance and resistance training. The target group will be patients 18 years and older receiving opioid agonist therapy in outpatient clinics in several centers in Western Norway. The primary outcome of the study is the effect on psychological distress measured by Hopkins' symptom checklist with ten items. Secondary outcome measures include physical functioning assessed with a 4-min step test, activity level, fatigue symptoms, quality of life, and changes in inflammation markers. This study will provide improved knowledge on the effects of an integrated exercise program in opioid agonist therapy. DISCUSSION: Systematically integrating exercise programs for people receiving opioid agonist therapy could lead to a shift towards a stronger focus on health behaviors in outpatient care. Integrating exercise could benefit patient recovery and reduce disease burden. Further scale-up will be considered if the provided exercise program is safe and effective. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05242848. Registered on February 16, 2022.

An evaluation of first responders' intention to refer to post-overdose services following SHIELD training.

BACKGROUND: First responders [law enforcement officers (LEO) and Fire/Emergency Medical Services (EMS)] can play a vital prevention role, connecting overdose survivors to treatment and recovery services. This study was conducted to examine the effect of occupational safety and harm reduction training on first responders' intention to refer overdose survivors to treatment, syringe service, naloxone distribution, social support, and care-coordination services, and whether those intentions differed by first responder profession. METHODS: First responders in Missouri were trained using the Safety and Health Integration in the Enforcement of Laws on Drugs (SHIELD) model. Trainees' intent to refer (ITR) overdose survivors to prevention and supportive services was assessed pre- and post-training (1-5 scale). A mixed model analysis was conducted to assess change in mean ITR scores between pre- and post-training, and between profession type, while adjusting for random effects between individual trainees and baseline characteristics. RESULTS: Between December 2020 and January 2023, 742 first responders completed pre- and post-training surveys. SHIELD training was associated with higher first responders' intentions to refer, with ITR to naloxone distribution (1.83-3.88) and syringe exchange (1.73-3.69) demonstrating the greatest changes, and drug treatment (2.94-3.95) having the least change. There was a significant increase in ITR score from pre- to post-test (ß = 2.15; 95% CI 1.99, 2.30), and LEO-relative to Fire/EMS-had a higher score at pre-test (0.509; 95% CI 0.367, 0.651) but a lower score at post-test (0.148; 95% CI - 0.004, 0.300). CONCLUSION: Training bundling occupational safety with harm reduction content is immediately effective at increasing first responders' intention to connect overdose survivors to community substance use services. When provided with the rationale and instruction to execute referrals, first responders are amenable, and their positive response highlights the opportunity for growth in increasing referral partnerships and collaborations. Further research is necessary to assess the extent to which ITR translates to referral behavior in the field.

Autonomic Recalibration: A Promising Approach for Alleviating Myofascial Pain Explored in a Retrospective Case Series.

This retrospective case series introduces autonomic recalibration (AR) as a novel approach for alleviating chronic myofascial pain. The manuscript explores the rationale, theory, and practice of AR, which targets the autonomic nervous system (ANS) to restore homeostasis and reduce pain. The involvement of the ANS in pain modulation and the role of autonomic imbalance in chronic pain are discussed, emphasizing the potential benefits of addressing autonomic dysregulation through AR. The technique combines manual interventions and patient education, relying on neuroplastic adaptations. Three diverse case reports are presented to illustrate the effectiveness of AR in patients with different sources of pain. Each case presents a unique clinical scenario, including a nine-year-old male diagnosed with spondylolisthesis, a 68-year-old male with a history of abdominal surgeries, and a 56-year-old male with chronic low back pain following lumbar fusion surgery. In all cases, AR resulted in pain relief, improved sleep, and restoration of functional abilities. These findings support the potential of AR as an effective alternative approach for myofascial pain. Further research is warranted to validate these outcomes and investigate the underlying mechanisms of AR.

Healthcare provider perspectives on emergency department-initiated buprenorphine/naloxone: a qualitative study.

BACKGROUND: Take-home buprenorphine/naloxone is an effective method of initiating opioid agonist therapy in the Emergency Department (ED) that requires ED healthcare worker buy-in for large-scale implementation. We aimed to investigate healthcare workers perceptions of ED take-home buprenorphine/naloxone, as well as barriers and facilitators from an ED healthcare worker perspective. METHODS: In the context of a take-home buprenorphine/naloxone feasibility study at a tertiary care teaching hospital we conducted a descriptive qualitative study. We conducted one-on-one in person or telephone interviews and focus groups with ED healthcare workers who cared for patients given take-home buprenorphine/naloxone in the feasibility study at Vancouver General Hospital from July 2019 to March 2020. We conducted 37 healthcare worker interviews from December 2019 to July 2020. We audio recorded interviews and focus groups and transcribed them verbatim. We completed interviews until we reached thematic saturation. DATA ANALYSIS: We inductively coded a sample of transcripts to generate a provisional coding structure and to identify emerging themes, which were reviewed by our multidisciplinary team. We then used the final coding structure to analyze the transcripts. We present our findings descriptively. RESULTS: Participants identified a number of context-specific facilitators and barriers to take-home buprenorphine/naloxone provision in the ED. Participants highlighted ED conditions having either facilitative or prohibitive effects: provision of buprenorphine/naloxone was feasible when ED volume was low and space was available but became less so as ED volume increased and space decreased. Similarly, participants noted that patient-related factors could have a facilitative or prohibitive effect, such as willingness to wait (willing to stay in the ED for study-related activities and buprenorphine/naloxone initiation activities), receptiveness to buprenorphine/naloxone, and comprehension of the instructions. As for staff-related factors, time was identified as a consistent barrier. Time included time available and time required to initiate buprenorphine/naloxone (including time building rapport). Healthcare worker familiarity with buprenorphine/naloxone was noted as either a facilitating factor or a barrier, and healthcare workers indicated that ongoing training would have been advantageous. Many healthcare workers identified that the ED is an important first point of contact for the target patient population. CONCLUSION: Integrating a buprenorphine/naloxone program into ED care requires organizational supports (e.g., for managing buprenorphine/naloxone within limitations of ED volume, space, and time), and ongoing education of healthcare workers to minimize identified barriers.

Effects of a Two-Month Exercise Training Program on Concurrent Non-Opiate Substance Use in Opioid-Dependent Patients during Substitution Treatment.

BACKGROUND: This randomized controlled trial aimed to evaluate the effects of a two-month exercise intervention on the concurrent non-opiate substance use (alcohol, cocaine, cannabis, and benzodiazepines) in opioid users during their medication treatment. METHODS: Ninety opioid users (41 females) in methadone and buprenorphine medication treatment were randomly divided into four groups: (a) buprenorphine experimental (BEX; n = 26, aged 41.9 ± 6.1 yrs); (b) buprenorphine control (BCON; n = 25, aged 41.9 ± 5.6 yrs); (c) methadone experimental (MEX; n = 20, aged 46.7 ± 6.6 yrs); and (d) methadone control (MCON; n = 19, aged 46.1 ± 7.5 yrs). The experimental groups (BEX and MEX) followed an aerobic exercise training program on a treadmill for 20 min at 70% HRmax, 3 days/week for 8 weeks. Socio-demographic, anthropometric, and clinical characteristics, as well as non-opioid drug use in days and quantity per week, were assessed before and after the intervention period. RESULTS: Following the exercise training, the weekly non-opioid substance consumption (days) decreased (p < 0.05) in both exercise groups and was lower in BEX compared to MEX, while no differences were observed (p > 0.05) between the control groups (BCON vs. MCON) or compared to their baseline levels. Similarly, the daily amount of non-opiate substance intake was reduced (p < 0.05) post-training in BEX and MEX, whereas it did not differ (p > 0.05) in BCON and MCON compared to the baseline. CONCLUSIONS: The two-month exercise intervention reduced the non-opioid drug use in both the methadone and buprenorphine substitution groups compared to the controls, suggesting that aerobic exercise training may be an effective strategy for treating patients with OUDs.

Characterizing Opioid Withdrawal Experiences and Consequences Among a Community Sample of People Who Use Opioids.

BACKGROUND: Opioid withdrawal symptoms are a highly salient and consequential health condition experienced by people who use opioids (PWUO). This study utilized qualitative interviews to explore opioid withdrawal experiences and consequences among PWUO in Los Angeles County, USA. METHODS: Semi-structured qualitative interviews were conducted with 22 PWUO (aged 27-63 years) between May 2021 and May 2022. Participants self-reported opioid and injection drug use in the last 30 days. We employed an inductive thematic approach to systematically code and synthesize textual interview data. RESULTS: Participants experienced withdrawal symptoms frequently, with many going to great lengths to avoid them. Withdrawal pain was described as incapacitating and interfered with PWUO's ability to sustain regular employment and ensure stable housing. Avoiding withdrawal was described as influential in driving decisions to continue using opioids. Mechanisms for managing withdrawal included using other substances to the point of sedation. PWUO who transitioned from heroin to fentanyl use revealed more frequent, painful, and faster onset of withdrawal symptoms. Adverse withdrawal experiences and fear of precipitated withdrawal from buprenorphine were barriers to treatment initiation and continuation. CONCLUSION: Withdrawal symptoms among PWUO increase health risk. Improved strategies to treat opioid withdrawal are urgently needed. Solutions such as safe supply and intentional opioid withdrawal interventions (educational trainings, withdrawal comfort kits) are needed to improve withdrawal management and reduce opioid-related harm.

Telehealth Use and Health Equity for Mental Health and Substance Use Disorder During the COVID-19 Pandemic: A Systematic Review.

Background: As a result of the COVID-19 public health emergency (PHE), telehealth utilization accelerated to facilitate health care management and minimize risk. However, those with mental health conditions and substance use disorders (SUD)-who represent a vulnerable population, and members of underrepresented minorities (e.g., rural, racial/ethnic minorities, the elderly)-may not benefit from telehealth equally. Objective: To evaluate health equality in clinical effectiveness and utilization measures associated with telehealth for clinical management of mental health disorders and SUD to identify emerging patterns for underrepresented groups stratified by race/ethnicity, gender, age, rural status, insurance, sexual minorities, and social vulnerability. Methods: We performed a systematic review in PubMed, Embase, Cochrane Central Register of Controlled Trials, and CINAHL through November 2022. Studies included those with telehealth, COVID-19, health equity, and mental health or SUD treatment/care concepts. Our outcomes included general clinical measures, mental health or SUD clinical measures, and operational measures. Results: Of the 2,740 studies screened, 25 met eligibility criteria. The majority of studies (n = 20) evaluated telehealth for mental health conditions, while the remaining five studies evaluated telehealth for opioid use disorder/dependence. The most common study outcomes were utilization measures (n = 19) or demographic predictors of telehealth utilization (n = 3). Groups that consistently demonstrated less telehealth utilization during the PHE included rural residents, older populations, and Black/African American minorities. Conclusions: We observed evidence of inequities in telehealth utilization among several underrepresented groups. Future efforts should focus on measuring the contribution of utilization disparities on outcomes and strategies to mitigate disparities in implementation.