We present the case of an immunocompetent, fully vaccinated 17-year-old female who developed severe, disseminated varicella-zoster virus (VZV) reactivation with visceral involvement, Ramsay Hunt Syndrome, and complications of suspected superimposed bacterial cellulitis, chronic pain, as well as postherpetic neuralgia. We aim to highlight the importance of early recognition and multidisciplinary management of varicella-zoster virus in immunocompetent patients to minimize disease complications. All data were obtained from the electronic medical record with permission from the patient and her parent. The patient underwent serial dermatologic examinations and a comprehensive immunologic workup. Positive VZV PCR testing of the lesion and blood confirmed active VZV infection. Despite an intensive multi-drug antiviral regimen, she developed suspected clinical drug resistance-although resistance testing was not performed-progressing to disseminated varicella with hepatic involvement. Inpatient complications included Ramsay Hunt Syndrome, suspected superimposed bacterial cellulitis, opioid withdrawal, and chronic pain. While outpatient, she developed postherpetic neuralgia and psychosocial impairment, preventing her from completing her academic year. This case illustrates a rare, but severe presentation of disseminated varicella-zoster virus with visceral involvement and concomitant Ramsay Hunt Syndrome in a healthy adolescent. It underscores the importance of considering VZV in the differential diagnosis of pediatric rash and neuropathy in all patients, irrespective of immune status.

Polysubstance use involving psychostimulants and opioids is increasingly prevalent and associated with elevated overdose risk, relapse vulnerability, and poor treatment outcomes. However, the neurobehavioral consequences of opioid-stimulant use remain poorly understood. We evaluated whether repeated methamphetamine-fentanyl polysubstance treatment disrupts social preference during withdrawal, whether psilocybin treatment restores sociability, and whether these manipulations alter corticolimbic expression of stress- and opioid-related genes. Methods Male and female rats received injections of methamphetamine and fentanyl or saline and were assessed for social preference at baseline and following 10 days of withdrawal. On withdrawal day 10, rats received psilocybin or saline and were reassessed for sociability 24 h later. CRHR1 and OPRM1 expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) were quantified by RT-qPCR. Results Withdrawal from 14-days of polysubstance treatment reduced social preference, replicating prior findings of withdrawal-associated social dysfunction. Psilocybin pretreatment did not restore social preference at the time point examined. In the mPFC, psilocybin bidirectionally altered CRHR1 expression depending on drug history, decreasing expression in saline-treated controls, while increasing expression following polysubstance treatment. In the NAc, polysubstance administration reduced CRHR1 expression. OPRM1 expression showed sex-dependent regulation with a marked reduction in the NAc of females following polysubstance treatment and evidence of sex-dependent effects in the mPFC. Conclusions Methamphetamine-fentanyl treatment produces persistent social deficits during withdrawal and region- and sex-dependent corticolimbic transcriptional adaptations in vivo . Although psilocybin did not restore sociability, it produced drug history-dependent regulation of cortical CRHR1 .

This study elucidated the structure-activity relationships (SAR) of three distinct opioid ligand series at the µ-opioid receptor (µ-OR) and investigated the ligand-dependent role of arrestin in downstream signaling. Radioligand binding assays across 13 compounds revealed that high-affinity µ-OR binding is not restricted to a single chemical scaffold. For fentanyl analogs, SAR analysis identified four key structural determinants: the N-phenethyl group (R1) is essential for µ-OR binding, the piperidine 4-position (R2) is sterically constrained and tolerates only small substituents such as carbomethoxy, the acyl side chain (R3) tolerates diverse chemical modifications including alkyl, alkoxy, and heteroaryl groups without substantial loss of affinity, and para-substitution on the phenethyl ring (R4) with electron-withdrawing groups like fluorine is well-tolerated. Analysis of non-fentanyl scaffolds (2-Methyl AP-237, W-15, and brorphine) demonstrated that specific side-chain functionalization, rather than core scaffold architecture, primarily determines binding potency. Comparison of classical opioids further revealed that structural flexibility, exemplified by methadone, can confer superior binding affinity compared to the rigid morphine scaffold. Consistent with this structural diversity, the contribution of arrestins to ERK activation varied substantially across compounds, suggesting that µ-OR-biased signaling is not dictated exclusively by intrinsic receptor properties but emerges from the interplay between receptor conformation and ligand-specific structural features. Collectively, our results provide a molecular framework for understanding opioid pharmacology with important implications for rational drug design aimed at minimizing adverse effects while maintaining analgesic efficacy.

Kratom and kratom products are increasingly used in Western countries for pain management, mood disorders, and opioid withdrawal. Despite perceptions of safety, kratom can cause hepatotoxicity and clinically relevant herb-drug interactions, particularly with medications metabolized by cytochrome P450 (CYP) enzymes. We report a 45-year-old male with stable psychiatric conditions on nortriptyline and lisdexamfetamine, who developed mild, reversible liver enzyme elevations and supratherapeutic nortriptyline levels during chronic kratom use (raw, dry leaf, two tablespoons daily for five to six years). Initial labs showed aspartate aminotransferase (AST) 33 U/L, alanine aminotransferase (ALT) 70 U/L, alkaline phosphatase (ALP) 136 U/L, gamma-glutamyl transferase (GGT) 141 U/L, and nortriptyline 350 mcg/L. Dose reduction of nortriptyline partially corrected serum levels, but liver enzyme elevations persisted. Kratom discontinuation led to normalization of both liver function tests and nortriptyline levels within three weeks. This case illustrates two clinically important considerations: kratom-induced liver injury (KILI) and a CYP-mediated herb-drug interaction. The patient's use of raw leaf contrasts with commercial products, which may include concentrated extracts, 7-hydroxymitragynine (7OHMG)-enriched formulations, or ethanol-based preparations, potentially increasing hepatotoxicity and interaction risk. Even mild liver enzyme elevations in patients using kratom warrant evaluation, particularly with concurrent CYP-metabolized medications. Clinicians should educate patients about product variability, monitor liver function and drug levels, and consider temporary kratom discontinuation to assess causality. This case reinforces the growing evidence of kratom's hepatotoxic potential and the importance of integrating pharmacokinetic considerations into patient care.

Buprenorphine micro-induction enables a gradual transition from full opioid agonists without requiring abstinence, minimizing the risk of precipitated withdrawal. This approach is particularly beneficial for older adults with chronic pain who remain on long-term opioid therapy and may be reluctant or medically unfit to undergo traditional induction protocols. A 68-year-old woman with Ehlers-Danlos Syndrome, complex surgical history, and severe opioid use disorder who was taking 280 (Morphine Milligram Equivalents per Day), including prescribed morphine and illicit hydromorphone. She underwent an outpatient buprenorphine-naloxone micro-induction while continuing full agonist use until target dose was reached. Doses were titrated over seven days with minimal withdrawal symptoms. She successfully transitioned to buprenorphine-naloxone 4-1 mg QID (Four Times Per Day), reporting improved pain, mobility, and overall functioning. Outpatient micro-induction can be safely implemented in older adults with chronic opioid exposure, particularly those receiving prescription opioids from outside prescribers for chronic pain. This case underscores the utility of pharmacogenomics, trauma-informed care, and interdisciplinary coordination to facilitate successful transition to MOUD.

International guidelines recommend rapid-start antiretroviral therapy (RS-ART) for people with HIV. Guidance for implementing RS-ART among people who inject drugs (PWID), a population often denied equitable treatment due to stigma and rights violations, remains limited. Using human-centered design, barriers and facilitators to combined RS-ART and opioid agonist therapy initiation in Ukraine were explored, where HIV is concentrated among PWID with opioid use disorder. Using nominal group technique, a human-centered design method involving client input, five focus groups (6-12 participants each and 42 participants total) with PWID with HIV in four Ukrainian cities most affected by HIV were conducted. Responses were rank-ordered and grouped using NVivo along the socioecological model. The most common barriers were organizational, including nonintegration of ART and opioid agonist therapy services (45%), followed by individual (22%), such as fear of withdrawal symptoms, policy/regulatory (20%), including the national addiction registry, and relationship (13%) barriers, including pervasive stigma. Solutions focused on equity, promoting behavioral design interventions like choice architecture, nudging, and message framing.

Kratom is an emerging drug of concern that poses significant challenges in perioperative care, but the public and many health professionals remain unaware of its use and effects. Patients may use kratom as a substitute for opioids or to increase focus or decrease anxiety, depending on the dose. Kratom binds with μ-opioid, α2-adrenergic, and serotonin receptors and has been associated with perioperative complications, including difficulty managing pain, hemodynamic instability, agitation, and withdrawal symptoms in patients undergoing surgery. Considering that 1.9 million Americans aged 12 years and older have used kratom, screening patients before surgery is important. Preoperative nurses can positively affect patient care by communicating a patient's use of kratom to the care team. With that knowledge, perianesthesia, intraoperative, and postoperative teams can be prepared for any untoward effects of kratom use across all perioperative settings.