The Foundational Science of Endogenous Opioids and Their Receptors.

The function of endogenous opioids spans from initiating behaviors that are critical for survival, to responding to rapidly changing environmental conditions. A network of interconnected systems throughout the body characterizes the endogenous opioid system (EOS). EOS receptors for beta-endorphin, enkephalin, dynorphin, and endomorphin underpin the diverse functions of the EOS across biological systems. This chapter presents a succinct yet comprehensive summary of the structure of the EOS, EOS receptors, and their relationship to other biological systems.

Physical Exercise as an Intervention for Depression: Evidence for Efficacy and Mu-Opioid Receptors as a Mechanism of Action.

Physical exercise is often cited as an important part of an intervention for depression, and there is empirical evidence to support this. However, the mechanism of action through which any potential antidepressant effects are produced is not widely understood. Recent evidence points toward the involvement of endogenous opioids, and especially the mu-opioid system, as a partial mediator of these effects. In this chapter, we discuss the current level of empirical support for physical exercise as either an adjunctive or standalone intervention for depression. We then review the extant evidence for involvement of endogenous opioids in the proposed antidepressant effects of exercise, with a focus specifically on evidence for mu-opioid system involvement.

The Roles of Endogenous Opioids in Placebo and Nocebo Effects: From Pain to Performance to Prozac.

Placebo and nocebo effects have been well documented for nearly two centuries. However, research has only relatively recently begun to explicate the neurobiological underpinnings of these phenomena. Similarly, research on the broader social implications of placebo/nocebo effects, especially within healthcare delivery settings, is in a nascent stage. Biological and psychosocial outcomes of placebo/nocebo effects are of equal relevance. A common pathway for such outcomes is the endogenous opioid system. This chapter describes the history of placebo/nocebo in medicine; delineates the current state of the literature related to placebo/nocebo in relation to pain modulation; summarizes research findings related to human performance in sports and exercise; discusses the implications of placebo/nocebo effects among diverse patient populations; and describes placebo/nocebo influences in research related to psychopharmacology, including the relevance of endogenous opioids to new lines of research on antidepressant pharmacotherapies.

Endogenous Opioid Activity as the Mechanism of Action for Mitragyna speciosa (Kratom): The Current State of the Evidence.

Kratom (Mitragyna speciosa) is a substance derived from botanical compounds native to Southeast Asia. This substance has been cultivated predominantly in Thailand, Malaysia, Vietnam, and Myanmar, where it has historically been used in traditional medicine as a near panacea for several health problems. Such ritualistic use of kratom has been present for centuries; however, recreational use appears to have increased globally, especially in the United States. Pharmacodynamic and pharmacokinetic studies have found that kratom demonstrates a unique parabolic, dose-dependent pattern of effects ranging from stimulation to opioid and analgesic effects. Pharmacological research indicates that kratom is both a mu opioid receptor (µ-OR; MOR) and a kappa opioid receptor (κ-OR; KOR) agonist, which mediates its analgesic effects. Other research suggests that kratom may simultaneously act on dopaminergic and serotonergic receptors, which mediate its stimulant effects. This chapter reviews the literature related to the structural, functional, and cultural characteristics of kratom use. We begin with an overview of current and historical patterns of kratom, followed by a review of data on the pharmacodynamics and pharmacokinetics of kratom thus far.

Depression, Cancer, Inflammation, and Endogenous Opioids: Pathogenic Relationships and Therapeutic Options.

Endogenous opioids and their associated receptors form a system that maintains survival by positively reinforcing behaviors that are vital to life. Cancer and cancer treatment side effects capitalize on this system pathogenically, leading to maladaptive biological responses (e.g., inflammation), as well as cognitive and emotional consequences, most notably depression. Psychologists who treat people with cancer frequently find depression to be a primary target for intervention. However, in people with cancer, the etiology of depression is unique and complex. This complexity necessitates that psycho-oncologists have a fundamental working knowledge of the biological substrates that underlie depression/cancer comorbidity. Building on other chapters in this volume pertaining to cancer and endogenous opioids, this chapter focuses on the clinical applications of basic scientific findings.

Introduction to the Volume: The Journey Ahead.

The endogenous opioid system (EOS) is complex. The line of research contributing to our current body of knowledge about this system is diverse, as are the ways in which endogenous opioids affect human health and behavior. This chapter serves as an introduction to the edited volume. It includes commentary about the current public discourse related to opioids, the rationale for this book, and the unique contributions of each chapter within this volume.

Use of ICD-10 Codes for Human Trafficking: Analysis of Data From a Large, Multisite Clinical Database in the United States.

OBJECTIVES: People experiencing trafficking often seek health care but are not identified. Although the Centers for Disease Control and Prevention added new International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes specific to human trafficking (hereinafter, HT ICD-10-CM codes) that could systematize the identification and documentation of human trafficking in US health care settings, the extent of their use is unknown. The objectives of this study were to investigate (1) the frequency of HT ICD-10-CM code use in US health care organizations (HCOs) and (2) demographic data associated with HT ICD-10-CM codes using a large clinical database. METHODS: This retrospective study used deidentified data collected from October 1, 2018, through March 30, 2021, from a clinical database (N = 69 740 144 patients) network (TriNetX) of 48 collaborating US HCOs. Data included number of patients with ≥1 HT ICD-10-CM code, diagnoses, and demographic characteristics (age, sex, race, ethnicity, and region). RESULTS: HT ICD-10-CM codes were associated with 298 patients in US HCOs, most of whom were young (mean [SD] age, 26 [16] y), White (53.0%; n = 158), and female (87.9%; n = 262). Thirty-seven of 48 (77.1%) participating HCOs used ≥1 HT ICD-10-CM code. The most frequently used HT ICD-10-CM codes were "forced sexual exploitation, suspected" (32.2%; n = 96) and "personal history of forced labor or sexual exploitation" (27.1%; n = 81). Labor trafficking codes were noted in approximately 3.7% of cases. CONCLUSIONS: HT ICD-10-CM codes are being used by health care professionals, as confirmed by large databases. Further research is needed to understand variation in code use and risk factors associated with human trafficking.

A Complex Case of Kratom Dependence, Depression, and Chronic Pain in Opioid Use Disorder: Effects of Buprenorphine in Clinical Management.

Mitragyna speciosa (Kratom) is a psychotropic tropical tree that is indigenous to Southeast Asia, Africa and New Guinea. Kratom has gained popularity in the United States in more recent years as an opioid agonist. Although Kratom is considered an opioid agonist with abuse potential, its use is not federally regulated. We report on a 47 year-old male presenting to our clinic for treatment of an opioid use disorder. This began with the use of prescription opioids from a doctor, and when this was no longer available this patient started using Kratom. He had used Kratom for one year to treat opioid withdrawal symptoms and chronic pain, resulting in worsening depression, anxiety and pain. He experienced tolerance and withdrawal symptoms related to Kratom. He was initiated on buprenorphine-naloxone at home with improved pain management. Four months after initiation, the patient's depression and anxiety symptoms resolved, and he was able to discontinue his antidepressant and anxiolytic medications. Kratom dependence and withdrawal appear similar to that of opioids, and may also lead to worsening depression and anxiety. Buprenorphine-naloxone may be a viable option to consider for treating opioid use disorder complicated by Kratom use, chronic pain, and depression.

Using Telehealth to Implement Cognitive-Behavioral Therapy.

Behavioral health issues are common among patients with comorbid medical conditions but often go unrecognized or untreated, resulting in worse clinical outcomes and avoidable medical expenditures. This column describes an innovative telehealth solution that includes proactive and targeted patient identification and engagement and nationwide delivery of a technology-enabled, standardized, and evidence-based behavioral health program delivered via phone or video. A retrospective before-after evaluation of the program demonstrated national reach, high patient satisfaction, and significant reductions in symptoms of depression, anxiety, and stress.

Ethical Considerations in Mandatory Disclosure of Data Acquired While Caring for Human Trafficking Survivors.

Accurate data on the prevalence and psychological effects of human trafficking as well as treatment outcomes for survivors are essential for measuring the impact of interventions and generating better understanding of this phenomenon. However, such data are difficult to obtain. A legal mandate for health care professionals to report trafficking opens opportunities for advancing our work in the field of human trafficking but also poses risks to survivors seeking services. In this article, we provide an analysis of some critical ethical considerations for the development and implementation of a mandatory reporting policy and offer recommendations for the ethical implementation of such a policy.

Elders' experiences of the death of an adult child.

The death of a child can result in complicated grief. Thirty-one adults, 60 years of age or older, who lost an adult child, participated in a qualitative study using a focus group format that allowed them to discuss their experience. A hermeneutical approach was used to develop an overall thematic description of what it meant to an older person to lose an adult child. Four major themes emerged: losses, limited influence/decision making power, regrets, and decreased quality of life. Suggested interventions to prevent complicated grief in elders who experienced the death of an adult child include attentive listening, storytelling, and the use of metaphors.

Abuse subtypes and nonsuicidal self-injury: preliminary evidence of complex emotion regulation patterns.

Research has identified complex relationships between abuse experiences, emotion regulation, and nonsuicidal self-injury (NSSI). Data generally indicate that individuals with an abuse experience, or those with NSSI, have difficulties with emotion regulation. However, it is unknown whether there are specific patterns of emotion regulation difficulties across abuse subtypes that are uniquely associated with engaging in NSSI. Using a sample of 2238 college students (n = 419; 18.1% with NSSI histories), the present study examined differences in emotion regulation difficulties across specific abuse types between those with and without a history of NSSI. Results indicate significantly greater difficulties with emotion regulation among abused and self-injuring participants as well as significant differences on specific emotion regulation problems between self-injuring and noninjuring participants within the physical abuse and combination physical/sexual abuse subtypes. Possible explanations and implications of these findings are discussed.

Nonsuicidal self-injury: a review of current research for family medicine and primary care physicians.

Self-injury is a dangerous behavior that is different from suicidal behavior but is associated with increased risk of suicide attempts. Some effective psychological treatments for self-injury exist. Physicians in family medicine and primary care settings play a vital role as a first step in the treatment process for those who self-injure. Physicians can enhance the care provided to those who self-injure via the accurate assessment of risk, the understanding of the functions of the behavior, assisting the patient in identifying motivations for treatment and treatment options, and provision of long-term behavioral and risk monitoring. This article summarizes the current scientific knowledge regarding the clinical features, epidemiology, assessment methods, and existing treatments of self-injury. The role of the primary care physician in the treatment of patients who self-injure is specifically outlined.

A quantitative estimate of schema abnormality in socially anxious and non-anxious individuals.

Although cognitive theories of anxiety suggest that anxious individuals are characterized by abnormal threat-relevant schemas, few empirical studies have estimated the nature of these cognitive structures using quantitative methods that lend themselves to inferential statistical analysis. In the present study, socially anxious (n = 55) and non-anxious (n = 62) participants completed 3 Q-Sort tasks to assess their knowledge of events that commonly occur in social or evaluative scenarios. Participants either sorted events according to how commonly they personally believe the events occur (i.e. "self" condition), or to how commonly they estimate that most people believe they occur (i.e. "other" condition). Participants' individual Q-Sorts were correlated with mean sorts obtained from a normative sample to obtain an estimate of schema abnormality, with lower correlations representing greater levels of abnormality. Relative to non-anxious participants, socially anxious participants' sorts were less strongly associated with sorts of the normative sample, particularly in the "self" condition, although secondary analyses suggest that some significant results might be explained, in part, by depression and experience with the scenarios. These results provide empirical support for the theoretical notion that threat-relevant self-schemas of anxious individuals are characterized by some degree of abnormality.