Addiction Science to Practice

Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals...

The human σ1 receptor is an enigmatic endoplasmic-reticulum-resident transmembrane protein implicated in a variety of disorders including depression, drug addiction, and neuropathic pain. Recently, an additional connection to amyotrophic lateral sclerosis has emerged from studies of human genetics and mouse models. Unlike many transmembrane receptors that belong to large, extensively studied families such as G-protein-coupled receptors or ligand-gated ion channels, the σ1 receptor is an evolutionary isolate with no discernible similarity to any other human protein...

Objective: The objective of this project was to develop core competencies for education on opioids and addiction to be used in all Pennsylvania medical schools. Methods: The Pennsylvania Physician General created a task force that was responsible for the creation of the core competencies. A literature review was completed, and a survey of graduating medical students was conducted. The task force then developed, reviewed, and approved the core competencies. Results: The competencies were grouped into nine domains: understanding core aspects of addiction; patient screening for substance use disorder; proper referral for specialty evaluation and treatment of substance use disorder; proper patient assessment when treating pain; proper use of multimodal treatment options when treating acute pain; proper use of opioids for the treatment of acute pain (after consideration of alternatives); the role of opioids in the treatment of chronic noncancer pain; patient risk assessment related to the use of opioids to treat chronic noncancer pain, including the assessment for substance use disorder or increased risk for aberrant drug-related behavior; and the process for patient education, initiation of treatment, careful patient monitoring, and discontinuation of therapy when using opioids to treat chronic noncancer pain...

While opioids are very effective analgesics for treating acute pain, humans have struggled with opiate addiction for millenia. An opium abuse epidemic in the early 1900's led the US government to develop a systematic research infrastructure and scientific plan to produce new compounds with analgesic properties but without abuse liability. This review describes the techniques that were developed for testing in the human laboratory, including empirically derived outcome measures and required elements for human abuse potential assessment...

Depression is a debilitating chronic illness that affects around 350 million people worldwide. Current treatments, such as selective serotonin reuptake inhibitors, are not ideal because only a fraction of patients achieve remission. Tianeptine is an effective antidepressant with a previously unknown mechanism of action. We recently reported that tianeptine is a full agonist at the mu opioid receptor (MOR). Here we demonstrate that the acute and chronic antidepressant-like behavioral effects of tianeptine in mice require MOR...

Substance use disorders are exceedingly complicated as is the treatment. In order to increase positive outcomes an understanding of all facets; bio, psycho/social/spiritual, economic, and interdisciplinary aspects are essential to successful treatment. There are an increasing number of integrative addictions treatment centers across the United States, and disciplines that care for this population who are committed to a holistic, integrative approach to addictions treatment. Whole-person interventions, the foundational underpinnings of complementary and integrative therapies that attend to mind, body, and spirit simultaneously, in combination with traditional health care, will serve to provide the most effective treatment and patient outcomes...

BACKGROUND: The high prevalence and severity of methamphetamine (MA) abuse demands greater neurobiological understanding of its etiology. METHODS: We conducted immunoblotting and in vivo microdialysis procedures in MA high/low drinking mice, as well as in isogenic C57BL/6J mice that varied in their MA preference/taking, to examine the glutamate underpinnings of MA abuse vulnerability. Neuropharmacological and Homer2 knockdown approaches were also used in C57BL/6J mice to confirm the role for nucleus accumbens (NAC) glutamate/Homer2 expression in MA preference/aversion...

In this review, we detail the clinical evidence supporting the role of psychological and physiological stress in instrumental motivation for alcohol consumption during the development of mild to moderate alcohol use disorders (AUDs) and in the compulsive, habitual alcohol consumption seen in severe, chronic, relapsing AUDs. Traditionally, the study of AUDs has focused on the direct and indirect effects of alcohol on striatal dopaminergic pathways and their role in the reinforcing effects of alcohol. However, growing evidence also suggests that alcohol directly stimulates the hypothalamic pituitary adrenal (HPA) axis and has effects on glucocorticoid receptors in extrahypothalamic, limbic forebrain, and medial Prefrontal Cortex (PFC) circuits, which contribute to the development of AUDs and their progression in severity, chronicity, and relapse risk...

The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) and to the widely consumed plant phytocannabinoid Δ9 -tetrahydrocannabinol (THC). The cannabinoid receptors have been the targets of intensive drug discovery efforts, because modulation of these receptors has therapeutic potential to control pain, epilepsy, obesity, and other disorders. Although much progress in understanding the biophysical properties of GPCRs has recently been made, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data...

OBJECTIVE: To explore the analgesic mechanism of small knife needle for treating transverse process syndrome of the third vertebra (TPSTV) by observing peripheral and central changesof β-endorphin (β-EP) and enkephalin (ENK) contents. METHODS: Totally 30 Japanese white big-ear rabbits of clean grade were divided into 5 groups according to random digit table, i.e., the normal control group, the model group, the small knife needle group, the electroacupunture (EA) group, and the small knife needle plus EA group, 6 in each group...

The factors causing the transition from recreational drug consumption to addiction remain largely unknown. It has not been tested whether dopamine (DA) is sufficient to trigger this process. Here we use optogenetic self-stimulation of DA neurons of the ventral tegmental area (VTA) to selectively mimic the defining commonality of addictive drugs. All mice readily acquired self-stimulation. After weeks of abstinence, cue-induced relapse was observed in parallel with a potentiation of excitatory afferents onto D1 receptor-expressing neurons of the nucleus accumbens (NAc)...

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.