Protracted Withdrawal

The anxiety caused by morphine protracted abstinence is considered to be an important factor contributes to drug-seeking and relapse. Endoplasmic reticulum (ER) stress plays important roles in many kinds of mental disorders including drug addiction and anxiety, but it is unclear whether ER stress is involved in anxiety-like behaviors induced by morphine withdrawal. In this study, by using behavioral test, western blot, immunofluorescence, electron transmission microscope, we found that: (1) Inhibition of endoplasmic reticulum stress by 4-Phenylbutyric acid (4-PBA) could attenuate anxiety-like behaviors induced by morphine withdrawal...

The relationship between pain and alcohol use disorder (AUD) is complex and bidirectional. The current study examines risk factors for pain in a large comprehensively phenotyped sample including individuals from across the spectrum of alcohol use and misuse. Participants (n = 1101) were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol and included treatment-seeking AUD inpatients (AUD+Tx, n = 369), individuals with AUD not seeking treatment (AUD+, n = 161), and individuals without AUD (AUD-, n = 571)...

The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period. We posit that underinvestment has occurred in part due to an underdeveloped understanding of opioid withdrawal syndrome...

Anxiety disorders, common symptoms during morphine withdrawal, are important negative reinforcement factors leading to relapse. Lateral habenula serves as a negative reinforcement center, however its role in morphine withdrawal-induced anxiety remains uncovered. The hyperpolarization activated cyclic nucleotide-gated (HCN) channels have been reported to be important in emotion processing and addiction, but the role of HCN in anxiety from drug protracted abstinence remains elusive. In this study, by using behavioral test, Western blot, immunofluorescence, electrophysiology and virus-mediated regulation of HCN, we found that: (1) Intra-LHb injection of selective HCN blocker ZD7288 alleviated anxiety-like behaviors in morphine protracted abstinent male mice...

BACKGROUND & AIMS: Durable remissions of Crohn's Disease (CD) have followed myeloablative conditioning therapy and allogeneic marrow transplantation. For patients with treatment-refractory disease, we used reduced-intensity conditioning to minimize toxicity, marrow from donors with low Polygenic Risk Scores for CD as cell sources, and protracted immune suppression to lower the risk of graft-versus-host disease (GVHD). Our aim was to achieve durable CD remissions while minimizing transplant-related complications...

BACKGROUND: Adolescent alcohol use can produce long-lasting alterations in brain function, potentially leading to adverse health outcomes in adulthood. Emerging evidence suggests that chronic alcohol use can increase pain sensitivity or exacerbate existing pain conditions, but the potential neural mechanisms underlying these effects require further investigation. Here, we evaluate the impact of chronic ethanol vapor on mechanical sensitivity over the course of acute and protracted withdrawal in adolescent and adult male and female mice, and its potential association with alterations in corticotropin-releasing factor (CRF) signaling within the bed nucleus of the stria terminalis (BNST)...

Loss of consciousness ranks among very common causes for emergency medical service actions and is common occurrence in the emergency department. Its differential diagnosis is very broad and includes many possible causes, not in the least an intoxication. The same applies to convulsive states. Clinical course of mushroom poisoning varies depending on the particular fungal species, with some of the species causing loss of consciousness. One typical representative of such species is panther cap (Amanita pantherina)...

The number of opioid overdose deaths has increased over the past several years, mainly driven by an increase in the availability of highly potent synthetic opioids, like fentanyl, in the illicit drug supply. While many previous studies on fentanyl and other opioids have focused on intravenous administration, other routes of administration remain relatively understudied. Here, we used a drinking in the dark (DiD) paradigm to model oral fentanyl self-administration using increasing fentanyl concentrations in male and female mice over 5 weeks...

A re-examination of clinical principles of long-term opioid therapy (LTOT) for chronic pain is long overdue amid the ongoing opioid crisis. Most patients on LTOT report ineffectiveness (poor pain control, function and health) but still find deprescribing challenging. Although prescribed as analgesics, opioids more likely provide pain relief primarily through reward system actions (enhanced relief and motivation) and placebo effect and less through antinociceptive effects. The unavoidable physiologic LTOT dependence can automatically lead to a paradoxical worsening of pain, disability and medical instability (maladaptive opioid dependence) without addiction due to allostatic opponent neuroadaptations involving reward/antireward and nociceptive/antinociceptive systems...

Excessive alcohol consumption in adolescence can disrupt neural development and may augment pain perception. Recent studies have shown that the nucleus accumbens (NAc) shell is involved in mediating pain sensitivity after peripheral inflammation in rodent models of chronic pain and alcohol use disorder. Interestingly, there have been very few studies examining the impact of chronic ethanol exposure during adolescence on pain sensitivity in adulthood. Therefore, in this project, we investigated the impact of adolescent chronic intermittent ethanol (aCIE) exposure on mechanical allodynia...

BACKGROUND: Despite the popularity of the Twin Block (TB) and the Hanks Herbst (HH) functional appliances, there is limited prospective research comparing these removable and fixed designs, respectively. OBJECTIVES: To evaluate and compare the skeletal and dental effects associated with TB and HH functional appliances as well as to detect factors that might influence the success or failure of treatment in adolescents with Class II malocclusion. DESIGN AND SETTING: A parallel-group randomized controlled trial was undertaken in a single-centre hospital in the United Kingdom...

The cognitive effects of nicotine are linked to persistent modifications in extended neural systems that regulate cognitive and emotional processes, and these changes occur during development. Additionally, acute stress has modulatory effects on cognition that involve broad neural systems and can be influenced by prior environmental challenges. The effects of nicotine and stress may be interconnected, leading to modifications in a network of shared brain substrates. Here, we explored the interaction between nicotine and stress by evaluating the effects of acute stress exposure in spatial memory retrieval for animals pretreated with nicotine during adolescence or adulthood...

BACKGROUND: Since the withdrawal of government forces from Northwest Syria due to the conflict, several national initiatives have aimed to create alternative governance approaches to replace the central governmental system. One of the recent initiatives was the formulation of so-called 'Central Bodies' as institutional governance structures responsible for thematic planning and service provision; for example, the referral unit is responsible for planning and delivering medical referral services...

BACKGROUND: An increasing amount of clinical evidence of acupuncture's effect on protracted opioid abstinence syndrome (POAS) has emerged in recent years. The aim of this study was to evaluating the evidence of efficacy of acupuncture for POAS. clinical and scientific research work. METHODS: Four English-language databases (PubMed, Medline, Embase, Cochrane Libraries) and three Chinese-language databases (CNKI, WanFang and VIP Libraries) were searched, with coverage from database inception to March 31, 2022...

Epidemiological studies and clinical observations suggest that nicotine, a major contributor of the global burden of disease, acts in a partially sex specific manner. Still, preclinical research has primarily been conducted in males. More research is thus required to define the effects displayed by nicotine on the female brain. To this end, female rats received 15 injections of either nicotine (0.36mg/kg) or saline, over a 3-week period and were then followed for up to 3 months. Behavioral effects of nicotine were assessed using locomotor activity measurements and elevated plus maze, while neurophysiological changes were monitored using ex vivo electrophysiological field potential recordings conducted in subregions of the dorsal and ventral striatum...

As clinical studies about subtypes of the cannabis withdrawal syndrome (CWS) are scant, we performed a re-analysis of longitudinal data with German adult cannabis-users seeking inpatient cannabis detoxification-treatment. Sixty-seven cannabis-dependents without active comorbidity were included for growth-mixture-analysis (GMM) of their CWS-severity-trajectories during a scheduled 24-day detox-treatment. As of treatment-day 12, thirty-six (53.7%) of 67 patients were discharged after successful detoxification...

Alcohol use disorder (AUD) can be defined by a compulsion to seek and take alcohol, the loss of control in limiting intake, and the emergence of a negative emotional state when access to alcohol is prevented. Alcohol use disorder impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). Compulsive drug seeking that is associated with AUD can be derived from multiple neuroadaptations, but the thesis argued herein is that a key component involves the construct of negative reinforcement...

BACKGROUND: Chronic opioid exposure leads to hedonic deficits and enhanced vulnerability to addiction, which are observed and even strengthen after a period of abstinence, but the underlying circuit mechanisms are poorly understood. In this study, we test the hypothesis that neurons expressing mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) are involved in addiction vulnerability associated with morphine abstinence, using both molecular and behavioral approaches. METHODS: MOR-Cre mice were exposed to chronic morphine then went through spontaneous withdrawal for 4 weeks, a well-established mouse model of morphine abstinence (ABS)...

INTRODUCTION: Protracted opioid abstinence syndrome (POAS) refers to a series of physical discomforts and neuropsychiatric symptoms after discontinuation of opioid-type substances for a certain amount of time and is one of the main causes of relapse. Studies have shown that acupuncture is effective in the treatment of POAS. We plan to conduct this systematic review and meta-analysis to assess the efficacy and safety of acupuncture for POAS. METHODS AND ANALYSIS: A comprehensive search of studies will be carried out in the following databases from inception to 31 January 2023: Web of Science, Embase, PubMed, Chinese Biology Medicine, China National Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database (VIP)...

INTRODUCTION: The hippocampus and striatum have dissociable roles in memory and are necessary for spatial and procedural/cued learning, respectively. Emotionally charged, stressful events promote the use of striatal- over hippocampus-dependent learning through the activation of the amygdala. An emerging hypothesis suggests that chronic consumption of addictive drugs similarly disrupt spatial/declarative memory while facilitating striatum-dependent associative learning. This cognitive imbalance could contribute to maintain addictive behaviors and increase the risk of relapse...