Opiate withdrawal

Aversive memories related to drug withdrawal can generate a motivational state leading to compulsive drug taking. However, the mechanisms underlying the generation of these withdrawal memories remain unclear. Limbic structures, such as the basolateral amygdala (BLA) and the dentate gyrus (DG) of the hippocampus, play a crucial role in the negative affective component of morphine withdrawal. Given the prominent role of glucocorticoids (GCs), noradrenaline (NA), and dopamine (DA) in memory-related processes, in the present study, we employed the conditioned place aversion (CPA) paradigm to uncover the role of GCs on NA and DA neurotransmission within the BLA and NA neurotransmission within the DG during opiate-withdrawal conditioning (memory formation consolidation), and after reexposure to the conditioned environment (memory retrieval)...

Opiate withdrawal induces an early aversive state which can be associated to contexts and/or cues, and re-exposure to either these contexts or cues may participate in craving and relapse. Nucleus accumbens (NAC), hippocampus (HPC) and basolateral amygdala (BLA) are crucial substrates for acute opiate withdrawal, and for withdrawal memory retrieval. Also HPC and BLA interacting with the NAC are suggested to respectively mediate the processing of context and cue representations of drug-related memories. Here we used a paradigm of conditioned suppression of operant food seeking, allowing to differentiate context and cue related responses, to study the influence of withdrawal memories on operant behavior and the underlying neural substrates...

BACKGROUND AND AIMS: Medication-overuse headache (MOH) is a common chronic headache caused by overuse of headache analgesics. It has similarities with substance dependence disorders. The treatment of choice for MOH is withdrawal of the offending analgesics. Behavioral brief intervention treatment using methods adapted from substance misuse settings is effective. Here we investigate the severity of analgesics dependence in MOH using the Severity of Dependence Scale (SDS), validate the SDS score against formal substance dependence diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and examine whether the SDS predicts successful withdrawal...

OBJECTIVE: To review the pharmacology, efficacy, and safety of lofexidine for the treatment of opioid withdrawal secondary to the recent Food and Drug Administration (FDA) approval. DATA SOURCES: A literature search using PubMed was conducted (inception to December 2018) using the terms lofexidine, opioid, opiate, and withdrawal. References from retrieved articles and the prescribing information were reviewed for any additional material. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in English that pertained to human pharmacology, pharmacokinetics, pharmacodynamics, dosing, efficacy, and safety regarding opioid withdrawal...

BACKGROUND: Patients with opioid withdrawal often present to the Emergency Department (ED), but many EDs do not have the infrastructure in place to initiate treatment with opioid agonists (methadone or buprenorphine). Therefore, ED management often entails symptomatic control. The purpose of this study was to compare olanzapine to clonidine for the treatment of opioid withdrawal symptoms. METHODS: This was a prospective, randomized clinical trial comparing 10 mg of IM olanzapine to 0...

OBJECTIVES: Neonatal abstinence syndrome (NAS) is characterized by withdrawal symptoms in neonates exposed to legal or illegal substances in utero , and it is often managed with medications such as opiates, phenobarbital, and clonidine. Clonidine use is increasing, but further safety data regarding its use in neonates are warranted. This study evaluated the effects of clonidine on heart rate and blood pressure in neonates treated for NAS at doses up to 24 mcg/kg/day. METHODS: A retrospective review via the electronic medical record of infants at least 35 weeks' gestation treated adjunctively with clonidine for NAS in the neonatal intensive care unit at St Elizabeth was conducted...

Objective: Individuals with chronic pain who misuse prescription opioids are at high risk for developing opioid use disorder and/or succumbing to opioid overdose. The current study conducted a survey to evaluate sex-based differences in pain catastrophizing, opioid withdrawal, and current pain in persons with co-occurring chronic pain and opioid misuse. We hypothesized that women with chronic pain who misused prescription opioids would self-report higher pain ratings compared with men and that the relationship between pain catastrophizing and self-reported current pain would be moderated by symptoms of opioid withdrawal in women only...

In this study, we aimed to investigate a potential role of small heterodimer partner (Shp, a nuclear receptor) in regulation of morphine withdrawal syndrome and to determine the mechanisms thereof. Somatic opiate withdrawal and pharmacokinetic experiments were performed with wild-type (WT) and Shp knockout (Shp-KO) mice. Regulatory effects of Shp on Ugt2b expression were assessed in vitro (using mouse hepatoma Hepa1-6 cells) and in vivo (using Shp-KO mice). Ugt2b mRNA and protein expression were determined by qPCR and Western blotting, respectively...

PURPOSE: Baclofen has been reported to cause both a metabolic encephalopathy and nonconvulsive status epilepticus. Baclofen is typically used in the management of muscle spasticity but is being increasingly used to manage alcohol withdrawal and opiate dependency. Given the increasing use of baclofen we describe the clinical and electrographical features of baclofen neurotoxicity seen at our institution. METHODS: The clinical and EEG features of patients with an encephalopathy in the setting of baclofen therapy were analyzed...

Neonatal abstinence syndrome (NAS) is a group of problems associated with withdrawal symptoms of a newborn who was exposed to maternal opiate use while in the womb. West Virginia (WV) is of utmost concern as this state exhibits among the highest rates of opioid abuse and consequently, NAS. In this manuscript, we review factors associated with the prevalence of NAS in WV. We provide evidence suggesting that states exhibiting high Medicaid participation demonstrate a high NAS rate, further associating these two factors...

Negative affective aspects of opiate abstinence contribute to the persistence of substance abuse. Importantly, interconnected brain areas involved in aversive motivational processes, such as the ventral tegmental area (VTA) and medial prefrontal cortex (mPFC), become activated when animals are confined to withdrawal-paired environments. In the present study, place aversion was elicited in sham and adrenalectomized (ADX) animals by conditioned naloxone-precipitated drug withdrawal following exposure to chronic morphine...

BACKGROUND AND OBJECTIVES: Polysubstance use is associated with relapse and poor treatment outcomes among people dependent on heroin. Despite the high prevalence of polysubstance use among patients detoxifying from heroin, little is known about patients' expectations to abstain or use non-opiate substances. The current study examined factors associated with expectations about abstaining from alcohol, cocaine, and benzodiazepines (BZDs) following heroin withdrawal management. METHODS: Between May and December of 2015, we surveyed 417 patients (71...

OBJECTIVES: To investigate the safety and efficacy of lofexidine for treating opioid withdrawal syndrome (OWS) and facilitating completion of opioid withdrawal. METHODS: A multicenter, double-blind, placebo-controlled study was conducted at 18 US centers from June 2013 to December 2014. Participants (n = 603) aged ≥18 years, dependent on short-acting opioids, and seeking withdrawal treatment, randomized 3:3:2 to receive lofexidine 2.88 mg/d (n = 222), lofexidine 2...

BACKGROUND: Opioid use disorder is one of the most prevalent addiction problems worldwide. Buprenorphine is used as a medication to treat this disorder, but in countries where buprenorphine is unavailable in combination with naloxone, diversion can be a problem if the medication is given outside a hospital setting. OBJECTIVE: The objective of this research is to evaluate the effect of a single, high dose of buprenorphine on craving in opioid-dependent patients over 5 days of abstinence from use of other opioids...

Somatic and motivational symptoms accompanying opiate withdrawal are considered one of the major reasons for relapse to opiate-seeking and opiate-taking behaviors. These symptoms are accompanied by the activation of stress-related processes including hypothalamic-pituitary-adrenal axis activity and noradrenergic (NA) signaling. In particular, the NA system plays an important role in the expression of somatic signs of opiate withdrawal, whereas glucocorticoid (GR) and mineralocorticoid receptors (MR) are activated during opiate abstinence...

Background: The need for effective and accepted method for opioid detoxification is ever increasing. Sublingual buprenorphine and oral clonidine have been effective in opioid detoxification. As often, there is a great variation in the dosage of buprenorphine and clonidine prescribed by the clinicians; hence, there is a felt need to find an effective dosage for a favorable outcome of opioid detoxification. Objective: The objective of this study was to compare the effectiveness of different doses of sublingual buprenorphine and clonidine in opioid detoxification...

BACKGROUND AND OBJECTIVES: Although buprenorphine/naloxone is widely recognized as first-line therapy for opioid use disorder, the requirement for moderate withdrawal prior to initiation in efforts to avoid precipitated withdrawal can be a barrier to its initiation. METHODS: We present a case utilizing transdermal fentanyl as a bridging treatment to eliminate withdrawal during the transition from methadone to buprenorphine/naloxone in a patient who had ongoing significant intravenous heroin use while on methadone...

BACKGROUND/AIMS: Opiates are potent analgesics but their clinical use is limited by sex-associated side effects, such as drug tolerance, opioid-induced hyperalgesia and withdrawal reaction. OPRM1, as the main receptor of opioids, plays an important role in the pharmacological process of opioids in rodents and human. We have previously investigated OPRM1, the μ opioid receptor gene, which have dozens of alternatively spliced variants probably correlating with opioid-induced effects in brain regions of four inbred mouse strains and demonstrated the strain-specific expressions of these splice variants...

Nalbuphine is an agonist of κ-opioid receptors and a partial agonist of μ-opioid receptors, which can stimulate κ-receptors and antagonize the acute rewarding effects of morphine. It is widely used either as an analgesic or as an adjuvant with morphine. This present study aimed to compare the acute and chronic effects of nalbuphine on the naloxone-precipitated opiate-withdrawal in rats. Male adult Wistar albino rats (150-175 g, n = 160) were made physically dependent by administrating increasing dose of morphine (5-25 mg/kg; i...

Opioid use disorder (OUD) is a public health crisis. Differences in opioid withdrawal severity that predict treatment outcome could facilitate the process of matching patients to treatments. This is a secondary analysis of a randomized controlled trial (RCT) that enrolled treatment seeking heroin-users (N = 89, males = 78) into a residential study. Participants maintained on morphine (30 mg, subcutaneous, four-times daily) underwent a naloxone (0.4 mg, IM = intramuscular) challenge session to precipitate withdrawal...