Tramadol misuse is a significant problem in Egypt, yet little is known about tramadol users. The aim of this study is to examine the motivations for use of tramadol or heroin among patients...

An examination of motives for tramadol and heroin use in an Egyptian sample.

Tramadol is an analgesic with monoamine reuptake inhibition and μ-opioid receptor activation. Although tramadol has been widely used for treatment of various pain conditions, there is controversy over the risk of abuse potential. We examined the effects of tramadol on the reward system in humans using functional magnetic resonance imaging (fMRI) to assess the potential of tramadol for drug abuse or dependence. A randomized, double-blind, placebo-controlled, crossover study was conducted for 19 healthy adults under tramadol or placebo. In association with subjective mood questionnaires, monetary incentive delay (MID) task was performed to assess the neural response to reward anticipation during fMRI. Subjective mood measures and blood oxygenation level-dependent (BOLD) signal during gain and loss anticipation were compared between tramadol and placebo. Tramadol significantly reduced anxiety (Z = − 2.513, p = 0.012) and enhanced vigor (Z = − 2.725, p = 0.006) compared with placebo. By Mood Rating Scale, tramadol provoked contented (Z = − 2.316, p = 0.021), relaxed (Z = − 2.236, p = 0.025), and amicable feelings (Z = − 2.015, p = 0.044) as well as increased alertness (Z = − 1.972, p = 0.049) and contentedness domains (Z = − 2.174, p = 0.030) compared with placebo. Several brain regions including nucleus accumbens (NAc) were activated during gain anticipation in the MID task under both tramadol and placebo. Tramadol increased the %BOLD signal change in NAc at +¥500 cue significantly more than the placebo (Z = − 2.295, p = 0.022). Tramadol enhances the reward system and thereby may have abuse potential or precipitate drug abuse in human.

Acute tramadol enhances brain activity associated with reward anticipation in the nucleus accumbens

Tramadol, an atypical μ-opioid receptor agonist, as a psychoactive drug, is frequently abused by human beings. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help prevent drug addiction and relapse. Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-d-aspartate (NMDA) receptors (Jafari-Sabet et al. Can J Physiol Pharmacol 96:45-50, 2018). To clarify the exact mechanisms involved, the activation of CA1 nitric oxide (NO) signaling pathway by l-arginine (a nitric oxide precursor) on the interaction between tramadol and MK-801 in memory retrieval was examined. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated and a single-trial step-down inhibitory avoidance apparatus was used for the assessment of memory retrieval. Post-training and/or pre-test microinjection of tramadol (0.5 and 1 μg/mouse) and/or a non-competitive NMDA receptor antagonist, MK-801 (0.25 and 0.5 μg/mouse), induced amnesia which were reversed when the same doses of the drugs were administered 24 h later in a pre-test session, suggesting tramadol state-dependent learning (SDL) and MK-801 SDL. The amnesia induced by post-training microinjection of tramadol (1 μg/mouse) was reversed by pre-test microinjection of MK-801 (0.25 and 0.5 μg/mouse). Pre-test microinjection of MK-801 (0.125 and 0.25 μg/mouse) with an ineffective dose of tramadol (0.25 μg/mouse) potentiated tramadol SDL. The amnesia induced by post-training microinjection of MK-801 (0.5 μg/mouse) was reversed by pre-test microinjection of tramadol (0.5 and 1 μg/mouse). Pre-test microinjection of tramadol (0.25 and 0.5 μg/mouse) with an ineffective dose of MK-801 (0.125 μg/mouse) potentiated MK-801 SDL. Pre-test microinjection of ineffective doses of l-arginine (0.125, 025, and 0.5 μg/mouse) improved amnesia induced by the co-administration of tramadol and MK-801. Pre-test microinjection of l-arginine (0.125, 025, and 0.5 μg/mouse) could not reverse amnesia induced by post-training microinjection of tramadol while same doses of l-arginine improved MK-801 response on tramadol SDL. The results strongly propose that activation of CA1 NO signaling pathway has a pivotal role in cross SDL among tramadol and MK-801.

Cross state-dependency of learning between tramadol and MK-801 in the mouse dorsal hippocampus: involvement of nitric oxide (NO) signaling pathway.

Tramadol is a common drug of abuse which has been shown to cause neurodegeneration in the rat brain. Cytidine-5'-diphosphocholine or citicoline is an intermediate in the synthesis of phosphatidylcholine and is in use in humans for the treatment of several brain pathologies. In this study, we aimed to investigate the effect of citicoline on oxidative stress and tissue injury caused by tramadol, an opioid drug. Rats were treated with tramadol at 30 mg/kg alone or in combination with citicoline at 50, 100, or 200 mg/kg orally, once a day, for 10 days. Other groups were treated with only 0.9% saline or only citicoline at 200 mg/kg. Lipid peroxidation (malondialdehyde), nitric oxide, reduced glutathione (GSH), and paraoxonase-1 (PON-1) activity were measured in the serum. Bone marrow DNA fragmentation assay and micronucleus test were also done. In addition, histopathological examination of the brain, liver, and kidney, and immunohistochemical staining for glial cell acidic fibrillary protein (GFAP) in the cerebral cortex were performed. Results indicated that compared to the saline-treated group, repeated tramadol administration led to significant increases in serum malondialdehyde and nitric oxide concentrations by 50.0% and 70.0%, respectively. There was also a decline in GSH content and PON-1 activity in the serum by 26.3% and 51.4%, respectively. Tramadol caused marked DNA fragmentation and increased the number of micronucleated polychromatic erythrocytes (MnPCE) in bone marrow by 192.8% and 876.3%, respectively, compared with the corresponding saline control values. Histopathological studies revealed neuronal degeneration (acidophilic cytoplasm and dark nuclei) and decreased GFAP immunostaining in the cerebral cortex of tramadol-treated rats. The liver exhibited fibrosis, apoptotic hepatocytes, and inflammatory cell infiltration. Vacuolar degeneration of the tubular lining epithelium and edema of glomeruli were observed in the kidney. Citicoline administered to saline-treated rats at a dose of 200 mg/kg showed no significant effect on serum malondialdehyde, nitric oxide, GSH concentrations, or PON-1 activity compared with the saline control group. Citicoline by itself had no effect on DNA fragmentation or the number of MnPCE in the bone marrow. In tramadol-treated rats, however, citicoline (50–200 mg/kg) resulted in a significantly decreased malondialdehyde by 23.8%–31.6%. Nitric oxide decreased by 29.2%–36.2% after citicoline at 50–200 mg/kg. There was also a significant increase in both GSH by 19.6%–33.6% and in PON-1 activity by 54.8%–125.7%. In addition, citicoline caused a significant decrease in DNA fragmentation (by 29.2%–52.4%) and the number of MnPCE in the bone marrow (by 20.5%–59.5%) in tramadol-treated rats. Histopathological changes caused by tramadol in the brain, liver, and kidney were ameliorated by treatment with citicoline. We conclude that citicoline treatment results in decreased lipid peroxidation and nitric oxide along with increased GSH content and PON-1 activity in the serum of rats treated with tramadol. These changes might account for the beneficial effect of citicoline in decreasing DNA fragmentation and tissue injury caused by tramadol.

Citicoline Protects against Tramadol-Induced Oxidative Stress and Organ Damage

Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors

Background and Objective: Substance abuse in the workplace is a major public health problem. The objectives of this study are to: (1) to determine the prevalence and associated risk factors of substance abuse, drug-related problems, and drug dependence among industrial workers; (2) to identify patients' views of the pros and cons of their drug use and their treatment readiness; and (3) to assess the severity of substance abuse according to the Addiction Severity Index (ASI) scale in substance users. Subjects and Methods: A total of 353 industrial workers from 5 factories in 10th of Ramadan city in Egypt were included in the study. The participants were interviewed to collect sociodemographic and clinical data using the Structural Clinical Interview for DSM-IV-Axis I (SCID-I), the Drug Use Disorder Identification Test (DUDIT), DUDIT-Extended version and the Addiction Severity Index (ASI). The participants were screened for drug abuse by urine analysis. Results: The prevalence rates of smoking and substance abuse were 27.6% and 18.3%, respectively. The most commonly abused drugs were tramadol (66.2%), cannabis (55.4%), and alcohol (38.5%). Compared with controls, smokers and substance users were more likely to be males and were older. Smokers were 7 times more likely to use substances. Substance dependence was associated with a younger age of substance use onset and alcohol abuse. Conclusions: Smoking and substance abuse are common among industrial workers. Tramadol and cannabis are the most commonly abused substances. Smoking, older age, and male sex are correlates of substance abuse. Alcohol abuse is associated with dependence.

Substance Use Disorders Among Industry Workers in Egypt

Background and objective Cognitive impairment is one of the consequences of substance abuse. Tramadol abuse is a public health problem in Egypt. The objective of this study was to estimate the prevalence and correlates of cognitive impairment among tramadol-abuse patients and control subjects. Methods This study included 100 patients with tramadol abuse and 100 control subjects (matched for age, sex, and education) who were recruited from Zagazig University Hospital, Egypt. Patients were divided into 2 groups: patients who used tramadol only (tramadol-alone group) and patients who used tramadol and other substances (polysubstance group). The participants were interviewed using Montreal Cognitive Assessment test and had urine screening for drugs. Results Twenty-four percent of the cases used tramadol alone, whereas the remaining used tramadol and other substances, mainly cannabis (66%) and benzodiazepines (27%). Tramadol-abuse patients were about 3 times more likely to have cognitive impairment than control subjects (81% vs 28%). Tramadol-alone patients were more than 2 times more likely to have cognitive impairment than control subjects (67% vs 28%). Cognitive impairment was significantly associated with polysubstance abuse. There was no association between cognitive impairment and sociodemographic or clinical factors. Conclusions Cognitive impairment occurs commonly among tramadol-abuse patients. Memory impairment is the most common cognitive domain to be affected. There is a significant association between cognitive impairment and polysubstance abuse.

Cognitive Impairment and Tramadol Dependence.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Dalia H. Ibrahim

Author Tools

Chat about Author

Papers

Substance Use Disorders Among Industry Workers in Egypt

Cognitive Impairment and Tramadol Dependence.