Tramadol Addiction Research Articles

Exploring the potential use of melatonin as a modulator of tramadol-induced rewarding effects in rats.

Melatonin is responsible for regulating the sleep-wake cycle and circadian rhythms in mammals. Tramadol, a synthetic opioid analgesic, is used to manage moderate to severe pain but has a high potential for abuse and dependence. Studies have shown that melatonin could be a potential modulator to reduce tramadol addiction. Male Wistar rats were used to investigate the effect of melatonin on tramadol-induced place preference. The rats were divided into four groups: control, tramadol, tramadol + melatonin (single dose), and tramadol + melatonin (repeated doses). Tramadol was administered intraperitoneally at 40mg/kg, while melatonin was administered at 50mg/kg for both the single dose and repeated-dose groups. The study consisted of two phases: habituation and acquisition. Tramadol administration produced conditioned place preference (CPP) in rats, indicating rewarding effects. However, melatonin administration blocked tramadol-induced CPP. Surprisingly, repeated doses of melatonin were ineffective and did not reduce the expression of CPP compared to that of the single dose administration. The study suggests that melatonin may be a potential therapeutic option for treating tramadol addiction. The results indicate that melatonin attenuates the expression of tramadol-induced CPP, supporting its uses as an adjunct therapy for managing tramadol addiction. However, further studies are needed to investigate its effectiveness in humans.

The frequency and impact of tramadol addiction on acute aneurysmal subarachnoid hemorrhage: cross-sectional multicenter study

BackgroundArterial hypertension, cigarette smoking, excessive alcohol abuse and drug addiction such as cocaine all are known risk factors for aneurysmal subarachnoid hemorrhage (SAH). However, there is little information on whether tramadol addiction should also be considered as a risk factor for SAH. The purpose of this study was to investigate the prevalence and the impact of tramadol addiction on the symptomatology of intracranial aneurysmal SAH. We recruited 237 cases with acute aneurysmal ASH with a mean age of 52.3 ± 11.8 ranging from 17 to 86 years old.ResultsThere were 124 males and 113 females; 43 cases had a history of tramadol addiction (18.1%). Tramadol addicts were significantly younger, more likely to be male (97.7%), and more commonly associated with seizure onset compared with non-addicts. Multiple aneurysms, wide neck, and sizable aneurysms were significantly more common in tramadol than non-tramadol addicts as were dissecting aneurysms. There is a high association of acute aneurysmal SAH with tramadol addiction, especially in young patients.ConclusionsTramadol addiction might be regarded as modifiable risk factor of aneurysmal ASH and tramadol addicts had a worse presentation than non-tramadol addicts. If this finding is proved, it will be of great importance in managing patients with ruptured and un-ruptured intracranial aneurysms. Tramadol is available over-counter in some countries, more studies are needed.

Sleep characteristics in patients with tramadol dependence

Introduction: Despite the fact that tramadol is commonly assumed as a therapeutic medication, it has the potential to create addiction, especially when taken for extended durations and in high dosages. In Egypt, tramadol misuse has recently get to be a severe health issue. Tramadol and other opioids, have a clinically known influence on sleep. However, just a few studies have evaluated the influence of tramadol addiction on sleep. Objectives: 1). Tcomparing the sleep architecture of Tramadol-dependent patients to that of normal controls; 2).To find out what variables are connected with Tramadol misuse and alterations in sleep architecture. Methodology: The research was a case-control, comparison study that was conducted on a convenient sample of male Egyptian Tramadol addicts. The study includes 40 patients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for tramadol addiction and were recruited from the inpatient addiction department at Cairo University's Psychiatry and Addiction Medicine Hospital, that were evaluated by comparing to a control group of 20 matched controls. The Addiction Severity Index (ASI), the Sleep Disorder Questionnaire (SDQ), and an overnight attended polysomnographic study (PSG) were administered to the participants.

Buprenorphine for High-dose Tramadol Dependence: A Case Report of Successful Outpatient Treatment.

IntroductionDuring the coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2, deaths from opiate drug overdoses reached their highest recorded annual levels in 2020. Medication-assisted treatment for opiate use disorder has demonstrated efficacy in reducing opiate overdoses and all-cause mortality and improving multiple other patient-centered outcomes. Treatment of tramadol dependence in particular poses unique challenges due to its combined action as opioid agonist and serotonin-norepinephrine reuptake inhibitor. Tramadol puts patients with dependence at risk for atypical withdrawal syndromes when attempting to reduce use. Little evidence is available to guide treatment of tramadol dependence.Case ReportWe present a case of high-dose tramadol addiction that began with misuse of medically prescribed tramadol for treatment of musculoskeletal back pain. The patient’s use reached oral consumption of 5000–6000 milligrams of illicit tramadol daily. She complained of common complications of tramadol use disorder including memory impairment, excessive sedation, and tramadol-induced seizures. The patient was referred to the emergency department in a withdrawal crisis seeking treatment where she was successfully managed with buprenorphine and phenobarbital and then linked to ongoing outpatient treatment.ConclusionOur report adds to the limited guidance currently available on the acute management of tramadol withdrawal and treatment of tramadol use disorder. Our case suggests the initiation of high-dose buprenorphine may be an effective and feasible option for emergency clinicians.

The Effect of Orexin-2 and Endocannabinoid-1 Antagonists on Neuronal Activity of Hippocampal CA1 Pyramidal Neurons in Response to Tramadol in Rats.

Background:CA1, as a major structure involved in learning and memory, has been shown to be affected by tramadol addiction. Both orexin and endocannabinoid receptors express in CA1 and play an important role in drug dependency. The aim of this study was to evaluate the modulatory effects of orexin-2 (OX2R) and endocannabinoid-1 (CB1R) receptors on neuronal activity in CA1, in response to tramadol in rats.Materials and Methods:Male Wistar rats were divided into 8 groups (n = 6–7); saline-dimethyl sulfoxide (DMSO), tramadol-DMSO, saline-TCS-OX2-29, saline-AM251, tramadol-TCS-OX2-29, tramadol-AM251, saline-TCS-OX2-29-AM251, tramadol-TCS-OX2-29-AM251. Tramadol was injected intraperitoneally, and then, AM251 (1 nmol/0.3 μL), CB1R antagonist and TCS-OX2-29 (1 nmol/0.3 μL), OX2R antagonist, were microinjected individually or concurrently into the CA1. Using in vivo extracellular single-unit recording, the firing of CA1 pyramidal neurons was investigated.Results:Tramadol decreased neuronal activity in CA1 (P < 0.01) but increased it after micro-injection of DMSO. TCS-OX2-29 increased neuronal activity in saline group (P < 0.05) but decreased it in tramadol group. AM251 had no effect on saline group but decreased neuronal activity in tramadol group (P < 0.05). Concurrent micro-injection of TCS-OX2-29 and AM251 had no effect on saline group but decreased neuronal activity in tramadol group (P < 0.05).Conclusions:Our findings suggest that neural activity in CA1 is rapidly affected by acute use of tramadol, and some of these effects may be induced through the endocannabinoid and orexin systems. Thus, the function of endocannabinoid and orexin systems in CA1 may play a role in tramadol addiction.

The acute effects of different doses of tramadol on neuronal activity of medial prefrontal cortex in rats

Background:Tramadol is an opioid analgesic with monoamine reuptake inhibitory effects. Although tramadol has been widely used to control pain, there is controversy about the risk of abuse. Therefore, in the present study, the acute effects of tramadol on neuronal activity in the medial prefrontal cortex (mPFC), which is one of the important centers of the reward system, were investigated electrophysiologically.Materials and Methods:Tramadol was injected interperitoneally (12.5 and 25 mk/kg) or subcutaneously (40 mg/kg) and its effect on the firing of mPFC neurons was investigated, using in vivo extracellular single unit recording.Results:Tramadol could not significantly affect neural activity in mPFC, suggesting no acute and rapid effect on mPFC.Conclusions:The present results showed that neural activity in mPFC was not rapidly affected by acute application of tramadol. Since the role of mPFC in tramadol addiction has been elucidated, it can be concluded that these effects may be due to delayed responses or chronic use of tramadol.

The effectiveness of a group cognitive behavioral therapy program in

the purpose of this study is to investigate the effectiveness of a group therapy program to reduce depression among tramadol addicts in Jeddah, Saudi Arabia. The study population consisted of a sample of tramadol addicts who visited a private clinic in Jeddah. The total number of the sample was 24 addicts who voluntarily agreed to participate in the study

Tramadol abuse and addiction

BackgroundAddiction to controlled or prescription drugs is an increasing health burden in most countries and Nigeria is not an exception. Tramadol abuse is a menace in Nigeria. There are few reports on the health consequences of tramadol addiction in the Niger Delta region of Nigeria.AimThe aim of the study was to determine and educate the public on the effects of tramadol addiction on learning, memory, and organ damage.Materials and methodsAdult rats were randomly assigned into four groups,n=5. Group 1 received 5 ml/kg of 0.9% normal saline orally, while groups 2, 3, and 4 were administered 50, 100, and 200 mg/kg of tramadol daily for 28 days, respectively. Behavioral tests (Y-maze and Morris water maze) were conducted on the first and last weeks of the experiment. On the 29th day, the animals were sacrificed under halothane anesthesia and organs were excised for histological examination. The results were analyzed using one-way analysis of variance (GraphPad Prism 6).ResultsThe behavioral assessments revealed dose-dependent aggression, anxiety, and spasms. Also, a reduction in escape latency in the Morris water maze and increased alternations in the Y-maze occurred to various degrees in the treated groups compared with the control. Different grades of histological abnormalities occurred in the brain, liver, and kidneys of treated rats.ConclusionTramadol misuse can lead to learning and memory impairment in addition to long-term organ damage involving the brain, liver, and kidneys.

Suicide Probability Among Tramadol Addicts

Abstract Background The magnitude of the problem of substance use in Egypt has been growing lately. Substance use disorders have been associated with depression and suicide, as well as impulsivity and specific personality traits. Suicide is closely linked to the substances use. Therefore it is very important to confirm the factors that affect the possibility of suicide. Aim of the Work This study aimed at evaluating suicide risk and its correlation with each of personality disorders and severity of addiction in a sample of 72 tramadol addicts from outpatient clinic of Institute of psychaitry Ain Shams University hospitals. Patients and Methods This is a descriptive Cross sectional study conducted in outpatient clinic of Institute of psychaitry Ain Shams University hospital. The present study aimed at analyzing the demographic data of 72 tramadol addicts, over six months period from January 2018 to August 2019. The severity of the addiction problem among those patients was assessed using Addiction Severity Index (ASI), suicidal probability was assessed using suicide probability scale (SPS), Structured Clinical Interview for DSM-VI Axis II (SCID-II) for assessing personality disorders and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I). Results The results showed that 32 (44.44%) of the patients had a risk of suicide probability. Also there was a statistically significant difference between risk of suicidal probability and personality disorders especially antisocial personality. It was found that the need for more power for work and pleasurable effects were the most risk factors for tramadol addiction. Conclusion Suicide probability was found to be (44.44%) among the studied tramadol addicts. The risk of suicide probability among them was found to be significant in each of the following: antisocial personality disorder, longer duration of addiction, being single and positive family history of addiction. Attention should be paid to include the assessment of suicidal risk as part of routine assessment of addicts.

Impulsivity and Decision-making Style Among Tramadol Drug Addicts and its Relation to Frontal Lobe Volume

Objectives: Drug addiction has its effects on different behavioral and personality traits including impulsivity and pattern of decision-making. The frontal lobe was the focus of many of these studies regarding its important role in decision-making and other higher cognitive processes. We aimed to detect the pattern of decision-making styles and impulsivity among people with tramadol addiction, and also to find out if tramadol addiction has effects on the volume of different regions of the frontal lobe. Materials and Methods: Two groups were included: group A included 12 patients with tramadol addiction and group B included 23 healthy cross-matching controls. Both groups were subjected to urine drug screening, Iowa gambling task (IGT), UPPS scales (negative urgency, lack of perseverance, lack of premeditation, and sensation seeking), and structural magnetic resonance imaging brain study. Results: The patients’ group has shown a significantly lower volume of the brain white matter, gray matter, and cortical thickness (P&lt;0.001). This group has also shown a significantly higher scores of IGT-A and IGT-B (P&lt;0.001 and P=0.02, respectively) and has shown a higher score of all subscales of UPPS. Conclusions: Tramadol addiction is associated with a reduced volume of the brain white matter, gray matter, and cortical thickness. All regions of the frontal lobe have shown significant volume reduction in the tramadol group. Tramadol addiction and its duration are associated with risky decision-making style and with higher impulsivity than nonaddicts.

Suicide Probability Among Tramadol Addicts

Objectives: Tramadol addiction is one of the major addiction problems in growing countries, especially in Egypt. Moreover, there is a strong relation between suicidality and addiction even after exclusion of personality disorders; the burden of suicide adds to the burden of substance abuse in those individuals and their families. Materials and Methods: A cross-sectional descriptive study was conducted on 72 tramadol-dependent patients who were recruited randomly in this study from the addiction outpatient clinic of Okasha Institute of Psychiatry of Ain Shams University, after obtaining an informed consent. They are assessed by (1) Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders for diagnosis of substance use disorder, (2) Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis II Disorders for exclusion of personality disorders, (3) suicide probability scale, and (4) Addiction Severity Index. Results: Regarding suicidal probability, 44.44% of the sample showed risk of suicide, which was severe among 19.44%, moderate among 11.11%, and mild among 13.89% of the sample. Regarding “Addiction Severity Index,” most patients had no real medical problem. In the employment domain, 38.89% had a slight problem. In the drug use domain, 80.56% had a moderate problem. There is a significant relation between the degree of medical, drug use, and legal problem and the severity of suicidal risk. Moreover, the longer duration of addiction and the advanced age of patients are risk factors for suicidal probability. Conclusions: There is a suicide probability among tramadol addicts. The duration of tramadol use could be considered a strong risk factor for suicide, as the longer the duration of tramadol, the higher the suicidal risk.

Tramadol-associated seizures in Egypt: Epidemiological, clinical, and radiological study

BackgroundTramadol intake related seizures have emerged as a common cause of seizures in Egypt affecting mainly young men. ObjectiveThis study aimed to determine the percentage of tramadol induced seizures, and to compare the clinical, neurophysiological, and radiological features of tramadol induced seizures group with idiopathic epilepsy group. MethodsTwo phases study; at first phase, data analysis for all Kasr-Alainy epilepsy clinic patients in Cairo during the period from January 2012 through June 2014, then at second phase a group of tramadol induced seizures’ patients were compared with a matching group of idiopathic epilepsy patients. Detailed history and examination, laboratory tests, electroencephalogram (EEG), Magnetic Resonance Imaging (MRI) of the brain, and Hamilton depression rating scale (HAM-D) were performed for both groups. ResultsTramadol induced seizures represented 7% of all patients (103 out of 1480) and 12% of male patients. All cases were males. Occupational driving was the most common job. Seizures were generalized tonic clonic (GTCs) in 86%. Seventy-seven percent of tramadol induced seizures developed with toxic tramadol dose (>400 mg/day). Inter-ictal EEG was normal in most patients (87.5%). Depression and EEG abnormalities were significantly less than idiopathic epilepsy patients. MRI brain for both groups was normal. ConclusionTramadol induced seizures represented 7% of cases. This deviates the attention to the problem of tramadol addiction in Egypt and raises our awareness of tramadol induced seizures.

Cannabis and tramadol addiction: Do they imply additive risk for acute myocardial infarction in adults younger than 45 years?

Objective:Acute myocardial infarction (AMI) is the main cause of cardiovascular events worldwide. AMI commonly occurs in elderly patients because of atherosclerotic process related to common risk factors. Consequently, the rupture of atheromatous plaque with deleterious sequela is the common etiology of the disease. However, there are less studied etiological factors in youth compared with the usual population. Therefore, this study aimed to examine the risk profile of Egyptian youth presenting with AMI.Methods:A study was conducted in 106 patients aged ≤45 years admitted with AMI in our university hospital to explore their clinical profile risk factors.Results:In the study, 71 (67%) and 35 (33%) patients presented with ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). Anterior wall MI was predominant in 49 patients (46.2%). Moreover, 93 patients (88%) were smokers, 31 (29.2%) used tramadol, 43 (40.6%) smoked cannabis, 50 (47.2%) had poor sleeping habits, 29 (27.4%) had high stress levels, 37 (34.9%) had hypertension, and 22 (20.8%) had diabetes. Twenty (18.9%) patients had a family history of premature coronary artery disease. High and low high-density lipoprotein (HDL) levels were observed in 20 (18.9%) and 47 (44.3%) patients, respectively. The left anterior descending artery (LAD) was involved in 56% of the studied population associated with tramadol use. A significant association was found between both tramadol use and cannabis smoking and presence of heavy thrombus burden on coronary angiography.Conclusion:AMI in Egyptian youth was predominantly observed in men, with anterior STEMI as the most common presentation. Cannabis and tramadol addiction were high risk factors for AMI in Egyptian youth.

Attention and Memory in Tramadol Addiction

Background and Objective: Impairment in cognitive domains occurs commonly in substance use disorders. Tramadol abuse is a common problemin Egypt. The objective of this study was to study the effect of tramadol addiction on attention and memory. Methods: This study included 30 patients with tramadol addiction and 30 control subjects (matched for age, sex, and education).The participants were interviewed using attention and memory subscales of Montreal Cognitive Assessmenttest (MoCA) and Trail making test A and B. Results: The average score of memory in the tramadol addiction group was 2.46±1.33, while the average score in the control group was4.47±1.04, there was significant difference between the two groups with P value <0.0001.There was no statistically significant impairment in Trail making tests A and B.Therewas no association between cognitive impairment and sociodemographicor clinical factors. Conclusions: Tramadol addiction causes impairment in memory.There is no effect of tramadol dose or duration of abuse on cognitive impairment.

Effect of Tramadol Addiction Alone and Its Co-abuse with Cannabis on Urinary Excretion of Copper, Zinc, and Calcium among Egyptian Addicts

Effect of Tramadol Addiction Alone and Its Co-abuse with Cannabis on Urinary Excretion of Copper, Zinc, and Calcium among Egyptian Addicts

Effect of tramadol addiction alone and its co-abuse with cannabis on urinary excretion of Copper, Zinc, and Calcium among Egyptian addicts.

The use of illicit drugs has become a worldwide health problem. Substances with the potential to be abused may have direct or indirect effects on physiologic mechanisms that lead to organ system dysfunction and diseases. The present study aims to investigate the structural and reabsorption integrity of the nephron among Egyptian addicts of tramadol alone and coabused with cannabis. Sixty-five males were included in the study, they were classified into control group (G1=19), tramadol addicts group (G2=18), and tramadol coabused with cannabis addicts group (G3=28). Parameters investigated for structural integrity were urinary levels ofleucineaminopeptidase and N-acetyl-β-D-glucosaminidase, and urinary parameters for reabsorption integrity were levels of copper and zinc as well as calcium, also urinary creatinine was measured. In addition, urinary levels of tramadol and tetrahydrocannabinol were estimated. Among the two addicted groups, all measured parameters were not significantly different in comparison with the control group except for urinary calcium excretion which was found to be significantly increased among the two addicted groups. Both tramadol addiction alone or coabused with cannabis causes increased urinary excretion of calcium, indicating reabsorption dysfunction of calcium without affecting structural integrity along the nephron.

Cognitive Profile in Tramadol Addicts

Background and Objective: Cognitive impairment is one of the consequencesof substance abuse. Tramadol abuse is a public health problemin Egypt. The objective of this study was to study the effect of tramadol addiction on cognitive functions, determine if cognitive impairment caused by tramadol is reversible or not and to study the impact of other related factors as duration of intake and dose of tramadol on cognition. Methods: This study included 30 patients with active tramadol abuse, 30 patients abstinent from tramadol for 3 to 6 months and 30 control subjects (matched for age, sex, and education) who were recruited from Kasr Al-Aini psychiatric and addiction hospital (from outpatient clinic and inpatient admitted patients), Egypt.The participants were interviewed using Montreal Cognitive Assessmenttest (MoCA), Trail making test A and B and had urine screening for drugs. Results: 53.33%(n=16) of active group had impaired total MoCA scores compared to 10 % (n=3) in control group.This was statistically significant with P value <0.0001.46.67% (n=14) of abstinent group had impaired total MoCA scores compared to 10 % (n=3) in control group. This was statistically significant with P value 0.002. As regard MoCAsubscores; we found statistically significant impairment in delayed recall and verbal fluency subscores in both the active and abstinent group. There was no statistically significant impairment in Trail making tests A and B.Therewas no association between cognitive impairment and sociodemographicor clinical factors. Conclusions: Cognitive impairment occurs commonly among tramadolabusepatients. Memory impairment and verbal fluencyare the most common cognitive domainsto be affected. Cognitive impairment is not reversible after 3 to 6 months.There is no effect of tramadol dose or duration of abuse on cognitive impairment.

Effects of Brown Heroin and Tramadol Dependency on Reproductive Axis in Adult Male Albino Rats

Objective: Drugs addiction is considered a general major problem all over the world causing massive detrimental effects for the addict, communities and governments. The study was designed to assess the dependency impact of concurrent brown heroin and Tramadol administration on reproduction in rats. Material and methods: Sixty adult male albino rats were divided into untreated control (I), vehicles groups citric acid (II), saline (III), brown heroin (IV), tramadol (V) and concurrent brown heroin and tramadol (VI) groups. The animals were treated daily for forty days by oral (saline and tramadol) and intra-peritoneal (citric acid and heroin) routes. The body weights, the reproductive hormonal assay (luteinizing hormone LH, follicle stimulating hormone FSH, free Testosterone, Estradiol E2 and prolactin PRL) and the hormones related gene expression (brain FSH-B gene, LH-B gene and testicular cytochrome 19 gene CYP-19) were evaluated. The histopathological changes of the brain and testis were demonstrated. Results: The brown heroin, tramadol and the concurrent brown heroin and tramadol administration reduced the rats' body weight, serum LH, FSH and Testosterone and increased the serum E2 and PRL levels. Moreover, both heroin and tramadol produced down regulation of brain LH-B and FSH-B with up regulation of testicular CYP-19 genes expression and induced histopathological alterations in both of the brain and testicular structures. Conclusion: The concurrent brown heroin and tramadol dependency affect the reproductive axis and impaired fertility in adult male albino rats via altering the circulating reproductive hormones and its related genes expression, moreover, affecting the histology of the brain and testis. Recommendation: Health education for the purpose of increasing public awareness regarding hazards of tramadol and heroin addiction, periodic urine screening for early detection and proper management which could be done for university students, employee in different community services….etc

Morphometric and ultrastructural analysis of tramadol effects on epididymis: an experimental study

ABSTRACTThe effect of tramadol addiction on epididymal structure was not investigated before. Therefore, this experimental study was carried out to investigate the effect of chronic tramadol use on the epididymal structure using light and electron microscopies. Thirty adult Wister Albino male rats were divided into two groups: control group (five rats) and tramadol-treated group (25 rats), which was further subdivided into five subgroups that received tramadol orally at 4.5, 9, 45, 90, and 135 mg/kg/day, respectively, for 18 weeks. Epididymal tissues were dissected and processed for histopathological examination. Morphometric analysis showed significantly reduced mean values of epididymal ducts’ diameters and epithelial height in the tramadol-treated group compared with the control group. Light microscopic examination revealed degeneration and necrosis of epididymal cells in the tramadol-treated group. Electron microscopic (EM) examination showed ultrastructure alterations in a dose-dependent manner. In conclusion, tramadol can adversely affect all epididymal cells, which subsequently deteriorate epididymal function and may affect sperm maturation, leading to subfertility.

Assessment of cognitive functions in tramadol-dependent patients

BackgroundTramadol is a synthetic opioid analgesic that acts mainly on the µ-opioid receptors with less activity on norepinephrine and serotonin by reuptake inhibition. In the last decade, tramadol addiction presents an increasing medical and legal crisis in Egypt.ObjectiveFew works in the literatur