NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study.

Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-D-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), and orbitofrontal cortex (OFC) were dissected from the brain of 101 drug addicts brains and were compared with the brains of non-addicts (N = 13). Western blotting technique was used to show the alteration in NMDAR subunits level. Data obtained using Western blotting technique showed a significant increase in the level of GluN1 and GluN2B, but not in GluN2A subunits in all the three regions (mPFC, lPFC, and OFC) of men whom suffered from addiction as compared to the appropriate controls. These findings showed a novel role for GluN1, GluN2B subunits, rather than the GluN2A subunit of NMDARs, in the pathophysiology of addiction and suggested their role in the drug-induced plasticity of NMDARs.

A tentative component analysis of Norjizak: A new abused drug in Iran.

Norjizak is a new drug abused in the past few years in Iran with symptoms and complications distinct from other common forms of drug and characterized by higher rate of mortality. The present study aims to analyze the chemical components of this substance. Five samples were obtained from abusers referring from different areas of Tehran to a treatment clinic. All samples were 2 ml vials with yellowish fluid. Thin Layer Chromatography (TLC) was performed first to analyze the samples semi-quantitatively and the quantitative levels of components were then explored using high-performance liquid chromatography (HPLC). TLC revealed steroid (in form of betamethasone), heroin, codeine, morphine and thebaine in all five samples. Four samples contained acetaminophen and two samples contained caffeine. None of them contained amphetamine, benzodiazepine, tricyclic antidepressant, aspirin, barbiturates, tramadol and buprenorphine. HPLC revealed that heroin, codeine, morphine and thebaine constituted the narcotic foundation in all samples. In addition, the heroin to acetylcodeine ratio was significantly lower in three samples, which indicates their higher toxicity. The results of the present study on the chemical components of Norjizak showed that this substance is an opiate one similar to heroin and the heroin-based crack prevalent in Iran which contains betamethasone.

Component Analysis of the Illegal Handmade Pills and Capsules for Self-Medicating Substance Dependence in Tehran, Iran.

BACKGROUND: To self-medicate substance dependence, many substance users consume herbal medicines delivered in herbal medicine shops which are prepared through non-standard methods using a variety of different materials. Hence, the present study was carried out aiming to investigate and analyze the content of such herbal medicines. METHODS: Four herbal medicine shops were selected from each of the 22 zones of Tehran City, Iran, and a total of 95 samples were purchased. A package containing 6 types of medication that was advertised by a satellite TV channel, was also purchased. Using high-performance liquid chromatography (HPLC) method, the samples were analyzed in the laboratory to detect different types of materials. FINDINGS: Among the samples, 23 and 72 samples were uncovered compressed pills (Dragon pills) and capsules filled with colored powders (handmade self-medicating substance dependence capsules), respectively. The package advertised in the satellite TV was prepared in 6 various forms. The most common substances present in all the samples were as follows: diphenoxylate, tramadol, opioids, acetaminophen, and codeine with values of 90%, 86%, 78%, 69%, and 68%, respectively. On average, 5 of the above mentioned substances were present in each sample; moreover, 63% of the samples contained 5 or more substances. In addition, 42 (41%) of the samples contained all the 5 main substances including opioids, codeine, tramadol, diphenoxylate, and acetaminophen. CONCLUSION: The findings of this study showed that handmade capsules and pills used for self-medicating substance dependence and also medicines advertised in the satellite TV channels contain different amounts of opioids, amphetamine, benzodiazepines, tramadol, codeine, and other substances that cause problems for substance users who are going to abandon substance abuse.

Alteration of dopamine receptors subtypes in the brain of opioid abusers: A postmortem study in Iran.

Dopamine is the most important neurotransmitter which is involved in reward and addiction. Repeated drug exposure can induce some adaptive changes in the molecular and cellular function of the mesolimbic dopaminergic system. Since the essential role of dopamine in the pathophysiology of drug addiction is proven, the changes in dopamine receptors level in the brain of opioid abusers and matched control subjects were investigated. Fifty-six opioid abusers and thirteen control subjects were obtained from Legal Medicine Center. The cause of death and the postmortem interval were determined by forensic pathologists. mRNA expression and protein level of dopamine receptors in the ventral tegmental area (VTA), nucleus accumbens (NAC) and amygdala were assessed. The mRNA and protein level of DRD1 increased in the VTA, NAC and amygdala of opioid abusers. DRD2 protein level increased in the VTA, NAC and amygdala of opioid abusers when compared with the control. DRD3 level decreased in all the brain regions except in the amygdala of opioid abusers in comparison with the control group. DRD4 mRNA level increased only in the amygdala of opioid abusers. There were no significant changes in the protein and mRNA levels of DRD4 in the VTA and NAC. In mRNA and protein level of DRD5, it followed the same pattern like DRD1. The current data suggest that adaptive changes in mRNA and protein level of dopamine receptors occurred in the brain of opioid abusers and the variations depended on the brain region.

Component analysis of Iranian crack; a newly abused narcotic substance in iran.

Iranian crack is a new form of narcotic substance that has found widespread prevalence in Iran in the past years. Crack only nominally resembles crack cocaine as it is widely different in its clinical signs. Thus the present study aims to quantify the chemical combination of this drug. The samples included 18 specimen of Crack collected from different zones of Tehran, Iran. All specimens were in the form of inodorous cream solid powdery substance. TLC and HPLC methods were used to perform semi-quantitative and quantitative analysis of the components, respectively. The TLC analysis showed no cocaine compound in the specimens while they all revealed to contain heroin, codeine, morphine and caffeine. All but two specimens contained thebaine. None of the specimens contained amphetamine, benzodiazepines, tricyclic antidepressants, aspirin, barbiturates, tramadol and buprenorphine. Acetaminophen was found in four specimens. HPLC revealed heroin to be the foundation substance in all specimens and most of them contained a significant amount of acetylcodeine. The present analysis of the chemical combination of Crack showed that this substance is a heroin-based narcotic which is basically different from the cocaine-based crack used in Western countries. Studies like the present one at different time points, especially when abnormal clinical signs are detected, can reveal the chemical combination of the target substance and contribute to the clinical management of its acute or chronic poisoning.