Brain-derived neurotrophic factor (BDNF) is linked to numerous brain functions. In addition, BDNF alterations contribute to neurological, mental, and addictive disorders. Cocaine dependence has received much attention recently due to its prevalence and psychological effects. Symptoms of psychosis are one of the most serious adverse events precipitated by cocaine use. It is particularly important to identify patients at risk of developing cocaine-induced psychosis (CIP). We described two cases of patients with cocaine dependence who presented with CIP and had changes in their BDNF levels during the psychotic episode. BDNF levels were initially low in both patients, and then decreased by more than 50% in association with CIP. The relationship between BDNF and psychosis is described in the literature. These cases revealed that BDNF levels decreased during a CIP episode and, thus, it is necessary to investigate BDNF and its relationship with CIP further.
Biomarkers ; Brain ; Brain-Derived Neurotrophic Factor ; Cocaine* ; Cocaine-Related Disorders* ; Humans ; Prevalence ; Psychotic Disorders*

Drug addiction is a major worldwide medical and social problem.Cocaine,nicotine,methamphetamine,heroin and other psychoactive substances,with small molecular weight,can easily cross the blood-brain barrier and eventually lead to addiction and other serious neuropsychological damage.There is no effective cure for addiction currently.The drug-antibody complex formed on the basis of active or passive immunotherapy could not cross the blood-brain barrier,which reduces the concentration of the free active drug and prevents its distribution in the brain,thereby weakening the drug addiction-related reward effects.It provides a promising way for the treatment of drug addiction.This article reviews the progress of immunotherapy against psychoactive substances such as cocaine,nicotine,methamphetamine and heroin in the past 50 years from the aspects of active immunity,passive immunity,drug metabolism-related enzymes,adjuvants and so on.The goal is to provide some ideas for the development of agents for the treatment of psychoactive substance addiction.
Cocaine ; Humans ; Immunotherapy ; Methamphetamine ; Nicotine ; Substance-Related Disorders/therapy*

BACKGROUND: The recovery and outcome of intoxicated patients depends on the kind of drugs they took and the total time of their initial management. The purpose of this study is to evaluate the usefulness of a Triage drug kit for detecting abused drugs. METHODS: From 2003 Feb. to 2003 July, we studied the patients who visited the emergency department with suspicious drug intoxication. In this case, we used a Triage drug kit for 134 patients with drug intoxication or who were clinically suspected of taking illegal drugs, with 30 of the patients initially admitting the substance they had used. The kit is an immunoassay kit for qualitative testing drug metabolites in urine. To compare with those cases of the preceding year, we studied 104 patients with drug intoxication that was detected between February 2002 and July 2002. RESULTS: Overall, 60% of the 30 cases who did not know what substance they abused and tested positive for, and 33% of the 27 cases with suspected intoxication confirmed their substance abuse. The positive rate for benzodiazepine use was the highest (46.7%), and there were no positive results regarding amphetamine, methamphetamine or cocaine. An appropriate antidote was administered significantly more frequently in the group for which we used the kit. CONCLUSIONS: A Triage drug kit is probably useful for diagnosing acute drug intoxication and for identifying the causative substance. However, the time required to decide whether or not a patient should be admitted is not reduced. If the kit can detect the frequently abused drugs in Korea, it will be helpful for treating drug intoxicated patients.
Amphetamine ; Benzodiazepines ; Cocaine ; Emergencies ; Humans ; Immunoassay ; Korea ; Methamphetamine ; Poisons ; Substance-Related Disorders ; Triage

Dilated cardiomyopathy is a primary myocardial disease characterized by ventricular dilatation and impaired ventricular contractility. The etiology of dilated cardiomyopathy has not been known yet, but toxin such as alcohol, thiamine deficiency, endocrine disorder, viral or bacterial infection, hereditary disorder, and muscular dystrophy may be related to dilated cardiomyopathy. Cocaine abuse and anticancer drugs (especially doxorubicin) were reported as the causes of drugs of dilated cardiomyopathy also. Recently we experinced a case of dilated cardiomyopathy in 30 years old man who developed dilated cardiomyopathy on chronic clomipramine (one of trcyclic antidepressant drugs) treatment for a obsessive-compulsive disorder. He became asymptomatic and normalization of left ventricular diameters and function was evidenced echocardiographically after withdrawal of the drug. The possible association of cardiomyopathy and tricyclic antidepressant drugs and possibility of functional improvement after tricyclic antidepressant drugs withdrawal should be kept in mind.
Adult ; Antidepressive Agents, Tricyclic ; Bacterial Infections ; Cardiomyopathies ; Cardiomyopathy, Dilated* ; Clomipramine ; Cocaine-Related Disorders ; Dilatation ; Humans ; Obsessive-Compulsive Disorder ; Thiamine Deficiency

Drug abuse has become a major social problem of the modern world and majority of these abusive drugs or their metabolites are excreted through the kidneys and, thus, the renal complications of these drugs are very common. Morphine, heroin, cocaine, nicotine and alcohol are the most commonly abused drugs, and their use is associated with various types of renal toxicity. The renal complications include a wide range of glomerular, interstitial and vascular diseases leading to acute or chronic renal failure. The present review discusses the renal toxicity profile and possible mechanisms of commonly abused drugs including morphine, heroin, cocaine, nicotine, caffeine and alcohol.
Caffeine ; Cocaine ; Heroin ; Kidney ; Kidney Failure, Chronic ; Morphine ; Nicotine ; Renal Insufficiency ; Social Problems ; Substance-Related Disorders ; Vascular Diseases

The dopamine transporter is responsible for recycling dopamine after release. Inhibitors of the dopamine transporter, such as cocaine, will stop the reuptake of dopamine and allow it to stay extracellularly, causing prominent changes at the molecular, cellular, and behavioral levels. There is much left to be known about the mechanism and site(s) of binding, as well as the effect that cocaine administration does to dopamine transporter-cocaine binding sites and gene expression which also plays a strong role in cocaine abusers and their behavioral characteristics. Thus, if more light is shed on the dopamine transporter-cocaine interaction, treatments for addiction and even other diseases of the dopaminergic system may not be too far ahead. As today's ongoing research expands on the shoulders of classic research done in the 1990s and 2000s, the foundation of core research done in that time period will be reviewed, which forms the basis of today's work and tomorrow's therapies.
Binding Sites ; Cocaine* ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Gene Expression ; Parkinson Disease ; Recycling ; Shoulder ; Substance-Related Disorders

BACKGROUNDBrazil is among the nations with the greatest rates of annual cocaine usage. Pharmacological treatment of cocaine addiction is still limited, opening space for nonconventional interventions. Homeopathic Q-potencies of opium and Erythroxylum coca have been tested in the integrative treatment of cocaine craving among homeless addicts, but this setting had not proven feasible, due to insufficient recruitment.

OBJECTIVEThis study investigates the effectiveness and tolerability of homeopathic Q-potencies of opium and E. coca in the integrative treatment of cocaine craving in a community-based psychosocial rehabilitation setting.

DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONSA randomized, double-blind, placebo-controlled, parallel-group, eight-week pilot trial was performed at the Psychosocial Attention Center for Alcohol and Other Drugs (CAPS-AD), Sao Carlos/SP, Brazil. Eligible subjects included CAPS-AD patients between 18 and 65 years of age, with an International Classification of Diseases-10 diagnosis of cocaine dependence (F14.2). The patients were randomly assigned to two treatment groups: psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca (homeopathy group), and psychosocial rehabilitation plus indistinguishable placebo (placebo group).

MAIN OUTCOME MEASURESThe main outcome measure was the percentage of cocaine-using days. Secondary measures were the Minnesota Cocaine Craving Scale and 12-Item Short-Form Health Survey scores. Adverse events were reported in both groups.

RESULTSThe study population comprised 54 patients who attended at least one post-baseline assessment, out of the 104 subjects initially enrolled. The mean percentage of cocaine-using days in the homeopathy group was 18.1% (standard deviation (SD): 22.3%), compared to 29.8% (SD: 30.6%) in the placebo group (P < 0.01). Analysis of the Minnesota Cocaine Craving Scale scores showed no between-group differences in the intensity of cravings, but results significantly favored homeopathy over placebo in the proportion of weeks without craving episodes and the patients' appraisal of treatment efficacy for reduction of cravings. Analysis of 12-Item Short-Form Health Survey scores found no significant differences. Few adverse events were reported: 0.57 adverse events/patient in the homeopathy group compared to 0.69 adverse events/patient in the placebo group (P = 0.41).

CONCLUSIONSA psychosocial rehabilitation setting improved recruitment but was not sufficient to decrease dropout frequency among Brazilian cocaine treatment seekers. Psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca were more effective than psychosocial rehabilitation alone in reducing cocaine cravings. Due to high dropout rate and risk of bias, further research is required to confirm our findings, with specific focus on strategies to increase patient retention.

TRIAL REGISTRATIONRBR-2xzcwz (http://www.ensaiosclinicos.gov.br).

Adolescent ; Adult ; Aged ; Cocaine ; adverse effects ; Cocaine-Related Disorders ; psychology ; rehabilitation ; therapy ; Craving ; drug effects ; Double-Blind Method ; Female ; Homeopathy ; Humans ; Male ; Middle Aged ; Opium ; therapeutic use ; Pilot Projects ; Treatment Outcome ; Young Adult

OBJECTIVE: To evaluate the features of autopsy cases involved in electronic weapon (TASER) in the State of Maryland, and to discuss the appraisable points. METHODS: Thirteen autopsy cases involving TASER were collected from 2004 to 2011 in the Office of the Chief Medical Examiner, State of Maryland. All the cases include detailed scene investigations, complete autopsy, toxicological analysis and histopathological examination. Statistical analysis were conducted including general information of victim, type of TASER, type of contact, toxicological results, manner and cause of death. RESULTS: Majority of victims were male with an acute onset of agitated and delusional behavior. Drugs were often involved. Deaths were attributed to multiple factors. CONCLUSION Most of cases involved in TASER resulted from multiple fatal factors. Further researches are needed for the principal mechanism. Thorough scene investigation and complete autopsy examination play crucial role in evaluation of such cases.
Adult ; Autopsy/methods* ; Cause of Death ; Cocaine/analysis* ; Conducted Energy Weapon Injuries/etiology* ; Female ; Forensic Pathology ; Humans ; Male ; Maryland/epidemiology* ; Mental Disorders/complications* ; Middle Aged ; Phencyclidine/analysis* ; Retrospective Studies ; Substance-Related Disorders/complications* ; Trauma Severity Indices

G protein-coupled receptor kinase 5 (GRK5) plays an important role in the regulation of GPCR-transduced signals. Our previous study showed that acute administration of morphine could significantly increase GRK5 mRNA level in the cerebral cortex and hippocampus of the rat brain. The current study investigated the potential effects of acute administration of addictive drugs including morphine, heroine and cocaine on GRK5 mRNA level in the rat brain using in situ hybridization and analyzed the effects of acute and chronic morphine treatments on GRK5 protein level in the rat brain using Western blotting assay. Our results showed that 2 h after the initial morphine (10 mg/kg), cocaine (15 mg/kg) and heroine (1 mg/kg) treatment, the mRNA level of GRK5 in the parietal cortex increased about 110% (P<0.01), 70% (P<0.05) and 100% (P<0.01), respectively. In the temporal cortex, GRK5 mRNA level increased about 90% (P<0.01), 40% (P<0.05) and 80.0% (P<0.01), respectively . In the hippocampus, the mRNA level of GRK5 increased about 60% (P<0.01), 30% (P<0.05) and 80% (P<0.01). However, the mRNA level of GRK5 remained unchanged after acute morphine, cocaine or heroine treatment. In the cerebral cortex of the rat brain, the acute administration of morphine (NS-Mor) increased GRK5 protein level by about 60% while the chronic morphine treatment (Mor-Mor) increased GRK5 protein level even higher [about 130% compared with the control group (chronic saline treatment, NS-NS) group, P<0.01]. In the hippocampus, GRK5 protein level remained unchanged after acute administration of morphine (P>0.1),while the level of GRK5 protein tended to decrease after chronic morphine treatment (P=0.098). In the thalamus, acute morphine treatment caused no change in GRK5 protein level (P>0.1) while after chronic morphine treatment, GRK5 protein level decreased significantly (more than 90%, P<0.01), Taken together, our results indicate that addictive drugs can regulate GRK5 in the rat brain on protein level as well as on mRNA level and suggest that GRK5 may play a role in addiction of psychoactive substances.
Animals ; Brain ; metabolism ; Cocaine ; adverse effects ; G-Protein-Coupled Receptor Kinase 5 ; Heroin ; adverse effects ; Male ; Morphine ; adverse effects ; Protein-Serine-Threonine Kinases ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Substance-Related Disorders ; metabolism

OBJECTIVE: To investigate the reproductive system impairment induced by cocaine in adult male rats and the possible underlying mechanism. METHODS: Thirty adult male rats were randomly divided into experimental and control groups, with 15 rats in each group. Rats of the experimental group were injected cocaine hydrochloride (15 mg/kg body weight) subcutaneously daily for four weeks. The weight of body and testis, as well as the level of serum hormone of the rats were examined. In addition, the apoptosis rate of testicular tissue by TUNEL and the expression of Fas gene in testicular tissue were examined by immunohistochemistry. RESULTS: Compared with the control, the weight of testis in the cocaine exposed group decreased significantly (P<0.05), and the serum testosterone level decreased significantly (P<0.05). Moreover, both the apoptosis rate and the expression of Fas gene increased in the testicular tissue of rats in the cocaine exposed group in comparison to the control group (P<0.05). The apoptosis rate was significantly correlated with the expression of Fas gene (r=0.9012, P<0.05). CONCLUSION Cocaine may cause reproductive system injury in adult male rats, and Fas-mediated apoptosis may be one of the functional mechanisms involved in the reproductive system injuried by cocaine.
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Apoptosis/drug effects* ; Cocaine/adverse effects* ; Forensic Toxicology ; Male ; Molecular Chaperones ; Nuclear Proteins/metabolism* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spermatids/pathology* ; Substance-Related Disorders ; Testis/pathology* ; Testosterone/blood*