Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D₃ receptor (D₃R) have effects on addiction in different animal models. We have previously reported that YQA14, a D₃R antagonist, exhibits very high affinity and selectivity for D₃Rs over D₂Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D₃R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats ; Mice ; Animals ; Analgesics, Opioid ; Dopamine ; Heroin/pharmacology* ; Dopamine Antagonists/pharmacology* ; Receptors, Dopamine D3/metabolism* ; Morphine/pharmacology* ; Behavior, Addictive/drug therapy* ; Self Administration

INTRODUCTION: Cannabis has consistently been the third most commonly abused drug among drug arrestees in Singapore over the past few years. Accordingly, this study aimed to understand the profile of cannabis users in Singapore and explore the effects of cannabis use on drug progression. METHODS: A total of 450 participants who had used cannabis at least once in their lifetime were recruited from the National Addictions Management Service, prisons, the Community Rehabilitation Centre and halfway houses from August 2017 to May 2018. A face-to-face questionnaire was administered and descriptive analyses were conducted. RESULTS: The mean participant age was 40.9 ± 14.51 years, and 93.1% of them were male. The participants generally initiated cannabis use during adolescence, at a mean onset age of 16.5 ± 4.46 years. Most (89.6%) were introduced to cannabis by peers. Approximately half of them (46.9%) had used cannabis before other illicit drugs and 42.1% of them had used heroin as the succeeding drug. CONCLUSION In Singapore, cannabis use is often initiated during adolescence, largely under peer influence. Cannabis users may progress to other illicit drugs, particularly heroin, later in life.
Adolescent ; Humans ; Male ; Adult ; Middle Aged ; Child ; Young Adult ; Female ; Cannabis ; Singapore/epidemiology* ; Heroin ; Substance-Related Disorders/epidemiology* ; Illicit Drugs

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology* ; Heroin ; Humans ; Illicit Drugs ; Methamphetamine/adverse effects* ; Substance Abuse Detection

OBJECTIVE: To explore the epidemic situation of cannabis use among drug users with compulsory detained detoxification treatment in China. METHODS: Using the data from the Drug Abuse Population Estimation in the Key Cities of the Ministry of Public Security, we analyzed the sociodemographic characteristics and substance use of cannabis abusers with compulsory detained detoxification treatment in 55 provincial capital cities and key cities of China. Chi-square test, Fisher exact test and Kruskal-Wallis rank sum test were used to compare the prevalence of cannabis, heroin, synthetic and mixed drug use among patients with detoxification treatment, as well as the differences in polydrug use and areas among cannabis users. RESULTS: In the study, 25 366 drug users with compulsory detained detoxification treatment were recruited, of whom 2.2% (546/25 366) used cannabis in the previous year before the treatment. The proportion of males was 83.5%, and the proportion of ethnic minorities was 41.0%. Those who received junior high school education or above accounted for 30.8%, and the unemployed accounted for 44.1%. The average age was (33.3±8.2) years, the average age of beginning drug use was (24.8±7.7) years, and the average duration between the first drug abuse and first detoxification treatment was (5.4±4.6) years. The prevalence of cannabis use was higher among those drug users who were 35-year-old and younger, ethnic minorities, employees and residents in Xinjiang. Of the cannabis users, 91.4% used polydrug, 13.6% combined with heroin alone, 42.1% combined with synthetic drugs alone and 35.7% combined with both of heroin and synthetic drugs. Of the cannabis users, 49.6% came from 3 regions: Xinjiang Uygur Autonomous Region, Jiangsu Province and Shanghai City. The cannabis users in Xinjiang had a high proportion of ethnic minorities who received junior high school education and below. Moreover, 79.6% of them combined cannabis use with heroin. The cannabis users in Jiangsu, Zhejiang and Shanghai areas had a higher proportion of ethnic Han who received better education (high school and above). Moreover, 92.7% of them combined cannabis use with methamphe-tamine. CONCLUSION The prevalence of cannabis use among the population with compulsory detained detoxification treatment is higher than that among drug users under surveillance, but there are obvious regional cluster effect and high possibility of polydrug abuse. Thus, it's important to strengthen the monitoring of cannabis use, to increase the control of cannabis and to formulate China's anti-cannabis policy among different population.
Adolescent ; Adult ; Cannabis ; China ; Drug Users ; Female ; Heroin Dependence ; Humans ; Male ; Opiate Substitution Treatment ; Young Adult

OBJECTIVE: Reaction time is defined as the time from the start of a stimulus to the start of the voluntary movement. Time plays an important role in undertaking daily living activities. Reaction time is an important factor in respect of both quality of life and of capabilities demonstrated in the work environment. Alcohol and some addictive substances have effect on RT. The aim of this study was to compare the visual and auditory reaction times of patients with opioid use disorder with healthy control subjects. METHODS: The study was applied to two groups as the opioid use disorder group and the control group. A Sociodemographic and Clinical Data Form was prepared for each patient including age, gender, marital status and education level. Using a computer program the response to visual screen color change (red/blue) and to an auditory ‘beep’ sound of the computer system were recorded. The Student’s t-test was applied as a statistical method. RESULTS: The results showed longer reaction times in the patients with opioid use disorder. CONCLUSION: To add improving reaction time approaches in opioid use disorder treatment may contribute to treatment by increasing quality of life and work performance.
Activities of Daily Living ; Computer Systems ; Drug Users ; Education ; Heroin Dependence ; Humans ; Marital Status ; Methods ; Mortuary Practice ; Opioid-Related Disorders ; Quality of Life ; Reaction Time ; Work Performance

OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are markers that can determine the presence of systemic inflammatory response. In this study, we examined the NLR and PLR levels in patients with heroin dependence compared to healthy controls. METHODS: The study sample included 90 male patients with heroin dependence aged 18 to 45 years and 60 healthy subjects who had similar socio-demographic characteristics as the patient group. The diagnoses of heroin dependence and other Axis I psychiatric disorders in the patient and control groups were screened with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID-I). The extent of heroin addiction was assessed with the Addiction Severity Index (ASI). RESULTS: The mean NLR and PLR levels of patients with heroin dependence were significantly higher than the control subjects (p=0.031 and p < 0.001, respectively). Positive correlations were found between NLR, PLR and duration of the disorder. CONCLUSION: Our results indicate that inflammatory processes may play a role in the pathophysiology of heroin dependence.
Diagnosis ; Diagnostic and Statistical Manual of Mental Disorders ; Healthy Volunteers ; Heroin Dependence ; Heroin* ; Humans ; Male* ; Prospective Studies*

OBJECTIVE: Low heart rate variability (HRV) has been confirmed in heroin users, but the effects of heart-rate-variability-biofeedback in heroin users remain unknown. This study examined (1) correlations between depression and HRV indices; (2) group differences in HRV indices among a heroin-user group, a group with major depressive disorder but no heroin use, and healthy controls; and (3) the effects of heart-rate-variability-biofeedback on depressive symptoms, HRV indices, and respiratory rates within the heroin group. METHODS: All participants completed a depression questionnaire and underwent electrocardiogram measurements, and group differences in baseline HRV indices were examined. The heroin group underwent electrocardiogram and respiration rate measurements at baseline, during a depressive condition, and during a happiness condition, before and after which they took part in the heart-rate-variability-biofeedback program. The effects of heart-rate-variability-biofeedback on depressive symptoms, HRV indices, and respiration rates were examined. RESULTS: There was a negative correlation between depression and high frequency of HRV, and a positive correlation between depression and low frequency to high frequency ratio of HRV. The heroin group had a lower overall and high frequency of HRV, and a higher low frequency/high frequency ratio than healthy controls. The heart-rate-variability-biofeedback intervention increased HRV indices and decreased respiratory rates from pre-intervention to post-intervention. CONCLUSION: Reduced parasympathetic and increased sympathetic activations were found in heroin users. Heart-rate-variability-biofeedback was an effective non-pharmacological intervention to restore autonomic balance.
Autonomic Nervous System ; Biofeedback, Psychology* ; Depression* ; Depressive Disorder, Major ; Electrocardiography ; Happiness ; Heart Rate* ; Heart* ; Heroin* ; Respiratory Rate

OBJECTIVES: To perform retrospective analysis on 20 dead cases related to heroin abuse, and to provide references for the forensic assessment of correlative cases. METHODS: Among 20 dead cases related to heroin abuse, general situation, using method of drug, cause of death and result of forensic examination were analyzed by statistical analysis for summarizing the cause of death and pathologic changes. RESULTS: The dead were mostly young adults, with more male than female. The results of histopathological examinations showed non-specific pathological changes. There were four leading causes of death, including acute poisoning of heroin abuse or leakage （13 cases, 65%）, concurrent diseases caused by heroin abuse （3 cases, 15%）, inspiratory asphyxia caused by taking heroin （2 cases, 10%）, and heroin withdrawal syndrome （2 cases, 10%）. CONCLUSIONS The forensic identification on dead related to heroin abuse must base on the comprehensive autopsy, and combine with the qualitative and quantitative analysis of heroin and its metabolites in death and the case information, as well as the scene investigation.
Adult ; Autopsy ; Cause of Death ; Drug Overdose/diagnosis* ; Female ; Forensic Pathology ; Forensic Toxicology ; Heroin/poisoning* ; Humans ; Male ; Retrospective Studies ; Young Adult

Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.
Administration, Inhalation ; Brain ; pathology ; Disease Progression ; Heroin ; administration & dosage ; Heroin Dependence ; complications ; Humans ; Leukoencephalopathies ; chemically induced ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nervous System Diseases ; chemically induced ; Singapore

To explore the relationship between the drug-seeking behavior, motivation of conditioned place preference (CPP) rats and the frontal association cortex (FrA) electroencephalogram (EEG) sample entropy, we in this paper present our studies on the FrA EEG sample entropy of control group rats and CPP group rats, respectively. We invested different behavior in four situations of the rat activities, i. e. rats were staying in black chamber of videoed boxes, those staying in white chamber of videoed boxes, those shuttling between black-white chambers and those shuttling between white-black chambers. The experimental results showed that, compared with the control group rats, the FrA EEG sample entropy of CPP rats staying in black chamber of video box and shuttling between white-black chambers had no significant difference. However, sample entropy is significantly smaller (P < 0.01) when heroin-induced group rats stayed in white chamber of video box and shuttled between black-white chambers. Consequently, the drug-seeking behavior and motivation of CPP rats correlated closely with the EEG sample entropy changes.
Animals ; Conditioning (Psychology) ; drug effects ; Drug-Seeking Behavior ; Electroencephalography ; Entropy ; Frontal Lobe ; drug effects ; physiology ; Heroin ; pharmacology ; Rats ; Rats, Sprague-Dawley