RESEARCH CENTRE SERIES
Addiction Research Centres and the Nurturing of Creativity
The Chinese National Institute on Drug Dependence, Peking University: past, present and future
Lin Lu, Director/Professor, National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing 100191, China. E-mail: firstname.lastname@example.org
In the 25 years since drug abuse re-emerged in China in the 1980s, the National Institute of Drug Dependence (NIDD) has made many contributions to China's antidrug campaign. This present paper offers an account of the history, current status and future of drug dependence research at NIDD. NIDD was originally a research centre at Beijing Medical University, founded by the Chinese Ministry of Health to address the rapid spread of drug abuse in China. Originally, the main task of NIDD was to complete the commissions assigned by the government and university. Further developments transformed NIDD into a national research institute in the field of drug addiction that began to conduct its own research. NIDD has now created a professional team spread across several independent departments involved in neurobiological mechanisms, epidemiological surveys and monitoring, pre-clinical and clinical evaluation of new drugs (mainly analgesic drugs and detoxification drugs) and informatics and data analysis. As a university-based research institute, NIDD's funding derives mainly from grants provided by the government and financial support from international organizations. Its past and present research has a gained NIDD a reputation with both practitioners and policy makers in the field of drug addiction. In the future, NIDD will continue to engage in various aspects of drug addiction research and will enter the field of brain function.
The first emergence of drug abuse in China can be traced to the widespread use of opium in the 19th century [1–3]. The importation of British opium into China spurred the prevalence of opium use across the country, with disastrous social and public health consequences during the Qing dynasty. Because of the lack of effective control and treatment, this opium abuse epidemic in China became the largest in world history . In 1952, with strict regulations and punishment, the government of the People's Republic of China announced that the demon of drug abuse had been eliminated [1,5]. During the next 30 years China maintained a relatively drug-free environment, due to its policies that isolated China from regular contact with many western countries. However, with the re-establishment of the open-door policy towards western nations many regions in China began encountering drug abuse problems, beginning in the 1980s [6,7]. The importation of illegal substances from the Golden Triangle region caused illicit drug abuse, particularly heroin abuse, to rise rapidly to epidemic levels during the last 10 years of the 20th century . The number of drug abusers registered by security agents increased from 70 000 in 1990 to 1.16 million in 2005, an increase of approximately 122% per year . The estimated total number of users, including unregistered drug abusers, is much higher . Drug abuse has also spread from urban to rural areas: 72.7% of Chinese counties (cities or districts) report drug problems . Heroin is the most widely used illicit drug, and in 2008 77.5% of drug users abused heroin . The most frequent route of drug administration is intravenous injection, which accounts for 50–75% of heroin administration. Additionally, many heroin abusers (25–50%) who previously administered heroin by ‘chasing the dragon’ changed to intravenous injection to achieve the same effect at lower doses .
Drug abuse, especially the high popularity of intravenous heroin administration, leads to many health-related problems, most notably the spread of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The first AIDS case was reported in China in 1985, but the disease spread rapidly to epidemic levels in the early 1990s through needle sharing among injecting drug users (IDUs). Unprotected sex among drug abusers also increased the risk of HIV infection in this population and provided a bridge for HIV transmission to the general population [11–14]. HIV infections have now been reported in 31 provinces, autonomous regions and municipalities (more than 90% of the regions in China) . By the end of 2007, the registered number of HIV infections in China was 223 501, with 62 838 registered cases of AIDS, accounting for 22 205 deaths. An estimated 700 000 Chinese people are now HIV-positive, with approximately 85 000 AIDS cases. Approximately 63.7% of this population comprises drug abusers . IDU accounted for 42.0% of the new HIV infections in 2007 [1,15]. In addition to HIV infection, IDU also enhances the risk of hepatitis C virus (HCV) infection. HCV is hyperendemic in IDU  and is generally acquired before exposure to other blood-borne viruses, such as HBV or HIV. These widespread drug abuse problems have elicited great vigilance by the government.
HISTORY OF THE NATIONAL INSTITUTE ON DRUG DEPENDENCE
The National Institute on Drug Dependence (NIDD) is a national institute engaged specifically in scientific research on drug dependence and drug abuse problems, with the goal of promoting national drug control and drug detoxification by offering guidance to government authorities. The establishment of NIDD coincided with the re-emergence of the drug abuse problem. Because of the severe situation in 1984, seven state ministries, including the Ministry of Health, Ministry of Foreign Affairs and Ministry of Public Security, submitted a joint report claiming that the government should establish a drug dependence research centre to strengthen drug abuse research and the control of new drug approvals in the categories of narcotics and psychotropic drugs, which would be advantageous in the fight against drug abuse in China. In the same year the Ministry of Health, with approval from the State Council, established the Research Center on Drug Dependence at Beijing Medical University. The centre was established (i) to evaluate pre-clinical pharmacodynamics and toxicology of analgesic drugs, anxiolytic drugs and drugs for detoxification; (ii) to conduct clinical studies on analgesic drugs, anxiolytic drugs and drugs for detoxification; and (iii) to investigate the mechanisms of drug dependence.
In 1988, to meet the needs of the development of drug abuse research and facilitate global cooperation, the Ministry of Health upgraded the centre to NIDD. Since then, NIDD has been defined as a national institute under the jurisdiction of the Ministry of Health, National Narcotics Control Commission and the State Food and Drug Administration, and is affiliated with Beijing Medical University. The financial contribution of NIDD was included in the Ministry of Health budget for Beijing Medical University. Correspondingly, the quota of staff at NIDD was allocated by Beijing Medical University. At the beginning, the main responsibility of NIDD was to complete the commissions assigned by the Ministry of Health, National Narcotics Control Commission, State Food and Drug Administration and Beijing Medical University, including drug dependence research, information collection and analysis, drug addict monitoring and cooperative work for the Convention on Narcotic Drugs. From 1989 to 2004, NIDD successfully completed several national epidemiological surveys on drug abuse and evaluated analgesics and narcotics assigned by the Ministry of Health and National Narcotics Control Commission. In 1991, the Ministry of Health established the National Monitoring Centre of Drug Abuse at NIDD. With these projects, NIDD laid foundations in pre-clinical and clinical research, epidemiological studies and informatics research of substance dependence. In the 21st century, NIDD has expended more effort into independent research and larger international research programmes. It has gained more financial support from local governments and international cooperative programmes outside the Ministry of Health.
With the integration of Beijing Medical University and Peking University, NIDD changed its name to the National Institute on Drug Dependence, Peking University, but it is still located at the Beijing Medical University campus, which is now the Peking University Health Science Center. NIDD has already gained more than 20 years of experience and developed into a general research institution conducting studies into the mechanisms of drug dependence, pre-clinical experiments, clinical trials, drug abuse surveys and monitoring and publication of journals and science books in the field.
CURRENT SITUATION AND RESEARCH ACTIVITY
NIDD consists of an administrative department and seven independent research departments, including the Department of Neuropharmacology, Department of Clinical Pharmacology, Clinical Treatment Center, Department of Drug Epidemiology, Department of Information on Drug Abuse, Department of New Drug Research and Development and Key Laboratory of Drug Abuse and Addiction. The organizational structure of the research departments at NIDD is characterized by a flat hierarchy. Each department engages in different fields of drug abuse, and the head of the department is responsible for coordination and information exchange with other departments and the director of NIDD. An interdisciplinary academic team has been formed at NIDD, consisting of academic leaders and several young academic researchers. Fourteen staff are at the level of professor or associate professor, nine of whom have a doctoral degree, and are dedicated to biological psychiatry, social psychiatry and psychiatric treatment. Additionally, two postdoctoral fellows and 28 postgraduate students work at the institute. From 2004 to 2008, 12 PhD students and 16 Master's students graduated, and three postdoctoral fellows completed their professional training at the institute.
One major research focus of NIDD is the study of the neurobiological mechanisms of drug dependence. The aim of our research is to demonstrate the mechanisms of drug dependence using experimental methods such as behaviour, immunology, neuropharmacology and molecular pharmacology. We established reliable animal models to mimic addictive behaviour in humans for opioid, cocaine and methamphetamine abuse. Based on these animal models, the characteristics of addictive behaviour were examined. We also investigated the role of key molecules and signalling pathways related to addiction. In recent years, novel findings have been achieved in studies on drug craving and relapse after withdrawal. For example, we have demonstrated that the extracellular-regulated kinase (ERK) signalling pathway in the central amygdala is involved critically in the incubation of opiate craving after withdrawal [17,18]. The ventral tegmental area glial cell line-derived neurotrophic factor (GDNF) also plays an important role in the incubation of cocaine craving . These findings have provided direct support for the hypothesis that drug-induced neuroadaptations are involved critically in drug craving and relapse, and have opened new avenues into the development of effective treatments for drug addiction and relapse.
A second focus of NIDD is the pre-clinical evaluation of analgesic drugs, anxiolytic drugs and drugs for detoxification. These studies include pharmacodynamics and toxicology testing. The Department of Neuropharmacology has established laboratories for drug self-administration, drug discrimination and conditioned place preference. The experimental animals include mice, rats and monkeys. Each year, using these animal models, several narcotic analgesics, psychostimulants and depressants are assessed. The evaluation of physical dependence on opiate analgesics and sedative–hypnotics is another focus of the department. Substitution or therapeutic effects of other drugs, such as drugs for detoxification, are also tested.
The Department of Clinical Pharmacology engages in clinical trials for new drugs and clinical therapy for drug dependence and is a National Clinical Trial Center for analgesics and detoxification drugs. Laboratories within the department perform studies on pharmacokinetics, bioequivalent estimations and tests for identifying illegal drugs in biological samples. The laboratory has also gradually established various methods for drug analysis, such as quick one-step detection, immunoassay and routine chromatography, including TCL (‘Toxi-Laboratory’), high-performance liquid chromatography and gas chromatography–mass spectrometry. Hair detection for polydrug abuse can also be performed to trace abuse history or for special examination. Another main task of the department is to evaluate the effects and safety profile of new drugs with abuse potential. The department has established a Phase I clinical trials ward according to the requirements of good clinical practice. For the implementation of Phases II–III clinical trials, several cooperative hospitals and detoxification institutes have been established in many provinces and cities, such as Beijing, Shanghai, Tianjin, Chongqing, Guangzhou and Xi'an. In the past 10 years, 70 Phases I–II clinical trials have been conducted, with the evaluation of more than 30 new analgesics at various dosages, nine detoxification drugs and 11 narcotic antitussives. Further studies on drugs for opioid dependence treatment, especially traditional Chinese medicine, are being carried out to explore the mechanisms underlying detoxification medicine and drug abuse both at the whole-body and cellular levels. Moreover, the department has made contributions to aiding clinics in formulating detoxification regimens in clinical therapy, thus improving and enhancing detoxification efficacy.
In particular, the evaluation of methadone in heroin addicts by NIDD has made a significant contribution to the government's decision of implementing a nation-wide methadone maintenance treatment (MMT) programme. In China, MMT remains a controversial treatment whose effectiveness has been disputed; adoption of MMT has been a subject of debate in China for a decade . In 2004, the Chinese government approved eight pilot studies of MMT for chronic opioid abusers in some provinces where opioid abuse is serious and HIV infection has become a major concern . We conducted studies in these pilot clinics to assess the effect of MMT. Our results showed that MMT is effective therapy for improvements in heroin use, health status, severity of dependence, depressive symptoms and criminal activity in heroin addicts, which support the broad beneficial effects of MMT in China . Based upon these remarkable results, the government decided to expand the MMT programme continuously to cover more drug abusers in more areas . In addition, we conducted a similar evaluation of buprenorphine for treatment of opioid addicts. The positive results have promoted the introduction and approach of buprenorphine in China.
In the past 20 years, NIDD has sought to provide survey and monitoring statistics on drug use and related problems. The Department of Epidemiology engages in the study of population monitoring in drug abusers nation-wide. The commission is under the direct supervision of, and is responsible for submitting national monitoring data to, the National Narcotics Control Commission and State Food and Drug Administration. With the development of a reporting system for drug abuse, a network of drug abuse monitoring currently covers 31 provinces, autonomous regions and municipalities. Online reporting and inquiry systems have also been implemented. The monitoring system plays an important role in understanding the general situation of drug abuse in China. The department is also involved actively in epidemiological surveys on national prevalence trends, prevalence characteristics and the regional spread of drug abuse and addiction. These surveys have been conducted in various areas across the country to elucidate the psychological and social factors of drug abuse, the relationships between drug abuse and HIV/AIDS, factors related to relapse and the consequences on social and public health. The types of drugs covered in these surveys include narcotics and psychotropics with abuse potential (e.g. dihydroetorphine, codeine and buprenorphine). The data collected by NIDD for drug abusers in China have been published as official documents in the Annual Report on Drug Control in China by China National Narcotics Control Commission. According to these data, the department provides guidance for drug abuse prevention and analyses intervention efficacy for the general public, health professionals and policy makers.
In recent years, NIDD has published more than 300 scientific papers, more than 100 of which have been published in international addiction journals. These studies have received much attention in the field of drug abuse, both domestically and world-wide. They have also resulted in patent applications. Each year, NIDD participates in editing and publishing scientific journals and books. The Department of Information on Drug Abuse is responsible for the publication of the Chinese Journal of Drug Dependence and Harm Reduction Bulletin: Drugs and HIV/AIDS. The Editorial Board for the NIDD Research Monograph and Popular Science books are also established in this department. The staff has made efforts to organize and compile textbooks and popular science books on drug-related problems. Currently, about 20 books have been published. The department also participates in organizing and preparing academic meetings, both domestically and abroad. For example, they sponsor the National Conference on Drug Dependence every 2 years. NIDD researchers may attend these meetings and contribute regularly to national and international conferences, which has effectively promoted drug dependence research communication.
Although it is a national institute, NIDD is tied directly to Peking University. Grants for which NIDD applies are under the auspices of Peking University. However, NIDD is also required to complete research commissioned by governmental agencies. In recent years, most financial support for NIDD has been in the form of grants from national and municipal foundations. NIDD has also received funding from international sources, including the World Health Organization cooperative programme, the Global Fund and the United States National Institutes of Health.
NIDD has become one of the major research institutes in the field of drug abuse in China. Because of its position in the field, NIDD receives an ever-increasing number of commissions from the government and is invited to cooperate with research centres and hospitals, both domestically and abroad.
The status of NIDD allows it to follow the most popular and politically sensitive research projects. The government has provided a number of grants to support the research activities of NIDD and permitted it to publish and disseminate its results. Moreover, the financial support for university-based research frees NIDD researchers to immerse themselves in project-related research activities.
Each semester, NIDD conducts courses on drug addiction and neuropharmacology for undergraduates and Master's and doctoral candidates. Most NIDD professors serve as Master's or doctoral supervisors. Peking University also provides opportunities to undergraduates to participate in laboratory activities as interns. These students not only play important roles in the implementation of research, but also stimulate exchange of ideas. However, teaching and training also require professors to devote much time to meeting frequently with students and supervising their theses. To promote effective communication various modes of contact, such as journal clubs and interdisciplinary laboratory meetings, are held each week.
THE ROAD AHEAD
In the future, NIDD will continue to propagate the study and practice of drug abuse research and will expand its research activities according to new developments in the field. Currently, China faces a severe drug abuse situation that may worsen over time. Trends have also emerged showing that the rates of opiate addiction have plateaued in some areas of China, as drug abusers have shifted to new types of addictive drugs. Although opiates, especially heroin, remain the most commonly abused drugs, amphetamine-type stimulants (ATS), including amphetamine, methamphetamine and methylenedioxymethamphetamine (‘ecstasy’), quickly emerged as a new problem in China [23–25]. The first report of MDMA abuse in China occurred in 1994, at first mainly in nightclubs in business districts in south-eastern China. Currently, ATS abuse has spread quickly throughout the country and has reached epidemic levels. Even the countryside faces the growing problem of new types of drug abuse . Increasing numbers of professional staff, entertainers and students have become ATS abusers. By 2005, registered abusers of ATS or ketamine, which is often abused in the same areas, accounted for 9.5% of all registered drug abusers, 7% higher than in 2001, although the actual number is difficult to estimate .
To stem this crisis, the Chinese government has sought to address the growing problem of drug abuse. The first Drug Control Law of the People's Republic of China was approved in 2007 and was implemented in June 2008. This legislation was a milestone of the anti-drug campaign in China, indicating a new stage in the strategy against drug abuse. The change implemented more requirements for NIDD researchers. As stipulated by the drug control law, prevention of drug abuse will be a main focus of anti-drug work in China. Accordingly, NIDD needs to devote more resources and effort towards prevention research.
To meet the new challenges, NIDD will perform further investigations into various aspects of drug addiction. Based upon previous studies, NIDD will strengthen its studies on heroin addicts. These studies will contribute to understanding of the psychosocial disorders induced by addictive drugs which cannot be conducted on animal models. Progress in this aspect will effectively improve prevention and treatment for addiction. Considering the evolving trends in drug abuse in China, NIDD will also invest more energy into the problem of new-type drug abuse. A study on the effects of polydrug abuse and drug interactions is progressing.
Besides illicit drug abuse, alcohol and nicotine use is another main consideration in the NIDD research programme. With the prosperity of the economy, alcohol and nicotine consumption is increasing and will lead to related health problems in China. Currently, the prevalence of alcohol dependence was 6.6% in men and 0.1% in women (3.4% over the total population) in China [28,29]. Alcohol dependence has been ranked as the third most prevalent cause of mental illness. Moreover, alcohol abuse causes millions of deaths or disability due to digestive system diseases, traffic accidents, suicides and social disruption . Smoking has now become another main cause of death in China. Smoking contributes to many deadly health problems, such as respiratory and vascular disease [30–32]. China has the largest population of cigarette smokers in the world. Currently, the total number of smokers is more than 350 million in China, which represents about one-third of all the world's smokers . Accordingly, smoking-related diseases are becoming epidemic and are of significant public health concern in China . We have conducted several research programmes into neurobiological mechanisms and epidemiological surveys on alcohol and nicotine abuse. In future, NIDD will focus responsibility on paying more attention to preventing alcohol and nicotine problems from becoming worse. Our programme of education to the general public has been carried out and comprehensive approaches are also needed.
NIDD also aims to expand studies on the neurobiological mechanisms of drug addiction and related psychiatric diseases. The ongoing research related to this aim includes studies on learning and memory, establishment of a model of neurocircuitry and investigating epigenetic components and proteomics of brain function in schizophrenia and depression. To meet international standards of research, the Key Laboratory of Drug Abuse and Addiction is being developed at NIDD.
To ensure that our research results can effectively aid the treatment of drug addiction, NIDD plans to construct a specific research centre that is involved mainly in drug research and development. Cooperative projects on the research and development of analgesic, detoxification, antirelapse, anti-inflammatory and cardiovascular drugs will be implemented between the Department of New Drug Research and Development and other research institutes or organizations.
The long-term development of NIDD will follow the requirement of the Chinese government to resolve the problem of drug abuse. Its research progress in various fields will maintain NIDD's leading position in China's antidrug campaign.
Declarations of interest
This work was supported in part by the National Basic Research Program of China (2009CB522000), Investigation on Methodology for Estimation and Prediction of HIV/AIDS Epidemic grant (no. 2008ZX100 [01-003]), and the 11th Five-Year Plan of the Chinese Ministry of Science and Technology.