Addiction Research Centres and the Nurturing of Creativity. Substance abuse research in a modern health care centre: the case of the Centre for Addiction and Mental Health
Jürgen Rehm, Centre for Addiction and Mental Health, 33 Russell Street, Room 2035, Toronto, Ontario, Canada M5S 2S1. E-mail: firstname.lastname@example.org
The Centre for Addiction and Mental Health is one of the premier centres for research related to substance use and addiction. This research began more than 50 years ago with the Addiction Research Foundation (ARF), an organization that contributed significantly to knowledge about the aetiology, treatment and prevention of substance use, addiction and related harm. After the merger of the ARF with three other institutions in 1998, research on substance use continued, with an additional focus on comorbid substance use and other mental health disorders. In the present paper, we describe the structure of funding and organization and selected current foci of research. We argue for the continuation of this successful model of integrating basic, epidemiological, clinical, health service and prevention research under the roof of a health centre.
HISTORY AND CONTEXT OF RESEARCH AT THE ADDICTION RESEARCH FOUNDATION (ARF) AND THE CENTRE FOR ADDICTION AND MENTAL HEALTH (CAMH)
The Alcoholism Research Foundation, later named the Addiction Research Foundation (ARF), was established as an alcoholism treatment hospital in 1949 by the Ontario legislature. While Alcoholics Anonymous had lobbied on behalf of the hospital, there was also a political background. Two years earlier, the province's premier had lost his parliamentary seat in an election fought on the issue of his having legalized cocktail lounges. For the new Conservative premier, establishing the Foundation provided the government with a needed quid pro quo, showing that it was addressing alcoholism as a way of compensating for increased alcohol consumption due to relaxed alcohol controls . Interestingly, in a parallel move about 40 years later, substantial funding for gambling treatment and research was established in the wake of legalization of (mostly) government-run gambling. In 1951, new legislation broadened the Foundation's scope, defining research, rehabilitation and education as its main responsibilities.
The sociologist John Seeley, who had served as executive officer of the Canadian Mental Health Association, became ARF's director of research in 1957. He played a defining role in establishing lines of research which continued after he had moved on. Seeley's analysis of the close relationship between the price of alcohol, levels of consumption and levels of cirrhosis mortality  was a founding document in the modern literature on the influence of alcohol availability on rates of alcohol problems. Other ARF researchers followed, with groundbreaking work on the distribution of alcohol consumption in the population and the effects of alcohol control measures [3,4]. In addition to this tradition of epidemiological and social research, ARF established and continued a strong pharmacological and clinical research programme .
The ARF was orientated internationally from the outset. The first international scientific exchange agreement was signed in 1954 with Finland ; perhaps the best-known fruit of this collaboration was the 1975 international collaborative report on Alcohol Control Policy in Public Health Perspective . In 1977, ARF was named the first World Health Organization (WHO) Collaborating Centre in the field of drugs and alcohol, with this international collaborative role continuing today.
In 1998, as part of a general reorganization of the Ontario hospital system, ARF was merged with two psychiatric hospitals and the Donwood Institute, an addiction treatment centre, to become the Centre for Addiction and Mental Health (CAMH) . One goal of the merger was to integrate more effectively addiction and mental health treatment and research. Thus, although many lines of substance use research continued following old traditions, new lines of research formed to address new topics.
It is not possible to do justice to the totality of research on substance use and abuse conducted at CAMH. Therefore, we will restrict ourselves to selected highlights, where we see either a strong impact on knowledge or special relevance for clinical practice or health policy, making links to ARF's roots where relevant. Although we touch upon clinical research below, we highlight especially the non-clinical side of research for two reasons: first, the clinical research has been well described and highlighted elsewhere; and secondly, because many of the important global contributions stem from non-clinical research.
Research at CAMH is organized currently in four departments, all within one Research Division: Clinical Research; Neuroscience; the Positron Emission Tomography Centre (PET Centre); and Social, Prevention and Health Policy Research. The salaries of core scientists in all research departments are supported by core hospital funds, with money to conduct research projects stemming from the following sources for 2008/2009 (in Canadian dollars): Canadian federal funding: 22.8 million; Canadian provincial funding: 5.7 million; US funding, mainly from the National Institutes of Health (NIH): 8.5 million; industry: 3.3 million; and other: 0.3 million. Most of the funds are tied to specific projects.
Part of the effect of this strong reliance upon external and project-specific funding has sometimes been a lack of coherence and collaboration between and within research sections and departments, with collaborations more likely to be focused externally. Greater internal coherence and collaboration is expected with the new multi-million dollar infrastructure grant from the Canada Foundation for Innovation (CFI), which was awarded to CAMH in 2008 to implement a new interdisciplinary vision in which basic, clinical, social and epidemiological scientists are housed under one roof and collaborate to improve population health via health services delivery, prevention and policy.
As indicated above, most funding is governmental, with industry funding amounting to less than 10% in recent years. Examples of industry funding include pharmaceutical support for pre-clinical drug testing (e.g. in vitro receptor binding, behavioural animal testing, PET receptor occupation) and clinical and community-based trials (e.g. smoking cessation). CAMH applies specific policies to ensure the appropriate vetting of proposed industry funding and other commercial interests as they apply both to research and educational activities. Tobacco-industry funding is prohibited for education and research, while any funding proposals involving alcohol, gaming or other addiction-related industry are examined based on the CAMH Policy on Relationships with Donors/Sponsors/Partners. Research contracts are generally reviewed by counsel in the Research Office, while some consulting agreements are vetted by procurement.
BASIC MEDICAL AND BIOBEHAVIOURAL RESEARCH AT ARF AND CAMH
Basic medical research has been a critical component of clinical (and preventive) practice both at ARF and CAMH. While impact on practice has not necessarily been immediately evident, there has been a remarkable impact of basic research on the global understanding of addiction. Specifically, early basic research at the ARF [8–13] led to advances in: the mechanisms underlying the effects of chronic exposure to alcohol as well as the pathological consequences; identification of the behavioral and neurochemical mechanisms contributing to alcohol tolerance, following repeated or chronic exposure; and determining the mechanisms underlying liver or neurological damage induced by chronic alcohol exposure.
The focus of research changed in the early 1980s, with emphasis then being placed upon [14–22]: developing animal models of alcohol self-administration; translational studies, focused primarily upon opiates and serotonergic agents; genetic studies of variation in cytochrome P450 (CYP) enzymes and the metabolism of various drugs (e.g. nicotine, benzodiazepines, codeine) as factors in vulnerability to drug abuse as well as variation in response to treatment; and developing rodent models of nicotine self-administration to determine the mechanisms underlying nicotine self-administration.
The formation of CAMH resulted in a doubling of the number of scientists involved in basic medical research. By merging basic addictions and mental health scientists within one department, the new organization took a substantial step forward by refocusing considerable effort on comorbidities (e.g. alcohol dependence and depression; tobacco dependence and schizophrenia). This basic medical and biobehavioural research group also made possible greater access to highly advanced technologies. In addition to technological and intellectual advances, the context for mental health and addictions research was broadened.
CAMH scientists are active in basic research in a number of areas of addictions. The first area, as mentioned, is the study of comorbidity, including animal models and the neurobiological mechanisms involved. For example, depression and schizophrenia are associated strongly with alcohol and tobacco abuse. Thus, the combination of expertise in animal models of depression and schizophrenia with expertise in animal models of alcohol and nicotine abuse and alcohol/nicotine co-abuse has advanced the understanding of the neurobiology of comorbidity [23,24]. As a second example, the current work on genetics dealing with CYPs and central nervous system (CNS) receptor targets in the vulnerability to addiction and variation in treatment response, as well as the addition of epigenetics, is at the forefront of the addiction field [25–28].
Another area of collaborative impact is the integration of behavioural and genetic work with advanced molecular biological and imaging techniques by experts in these areas [29–34], thereby leading to important advances in understanding the biological processes involved in addiction, including gambling. In addition, a key thrust of recent research has been the integration of basic research with human and clinical research with, for example, the testing of novel treatment drugs proposed from animal models and clinical observation, and the initiation of pharmacogenetics testing from human experimental results in our clinical populations. These initiatives reflect the transfer of ideas in both directions between basic and clinical research and a focus of basic research on clinically important topics.
EPIDEMIOLOGY TO INFORM POLICY AND CLINICAL RESEARCH
Since the early days of ARF, epidemiology has been a key element of the organization's research agenda. Robert Popham in 1972 and Wolfgang Schmidt in 1981 received the Jellinek award for their contributions in epidemiology. More than two decades later, Jürgen Rehm received the same award for research contributions in alcohol epidemiology and for international leadership in the application of state-of-the-art methods in population studies (http://www.jellinekaward.org/jellinekawards.aspx). Currently, CAMH research underlies the two most recent resolutions of the World Health Assembly with respect to alcohol [35,36]. CAMH also houses the Global Information System on Alcohol and Health (GISAH; http://www.who.int/substance_abuse/activities/gad/en/) as part of its contributions as a WHO Collaborating Centre. CAMH research has made substantial contributions to international epidemiology with the development of methodologies and techniques that have been applied in many countries, and continues to impact policy decision making with respect to alcohol, tobacco and illegal drugs. Recent examples include the comparative risk analyses for alcohol within the Global Burden of Disease Studies 2000 and 2005 [37,38], used widely to define alcohol policy (e.g. [35,36]; http://www.who.int/topics/alcohol-drinking/en/); the contribution to a project by the World Bank on developing disease priorities for developing countries ; and the various contributions to combine epidemiological and economic research on cost of use and abuse of various substances in Canada and worldwide (e.g. [40–42]).
Provincial and national policy have also been influenced by the ongoing adult (CAMH Monitor) and adolescent surveys (Ontario Student Drug Use and Health Survey), which combine substance use and mental health topics (http://www.camh.net/Research/Areas_of_research/Population_Life_Course_Studies/population_life_course.html). These surveys, which have been conducted since 1977 mainly under the management of Edward Adlaf, are among the longest ongoing surveys of their kinds in the world.
COMMUNITY PREVENTION RESEARCH
In 1978, ARF established a specialized regional research centre in London, Ontario, devoted to community research and programme evaluation. Its formation was instrumental in forging a mandate for community-based research and evaluation, tied closely to provincial programmes and policy related to prevention and health promotion (and health systems—see section below). Numerous prevention and health policy programmes have stemmed from community-based research conducted by CAMH/ARF researchers including, for example, server training , municipal alcohol policies , work-place  and education programmes [46,47]. CAMH/ARF's community consultants located across the province of Ontario [now operating in the Policy, Education and Health Promotion (PEHP) department] facilitate the translation of knowledge into local community programming.
The ‘Safer Bars’ programme to reduce violence in licensed premises is a recent example of community-based harm reduction research stemming from this tradition. Its development and evaluation spanned almost 10 years, starting under ARF and completed under CAMH (http://www.camh.net/Publications/CAMH_Publications/safer_bars_program.html). Safer Bars was developed and tested in an iterative process over 4 years by a multi-disciplinary working group of researchers and community professionals . The effectiveness of the final programme was demonstrated in a randomized controlled evaluation funded by NIH . Safer Bars has since been licensed for distribution in a number of locations both within and outside Canada. Analyses from this database have identified the key role of intoxication, bar staff and the environment in the occurrence and severity of aggression [50,51].
Harm reduction and preventive interventions have also included population-level initiatives focused upon reducing problem drinking. Brief interventions for problem drinkers, pioneered in part at ARF [52,53], have recently been made available as online interventions. As an example, the Check Your Drinking screener (CYD; http://www.CheckYourDrinking.net), a brief personalized feedback programme, was modeled after the Drinker's Check-up  and the Fostering Self-Change intervention . A recently completed randomized controlled trial found that access to the CYD resulted in a significantly larger reduction in alcohol consumption compared to the reduction that occurred in the control group .
One of the main values of CAMH as a modern health care centre has been to reach out to special populations, such as Aboriginal populations, the lesbian/gay/bisexual/transgendered community, youth, university students and the elderly. One example is the Aboriginal community alcohol harm reduction policy (ACAHRP) project implemented in some First Nation communities in the mid-1990s under ARF. Implementation of this policy was associated with a reduction in alcohol intoxication, nuisance behaviors, criminal activity, liquor licence violations and personal harm and was viewed by administrators and facility staff in each community as having a positive effect on events at which alcohol was sold or served .
The CFI infrastructure grant (mentioned above) will further enhance knowledge exchange in the community and facilitate multi-disciplinary collaborations. Aligned with CAMH's strategic plan of fostering innovation and knowledge exchange, one initiative within this grant is a mobile research laboratory that will be outfitted with computers and data entry equipment, monitoring devices, equipment for health examinations and storing body fluids, as well as interview rooms and training space. The mobile laboratory will allow for data collection in diverse communities across Ontario, including remote and disadvantaged communities (see marginalized populations, below). Future use of the mobile laboratory, which has just received funding, will include the development of a community indicator database of individual and community-level variables relating to substance use and other mental disorders, led by a multi-disciplinary team of researchers. This team will integrate biological, social and behavioural science research to gain a better understanding of individual and community factors that play a role in the aetiology and treatment of addictions and mental illness. This new community initiative will be conducted in partnership with local community agencies, facilitated through existing alliances with community consultants from PEHP.
HEALTH SERVICES RESEARCH
Since the 1970s, ARF research has included a focus on addictions services, with evaluative studies of Ontario's overall treatment system and innovative elements such as non-medical detoxification services . This work also included development of a client treatment information system for the province [58,59] and a treatment registry to provide up-to-date information on waiting times and other programme characteristics related to availability and accessibility of services [Connex Ontario: http://www.connexontario.ca (accessed 31 July 2009)]. Both information systems became integral sources of data for treatment system planning across Ontario as well as services research at CAMH (e.g. ).
With the 1998 merger, addictions services research was integrated with a mental health services research programme located in one of the other founding partners (Clarke Institute of Psychiatry) and became affiliated with the Department of Psychiatry at the University of Toronto. The core addictions services research agenda continued, for example, with provincial studies aligned closely with government addictions treatment policy, such as the implementation of standardized assessment and discharge criteria, feasibility assessment of a provincial outcome monitoring system, development of performance indicators for the treatment system and best practice reviews. However, the services research agenda also expanded, with a much stronger focus upon harm reduction, marginalized populations and comorbidity of mental and substance use disorders.
The creation of CAMH not only increased the total scientific cadre that has a mandate for addictions and mental health services research; it also extended significantly the reach and impact of the work in the relevant policy domains provincially and nationally. In 2001, the first pan-Canadian best practice review on co-occurring mental and substance use disorders was undertaken which, in turn, spawned a host of CAMH-led treatment system development activities, epidemiological studies of comorbidity and help-seeking in community and treatment samples (e.g. [61–64]). It also led to validation and translational studies of screening tools (e.g. ) and research syntheses focused upon the integration of mental health and substance use services and systems .
Research at CAMH has informed alcohol, tobacco and drug policy for decades, contributed to assessing policy changes and facilitated knowledge exchange with public health and policy specialists. Again, we highlight selected contributions.
The population-based orientation promoted by ARF researchers in the 1960s and 1970s was a novel perspective—at odds with the dominant view that alcohol-related problems and dependence were independent of population drinking levels . However, this perspective has received substantial research support [68–70]), demonstrating that population patterns of drinking impact societal level rates of trauma and other problems experienced by drinkers who are not dependent upon alcohol and contribute to risk of chronic disease such as cancer . As indicated above, population surveys at CAMH have been providing tools for policy tracking and assessment in Ontario. CAMH researchers also played leading or substantial roles in national surveys focusing upon alcohol and other drugs [71,72].
Alcohol as a public health issue has been a focus of four projects under the co-sponsorship of the World Health Organization, where ARF/CAMH researchers played important roles [6,68–70]. These projects reviewed the effectiveness and cost-effectiveness of policy interventions to reduce consumption and alcohol-related harm. Additional contributions focused upon cultural and social dimensions of trends in consumption and societal-level damage and policy responses [73,74] and upon provincial and national policy case studies .
ARF/CAMH research influencing provincial, national and international policy also includes tobacco and traffic safety. The Ontario Tobacco Research Unit (OTRU; http://www.otru.org/), founded in 1993, has been hosted by ARF/CAMH from its inception and CAMH remains one of three co-sponsors. OTRU has played an influential role in tobacco control in Canada and has been at the forefront of international developments.
Impaired driving has been the focus of research since the early days of ARF. David Archibald participated in the first international conference on alcohol and traffic safety ; Popham was involved in one of the original case–control studies demonstrating the impact of alcohol on collision risk ; and Schmidt & Smart pioneered the exploration of the role of alcohol abuse in motor vehicle collisions . CAMH researchers have continued to examine the nature of the impaired driving problem (e.g. ), including work to document the role of alcohol availability , and to provide some of the first evidence on the problems presented by driving after using drugs other than alcohol . They have worked closely with clinical and community partners to promote the introduction of educational, deterrent and remedial programmes to reduce deaths and injuries resulting from impaired driving (e.g. ), and were instrumental in many effective legal changes and enforcement initiatives in Ontario and more widely. CAMH research also has greatly facilitated our understanding of the mechanisms by which legal measures such as per se laws, alcohol policy measures and remedial programmes have reduced drinking–driving fatality rates over the years [82–84].
CAMH researchers have collaborated in knowledge exchange with the organization's community consultants, public health and policy specialists. This includes frequent presentations to national or provincial parliamentary standing committees, city councils and boards of health and participation on provincial and national policy advisory boards. Topics have covered a considerable range, e.g. harm reduction in drug policy, gambling treatment service provision, privatization of retail alcohol sales, drinking–driving countermeasures, alcohol taxation policies, social costs of alcohol, drug and tobacco, and alcohol and cancer.
Work by ARF scientists Mark and Linda Sobell, Helen Annis and Martha Sanchez-Craig on programmes such as fostering self-change and structured relapse prevention [85–89] had a significant role in re-shaping behavioural therapy for substance use problems. These research traditions have continued under CAMH, including online interventions (described above under ‘Community interventions’) and using new generation behavioural therapies, both as stand-alone interventions and within more comprehensive treatment approaches involving pharmacotherapy.
Current research is more focused upon comorbidities such as the ongoing randomized clinical trials by Tony George on the use of varenicline to treat tobacco addiction in people with schizophrenia or bipolar disorder, and the use of repetitive transcranial magnetic stimulation for nicotine in schizophrenic patients. In addition, a trial is under way to examine acamprosate effects on alcohol abuse/dependence in people with schizophrenia. These trials fit well into a larger interdisciplinary CAMH research agenda on understanding and treating substance dependence in people who also have other mental disorders.
OPPORTUNITIES AND CHALLENGES
By all accounts, the impact of substance use research conducted at ARF and now CAMH can be described as a success story, both with respect to increasing scientific knowledge and improving interventions from clinical practice to policy. The tradition established under ARF of housing basic science and epidemiological, clinical, health services, prevention, community and policy research within a single organization has continued and largely flourished under CAMH, at least in part because the core funding has remained relatively stable. The umbrella and infrastructure of a health care centre with a hospital at its core, but with research, preventive services, health systems planning and community outreach as integral parts, provide a stimulating environment for research. Many of the current new initiatives stem from interdisciplinary interactions, more traditionally between basic and clinical research, but also integrating social epidemiology and community perspectives. The construction of new research facilities, involving the CFI funding mentioned above, will enable the physical integration of different disciplines, departments and perspectives under one roof to enable further innovative interdisciplinary research. This initiative has prompted researchers from multiple disciplines to meet on a regular basis and discuss common points of interest and project ideas to stimulate a more coherent research programme and even some breakthroughs rather than the traditionally more restricted activities of ‘normal science’ within departmental confines. Preliminary experiences suggest that informal day-to-day contact will result in more numerous and more fruitful collaborations compared with more formal integrating structures such as lecture series or extensive meetings and strategic planning.
The model of substance use and addictions research developed by ARF and continued at CAMH, although successful, is also threatened from time to time. For example, pressures to exclude some areas of research stem from the narrow perspective of health research as ‘bench to bedside’, which does not recognize the more systemic view of health care provision or consider important contributions of prevention, health promotion and early intervention to avoid substance abuse and dependence in the first place. This restricted perspective ignores the clear evidence from research at ARF/CAMH and elsewhere, for example, that taxation can lead to a higher reduction in dependence rates in the Ontario population than application of the best current treatment programme available . Of course, not all prevention efforts are able to show such substantial impact; however, it is clear that prevention and treatment are both important in reducing harmful substance use and related health impacts. Preventive interventions can and should provide the same level of evidence for success as clinical interventions and even the methodology, such as randomized trials, is often the same.
As CAMH moves into its second decade as a multi-disciplinary institution that addresses both addictions and mental health, the challenge remains to build upon these strengths by integrating different disciplines as well as integrating research and practice. Some of the research examples above demonstrate not only the depth and expertise of individual scientists and research traditions, but also the potential for innovation and increased impact when diverse elements are brought together for common goals. Especially during times of shrinking resources, it is important to recognize and develop these opportunities, valuing and learning from the past but focused firmly on the future.
H. D. Archibald (1919–2009), Founding Director, Addiction Research Foundation of Ontario (ARF).
Declarations of interest
Drs Graham and Rehm have received financial support to travel to and participate in meetings sponsored in whole or in part by the alcohol industry. Dr Rehm also received various unrestricted funds for projects by the pharmaceutical industry. Dr Tyndale owns shares and participates in Nicogen Research Inc., a company focused on novel smoking cessation treatment approaches. Dr Tyndale also consults for pharmaceutical companies.
Support to CAMH for the salary of scientists and research support staff has been provided by the Ontario Ministry of Health and Long-Term Care. The views expressed do not necessarily reflect those of the Ministry of Health and Long-Term Care. We would like to thank John Cunningham, Griffith Edwards, Debbie Thompson and two anonymous reviewers for their helpful comments on earlier versions of this submission.