Clinical Toxicology includes acute and chronic medicine and chemical poisoning, serious adverse prescribed and non-prescribed drug reactions, and toxicology that contributed to a substantial source of morbidity and mortality across the world. The team (led by Professors Andrew Dawson and Nick Buckley) has established large prospective cohorts of acute poisoning and developed treatment guidelines resulting in national and international policy and regulatory changes. Much of their national research is based on detecting early signals of significant drug toxicity and measuring the public health impact of regulatory change. This group has led the development of the NSW Poisons Information Centre research program and used data to describe many developing trends in poisoning including pharmaceuticals and drug use. The team has been funded by NHMRC Program and Centres of Research Excellence (CRE) Grants (CRE in Medicines Intelligence, and CRE in Translational Venom and Antivenom Research) along with Project grants and other forms of support. Recent projects include: 

• The Australian Toxicology Monitoring (ATOM) and Australian Snakebite Projects (ASP), which identify the clinical effect and response to treatment from various poisonings and snakebites. 
• An evaluation of the patterns of use and poisoning with various substances like codeine, paracetamol, pregabalin, etc.
• A randomised stepped wedge trial of scaling up of a community-based alcohol education program in rural Sri Lankan villages, and its effects on alcohol use, associated harms, depression and social capital. 
• A comparative study of oral and intravenous antidotes for acute paracetamol poisoning
• Long-term effects on kidney function and health after severe acute pesticide poisoning and snake envenomation

Indigenous Health and Substance Use research (led by Professor Kate Conigrave, Associate Professor Kylie Lee and Dr Michael Doyle) involves developing culturally appropriate, accessible and innovative approaches to prevent or treat alcohol or other drug use disorders among Aboriginal and Torres Strait Islander peoples and other priority populations. Founded on longstanding partnerships with these communities and services across Australia, focus is on culturally appropriate and relevant work. Current research activities in the area include:

• A Centre for Research Excellence (CRE): Indigenous Health and Alcohol was opened in May 2017 to recruit and support Indigenous Australian researchers. The CRE, funded by the NHMRC, aims to reduce alcohol harm experienced by Indigenous Australians, and works to draw on the diverse range of skills among the investigators and the Indigenous research trainees. It combines cultural, community, health service, research and policy expertise. To date the CRE has mentored 9 post-graduate research students, 3 early career researchers, and 3 trainees, all of whom are Aboriginal descent.
• The design of a world-first iPad App that has been shown to be an accurate and acceptable tool to help Aboriginal and Torres Strait Islander peoples to self-report their drinking and provides them with immediate tailored feedback on the App ('brief intervention').
• A cluster randomised trial that examines a model of support for 22 Aboriginal and Torres Strait Islander community controlled primary care services around alcohol care.
• Several studies that are identifying the need for treatment for alcohol use disorders in the NSW prison system, and if there are ways to better meet any unmet need.

Alcohol biology and genetics of liver disease is an important area of research at Drug Health Services within the Alcoholic Liver Disease Research Program. The program led by Associate Professor Devanshi Seth, undertakes a range of clinical, fundamental and translational research. This research is internationally recognised for significantly advancing the field by contributing to the understanding of genetics and molecular mechanisms of alcohol-related liver disease (ALD). Current research involves:

• Clinical research: the multinational GenomALC Consortium led by Seth is investigating the genetic/genomic factors associated with the risk of alcoholic cirrhosis across Australia, UK, USA and Europe. The team established the world's largest biobank and database from ~6700 drinkers and identified novel genetic risks associated with alcohol-related cirrhosis. This ongoing research, funded by the National Institutes of Health (NIH)/National Institute on Alcohol Abuse & Alcoholism (NIAAA), USA, continues to explore the genetic architecture of this disease
• Fundamental research: This research focuses on understanding the molecular mechanism underlying progression of ALD using experimental models, including animal (mouse, zebrafish) models of fatty liver. Research using state-of-the-art gene-editing tools (Crispr-Cas9) in a zebrafish model of alcohol-induced fatty liver is underway studying the mechanisms of action of the genes (identified through GenomALC findings) involved in lipid (fat) metabolism 
• Translational research: (i) The GenomALC study developed a novel genetic risk score (GRS) and combined with clinical risk (diabetes) developed a predictive model to identify patients at higher risk of cirrhosis. This novel concept is now being planned for a randomized clinical trial that underpins the implementation of this research with a potential to significantly impact the field of genomics and personalised medicine for ALD patients. (ii) PETH test, a semi-quantitative measure for alcohol use, was established by Dr Seth's research group at RPA Hospital. This test is now routinely used in clinical settings by Drug Health and Liver clinics to determine alcohol use, changing the management of Alcohol Use Disorder (AUD) patients and used in clinical trials to evaluate alcohol addiction treatment.

Clinical Research in Alcohol & Addictive behaviours and Treatment is a major area of interest with ongoing randomised control trials, including comorbid substance abuse and suicide risk. The team (led by Associate Professor Kirsten Morley) is leading world first research into alcohol dependence, alcoholic liver disease and their associated psychological comorbidities. The team is currently conducting a number of randomised clinical trials testing novel treatments for alcohol addiction, and how to optimise the response to treatment and improve translation of evidence-based approaches into practice. These include:

Discovery

• A study of cannabidiol (CBD) examining the effect of CBD on a range of different functions such as functional connectivity between brain regions, brain activity in response to alcohol and anxiety cues, brain metabolite levels in addition to measures of craving, sleep and mood.
• An MRI study comparing the action of topiramate and naltrexone on functional connectivity between brain regions, brain activity in response to alcohol and anxiety cues, brain metabolite levels and the role of genotypes in these actions.
• A predictive MRI study examining neural, cognitive and epigenetic predictors of response to MDMA assisted exposure therapy to treat comorbid PTSD and AUD.

Treatment

• A randomised, double blind, controlled trial comparing naltrexone to topiramate in the treatment of alcohol dependence. It comprises of a 12-week treatment program with study medications (naltrexone or topiramate) and medical management. NHMRC funded. (2019-2021)
• A randomised, double blind, controlled trial investigating whether N-acetylcysteine is a safe and effective treatment for reducing heavy alcohol consumption. In this study participants are randomly allocated to N-acetylcysteine or matched placebo and undergo a 12-week treatment program with study medications (NAC or placebo) and medical management.

Translation

• National clinical guidelines for treatment of Alcohol problems. The ECC team led a national working group to revise and update these guidelines and generate implementation tools. (2018-2021)
• An evaluation of the effectiveness of the Pathways to Comorbidity Care (PCC) training program in improving the management of comorbid substance use and mental disorders using an integrated comorbidity management approach. Both the clinical practice outcomes and the implementation outcomes were evaluated. Funded by the NSW Health Translational Research Grant Scheme. (2017-2020)
• Following on from the PCC project, a need assessment of drug and alcohol and mental health nurses is being conducted to inform a process of engaging leadership in implementing an integrated care management approach to comorbid drug and alcohol and mental disorders with nurses. (2021-2023)

Illicit Drug use team (led by Associate Professor Carolyn Day) examines substance use and related harms in vulnerable populations. In particular it evaluates the influences and improvements to service use and delivery in this area. The program has close connections with the Sydney Women's and Drug Research group (SWaDR) as well as NGOs including Uniting Sydney Medical Supervised Injecting Centre and the NSW Alcohol and Drug Foundation. Recent projects include: 

• Alcohol and other Drugs Outcomes Register (AoDOR): Health Systems Access and Patient Journey
• Validation and international comparison of the street value of prescription and illicit drugs using Street Rx data
• Examining COVID-19 related changes to delivery of opioid agonist treatment
• Development of a model of care for substance use in pregnancy and parenting for Sydney Local Health District. 
• Understanding driving-related safety for individuals who receive opioid agonist treatment (OAT).
• The ADM users into treatment (ADMiT) study: linking people who use automatic dispensing machines with the hepatitis c cascade of care
• Characteristics and needs of women seeking treatment for substance use disorders in NSW
• Understanding the factors facilitating or hindering utilisation of drug and alcohol services for the Muslim and Arabic speaking community in Sydney
• Suicide prevention project at Uniting Medically Supervised Injecting Centre (Uniting MSIC) 
• Evaluation of drug and alcohol services for young people in Sydney including client and practitioner perspectives, cultural competency and the role of agency and aspiration in youth treatment