What Can Science Contribute to the Treatment of Alcoholism? George F. Koob, Ph.D. Director National Institute on Alcohol Abuse and Alcoholism National Institutes of Health
Flow of Talk 1. Conceptual Framework for Addiction: Stages of the Addiction Cycle 2. Neurobiological Circuits as Targets for Treatment 3. Current Treatments 4. Future Treatments
Addiction Addiction Defined as a chronically relapsing disorder that is characterized by a compulsion to seek and take drug or stimulus, loss of control in limiting intake, and emergence of a negative emotional state (e.g. dysphoria, anxiety, irritability) when access to the drug or stimulus is prevented (here, defined as the dark side of addiction)
Stages of the Addiction Cycle
Treatment for Alcoholism What We Know Works: Screening and Brief Interventions Family Therapy Motivational Interviewing Cognitive-Behavioral Therapy (CBT) Mutual Help Groups Aftercare/Continuing Care Medications: Acamprosate (Campral) and Naltrexone (Vivitrol)
Conceptual Framework for Neurobiological Bases of the Transition to Excessive Drinking
Bottom Line 1. Addiction is an incentive salience-reward deficit disorder. 2. Addiction is a stress surfeit disorder. 3. Addiction is an executive function disorder.
Medications Development for Alcoholism- Milestones 1954 - Disulfiram (Antabuse) approved by the FDA for treatment of alcoholism Prior to 1991 less than half dozen clinical pharmacotherapy grants After 1991- Request for Applications (RFA) issued leading to the funding of 10 clinical pharmacological trials 1994 - Oral naltrexone approved by FDA 2004 - Acamprosate approved by FDA 2006 Extended-release injectable naltrexone (Vivitrol) approved by FDA 2007 NIAAA Clinical Investigations Group (NCIG) trial established (three Phase 2 trials completed to date) 2013 Nalmefene approved by EMA
Existing and Future Medications for Addiction: Binge/Intoxication Stage Existing medications disulfiram (Antabuse) naltrexone (Vivitrol) Future targets partial agonists (intoxication blockers) ghrelin
Existing and Future Medications for Addiction: Withdrawal/Negative Affect Stage Existing medications acamprosate (Campral) Future targets GABA modulators (homeostatic resetters) CRF 1 antagonists (stress reducers) κ opioid antagonists (dysphoria reducer)
Existing and Future Medications for Addiction: Preoccupation/Anticipation Craving Stage Existing medications acamprosate (Campral) Future targets GABA modulators (homeostatic resetters such as gabapentin- Norontin) CRF 1 antagonists (stress reducers) Glutamate modulators (habit reducers)
NIAAA Medications Development Program for Alcohol Use Disorder (AUD), High-Risk Drinking, and Alcohol-Related Medical Disorders Mission: To improve the care and treatment of those affected by AUD, high-risk drinking, and alcoholrelated medical disorders by supporting the development of effective and safe medications that are accepted and used by clinicians and patients. Overall Goal: Translate promising medications from discovery to preclinical and human clinical testing to real-world effectiveness and implementation studies.
Conceptual Framework For Medications Development Animal Models Group Human Laboratory Models Group NIAAA Clinical Investigation Group (NCIG) Network of Sites for Proof of Concept Trials Molecular Targets Animal Models Human Laboratory Models Clinical Trials Validation Process: Bidirectional Integration
National Center for Advancing Translational Science (NCATS) Discovering New Therapeutic Uses (NTU) for Existing Molecules Program Applicants identify new uses for compounds from pharma s virtual medicine cabinet Participants include AstraZeneca, Janssen, Pfizer, and Sanofi 26 Agents available including 12 for pediatric indications and 18 new agents Memorandum of Understanding Between NIH and Industry Partners Industry partners provide pre-clinical and clinical supply including placebo
Screening & Brief Intervention for Adults NIAAA Clinician s Guide - 2005 Edition Updated in 2007 An evidence-based guide for primary health care practitioners to provide screening for their adult patients, provide brief intervention for risk drinkers, diagnose DSM-IV alcohol use disorders and provide treatment or referral to specialty treatment services. The Guide makes it is easier for clinicians to address alcohol use with their patients. The Guide provides up-to-date information on the latest evidencebased practices, including medications.
Screening & Brief Intervention for Youth NIAAA Alcohol Screening Guide A brief, easy to score, empirically-based screen for risk, alcohol use, and problems that overcomes time constraints and other common barriers to youth alcohol screening. It is based on just two questions one about friends drinking and the other about personal drinking frequency. Analysis of data from more than 160,000 youth indicated these questions had the greatest predictive power. The Guide is endorsed by the American Academy of Pediatrics. A Medscape course based on the guide with CME credit is available to date over 15,000 clinicians have been Medscape. certified.
Special Thanks Vivian Faden Joanne Fertig Bob Huebner Raye Litten Patricia Powell Kate Tepas-Wise Kenneth Warren Bridget Williams-Simmons
Thank You! George F. Koob, Ph.D. Director National Institute on Alcohol Abuse and Alcoholism National Institutes of Health