NIAAA Director's Report on Institute Activities to the 153rd Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism

Thursday, February 6, 2020

Table of Contents

• NIAAA BUDGET
• DIRECTOR'S ACTIVITIES
• STAFF TRANSITIONS
• HONORS & AWARDS
• RECENTLY ISSUED NOTICE OF FUNDING OPPORTUNITIES
• NOTABLE NIAAA STAFF ACTIVITIES
• WHAT'S AHEAD?
• NIH RESEARCH HIGHLIGHTS
• NIAAA COMMUNICATIONS ACTIVITIES

IN MEMORIAL

Dr. Richard Veech, Chief of NIAAA’s Intramural Laboratory of Metabolic Control, passed away last week. He was a world-renowned scientist with expertise in cellular energy metabolism. He is also known for his work that characterized therapeutic benefits of a ketone-rich diet in various metabolic and neurodegenerative disorders. Dr. Veech served as a scientist in the Federal government for over 50 years.

NIAAA BUDGET

Fiscal Year (FY) 2019

NIAAA closed FY 2019 on September 30, 2019; the final FY 2019 appropriation for NIAAA was $525.6 million. This represented a $16.0 million (3.1 percent) increase over the FY 2018 budget level. The NIAAA appropriation included a $5.8 million set-aside for the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. Key funding actions within this appropriation were:

• NIAAA awarded 760 research project grants (RPGs), including 159 competing awards (up from 738 awarded in FY18). 
• NIAAA funded 21 research centers for a total of $31.6 million.
• NIAAA funded 182 other research grants for a total of $45.6 million, including career awards, one cooperative clinical agreement, and several resource and conference grant awards.
• NIAAA supported 326 full-time training positions for a total of $15.0 million (up from 305 positions in FY18).
• NIAAA funding for its Research and Development (R&D) contract portfolio was $34.2 million.
• NIAAA support for intramural research totaled $54.4 million.

FY 2020

On December 20, 2019, the President signed H.R.1865 - Further Consolidated Appropriations Act, 2020 Public Law No. 116-94. NIH received a total of $41.6 billion, $2.3 billion above the FY 2019 enacted level. This funding includes allocations for the Helping to End Addiction Long-term (HEAL) Initiative, the 21^st Century Cures Act, the BRAIN Initiative, and research on influenza. The bill provides a general increase to NIH institutes and Centers and it continues support for the Gabriella Miller Kids First Act pediatric research initiative.

The FY 2020 appropriation for NIAAA provides $545.4 million. This represents a $19.8 million (3.8 percent) increase over the FY 2019 budget level. 

FY 2021

The preparation of the FY 2021 President’s Budget is underway as of January 2020.

DIRECTOR’S ACTIVITIES

NIAAA Director Dr. George F. Koob made the following plenary presentations between August 1, 2019, and Dececouncil/niaaa-directors-report-institute-activities-153rd-meeting-national-advisory-councilmber 31, 2019:

• “Drug Addiction: The Gain in the Brain is in the Pain” for the International Drug Abuse Research Society in Casablanca, Morocco, on September 3, 2019
• “A Heuristic Domain Framework for Understanding the Prevention, Diagnosis, and Treatment of Alcohol Use Disorder” at the University of Illinois Research Extravaganza in Urbana, Illinois, on September 17, 2019
• “Drug Addiction: The Gain in the Brain is in the Pain” as the 36^th Annual Feldman Lecture in Alberta, Canada, on October 4, 2019
• “The Gain in the Brain is in the Pain” for the Asian College of Neuropsychopharmacology in Fukuoka, Japan, on October 12, 2019
• “NIAAA Update: Progress and Priorities” for the American Academy of Addiction Psychiatry in San Diego, California, on December 7, 2019
• “NIAAA Update” for the American College of Neuropsychopharmacology in Orlando, Florida, on December 6, 2019
• “Alcohol Use Disorder and Sleep Disturbances: A Feed Forward Allostatic Framework” for the American College of Neuropsychopharmacology in Orlando, Florida, on December 9, 2019 

STAFF TRANSITIONS

New Staff

Internal Transitions

Karen Harrington transitioned from her role as the Intramural Section Chief in the Administrative Services Branch to Chief of the Administrative Services Branch.

Depating Staff

Dr. Anita Bechtholt, former Health Scientist Administrator in the Division of Treatment and Recovery Research, transferred to the National Institute of Mental Health, where she now serves as the Associate Director for Research Training & Career Development in the Division of Translational Research.

Bonnie Ellis, Former Administrative Services Branch Chief, accepted a new position as Executive Officer with the Center for Scientific Review.

Dr. Mehdi Farokhnia, Research Fellow in the Laboratory on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, has accepted a position as Staff Scientist at the National Institute on Drug Abuse.

Bridgette Green left NIAAA to join the Nursing Department at the NIH Clinical Center as a Lead Extramural Assistant in September. During her four years with NIAAA, she worked as a Program Specialist in the Division of Metabolism and Health Effects.

Dr.Dale Hereld retired in September after 11 years as a Health Scientist Administrator in the Division of Metabolism and Health Effects. Prior to coming to NIAAA, he had an academic career at the Medical School of the University of Texas Health Science Center at Houston. Dr. Hereld's specific areas of expertise included signal transduction and chemotaxis. He came to NIAAA in 2008 to oversee the basic research portfolio on fetal alcohol spectrum disorders (FASD). He was also a staff collaborator on three FASD-related cooperative agreements: the Prenatal Alcohol, SIDS, and Stillbirth Research (PASS) Network; the Collaborative Initiative on FASD (CIFASD) research consortium; and the Collaboration on FASD Prevalence (CoFASP) research consortium. Dr. Hereld was the NIAAA representative on many trans-NIH committees and projects, including the Trans-NIH Environmental Influences on Child Health Outcomes (ECHO) program from 2015 until his retirement.

Minoo McFarland, Nurse Practitioner with the Laboratory of Neuroimaging, departed NIH to spend time with her family.

Alesia Wilbur, Office of the Director, NIAAA, retired after 30 years of federal service. During her time at NIAAA, she worked closely with the Director and managed administrative staff and functions within the Office of the Director.

HONORS AND AWARDS

Dr. Bill Dunty received a Eunice Kennedy Shriver National Institute on Child Health and Human Development Collaboration Award for his efforts with the Trans-NIH Pediatric Research Consortium (N-PeRC) Group.

Dr. Robert Freeman received a Certificate of Recognition from the Office of Behavioral and Social Science Research for “Outstanding Contributions Supporting Implementation of a Clinical Trials Policy for Behavioral and Social Science Researchers”.

Dr. Ralph Hingson was awarded the Woodrow Wilson Lifetime achievement award from Johns Hopkins University on October 3, 2019.

Several NIAAA staff members received NIH Office of the Director Honor Awards:

• Dr. Robert Freeman, for outstanding contributions to the development and execution of the Sexual and Gender Minority Research Investigator Awards Program
• Deborah Langer, for contributions to the Pathways to Prevention Program Coordination Team
• Dr. Steven Vogel, for professional oversight and development of training opportunities to promote the responsible conduct of research at NIH
• Dr. Pamela Wernett, in recognition of extraordinary dedication and teamwork for creating the online resource "HeLa Cells: A Lasting Contribution to Biomedical Research"

RECENTLY ISSUED NOTICE OF FUNDING OPPORTUNITIES

Notice of Funding Opportunities (NOFO) Issued by NIAAA:

Consortium on the Neurobiology of Adolescent Drinking in Adulthood (U01 Clinical Trial Not Allowed; U24 Clinical Trial Not Allowed): This NOFO supports research projects and research resource cooperative agreements as components of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) consortium to elucidate persistent changes in complex brain function-behavior relationships following adolescent alcohol exposure. RFA-AA-20-003; RFA AA 20-004;RFA AA-20-005

Impact of Alcohol on the Onset and Progression of Alzheimer’s Disease and Its Related Dementias (R01 - Clinical Trial Optional): In collaboration with National Institute on Aging, this NOFO supports basic and clinical research on the influence of alcohol on susceptibility and progression of Alzheimer's disease and its related dementias. RFA-AA-20-006

Medications Development for the Treatment of Alcohol Use Disorder (AUD) or Alcohol-Related Organ Damage (AROD), or the Combination of AUD and AROD (U01 Clinical Trial Optional): The purpose of this NOFO is to support cooperative agreement applications for research that advances promising compounds through the drug development pipeline for the treatment of alcohol use disorder (AUD) or alcohol-related organ damage (AROD), or the combination of AUD and AROD; and move candidate compounds through any single phase, or multiple phases of the development spectrum. RFA-AA-20-007

Notices of Spechial Interest (NOSIs) Issued by NIAAA:

Notice of Special Interest in Administrative Supplements for Regulatory Support for [Small Business Innovation Research/Small Business Technology Transfer] SBIR/STTR Awardees: Administrative supplements are intended to provide support for the time, expertise, and personnel costs associated with interacting with the U.S. Food and Drug Administration (FDA) to validate development plans and to obtain regulatory support from a Contract Research Organization or other regulatory expert. NIAAA will also support administrative supplement applications where submission of an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application to the FDA is proposed in the parent grant award. NOT-AA-19-029

Notice of Special Interest on Neurobehavioral Mechanisms of Social Isolation and Alcohol Use Disorder: The purpose of this NOSI is to support integrative research studies focusing on understanding the behavioral, cognitive, and neurobiological mechanisms underlying the interactions between social isolation and alcohol use disorder. NOT-AA-19-031

NIH-Wide NOFOs with NIAAA Participation:

Identification, Validation, and Manipulation of Neural Circuits Related to Mental Illness and Alcohol and Substance Use Disorders in Non-human Primates (R01 Clinical Trial Not Allowed) RFA-MH-20-320

Integrative Research on Polysubstance Abuse and Disorder (R61/R33 Clinical Trial Optional) PAR-20-035

HEAL INITIATIVE: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 Clinical Trial Not Allowed; R43/R33 Clinical Trial Required; and R41/R42 Clinical Trial Not Allowed) RFA-NS-20-011; RFA-NS-20-010; RFA-NS-20-008; RFA-NS-20-009

BRAIN Initiative: Biology and Biophysics of Neural Stimulation and Recording Technologies (R01 Clinical Trials Optional) RFA-NS-20-006

BRAIN Initiative: Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00 Independent Clinical Trial Not Allowed; K99/R00 Independent Clinical Trial Required) RFA-NS-19-043; RFA-NS-19-044

Maximizing Opportunities for Scientific and Academic Independent Careers (MOSAIC) Postdoctoral Career Transition Award to Promote Diversity (K99/R00 Independent Clinical Trial Not Allowed) PAR-19-343

Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Optional; R01 Clinical Trial Not Allowed) PAR-20-038; PAR-20-037

Engineering Next-Generation Human Nervous System Microphysiological Systems (R01 Clinical Trials Not Allowed; R21 Clinical Trials Not Allowed) PAR-20-055; PAR-20-082

Intersection of Sex and Gender Influences on Health and Disease (R01 Clinical Trial Optional) RFA-OD-19-029

Administrative Supplements for Research on Sexual and Gender Minority (SGM) Populations (Admin Supp Clinical Trial Optional) NOT-OD-20-032

Small Research Grants for Establishing Basic Science-Clinical Collaborations to Understand Structural Birth Defects (R03 Clinical Trial Not Allowed) PAR-20-065

NIH Blueprint Program for Enhancing Neuroscience Diversity through Undergraduate Research Education Experiences (BP-ENDURE) (R25 Clinical Trial Not Allowed) RFA-NS-20-015

Tobacco Regulatory Science (R01 Clinical Trial Optional) RFA-OD-19-028

Research on biopsychosocial factors of social connectedness and isolation on health, wellbeing, illness, and recovery (R01 Clinical Trials Not Allowed; R01 Basic Experimental Studies with Humans Required) PAR-19-373;PAR-19-384

Fogarty HIV Research Training Program for Low-and Middle-Income Country Institutions (D43 Clinical Trial Optional) PAR-19-283

NIH-Wide NOSIs with NIAAA participation:

HEAL INITIATIVE: Back Pain Consortium (BACPAC) Research Program Notice of Special Interest regarding the Availability of Urgent Competitive Revisions NOT-AR-20-016; NOT-AR-20-012

Notice of Special Interest: Alzheimer’s-focused administrative supplements for NIH grants that are not focused on Alzheimer’s disease NOT-AG-20-008

Notice of Special Interest: Administrative Supplements to Promote Research Continuity and Retention of NIH Mentored Career Development (K) Award Recipients and Scholars NOT-OD-20-054

Notice of Special Interest: Administrative Supplement for Research on Bioethical Issues (Admin Supp Clinical Trial Optional) NOT-OD-20-038

Notice of Special Interest: Administrative Supplements for Research on Sex/Gender Influences (Admin Supp Clinical Trial Optional) NOT-OD-20-049

Notice of Special Interest: Research on the Health of Women of Understudied, Underrepresented and Underreported (U3 Admin Supp Clinical Trial Optional) Populations NOT-OD-20-048

Notice of Special Interest: Administrative Supplements to NIH-funded T32 and TL1 Training Grants to Better Integrate Behavioral and Social Sciences (BSS) with other Health-Related Sciences NOT-OD-19-147
 

NOTABLE NIAAA STAFF ACTIVITIES 

Dr. Veronica Alvarez presented “Synaptic and Circuit Mechanisms for Treating Drug Relapse” at the annual meeting of the American College on Neuropsychopharmacology in Orlando, Florida, in December 2019.

Dr. Tatiana Balachova spoke about the Interagency Coordinating Committee on Fetal Alcohol Spectrum Disorders at the Annual NOFAS Affiliate Network Summit in Washington, DC, on September 24, 2019.

Drs. Tatiana Balachova and Bill Dunty represented NIAAA at the Fetal Alcohol Spectrum Disorders: Policy Challenges and Opportunities Technical Expert Panel Meeting convened by the Office of the Assistant Secretary for Planning and Evaluation, U.S. Department of Health and Human Services, on September 12, 2019.

Dr. Bill Dunty and Dr. Michael Charness of the Harvard Medical School and Veterans Affairs Boston Healthcare System co-chaired an FASD Consensus Conference, held October 29–30, 2019, in Bethesda, Maryland. NIAAA convened this conference with the goal of harmonizing the various international research classification systems for FASD. 

Dr. Robert Freeman organized a two-day meeting, “Advancing Uptake, Retention, and Adherence to Antiretroviral Therapy and to Pre-Exposure Prophylaxis (PrEP) for HIV/AIDS Prevention among Alcohol-Using Populations,” on September 23–24, 2019. The meeting was co-funded by the Office of AIDS Research and the Office of Disease Prevention.

Dr. Brett Hagman presented discussant remarks at the annual American Psychological Association meeting for two symposia:

• “Adapting Alcohol Interventions to Specific Populations: Factors to Consider and Lessons Learned” on August 9, 2019
• “(Re)Defining Recovery: Why is it hard to define, and what are the contentious issues in defining it?” on August 11, 2019

Dr. Ralph Hingson presented “State Performance and Best Practices Report” to the Interagency Coordinating Committee on the Prevention of Underage Drinking (ICCPUD) on August 21, 2019.

Dr. Ralph Hingson presented “The Current Landscape of Underage Drinking” to the Interagency Coordinating Committee on the Prevention of Underage Drinking (ICCPUD) on October 24, 2019.

Dr. Kathy Jung co-chaired a session, with Dr. Mack Mitchell (University of Texas Southwestern), titled “Clinical and Translational Advances in Alcoholic Liver Disease” at The Liver Meeting, which took place November 8–12, 2019, in Boston, Massachusetts.

Dr. George Kunos gave a plenary lecture at the Bioactive Lipids 16^th International Conference titled “Endocannabinoids modulate Appetitive and Addictive Behaviors via Distinct Pathways of Periphery to Brain Signaling” in St. Petersburg, Florida, in October 2019.

Dr. Laura Kwako presented “The Addictions Neuroclinical Assessment: Deep Phenotyping for Alcohol Addiction” at the annual meeting of the American College on Neuropsychopharmacology in Orlando, Florida, on December 10, 2019.

Dr. Lorenzo Leggio gave a talk titled “Traversing the Gut-Brain Axis: Translation to Addiction Medicine” for the NIH Director’s Seminar Series in Bethesda, Maryland, on December 6, 2019.

Dr. Gary Murray participated in The Cancer Moonshot Collaborative Meeting (CMCM) held November 18–20, 2019, at the Bethesda North Marriott Hotel & Conference Center, in Rockville, Maryland.

Dr. Gary Murray presented “Helping Patients Who Drink Too Much” and “Research Opportunities At NIAAA” as part of the NIH Corner at The Liver Meeting, held November 8–12, 2019, in Boston, Massachusetts.

Dr. Mariela C. Shirley led an NIAAA conference titled “Brief Alcohol Interventions for Young Adults: Strengthening Effects and Disentangling Mechanisms of Action to Build Personalized Interventions for Widespread Uptake” on October 10-11, 2019. The overall goal of this conference was to build upon the existing base of evidence-supported alcohol brief interventions for college and young adult populations and address key areas that will advance the field, including: 1) methods and challenges to optimizing intervention design, and 2) implementation and scale up of brief intervention approaches. The two-day event is available to the public via NIH VideoCast at https://videocast.nih.gov/summary.asp?Live=34868&bhcp=1 (Day 1) and https://videocast.nih.gov/summary.asp?Live=34872&bhcp=1 (Day 2).

Multiple NIAAA staff members participated in the Alcoholic and Nonalcoholic Steatohepatitis: Pathogenesis and Mechanisms of Liver Injury Workshop held September 16–17, 2019, in Bethesda, Maryland. NIAAA and the National Institute on Diabetes Digestive and Kidney Diseases (NIDDK) held this workshop to promote collaboration between investigators in alcoholic and nonalcoholic fields and summarize the current and evolving concepts in the pathogenesis of fatty liver.

• Drs. Svetlana Radaeva and Joe Wang co-organized and co-chaired the workshop with Drs. Bonnie Burgess-Beusse, Edward Doo and Jay Hoofnagle from NIDDK.
• Dr. Svetlana Radaeva gave introductory remarks.
• Dr. Kathy Jung served as a discussant.

Multiple NIAAA staff members presented at the 2019 Congress of the European Society for Biomedical Research on Alcoholism (ESBRA), which took place September 21–24, 2019, in Lille, France:

• Dr. Lorenzo Leggio presented “Pharmacological Treatments for Alcohol Use Disorder: Riding the Waves of Medications Development” and “The Gut Microbiome in Binge Alcohol Drinking: Recent Translational Efforts.”
• Dr. Gary Murray presented “Alcohol, Cytochrome P450, and Cancer.”
• Dr. Kathy Jung served as a co-organizer and co-chair, with Dr. Sebastian Mueller (University of Heidelberg), for a session titled “Insights into Alcohol-associated Cancers.

WHAT'S AHEAD?

The Interagency Coordinating Committee on Fetal Alcohol Spectrum Disorders (ICCFASD) Annual Public Meeting will be held on March 9, 2020, at the NIH Conference Center, 6700B Rockledge Drive, Bethesda, Maryland. ICCFASD, sponsored and chaired by NIAAA, fosters improved communication, cooperation, and collaboration among disciplines and federal agencies that address issues related to prenatal alcohol exposure. The meeting will be convened by Dr. Trish Powell, ICCFASD Chair, and Dr. Tatiana Balachova, Scientific Coordinator and Executive Secretary of the ICCFASD.

The 9^th International Conference on Adolescents and Adults with FASD, Review Respond and Relate: Integrating Research, Policy and Practice Around the World will be held in Vancouver, British Columbia, on April 22–25, 2020. Dr. Bill Dunty serves on the conference Expert Planning Committee and Dr. Tatiana Balachova is a member of the Expert Advisory Committee.
 

NIAAA RESEARCH HIGHLIGHTS

Cannabinoids Exacerbate Alcohol Teratogenesis by a CB1-Hedgehog Interaction

Significance: Using mouse and zebrafish models of early prenatal substance exposure, this study demonstrated that a one-time exposure to cannabinoids (CBs), including cannabidiol (CBD) and tetrahydrocannabinol (THC), caused eye, brain, and facial malformations similar to those caused by prenatal alcohol exposure alone. Furthermore, exposure to both CBs and alcohol increased the likelihood of these birth defects in both animal models, even at low doses. Mechanistic studies demonstrated that alcohol and CBs converge to inhibit Sonic Hedgehog (Shh) signaling which is important for normal embryonic development. These findings shed light on the mechanism of alcohol and CB-induced birth defects and further highlight the dangers of co-substance use during pregnancy.

We tested whether cannabinoids (CBs) potentiate alcohol-induced birth defects in mice and zebrafish, and explored the underlying pathogenic mechanisms on Sonic Hedgehog (Shh) signaling. The CBs, Δ9-THC, cannabidiol, HU-210, and CP 55,940 caused alcohol-like effects on craniofacial and brain development, phenocopying Shh mutations. Combined exposure to even low doses of alcohol with THC, HU-210, or CP 55,940 caused a greater incidence of birth defects, particularly of the eyes, than did either treatment alone. Consistent with the hypothesis that these defects are caused by deficient Shh, we found that CBs reduced Shh signaling by inhibiting Smoothened (Smo), while Shh mRNA or a CB1 receptor antagonist attenuated CB-induced birth defects. Proximity ligation experiments identified novel CB1-Smo heteromers, suggesting allosteric CB1-Smo interactions. In addition to raising concerns about the safety of cannabinoid and alcohol exposure during early embryonic development, this study establishes a novel link between two distinct signaling pathways and has widespread implications for development, as well as diseases such as addiction and cancer. (Fish EW, Murdaugh LB, Zhang C, Boschen KE, Boa-Amponsem O, Mendoza-Romero HN, Tarpley M, Chdid L, Mukhopadhyay S, Cole G, Williams KP, and Parnell SE. Sci Rep. 2019 Nov 5;9(1):16057. doi: 10.1038/s41598-019-52336-w)

Bacteriophage Targeting of Gut Bacterium Attenuates Alcoholic Liver Disease

Significance: This report demonstrates that the presence of cytolysin-positive E. faecalis in the gut, a bacterium that secretes the cell-destroying toxin cytolysin, correlates with severity of liver disease and mortality in patients with alcoholic hepatitis. Further, using a mouse model of alcohol-associated liver disease, the study also demonstrated that bacteriophages that specifically target cytolysin-positive E. faecalis are effective in reducing liver injury, suggesting a potential therapeutic target for the treatment of alcoholic hepatitis.

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis. (Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L, White RC, Clarke TH, Nguyen K, Torralba M, Shao Y, Liu J, Hernandez-Morales A, Lessor L, Rahman IR, Miyamoto Y, Ly M, Gao B, Sun W, Kiesel R, Hutmacher F, Lee S, Ventura-Cots M, Bosques-Padilla F, Verna EC, Abraldes JG, Brown RS Jr, Vargas V, Altamirano J, Caballería J, Shawcross DL, Ho SB, Louvet A, Lucey MR, Mathurin P, Garcia-Tsao G, Bataller R, Tu XM, Eckmann L, van der Donk WA, Young R, Lawley TD, Stärkel P, Pride D, Fouts DE, and Schnabl B. Nature. 2019 Nov;575(7783):505-511. doi: 10.1038/s41586-019-1742-x)

Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis

Significance: Previous research has shown that increased glutamate signaling in the brain plays a role in driving alcohol-seeking behavior through actions at the metabotropic glutamate receptor. The current study demonstrates that glutamate signaling via these receptors is also involved in mediating alcohol-associated fatty liver disease. These results suggest that inhibition of a single pharmacological target, metabotropic glutamate receptors, may have therapeutic value in the treatment of both alcohol use disorder and alcohol-associated liver disease.

Activation of hepatocyte cannabinoid receptor-1 (CB₁R) by hepatic stellate cell (HSC)-derived 2-arachidonoylglycerol (2-AG) drives de novo lipogenesis in alcoholic liver disease (ALD). How alcohol stimulates 2-AG production in HSCs is unknown. Here, we report that chronic alcohol consumption induced hepatic cysteine deficiency and subsequent glutathione depletion by impaired transsulfuration pathway. A compensatory increase in hepatic cystine-glutamate anti-porter xCT boosted extracellular glutamate levels coupled to cystine uptake both in mice and in patients with ALD. Alcohol also induced the selective expression of metabotropic glutamate receptor-5 (mGluR5) in HSCs where mGluR5 activation stimulated 2-AG production. Consistently, genetic or pharmacologic inhibition of mGluR5 or xCT attenuated alcoholic steatosis in mice via the suppression of 2-AG production and subsequent CB₁R-mediated de novo lipogenesis. We conclude that a bidirectional signaling operates at a metabolic synapse between hepatocytes and HSCs through xCT-mediated glutamate-mGluR5 signaling to produce 2-AG, which induces CB₁R-mediated alcoholic steatosis. (Choi WM, Kim HH, Kim MH, Cinar R, Yi HS, Eun HS, Kim SH, Choi YJ, Lee YS, Kim SY, Seo W, Lee JH, Shim YR, Kim YE, Yang K, Ryu T, Hwang JH, Lee CH, Choi HS, Gao B, Kim W, Kim SK, Kunos G, and Jeong WI. Cell Metab. 30 (5), 877-889.e7. 2019 Nov 5)

PCSK9 Inhibition as a Novel Therapeutic Target for Alcoholic Liver Disease

Significance: This study tested the PCSK9 inhibitor alirocumab, a monoclonal antibody that reduces low-density lipoprotein cholesterol, in a rat model of ALD. The findings demonstrated that alirocumab significantly reduced alcohol-induced hepatic triglyceride accumulation, hepatocellular injury, and hepatic inflammation. Further research is needed to investigate the therapeutic efficacy and safety of anti-PCSK9 treatment in individuals with ALD and alcohol use disorder.

Alcoholic liver disease (ALD) causes significant morbidity and mortality, and pharmacological treatment options are limited. In this study, we evaluated the PCSK9 inhibitor alirocumab, a monoclonal antibody that robustly reduces low-density lipoprotein cholesterol (LDL-C), for the treatment of ALD using a rat model of chronic alcohol exposure. Alirocumab (50 mg/kg) or vehicle was administered weekly for 6 weeks to rats receiving a 12% alcohol liquid diet or an isocaloric control diet. At the end of the alcohol exposure protocol, serum and liver samples were obtained for molecular characterization and histopathological analysis. PCSK9 inhibition with alirocumab attenuated alcohol-induced hepatic triglyceride accumulation through regulation of lipid metabolism (mRNA expression of modulators of fatty acid synthesis (FAS) and catabolism (PPARα and CPT1)), hepatocellular injury (ALT), hepatic inflammation (mRNA expression of pro-inflammatory cytokines/chemokines (TNFa, IL-1β, IL-22, IL-33, IL-17α, IL-2, MIP-2, and MCP-1), and neutrophil infiltration (myeloperoxidase staining)). Alirocumab treatment also attenuated alcohol-induced PCSK9 mRNA elevation and upregulated LDL-receptor (LDL-R) via modulation of the transcription factors (SREBP-1, SREBP-2, and E2F1) in liver. We demonstrated that chronic anti-PCSK9 treatment using the monoclonal antibody alirocumab attenuated alcohol-induced steatohepatitis in the rat model. Given the large unmet clinical need for effective and novel treatments for ALD, anti-PCSK9 treatment with the monoclonal antibody that spares liver metabolism is a viable new therapeutic possibility. Future studies are needed to elucidate the exact role of PCSK9 in ALD and alcohol use disorder (AUD) and to evaluate efficacy and safety of anti-PCSK9 treatment in clinical populations with ALD/AUD. (Lee JS, Mukhopadhyay P, Matyas C, Trojnar E, Paloczi J, Yang YR, Blank BA, Savage C, Sorokin AV, Mehta NN, Vendruscolo JCM, Koob GF, Vendruscolo LF, Pacher P, and Lohoff FW. Sci Rep. 9 (1), 17167. 2019 Nov 20)

Early Detection and Staging of Chronic Liver Diseases with a Protein MRI Contrast Agent

Significance: This study reports the development of a sensitive protein-based magnetic resonance imaging (MRI) contrast agent, ProCA32.collagen1, that can detect and accurately quantify early stage fibrosis in mouse models of alcohol-, diet- and chemical-induced liver diseases. This reagent can also monitor the regression of liver fibrosis after treatment with the anti-fibrotic drug pirfenidone in a mouse model. ProCA32.collagen1 had high binding affinity and specificity in human hepatocellular carcinoma tissues with cirrhosis, suggesting strong translation potential for this reagent. With further validation, this contrast agent could potentially be used to noninvasively and accurately detect early stage fibrosis in liver and other organs, allowing for earlier treatment and better patient outcomes.

Early diagnosis and noninvasive detection of liver fibrosis and its heterogeneity remain as major unmet medical needs for stopping further disease progression toward severe clinical consequences. Here we report a collagen type I targeting protein-based contrast agent (ProCA32.collagen1) with strong collagen I affinity. ProCA32.collagen1 possesses high relaxivities per particle (r1 and r2) at both 1.4 and 7.0 T, which enables the robust detection of early-stage (Ishak stage 3 of 6) liver fibrosis and nonalcoholic steatohepatitis (Ishak stage 1 of 6 or 1 A Mild) in animal models via dual contrast modes. ProCA32.collagen1 also demonstrates vasculature changes associated with intrahepatic angiogenesis and portal hypertension during late-stage fibrosis, and heterogeneity via serial molecular imaging. ProCA32.collagen1 mitigates metal toxicity due to lower dosage and strong resistance to transmetallation and unprecedented metal selectivity for Gd3+ over physiological metal ions with strong translational potential in facilitating effective treatment to halt further chronic liver disease progression. (Salarian M, Turaga RC, Xue S, Nezafati M, Hekmatyar K, Qiao J, Zhang Y, Tan S, Ibhagui OY, Hai Y, Li J, Mukkavilli R, Sharma M, Mittal P, Min X, Keilholz S, Yu L, Qin G, Farris AB, Liu ZR, and Yang JJ. Nat Commun. 2019 Oct 29;10(1):4777. doi: 10.1038/s41467-019-11984-2)

Targeting Liver Aldehyde Dehydrogenase-2 Prevents Heavy but Not Moderate Alcohol Drinking

Significance: Aldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for the breakdown of acetaldehyde, a toxic by-product of alcohol metabolism. In the current study, researchers compared acetaldehyde concentrations after alcohol administration in knockout mice lacking Aldh2 throughout the body to knockout mice lacking liver-specific Aldh2. The study found that, while the liver was the primary organ responsible for acetaldehyde metabolism, cumulative effects of ALDH2 produced by other organs may also contribute to acetaldehyde metabolism. Genetic deletion or knockdown of liver-specific Aldh2 decreased excessive but not light-to-moderate alcohol drinking, suggesting that liver-specific ALDH2 inhibition may be a potential treatment approach for AUD.

Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for detoxification the ethanol metabolite acetaldehyde, is recognized as a promising therapeutic target to treat alcohol use disorders (AUDs). Disulfiram, a potent ALDH2 inhibitor, is an approved drug for the treatment of AUD but has clinical limitations due to its side effects. This study aims to elucidate the relative contribution of different organs in acetaldehyde clearance through ALDH2 by using global- (Aldh2 ^-/-) and tissue-specific Aldh2-deficient mice, and to examine whether liver-specific ALDH2 inhibition can prevent alcohol-seeking behavior. Aldh2 ^-/- mice showed markedly higher acetaldehyde concentrations than wild-type (WT) mice after acute ethanol gavage. Acetaldehyde levels in hepatocyte-specific Aldh2 knockout (Aldh2 ^Hep-/-) mice were significantly higher than those in WT mice post gavage but did not reach the levels observed in Aldh2 ^-/- mice. Energy expenditure and motility were dramatically dampened in Aldh2 ^-/- mice, but moderately decreased in Aldh2 ^Hep-/- mice compared to controls. In the 2-bottle paradigm and the drinking-in-the-dark model, Aldh2 ^-/- mice drank negligible volumes from ethanol-containing bottles, whereas Aldh2 ^Hep-/- mice showed reduced alcohol preference at high but not low alcohol concentrations. Glial cell- or neuron-specific Aldh2 deficiency did not affect voluntary alcohol consumption. Finally, specific liver Aldh2 knockdown via injection of shAldh2 markedly decreased alcohol preference. In conclusion, although the liver is the major organ responsible for acetaldehyde metabolism, a cumulative effect of ALDH2 from other organs likely also contributes to systemic acetaldehyde clearance. Liver-targeted ALDH2 inhibition can decrease heavy drinking without affecting moderate drinking, providing molecular basis for hepatic ALDH2 targeting/editing for the treatment of AUD. (Guillot A, Ren T, Jourdan T, Pawlosky RJ, Han E, Kim SJ, Zhang L, Koob GF, and Gao B. Proc Natl Acad Sci U S A. 2019 Dec 2. pii: 201908137. doi: 10.1073/pnas.1908137116)

A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors

Significance: 

This preclinical study demonstrates a causal link between two risk factors for developing alcohol use disorder that were previously considered to be independent: increased sensitivity to alcohol’s stimulatory effects and low levels of striatal dopamine D2 receptors. Using transgenic mouse lines and other genetic manipulations, this study provided direct evidence that lowering levels of D2 receptors on striatal projection neurons heightens alcohol-related stimulatory effects and escalation of alcohol intake, which continues despite aversive outcomes. The study also demonstrates that upregulation of dopamine D1 receptor functioning is responsible for these effects, suggesting that low striatal D2 receptor levels trigger D1 receptor hypersensitivity, ultimately leading to compulsive-like drinking and other factors related to risk for alcohol use disorder.

Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinking. (Bocarsly MR,da Silva e Silva D, Kolb V,Luderman KD, Shashikiran S, Rubinstein M, Sibley DR, Dobbs LK, and Alvarez VA. Cell Rep. 29 (5), 1147-1163.e5. 2019 Oct 29)

Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinking. (Bocarsly MR,da Silva e Silva D, Kolb V,Luderman KD, Shashikiran S, Rubinstein M, Sibley DR, Dobbs LK, and Alvarez VA. Cell Rep. 29 (5), 1147-1163.e5. 2019 Oct 29)

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

Significance: Alcohol use disorder and chronic pain frequently co-occur and share overlapping mechanisms. This review establishes a broader translational focus on chronic pain and alcohol use that provides updates on recent models and research findings; reviews overlapping behavioral, social, and biological mechanisms; and suggest future directions for research and treatment. 

Alcohol use disorder (AUD) and chronic pain are enduring and devastating conditions that share an intersecting epidemiology and neurobiology. Chronic alcohol use itself can produce a characteristic painful neuropathy, while the regular analgesic use of alcohol in the context of nociceptive sensitization and heightened affective pain sensitivity may promote negative reinforcement mechanisms that underlie AUD maintenance and progression. The goal of this review was to provide a broad translational framework that communicates research findings spanning preclinical and clinical studies, including a review of genetic, molecular, behavioral, and social mechanisms that facilitate interactions between persistent pain and alcohol use. We also consider recent evidence that will shape future investigations into novel treatment mechanisms for pain in individuals suffering from AUD. (Edwards S, Vendruscolo LF, Gilpin NW, Wojnar M, and Witkiewitz K. Alcohol Clin Exp Res. 2019 Dec 16 doi: 10.1111/acer.14260)

Trait Self-Control Predicts Drinking Patterns During Treatment for Alcohol Use Disorder and Recovery Up to Three Years Following Treatment

Significance: Given the variety of outcomes following treatment for alcohol use disorder, it is important to identify factors that predict recovery. Previous research has identified demographic and clinical indicators as being related to recovery outcomes, but behavioral traits such as self-control have received less attention. Using latent class analysis, this study confirmed seven classes of drinking patterns among participants in AUD treatment identified in previous research. The consistent low-risk drinking group had significantly higher self-control than both the persistent heavy drinking and consistent abstinent groups. This finding has important clinical implications, suggesting that achieving low-risk drinking (defined in the study as one or more days with less than 4/5 drinks for women/men and no heavy drinking days during a given week) throughout treatment may require even more self-control than achieving abstinence.

To more fully understand recovery from alcohol use disorder, we must consider several ways in which reductions in drinking and improvements in psychosocial functioning may occur. Previous research has demonstrated various patterns of drinking and functioning during and after behavioral treatment for alcohol use disorder, including groups of individuals who consume alcohol at low-risk levels and those that report occasional heavy drinking yet good psychosocial functioning. This study aimed to identify whether trait self-control, which has previously been associated with alcohol treatment outcomes, was a predictor of drinking patterns during treatment as well as three years following treatment. Latent variable mixture modeling was used to identify seven classes of drinking patterns during treatment and four profiles of drinking and psychosocial function after treatment. We found that membership in the low-risk drinking class was predicted by greater trait self-control than several of the other classes, including the consistent abstinence class. Furthermore, we found that greater trait self-control predicted membership in two high-functioning recovery profiles at three years following treatment, including a high functioning occasional heavy drinking profile. These findings suggest that self-control is an important predictor of recovery, particularly for a non-abstinent recovery. (Stein E and Witkiewitz K. Addict Behav, 99, 106083. Dec 2019. doi:10.1016/j.addbeh.2019.106083)

Association of Prior Convictions for Driving Under the Influence with Risk of Subsequent Arrest for Violent Crimes Among Handgun Purchasers

Significance: Given the association between alcohol use and violence, many states have limited firearm purchase or possession by persons with a history of alcohol misuse. In this study of authorized handgun purchasers in California, a history of DUI conviction at the time of purchase was associated with a significant increase in the risk of subsequent arrest for a violent crime, independent of a range of individual and community-level measures. Purchasers with a previous DUI conviction and other non-DUI arrests or convictions were at greatest risk of subsequent arrest for a violent crime. This finding extends previous links between alcohol use and violence specifically to legal purchasers of handguns, suggesting that alcohol-related prohibitions on firearms purchase based on DUI convictions may reduce firearm-related injury and death.

IMPORTANCE: Alcohol use is a risk factor for firearm-related violence, and firearm owners are more likely than others to report risky drinking behaviors. OBJECTIVE: To study the association between prior convictions for driving under the influence (DUI) and risk of subsequent arrest for violent crimes among handgun purchasers. DESIGN: In this retrospective, longitudinal cohort study, 79 678 individuals were followed up from their first handgun purchase in 2001 through 2013. The study cohort included all legally authorized handgun purchasers in California aged 21 to 49 years at the time of purchase in 2001. Individuals were identified using the California Department of Justice (CA DOJ) Dealer's Record of Sale (DROS) database, which retains information on all legal handgun transfers in the state. EXPOSURES: The primary exposure was DUI conviction prior to the first handgun purchase in 2001, as recorded in the CA DOJ Criminal History Information System. MAIN OUTCOMES AND MEASURES: Prespecified outcomes included arrests for violent crimes listed in the Crime Index published by the Federal Bureau of Investigation (murder, rape, robbery, and aggravated assault), firearm-related violent crimes, and any violent crimes. RESULTS: Of the study population (N=79 678), 91.0% were males and 68.9% were white individuals; the median age was 34 (range, 21-49) years. The analytic sample for multivariable models included 78 878 purchasers after exclusions. Compared with purchasers who had no prior criminal history, those with prior DUI convictions and no other criminal history were at increased risk of arrest for a Crime Index-listed violent crime (adjusted hazard ratio [AHR], 2.6; 95% CI, 1.7-4.1), a firearm-related violent crime (AHR, 2.8; 95% CI, 1.3-6.4), and any violent crime (AHR, 3.3; 95% CI, 2.4-4.5). Among purchasers with a history of arrests or convictions for crimes other than DUI, associations specifically with DUI conviction remained. CONCLUSIONS AND RELEVANCE: This study's findings suggest that prior DUI convictions may be associated with the risk of subsequent violence, including firearm-related violence, among legal purchasers of handguns. Although the magnitude was diminished, the risk associated with DUI conviction remained elevated even among those with a history of arrests or convictions for crimes of other types. (Kagawa RMC, Stewart S, Wright MA, Shev AB, Pear VA, McCort CD, Pallin R, Asif-Sattar R, Sohl S, Kass PH, Cerdá M, Gruenewald P, Studdert DM, and Wintemute GJ. JAMA Intern Med. 2019 Sep 30. doi: 10.1001/jamainternmed.2019.4491)

NIAAA COMMUNICATIONS ACTIVITIES

Press and Publications Activities

Recent News Media Interviews: 

Dr. Koob continues to speak with a variety of national and international news outlets on timely topics related to NIAAA’s research and its impact on treatment and prevention of alcohol misuse and AUD. Additional notable interviews by Dr. Koob and other staff since August 2019 include The Washington Post, NPR, Wall Street Journal, NBC, Agence France-Presse, Christian Science Monitor, and Politico.

 On January 8, 2020, NIAAA conducted a satellite media tour (SMT) with Dr. Koob. These interviews focused on recognizing signs of an alcohol problem after the holidays, treatment resources, and potential benefits of participating in “Dry January.” He also used the opportunity to mention that this year marks NIAAA’s 50th anniversary

Dr. Koob completed more than 20 live and recorded interviews with television and radio stations around the country, resulting in more than 30 TV and website postings. Outlets included NBC News Radio; USA Radio Network; California Life TV, KDFW-TV/FOX-5 Dallas; KEYE-TV/CBS, Austin; WWL-TV/CBS, New Orleans; The Kristen Hagopian Show (nationally syndicated radio); Health Professional Radio; Daily Flash TV; and KOMO Radio.

On January 14, Dr. Koob appeared on a live TV broadcast of WUSA9’s Great Day Washington program. The segment provided Dr. Koob with a forum to help viewers understand that AUD is a “hidden addiction” and to discuss how taking part in Dry January gives people an opportunity to reevaluate their relationship with alcohol, make a choice about whether to drink without the stigma of not drinking, and improve their health and well-being. Dr. Koob also promoted NIAAA’s Alcohol Treatment Navigator and Rethinking Drinking websites. The segment can be viewed at: www.wusa9.com/video/entertainment/television/programs/great-day-washington/hidden-addiction-alcoholism-effects-drinking-health-dry-january/65-d662e01e-36c7-486d-a915-39ee9d45941e

Press Releases:

• Combined prenatal smoking and drinking greatly increases SIDS risk (January 20, 2020) 
• Alcohol-related deaths increasing in the United States (January 8, 2020)
  News coverage of the mortality study alone resulted in more than 1,000 stories. 
• Bacteriophage therapy may ease severity of alcoholic hepatitis (November 14, 2019)
• Using both marijuana and alcohol during early pregnancy may increase the likelihood of disrupting fetal development (November 08, 2019)
• Media Advisory: New compound helps find early signs of liver damage (October 29, 2019) 

Publication Statistics: In the month of November 2019, NIAAA filled orders for 9,002 copies of print publications. As of December 26, 2019, there were 29,033 Granicus/GovDelivery listserv subscribers to Alcohol Research: Current Reviews; 23,910 to the NIAAA Spectrum; 1,127 to News Alerts; and 22,877 to receive general information. 

New and Updated Publications:

• CollegeAIM—NIAAA’s College Alcohol Intervention Matrix: After extensive review, NIAAA has released a revised version of CollegeAIM—the College Alcohol Intervention Matrix—its comprehensive resource to help colleges and universities address harmful and underage drinking among their students.

Information in the original CollegeAIM was grounded in scientific articles on college alcohol interventions published through 2012. This year, CollegeAIM has been updated to include new research findings from peer-reviewed studies published from 2013 through 2017. :

• As a result of this additional research, 7 interventions were added to the nearly 60 interventions already included.
• Also, based on this additional research, some interventions received updated ratings of their effectiveness and amount of research evidence.

NIAAA will issue a news release regarding the CollegeAIM update and is developing a multi-faceted promotion plan, including:

• a mailing to all U.S. college and university presidents
• a collaboration with the International Town & Gown Association to host regional workshops for college staff
• presentations at professional meetings and conferences
• social media activities
• other efforts continuing through 2020 and into 2021.

• “Entender los riesgos de sobredosis de alcohol” [Spanish translation of “Understanding the Dangers of Alcohol Overdose”]
  www.niaaa.nih.gov/publications/brochures-and-fact-sheets/entender-los-riesgos-de-sobredosis-de-alcohol
• “The Truth About Holiday Spirits”
  www.niaaa.nih.gov/publications/brochures-and-fact-sheets/truth-about-holiday-spirits

Social Media Highlights:

NIAAA Twitter: The NIAAA Twitter account (@NIAAAnews) currently has more than 24,400 followers and averages about 143,000 impressions per month.

On October 24, 2019, NIAAA co-hosted a Twitter chat with the American Society of Addiction Medicine (ASAM) on alcohol use disorder. The event was part of National Addiction Treatment Week. NIAAA’s Dr. Laura Kwako, Division of Treatment and Recovery Research, served an expert contributor along with ASAM expert Dr. Michael F. Weaver of the University of Texas Health Science Center at Houston. The chat’s estimated reach was about 1.9 million accounts and 4 million exposures (the number of times a tweet from the chat was delivered to someone’s feed).

Instagram: NIAAA’s Instagram account (@NIAAAnews) has grown to almost 1,000 followers. Recent posts include messages about alcohol’s impact on women’s health, the NIAAA Alcohol Treatment Navigator, fetal alcohol spectrum disorders, and recognition of Postdoc Appreciation Week, featuring staff in the Intramural Research Program. Also, this year NIAAA will feature a special series of posts with the #NIAAA50 to highlight the Institute’s 50^th anniversary.

Throughout December 2019, NIAAA highlighted a holiday drinking video on Instagram. The videoreceived the most views of any video posted on NIAAA’s Instagram account to date; see the video at https://www.instagram.com/p/B6l8RP4gbjG/.

NIAAA Director’s Blog: In September 2019, Dr. Koob updated his blog with a new entry spotlighting awareness about fetal alcohol spectrum disorders (FASD) and celebrating Recovery Month. In December, Dr. Koob updated the blog with a feature on the science of hangovers. Posts can be read at https://www.niaaa.nih.gov/directors-blog.

Partnerships, Outreach, and Public Liaison Activities

Holiday Safety Outreach: NIAAA disseminated its fact sheet titled “The Truth About Holiday Spirits” to the media through PR Newswire’s US1 distribution with AP photo release on December 4 and 16, 2019. The fact sheet was posted by Internet news outlets such as Seeking Alpha, MarketWatch, Benzinga, The Herald-Mail, One News Page, and Suncoast News Network, as well as blogs, business journals, industry publications, and numerous major television network (FOX, NBC, CBS, ABC) local affiliates nationwide. The release had a total of 146 unique links, representing a total potential audience of 84,563,347 people.

NIAAA tweeted holiday safety messages throughout November and December, resulting in 130 retweets. Other stakeholder groups were also encouraged to disseminate the message on their social media channels. Overall, the total potential audience for the social media outreach effort was 15,482 followers.

NIAAA College Drinking/Fall Semester Outreach: The “Fall Semester—A Time for Parents to Discuss the Risks of College Drinking” fact sheet was disseminated to the media through PR Newswire’s US1 distribution with AP photo release on August 13 and 20, 2019. It was posted by Internet news outlets such as the Evening Leader, Daily Herald, Valley City Times-Record, Pittsburgh Post-Gazette, Arizona Republic Online, Morning News, KWTV-TV and WFMG-TV, as well as business journals, industry publications, and numerous major television network (FOX, NBC, CBS, ABC) local affiliates nationwide. The release had a total of 122 unique links, representing a total potential audience of 36,186,284 people.

In addition to the PR Newswire releases, three Cision email blasts were distributed on August 1 and 20, and September 3 to a total of 14,500+ local and national TV, radio, print, consumer, health/wellness, recreational, drinking/holidays, and parenting blogs (including Mayo Clinic Radio, WAMU-FM, MSNBC, Thrillist, LA Times, Huff Post, Washington Post, Good Housekeeping, USA Today, Woman’s Day, etc.) WTOP Radio, MSN.com, Massapequa Observer, and Metro Parent ran related articles after receiving the Cision emails.

Select Partnership Updates

• ACHA Publications: NIAAA collaborated with the American College Health Association (ACHA) to promote several publications, inlcuding an article on blackouts in “College Health & Wellness in ACTION” (Summer 2019), and a feature about CollegeAIM for “Healthy Campus Executive Update” (Fall 2019).
• NOFAS Webinar: Kathleen Mitchell MHS, LCADC, Vice President of the National Organization on Fetal Alcohol Syndrome (NOFAS), participated on November 22, 2019, in a webinar on women, pregnancy, and addiction. The event was co-sponsored by NIAAA’s Division of Treatment and Recovery Research and the Interagency Work Group on Drinking and Drug Use in Women and Girls.
• CADCA Partnership Conference: NIAAA joined the federal partners meeting with Community Anti-Drug Coalitions of America (CADCA) and met with General Arthur Dean, Chairman & CEO of CADCA, to discuss plans for the upcoming annual National Leadership Forum.

Web Updates

Redesigned Health Tab: The web team recently redesigned part of the main site architecture called "Alcohol's Effects on Health." The revamped section features an easy to navigate, graphic-based format with quick links to popular web resources.