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2012 March

A Pilot Study of Vivitrol (Injectable Naltrexone) as a Psychopharmacological Support for Alcohol Harm Reduction Among Chronically Homeless Individuals with Alcohol Dependence

Susan E. Collins, Ph.D., Research Assistant Professor
Psychiatry & Behavioral Sciences

Richard Ries, MD; Andrew Saxon, MD; Ron Jackson, MSW; Daniel Malone, MPH

Description: Chronically homeless individuals evince high rates of alcohol use and dependence that are associated with greater experience of alcohol-related problems. Unfortunately, traditional, abstinence-based treatments often fail to engage them and address their needs. For this reason, new psychosocial interventions that focus on alcohol harm reduction are being introduced. Although harm reduction interventions have shown initial effectiveness for this population, there are few psychopharmacological counterparts to support these psychosocial harm-reduction approaches.

This study aims to fill this clinical and research gap by testing Vivitrol--an injectable, extended release form of the opioid receptor antagonist naltrexone--as a psychopharmacological adjunct for alcohol harm reduction among chronically homeless individuals with alcohol dependence. Unlike other medications for alcohol dependence (e.g., antabuse, acamprosate, baclofen), naltrexone and Vivitrol have been shown to be safe and effective in reducing alcohol craving and use among people who are abstinent and among current heavy drinkers. Vivitrol is therefore congruent with the drinking patterns of this population, specifically, and harm-reduction approaches more generally. We are therefore proposing an open-label, 3-month pilot study, to a) develop and pilot procedures and b) descriptively document initial feasibility, tolerability, acceptability and effectiveness of Vivitrol for chronically homeless individuals with alcohol dependence. We will recruit 20 clients from two, community-based agencies in Seattle (i.e., the Downtown Emergency Service Center [DESC] and REACH) that serve the proposed population. In doing so, we will be able to develop and pilot the study materials and procedures as well as document outcomes both among formerly (DESC’s 1811 Eastlake housing project; n = 10) and currently (REACH homeless outreach services; n = 10) chronically homeless individuals with alcohol dependence.

This study will provide data to inform a future effectiveness RCT of Vivitrol in this underserved and severely affected population in “real-world,” community-based settings.

Resulting articles & projects:

  • Collins SE, Duncan MH, Smart BF, Saxon AJ, Malone DK, Jackson TR, Ries RK.. Extended-release naltrexone and harm reduction counseling for chronically homeless people with alcohol dependence. Substance Abuse (in press 2014). PMID: 24779575. Pubmed abstract
  • Collins SE, Saxon AJ, Duncan MH, Smart BF, Merrill JO, Malone DK, Jackson TR, Clifasefi SL, Joesch J, Ries RK. Harm reduction with pharmacotherapy for homeless people with alcohol dependence: Protocol for a randomized controlled trial. Contemp Clin Trials 2014;38(2):221-234. doi: 10.1016/j.cct.2014.05.008. PMID: 24846619. Pubmed abstract
  • Collins SE, Grazioli VS, Torres NI, Taylor E, Jones C, Hoffman G, Haelsig L, Zhu M, Hatsukami A, Koker M, Herndon P, Greenleaf S, Dean P. Qualitatively and quantitatively evaluating harm-reduction goal setting among chronically homeless individuals with alcohol dependence. (ms. submitted 6/14)
  • The initial study findings informed Dr. Collins' subsequent R01 application to NIAAA entitled “Harm Reduction with Pharmacotherapy (HaRP) for Alcohol Dependence.” This application received a near-perfect score of 11 on the first grant review round. The funding start date was 8/1/13, and because the ADAI-funded pilot study had prepared us so well for the work, we began recruitment for the study on 10/14/13. The amount of the NIAAA grant is $$685,880 1R01AA022309-01
  • This research has also been featured in popular media:

Recruiting Emerging Adults for Alcohol Use Screening and Brief Interventions Via Social Networking Sites

Melissa A. Lewis, Ph.D., Associate Professor
Psychiatry & Behavioral Sciences

Christine Lee, PhD, Psychiatry & Behavioral Sciences

Description: Alcohol use, misuse, and resulting negative consequences among high school and college students have been extensively documented; however, research focusing on drinking behavior or the use of brief interventions for adolescents and emerging adults (EAs) not in school is limited. Little research has also explored the use of social networking sites (SNS) as a means to access adolescent and non-college EAs.

In this proposal, we will collect pilot data for two larger NIAAA R01 projects “Informing Alcohol-Related Risk Intervention with the Prototype Willingness Model” (PI: Melissa A. Lewis) “Developmentally-Enhanced Alcohol Use Prevention during Emerging Adulthood” (PI: Christine M. Lee; Co-I: Melissa A. Lewis), which both propose to recruit emerging adult samples via SNS to evaluate brief alcohol interventions. The pilot study will consist of a cross-sectional survey in which 300 EAs aged 17-20 will be recruited via SNS. We will examine sample representativeness, possible selection bias, and the processes of obtaining parent consent and validation of participant age. The results of the pilot study will extend the literature on recruitment using SNS as this study will be well poised to assess and document the benefits, limitations, barriers, and strategies of using SNS for alcohol research among emerging adult populations and directly address reviewer comments made during the original submission of both grants to NIH. Further, this pilot study will document stress and coping during the transition to adulthood, and how these relate to alcohol use, again addressing a specific reviewer comment in Dr. Lee’s R01.

Resulting articles & projects:

  • "Developmental Models of High-Risk Alcohol Use and Social Roles in Young Adulthood," awarded to Dr. Lee. NIAAA R01AA016979, $359,678.
  • "Informing Alcohol-Related Risk Intervention with the Prototype Willingness Model," awarded to Dr. Lewis. NIAAA R01AA021379, $466,774.
  • "Evaluation of Brief Intervention for Young Adult Alcohol-Related Risk Behaviors, awarded to Dr. Lewis. NIAAA R21AA021767, $135,450.
  • Three additional grants using the data are under review or awaiting funding, as of February 2015.

  • Abdallah D, Lee CM, Lewis MA. Similarities and differences in substance use patterns and consequences among 2- and 4-year college students. Poster submitted, Society of Prevention Research annual meeting, Washington DC, May 2015.
  • Lee CM, Lewis MA, Litt DM. Recruitment through social networking sites: Are substance use patterns similar to other recruitment methods? Poster presented, Medicine 2.0: Social Media, Mobile Apps, and Internet/Web 2.0 in Health, Medicine, and Biomedical Research, Maui, HI, Nov 2014.
  • Litt DM, Lewis MA, Lee CM. Lighting up on Facebook: The relationship between tobacco-related postings on Facebook and feelings of nicotine dependence in young adults. Paper presented, Medicine 2.0: Social Media, Mobile Apps, and Internet/Web 2.0 in Health, Medicine, and Biomedical Research, Maui, HI, Nov 2014.
  • Swanson AJ, Anderson JM, Mittmann A, Lewis MA, Litt DM. Investigating how drinking behavior relates to life transitions in young adults. Poster presented, Research Society on Alcoholism, Bellevue, WA, June 2014.

Psychostimulant-Induced Changes in Striatal Cholinergic Interneuron Physiology

Granville Storey, Ph.D., Senior Fellow
Neurology

Nigel S. Bamford, PhD, Neurology (Mentor)

Description: Substance abuse is a chronic relapsing disorder in which drug reinstatement is thought to return the addict to a more stable, normalized state. We have shown that repeated psychostimulants, when delivered in a manner which produces elevated synaptic dopamine and behavioral sensitization, causes a chronic presynaptic depression (CPD) of striatal glutamate release in withdrawal and a paradoxical presynaptic potentiation (PPP) in glutamate release following drug reinstatement. CPD is caused by a dopamine D2 receptor-dependent reduction in tonic acetylcholine availability at presynaptic terminals of corticostriatal projections, while PPP is produced by a D1 receptor-dependent increase in acetylcholine at those same synapses. Thus, short-term increases in dopamine availability via amphetamine can act to produce long-term, yet reversible changes in corticostriatal activity, which are generated through acetylcholine-producing striatal interneurons. This mechanism underlies aspects of drug dependence, since nicotinic and dopaminergic receptor ligands can prevent locomotor sensitization and the escalation of cocaine self-administration, both hallmarks of addiction.

We hypothesize that repeated amphetamine produces long-term changes in the activity of striatal cholinergic interneurons that are initiated by dopamine yet maintained by changes in acetylcholine autoreceptor sensitivity. We will perform electrophysiology experiments in striatal slices and in dissociated cells from amphetamine-sensitized mice to determine how repeated amphetamine produces plasticity in cholinergic interneuron firing patterns and responses to drug reinstatement in vitro. This work will determine the central mechanism underlying striatal presynaptic plasticity following repeated amphetamine, explore possible novel therapeutic targets for addiction, elucidate mechanisms underlying normal motor learning and behaviors and will generate preliminary data for funding through NIH.

Resulting articles & projects:

  • Wang W, Nitulescu I, Lewis JS, Lemos JC, Bamford IJ, Posielski NM, Storey GS, Phillips PEM, Bamford NS. Overinhibition of corticostriatal activity following prenatal cocaine exposure. Ann Neurology 2012 (Nov 9 ahead of print). doi: 10.1002/ana.23805. [PubMed abstract ]