TITLE: STRESS AND DRUG ABUSE: EPIDEMIOLOGY, ETIOLOGY, PREVENTION, AND TREATMENT SPONSOR: National Institute on Drug Abuse

(NIDA) (http://www.nida.nih.gov)

RESEARCH OBJECTIVES Areas of Research Interest The examples listed in the sections below illustrate the types of research that would be responsive to this RFA. Types of research encouraged include but are not limited to: Epidemiology Population-based and clinical research on the extent to which exposure to chronic stress signals an increase in the risk of drug use, abuse and dependence is of interest. Epidemiological studies that focus on individual and environmental factors specific to chronically stressed individuals that enhance vulnerability to drug use or relapse to drug use are specifically sought. Studies are sought examining the epidemiology of co-occurring chronic stress and drug abuse or dependence in the general population. This includes research investigating moderators of the relationship between these variables. For example, it is important to understand gender differences in the effects of chronic stress and the effects of biological and physiological mechanisms that contribute to differential response to stress. Also, the identification of "protective" factors that might attenuate the impact of chronic stress on drug abuse is particularly important due to implications for prevention and treatment. o Studies to examine social, cultural and environmental influences on chronic stress and drug abuse/dependence within and across racial and ethnic groups. o Differential effects of chronic stress during stages of drug use and the influence of other co-existing psychiatric disorders. o The influence of gender on pathways from chronic stress to stages of drug use. o Studies to examine the influence of environmental conditions (e.g., neighborhood disadvantage, crime, violence) on the co-occurrence of chronic stress and drug abuse/dependence. o Studies to examine differential effects of continued, repetitive, traumatic events on drug use across different age groups, especially during adolescence and young adulthood (to expand our understanding the relationship between chronic stress and drug abuse). Etiology This RFA encourages human research studies on how chronic stress across the developmental trajectory (e.g., prenatal, perinatal, childhood, adolescence, early/mid/late adulthood) affects risk for drug-seeking or drug-taking behavior and abuse/dependence or relapse. Studies utilizing objective measures of stress-induced developmental changes are sought. This includes studies measuring physiological (e.g., pupillary dilation, cortisol secretion) reactivity to stressful situations or to laboratory events such as

acoustic startle. While such physiological responses to stress currently are studied, their relationships to vulnerability to drug abuse are virtually unexplored. Genetic effects are strongly associated with drug abuse as are environmental effects, but the contribution of each of these factors, and especially gene-environment interactions, are much less studied and constitute a research gap. Personality characteristics of children and their interaction with home (including, for example, foster care) and school environments constitute one research focus relevant to the gene-environment question. Less obvious sources of early stress, such as natural disasters or death of a parent, might be contributory and thus, constitute an important additional focus for research. Examples include: o Effect of long-term early stress on adult stress response and drug abuse, particularly with respect to neurobiological aspects of stress. o Effects of early stress on neurobiological and neurobehavioral processes in development, and how changes may place a child or adolescent at risk for drug abuse. o Studies on how drug abuse may contribute to or bring about stress (e.g., physical or sexual assault, victimization, violence) and/or PTSD. o Studies on how drugs can be used to "self-medicate" or to produce relief from stress. o Objective measures of chronic stress either as a precursor to, or concurrent with, drug abuse. o Studies of biological/psychological/environmental/social factors that might protect an individual from stress and thereby reduce drug abuse risk. o Investigations of individual differences in response to chronic (external) stressors and their relation to drug abuse. o Characterization of etiological effects of early sub-optimal environments (e.g., orphanages, poverty- or crime-ridden neighborhoods) and later drug use. o Determination of the role of chronic stress in drug abuse relapse. Studies on the neurobiology of trauma, particularly as related to the subsequent experience of PTSD concurrent with drug abuse Prevention Applications are desired for interventions to prevent the onset of drug use or its escalation to abuse as a result of chronic stress. Interventions can be delivered in many types of environments, including hospitals, emergency rooms, faith-based and community organizations, schools, workplaces, etc. Examples include: o Development and testing of strategies to prevent drug abuse initiation among individuals who have experienced long-term physical, sexual, and/or psychological/emotional abuse. o Testing community-based interventions designed to prevent onset of use or escalation to drug abuse among chronically stressed children, youth, and families living in neighborhoods with characteristics that have been associated with chronic stress (e.g., crime, victimization, chronic unemployment, unsafe streets, etc.)

o Testing strategies designed to prevent dependence on prescription drugs in chronically stressed individuals who live with chronic pain. o Development and testing of early prevention interventions that target chronically stressed children who have lived in multiple out-of-home placements such as foster care, group homes, and institutions. o Development and testing of strategies for preventing drug abuse conditions in chronically stressed individuals who are part of minority groups and communities that may have experienced intergenerational stress or historical trauma (such as American Indians and African Americans). Treatment Research is encouraged on the treatment of drug abusing or dependent individuals who concurrently are experiencing chronic stress or PTSD. This includes research on innovative approaches to stop the progression from drug use to abuse and dependence due to the effects of chronic stress, including the development and testing of behavioral treatments, alone or in combination with pharmacotherapies, for drug abusing or dependent individuals with comorbid PTSD or chronic stress. Given that individuals with the foregoing problems also can be at high risk for HIV/AIDS and other medical conditions, research also is encouraged that includes attention relevant to these factors. Behavioral treatment and combined behavioral and pharmacological treatment studies in response to this RFA should be guided by NIDA's Behavioral Therapies Development Program, PA NUMBER: PA-99-107 http://grants.nih.gov/grants/guide/pa-files/PA-99-107.html. Although PA-99107 delineates three stages of behavioral therapy research, this RFA solicits only applications for Stage I and Stage II studies of all forms of behavioral treatment, including psychotherapy, relapse prevention, counseling, group therapy, family therapy, couples therapy, etc. Stage I research involves the development, modification, and pilot testing of novel behavioral interventions. Stage I projects also may focus on incorporating novel technologies (e.g., information technologies such as hand-held computers, multimedia CD ROM programs, and instant messaging) into behavioral interventions. Stage II behavioral treatment research involves testing behavioral interventions and studies that are designed to identify the efficacious components of behavioral interventions. Behavioral treatment studies also can extend to the identification of moderators and mediators of the effects of potentially efficacious components of behavioral interventions. Treatment research proposals responsive to this RFA should focus on drug abusing/dependent individuals who also are experiencing chronic stress or PTSD. Examples are: o Enhancement of treatments with existing or novel stress management interventions. o Using innovative models of successful coping with stress (e.g., resilience, toughening) to inform the development of novel treatments. o Studies to determine if additional trauma-specific interventions enhance the outcome of treatment when used for drug abusers with PTSD. o Studies to determine new or more effective ways to combine medications with behavioral treatments for individuals with concurrent drug use disorders and PTSD.

o Treatments designed to treat individuals who are dependent upon or abusing prescription drugs for chronic pain or for other medical conditions that are associated with chronic stress. o Treatments to enhance adherence to medication, including medication for comorbid psychiatric conditions, HIV, or for other infectious disease o Treatments that incorporate behavioral risk-reduction interventions for HIV or other infectious diseases for drug abusers who also suffer from chronic stress. o Studies of efficacious therapies in which dismantling or additive designs are used to identify their main active components, and/or the moderators and mediators of potential effects of active components of efficacious treatments. o Studies of the role of chronic stress in behavioral treatment engagement, retention, and/or maintenance of treatment gains. o Evaluation of potential efficacy of medications which alter responsiveness of HPA axis, in combination with behavioral therapy, as potential therapies for drug dependence. o Studies examining the value of gender-specific treatment of individuals with comorbid drug abuse and PTSD FUNDS AVAILABLE NIDA intends to commit approximately $2,500,000 in FY 2003 to fund 8 to 10 new grants in response to this RFA. An applicant may request a project period of up to 5 years. ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic or foreign o Faith-based or community-based organizations RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: May 19, 2003 Application Receipt Date: June 18, 2003 Peer Review Date: November/December 2003 Council Review: February 2004 Earliest Anticipated Start Date: June 2004