New NIDA PAs and RFAs
On November 3, 2004, NIDA issued an RFA entitled Lapse or Relapse to Drug Abuse and Other Chronic Conditions (RFA-DA-05-004). This RFA invites applications in which a behavioral, cognitive, social cognitive or neurobiological approach is used to advance our understanding of the causes, consequences and treatment of drug abuse relapse. The purpose of this RFA is to stimulate research that will lead to an improved understanding of the relapsing nature of drug addiction. This RFA particularly encourages interdisciplinary research that fosters collaboration between basic and applied researchers, between those studing humans in laboratory settings and those studying clinical populations. In addition, researchers who study other chronic relapsing conditions (e.g., obesity, depression, anxiety disorders) are encouraged to apply their research approaches or paradigms to the problem of drug abuse and addiction. Letter of Intent Receipt Date for this RFA was December 27, 2004; Application Receipt Date was January 25, 2005.
On January 3, 2005, NIDA issued an RFA entitled Neurobiology of Behavioral Treatment: Recovery of Brain Structure and Function (RFA-DA-05-006). Through this RFA NIDA invites exploratory/developmental, interdisciplinary research applications to investigate the human central nervous system effects of behavioral therapies, alone or in combination with pharmacotherapies, used for the treatment of drug abuse/addiction. Major advances have been made in understanding how drugs of abuse alter various brain processes and systems both structurally and functionally. Likewise, after a course of treatment the brain is also changed in some way. Further, many of these changes can be very persistent, even after long-term abstinence from drugs. Through the use of clinical neurobiological approaches, such as brain imaging (e.g., PET, MRI, MRS, EEG) and other related neurobiological methodologies (e.g., ERP, neuropsychological testing, genetics) considerable information is now being amassed that reveals how acute and chronic drug abuse alters brain structure and/or function. However, relatively little is yet known of the brain's specific response to detoxification/withdrawal and protracted abstinence, and even less is known of how treatment (both behavioral and/or pharmacological) might affect brain structure and function. A critical question that remains to be addressed is how drug addiction therapies, particularly behavioral treatments, might affect the structure and/or function of a brain altered by drugs of abuse with specific implications for consequential behavior change. Therefore, it is important to understand the specific role of various treatments in the recovery of neurobiological systems altered by extended drug exposure and behavioral therapy. Exploratory studies that will detect and characterize neurobiological mechanisms predictive of treatment outcome and efficacy are especially encouraged. Letter of Intent Receipt Date for this RFA is February 21, 2005; Application Receipt Date is March 21, 2005.
On January 21, 2005, NIDA issued an RFA entitled HIV and Drug Abuse Interventions among Pregnant Women in Drug Abuse Treatment (RFA-DA-05-008). The purpose of this RFA is to encourage research on HIV prevention and risk reduction interventions among pregnant women in drug abuse treatment. (For the purposes of this RFA, drug abuse treatment refers to behavioral or combined behavioral and pharmacological treatment of drug abuse and/or dependence.) Pregnancy is a time of increased risk for HIV infection, both for drug-using women and for their infants through mother-to-child transmission. Behavioral HIV prevention and risk reduction interventions have shown promise in reducing HIV risk behaviors with a wide variety of drug-using populations, including drug-abusing pregnant women. For HIV-infected pregnant women, evidence suggests that proper HIV intervention care, including the use of certain antiretroviral medications, can reduce the maternal transmission of HIV to the child and can reduce other maternal and fetal complications. This RFA invites applications for studies to prevent or reduce HIV risk among pregnant women in drug abuse treatment through: 1) targeted behavioral HIV prevention and risk reduction interventions; and 2) behavioral interventions aimed at improving adherence to prenatal care among HIV-positive, pregnant drug-abusers. Letter of Intent Receipt Date for this RFA is February 21, 2005; Application Receipt Date is March 21, 2005.
PAs and RFAs Issued With Other NIH Components/Agencies
On September 29, 2004, NIDA, in conjunction with numerous other NIH components, the FDA and the CDC issued a Program Announcement (PA) entitled Manufacturing Processes of Medical, Dental, and Biological Technologies (SBIR/STTR). Through this PA the NIH, CDC, and FDA encourage research related to advanced processing in the manufacture of biomedical products and the implementation of new technologies in medical care. New methods, procedures, measures, and controls are needed for manufacturing a broad range of technologies and products with unsurpassed quality and to lower manufacturing costs for existing and/or new processes. Research is also encouraged that can contribute to the containment and reduction of health care costs and that can improve the cost effectiveness, quality, and accessibility of the health care system.
On October 20, 2004, NIDA, in conjunction with a number of other NIH components, issued a PA entitled The Effect of Racial and Ethnic Discrimination/Bias on Health Care Delivery (PA-05-006). The purposes of this PA are: (1) to improve the measurement of racial/ethnic discrimination in health care delivery systems through improved instrumentation, data collection and statistical/analytical techniques; (2) to enhance understanding of the influence of racial/ethnic discrimination in health care delivery and its association with disparities in disease incidence, treatment and outcomes among disadvantaged racial/ethnic minority groups; and (3) to reduce the prevalence of racial/ethnic health disparities through the development of interventions to reduce the influence of racial/ethnic discrimination in health care delivery systems in the United States. For the purposes of this PA, health care delivery is defined as the provision or receipt of a broad range of health-related services including preventive, primary, ambulatory and in-patient, emergency, specialty and long-term care. Health care delivery systems are defined as insurance plans, hospitals, clinics, private physician offices, or public and community health facilities that provide or finance health care delivery.
On October 20, 2004, NIDA in conjunction with NIMH and NIAAA, issued a PA entitled Co-Occurring Mental Illness, Alcohol and/or Drug Abuse and Medical Conditions (PA-05-007). Through this PA, NIDA, NIMH, and NIAAA invite research grant applications to conduct services research on co-occurring mental illness, alcohol and/or drug abuse, and commonly co-occurring medical conditions. A significant number of individuals simultaneously suffer from mental illness, problem alcohol and/or drug use, and other medical or physical disorders, such as mood disorders compounded with substance abuse, chronic pain with depression and/or alcohol abuse, schizophrenia with heroin use and hepatitis C. This PA encourages innovative and theory-driven empirical research to examine the organization, management, integration, dissemination and implementation, and financing of services for co-occurring mental illness, alcohol and/or drug abuse, and commonly co-occurring medical conditions, as well as the impact of these factors on the quality, cost, access, utilization, outcomes, and cost and cost effectiveness of care.
On November 22, 2004, NIDA in collaboration with NCI and NIAAA, issued a PA entitled Decision Making in Health: Behavior Maintenance (PA-05-016). The purpose of this initiative is to invite applications for research projects that will expand our knowledge of basic decision-making processes underlying initiation and long-term maintenance of healthy lifestyle behaviors that may reduce one's risk of cancer and other chronic diseases, such as cardiovascular disease, diabetes, and addiction. The NCI, NIDA, and NIAAA encourage collaborations between basic judgment and decision-making researchers, and applied cancer control or addiction researchers that will elucidate the basic cognitive and affective processes involved in decisions that are made repeatedly over time, such as adhering to weight-loss programs or smoking cessation programs.
On December 2, 2004, NIDA, in collaboration with other components of the NIH and DHHS, issued a PA entitled Community Participation in Research (PAR-05-026). The goal of this PAR is to support research on health promotion, disease prevention, and health disparities that is jointly conducted by communities and researchers. This PAR invites NIH research project grant (R01) and exploratory/developmental grant (R21) award mechanisms. Community-based participatory research (CBPR) is defined as scientific inquiry conducted in communities and in partnership with researchers. The process of scientific inquiry is such that community members, persons affected by the health condition, disability or issue under study, or other key stakeholders in the community's health have the opportunity to be full participants in each phase of the work (from conception - design - conduct - analysis - interpretation - conclusions - communication of results). CBPR is characterized by substantial community input in the development of the grant application.
On December 10, 2004, NIDA, in collaboration with numerous other NIH components, issued a PA entitled Research on Mind-Body Interactions and Health (PA-05-027). Through this PA, the participating Institutes, Centers, and Offices invite applications in support of research on mind-body interactions and health. "Mind-body interactions and health" refers to the relationships among cognitions, emotions, personality, social relationships, and health. A central goal of this program is to encourage interdisciplinary collaboration and innovation towards understanding the processes underlying mind-body interactions and health as well as towards the application of such basic knowledge to interventions and clinical practice in the promotion of health and the prevention or treatment of disease and disabilities.
On December 21, 2004, NIDA, in collaboration with numerous other NIH components, issued a PA entitled Social and Cultural Dimensions of Health (PA-05-029). The ultimate goal of this PA is to encourage the development of health research that integrates knowledge from the biomedical and social sciences. This involves the further development of health-related social science research relevant to the missions of the NIH Institutes and Centers (ICs) and the development of multi- or inter-disciplinary research that blends the theories and approaches of the social and biomedical sciences. Within the broad spectrum of research identified in this announcement, applicants are encouraged (but are not required) to employ multiple (i.e., biological, behavioral, and/or social) levels of analysis. This announcement invites applications to (a) elucidate basic social and cultural constructs and processes used in health research, (b) clarify social and cultural factors in the etiology and consequences of health and illness, (c) link basic research to practice for improving prevention, treatment, health services, and dissemination, and (d) explore ethical issues in social and cultural research related to health.
On January 24, 2005, NIDA, in conjunction with numerous other NIH components, issued a PA entitled Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) to Improve The Chemistry and Targeted Delivery of RNAi Molecules (PA-05-041). Through this PA the participating institutes of the NIH invite the small business community to apply cutting edge-technology to develop new approaches and chemical modifications that will increase the long term stability, delivery and targeting of siRNAs in cells and tissues for laboratory and therapeutic applications.
On October 26, 2004, NIDA, in collaboration with numerous other NIH components, issued an RFA entitled International Cooperative Biodiversity Groups (ICBG) (RFA-TW-04-004). The unifying theme underlying the ICBG program is the concept that the discovery and development of pharmaceutical and other useful agents from natural products can, under appropriate circumstances, promote economic opportunities and enhanced research capacity in developing countries while conserving the biological resources from which these products are derived. This RFA calls for the development of interdisciplinary programs through the establishment of International Cooperative Biodiversity Groups (ICBGs), with active and substantial participation by U.S. and developing country scientists and institutions. It is the intent of this RFA to promote the conservation of biological diversity through the discovery of bioactive agents from natural products, and to ensure that benefits accruing from both the research process and any discoveries are shared with the country of origin. The RFA is seeking applications that will build institutional relationships with developing countries that will continue to grow beyond the life of the RFA and will serve as effective models for others to develop similar relationships.
On November 19, 2004, NIDA, in collaboration with numerous other NIH components, issued an RFA entitled Leadership for HIV/AIDS Clinical Trials Networks (RFA-AI-05-001). The objective of this RFA is to establish the Leadership of three to six HIV/AIDS Clinical Trials Networks to carry out the NIAID research agenda in the following areas: (1) Vaccine Research and Development; (2) Translational Research/Drug Development; (3) Optimization of Clinical Management, Including Co-Morbidities; (4) Microbicides; (5) Prevention of Mother-to-Child Transmission (MTCT) of HIV; and (6) Prevention of HIV Infection. Each Network Leadership will consist of three components: (1) a Coordinating and Operations Center (CORE) to provide scientific and administrative leadership, central operations, and communications; (2) a Statistical and Data Management Center (SDMC) to provide biostatistical leadership and central data management; and (3) a Network Laboratory Structure to provide the laboratory services necessary to conduct the clinical research. These Network Leadership components may be combined in a single application or in separate, but linked applications. Resulting Networks may be funded through one to three Cooperative Agreements (U01). Clinical Trial Units will be solicited in a subsequent, linked RFA titled " Units for HIV/AIDS Clinical Trials Networks ". The resulting combination of a Network Leadership and affiliated Clinical Trial Units will constitute an HIV/AIDS Clinical Trials Network. Each Network will give high priority to collaborations with other NIH HIV/AIDS clinical research programs, the other Networks funded through this RFA and other HIV research entities in order to effectively develop and implement a clinically relevant, interdisciplinary and cost-efficient research program.
On November 24, 2004, NIDA, NIMH and NICHD jointly issued an RFA entitled Adolescent Medicine Trials Network for HIV/AIDS Interventions (RFA-HD-04-025). Through this RFA participating institutes invite applications from investigators willing to participate with NICHD under a cooperative agreement to sustain the Adolescent Medicine Trials Network (ATN). This network will have the capacity for developing and conducting selected behavioral, community-based translational, prophylactic, therapeutic, and vaccine trials based on and adding to the information developed through the Adolescent Medicine HIV/AIDS Research Network (1994-2001) and the current Adolescent Trials Network for HIV/AIDS Interventions (2001-2006). The primary mission of the Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions will be to conduct research, both independently and in collaboration with existing research networks and individual investigators, in HIV-infected and HIV-at-risk pre-adolescents, adolescents, and young adults up to age 25 years. The objective of this RFA is to continue and expand the infrastructure required for a network of 14-17 clinical sites, one data and operations center, and one scientific leadership group with discipline-specific subgroups. This network will design, develop, and conduct multiple common clinical trials as well as pertinent formative and translational research studies collaboratively or independently when needed. This network will bring the required numbers of subjects into rigorously designed common protocols and thus address pressing research questions in youth more quickly than could individual centers acting alone.
On November 24, 2004, NIDA, in collaboration with other NIH components and the Agency for Healthcare Research and Quality (AHRQ), issued an RFA entitled Building Interdisciplinary Research Careers in Women's Health (RFA-OD-05-002). The cosponsors of this RFA invite institutional career development award applications for Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Career Development Programs, hereafter termed "Programs." Programs will support research career development of junior faculty members, known as Interdisciplinary Women's Health Research (IWHR) Scholars, who have recently completed clinical training or postdoctoral fellowships, and who are commencing basic, translational, behavioral, clinical and/or health services research relevant to women's health. The goal of this initiative is to promote the performance of interdisciplinary research and transfer of findings that will benefit the health of women, including sex/gender similarities or differences in biology, health or disease. The programs will accomplish these goals by bridging advanced training with research independence, as well as bridging scientific disciplines or areas of interest. This will increase the number and skills of investigators at awardee institutions through a mentored research and career development experience leading to an independent interdisciplinary scientific career addressing women's health.
On December 3, 2004, NIDA, in collaboration with several other NIH components, issued an RFA entitled Pediatric HIV/AIDS Cohort Study (PHACS) (RFA-HD-05-018). Through this RFA, participating Institutes invite applications from investigators willing to participate with the Institutes under a cooperative agreement (U01) to address two critical pediatric HIV research questions: the long term safety of fetal and infant exposure to prophylactic antiretroviral chemotherapy, and the effects of perinatally acquired HIV infection in adolescents. This effort will include refocus of a currently ongoing NIH-funded project (the Women and Infants Transmission Study [WITS]) and may include merger with data from other U.S.-based pediatric HIV cohort studies. This joint effort will take the form of the Pediatric HIV/AIDS Cohort Study (PHACS). The objective of this RFA is to create a body of data to understand more fully the effect of HIV on sexual maturation, pubertal development, and socialization of perinatally HIV-infected pre-adolescents and adolescents, and to acquire more definitive information regarding long-term safety of antiretroviral agents when used during pregnancy and in newborns.
On December 22, 2004, NIDA and NIAAA issued an RFA entitled Secondary Analysis of the NESARC and NSPY Datasets (RFA-DA-05-005). This RFA requests applications to support the secondary analysis of data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) or the National Survey of Parents and Youth (NSPY) to study the epidemiology and etiology of alcohol and drug abuse, as well as the utilization of alcohol and drug abuse services and the prevention of these behaviors. The purpose of this RFA is to take advantage of these rich data sets and to provide support for innovative research using state of the art analytical strategies. Findings from these studies are expected to provide context for the development of prevention and treatment interventions that are likely to have a direct impact on public health outcomes.
On January 10, 2005, NIDA, in conjunction with the National Human Genome Research Institute (NHGRI) and the NIH Office of Rare Diseases issued an RFA entitled K23 with Emphasis on Therapeutic Interventions Employing Genomic or Proteomic Technologies (RFA-HG-05-013). The purpose of the Mentored Patient-Oriented Research Career Development Award (K23) is to support the career development of translational researchers in genomics. The program will support clinicians who propose an integrated clinical research and bench research project that applies genomics and proteomics tools to the study of human patients whose disease has a genetic component. For the purpose of this award, genomics and proteomics are being broadly interpreted to include the application of increasing knowledge of the genome and the proteome to the development and implementation of novel therapeutic strategies as applied to genetic diseases and complex diseases with a genetic component. Priority will be given to projects that have a near-term objective that will lead to the development of effective therapeutic interventions. This award will provide support for three to five years of supervised study and research for clinically trained professionals who plan to become independent, productive clinical investigators focusing on patient-oriented research.
On February 2, 2005, NIDA and NIAAA jointly issued an RFA entitled Consequences of Drug Abuse and Alcohol Exposure on Brain and Behavioral Development (RFA-DA-05-007). The purpose of this RFA is to support research to further our understanding of the consequences of drug use, abuse, and addiction on the human brain and behavior during development. Research has demonstrated adverse consequences of drugs of abuse across multiple domains, however little is understood about the effects of drugs of abuse on development per se. The rapid advancement and refinement of new technologies offer unprecedented opportunities to characterize the neurobiological consequences of drugs of abuse on the developing human brain, and to address the relationships between the neurobiological aspects of development and the behavioral consequences of drug exposure. For example, advances in behavioral assessment, neuroimaging technologies, and statistical methods have the potential to define the effects of abused drugs on the human brain and behavior, effects that are very likely to be strongly influenced by the developmental state of the nervous system at the time that exposure occurs and, importantly, by a wide variety of environmental factors. This RFA calls for research that addresses the effects of drug exposure on neurobiological and behavioral development, spanning the continuum of human development through the transition to adulthood with a focus on the following areas: (1) documentation of the effects of exposure on development, (2) examination of the effect of timing of exposure on development, (3) examination of mechanisms that link exposure to adverse consequences, and (4) determination of the role of environmental context on the effects of exposure.
Other Program Activities
Cooperative Research and Development Agreement with IVAX Research to Test an AMPA Antagonist (Talampanel) for the Treatment of Cocaine Dependence
The Division of Pharmacotherapies and Medical Consequences of Drug Abuse has successfully negotiated a Cooperative Research and Development Agreement (CRADA) to test talampanel, a unique proprietary inhibitor of the amion-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate excitatory amino acid receptors as a treatment for cocaine dependence. Talampanel is already in Phase II clinical studies as a potential treatment for epilepsy so a substantial amount of preclinical and clinical data will be available to shorten the lead time necessary to test the hypotheses (prevention of locomotor sensitization, blockade of cocaine-cue induced drug seeking behavior, and blockade of cocaine-primed reinstatement in animal models of cocaine self-administration) generated by NIDA grantees that this class of compound may be useful as a treatment for cocaine dependence.
Ondansetron Shows Effect in Clinical Trial
Ondansetron a 5-HT3 antagonist, has been shown to modulate the behavioral effects of cocaine in animals and to block some of the subjective effects of cocaine in humans. In a pilot dose ranging double blind phase II study of ondansetron the highest dose of 8mg/day was superior to placebo and the lower two doses in reducing cocaine use. This study will be followed up by a larger confirmatory study.
NIDA Medications Development Program Expands Capabilities for Preclinical Safety Testing
On September 30, 2004, NIDA contract N01DA-4-8841, entitled "Toxicological Evaluations of Potential Medications to Treat Drug Addiction," was awarded to Gene Logic Laboratories, Inc., of Gaithersburg, MD. The Principal Investigator is Dr. Eias Zahalka. This contract not only allows the NIDA Medications Development Program to continue it's support of the standard preclinical safety tests required for IND and NDA filings, but it also expands NIDA's capability to conduct predictive toxicology testing during the medications discovery process. Predictive toxicology, exemplified by the in vitro HERG assay to predict QT prolongation problems, the Spot Ames test to predict genotoxicity, etc., first became incorporated into NIDA's medication discovery programs in 2000. With the advent of gene expression profiling techniques, the field of toxicogenomics has played an important role in developing new predictive toxicology assays, and Gene Logic has been a pioneer in this area of research. With the new award, NIDA's medications discovery programs immediately have access to in vitro assays that are predictive of hepatotoxicity, a common finding that terminates many drug development projects. By addressing safety issues such as hepatotoxicity during the drug discovery process, development candidates have a better chance of succeeding in preclinical development.
NIDA Medications Development Program Renews and Expands Contract to Support Test Compound Evaluation in Relapse Models
Dating back to the inception of the NIDA Cocaine Treatment Discovery Program (CTDP) in 1992, it has been recognized that different stages of the cocaine addiction cycle must be targeted with different types of medications. Initially, the CTDP's focus was limited to the discovery of potential "agonist therapies" for initiation of abstinence (analogous to the use of mu-opioid agonists in opiate addiction) and "antagonist therapies" to prevent relapse in abstinent addicts (analogous to naltrexone's use in opiate addiction). In 1997, NIDA staff began efforts to expand CTDP testing to include animal models that focus on relapse triggers such as stress and conditioned cues. The first related RFP was released in early 1999 but it did not yield any acceptable proposals (as judged by the peer review process). Persistence and the reissue of a revised RFP resulted in a contract award to Virginia Commonwealth University (Patrick Beardsley, PI) September, 2000. At that time, VCU staff did not have hands-on experience conducting stress- or cue-induced relapse studies; however, over the course of their first contract, the laboratory evolved into an experienced and productive group (e.g., see discussion of JDTic studies under "Research Findings", above). The contract, entitled "Medication Discovery using Rat Models of Relapse to Drug Self-Administration," went through the competitive renewal process during FY 2004 and on September 30, VCU was again selected as NIDA's contractor. The new contract (number N01DA4-8848) provides an expanded level of support for test compound evaluation in relapse models and will give NIDA the additional flexibility to address relapse to methamphetamine, nicotine, and perhaps cannabinoids.
NIDA Medications Development Program Awards Contract for Discovery of Medications to Treatment Methamphetamine-Induced Cognitive Impairment
Building on the concept that different stages of the addiction process should be targeted with different types of medications, the NIDA MDP has expanded its focus to address an important long-term consequence of methamphetamine abuse, cognitive impairment. Two different consultant meetings, held in 2000 and 2003, helped shape NIDA's planning for this new contract. During the 2000 meeting, clinicians stressed the fact that methamphetamine addicts are more cognitively impaired than cocaine addicts and they argued that restoration of normal cognitive function would facilitate behavioral therapy. Although animal models of methamphetamine-induced cognitive impairment did not exist in 2000, the field progressed rapidly and by 2003, consultants concluded that the state of the science was sufficient to support the development of relevant models under a NIDA contract. An RFP was released in early 2004 and the resulting contract (N01DA-4-8849; "Animal Models of Methamphetamine-Induced Cognitive Impairment") was awarded September 29, 2004 to the U.C. Irvine (John Marshall, PI). During the life of this contract, consultants with pharmaceutical company and/or neurotoxicology backgrounds will assist NIDA staff and the contract PI in developing models and establishing appropriate protocols for evaluation of test compounds. To this end, a contract kickoff meeting was held at UCI on October 20, 2004. NIDA attendees were Mr. Hirsch Davis (Project Officer), Dr. David McCann, and Dr. Jane B. Acri. UCI attendees included Dr. John Marshall and Dr. Steven O'Dell. NIDA's consultants were Dr. Rex Denton (Bristol-Myers Squib), Dr. Mary Jeanne Kallman (Lilly Research Laboratories) and Dr. Victoria Luine (Hunter College of the City University of New York).
NIDA/Portland VA Medical Center IAG is Expanded in Scope to Address Abuse Liability Testing as well as Medications Discovery
Over the past several years, NIDA's Cocaine Treatment Discovery Program (CTDP) has shifted away from a major emphasis on Biogenic Amine Transporter- (BAT-) directed "agonist medications" and toward the evaluation of compounds that target common triggers of relapse, such as stress (see above). This has resulted in a decreased need for BAT-directed testing, supported until August 2004 through an IAG with the Portland VA Medical Center (Aaron Janowsky, PI). At the same time, the DEA has increased its requests to NIDA for abuse liability testing of new street drugs, which primarily show mixed hallucinogen/psychostimulant properties. NIDA has an obligation to provide data to support DEA scheduling recommendations for these compounds, in vitro testing is part of the requirement, and assays targeting BATs are essential. To accommodate the small but remaining needs of the CTDP for BAT-directed testing, as well as NIDA's increased need for in vitro data relevant to abuse liability testing, a new IAG (Y1DA 5007 "In Vitro Receptor, Transporter, and Release Assays for NIDA Medications Discovery and Abuse Liability Testing") was established with the Portland VA Medical Center in December 2004. Assays are being expanded in scope to include 5-HT2a receptors, PCP receptors, and other targets relevant to abuse liability.
The PA, "Collaborative Clinical Studies in Drug Abuse" has resulted in the funding of a Multi-Site Clinical Trial entitled "Maternal Opioid Treatment Human Experimental Research" (MOTHER) to six domestic and two international sites
Promising preliminary data from a double-blind randomized trial at the Johns Hopkins School of Medicine suggest that buprenorphine results in improved birth outcomes and less neonatal abstinence syndrome (NAS) relative to methadone. The current randomized parallel group study will be the first multi-site trial to assess the efficacy of buprenorphine for reducing NAS relative to methadone in opioid dependent pregnant women. Overall, this study will provide pivotal data to support an indication for the use of both methadone and buprenorphine during pregnancy and for establishing efficacy of buprenorphine for reducing NAS relative to methadone. The Kickoff Meeting for the MOTHER Project was held December 15 - 17, 2004, in Washington, D.C.
Translationally Oriented Approaches, Devices and Strategies (TOADS) work-group
The Translationally Oriented Approaches, Devices and Strategies (TOADS) work-group, co-chaired by Dr. Nemeth-Coslett, DCNDBT, has set aside money to support up to 8 junior researchers to attend the 11th International Conference on Human-Computer Interaction. Researchers who have an interest in using state-of-the-art technologies as an investigative tool in drug abuse research, prevention and treatment were invited, via fliers at Neuroscience and through several ListServes, to submit proposals.
Update on the National Drug Abuse Treatment Clinical Trials Network (CTN)
The proposals for the Request for Applications (RFA) DA-05-001 for the fourth solicitation for the CTN were received October 14, 2004. This RFA includes both new applications (new Nodes) and competing continuations. The anticipated award date is July 2005.
Two new Requests for Proposal (RFPs) were issued: DA-5-2207 for the Data and Statistics Center for the CTN, and DA-5-2208 for the Clinical Coordinating Center for the CTN. Responses were due in January 2005. Both contracts are to be awarded in April 2005.
Nine protocols have completed enrollment since 2001. These studies enrolled 2,692 patients who were randomized in 53 community treatment programs located in 16 states. Twelve additional protocols are currently recruiting & enrolling patients. These protocols will enroll 4,674 patients across 88 Community Treatment Programs when completed. Highlights of the active protocols include:
- Protocol CTN 0003 (Bup/Nx: Comparison of Two Taper Schedules) began enrollment June 30, 2003. The study involves 11 sites across 8 nodes; the targeted enrollment is 480 participants. Participation has reached 2/3 of the targeted enrollment.
- Protocol CTN-0004 (Motivational Enhancement Treatment to Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse) closed enrollment August 9, 2004 and has a target for study completion in early 2005.
- Protocol CTN 0010 (Buprenorphine/Naloxone Facilitated Rehabilitation for Opioid Dependent Adolescents/Young Adults) began enrollment in July 2003. This is the first protocol in the CTN that targets adolescent substance abusers. Enrollment is at 1/3 of the projected target of 240 adolescents.
- Protocol CTN 0011 (A Feasibility Study of a Telephone Enhancement Procedure to Improve Participation in Continuing Care Activities) has completed enrollment and follow-up and is now at the analysis stage.
- Protocol CTN 0013 (Motivational Enhancement Therapy to Improve Treatment Utilization and Outcome In Pregnant Substance Abusers.) This protocol has recently begun enrollment and has reached 1/3 of the projected target of 200 pregnant substance-abusing women.
- Protocol CTN 0014, Brief Strategic Family Therapy for Adolescent Drug Abusers (BSFT), is in the final stages of provider training and will involve three phases of implementation. The first wave of sites has finished protocol training and moved to patient enrollment in August 2004. BSFT will be implemented at 8 sites across 6 nodes plus Puerto Rico. This intervention is the first CTN study to target adolescents and their families.
- Protocol CTN 0015 (Women's Treatment for Trauma and Substance Use Disorder: A Randomized Clinical Trial) began in March 2004. This study is being carried out at 8 sites across 7 Nodes and targeted enrollment is 480. The study has reached nearly 50% of the targeted patient enrollment.
- Protocol CTN 0017 (HIV and HCV Intervention in Drug Treatment Settings). The study has recently begun enrollment in November 2004. It will be carried out at 8 CTP sites across 5 nodes.
- CTN 0018 (Reducing HIV/STD Risk Behaviors: A Research Study for Men in Drug Abuse Treatment) began enrolling in April 2004. This study will be carried out at 14 CTP sites across 11 nodes. The enrollment has reached 25% of the target of 560 patients.
- CTN 0019 (Reducing HIV/STD Risk Behaviors: A Research Study for Women in Drug Abuse Treatment) began enrollment in April 2004. This study will be carried out at 12 CTP sites across 7 nodes. The targeted enrollment is 480 patients for each study. The enrollment has reached nearly 1/3 of the target goal.
- CTN 0020 (Job Seekers Training for Substance Abusers). The protocol recently began enrollment in October 2004. It will be conducted at 12 CTP sites across 7 nodes. The targeted enrollment is 624 patients.
- Protocol CTN 0021(Motivational Enhancement Treatment to Improve Treatment Engagement and Outcome for Spanish-Speaking Individuals Seeking Treatment for Substance Abuse) began enrollment in November 2003. This is the first Spanish only protocol in the CTN. It will be conducted at 6 bi-lingual sites across 5 nodes and has a target enrollment of 480 patients. The study has reached nearly 50% of the target goal.
- In addition to the primary CTN trials, there are 12 studies supported by independent grants or as supplements that use CTN studies as a platform.
- New Collaborative Study: Starting Treatment with Agonist Replacement Therapies (START) Study: The CTN will participate with the Division of Pharmacotherapies & Medical Consequences of Drug Abuse on a multi-centered trial to compare the effect of buprenorphine/naloxone (Bup/Nx) and methadone (MET) on liver function in the outpatient setting. This is a randomized, open-label, multi-center, Phase 4 study in participants entering opioid agonist treatment programs at community centers (methadone centers) throughout the country. It is anticipated that 1,000 patients will be entered into the trial starting second quarter of 2005.
3 Additional Protocols to begin enrollment in FY 05.
Three new studies will address emerging needs of ADHD in adolescents, ADHD in smoking adults, and the problem of treatment for prescription opiate abuse. In addition, a genetics component will be tested in the START Bup/Nx study.
The NIH Summer Internship Program (SIP) and the Minority Recruitment & Training Program (MRTP)
The NIH Summer Internship Program (SIP) and the Minority Recruitment & Training Program (MRTP) are now accepting applications for the Summer, 2005. Both programs provide training opportunities for students who are interested in the scientific basis of drug abuse. In these programs, students gain basic science and/or clinical laboratory experience, attend student seminars, and participate in a summer poster presentation. The goal of the programs is to expose students to the realities of research, from experimental design to data analysis, interpretation and presentation. For information and an application for the SIP, go to www.training.nih.gov or contact Dr. Stephen Heishman (firstname.lastname@example.org). For an application or to receive information about the MRTP, contact Christie Brannock (email@example.com)
NIDA's New and Competing Continuation Grants Awarded Since September 2004
Alemagno, Sonia A. -- University of Akron
HIV Prevention For Community-Based Drug-Using Offenders
Anokhin, Andrey P. --Washington University
Neurocognition, Genetics and Adolescent Substance Abuse
August, Gerald J. -- University of Minnesota Twin Cities
Early Risers Multi-Site Implementation Study
Bauman, Laurie J. -- Yeshiva University
Reducing Risk Among Highly Vulnerable Youth
Beaston-Blaakman, Aaron -- Brandeis University
A Conceputal and Empirical Analysis of Cost Analysis
Bellack, Alan S. -- University of Maryland Baltimore Professional School
Behavioral Treatment for Drug Abuse In SPMI Patients
Bergman, Jack -- Mc Lean Hospital, Belmont, MA
CB-1 Antagonists for Cannabis Addiction
Blankenship, Kim M. --Yale University
Criminal Justice, Race and HIV Risk In CT Drug Users
Block, Robert I. -- University of Iowa
Brain Development of Adolescent Marijuana Users
Bohn, Laura M. -- Ohio State University
Physiological Implications of Opioid Receptor Regulation
Bolland, John M. -- University of Alabama In Tuscaloosa
Decision Making & Substance Abuse Among Inner-City Youth
Botvin, Gilbert J. -- Weill Medical College of Cornell University
Enhancing Implementation Fidelity In A Multi-Site Trial
Bowen, Scott -- Wayne State University
A Preclinical Model of Adolescent Toluene Abuse In Rats
Boyd, Carol J. -- University of Michigan at Ann Arbor
Prescription Abuse and Diversion By Secondary Students
Brody, Gene H. -- University of Georgia
Preventing Drug Use In Rural African Americans
Broner, Nahama -- Research Triangle Institute
HIV/AIDS and Diverted Offenders
Brown, Richard A. -- Butler Hospital, Providence, RI
MI For Teen Substance Abuse With Psychiatric Comorbidity
Bryan, Angela -- University of Colorado at Boulder
Marijuana Use, Gender and Adolescent HIV Sexual Risk
Burstein, Sumner H. -- University of Massachusetts Medical School Worcester
Endocannabinoid Analogs As Anti-Inflammatory Agents
Casey, Betty J. -- Weill Medical College of Cornell University
Development of Basic Components of Decision Making
Chawarski, Marek C. -- Yale University
Brief Introductory Therapy For Opioid Dependence
Choi, Kyung-Hee -- University of California San Francisco
Asian Men's Health Study
Conklin, Cynthia A. -- University of Pittsburgh at Pittsburgh
Extinction In Smokers: Renewal and Spontaneous Recovery
Cornelius, Jack R. -- University of Pittsburgh at Pittsburgh
Fluoxetine For MDD/Cannabis Disorder In Young People
Coscia, Carmine J. -- St. Louis University
Opioid Modulation of Astrocyte Proliferation
Cottler, Linda B. -- Washington University
Deconstructing HIV Interventions For Female Offenders
Cozzi, Nicholas V. -- Physiogenix, Inc.
Amphetamine-Related Photoaffinity Probes
Crits-Christoph, Paul F. -- University of Pennsylvania
The Process of Group Therapy For Cocaine Dependence
Dahl, Ronald E. -- University of Pittsburgh at Pittsburgh
Pubertal Maturation & Drug Use Vulnerability
D'Amico, Elizabeth J. -- Rand Corporation
Brief Youth Substance Use Intervention For Primary Care
Daughters, Stacey B. -- University of Maryland at College Park
Distress Tolerance and Drug Treatment Drop-Out
Dimmitt Champion, Jane -- University of Texas Health Science Center, San Antonio
Behavioral Invervention For Minority Adolescent Women
Dow-Edwards, Diana L. -- Suny Downstate Medical Center
THC Affects the Development of Executive Function
Ehlers, Cindy L. -- Scripps Research Institute
Adolescent Marijuana Use In Native Americans
Faraone, Stephen V. -- Upstate Medical University
Validating Novel Familial Phenotypes of Drug Abuse
Fava, Maurizio -- Massachusetts General Hospital
Drug Discovery Group for Nicotine Dependence Treatment
Ferris, Craig F. -- University of Massachusetts Medical School Worcester
Neurobehavioral Effects of MDMA In Adolescent Monkeys
Fischer, Gabriele -- Medical University of Vienna
Maternal Opioid Treatment: Human Experimental
Forman, Robert F. -- University of Pennsylvania
Group Drug Counseling Toolkit
Frank, Deborah A. -- Boston Medical Center
Prenatal Cocaine Exposure: Adolescent Follow-Up
Gabbay, Frances H. -- Henry M. Jackson Foundation for the Adv. of Military Medicine
Inhibitory Control: Toward A Vulnerability Phenotype
Gerzanich, Vladimir V. -- University of Maryland Baltimore Professional School
Nicotinic ACH Receptors In Cerebrovascular Endothelium
Gibbons, Frederick X. -- Iowa State University
Social-Cognitive Model of Adolescent Substance Use
Gibson, Laura E. -- University of Vermont & State Agricultural College
Smoking Cessation and PTSD
Green, Alan I. -- Dartmouth College
Cannabis & Schizophrenia: fMRI Reward Circuit Biomarker
Gwaltney, Chad J. -- Brown University
Effect of Mood on Impulsivity Among Adolescent Smokers
Halpern, John H. -- Mc Lean Hospital, Belmont, MA
Neurocognitive Consequences of Long-Term Ecstasy Use
Haney, Margaret -- New York State Psychiatric Institute
Medication Development For Marijuana Relapse
Hart, Carl L. -- New York State Psychiatric Institute
Drug Effects on Behavior: Workplace Implications
Hasin, Deborah S. -- New York State Psychiatric Institute
Phenotypes For Drug Abuse: Epidemiologic-Genetic Approach
Heil, Sarah H. -- University of Vermont & State Agricultural College
Maternal Opioid Treatment: Human Experimental Research
Hester, Robert -- University of Dublin Trinity College
Executive Functions In Cannabis Dependence
Huber, Robert -- Bowling Green State University at Bowling Green
Ethopharmacological Characterization of Reward Systems
Hurd, Yasmin L. -- Karolinska Institute
Neurodevelopmental Effects of Adolescent Cannabis Use
Hurt, Hallam -- Children's Hospital of Philadelphia
Adolescent Drug Use: Exploring Neurocognitive Precursors
Itzhak, Yossef -- University of Miami-Medical School
Adolescent Exposure To Psychostimulants: Role of Nnos
Jacobsen, Leslie K. -- Yale University
Brain Functional Correlates of MDMA Use In Adolescence
Jainchill, Nancy -- National Development & Research Institutes
Integrated Continuity of Care for Adolescent Drug Users
Johnson, Knowlton -- W Pacific Institute For Research and Evaluation
A Community Trial To Prevent Inhalant Use In Alaska
Jones, Hendree E. -- Johns Hopkins University
Maternal Opioid Treatment: Human Experimental Research
Jones, Sara R. -- Wake Forest University Health Sciences
Voltammetry In Freely Moving Mice
Juliano, Laura M. -- American University
Disentangling Pharmacological and Expectancy Effects
Kelleher, Kelly J. -- Children's Research Institute
Trial of Automated Risk Appraisal for Adolescents
Kelley, Michelle L. -- Old Dominion University
Effect of Treatment for Drug-Abusing Fathers on Children
Kirby, Kimberly C. -- Treatment Research Institute, Inc. (TRI)
Craft Behavior Therapy Phase 2 Study: Tx Entry Component
Knight, John R. -- Children's Hospital, Boston, MA
Screening and Brief Advice to Reduce Teen Substance Use
Kobilka, Brian K. -- Stanford University
Biophysical Analysis of Opioid Receptor Structure
Konradi, Christine -- Mc Lean Hospital, Belmont, MA
Adolescent Drug Exposure and Adult PFC Function
Kosten, Thomas R. -- Yale University
Heroin Addiction Treatment: Naltrexone and Lofexidine
Kuhn, Cynthia M. -- Duke University
Dopamine Function During Adolescence
Landry, Charles F. -- University of Wisconsin, Madison
Nicotine and Gene Expression in Adolescent Brain
Law, Ping-Yee -- University of Minnesota Twin Cities
Neuronal Regulation of Opioid Receptor Trafficking
Lee, Christine M. -- University of Washington
Personalized Feedback Intervention For Marijuana Use
Leonard, Noelle R. -- National Development & Research Institutes
HIV Risk and Substance Use In Adolescent Couples
Leslie, Frances M. -- University of California, Irvine
Mechanisms of Adolescent Vulnerability to Drugs of Abuse
Lester, Barry M. -- Women and Infants Hospital-Rhode Island
Maternal Opioid Treatment: Human Experimental Research
Levin, Frances R. -- New York State Psychiatric Institute
Marijuana Abusing ADHD Teens: Atomoxetine Treatment
Lopez-Zetina, Javier -- California State University Long Beach
Comparison of Drug Use In the US/Mexico Border
Lukas, Scott E. -- Mc Lean Hospital, Belmont, MA
Cannabis Dependence: Imaging and Medication Development
Lundahl, Leslie H. -- Wayne State University
Cue Reactivity Model/Pharm. Intervention In Cannabis Use
Lynch, Thomas R. -- Duke University
Developing Computer Based Treatments For Addiction
Lynskey, Michael T. -- Washington University
Cannabis Use, Abuse and Dependence: Exploring Phenotypes
Lysle, Donald T. -- University of North Carolina, Chapel Hill
Behavioral Factors In Heroin's Effect On Nitric Oxide
Mackenzie, Robert G. -- Wayne State University
Metabolic Regulation of Midbrain Dopamine Neurons
Mains, Richard E. -- University of Connecticut School of Medicine/ Dentistry
Constructing A Conditional Kalirin Null Mouse
Maldonado, Rafael -- Pompeu Fabra University
Vulnerability To Nicotine Addiction
Malow, Robert M. -- Florida International University
HIV Prevention Groups For AOD Using SMI Women
Marsch, Lisa A. -- National Development & Research Institutes
Science-Based Treatment For Opioid-Dependent Adolescents
Martin, Peter R. -- Vanderbilt University
Maternal Opioid Treatment: Human Experimental Research
McCance-Katz, Elinore F. -- Virginia Commonwealth University
Opioids & HIV Medications: Interactions In Drug Abusers
McMahon, Lance R. -- University of Texas Health Sciences Center, San Antonio
Treatment of Cannabinoid Withdrawal In Rhesus Monkeys
Mendelson, John E. -- California Pacific Medical Center-Pacific Campus
Clinical Pharmacology Of 3,4-Methylenedioxy Amphetamines
Meucci, Olimpia -- Drexel University College of Medicine
Cellular and Molecular Mechanisms of HIV Neuropathology
Milligan, Erin D. -- University of Colorado at Boulder
Pain Control Via Spinal Interleukin-10 Gene Therapy
Milner, Teresa A. -- Weill Medical College of Cornell University
Estrogen-Opioid Interactions In Hippocampus
Moore, Brent A. -- Yale University
Selegiline for Treatment of Cannabis Dependence
Murphy, Susan A. -- University of Michigan at Ann Arbor
Methodology For Adaptive Treatment Strategies
Nair, Madhavan P. -- State University of New York at Buffalo
Cocaine/Immuno and Neuropathogenesis of HIV-1 Infection
Neale, Michael C. -- Virginia Commonwealth University
Psychometric and Genetic Assessments of Substance Use
Patten, Christi A. -- Mayo Clinic College of Medicine, Rochester NY
Intervention For Support Persons To Help Smokers Quit
Paulus, Martin P. -- University of California, San Diego
Stimulant Dependence: Neural Mechanisms of Relapse
Peck, James -- University of California, Los Angeles
Behavioral Therapy Development for Methamphetamine Abuse
Penetar, David M. -- Mc Lean Hospital, Belmont, MA
Bupropion Effects On Marijuana Withdrawal Symptoms
Petry, Nancy M. -- University of Connecticut School of Medicine/Dentistry
Group-Based Contingency Management/Outpatient Treatment
Pillay, Srinivasan S. -- Mc Lean Hospital, Belmont, MA
fMRI of Pain In Cannabis Dependence
Prado, Guillermo -- University of Miami-Medical
Ecodevelopmental Classes of Youth Drug Use/Risky Sex
Prendergast, Michael L. -- University of California, Los Angeles
Gender-Responsive Treatment for Women Offenders
Reich, Warren A. -- Family Center, Inc.
Images of Self and Others In AIDS-Orphaned Youth
Rivkees, Scott A. -- Yale University
CB1 Receptor Action on the Developing Hippocampus
Sadee, Wolfgang -- Ohio State University
Polymorphisms In Regulatory Regions of Addiction Genes
Salina, Doreen D. -- Northwestern University
Integrated Health Treatment for Women Drug Users
Sanders-Bush, Elaine -- Vanderbilt University
Hallucinogens and Serotonin Signal Transduction
Selby, Peter L. -- St. Joseph's Health Centre
Maternal Opioid Treatment: Human Experimental Research
Sharp, Burt M. -- University of Tennessee Health Sciences Center
Opiate Receptor-Mediated Effects of Stress on Immunity
Simoni-Wastila, Linda J. -- University of Maryland Baltimore Professional School
Prescription Drug Abuse In Adolescents and Young Adults
Sinha, Rajita -- Yale University
Lofexidine To Prevent Stress-Related Opiate Relapse
Sowell, Elizabeth R. -- University of California, Los Angeles
Longitudinal MRI In Prenatal Methamphetamine or Alcohol
Spear, Linda P. -- State University New York, Binghamton
Adolescence: Natural Incentives, Motivation and Affect
Staley, Julie K. -- Yale University
Tobacco Smoking & Nicotinic Acetylcholine Receptors
Stein, Lynda A. -- Brown University
Motivation and Skills For THC/Etoh+ Teens In Jail
Stein, Michael D. -- Rhode Island Hospital, Providence, RI
A Brief Marijuana Intervention For Adolescent Women
Stine, Susan M. -- Wayne State University
Maternal Opioid Treatment: Human Experimental Research
Strain, Eric C. -- Johns Hopkins University
Medications Development for Drug Abuse Disorders
Swartzwelder, H. Scott -- Duke University
Developmental THC Sensitivity In Male and Female Rats
Taylor, Palmer -- University of California, San Diego
Nicotinic Receptor Template-Guided Drug Design
Thomas, Brian F. -- Research Triangle Institute
Analogs: Unique Probes for Cannabinoid Receptors
Tompkins, Christopher P. -- Brandeis University
Adolescent Primary Care Adoption of Substance Use SBI
Tsuang, Ming T -- University of California, San Diego
Alternate Phenotypes of Substance Abuse
Unger, Jennifer B. -- University of Southern California
Acculturation and Drug Use in Family and Peer Contexts
Unterwald, Ellen M. -- Temple University
Cocaine-Induced Opioid, Dopamine & Behavioral Changes
Vanyukov, Mcihael M. -- University of Pittsburgh at Pittsburgh
Substance Use Disorder Liability: Candidate Gene System
Wang, Gene-Jack -- Brookhaven Science Associates-Brookhaven National Lab
PET In Obese Monkeys
Watson, Donnie W. -- Friends Research Institute, Inc.
Substance Use and HIV Prevention
Wells, Gregg B. -- Texas A&M University Health Science Center
Bacterial Proteins in the Nicotinic/GABA Receptor Family
Wenzel, Suzanne L. -- Rand Corporation
Prevention for Impoverished Young Women In Shelters
Werch, Chudley E. -- University of Florida
Brief Positive Image Communications for Adolescents
Werch, Chudley E. -- University of Florida
A Selective Prevention Program For High School Seniors
Wetter, David W. -- University of Texas MD Anderson Cancer Center
Group Therapy for Nicotine Dependence
Wigdahl, Brian -- Drexel University College of Medicine
High Specificity HIV-1 Markers Predictive of Neuro-AIDS
Winder, Danny G. -- Vanderbilt University
Periadolescent Noradrenergic Regulation In the BNST
Windle, Michael T. -- University of Alabama at Birmingham
Parenting, Adolescent Substance Use and Delinquency
Wood, Evan -- University of British Columbia
Evaluating the Natural History of Injection Drug Use
Yacoubian, George S. -- Pacific Institute for Research and Evaluation
Preventing Club Drug Use Among Rave Attendees