Strategic Planning Workgroup on the Complexity of Substance Use Disorders and the Continuum of Substance Use Problems

Workgroup Proposal


The central concepts of the Workgroup’s recommendations are: 

Substance Use Disorders (SUDs) commonly co-occur with psychiatric and medical conditions, disruptions in neurological, cognitive, self-regulatory, and other impaired behavioral and biological processes, and impoverishments and obstacles associated with economic, educational, employment, and other social-environmental conditions. Substance use problems which may not meet criteria for a SUD diagnosis are a major concern themselves, as well as a complicating condition of other psychiatric, behavioral, and medical conditions.

The most accurate description of at least some patterns of the SUD phenotype is a characterization involving a complex of disorders, dysfunctions and deficient conditions. Precise description of SUDs and substance use problems must be understood from a developmental and developmental psychopathology approach, considering the trajectory of substance use initiation, addiction, recovery, and relapse as they relate to developmental stages, transitions, and influences. Further, the high prevalence of psychiatric comorbidity involving SUDs — or at least substance use problems — in addition to the high prevalence of impaired behavioral development and developmental transitions of individuals with SUDs or other substance use problems strongly suggest that common underlying substrates may typically be involved.

There is general agreement that the dynamic interplay between problematic substance use and SUDs, on the one hand, and the complex of associated detrimental factors, on the other, has important implications for the status of the affected individuals and the interventions which may improve their well-being. Despite this, much SUD-focused research does not seek to address these interactions, and often deliberately attempts to screen out or control for the complexities, treating them as noise masking the signal.

Further, insufficient consideration of the complex relationships between coexisting SUDs and other impairing conditions has limited the development of maximally effective interventions. This has been magnified by inadequacies in the health care systems that do not provide services that are responsive to the multiple interconnected problems experienced by most patients with SUDs and substance use problems.

The Precision Medicine Initiative, implemented primarily by the NIH, envisions a near future in which treatment and prevention protocols take into account individual differences and needs as well as individual variability in genes, environment, and lifestyle. The workgroup endorses the view that this is a worthwhile ultimate clinical aim of what we hope will be a concerted effort to investigate the heterogeneity of people with SUDs and substance use problems. That critical clinical goal can only be reached by the careful accrual of systematic research to characterize the nature of the complexity; to evaluate the impact of various complex factors on substance use problems and disorders and vice versa; to develop and assess clinical methods for addressing complex issues in clinical practice; and to seek and evaluate approaches to optimize health care organizational and system considerations for effective integration of these methods.

The workgroup identified three research priority areas that can significantly increase our understanding of the complexities of people with substance use disorders and the continuum of substance use problems. Within each area, more specific research priorities are described in bullets expounding on the three areas; they are listed in order of importance and feasibility for each area. The bullets listed in bold type were ranked by the Workgroup as having the highest overall priority for Complexities research. The Workgroup ranked the underlined bullets as being in the second tier of overall priority with those in plain type being in third tier. However, all bullets represent priorities that the Workgroup endorses.

Priority 1

Conduct research to characterize substance-using individuals with complex conditions that relate to multiple dysfunctions and problems and study their different trajectories of substance use initiation, addiction, recovery, and relapse. This includes those with diagnosable substance use disorders, as well as individuals with emerging, concurrent, and manifest substance use problems that do not meet criteria for diagnosis of a clinical disorder.


  • Investigate the influence of genetic and environmental factors, rearing environment and family function, maternal and parental stress, and social determinants of addiction, and identify the implications of these influences on optimal interventions and outcomes. Seek opportunities to take advantage of existing research platforms and infrastructure, such as the Adolescent Brain Cognitive Development (ABCD) study.
  • Investigate developmental trajectories of SUDs, different patterns of influences on different trajectories, and the optimally effective interventions and outcomes.
  • Use epidemiological, population based, clinical, and case method research to identify and investigate the common patterns of complex disorders and problems experienced by individuals with SUDs and the continuum of substance use problems.
  • Further develop and evaluate methods to screen for and assess SUDs and developing or subclinical substance use in general and pediatric-adolescent medical and dental settings, emergency department, urgent care, and hospital settings, specialty care settings including child and adolescent psychiatry, psychology, and educational-developmental assessment, schools and colleges, and criminal justice settings. Determine the barriers to adoption of screening and approaches to further implementation and to facilitate the adoption of validated screening/assessment methods, conduct research to evaluate the effectiveness of the methods in improving SUD outcomes and other health and quality of life outcomes, and conduct implementation research to assess provider, organization, and system factors that can impact adoption.
  • Establish models for phenotyping that recognize and capture the common underlying causal substrates that can contribute to the development of both SUDs and other impairments and determine the implications of these influences on optimal interventions and outcomes. Incorporate findings and models from developmental psychopathology research to further this goal.
  • Use epidemiological, population based, clinical, and case method research to identify and investigate the role of the use of multiple and/or different combinations of substances and their impact on the continuum of substance use problems, optimally effective interventions, and outcomes.
  • Translate multiplicity of conditions and mechanisms involved into developing methods to screen for and clinically assess the substance-using population, across the continuum of substance use problems.

Priority 2

Explore, evaluate, and implement novel approaches for characterizing the complex phenotypes of people with SUDs and substance use problems.


  • Consider the development of a phenotypic system based on a framework of functional domains, similar to the NIMH RDoC framework and the NIAAA AARDoC framework. Integrate results of basic research and neurocircuitry findings into the framework that would encompass molecular factors, and link those to neurobiological diagnosis.
  • Determine the extent and ways in which the most common patterns of SUDs and substance use problems indicate that their fundamental character and phenotype involves a complex of multiple problems including disorders, dysfunctions, and social- environmental obstacles and deficits.
  • Conduct secondary analyses of existing datasets, such as the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) dataset, data from the Clinical Trials Network (CTN), and data collected as part of NIDA funded investigator grants in order to characterize the constellations of multiple factors that are present in complex phenotypes of people with SUDs and substance use problems.
  • Conduct research to develop methods for characterizing non-treatment-seeking populations of individuals with problematic substance use behaviors, in order to better understand these populations’ patterns of function and substance use trajectories.
  • Collaborate with Collaborative Research on Addiction at NIH (CRAN) partners and other agencies and non-federal partners to develop and implement optimal methods for harmonizing and aggregating biomedical big data across large studies and clinical datasets, to enable capturing domain-level factors that fit into more systematic characterization of patients’ complex phenotypes. Continue to investigate and encourage the adoption of common data elements into electronic health record systems to facilitate the harmonized documentation of substance use information and other related data. Continue to work with other federal partners to support research that cuts across the domains of other Institutes and agencies.
  • Extend existing animal models of substance use and addiction and/or animal models of other conditions or environmental factors for use in the study of interactions among drug exposure and addiction, other co-occurring conditions, and environmental influences, mapping the overlap and defining boundaries where possible.

Priority 3

Recognizing the complexities of SUD patients requires reconsideration of the standards, qualifications, and practices necessary for effective service systems, appropriate interventions, successful implementations, and competent treatment professionals. Building upon the research conducted to address Priority 1 and Priority 2, but proceeding without delay where possible, engage in a multi-pronged research and implementation effort aimed at improving the treatment and prevention services available and accessible to patients with SUDs and complex complicating conditions and other factors.


  • Conduct research to determine how effectively interventions in current use address the complex needs of patients with SUDs; continue to study existing approaches for simultaneously addressing SUDs and co-occurring conditions. Investigate the relative effectiveness of interventions at various levels of substance use (mild, regular, daily).
  • Develop approaches and algorithms for solo and combined pharmacologic and behavioral treatment methods in patients with co-occurring conditions and comorbidities that would be the basis for personalized treatment of addiction. Utilize the progress in neurobiology/neurocircuitry and pharmacogenetics of addiction.
  • Investigate the extent to which SUD treatment providers (and general health care providers) are well trained and prepared to assess and address their patients’ co-occurring conditions and other problems; conversely, investigate how well trained and prepared other health care and social services providers are to assess and address their patients’ substance use disorders and problems, and investigate the impact of the level of training and preparation on patient outcomes.
  • Assess the effectiveness of linkage and referral protocols to develop efficient models for connecting patients with the specific medical and psychiatric care, and social services, required.
  • Investigate relevant implementation factors that can affect the adoption of novel treatment and prevention approaches, including issues of increased clinician effort, diversion and overstretching of other health care resources, use of technological aids, and family and community support.
  • Investigate the longer term outcomes of different treatment paradigms and approaches (pharmacological, psychotherapeutic, structural changes, combined, 12 step, etc.), and, in addition, outcomes of different approaches in relationship to the provider professional characteristics and qualifications.
  • Conduct research on implementation of new interventions in multiple types of systems.
  • In order to ameliorate inadequacies identified in investigations of the impact of provider qualifications and treatment approaches on treatment outcomes, conduct research to develop, evaluate, and improve training courses and programs aimed at various professional groups on treatment of SUDs and the continuum of substance use problems including their intersection with other conditions and complexities.
  • Conduct research to develop and evaluate novel holistic treatment approaches, including integrated interventions, coordinated care, linkage and referral protocols.
  • Transition to developing pharmacologic and other treatment approaches to addiction in pathophysiologically homogenous groups of patients versus those currently defined by subjective behaviorally-based descriptive approaches.
  • Set up frameworks to implement personalized combined interventions (e.g., combined pharmacological and behavioral therapy, polypharmacy) addressing the multiplicity of co-occurrences and comorbidities of addiction phenotypes.
  • Investigate the impact of changes in service provision as a result of changes in health care insurance and financing (e.g. ACA).


NIDA co-chairs:  Meyer Glantz, PhD and David Liu, MD
External Scientific Matter Experts: Kathleen Brady, MD, PhD; Joseph Guydish, PhD, MPH; Lisa Metsch, PhD; Jenae Neiderhiser, PhD; Edward Nunes, Jr, MD; John Rotrosen, MD; Constance Weisner, DrPH, MSW
NIDA staff:  Will Aklin, PhD; Maureen Boyle, PhD; Emily Einstein, PhD; Jacques Normand, PhD; Karran Phillips, MD, MSc; Tonya Ramey, MD, PhD; Geetha Subramaniam, MD; Dave Thomas, PhD; Susan Volman, PhD