Strategic Plan

National Institute on Drug Abuse

National Institutes of Health

U.S. Department of Health and Human Services 

Strategic Plan

National Institute on Drug Abuse

National Institute on Drug Abuse 

National Institutes of Health

U.S. Department of Health and Human Services

6001 Executive Boulevard

Bethesda, MD 20892-9561
ii

This publication is in the public domain and may be used or reproduced 

in its entirety without permission from NIDA. Citation of the source is appreciated. 

NIH Publication Number 10-6119 

Printed September 2010
1

Contents

INTRODUCTION...................................2

EXECUTIVE SUMMARY.......................4

FOCUS ON PRESCRIPTION 

DRUGS..................................................7

I. PREVENTION ..................................10

Strategic Goal............................................. 10

Objectives .................................................. 10

Introduction––The Value of ResearchBased Prevention Approaches ................... 10

Strategic Approaches to Prevention 

Research.....................................................12

1. How can NIDA research inform the 

 focus of prevention?......................12

2. Why do some people become 

 addicted while others do not?........12

3. Which parts of the brain are 

 involved in drug abuse? ................19

4. How are research results used 

 to improve practice?......................19

Our Vision for the Future of Prevention 

of Drug Abuse and Addiction....................21

II. TREATMENT ..................................21

Strategic Goal.............................................21

Objectives ..................................................21

Introduction––The Value of a Multipronged 

and Integrated Approach to Addiction 

Treatment ...................................................21

Strategic Approaches to Treatment............22

1. How can NIDA research help develop 

 and enhance medications and behavioral 

 therapies to reduce drug abuse and 

 prevent relapse?.............................23

2. What if people have another mental 

 disorder—how does that affect treatment 

 for addiction? ................................29

3. How will treatments be tailored for 

 optimal effectiveness?...................30

4. How will drug abuse treatment reach 

 the people who need it? ................31

Our Vision for the Future of Treatment 

for Drug Abuse and Addiction...................33

III. HIV/AIDS........................................34

Strategic Goal.............................................34

Objectives ..................................................34

Introduction––The Need for Responsive 

Prevention and Treatment Strategies.........34

Strategic Approaches to HIV/AIDS 

Research.....................................................36

1. How has the HIV/AIDS epidemic

 changed over the past few decades 

 in the United States?......................36

2. How does NIDA plan to focus research 

 efforts to better understand and prevent 

 HIV infection in drug abusers and limit 

 its progression?..............................37

3. What can be done to mitigate the 

 health disparities associated with 

 HIV/AIDS? ................................... 39

4. How is NIDA’s HIV research program 

 contributing to global HIV prevention 

 and treatment? ...............................40

5. What are we doing to improve 

 HIV/AIDS treatment and outcomes in 

 drug abusers?.................................41

What Is NIDA’s Vision of the Future?......43

IV. CROSS-CUTTING PRIORITIES....44

Major Goals ...............................................44

1. What are other health conditions 

 that interact with drug abuse and 

 addiction? ......................................44

2. How is NIDA addressing health 

 disparities related to drug abuse 

 and its consequences? ...................45

3. How does NIDA “get the word out” 

 about the many facets of drug abuse and 

 addiction to better prevent it?........46

4. How does NIDA help ensure a continuing 

 supply of well-trained scientists equipped 

 to conduct high-impact drug abuse

 research?........................................47 

5. What are NIDA’s strategic international 

 priorities?.......................................49 

REFERENCES....................................50
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National Institute on Drug Abuse Strategic Plan

Introduction

The mission of the National Institute on Drug Abuse 

(NIDA) is to lead the Nation in bringing the power of science 

to bear on drug abuse and addiction. This charge has two 

critical components: (1) to support and conduct research 

across a broad range of disciplines and (2) to ensure the 

rapid and effective dissemination and use of research results 

to improve practice and inform policy. The ultimate goal 

of NIDA’s drug abuse research program is to reduce the 

burden of drug abuse and addiction*

 and their many adverse consequences 

for individuals and society at large. By advancing the science of addiction, 

NIDA is helping to change people’s perceptions, replacing stigma and shame 

with a new understanding of addiction as a treatable disease. Much like any 

other medical disease, addiction demands a public health solution. 

Indeed, NIDA-supported scientific advances over the past three decades 

have revolutionized our understanding of drug abuse and addiction. We 

have informed the development of more effective prevention and treatment 

approaches and have identified areas where more work is needed. For 

example, while our national research surveys show continuing declines 

in illicit drug use among teens––down 19 percent since 2001, according 

to NIDA’s 2009 Monitoring the Future (MTF) survey of 8th-, 10th-, and 

12th-graders––difficult challenges remain. These challenges include the 

persistence of chronic drug abuse in a considerable number of teens (e.g., 

5 percent of 12th-graders are daily marijuana users, a level statistically 

unchanged since 2001)1

 and the high rates of prescription drug abuse among 

both adolescents and adults. This trend has prompted a near-doubling of 

unintentional poisoning deaths nationwide since 1999,2 mainly from opioid 

analgesic abuse (see “Emerging Issues and Challenges”). 

* “Drug abuse,” as used throughout this report, refers to the repeated use of licit or illicit psychoactive 

substances, which may or may not lead to “addiction,” which is defined as a complex brain disease 

characterized by compulsive, at times uncontrollable, drug craving, seeking, and use that persist even 

in the face of extremely negative consequences. These definitions differ from those in the Diagnostic 

and Statistical Manual of Mental Disorders (DSM), which provides diagnostic criteria for drug abuse 

and dependence, and does not in its present form include the term “addiction.” We use the term 

“addiction” to refer to what the DSM defines as “dependence.” 
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National Institute on Drug Abuse Strategic Plan

We must continue to aggressively meet these challenges and work to prevent 

the often devastating consequences of drug abuse and addiction that affect 

all segments of society. Economic costs alone are estimated to exceed onehalf trillion dollars annually in the United States—including health- and 

crime-related costs, as well as productivity losses, such as those stemming 

from workplace injuries and accidents. In 2008, 20 million Americans, or 8 

percent of the population, aged 12 or older were current (past-month)illicit 

drug users.3

 Staggering as these numbers are, however, they do not fully 

describe the breadth of deleterious public health––and safety––implications, 

which include family disintegration, loss of employment, accidents, failure 

in school, and domestic violence and other crimes. Substance use and abuse 

can also exacerbate a variety of health problems, including the spread 

of infectious diseases such as HIV/AIDS, sexually transmitted diseases 

(STDs), tuberculosis, and hepatitis C. Frequently comorbid with other 

mental disorders, drug abuse also contributes significantly to the risk of 

suicide and suicidal behaviors.4

It is plain to see that drug abuse is a ubiquitous, complex, and urgent 

problem that affects us all. Thus, NIDA continues to engage multiple 

stakeholders across the community in efforts to integrate substance abuse 

and addiction diagnosis, referral, and treatment into standard medical 

practice as well as criminal justice settings, where drug abuse problems are 

widespread. These settings offer good opportunities for treatment, which can 

have considerable societal impact.

The pages that follow describe broad strategies that NIDA plans to implement 

over the coming years. A flexible, dynamic approach allows us to adapt to 

changing needs and take advantage of scientific opportunities as they arise and 

are revealed through our ongoing research.

Nora D. Volkow, M.D. 

Director, NIDA
National Institute on Drug Abuse Strategic Plan

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Executive Summary

For the past three decades, the National Institute on Drug Abuse (NIDA) has led the 

way in supporting research to prevent and treat drug abuse and addiction and mitigate 

the impact of their consequences, which include the spread of HIV/AIDS and other 

infectious diseases. To confront the most pressing aspects of this complex disease and 

to tackle its underlying causes, our strategic approach is necessarily a multipronged 

one. It takes advantage of research programs in basic, clinical, and translational 

sciences. This includes genetics, functional neuroimaging, social neuroscience, 

medication and behavioral therapies, prevention, and health services, including 

effectiveness and cost-effectiveness research. Our burgeoning portfolio has given us a large and 

growing body of knowledge that informs our strategic directions for the future. These directions 

are grouped into four major goal areas, reflected in the sections that follow:

I. PREVENTION

II. TREATMENT

III. HIV/AIDS

IV. CROSS-CUTTING PRIORITIES 

These four sections and accompanying strategic goals and objectives are summarized below.

I. Prevention

Strategic goal: To prevent the initiation of drug use and the escalation to 

addiction in those who have already initiated use. 

Our prevention research has led to today’s 

improved understanding of addiction and 

has positioned NIDA to build upon solid 

epidemiological findings and new insights 

from genetics and neuroscience. Findings 

have revealed myriad contributors to 

addiction and the involvement of multiple 

brain circuits in addiction processes. A major 

goal of our efforts is to better understand 

why some people become addicted while 

others do not. Our prevention efforts 

encompass both illicit and licit drugs, such 

as nicotine and prescription medications. We 

support research that strives to identify the 

factors that put people at increased risk of 

drug abuse or protect them from it. Results 

will lead to more effective counterstrategies, 

particularly to prevent young people from 

ever using drugs in the first place. We are 

applying modern technologies (e.g., genetics 

and brain imaging tools) to our 

prevention studies and are devising creative 

and targeted communications strategies to 

encourage their use. 

NIDA’s Prevention Objectives Include:

1. To identify the characteristics and patterns 

of drug abuse.

2. To understand how genes, environment, 

and development influence the various 

risk and protective factors for drug abuse. 

3. To improve and expand our understanding 

of basic neurobiology as it relates to the 

brain circuitry underlying drug abuse and 

addiction.

4. To apply this knowledge toward the development of more effective strategies to 

prevent people from ever taking drugs and 

from progressing to addiction if they do.
National Institute on Drug Abuse Strategic Plan

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II. Treatment

Strategic goal: To develop successful treatments for drug abuse and addiction 

and improve treatment accessibility and implementation. 

Given the complex interactions of biological, 

social, environmental, and developmental 

factors that underlie drug abuse and 

addiction, NIDA acknowledges the need to 

take a “whole systems” approach to treating 

this disease. We are well-positioned to 

capitalize on recent discoveries that have 

uncovered an expanded range of possible 

brain targets that affect craving, euphoria, 

motivation, learning, memory, and inhibitory 

control––key contributors to addiction and 

relapse. To bring about more customized 

treatments, our comprehensive therapeutic 

research portfolio pushes for more effective 

medication and behavioral therapies. 

Innovative approaches that consider genetic 

variation, comorbid conditions (e.g., mental 

illness, chronic pain), and the addicted 

person’s changing needs over time will 

usher in promising medications to counteract 

drug-induced changes in the brain and 

enhance behavioral therapies. Effectiveness 

research helps us optimize strategies for 

disseminating and implementing researchbased treatments in health care and criminal 

justice settings. This objective requires that 

we continue to strengthen our productive 

partnerships with treatment practitioners, 

state substance abuse programs, and other 

Federal agencies to move proven treatments 

into clinical practice at the community level. 

NIDA’s Treatment Objectives Include:

1. To develop effective medications and 

behavioral interventions to treat drug 

abuse and addiction and to prevent 

relapse.

2. To develop treatments for drug abuse and 

addiction in association with comorbid 

conditions.

3. To develop the knowledge that leads to 

personalized or customized treatments.

4. To translate research-based treatments to 

the community.

III. HIV/AIDS

Strategic goal: To diminish the spread of drug abuse-related human 

immunodeficiency virus (HIV) and minimize the associated health and social 

consequences, including acquired immunodeficiency syndrome (AIDS).

Drug abuse continues to be a major vector 

for the spread of HIV/AIDS through its 

connection with other risky behaviors, such 

as needle sharing and unprotected sex. Our 

research advances the less-acknowledged 

link between drug abuse in general and the 

resulting impaired judgment that can lead to 

risky sexual behavior and HIV transmission. 

This linkage highlights the value of drug 

abuse treatment in preventing the spread 

of HIV. We plan to continue supporting 

primary prevention research to find the most 

effective HIV risk-reduction interventions 

for different populations. Young people are 

a major focus for these efforts, prompting 

strategies that start early and can be 

adapted as the individuals age. NIDA also 

supports research to develop effective 

secondary prevention strategies designed 

to reduce HIV transmission. This includes 

seeking out the best ways to incorporate 

HIV education, testing, counseling, and 

treatment referral, and supporting research 

to identify and overcome barriers such as 
National Institute on Drug Abuse Strategic Plan

6

stigma and access to treatment for HIV and 

drug abuse. NIDA also sponsors research to 

learn more about the multiple interactions that 

occur with neurological complications from 

HIV, substance abuse, and other comorbid 

psychiatric disorders. This knowledge can 

inform the development of more responsive 

counterinterventions. Additionally, we 

continue to target HIV/AIDS-related health 

disparities and integrate HIV/AIDS initiatives 

worldwide. 

NIDA’s HIV/AIDS Objectives Include:

1. To support research to better understand 

the etiology, pathogenesis, and spread 

of HIV/AIDS among drug-abusing 

populations.

2. To help prevent the acquisition (primary 

prevention) and transmission (secondary 

prevention) of HIV among drug abusers 

and their partners.

3. To decrease the health disparities 

associated with HIV/AIDS.

4. To support international research on the 

intertwined epidemics of drug abuse and 

HIV/AIDS.

5. To improve HIV treatment and outcomes 

in drug abusers through a better understanding of interactions with drugs of 

abuse, HIV/AIDS disease processes, and 

the medications used to treat both.

IV. Cross-Cutting Priorities 

Several additional priority areas span NIDA’s portfolio and contribute to our 

overall mission to prevent or reduce drug abuse and addiction. These areas are 

highlighted below.

1. To foster research on other health 

conditions that may inform, influence, 

or interact with drug abuse and addiction 

(e.g., pain, compulsive behavioral disorders).

2. To decrease health disparities related to 

drug addiction and its consequences.

3. To educate a variety of audiences (e.g., 

criminal justice, medical, and educational 

systems in the community; media; and 

legislators) about the science underlying 

drug abuse.

4. To train and attract new investigators 

with diverse experiences––including 

those from minority or disadvantaged 

backgrounds––and to actively recruit 

chemists, physicists, bioengineers, and 

mathematicians to conduct translational 

research on drug abuse.

5. To promote collaborative international 

research activities that address nicotine 

addiction, HIV/AIDS, and emerging 

trends, as well as training and dissemination of science-based information on drug 

abuse.
National Institute on Drug Abuse Strategic Plan

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Focus on Prescription Drugs

Unlike illicit drug use, which shows a continuing downward trend, prescription drug abuse––particularly of stimulants and opioid pain medications––

has seen a continual rise through the 1990s, and since 2002 has been at 

unacceptably high levels among persons age 12 or older.5

†

 The terms “prescription drug abuse” and “nonmedical use” are used interchangeably in this document and are based on the definitions 

used by most national surveys measuring nonmedical use (i.e., the intentional use of an approved medication without a prescription, 

in a manner other than how it was prescribed, for purposes other than prescribed, or for the experience or feeling the medication can 

produce). Misuse refers to unintentional use of an approved medication in a manner other than how it was prescribed.

Figure I-1

8 of the top 13 drugs most commonly abused by high 

school seniors are prescription or over-the-counter

Past-Year Drug Abuse Among 12th-Graders, 2009

Source: University of Michigan, 2008 Monitoring the Future Survey

Nature and Scope 

of the Problem

In 2008, approximately 

6 million Americans 

reported current (in the 

past month) nonmedical 

use† of prescription 

drugs—more than the 

number abusing cocaine, 

heroin, hallucinogens, 

and inhalants combined.6

According to the 

Monitoring the Future 

(MTF) survey supported 

by NIDA, 8 of the top 13 

drugs most commonly 

abused by high school 

seniors are either 

prescribed or purchased 

over the counter (see Figure I–1). 

While the MTF surveys students in the 

8th, 10th, and 12th grades, other survey 

research shows that young adults ages 

18–25 are by far the greatest users 

overall. This age group also shows the 

biggest increases, compared to others, 

in past-month, past-year, and lifetime 

non-medical use between 2002 and 2008 

(National Survey on Drug Use and Health 

[NSDUH], 2009). Even though not prescribed 

for them, many are using prescription drugs 

for their intended purposes, such as to 
National Institute on Drug Abuse Strategic Plan

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relieve pain in the case of prescription opioids, 

or to enhance alertness in the case of attentiondeficit hyperactivity disorder (ADHD) medications. 

A common perception is that because these are 

legitimate pharmaceuticals that emanate from a 

controlled system, they are less harmful than illicit 

drugs. This belief is false, as evidenced by rising 

numbers of people overdosing on or becoming 

addicted to prescription drugs. Whether the intent is 

to relieve pain, stay alert for a test, or get high, any 

use without a physician’s evaluation or monitoring 

can pose potentially grave health risks. 

At the other end of the age spectrum is the 

swelling population of older people who are 

frequently prescribed psychotherapeutic drugs and 

who may be especially vulnerable to the health 

consequences of their abuse or misuse. This is 

especially true if other medications or underlying 

health conditions are involved. Thus, prescription 

drug abuse and misuse affects populations of 

all ages and is further complicated by differing 

motivations and consequences for each. 

Different Approach Needed From That 

for Other Licit or Illicit Drugs

Because they can greatly benefit health as well 

as pose risks, prescription drugs present several 

challenges on how best to guard against their 

abuse. 

Some patients, such as those with chronic pain, 

may require prescription painkillers to effectively 

alleviate their suffering. But for these patients and 

their physicians, the issues can quickly become 

complex and difficult to manage. For example, 

physicians may need to decide whether presenting 

symptoms indicate a need to increase the dose of 

an opioid analgesic to adequately manage pain, or 

signal a potential drug abuse problem. Moreover, 

predicting who is at greatest risk for addiction is a 

difficult and increasingly relevant problem, one that 

is particularly urgent for war veterans returning from 

Iraq and Afghanistan who sustain serious injuries. 

Thus, NIDA continues to diligently support research 

in this area, including pursuing pain medications 

that have little or no addiction liability.

Another challenge involves crafting prevention 

messages to effectively combat the abuse of 

prescription drugs without alarming patients who 

need them. Because physicians are usually the 

prescribers of these medications, involving them in 

our efforts to curb prescription drug abuse is critical. 

Dramatic increases in the number of prescriptions 

written, greater social acceptance of using medications, and aggressive marketing by pharmaceutical 

companies have likely contributed to the current 

broad “environmental availability” of prescription 

drugs (see Figure I–2). This notion is consistent with 2008 NSDUH survey data wherein most 

people report obtaining prescription drugs from 

friends and family members for whom they were 

prescribed. Thus, physicians need to be cognizant 

of the various risks and serve as the front-line responders when a problem is suspected, particularly 

if a patient may be developing abuse or addiction 

problems. NIDA continues to engage physicians 

and physicians-in-training to raise their awareness.

We are bolstering efforts to test and evaluate 

treatments for addiction to prescription drugs, 

tailoring interventions according to type of 

medication and reason for its abuse. These 

variables are often biased by age and gender. 

To stay on top of who is using and why, NIDAsupported researchers continue to gather 

information about the latest trends through 

large-scale epidemiological studies investigating 

the patterns and sources of nonmedical use, 

particularly in high school and college students. 

These years are often when young people initiate 

or increase their abuse of prescription medications 

and other drugs. 

Again, our approach must address the question of 

balance, which is difficult to achieve, so that people 

suffering from chronic pain, ADHD, or anxiety can 

get the relief they need while minimizing abuse 

potential.
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National Institute on Drug Abuse Strategic Plan

Figure I-2

Projected Number of Prescriptions for Stimulants* Dispensed by 

U.S. Retail Pharmacies, 1991-2009

*excludes modafinil and atomoxetine products

Dramatic increases in stimulant and opioid prescriptions

Source: SDI’s Vector One®: National 

Total Number of Prescriptions for Hydrocodone and Oxycodone 

Products Dispensed by U.S. Retail Pharmacies, 1991-2009
National Institute on Drug Abuse Strategic Plan

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I. Prevention

Strategic Goal

To prevent the initiation of drug use and the escalation to addiction in 

those who have already initiated use.

Objectives

1. To identify the characteristics and patterns of drug abuse.

2. To understand how genes, environment, and development influence 

the various risk and protective factors for drug abuse. 

3. To improve and expand our understanding of basic neurobiology as 

it relates to the brain circuitry underlying drug abuse and addiction.

4. To apply this knowledge toward the development of more effective 

strategies to prevent people from ever taking drugs and from 

progressing to addiction if they do.

Introduction: The Value of Research-Based 

Prevention Approaches

The basic and clinical research sponsored by NIDA for more than 30 years 

has led to a vast and growing body of knowledge that informs our strategic 

directions for the future. And while multiple challenges remain, NIDA continues 

to capitalize on opportunities to meet our short- and long-term goals. These are, 

respectively, to prevent those who are abusing drugs from intensifying their 

abuse and becoming addicted, and to develop and deploy the best strategies to 

prevent drug use. 

This expanding body of knowledge is leading to evidence-based prevention 

strategies that build upon solid epidemiological, genetic, and neuroscience 

research. Our prevention portfolio continues to examine the impact of both 

micro- (e.g., family, peers) and macro- (e.g., poverty, stigma) environments, 

using a data-driven approach to prevent drug abuse and addiction in all 

populations. 

Although NIDA recognizes that addiction only affects a subset of those 

exposed, any illicit or inappropriate drug exposure can place an individual 

at risk for serious health consequences. Even a one-time drug experience 
National Institute on Drug Abuse Strategic Plan

11

could lead to accidents (e.g., drugged 

driving) or disease (e.g., HIV/AIDS) 

stemming from drug intoxication. 

Because experimentation is a common 

motivation for adolescents to use drugs, 

our prevention messages must be aimed 

at keeping young people from trying 

drugs in the first place. 

Indeed, the adolescent population 

is of particular interest for NIDA 

because drug abuse typically begins 

during this period of heightened risktaking (see Figure 1). By supporting 

epidemiological studies, such as the 

MTF survey, we are able to identify 

emerging trends among adolescents and 

guide responsive national prevention 

efforts. For example, MTF revealed that 

in 2008, prescription medications along 

with over-the-counter drugs (cough 

medicine), accounted for 8 of the top 13 

drug abuse categories reported by 12thgraders7 (see “Focus on Prescription 

Drugs”). 

NIDA is vigorously pursuing research 

on the effects of abusable substances 

and how multiple factors––genes, the 

environment, developmental variables, 

and their interactions––influence 

vulnerability to and protection 

against addiction. The impact of drug 

abuse varies throughout the lifespan. 

NIDA therefore supports research 

that spans from prenatal exposure to 

older adulthood to uncover how life 

transitions influence the likelihood and 

trajectory of drug abuse and addiction. 

Future studies will examine how 

developmental shifts interact with genes 

and the environment to influence disease 

vulnerability and progression. 

Adding to this understanding is our growing knowledge of 

the multiple brain circuits associated with drug abuse and 

addiction, such as those implicated in reward, inhibitory control, 

emotional states, learning and memory, and interoception 

(sensitivity to stimuli originating inside the body). In addition, 

basic research on brain development is illuminating how age 

affects the response to drugs, as well as addiction propensity and 

progression. With the powerful tools of modern neuroimaging, 

we can “see” how various brain mechanisms interact with drugs 

of abuse to influence decisionmaking (e.g., willingness to take 

risks). We can do this in real time, throughout development, and 

as people engage socially. 

Finally, NIDA is moving aggressively to tap into the power of 

imaging research in order to develop more effective prevention 

interventions. We know that specific target audiences––

adolescents, young adults, pregnant women, and older adults––

require tailored prevention approaches to more effectively 

reduce their risks and enhance the value of protective factors. 

Source: National Epidemiologic Survey on Alcohol and Related Conditions, 2003

Individuals who initiate drug use early are more 

likely to develop subsequent dependence.

Figure 1
National Institute on Drug Abuse Strategic Plan

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Sidebar 1

Whether or not the exposure to drugs of 

abuse will lead to addiction is a function 

of the interaction between multiple 

domains, including genetic background, a 

person’s response to a drug, and his or her 

environment and developmental stage.

Strategic Approaches to 

Prevention Research

The following section is organized according to four 

guiding questions to describe NIDA’s approach of using 

basic, clinical, and health services research to improve 

our prevention efforts. 

1. How can NIDA research inform the focus of 

prevention?

NIDA continues to identify areas of particular concern 

and to spot trends early through our epidemiological 

work in the field. We monitor national and regional 

substance abuse trends through our nationwide 

Community Epidemiology Work Group (CEWG), the 

MTF survey, and other sources. These mechanisms help 

us identify the who, what, where, and when 

of drug abuse trends as well as associated 

attitudes and consequences. 

We also encourage research that capitalizes 

on other databases available through our 

sister Institutes and Federal agency partners,

such as the National Epidemiologic Survey 

on Alcohol and Related Conditions, 

sponsored by the National Institute on 

Alcohol Abuse and Alcoholism (NIAAA), 

and the National Survey of Parents and 

Youth, sponsored by the White House Office

of National Drug Control Policy. In addition, 

we support a number of longitudinal studies 

that gather information on children’s 

cognitive and emotional development, as 

well as their vulnerability to addiction later 

in life if they have been exposed to drugs.

To continue to make the most of these 

rich data sources and to improve upon 

them, NIDA is encouraging researchers to 

include genetics in epidemiological studies, 

whenever relevant, to try to zero in on 

gene-environment interactions at different 

developmental stages. This potential treasure 

trove of genetic information, combined with

brain imaging data, is likely to reveal even 

more about the trajectory of addiction and 

the contribution of social–environmental 

factors. This, in turn, will lead to 

increasingly customized interventions for 

those at risk.

2. Why do some people become addicted 

while others do not?

Our research has already identified many 

factors that can either enhance or mitigate an 

underlying propensity to initiate or continue 

drug use. Exposure to drugs is, of course, 

an environmental risk factor—along with 

socioeconomic status, quality of parenting, 

and peer group influence, to name a few. 

Advances in genetics are allowing us to 

identify biological factors, such as genetic 
National Institute on Drug Abuse Strategic Plan

13

polymorphisms (normal genetic variations) Why genes matter

that confer increased vulnerability or A person’s genetic makeup plays an important role in his protection. Epigenetics research––the study or her addiction vulnerability and, possibly, in the decision of long-term changes in gene function that to take drugs in the first place. Research shows that result from environmental impacts––will approximately 50 percent of the predisposition to addiction lead to discoveries about the dynamic can be attributed to genetics. However, this influence is interactions of genes with environment, not a simple one. Like many complex diseases, addiction along with developmental factors (see is likely to display a multifactorial pattern of inheritance— Sidebar 1). We know that addiction is a which means that many genes contribute, each having multifactorial, complex, and chronic disease a relatively small effect—influenced by environmental of the brain so a better understanding factors. A better understanding of these genetic influences of the many contributors to drug abuse is critical to our prevention efforts. Indeed, ongoing and addiction, and the different ways developments in the field of high-throughput genomic they operate at the individual, group, and screens herald a much faster means of identifying community levels, is critical to designing specific gene variants that can contribute to (or guard more effective prevention messages. against) addiction. The resulting knowledge could then 

be leveraged preventively to identify people at risk, well The influence of biological factors before a substance use disorder emerges. on a person’s addiction risk

Numerous biological factors confer In addition to the genetic vulnerabilities one is born 

risk of or protection against drug abuse with, gene function or gene expression is also influenced 

and addiction. These include genetics, by environmental events. These in turn can alter brain 

developmental stage, gender, comorbid function and behavior, and ultimately addiction risk or 

diseases, and pharmacological response resilience. Epigenetic changes can be triggered, not just 

or sensitivity to a drug’s effects. As by drug exposure, but also by factors such as maternal 

particular biological factors emerge from behavior, aggression, and stress. Understanding the 

epidemiological and clinical studies, they causes and effects of epigenetic changes will engender 

can be put to the test in animal models (and interventions to counter, prevent, or capitalize on them. 

possibly even in vitro) to help validate, How a person’s environment affects his or her trace, and explore their mechanisms for 

conveying addiction risk. risk of drug abuse or addiction

Working in concert with biological risk and protective The use of animal models allows the factors are those that stem from our environment as manipulation of genetic, environmental, we progress from fetal development to adulthood. For and developmental conditions to investigate example, an individual’s genetic predisposition to drug related changes in the brain and behavior. abuse will never manifest itself without drug exposure. A NIDA researchers have developed relevant variety of factors need to be taken into account and better models in different species that help reveal characterized to fully understand what contributes to drug various behavioral components of addiction. abuse and addiction and what is amenable to modification. For example, these models can help tease 

apart susceptibility to drug taking, the role 

of stress and social factors in triggering 

drug-taking behaviors, and the transition 

from controlled intake to compulsive drug 

self-administration. 
National Institute on Drug Abuse Strategic Plan

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Social neuroscience. The initial decision to 

use drugs is often made in group situations, 

yet little is known about how social dynamics 

influence the basic cognitive and motivational 

processes that go into that decision and 

others involving risky behaviors. Social 

neuroscience seeks to explain social behavior 

in terms of its underlying neurobiological 

mechanisms (genetic, epigenetic, hormonal, 

biochemical, physiological). This discipline 

is being increasingly applied to understand 

a range of behaviors and experiences, 

including aggression, affiliation, attitudes, 

social decisionmaking, moral judgment, 

sexuality, communication, and others. NIDA 

is encouraging basic and clinical research 

that applies a social neuroscience perspective 

to drug abuse and decisionmaking over the 

course of a person’s lifespan.

Stress and trauma. Particularly if 

experienced early in life, stress and trauma 

can alter the brain and the response to stress 

throughout life. In humans, subsequent social 

stressors such as economic adversity, isolation, 

and parental abuse and neglect are known 

to influence age of first drug use, level and 

duration of use, and psychiatric comorbidities. 

The reasons are complex, but many people 

who have experienced trauma may turn to 

alcohol or other drugs to help themselves feel 

better. Often, a vicious cycle ensues in which 

abusing drugs to self-medicate engenders 

additional stress and leads to repeated 

substance abuse. 

NIDA is seeking to better understand 

how these variables influence drug abuse 

vulnerability (see Sidebar 2) and how they 

work in concert with a person’s larger 

environment. Studies continue to reveal 

that the interplay of biological and social 

influences affects individual choices and 

decisions about drugs. To learn more about 

this interplay, NIDA supports research to 

develop a comprehensive classification of 

Sidebar 2

Environmental Factors Can 

Increase Drug Abuse Risk

Research demonstrates a relationship 

between illicit drug use and adverse 

childhood experiences (ACEs). A 

retrospective study cohort of 8,603 adults 

who attended a primary care clinic in 

California completed a survey about 

childhood abuse, neglect, and household 

dysfunction; illicit drug use; and other healthrelated issues. Each ACE reported increased 

the likelihood for early drug use (by age 14) 

two- to fourfold and raised the risk of later 

addiction; people with 5 or more ACEs were 

7–10 times more likely to report illicit drug 

use problems than those with none. 

Why it’s important: Research is needed 

to understand and evaluate the impact of 

environment and experience on the initiation 

of drug use and subsequent problems at 

any age. Progress in reducing drug use will 

demand attention to various types of stressful 

experiences, such as those identified in this 

study.

Source: Dube et al., 2003 – J Pediatr 111:564–572 
National Institute on Drug Abuse Strategic Plan

15

social and built environments (including 

family, peers, school, neighborhood, 

community, and culture). 

Neurobiological underpinnings. Research 

is needed to unravel how environmental 

factors like social stress induce brain changes 

that interact with drugs of abuse and alter 

behavior. We also need research to learn how 

to identify ways to counter or minimize stress 

effects. Animal research has begun to reveal 

mechanisms by which environmental variables 

can positively and negatively affect drug abuse 

risk. Further, brain imaging technologies 

are increasingly being used as part of drug 

abuse and addiction research in both animals 

and humans to illuminate how the brain is 

affected by stress and social influences (e.g., 

peer pressure) within the context of drug 

abuse or decisionmaking (see Sidebar 3). A 

better understanding of how social and other 

environmental factors influence behavior and 

how they might be reversed is important for 

prevention, particularly in adolescents.

Why young people are at special risk

The trajectory of drug use, abuse, and 

addiction typically begins in adolescence but 

sometimes even earlier. The greater risk of 

young people becoming addicted involves 

two major components. First, children and 

adolescents are naturally inclined, and much 

more likely than adults, to engage in risky 

behaviors, which may include experimenting 

with drugs of abuse. Current evidence––

derived mainly from human brain imaging 

studies––suggests that this phenomenon stems 

from still-developing brain regions involved 

in judgment, decisionmaking, and emotional 

control, which do not fully mature until early 

adulthood (see Sidebar 4). Second, because 

the young developing brain is constantly 

changing—physically and functionally—the 

effects of psychoactive drugs may be more 

pronounced and enduring if drug use starts 

Sidebar 3

Study Sheds Light on the 

Underlying Connections Between 

Social Stress and Drug Abuse 

Behaviors

In this study, monkeys that were transferred 

from isolation to group living and became 

dominant in the new social structure underwent biological changes that gave them 

stronger 

dopamine 

signaling and 

less interest 

in cocaine 

compared 

to animals 

that became 

submissive. 

These findings demonstrate that 

alterations 

in an organism’s social 

environment 

can produce 

profound 

biological 

changes that 

have important behavioral consequences, including vulnerability to cocaine’s 

rewarding effects.

Why it’s important: The 

emerging field of social neuroscience will examine how 

neurobiology and the social 

environment interact in abuse 

and addiction processes to influence initiation, maintenance, 

treatment, and relapse.

Source: Morgan et al., 2002 – Nat Neurosci 5:169 
National Institute on Drug Abuse Strategic Plan

16

early. Although this question is difficult to 

investigate in humans, animal studies have 

provided considerable evidence supporting this 

hypothesis. NIDA continues to encourage both 

basic and clinical research in this area. 

Even the very earliest exposure (i.e., in 

utero) can affect a variety of cognitive 

and mental health outcomes later in life. 

Abilities related to problemsolving, memory, 

learning, language, and reasoning are all 

vulnerable, as is a person’s risk for addiction. 

For example, prenatal exposure to nicotine 

was recently shown to influence the risk 

for nicotine addiction 30 years later.8

 This 

outcome could reflect nicotine’s ability to 

influence the expression of genes affecting 

fundamental processes in the developing 

brain. NIDA-supported longitudinal studies 

of prenatal exposure to several drugs of abuse 

help us understand the drug-specific impacts 

on developmental outcomes. These include 

outcomes affecting health, cognition, executive 

function, emotion, and attention regulation. 

How drug abuse risk varies across 

the life span

Significant developmental shifts occur 

throughout life and can shape drug abuse 

trajectories. Such transitions include posthigh school, a time of greater independence 

(associated with increased substance use and 

progression from abuse to addiction); adult 

role transitions, such as marriage, parenting, 

and full-time work (associated with decreased 

substance abuse); and older-age transitions, 

such as retirement and age-related medical 

issues (associated with increased potential for 

substance abuse-related medical consequences). 

Because the risk factors associated with a 

person’s biology and environment vary as a 

function of age, NIDA supports studies across 

all age groups, with a particular focus on life 

transitions. 

Sidebar 4

Differential Rates of Brain 

Maturation May Account for 

Teenagers’ Risk-Taking Proclivity

This study reported that the nucleus 

accumbens, a part of the brain’s reward 

circuitry, matured faster than the orbital 

frontal cortex, which is involved in behavioral 

inhibition and control. This pattern of 

brain development was associated with a 

different valuing of rewards by adolescents 

as compared with adults and children, 

suggesting that the relative immaturity of the 

orbital frontal cortex in adolescents might 

underlie their propensity toward risk-taking 

behavior. 

Why it’s important: These findings 

suggest that maturing subcortical systems 

become disproportionately activated (relative 

to later maturing top-down control systems), 

biasing the adolescent’s action toward 

immediate gratification over long-term gains.

Source: Galvan et al., 2006 – J Neurosci 26:6885 

nucleus 

accumbens

orbital frontal 

cortex

Rate of maturation
National Institute on Drug Abuse Strategic Plan

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It is clear that the course of drug addiction 

is related to both biological and cultural 

transitions. However, we need to further 

investigate how these developmental 

shifts interact with individual genetic and 

environmental backgrounds to influence the 

course of the disease. Doing so will lead to 

developmentally appropriate interventions.

The role of gender in drug abuse 

and addiction

Research has repeatedly shown that a broad 

spectrum of differences related to gender (e.g., 

social environment, physiological response to 

drugs, sexual dimorphisms in brain circuitry 

and hormones) can greatly influence not 

only drug abuse trajectories but also the 

characteristics of prevention (and treatment) 

programs that work best for either females or 

males. 

For example, research has identified the 

menstrual cycle (i.e., the estrous cycle in 

animals) as a determinant of drug action––

pharmacokinetic and behavioral––in both 

animals and humans. In animals, many 

behavioral effects of drugs are influenced 

by the estrous cycle and are eliminated by 

ovariectomy and subsequently restored by 

administering estradiol.9

 Suggestive evidence 

from both animal and human studies indicates 

that progesterone may also play a role in the 

subjective effects of drugs and contribute to 

gender differences in sensitivity to the drugs. 

These differences, observed in preclinical and 

clinical studies, highlight the complexities 

of just one influence on behavior—hormonal 

cycles in females––and emphasize the 

continuing need for studies targeting the ways 

in which gender influences drug abuse and 

addiction risk.

Sidebar 5

People With Particular Gene 

Variants May Suffer More Harmful 

Effects From Drugs of Abuse

A longitudinal study of people followed 

from birth to adulthood highlights the 

complex interactions between genetics, 

drug exposure, and age of use in the risk of 

developing a mental disorder. The catecholO-methyltransferase (COMT) gene, which 

comes in two forms, “Met” and “Val,” produces 

an enzyme that regulates dopamine, a 

brain chemical involved in schizophrenia. 

Individuals with one or two copies of the 

“Val” variant have a higher risk of developing 

symptoms of psychosis (e.g., hallucinations, 

delusions) or schizophrenic-type disorders if 

they used cannabis in adolescence; no effect 

was seen in those who did not carry this allele.

Why it’s important: This study reveals 

a new approach for understanding how 

genetics, environment, and development 

interact to increase vulnerability to drugrelated consequences. 

Source: Caspi et al., 2005 – Biol Psychiatry 57:1117–1127

20

15

10

5

0

COMT genotype

No adolescent cannabis use

Adolescent cannabis use

Percent with schizophreniform

disorder at age 26

Met/Met

n= (151) (48)

Val/Met

(311) (91)

Val/Val

(148) (54)

Genetic variation in COMT influences

the harmful effects of abused drugs
National Institute on Drug Abuse Strategic Plan

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Sidebar 6

Individuals vary in their response to drugs of abuse, 

in part, because of genetic influences on brain circuits 

that control emotional reactivity. The emerging field 

of neurogenomics is beginning to reveal the crucial 

pathways that connect genes to behaviors. 

Genetic research has shown that functional variants 

in the enzymes catechol-O-methyltransferase (COMT) 

and monoamine oxidase (MAO); and in the serotonin 

transporter (SERT) can affect the processing of 

emotional stimuli, which may also be influenced by 

other developmental and environmental factors. 

COMT. This enzyme degrades the catecholamine neurotransmitters dopamine, 

epinephrine, and norepinephrine. A less active variant of the gene for COMT 

has been associated with improved working memory, executive functioning, and 

attentional control, but also with a higher risk of anxiety-related behaviors. 

MAO. This enzyme degrades the monoamines serotonin and dopamine. Several 

genetic variations have been described that affect the levels of the MAO enzyme, 

particularly during brain development, that contribute to individual differences in 

aggressiveness.

SERT. This protein on the surface of some neurons plays a role in turning off 

the response to serotonin. Variations in a gene that regulates SERT expression 

affect the processing of aversive stimuli in the amygdala, the emotion center of the 

brain. Carriers of a short variant show stronger amygdala reactivity to stimuli and to 

particular contexts that are relatively uncertain and perhaps more stressful. This may 

put them at increased risk for developing anxiety disorders. 

Why it’s important: Vulnerability to addiction and other mental disorders likely 

resides in brain circuits regulating such functions as executive control and emotional 

reactivity. Identification of the genetic factors that influence these functions will 

enhance our ability to identify those most at risk, allowing us to more effectively 

target our prevention efforts. 

Sources: Heinz et al., 2006 – Rev Neurosci 17(3):359–367; Volavka et al., 2004 – Ann NY Acad Sci 1036:393–398; 

Heinz et al., 2007 – Biol Psychiatry 61(8):1011–1014
National Institute on Drug Abuse Strategic Plan

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Sidebar 7

Research has revealed a number of basic 

principles that underlie effective drug 

prevention programs for youth. These are 

highlighted in NIDA’s Preventing Drug 

Use among Children and Adolescents, 

a research-based guide for multiple 

audiences, including parents, educators, 

and community leaders.

The relationship between drug abuse 

and other mental illnesses

Many people who have a substance abuse 

disorder also have some other psychiatric 

disorder, and vice versa. For example, close 

to 90 percent of people with schizophrenia smoke,10,11 for reasons that are not fully 

understood. Other studies show that exposure 

to certain drugs may increase risk for mental 

illness in vulnerable individuals (see Sidebar 5 

on page 17). Thus, a continuing NIDA priority 

is to unravel the intimate connections between 

drug abuse and addiction and other mental 

disorders. Good prevention hinges on a better 

understanding of whether these disorders have 

a shared origin, and of when early drug use 

increases the risk for mental illness––or vice 

versa. 

Because comorbidity intersects with the 

missions of other National Institutes of Health 

(NIH) constituents (e.g., National Institute of 

Mental Health), NIDA continues to work with 

our colleagues to encourage research on the 

epidemiology, genetics, and neurobiological 

bases of comorbidities. 

3. Which parts of the brain are involved in 

drug abuse?

Research shows that the brain circuits 

affected by drugs of abuse are mainly 

those involved in reward, decisionmaking, 

emotional reactivity (Sidebar 6), motivation, 

and cognitive inhibition. Drugs of abuse tend 

to activate reward and motivational circuits 

more effectively than natural rewards, leaving 

behind robust memories of their effects. The 

interactions among the densely interconnected 

circuits mentioned above determine the 

final course of action for an individual. For 

example, if the reward, motivation, and 

memory circuits overcome the inhibitory 

control circuit, a person may compulsively 

seek the rewarding stimulus, which could be 

drugs of abuse. Again, some of these circuits 

are not fully mature until early adulthood, 

making them potentially more vulnerable to 

disruption by exposure to drugs. 

Our vision is broad and applies the full power of basic 

and clinical research, neuropsychological testing, and 

functional neuroimaging to help us understand not just 

one molecule or one pathway at a time, but the addiction 

circuitry as an integral part of a wider network. In this 

network, pathways influence one another in highly 

complex ways.

4. How are research results used to improve practice?

A general set of science-based prevention principles 

has emerged from biological, psychological, and social 

science discoveries. This knowledge has been used to 

develop prevention programs with proven efficacy and 

effectiveness (see Sidebar 7). Similarly, to capitalize 

on new research findings, NIDA sponsors a Prevention 
National Institute on Drug Abuse Strategic Plan

20

Network of research centers nationwide. This network 

integrates research from various disciplines to stimulate 

its translation and to inform basic science hypotheses 

that may help develop new approaches or refine existing 

programs. 

NIDA is also exploring new areas in prevention science, 

such as the effects of physical activity on substance 

abuse. Assessing aggregated neighborhood risk factors 

can inform strategies for more effective programs that 

yield lasting results. These would synthesize 

family, school, and community efforts. 

Indeed, emerging research demonstrates 

that prevention interventions can have 

long-term and even cross-over effects (e.g., 

on driving behaviors and psychological 

functioning),12,13 and can alter life 

trajectories. 

Although NIDA-supported research has 

identified effective prevention programs, 

they are not being widely implemented. 

Therefore, we are looking to expand 

research efforts on the factors that influence 

the adoption and long-term sustainability 

of evidence-based prevention initiatives in 

schools and other settings.

How science can help refine prevention 

messages

NIDA recognizes that, along with addressing 

risk and protective factors, effective 

messages also depend on incorporating 

imaginative communication strategies aimed 

at different target audiences. Such a tailored 

approach is reflected in NIDA’s successful 

school-based prevention programs for male 

and female athletes (see Sidebar 8). 

Changing times require innovative researchbased communication tools to help us 

decode and incorporate the preferences 

of young people, so that our prevention 

messages are salient. Closer attention to 

prevention science is increasingly critical in 

a media environment where the landscape is 

constantly changing. For example, research 

on health-related e-tools, social networking 

sites, virtual worlds, and other new media is 

crucial. Trends suggest that the Internet may 

be an inexpensive and effective means of 

delivering interventions with a wide reach. 

Our ultimate goal is to improve message 

effectiveness with the intended audience. 

The addition of new tools and methods of 

Sidebar 8

Schools Adopt 

Smarter Strategies 

To Get the Message 

Across

Similar to ATLAS (Athletes 

Training and Learning 

to Avoid Steroids) for 

male athletes, ATHENA 

(Athletes Targeting Healthy 

Exercise and Nutrition Alternatives) for 

female athletes has the goal of increasing 

healthy behavioral choices and preventing 

drug abuse. Program activities, delivered 

by coaches during a sports team’s usual 

practice schedule, focus on the benefits 

of healthy sports nutrition and effective 

exercise training, as well as the dangers 

associated with drug abuse and other 

unhealthy behaviors. This intervention 

correlated with reduced use of drugs— 

including abuse of diet pills, stimulants, 

and steroids—as well as with other 

positive changes, such as healthier eating 

behaviors.

Why it’s important: Innovative 

prevention programs incorporated into the 

school setting present an effective way 

to reach young people, particularly when 

delivered by role models whom young 

people naturally admire and respect.

Source: Elliot et al., 2004 – Arch Pediatr Adolesc Med 158:1043
National Institute on Drug Abuse Strategic Plan

21

analysis help refine our interventions 

and provide a means of testing how the 

brain reacts to prevention messages. 

Neuroimaging technology could be 

applied to reveal how people process 

media messages in anti-drug advertising. 

Though we are not yet ready to design a 

prevention strategy on the basis of how 

adolescents might view a message in 

comparison to adults, the fundamental 

research that will form the basis for 

scientifically rational design is now 

under way. Indeed, these studies may 

spark a new generation of effective, 

tailored, anti-drug messaging that 

integrates cultural and social influences. 

Our Vision for the Future 

of Prevention of Drug 

Abuse and Addiction 

We envision a future where new 

knowledge and leading-edge 

technologies produce selective, costefficient, and effective prevention 

products and initiatives. Our prevention 

toolkit someday will allow us to develop 

messages that flow from a dramatically 

better understanding of the many 

complex and interdependent phenomena 

that characterize drug abuse and 

addiction. Improved prevention efforts 

will incorporate what we have learned 

about genetic contributions to addiction 

vulnerability, about the function of 

the human brain and developmental 

processes under normal conditions 

or after drug exposure, and about 

specific brain and behavioral responses 

associated with an individual’s age and 

social context. We are working toward 

a future in which early recognition of 

significant addiction risk is no different 

from early recognition of any other 

chronic disease, such as hypertension, 

diabetes, or asthma. 

II. Treatment

Strategic Goal

To develop successful treatments for drug 

abuse and addiction and improve treatment 

accessibility and implementation.

Objectives

1. To develop effective medications and 

behavioral interventions to treat drug abuse 

and addiction and to prevent relapse.

2. To develop treatments for drug abuse and 

addiction in association with comorbid 

conditions.

3. To develop the knowledge that leads to 

personalized or customized treatments.

4. To translate research-based treatments to 

the community.

Introduction: The Value of a Multipronged and 

Integrated Approach to Addiction Treatment 

Decades of research have led to today’s improved understanding of 

addiction as a chronic, relapsing brain disease caused by the complex 

interaction of genetic, social, environmental, and developmental 

factors. NIDA therefore recognizes the need for a whole systems 

approach to treating drug abuse and addiction. 

Drugs of abuse alter normal brain functioning in profound and longlasting ways so that the brain can become “reengineered” to seek 

the drug above all else. This behavior occurs because the addicted 

person is conditioned to need the drug and finds it difficult, if not 

impossible, to resist. This dysfunctional state makes the addicted 

individual vulnerable to relapse triggers, even absent of conscious 

awareness of them. 

NIDA supports multidisciplinary research addressing the multiple 

factors that can influence drug abuse and addiction trajectories. 

Research results inform treatment strategies to facilitate abstinence 

and prevent relapse. New findings continue to inspire development 
National Institute on Drug Abuse Strategic Plan

22

of medications and behavioral interventions to 

counteract drug-induced alterations in the circuits 

responsible for motivational, cognitive, and emotional 

functions. Advances come from the continued 

application of approaches that tap into potential benefits 

of the following:

• Expanding the range of drugs or populations that 

can be targeted with addiction medications that have 

already been approved. 

• Developing medications for molecules and circuits 

affected by specific drugs, as well as for targets more 

generally affected by many drugs. 

• Developing research-based treatments that match an 

addicted person’s changing needs, attitudes, and 

motivations over time. 

• Developing medications to restore cognitive functions 

disrupted by addiction, which may have impeded the 

success of behavioral therapies. 

• Weakening the power of relapse triggers.

• Taking into account the influence of 

comorbid conditions (e.g., mental 

illness, chronic pain, HIV/HCV) 

and genetic makeup to achieve truly 

customized treatments. 

NIDA recognizes that despite major 

strides in treatment research, only limited 

improvements have occurred in nonresearch 

settings. A scientific approach must be 

brought to bear on understanding how to 

most effectively test and disseminate 

research-based treatments and how health 

services systems and settings influence 

treatment implementation. Ultimately, it is 

our goal to make research-based treatments 

user-friendly, cost-effective, and available 

to a broad range of practitioners and their 

patients.

Strategic Approaches to 

Treatment

NIDA supports research to develop 

treatments that address the multiple and 

specific needs of a person trying to recover 

from drug abuse and addiction. The 

addition of tools such as neuroimaging 

technologies and those designed to generate 

detailed genetic information may help us 

to individualize treatments and predict 

treatment response. This knowledge will 

lead to more targeted and cost-effective 

approaches for greater specificity.

For more information 

visit our Web site at: 

www.drugabuse.gov
National Institute on Drug Abuse Strategic Plan

23

1. How can NIDA research help develop 

and enhance medications and 

behavioral therapies to reduce drug 

abuse and prevent relapse?

NIDA’s approach to medications 

development

NIDA supports a dual strategy: one that 

takes advantage of already-approved 

medications with putative addiction 

applications, and the other that develops 

new compounds to interact with novel 

targets for treating drug abuse and addiction 

and their health consequences. In both cases, 

NIDA encourages researchers to work with 

commercial companies. The advantages 

of testing already-approved medications 

include the availability of safety profile 

information, lower development costs, and 

shorter times for obtaining FDA approval.

On the other hand, the development of 

new compounds may be more responsive 

to breakthrough scientific discoveries. For 

instance, NIDA research has uncovered 

several components of the cannabinoid 

system, along with heterodimeric receptors 

(i.e., receptors that combine, or “dimerize,” 

to create targets with novel biological 

properties that could be harnessed to provide 

a broader array of medication options). 

This approach is already being exploited 

to develop medications for chronic pain 

that could circumvent the problematic side 

effects (e.g., tolerance and dependence) of 

many current medications (see Sidebar 9).

Sidebar 9

Pain Management: Alternative 

Approaches Promise Pain Relief 

Without Abuse Liability

Glia. Research reveals that glial cells 

(historically regarded as supporting 

players) play key roles in regulating pain 

signals. Through the secretion of a host of 

molecules, glial cells influence pain and 

inflammatory processes. Targeting glia and 

their soluble products may provide a novel 

and effective therapy for controlling clinical 

pain syndromes.

CB2. Activation of cannabinoid type 2 

(CB2) receptors inhibits acute, inflammatory, 

and neuropathic pain responses in animal 

models. Since these receptors are located 

largely outside the brain, selective CB2 

agonists are promising candidates for the 

treatment of acute and chronic pain without 

the psychoactive effects. 

Opioid receptor heterodimers. 

Opioid receptors exist as dimers––protein 

molecules composed of two linked 

subunits––whose variable makeup affects 

resulting pharmacology. Strategies are being 

developed to identify compounds that will 

specifically bind and activate different opioid 

receptor combinations. Such compounds 

could represent the next generation of 

pain relievers with decreased side effects, 

including reduced drug abuse liability.

Sources: Watkins LR et al., 2007 – Brain Behav Immun 21:131–146; 

Whiteside GT et al., 2007 – Curr Med Chem 14:917–936; Daniels et al., 

2005 – PNAS 102(52):19208–19213 
National Institute on Drug Abuse Strategic Plan

24

Regardless of the approach used, NIDA 

takes advantage of the combination of 

validated animal models and translational 

human laboratory studies to develop and test 

medications (see Sidebar 10).

How behavioral treatments help drug 

abusers

Behavioral therapies have already 

been successfully developed to help 

individuals with addictions engage in the 

treatment process, modify their attitudes 

and behaviors, and nurture those skills 

that are conducive to a healthy lifestyle. 

These treatments can also enhance the 

effectiveness of medications (and vice versa) 

and help people stay in treatment longer. 

Addiction to drugs such as cocaine and 

methamphetamine can disrupt cognitive 

functioning and interfere with treatment 

retention and efficacy. Therefore, NIDA is 

supporting research on medications such 

as Modafinil (which is currently FDAapproved for treating narcolepsy) as an 

adjunct to behavioral therapy because of 

their proven cognitive-enhancing properties. Early results are promising for cocaine 

treatment, and research in methamphetamine 

abusers is under way.14

NIDA also plans to explore cutting-edge 

cybertechnologies for both developing new 

treatments and expanding treatment delivery. 

New technologies are opening the door to 

shared virtual worlds (environments, social 

networks, communities), digitally controlled 

environments, augmented realities, 

robotics, and brain computer interfaces, 

among many others. All these could have 

applications in drug abuse treatment. 

NIDA is already exploring the potential 

of computer-delivered interventions as a 

comparatively low-cost means of widely 

disseminating evidence-based approaches 

while ensuring treatment fidelity. Early 

Sidebar 10

Animal Models Are Crucial to 

Research on Drug Abuse and 

Addiction

Animal models have greatly contributed 

to our understanding of addiction’s 

underlying substrates, the abuse liability 

of novel compounds, the role of candidate 

vulnerability genes and stress in relapse, and 

the persistence of drug taking. They allow 

scientists to rigorously control and analyze 

biological and environmental factors related 

to drug abuse and test novel approaches to 

prevention and treatment. The noteworthy 

development of buprenorphine as a treatment 

for opiate addiction began with studies 

using animal models, as is the case for most 

medications being tested in human clinical 

trials. 

Self-administration, or the voluntary intake 

of abusable substances by animals, is now 

among the most widely used paradigms 

by pharmaceutical companies around the 

world to evaluate the abuse liabilities of new 

medications. Because animals will selfadminister nearly all drugs of abuse and 

continue to take them when available, they 

allow us to study the chronic effects of drugs 

on their brains and behavior.

Source: Caine, et al. (ed), 1993 – Behavioural Neuroscience: A 

Practical Approach, Vol. 2 117–143
National Institute on Drug Abuse Strategic Plan

25

studies of cognitive-behavioral therapy 

and community reinforcement approaches 

support the feasibility and acceptability of 

this strategy.15,16

What effective treatments are 

designed to do

Drug abuse disrupts the brain circuits 

involved in reward, memory/learning, and 

control over behavior. Memories linked to 

the drug experience, for example, can trigger 

powerful drug cravings that can “mute” 

other parts of a person’s life so that drug 

seeking and use become an all-consuming 

focus. Craving is therefore a major 

contributor to relapse, posing what seems 

an insurmountable challenge to an addicted 

person (see Sidebar 11). NIDA’s strategic 

approaches to treatment are thus being 

employed to (1) counter relapse triggers, (2) 

strengthen self-control, and (3) reinstate the 

reward value of natural reinforcers while 

decreasing that of drug stimuli.

Prevent Relapse. The most frequent 

triggers of relapse include stress, exposure to 

conditioned cues, and priming (re-exposure 

to drugs of abuse). Medications that block 

reinstatement of drug-taking behaviors in 

animals by these three triggers are now 

being tested in humans.

Both clinical reports and preclinical studies 

have documented the important role that 

stress plays in relapse. Medications or 

behavioral treatments that can interfere 

with or mitigate the response to stress may 

thus offer promise for relapse prevention. 

Corticotropin-releasing factor (CRF) is 

known to be a key brain chemical involved 

in organizing the brain and body response to 

stress. Thus, medications that target CRF are 

of interest. Animal studies have shown that 

compounds that block CRF signals attenuate 

the reinstatement of drug taking following 

exposure to stressors. Since drug withdrawal syndromes 

and the often chaotic lifestyles of drug abusers are 

manifestly stressful states, strategies that improve coping 

mechanisms or reduce the stress response could help 

prevent stress-induced relapse.

Sidebar 11

Brain Region Linked to Reduced 

Drug Craving

Despite being aware of negative 

consequences, many smokers have 

serious difficulty quitting, and those who 

quit experience urges to smoke and often 

relapse. A recent study of patients who 

had suffered various brain injuries revealed 

a new role for the insula (shown in red) in 

regulating conscious urges, including drug 

craving. Researchers at the University 

of Iowa monitored the quit histories of 

approximately 70 smokers and found that 

those with specific damage to the insula 

were much more likely to quit easily and 

immediately and to remain abstinent than 

those with damage to other brain areas. 

Why it’s important: This discovery could 

identify a new target to inhibit craving.

Source: Naqvi, N. et al., 2007 – Science 315:531
National Institute on Drug Abuse Strategic Plan

26

Conditional cues are stimuli (e.g., people, 

places, moods, things) that become 

associated with the drug experience 

and can serve as triggers to relapse. 

Conditioned cues can pose formidable 

obstacles to successful therapy for many 

individuals because they can elicit craving 

without conscious recognition of their 

influence. Medications designed to blunt 

conditioned responses or promote their 

extinction (an active process whereby 

previously learned associations are 

weakened) could enhance the efficacy of 

psychotherapeutic interventions. A proofof- concept for this approach has already 

been shown with D-cycloserine (DCS), a 

partial agonist of the NMDA (glutamate) 

receptor. DCS may facilitate extinction 

and promote new learning, and has been 

successfully used in conjunction with 

psychotherapy for treating acrophobia (the 

fear of heights).17 Medications available 

for other indications are also being tested 

for their ability to reduce cue-induced 

drug cravings.

Priming, or drug exposure, is the response 

to a drug in a formerly addicted person 

that propels him or her to further drug 

use and, often, to relapse. Data show that 

people in treatment who “slip” are at 

higher risk of relapse or of returning to 

former levels of drug abuse. 

Research in this area has already produced 

positive results. Cannabinoid and opioid 

antagonists, for example, have been shown 

to block the priming response in animals 

and suppress their self-administration of 

drugs in a relapse model of drug seeking 

(see Sidebar 12). 

Another strategy being explored is to 

block priming attempts by harnessing 

the immune response. The rationale is to 

develop “vaccines” that induce the body 

to produce drug-specific antibodies. At 

Sidebar 12

Compound Reduces Marijuana’s 

Intoxicating Effects and May Help 

Prevent Relapse From Drug Exposure 

(Priming) and Environmental Cues

Marijuana smokers 

given an experimental 

compound (SR141716, 

rimonabant) reported 

reduced highs (and smaller 

heart rate increases) 

compared with untreated 

smokers (see A). Because 

SR141716 partially blocks 

the intoxicating effects 

of marijuana’s active 

ingredient (THC), it may 

prove valuable in treating 

marijuana addiction and 

perhaps other addictions 

as well. Indeed, in a rat 

model of relapse to drug seeking, SR141716 

dramatically reduced resumption of cocaineseeking triggered by two of the three most 

common relapse triggers: a priming dose of 

cocaine and conditioned cues associated with 

cocaine reward (see B). The compound did not 

reduce cocaine-seeking triggered by stress.

Why it’s important: The cannabinoid system 

is a new player in our understanding of the 

rewarding effects of drugs, and compounds 

that target this system may have application for 

not only marijuana treatment, but also for other 

drugs since they can block relapse triggers.

(A)

(B)

Sources: Huestis et al., 2001 – Arch Gen Psychiatry 58(4):322–328; 

De Vries et al., 2002 – Pharmacol Rev 54:1–42
National Institute on Drug Abuse Strategic Plan

27

high enough concentration, these antibodies 

would sequester drug molecules while they 

are still in the bloodstream, preventing them 

from reaching the brain and exerting their 

psychoactive effects. Nicotine and cocaine 

vaccines have already been developed and 

are undergoing further testing in animals 

and humans. A methamphetamine vaccine 

is in development. NIDA has also requested 

proposals for a heroin vaccine, which could 

be particularly valuable in areas of the 

world where opioid agonist medications 

are not accepted. NIDA plans to continue 

supporting research on strategies designed to 

block the priming response.

Strengthening Self-Control. The decisionmaking circuits of the human brain, which 

are not even fully developed until a person’s mid-20s, govern our ability to control 

impulses. Drug abuse and addiction can 

severely disrupt these processes, contributing to the compulsive features of addiction. 

A complementary strategy supported by 

NIDA is to strengthen the function of brain 

regions involved with decisionmaking and 

inhibitory control (distributed throughout the 

frontal cortex). 

Noninvasive brain stimulation and 

“neurofeedback” may prove to be useful 

therapeutic tools in this context. Researchers 

are exploring the use of technologies 

such as repetitive transcranial magnetic 

stimulation (rTMS) and feedback training 

using real-time functional magnetic 

resonance imaging (fMRI) (see Sidebar 

19 on page 33) to noninvasively influence 

brain activity in specific regions. Though 

not yet demonstrated for addiction, these 

techniques show promising results in 

managing depression and in influencing pain 

perception, respectively.18 Further validating 

research could render these technologies 

powerful psychotherapeutic interventions for 

rescuing the circuits and behaviors impaired 

by addiction. 

Sidebar 13

Overexpression of Dopamine D2 

Receptors Reduces Alcohol SelfAdministration in Rats 

Addiction is characterized 

by decreased sensitivity 

to natural rewards, likely 

related to diminished function 

in dopamine brain circuits. 

Human brain imaging studies 

have provided substantial 

evidence showing that 

individuals addicted to a variety 

of substances have low levels 

of dopamine type 2 receptors 

(DRD2) in the striatum (a part 

of the reward circuit).

In this experiment, researchers 

sought to determine whether 

increasing levels of DRD2 in 

the brain could reduce alcohol 

consumption in animals trained 

to self-administer the drug. 

Brain levels of DRD2 in rats 

were increased by injecting a 

virus that expresses high levels 

of DRD2 protein in a key area 

of the brain’s reward pathway 

(see A). This manipulation led 

to an overexpression of DRD2 

receptors that dissipated over 

time (see B) and a corresponding decrease in alcohol 

consumption that resumed 

when the receptors returned to 

baseline (low) levels (see C).

Why it’s important: 

Although the use of viral 

vector–delivered genes is not 

practical for clinical use, these 

results provide a proof-ofconcept that enhancement 

of dopamine D2 receptors 

may be a useful approach 

for treating drug abuse. Medications and 

behavioral strategies to reinstate dopamine 

receptor function in the reward circuitry may be 

beneficial in treating addiction. 

Source: Thanos et al., 2001 – J Neurochem 78(5):1094–1103
National Institute on Drug Abuse Strategic Plan

28

Reinstating the Value of Natural Rewards. Drug abuse 

and addiction impair the reward system, diminishing the 

value of formerly rewarding stimuli in a person’s life. 

NIDA therefore seeks approaches to counter drugs’ effects 

on brain systems affecting reward and motivation—and 

help restore the value of natural rewards. 

Animal research has demonstrated the 

feasibility of modulating the dopamine 

reward system in ways that affect sensitivity 

to drug taking. For example, alcoholpreferring rats induced to overexpress 

dopamine receptors in the nucleus 

accumbens (a part of the reward circuitry) 

decreased their alcohol consumption (see 

Sidebar 13 on page 27). Further, in studies 

of nonhuman primates, social factors have 

been shown to influence the function of 

the dopamine system and vulnerability to 

drug taking (see Sidebar 4 on page 16). 

These studies suggest a malleable reward 

system that may be capable of recovering 

from drug addiction. The goal would be to 

heighten dopamine system sensitivity in 

drug-addicted individuals so as to enhance 

the value of natural reinforcers (i.e., social 

interactions, eating good food, etc.).

How patients sustain recovery

There are many pathways to recovery. Some 

patients may require lengthy treatment 

protocols in residential therapeutic settings, 

while others may benefit from less intensive 

outpatient treatment. The goal is the same: to 

help patients develop the internal motivation 

and skills to abstain from drugs and regain 

their lives.

However, because of the chronic nature of 

addiction, continuing care (e.g., “booster” 

treatment sessions, recovery groups, and 

other social support systems) can be crucial 

to a person’s ability to sustain a drug-free 

lifestyle. A patient may require varying 

combinations of services and treatment 

components during the course of recovery. 

Along with counseling, psychotherapy, and 

medical services, patients may also benefit 

from family therapy, parenting instruction, 

vocational rehabilitation, and social and 

legal services. NIDA continues to support 

Sidebar 14

Co-occurrence of addiction and other 

mental disorders is common. Substance 

abuse sometimes begins as a way to 

alleviate symptoms of a mental illness. 

Further, substance abuse may increase 

the vulnerability to other mental illnesses. 

Also, some of the factors that contribute to 

substance abuse and other mental illnesses 

are the same. Stress is one example, and 

patients suffering from post-traumatic stress 

disorder (PTSD) have high rates of drug and 

alcohol abuse. Because of the projected 

increases in PTSD due to members of the 

military returning from service, NIDA will 

increase its research investment in this 

area and collaborate with the Department 

of Veterans Affairs, the Substance Abuse 

and Mental Health Services Administration 

(SAMHSA), and multiple NIH Institutes—

NIMH, National Cancer Institute, NIAAA, 

and the National Heart, Lung and Blood 

Institute––in developing its research agenda.
National Institute on Drug Abuse Strategic Plan

29

research to better understand how such 

therapies work and how to implement them 

in community settings to engage and keep 

patients in treatment and prevent relapse.

2. What if people have another mental 

disorder—how does that affect 

treatment for addiction?

Mental illness is highly comorbid with 

substance use disorders. In fact, as many 

as 6 in 10 people who have an illicit drug 

use disorder also suffer from other mental 

illnesses.19 Having both can greatly increase 

the challenge of diagnosing and treating the 

disorders; and ignorance of or failure to treat 

one disorder can jeopardize the chances of a 

successful intervention for the other. Patients 

with co-occurring disorders often exhibit 

symptoms that are more persistent, severe, 

and refractory to treatment, compared with 

those with just one disorder. Health care 

providers and caregivers should therefore 

be aware that drug abuse and other mental 

illnesses often occur together, necessitating 

a comprehensive treatment approach (see 

Sidebar 14). Thus, NIDA supports research 

aimed at adapting and integrating treatments 

that tackle these overlapping conditions, 

which affect some of the same circuits in the 

brain. 

For some mental disorders, pharmacotherapies are already available to alleviate 

symptoms. Medications such as stimulants, 

antidepressants, mood stabilizers, and neuroleptics may be critical to treatment success 

for ADHD, depression, anxiety disorders, 

bipolar disorder, and schizophrenia. How 

these medications are affected by, or alter 

the effects of, abused substances is not well 

understood. Some medications may even 

prove efficacious for treating both drug addiction and other mental illnesses. Effective 

Sidebar 15

Groundbreaking Genetics Tools 

Will Lead to More Personalized 

Prevention and Treatment 

Approaches for Drug Abuse and 

Addiction

New knowledge derived from large, 

comprehensive genetic databases, combined with new genetics technology, will 

allow researchers to study thousands of 

addiction-relevant gene variants at once. 

Potential applications of this knowledge 

include studies to understand how genetic 

differences contribute to brain development and to differential brain responses 

to drugs of abuse. This knowledge could 

also be applied to prospective epidemiological studies to understand how genes 

and environment interact throughout the 

lifespan to modulate addiction risk. Clinical trials could use genetic information to 

tailor treatments based on a patient’s genetic makeup (i.e., to enhance treatment 

effectiveness and minimize, or even prevent, adverse effects). Finally, genetics 

could inform studies aimed at advancing 

the understanding of disease vulnerability 

in relation to psychiatric comorbidity (i.e., 

depression, ADHD, schizophrenia).
National Institute on Drug Abuse Strategic Plan

30

medications also exist for opioid, alcohol, 

and nicotine addictions. However, their use 

has not been well studied in comorbid populations or among those taking other psychoactive medications. Various forms of behavioral treatment, alone or in combination 

with medications, can be the cornerstone 

to achieving successful outcomes for both 

substance abuse and other mental disorders. 

Their use in comorbid populations should 

also be evaluated. 

3. How will treatments be tailored for 

optimal effectiveness?

NIDA’s research program is poised to 

play an important role in developing 

treatments that can take individual and 

group vulnerabilities into account. Doing so 

will help us derive more personalized and, 

thus, more effective treatments for people 

with drug use disorders. To this end, NIDA 

is capitalizing on advances in genetics, 

epigenetics, and brain imaging technology, 

and on research revealing the influence of 

environmental and developmental factors. 

Genetic expression profiles are affected 

by substance abuse and can change 

throughout development. To investigate, 

NIDA researchers are constructing a 

comprehensive database of single nucleotide 

polymorphisms (SNPs) relevant to addiction 

(http://zork.wustl.edu/nida/neurosnp.html) 

(see Sidebar 15 on page 29). SNPs are 

variations in DNA sequence that occur when 

a single nucleotide in the genome sequence 

is altered. By assembling all genes identified 

as biologically relevant to addiction, NIDA 

is helping to identify potential novel targets 

for the development of medications (see 

Sidebar 16). We are also expanding the 

knowledge base so that next-generation 

pharmaceuticals can use information about 

a person’s genetic makeup to predict how 

Sidebar 16

Gene Cluster Linked to Nicotine 

Dependence and Associated 

Diseases

A recent study provides an example of how 

genome-wide analyses are being used to 

identify novel candidate mechanisms of 

disease vulnerability and therapeutic targets. 

Here, investigators interrogated the genomes 

of close to 11,000 Icelandic smokers with 

a platform displaying over 306,000 single 

nucleotide polymorphisms (SNPs)––or 

single-base changes in a person’s DNA 

(millions of which have been catalogued 

by the Human Genome Project). The study 

identified a cluster of three nicotinic receptor 

subunit genes (α3, α5, and β4) linked to 

smoking quantity, nicotine dependence, and 

the risk of two smoking-related diseases: lung 

cancer and peripheral arterial disease.

Why it’s important: Identification of 

this genetic cluster converges with growing 

evidence from prior studies of its linkage 

to nicotine dependence and to serious 

health consequences. This new information 

reveals a novel target for the development of 

medications to treat tobacco addiction and 

related diseases. 

Source: Thorgeirsson et al., 2008 – Nature 452:638–642
National Institute on Drug Abuse Strategic Plan

31

he or she will respond to a therapeutic 

medication. Promising findings have 

already emerged relative to the treatment 

of nicotine and alcohol addictions. 

NIDA is encouraging research that 

develops and evaluates new platforms 

for potential use in screening for the 

telltale signatures of chronic drug abuse 

in blood cells, serum, or saliva. Looking 

at messenger RNA (mRNA), epigenetic 

marks, and protein expression profiles 

(proteomics) could dramatically enhance 

our ability to diagnose chronic drug 

exposure in primary care and other 

settings.

4. How will drug abuse treatment reach 

the people who need it?

NIDA’s clinical trials are the foundation 

for testing and evaluating promising 

drug abuse and addiction treatments. We 

support research trials for all phases of 

medications and behavioral treatment 

development. We also encourage 

collaboration with industry to optimize 

costs and resource allocation and to more 

efficiently develop or adapt treatments. 

As effective treatments emerge, NIDA 

tests them in real-world settings. These 

efforts are exemplified by our National 

Drug Abuse Treatment Clinical Trials 

Network (CTN) and our collaborative 

Criminal Justice Drug Abuse Treatment 

Studies (CJ-DATS) (see Sidebar 18 on 

page 32). The CTN studies, for example, 

continue to reveal information for 

optimizing the treatment of comorbid 

conditions and the translation of new 

medications to community settings. 

They also assess novel interventions to 

reduce HIV risk among drug-abusing 

populations. CJ-DATS broadens the 

testing of proven drug abuse treatments 

Sidebar 17

Methadone 

Maintenance 

Works for Prisoners 

More than 200 heroindependent inmates in 

Baltimore were randomly 

assigned to one of three 

groups: (1) educational 

counseling only; (2) 

counseling in prison with 

the opportunity to enroll in 

methadone maintenance 

treatment upon release; 

and (3) counseling and 

methadone maintenance 

during incarceration, 

with transfer to 

community-based 

methadone maintenance after release. Six 

months after release, those who began 

methadone maintenance in prison were 

significantly more likely to enter and remain 

in community-based treatment, were less 

likely to test positive for illicit opioids, and 

had significantly fewer days of heroin use 

and criminal activity than participants who 

received counseling only. 

Why it’s important: Despite its 

demonstrated effectiveness in treating 

opioid abuse, methadone maintenance 

is rarely provided in correctional facilities. 

However, this study shows that methadone 

maintenance treatment begun prior to or 

upon release from prison is an inexpensive 

and effective intervention that may prevent 

the devastating cycle that can happen to 

formerly incarcerated drug abusers who go 

untreated—that is, a return to drug abuse 

upon re-entry to the community, further 

criminal activity, exposure to infectious 

diseases, and re-arrest and imprisonment.

Sources: Kinlock et al., 2007 – Drug Alcohol Depend 91(2–3): 220-227; 

Kinlock et al., 2008 – Crim Justice Behave 35(1): 34-47; Gordon et al., 

2008 – Addiction 103: 1333–1342 
National Institute on Drug Abuse Strategic Plan

32

in criminal justice settings, including CJ settings with adolescents. 

It continues to solicit the greater involvement of public health and 

public safety institutions across all system levels. NIDA plans to 

support ongoing research on drug courts to learn how they work and 

how to advance their use, looking at the judge’s role in changing 

drug court participant behavior and outcomes, for example. 

All of these initiatives allow NIDA to exploit an open-channel 

communication approach with relevant stakeholders to collect 

information on how to generalize and further enhance treatments so 

they are more community/justice system-friendly. 

Overcoming barriers to more rapidly translate 

research findings 

NIDA’s overall mission is not just to develop knowledge about drug 

abuse but also to disseminate that knowledge into practical use. 

We engage in multiple activities aimed at closing the unacceptably 

long lag between the discovery of effective treatment interventions 

and their integration into community clinical practice.20 Despite 

major strides in drug abuse treatment research, the adoption of 

science-based programs has been rather limited. This may relate to 

several unique characteristics that distinguish 

treatment for drug abuse from that for most 

other diseases, including: 

• service delivery outside of mainstream 

health care settings;

• overburdened treatment systems, often 

with low pay and high staff turnover rates;

• external (i.e., court-mandated) pressure on 

individuals seeking care;

• nonreimbursement for costs of care;

• reliance on public sources for program 

funding; and

• stigma attached to the disease and to those 

seeking treatment for it.

NIDA continues to support research that 

addresses the organizational, workforce, 

funding, and policy issues known to 

influence the success of addiction treatment. 

This includes cost-effectiveness and 

implementation research to determine how 

best to overcome systemic obstacles and 

foster the adoption of proven treatments 

by communities nationwide (see Sidebar 

18). Moreover, we continue to build our 

productive partnerships with state agencies 

and encourage them to team with research 

organizations to enhance their research 

capacity and their delivery of publicly 

supported drug abuse treatments. 

NIDA is also working to engage the medical 

community in drug abuse screening and 

referral to treatment. Primary care physicians 

are ideally positioned to serve as the first 

line of defense for detecting drug use 

early and for referring symptomatic drugabusing patients to specialized treatment. 

Therefore, NIDA continues to make research 

on screening and brief intervention (SBI) a 

strategic priority, focusing first on primary 

care and emergency room physicians. SBI 

has already been shown to be effective in 

reducing alcohol and tobacco use, though 

more research is needed for effects on illicit 

and prescription drug abuse. Also, drug abuse 

can influence the course and progression of 

Sidebar 18

Science Reveals Treatments that 

Work for Drug Abuse and Addiction

Research has revealed a number of basic 

principles that underlie effective drug 

addiction treatment, as highlighted in NIDA’s 

treatment guides for the general population 

and for criminal justice offenders.
National Institute on Drug Abuse Strategic Plan

33

other medical diseases (including adherence 

to treatment regimens), underscoring the need 

for screening. 

Our Vision for the Future of 

Treatment for Drug Abuse and 

Addiction 

NIDA’s research program is entering an 

exciting new era in which treatments will 

be increasingly tailored to the individual––a 

more personalized approach that will 

translate into better and more cost-effective 

treatments for substance abuse disorders. This 

approach will be more effective than past 

approaches thanks to our new understanding 

of the plastic adaptations that characterize 

addiction. These adaptations erode the very 

same neural substrates that enable functions 

such as self-control, decisionmaking, accurate 

reward prediction, motivation, and memory. 

We are committed to harnessing knowledge 

on how drugs affect circuits and behaviors 

and parlaying it into effective treatments to 

restore the addicted brain and allow people to 

regain their cognitive abilities and capacity to 

enjoy life.

Glimpses of this future can already be 

seen in various research areas. Indeed, 

next-generation screening and monitoring 

devices, therapeutic compounds, behavioral 

interventions, and neurofeedback training 

(see Sidebar 19) suggest a panoply of 

treatment options to efficiently counteract 

the drug-induced breakdown in brain 

neurochemistry. Addiction treatments will 

become increasingly adept at reducing 

the rewarding properties of drugs while 

enhancing those of healthier alternatives. 

Inhibiting conditioned memories and 

strengthening cognitive control are other 

treatment objectives. 

In the future, we will seize upon new 

therapeutic opportunities stemming from 

deciphering an individual’s genetic code to 

better prevent and cure disease. At the same 

time, however, we must recognize the responsibility that comes 

with such technological advances to ensure confidentiality and 

privacy. 

NIDA is constantly striving to transform scientific insight into 

effective and responsible public health interventions. This 

endeavor continues to be shaped by promising discoveries and by 

the accompanying need to consider ethical concerns when treating 

illnesses like drug addiction.

Sidebar 19

Neurofeedback Offers Exciting 

Potential for Future Use with 

Addicted Patients

Researchers are exploring the use of 

neurofeedback, where subjects are trained 

to modulate neural activity in specific 

regions of their brains by having pictorial 

representations of the activity in those areas 

fed back to them in real time. Though not yet 

demonstrated for addiction, this technique 

has shown promising results for altering the 

perception of pain in some healthy adults 

and chronic pain patients. 

Why it’s important: This line of 

research could evolve into a powerful 

psychotherapeutic intervention capable 

of restoring function to the circuits and 

behaviors impaired by addiction.

Source: DeCharms et al., 2006 – Proc Natl Acad Sci 102(51):18626–

18631
National Institute on Drug Abuse Strategic Plan

34

III. HIV/AIDS

Strategic Goal

To diminish the spread of drug abuse-related human immunodeficiency 

virus (HIV) and minimize the associated health and social consequences, 

including acquired immunodeficiency syndrome (AIDS).

Objectives

1. To support research to better understand the etiology, pathogenesis, 

and spread of HIV/AIDS among drug-abusing populations.

2. To help prevent the acquisition (primary prevention) and transmission 

(secondary prevention) of HIV among drug abusers and their partners.

3. To decrease the health disparities associated with HIV/AIDS.

4. To support international research on the intertwined epidemics of drug 

abuse and HIV/AIDS.

5. To improve HIV treatment and outcomes in drug abusers through a 

better understanding of interactions with drugs of abuse, HIV/AIDS 

disease processes, and the medications used to treat both.

Introduction: The Need for Responsive Prevention 

and Treatment Strategies

HIV/AIDS remains one of the most serious medical consequences of drug abuse. 

Thus, NIDA continues to support research to improve HIV prevention among 

drug abusers and enhance treatment access and use for HIV/AIDS and other cooccurring conditions, particularly hepatitis C (HCV) infection (85–90 percent of 

HIV-positive injection drug users [IDUs] are also HCV-positive). For example, 

NIDA continues to study HCV treatment patterns in patients with and without 

HIV co-infection to examine clinical outcomes following treatment. 

Our strategic plan relies on research across diverse areas, including basic science, 

epidemiology, prevention, health disparities, medical interactions, and disease 

consequences. To effectively diminish the spread and consequences of HIV/

AIDS, we must better understand how HIV is transmitted among different 

groups and communities. Genetics research will elucidate individual factors that 

determine vulnerability or resistance to infection and to disease progression. 

Epigenetic studies may offer clues as to how the virus becomes incorporated into 
National Institute on Drug Abuse Strategic Plan

35

cells, but remains latent. In addition, studies 

that advance our knowledge of the changing 

behavioral and social epidemiology of drug 

abuse, HIV/AIDS, and comorbid conditions 

will help guide our approach to preventing 

HIV transmission. We have already learned 

important lessons by focusing on (1) the 

link between drug abuse and risky sexual 

behaviors and (2) the distinct characteristics 

of the epidemic among special populations 

(women, youth, minorities, prisoners).

A key step in curtailing the spread of HIV 

is improving our understanding of why 

certain populations are exceptionally 

vulnerable, along with developing primary 

prevention strategies that target infection 

among high-risk groups. The Centers for 

Disease Control and Prevention (CDC) 

estimates that 21 percent of people living 

with HIV in the United States do not know 

they are infected,21 which heightens their 

risk of unknowingly transmitting the virus. 

Therefore, NIDA also supports research to 

develop effective secondary prevention

strategies that promote testing and education 

among the undiagnosed to further reduce 

HIV transmission. NIDA is building on 

earlier research that helped prompt the 

CDC’s decision to broaden its guidelines 

for providing HIV screening to populations 

at risk. An important aspect of encouraging 

testing and counseling is the need to make 

followup treatment more accessible to 

people with HIV and substance abuse 

problems.

A disproportionate number of affected 

people are ethnic minorities, whose access to 

and utilization of treatment options is often 

limited. Such health disparities particularly 

affect African-Americans, who also tend to 

be late testers, putting them at greater risk 

for disease transmission and accelerated 

disease progression. Gathering meaningful 

data on the various factors contributing to 

these disparities is integral to efforts to resolve them 

through earlier diagnosis and treatment. Moreover, HIV/

AIDS associated with drug use continues to expand 

globally. International research that systematically 

monitors changes and patterns in the transmission and 

manifestation of HIV disease will more effectively 

prevent and treat the AIDS epidemic.

Treatment with highly active antiretroviral therapy 

(HAART) can dramatically reduce HIV-related 

morbidity and mortality. HAART is enabling more 

people to live longer with HIV, helping to redefine 

it as a chronic illness. This circumstance brings 

about accompanying chronic medical disease 

consequences—particularly, adverse consequences 

for the brain. Moreover, interactions between 

neurological complications, substance abuse, and other 

comorbid psychiatric disorders may contribute to poor 

adherence and worse outcomes, requiring responsive 

counterinterventions. To optimize HAART for drug 

abusers, we must investigate interactions between 

HAART, drugs of abuse, and medications used to treat 

addiction. More research is needed to better understand 

and address the long-term clinical complications in drugabusing populations. 

Finally, because HIV/AIDS extends across many public 

health domains, NIDA is collaborating on projects 

with other NIH Institutes and Centers, focusing on 

complementary work in the areas of drug abuse, HIV/

AIDS, and other sexually transmitted diseases (STDs). 
National Institute on Drug Abuse Strategic Plan

36

Strategic Approaches to 

HIV/AIDS Research

NIDA continues to encourage basic, clinical, services, 

and natural history research that explores the underlying 

mechanisms of HIV-associated health outcomes in the 

context of drug abuse. 

1. How has the HIV/AIDS epidemic changed over the 

past few decades in the United States?

The patterns of HIV/AIDS relative to drug abuse are 

changing in this country. Formerly, injection drug use 

was a main vector through which HIV was spread. 

However, over the past three decades, a substantial 

reduction has occurred in the proportion of new HIV/

AIDS cases attributable to injection drug use. NIDA 

research that has resulted in improved 

treatment for injection drug users (e.g., 

methadone and buprenorphine for heroin 

addiction) has contributed to this decline. 

At the same time, the proportion of cases 

attributable to high-risk heterosexual 

contact has increased steadily (see 

Figure 2). 

Recent findings illustrate the trend in HIV 

infection moving from injection drug use 

to noninjection drug use (see Sidebar 20). 

Drug use impairs people’s judgment and 

lowers their inhibitions, which can lead to 

impulsive and unsafe behaviors; therefore, 

effective drug abuse treatment is also HIV 

prevention. Indeed, the integration of HIV 

risk-reduction interventions into drug abuse 

treatment is imperative. 

Epidemiological and natural history 

studies help us to monitor epidemic 

trends, follow more closely the changing 

clinical manifestations of HIV disease 

and comorbid conditions, and measure the 

effects of HIV prevention efforts among 

drug abusers. New studies will also inform 

the development of effective primary 

and secondary prevention interventions. 

Looking at diverse settings can help us 

characterize individual risk factors as 

well as the influence of social and sexual 

networks, environmental contexts, and 

their interactions. Such research will help 

elucidate HIV transmission dynamics, the 

disparate health effects of drug use and 

HIV/AIDS among different populations, 

and the best ways to reach them. 

NIDA is focusing more intently on criminal 

justice populations to learn how best to 

address the special risks of a group with 

high drug abuse and background infection 

rates compared with the general population. 

This pertains to populations both in prison 

or jail and upon return to the community.

Figure 2

AIDS from injection drug use has declined steadily 

while risk from heterosexual contact has increased

*Heterosexual contact with a person known to have, or to be at high risk for, HIV infection.

Percentages of AIDS Cases Among Adults and 

Adolescents by Transmission Category and Year of 

Diagnosis In United States and Dependent Areas

Note: Data have been adjusted for reporting delays and missing 

risk-factor information. 

Source: CDC, U.S. Department of Health and Human Services, 2008
National Institute on Drug Abuse Strategic Plan

37

2. How does NIDA plan to focus research 

efforts to better understand and 

prevent HIV infection in drug abusers 

and limit its progression? 

NIDA’s basic research portfolio will focus 

on host and viral factors related to HIV 

susceptibility and progression in drug 

abusers. Genetics, epigenetics, proteomics, 

and other related high-throughput 

technologies will be employed. These can 

help identify changes in gene and protein 

expression, as well as molecular signatures 

of disease vulnerability and progression in 

both humans and model organisms. 

Another promising new area of study with 

respect to AIDS progression involves 

the depletion of T cells in gut-associated 

lymphoid tissue (GALT) in the very early 

stages of HIV infection. This depletion––and 

how well it is restored with antiretroviral 

treatment––seems to determine the 

outcome of infection, or how quickly AIDS 

progresses. NIDA is interested in research 

on the link between substance abuse and 

the GALT immune responses. We also want 

to learn more about the impact of HAART 

on the restoration of the gastrointestinal 

mucosal immune system––within the 

context of substance abuse. A new research 

initiative will encourage basic and clinical 

research in these areas. 

Primary prevention efforts to reduce drug 

abuse–HIV risk behaviors

HIV prevention must be a component of early drug abuse 

prevention efforts. Therefore, NIDA-supported research aims 

to develop and test new age-appropriate behavioral HIV 

risk-reduction interventions that start with the youngest age 

groups and “grow” along with them. NIDA is supporting 

initiatives aimed at developing youth- and communitybased HIV prevention programs designed specifically for 

urban youth, a population that is considered particularly 

Sidebar 20

Non-Injection Drug Abuse is Also 

Risky for Spreading HIV

Rates of HIV infection are converging in 

drug abusers who inject drugs and those 

who do not inject. This indicates that HIV is 

being spread among drug abusers by means 

other than needle sharing (i.e., risky sexual 

behaviors). 

Why it’s important: We need to shift 

focus toward reducing risky sexual behaviors 

among drug abusers, regardless of the route 

of drug administration.

Source: Des Jarlais et al., 2007 AIDS, 21:231–235

For more information 

visit our Web site at: 

www.drugabuse.gov
National Institute on Drug Abuse Strategic Plan

38

Sidebar 21

Interactive “Video Doctor” 

Approach Shows Promise for 

Reducing Drug Use and HIV Risk 

Behaviors

A novel “video doctor” intervention in primary 

care settings reduced risky behaviors among 

HIV-positive patients. Using computer 

simulation, an actor-portrayed physician 

engaged patients in a confidential “faceto-face” discussion about their behaviors. 

The intervention group reported significantly 

reduced drug use, risky drinking, and 

unprotected sex, an effect that persisted at 

the 6-month followup. 

Why it’s important: Such interventions 

could provide a comparatively low-cost 

means of reaching and teaching patients and 

may be an important addition to risk reduction 

efforts in routine clinical practice.

Source: Gilbert P. et al., April 2008 – PLoS ONE 3(4): e1988.

vulnerable to drug abuse and HIV exposure. 

We continue to support research to develop 

innovative means of delivering prevention 

programs to various high-risk populations.

Secondary prevention efforts to reduce 

HIV risk behaviors 

More attention needs to be given to strategies for how best to incorporate HIV education, testing, counseling, and referral into 

drug abuse treatment and outreach efforts. 

This direction requires that we identify 

and address barriers, including stigma and 

treatment access—both for HIV and drug 

abuse––that restrict the benefits associated 

with early HIV detection and linkage to 

care. It also requires finding creative new 

ways to reach and motivate patients (see 

Sidebar 21).

To assist in these efforts, NIDA is pursuing 

research on the best ways to integrate testing 

and counseling into drug abuse treatment 

settings in communities, among criminal 

justice populations, and in international 

regions hit especially hard by the epidemic. 

This includes efforts to advance the 

adoption of rapid-screen technologies. 

Screening for HIV in health care settings 

is as cost-effective as screening for other 

common diseases;22 thus, it makes sense to 

incorporate screening among populations 

where HIV risk is higher than average. 

Individuals who learn they are HIV-positive 

can significantly reduce their risk behaviors 

and, when linked to HAART, become less 

efficient transmitters from the resulting 

reduction in viral load. Therefore, such 

screening would not only provide important 

health and survival benefits for those 

with HIV, but would also help mitigate 

the likelihood of HIV transmission to 

noninfected people. 

In community treatment programs affiliated with NIDA’s CTN and in the criminal 

justice system through our collaborative 

CJ-DATS initiative, NIDA plans to test HIV 
National Institute on Drug Abuse Strategic Plan

39

rapid-screen technologies plus counseling to 

reduce risky sexual behaviors. To improve 

HIV outcomes for criminal justice populations before and after release, NIDA will 

test a new approach termed “Seek, Test, and 

Treat,” which involves reaching out to highrisk, hard-to-reach groups who have not 

recently been tested (seek), providing HIV 

testing (test), and initiating, monitoring, and 

maintaining HAART therapy for those who 

test positive (treat). It also involves providing drug abuse treatment, without which 

individuals may not comply with their antiviral medications. NIDA hopes this initiative 

will not only expand access to HIV testing 

for those in the criminal justice system, but 

will improve the provision and maintenance 

of HAART following community reentry, 

when treatment lapse and viral load rebound 

can heighten risk of HIV transmission. 

3. What can be done to mitigate the 

health disparities associated with HIV/

AIDS?

While all groups are affected by HIV/

AIDS, not all are affected equally. Associated health disparities fall disproportionately 

on ethnic minorities, particularly AfricanAmericans, who are at especially high risk 

for developing AIDS. Even though they 

comprise only 13 percent of the U.S. population, African-Americans accounted for 

approximately half of the total AIDS cases 

diagnosed in 2007.23 Consequences have 

been particularly harsh on African-American 

women, who accounted for 68 percent of the 

female HIV/AIDS diagnoses from 2001 to 

2004.24 Focused research is needed to understand the factors leading to such disparities and to develop targeted interventions to 

reduce HIV/AIDS and its consequences.

Studies are also needed to characterize the 

risk-mitigating roles of culture, family, 

and environmental factors. Indeed, recent 

research suggests that a strategy of targeting 

risk behaviors at the individual level may 

work for Caucasians but not for African-Americans, a population 

that appears to be at very high risk for STDs even if their behavior is 

normative25 (see Sidebar 22).

In addition, although the rates of testing are approximately equal 

across ethnic groups, minority members tend to be tested late in 

the course of infection and frequently experience delays in being 

linked to treatment. This delay contributes to meaningful health 

disparities in terms of disease consequences. We hope to improve 

this situation by increasing knowledge of HIV treatment, which is 

currently less among African-Americans and Hispanics than among 

Sidebar 22

Racial Health Disparities Go 

Beyond Individual Risk Factors

A study examining the relationship between 

race and sexually transmitted disease (STD)/

HIV prevalence showed Caucasian young 

adults in the United States to be at elevated 

STD/HIV risk only when their behavior is 

high-risk; whereas African-American young 

adults are at high risk even when their 

behavior is normative. 

Why it’s important: This study suggests 

that factors other than individual risk 

behaviors appear to account for racial health 

disparities, which argues for population-level 

interventions.

Source: Hallfors et al., 2007 – Am J Public Health 97(1):125–132
National Institute on Drug Abuse Strategic Plan

40

Caucasians. NIDA is encouraging studies investigating 

the relationship of disease progression to treatment and 

service availability, awareness, and use by AfricanAmericans and other minority groups. 

Finally, aggressive outreach must be part of our 

strategy. Media campaigns must strive to inform highrisk subgroups of the prevalence of HIV infection (see 

Sidebar 23); reduce stigma associated with testing; 

and provide testing, counseling, and treatment services 

through nontraditional avenues.

4. How is NIDA’s HIV research program 

contributing to global HIV prevention 

and treatment?

It is estimated that about 30 percent of 

new HIV infections worldwide (outside 

sub-Saharan Africa) stem from injection 

drug use.26 Drug intoxication contributes 

an additional burden of new infections by 

facilitating risky sexual behaviors that can 

transmit HIV. In Eastern Europe and Central 

Asia, for example, intravenous drug use is 

driving 62 percent of new infections27 and 

fueling a multidrug-resistant tuberculosis 

epidemic as well as higher rates of sexually 

transmitted diseases and HCV. Thus, our 

disease prevention strategies seek both 

to increase rates of HIV screening and to 

advance culturally relevant educational 

interventions that include information about 

drug abuse as a major vector for the spread 

of disease.

NIDA’s multifaceted response works to 

better integrate international initiatives 

by region and to take advantage of the 

international research infrastructure funded 

by the National Institute of Allergy and 

Infectious Diseases. The latter aims to 

develop research that targets drug abuse 

treatment programs for their utility as HIV 

and HCV prevention approaches in different 

international settings (see Sidebar 24). These 

involve behavioral as well as medication 

interventions, such as the development of 

a heroin vaccine to help decrease injection 

transmission of HIV.

Sidebar 23

NIDA Public Health Campaign 

Encourages Teens to ‘Learn the 

Link’ Between Drug and Alcohol 

Use and HIV

NIDA’s multimedia “Learn the Link” campaign 

uses TV, print, and Web public service 

announcements to send the message to 

America’s youth that using drugs and alcohol 

can have serious consequences, including 

HIV infection (http://hiv.drugabuse.gov/

index.html). NIDA’s new Spanish-language 

public service announcement is designed to 

reach Hispanic youth with culturally sensitive 

messages about HIV prevention.

For more information 

visit our Web site at: 

www.drugabuse.gov
National Institute on Drug Abuse Strategic Plan

41

5. What are we doing to improve HIV/

AIDS treatment and outcomes in drug 

abusers?

The development of HAART has enabled 

many HIV-infected individuals to experience 

remarkable improvements in their general 

health and quality of life. However, since 

drug abuse can interfere with the efficacy 

of HAART, an urgent need exists to better 

understand drug interactions, both between 

drugs of abuse and HAART and between 

prescribed anti-addiction medications and 

HAART. This interaction can decrease the 

efficacy of a given treatment.

Recent studies show that injection drug 

users can benefit from HAART therapy 

just as people do who do not inject drugs.28

Nonetheless, nonadherence to antiretroviral 

therapy could impact treatment response or 

the development of resistance to HAART. 

Adherence can be particularly problematic 

for drug abusers with chaotic lifestyles, 

which can interfere with their ability to 

follow prescribed regimens. In addition, 

because HAART reduces viral load, some 

patients mistakenly believe that they do not 

need to adhere to the treatment regimen or 

that reduced viral load means elimination 

of the risk of transmitting HIV. This belief 

can, in turn, lead to complacency about 

risk behaviors and resumption of unsafe 

sex and injection practices. NIDA supports 

research to better assess the extent to which 

HIV-positive drug abusers adhere to their 

HAART medications, along with research 

to improve medication adherence among 

substance abusers. 

Sidebar 24

Effective Drug Abuse Medications 

Being Adopted by HIV-Plagued 

Countries

Malaysia has lagged behind in the treatment 

of drug addiction and related disorders, even 

as it is coping with the second highest HIV 

prevalence rate among adult populations 

and the highest proportion of HIV cases 

from injection drug use. Historically, drug 

abusers were “rehabilitated” involuntarily 

in correctional facilities. This primarily 

criminal treatment approach had limited 

effectiveness, which led to widespread public 

dissatisfaction and the recent introduction 

of medications for addiction. These include 

naltrexone (1999), buprenorphine (2001), 

and methadone (2003). 

Why it’s important: These drug 

treatment programs, rapidly embraced by 

the country’s medical community, have 

resulted in tens of thousands of opiatedependent patients receiving medical 

treatment. A similar success story is starting 

to unfold in China as well. Such treatment 

success stories encourage other countries to 

establish their own drug treatment programs. 

Russia, for example, continues to prohibit 

the use of opioid agonist maintenance 

treatments.

Source: Mazlan et al., 2006 – Drug Alcohol Rev 25(5):473–478
National Institute on Drug Abuse Strategic Plan

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Integrating treatment of HIV and HCV 

with drug abuse treatment services is one 

of NIDA’s pivotal goals. This requires us to 

identify the organizational factors that limit 

the provision of coordinated drug abuse, 

HIV, HCV, and other treatment services; 

evaluate innovative approaches to achieve 

better treatment coordination; and determine 

the behavioral and social supports needed by 

drug abusers to engage in and adhere to HIV 

treatment regimens.

Sidebar 25

Pharmacogenomics is Transforming 

our Ability to Predict Medication 

Effectiveness

The harnessing of increasingly powerful genomic 

tools and databases is already having an impact on 

our ability to predict response to medications and 

to deliver treatments. Continuous advances in the 

nascent field of pharmacogenomics are bound to 

greatly increase the efficacy of pharmacotherapeutics 

by matching a medication with the patients who, 

based on their genetic background, are most likely to 

benefit from it and suffer the least adverse effects.

Case in point: Abacavir (Ziagen) is an antiretroviral medication that works by slowing 

the spread of HIV infection in the body. Abacavir is not a cure and does not prevent the 

spread of HIV, but it is used in combination with other medications to treat HIV infection 

in patients with or without AIDS. Unfortunately, excitement over abacavir’s therapeutic 

promise has been dampened by severe allergic reactions that can lead to death. However, 

recent studies have established that the serious and sometimes fatal hypersensitivity 

reactions are significantly more common in patients with a particular human leukocyte 

antigen (HLA) allele, HLA-B*5701. 

Why it’s important: The research suggests that a pretreatment genetic screen for 

HLA-B*5701 can reduce the risk of hypersensitivity reaction to abacavir by close to 100 

percent, enhancing the therapeutic potential of this promising medication. 

HIV

Source: Mallal et al., 2008 – NEJM 358:568–579

Supporting studies to examine conditions 

that result from HIV/AIDS infection and 

drug abuse 

Because of HIV’s ability to invade the brain, 

it is often complicated by central nervous 

system dysfunction. Before the advent of 

HAART, approximately 20 percent of those 

living with HIV eventually developed HIVassociated dementia (HAD),29 characterized 

by a loss of mental functioning with notable 
National Institute on Drug Abuse Strategic Plan

43

motor deficits. HAART has reduced the 

prevalence of HAD; however, the prevalence of milder forms of neurological 

complications may be increasing because 

more people are living longer with the 

disease.30

Emerging evidence suggests a relationship 

between drug abuse (particularly 

stimulants) and accelerated or more 

severe nervous system complications 

of HIV (or neuroAIDS). Because HIVpositive drug abusers can suffer greater 

neurological complications, it is critical to 

better understand how drug abuse affects 

disease progression and pathology. NIDA 

is encouraging both animal and human 

studies examining the interactions between 

drugs of abuse and HIV with respect to 

neuropathological and neurobehavioral 

effects.

We are also interested in research tools 

that may provide information on latent 

viral infection in the brain. Animal 

models are valuable for examining the 

basic mechanisms of HIV-associated 

disease progression and resulting brain 

dysfunction in the context of substance 

abuse. A broad range of anticipated 

studies will increase collaboration among 

researchers in multiple areas, including 

drug abuse, virology, neurobiology, and 

immunology. 

What Is NIDA’s Vision of the Future?

Our ultimate vision is the eradication of HIV/

AIDS throughout the world. This would require the 

development and worldwide distribution of effective 

prevention strategies (behavioral interventions and, 

perhaps, a vaccine) and therapeutic interventions. We 

will also ensure that drug abusers are represented in 

trials for all types of interventions as we strengthen 

our national collaborative network to conduct clinical 

trials. Expected areas of research concentration include 

promising behavioral, microbicidal, prophylactic, 

therapeutic, and vaccine modalities in HIV-infected 

patients and those at risk of infection. Further, through 

pharmacogenomic studies, we expect to be able to 

tailor therapies to minimize adverse reactions and 

drug interactions (see Sidebar 25). And, given that 

drug abuse may play a unique role in exacerbating 

neurologic and psychiatric consequences, the future 

should see significant efforts applied to understanding 

their pathogenesis and to developing better therapies for 

addressing associated impairments. Finally, we envision 

adapting and translating interventions proven effective in 

this country to other areas of the world. 

For more information 

visit our Web site at: 

www.drugabuse.gov
National Institute on Drug Abuse Strategic Plan

44

IV. CROSS-CUTTING PRIORITIES

Several additional priority areas span NIDA’s portfolio and contribute 

to our overall mission to prevent or reduce drug abuse and addiction.

These areas are highlighted below.

Major Goals 

1. To foster research on other health conditions that may inform, 

influence, or interact with drug abuse and addiction (e.g., pain, compulsive 

behavioral disorders).

2. To decrease health disparities related to drug addiction and its 

consequences.

3. To educate a variety of audiences (e.g., criminal justice, medical, and 

educational systems in the community; media; and legislators) about the 

science underlying drug abuse.

4. To train and attract new investigators with diverse experiences—

including those from minority or disadvantaged backgrounds—and to 

actively recruit chemists, physicists, bioengineers, and mathematicians to 

conduct translational research on drug abuse.

5. To promote collaborative international research activities that address 

nicotine addiction, HIV/AIDS, and emerging trends, as well as training 

and dissemination of science-based information on drug abuse.

.

NIDA has built a solid foundation designed to 

achieve these goals by nurturing interactions 

with different NIH Institutes, agencies, and 

other stakeholders, and by supporting research 

and outreach that respond to the following five 

questions:

1. What are other health conditions that 

interact with drug abuse and addiction?

Multiple health conditions share important 

features with drug abuse and addiction. 

Thus, research in these areas may inform and 

impact drug abuse research and vice versa. 

For example, the brain circuitry involved in 

natural rewards that motivate us to engage in 

everyday survival behaviors, such as eating, 

overlaps with the neural circuitry engaged 

by addictive drugs to reinforce drug taking. 

These brain circuits are part of normal adaptive 

processes; and when challenged with powerful

reinforcers such as drugs of abuse or fattening 

foods, these circuits can bring about a loss of 

control and subsequent addiction or obesity, 

respectively. 

Understanding the biological underpinnings 

of how addiction and other independent or 

co-occurring disorders (e.g., compulsive 

behavioral disorders, pain, etc.) interrelate 

may give us insight into more effective 

treatment and prevention approaches for 

these disorders. NIDA continues to encourage 

research to explore these linkages from several

perspectives—basic biology, epidemiology, 

prevention, and treatment––with the hope of 

leveraging the science from one disorder to 

inform another.
National Institute on Drug Abuse Strategic Plan

45

Compulsive Behavior Disorders. A number of 

mental disorders have hallmark symptoms (e.g., 

compulsive behaviors and obsessive thinking) 

similar to those of addiction, with obsessivecompulsive disorders (OCDs) and eating disorders among the most common. Their shared 

symptomatology may reflect similarities in 

the brain regions affected by the disorder. For 

example, the orbitofrontal cortex, which has 

been associated with the subjective experience 

of drug craving in addicted subjects, has also 

been implicated in OCD behaviors. Similarly, 

reduced brain activity of dopamine, a naturally 

occurring substance that regulates feelings of 

pleasure, has been implicated both in drug addiction and in obesity, which may reflect a common motivational deficit, but with food instead 

of drugs. Thus, NIDA seeks to understand the 

common etiologies of these disorders at the 

genetic, molecular, cellular, and circuit levels. 

Pain. For the more than 50 million Americans 

with chronic pain, prescription opioid pain 

medications are a necessary and useful treatment. However, opioid treatment can produce 

negative health consequences, such as physical 

dependence and addiction. The prevalence of 

chronic pain and how to prevent, reduce, and 

treat its negative health consequences are not 

well understood. NIDA continues to examine 

the factors (including pain itself) that predispose or protect pain patients from opioid abuse 

and addiction. We also are pursuing ways 

to prevent opioid abuse when treating pain, 

including supporting development of novel 

pain medications with reduced or no abuse and 

addiction liability. 

2. How is NIDA addressing health 

disparities related to drug abuse and its 

consequences?

The pattern of addictions and the burden of 

disease are not shared equally among members 

of our population. For example, the disproportionate abuse of methamphetamine among 

American Indians and Alaskan Natives––higher 

than any other subgroup––prompts a need for 

targeted interventions that can effectively reach 

these groups. However, contrary to a common stereotype, overall 

rates of drug abuse among racial and ethnic minorities, particularly 

African-Americans and Hispanics, are similar to rates in the general population. Nonetheless, these groups incur greater medical and 

social consequences of their drug use than Whites (see Figure 3), 

including involvement with the criminal justice system and greater 

disease vulnerability (see section III, “HIV/AIDS”).

Figure 3

Incarceration rates and HIV incidence in IDUs are 

disproportionately higher in ethnic minorities 

Ethnic Breakdown of (A) Incarceration Rates for Drug 

Abusers, 2006, and (B) Incidence of HIV in IDUs, 2007

Sources: (a) U.S. Census Bureau, Population Estimates Program, 2006; 

NSDUH, 2007; U.S. DOJ, BJS, Prisoners in 2006, Bulletin (b) U.S. Census 

Bureau, Population Estimates Program, 2007; NSDUH, 2008; CDC, HIV/

AIDS Surveillance in Injection Drug Users (through 2007)

(A)

(B)
National Institute on Drug Abuse Strategic Plan

46

NIDA has developed a separate Strategic Plan on Reducing Health Disparities that includes research, infrastructure and capacity building, and community outreach 

components (for more details, see http://www.drugabuse.

gov/StrategicPlan/HealthStratPlan.html). Brief highlights of our ongoing and planned activities follow:

• Epidemiologic data clearly show that minority groups 

differ in drug use patterns, preferences, accessibility, 

and risks. Thus, research is needed to look at factors 

that convey protection or risk across different ethnic 

and age categories. Studies must examine the role 

of culture, religion, ethnic identity, family, peer, 

and environmental/community-level factors in drug 

initiation and drug abuse trajectories. 

• We must also better understand the racial/

ethnic implications of genetic variation 

that modifies the neurotoxicity of different drugs, as well as the neurobiological 

processes underlying tolerance, dependence, and relapse. Pharmacokinetic 

studies have revealed distinct differences 

in some ethnic populations’ ability to 

metabolize different drugs–– this affects 

sensitivity to the drugs’ or medications’ 

pharmacological effects.

3. How does NIDA “get the word out” 

about the many facets of drug abuse 

and addiction to better prevent it? 

As the supporter of most of the world’s 

research on the health aspects of drug abuse 

and addiction, NIDA is uniquely positioned 

to educate the public and displace long-held 

mistaken beliefs about drug abuse with scientific evidence about drugs and addiction. 

Because most drug use begins during adolescence, it is vitally important that youth 

are informed of drugs’ effects on their developing brains and bodies to help them choose 

not to use drugs. 

• NIDA continues to develop and update 

science-based educational materials for 

grades K–12 (and beyond) and disseminate them for free to schools (see Sidebar 

26). By exposing children of all ages to 

neurobiology and drug education in fun, 

age-appropriate, and relevant ways, we 

hope to prevent them from using drugs 

and also spark their interest in scientific 

careers. 

• NIDA is updating the design of our 

“NIDA for Teens” Web site (http://teens.

drugabuse.gov), aimed primarily at 

educating middle school adolescents ages 

11–15 (as well as their parents and teachers) on the science behind drug abuse. We 

have enlisted the help of teens in developSidebar 26

NIDA-Developed Materials on 

Drug Abuse Widely Used in School 

Curricula 

Brain Power! The NIDA Junior Scientist 

Program is designed to take students 

through a step-by-step exploration of the 

scientific process and how to apply it to learn 

about the brain and the effects of drugs 

on the nervous system and body. Such 

materials have already been developed for 

elementary and middle school grades K-9.
National Institute on Drug Abuse Strategic Plan

47

ing this site to ensure that the content addresses appropriate questions and timely 

concerns. Interactive games are among 

the recent additions. 

• NIDA intends to expand our foray into 

new media. We have begun a blog aimed 

at teens and use it as a two-way communications tool, responding to the 

many comments it elicits. NIDA has 

also started “tweeting” and continues to 

place short, topical videos on YouTube, as 

well as host a MySpace page on the link 

between drugs and HIV. As an expansion 

of our annual “Chat Day,” where students 

from across the country learn the facts 

about drug abuse from NIDA scientists, 

NIDA plans in 2010 to launch “National 

Drug Facts Week,” with Chat Day at 

its center. Other events will take place 

nationwide to arm teens with information 

that can help them make healthy decisions.

• NIDA continues to design and develop 

public information and education campaigns, as well as materials on drug abuse 

and addiction for a variety of audiences. 

For example, we are building on the success of our award-winning public service 

announcement on the link between drug 

abuse and HIV/AIDS risk, and continue 

to take advantage of mainstream and 

emerging media vehicles such as HBO 

broadcasts (see Sidebar 27) and Internet 

chats. 

4. How does NIDA help ensure a 

continuing supply of well-trained 

scientists equipped to conduct highimpact drug abuse research? 

An important part of NIDA’s mission is 

to promote an ongoing source of trained 

clinicians and clinical research scientists 

from diverse backgrounds who can conduct 

research on various aspects of addiction, 

including HIV/AIDS, health disparities, 

Sidebar 27

NIDA Works with HBO and Other 

Partners to Present ‘Addiction’ 

Documentary

NIDA partnered with HBO, NIAAA, and 

the Robert Wood Johnson Foundation 

on a groundbreaking and Emmy Award–

winning documentary called Addiction. 

The feature-length film is part of a 

multimedia public health campaign that 

also included a Web site, book, and 

community outreach activities. The goal 

of this project, launched in 2007, was to 

help Americans understand addiction 

as a chronic yet treatable brain disease 

through spotlighting promising scientific 

advancements and personal testimonials. 

Circulation of these materials has reached 

tens of millions.
National Institute on Drug Abuse Strategic Plan

48

and other issues critical to drug abuse research. We also 

need to reach across domains to engage scientists from 

fields such as mathematics, bioengineering, and physics 

to apply their knowledge to the study of drug abuse and 

addiction. 

To sustain our research infrastructure, NIDA continues 

to support training initiatives that support a broad range 

of scientists, from diverse backgrounds, both within 

and across scientific boundaries (see Sidebar 28). The 

following briefly summarize several initiatives:

• National Research Service Awards 

(NRSA) to institutions and individuals, 

including the predoctoral diversity 

awards. NIDA currently funds more than 

50 institutional training sites for both 

predoctoral and postdoctoral fellows 

nationwide.

• Career Development (Mentored K) 

Awards for emerging scientists or those 

changing career trajectories to study drug 

abuse and its related consequences (e.g., 

HIV/AIDS). These include the Mentored 

Clinical Scientist Development Award 

(K08) and Mentored Patient-Oriented 

Research Career Development Award 

(K23), designed to provide “protected 

time” for clinically trained individuals 

to participate in an intensive, supervised 

training program in biomedical or patientoriented drug abuse research. The K25 

Award is for quantitative scientists 

interested in applying their expertise to 

research related to drug abuse or HIV/

AIDS.

• Pathway to Independence (PI) 

Award Program (K99/R00), designed 

to augment existing programs that 

provide mentored research and career 

development experiences for new 

investigators. This program provides a 

unique opportunity for highly promising 

postdoctoral scientists to obtain support 

for both the initial 1–2-year mentored 

phase and the later independent phase, 

before applying for an NIH R01 grant. 

• Dissertation Awards (R36) for specific 

drug abuse topic areas; Research 

Education Awards (R25) for curriculum 

and program development; and Small 

Grant Programs (R03) to allow 

researchers new to a field to obtain data 

for developing research programs in 

needed areas, such as imaging, AIDS, 

behavioral research, and chemistry. 

Sidebar 28

Research Training Programs 

Ensure Continuing Supply of 

Investigators Studying Drug Abuse 

and Addiction

NIDA offers a strategic set of funding 

mechanisms to support the development of 

research scientists through various stages 

of their careers. These awards are designed 

to ensure that scientists of the very highest 

caliber are available in adequate numbers 

and in the appropriate research areas and 

fields to meet the Nation’s need for drug 

abuse and addiction research.
National Institute on Drug Abuse Strategic Plan

49

Diversity Supplements and other 

training experiences are available for 

minority students, beginning in high 

school and continuing through their 

postdoctoral phase and beyond. 

• NIH Loan Repayment Programs, 

a vital component of our Nation’s 

efforts to attract health professionals to 

research careers, are reflective of NIDA’s 

commitment to developing clinical and 

pediatric researchers.

• Diversity-Promoting Institutions’ Drug

Abuse Research Programs (DIDARP) 

include grants and cooperative 

agreements, aimed at building research 

capacity at institutions serving minority 

populations.

5. What are NIDA’s strategic 

international priorities? 

Since the early 1990s, the NIDA 

International Program has worked to create 

local, regional, national, and international 

networks that advance scientific knowledge 

through research. The International Program 

extends our mission through building 

up other countries’ research capacities 

to address the public health impact of 

drug abuse and addiction by creating 

opportunities for collaboration, training, 

and scientific exchange, and disseminating 

that knowledge to scientists, treatment 

providers, and policymakers around the 

world. These efforts help to translate our 

domestic successes in curtailing drug abuse 

and related consequences, such as with HIV/

AIDS, to other countries, and allow us to 

learn from their strides in disease prevention 

and eradication.

Stemming the global spread of drug abuse-related HIV 

is a top NIDA priority for our international efforts (see 

section III, question 5), and one for which international 

collaboration is vital. Through our International 

Program, NIDA is facilitating collaborations with 

partners in about 20 countries, developing research 

networks and tailoring studies to meet local needs 

and conditions. In addition, NIDA is to become a 

Collaborating Center of the World Health Organization, 

formalizing the long-standing cooperation between the 

two agencies. 

Among the top priorities are reducing nicotine addiction 

and gaining knowledge about new drug abuse trends 

internationally. While smoking prevention and cessation 

programs have contributed to a significant decline 

in the United States, the rest of the world continues 

to experience high rates of smoking and associated 

illnesses. NIDA continues to work cooperatively with 

other countries to reduce smoking worldwide and 

to share the latest research findings by facilitating 

collaboration with U.S.-based resources. 

As new drug abuse threats emerge around the world, 

we identify and address them. NIDA has identified 

five research priorities for which we are advancing 

international collaborative efforts to set standards, 

design comparative research protocols, and improve data 

collection on core variables—all to ensure a scientific 

approach to the study of these priorities. These five 

priorities are (1) linkages between HIV/AIDS and drug 

abuse; (2) adolescent and prenatal tobacco exposure; (3) 

inhalant abuse; (4) methamphetamine; and (5) drugged 

driving. 

As part of efforts to increase the capacity and capability 

of affected countries, NIDA’s International Program 

works closely with the Fogarty International Center, 

whose mission is to facilitate international cooperation 

throughout NIH. In collaboration with the Fogarty 

International Center’s AIDS International Training 

and Research Program, we support joint research 

training and infrastructure-building programs through 

partnerships with U.S.-based academic centers.

For more information 

visit our Web site at: 

www.drugabuse.gov
National Institute on Drug Abuse Strategic Plan

50

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National Institute on Drug Abuse.

2 Paulozzi, L.J., Budnitz, D.S., and Yongli, X. (2006). Increasing deaths from opioid analgesics in the United 

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National Institute on Drug Abuse Strategic Plan


NIH Publication Number 10-6119 

Printed September 2010