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Drug 

Abuse 

Treatment
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Abuse 

Treatment

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Introduction

The National Institute on Drug Abuse (NIDA) supports most of the world’s research on drug abuse and addiction. 

NIDA-funded research enables scientists to apply the most advanced techniques available to the study of every aspect of 

drug abuse, including:

• genetic and social determinants of vulnerability and response to drugs;

• short- and long-term effects of drugs on the brain, including addiction;

• other health and social impacts of drug abuse, including infectious diseases and economic costs;

• development and testing of medications and behavioral treatments for abuse and addiction; and

• development and evaluation of effective messages to deter young people, in particular, from abusing drugs.

Included in this document are selections of topic-specific articles reprinted from NIDA’s research newsletter, 

NIDA NOTES. Six times per year, NIDA NOTES reports on important highlights from NIDA-sponsored research, 

in a format that specialists and lay readers alike can read and put to use. Selections like the current one are intended 

to remind regular NIDA NOTES readers and inform other readers of important research discoveries during the periods 

they cover.

We hope the information contained here answers your needs and interests. To subscribe to NIDA NOTES and for 

further information on NIDA’s drug abuse and addiction research, please visit our Web site at www.drugabuse.gov.
iii

Court Mandates Help Men With Antisocial Personality 

Disorders Stay in Treatment (V22-3; April 2009) .........1

Research Addresses Needs of Criminal Justice Staff and 

Offenders (V22-3; April 2009) ......................................2

Effective Treatment Is Not Widely Available 

(sidebar) (V22-3; April 2009) ........................................2

Legal Pressure Increases Treatment Retention 

(V22-3; April 2009).......................................................4

High-Risk Drug Offenders Do Better With Close 

Judicial Supervision (V22-2; December 2008)...............5

Drug Courts Add Value (sidebar)

(V22-2; December 2008)...............................................6

Reducing Postpartum Drug Use 

(V22-2; December 2008)...............................................7

Lofexidine May Enhance Naltrexone Efficacy 

(V22-2; December 2008)...............................................7

New Therapy Reduces Drug Abuse Among Patients 

With Severe Mental Illness (V21-6; June 2008).............8

Combination Treatment Extends Marijuana 

Abstinence (V21-5; March 2008) ................................10

Sertraline Does Not Help Methamphetamine Abusers 

Quit (V21-5; March 2008)..........................................12

Chronic Cocaine Abusers Have Occult Insomnia in 

Early Abstinence (V21-5; March 2008) .......................14

Bupropion Reduces Meth’s Subjective Effects and 

Cue-Induced Craving (V21-5; March 2008)................16

NIDA’s Newest Division Mines Clinical Applications 

From Basic Research (V21-4; October 2007) ..............17

Standard Treatments Help Depressed Smokers Quit 

(V21-3; April 2007).....................................................19

Computer Feedback Nurtures Change 

(sidebar) (V21-3; April 2007) ......................................20

Depot Naltrexone Appears Safe and Effective for 

Heroin Addiction (V21-3; April 2007)........................21

Interim Methadone Raises Odds of Enrolling in 

Comprehensive Treatment (V21-3; April 2007)..........23

Study Specifics (sidebar) (V21-3; April 2007)..............24

Incentives Reduce Stimulant Abuse During Methadone 

Maintenance (V21-3; April 2007)................................25

Naltrexone-Nicotine Patch Combination Shows Promise 

(V21-3; April 2007).....................................................25

Cocaine Abusers’ Pretreatment Cue Responses Predict 

Recovery Success (V21-2; February 2007) ...................26

Stress Cues Also Signal Relapse Risk (sidebar) 

(V21-2; February 2007)...............................................28

NIDA’s division of Basic Neuroscience and Behavioral 

Research (V21-2; February 2007) ............................... 29

Medical Care During Addiction Treatment Reduces 

Hospital Use (V21-2; February 2007)......................... 31

Low-Cost Incentives Improve Outcomes in Stimulant 

Abuse Treatment (V21-1; October 2006)....................32

Study Finds Withdrawal No Easier With Ultrarapid 

Opiate Detox (V21-1; October 2006) .........................34

Buprenorphine Plus Behavioral Therapy Is Effective 

For Adolescents With Opiod Addiction 

(V21-1; October 2006)................................................36

Court-Mandated Treatment Works as Well as 

Voluntary (V20-6; July 2006)......................................38

Checkup System Catches Relapse Early and Facilitates 

Return to Treatment (V20-6; July 2006).................... 40

Medications Development Division Nurtures 

the Creation of New Addiction Treatments 

(V20-6; July 2006)...................................................... 42

Community-Based Treatment Benefits 

Methamphetamine Abusers (V20-5; April 2006)........ 44

Treatment During Work Release Fosters Offenders’ 

Successful Community Reentry (V20-5; April 2006)..... 46

A Brief Encounter With Peer Educator Can Motivate 

Abstinence (V20-3; October 2005)............................. 48

Telephone-Based Continuing Care Sustains 

Abstinence (V20-3; October 2005)............................. 50

Successful Drug Abuse Treatment in Adolescents

Should Address Co-Occuring Mental Health

Problems (V19-6; May 2005) ..................................... 53

Economists Offer Program for Costing Out

Drug Abuse Treatment (V19-5; January 2005)........... 55

Adults With Co-Occuring Depression and

Substance Abuse Benefit From Treatment

of Depression (V19-4; December 2004) ..................... 58

Table of Contents
CTN Update: Teamwork Develops Treatment

Concept Into Study Protocol 

(V19-4; December 2004)............................................ 59

Testing New Treatments in the Nation’s Clinics

(V19-1; April 2004).................................................... 60

Developing Effective Addiction Treatments

(V19-1; April 2004).................................................... 64

Animal Studies Suggest D3 Receptors Offer

New Target for Treatment Medications

(V18-4; November 2003)............................................ 66

Network Therapy Expands Treatment Capabilities

Of Small Practice Providers (V18-2; August 2003)...... 70

A Double Dose of Research for Patients Addicted

to Both Drugs and Alcohol (V18-1; June 2003)......... 72

Treating Adolescent Substance Abuse by Addressing 

Family Interactions (V18-1; June 2003)...................... 74

Family-Based Treatment Programs Can Reduce

Adolescent Drug Abuse (V17-4; November 2002)...... 75

New Insights Into Relapse (V17-3; October 2002)..... 77

In Drug Abuse, Gender Matters

(V17-2; May 2002)..................................................... 79

Adolescent Treatment Programs Reduce

Drug Abuse, Produce Other Improvements

(V17-1; April 2002).................................................... 81

NIDA Clinical Trials Network Begins First 

Multisite Tests of New Science-Based Drug Abuse 

Treatments (V15-6; January 2001)............................. 83

Gender Differences in Drug Abuse Risks and 

Treatment (V15-4; September 2000).......................... 85

Treating the Brain in Drug Abuse 

(V15-4; September 2000) ........................................... 86

Drug Abuse Treatment Programs Make Gains 

in Methadone Treatment and HIV Prevention 

(V15-3; August 2000)................................................. 88

Adding More Counseling Sessions and 12-Step 

Programs Can Boost Drug Abuse Treatment 

Effectiveness (V14-5; December 1999)....................... 90

The State of the Art in Drug Addiction Treatment 

(V14-5; December 1999)............................................ 92

Thirteen Principles of Effective Drug Addiction

Treatment (V14-5; December 1999) .......................... 94

Medications Reduce Incidence of Substance 

Abuse Among ADHD Patients 

(V14-4; November 1999) ........................................... 95

Drug Abuse and Mental Disorders: Comorbidity 

Is Reality (V14-4; November 1999)............................ 98

Clinical Trials Network Will Speed Testing and 

Delivery Of New Drug Abuse Therapies 

(V14-1; April 1999).................................................. 100

Antistress Medications May Help Drug Abuse 

Patient Avoid Relapse (V14-1; April 1999)............... 102

Treating Mood Disorders in Drug Abuse Patients 

Yields Improvements in Both Conditions 

(V13-6; March 1999)................................................ 103

Matching Drug Abuse Treatment Services to 

Patient Needs Boosts Outcome Effectiveness 

(V13-5; February 1999)............................................ 105

Men and Women in Drug Abuse Treatment 

Relapse at Different Rates and for Different Reasons 

(V13-4; November 1998) ......................................... 107

Drug Addiction Treatment Conference Emphasizes 

Combining Therapies (V13-3; July 1998) ................ 109

Study Sheds New Light on the State of Drug Abuse 

Treatment Nationwide 

(V12-5; September/October 1997) ........................... 111

Peer Community Helps Homeless Drug Abusers 

With Mental Illnesses Reduce Drug Use 

(V12-4; July/August 1997) ....................................... 115

Access to Housing and Job Training Helps 

Recovering Homeless People Stay Drug Free 

(V12-4; July/August 1997) ....................................... 118

iv
Research Findings

Volume #, Number (Month Year)

1

Court Mandates Help Men With Antisocial Personality Disorders 

Stay in Treatment

Volume 22, Number 3 (April 2009)

Men with co-occurring substance abuse and antisocial personality disorders may particularly benefit from judicially 

mandated addiction treatment. Such legal pressure has 

been shown to exert a positive effect on treatment retention in a general population of drug abusers (see What the 

Numbers Say).

Dr. Stacey B. Daughters and colleagues at the University 

of Maryland recently studied 236 men who began therapy 

for substance abuse problems. Ninety-three of the men 

met standard criteria for antisocial personality disorder 

(ASPD), a condition characterized by chronic behavior 

problems, deceitfulness, and lack of conscience and regard 

for others.

Among men without ASPD, 85 percent remained in 

therapy whether the treatment was voluntary or mandated. However, the investigators found that among men 

with ASPD, about 94 percent of those who were legally 

required to participate in residential substance abuse 

treatment remained for a month, compared with just 63 

percent of those who had volunteered to enter treatment.

Although ASPD is rare in the general population, 

researchers estimate that 40 to 50 percent of people 

in drug treatment programs have the disorder. 

Moreover, prior research 

suggests that ASPD 

increases the risk for a

ddiction treatment dropout, relapse, and, among 

those with jail sentences, a 

return to criminal behavior.

The Maryland team’s findings have two important 

implications for substance 

abusers with ASPD: Judicial mandates offer a way to keep 

them in addiction treatment programs, and voluntary 

participants may require special interventions to keep 

them actively engaged in therapy.

Source

• Journal of Substance Abuse Treatment 34(2):157-164, 

2008. 

1
Research Addresses Needs of Criminal Justice Staff and Offenders

By Lori Whitten, NIDA Notes Staff

Research Findings

Volume 22, Number 3 (April 2009)

NIDA established the Criminal 

Justice-Drug Abuse Treatment Studies 

(CJ-DATS) project in 2002 to reduce 

substance abuse and recidivism among 

offenders following their release from jail 

or prison. CJ-DATS investigators in nine 

research centers collaborate with criminal 

justice partners to fashion and test sciencebased, practical tools for integrating drug 

abuse treatment in the Nation’s prisons 

and probation and parole programs.

Dr. Bennett Fletcher serves as CJ-DATS 

program scientist and provides NIDA 

input to the network’s planning and decisionmaking. According to Dr. Fletcher, 

“As many as half of the individuals serving 

sentences in the Nation’s jails and prisons 

have drug problems. The transition from 

detention or incarceration is a period of 

high risk for relapse to drug use, acquisition and transmission of infectious diseases, and drugrelated recidivism. In its first 5 years, CJ-DATS identified 

a range of effective practices to reduce these risks. The 

project is now beginning a new phase of research to determine how correctional and community agencies can most 

efficiently and effectively implement and sustain these 

practices.”

Identifying Effective Practices

The first phase of CJ-DATS encompassed 13 studies in 

three areas:

Brief Screening and Assessment Instruments—These 

studies give criminal justice staff user-friendly tools to 

identify an offender’s need for treatment and criminal justice services and to monitor his or her treatment progress. 

The researchers have designed a variety of instruments to 

help providers determine whether a prisoner is responding 

to therapy, requires referral to a mental health provider, 

or will need intensive treatment after release. Studies show 

that these instruments have good reliability, validity, sensitivity, and specificity.

Strategies to Promote Successful Community 

Re-entry—Many individuals need help to stay engaged 

in addiction treatment as they re-enter communities following release from prison. Many also require assistance 

with housing, employment, family relationships, health 

issues, and building a social support network. CJ-DATS 

researchers and their criminal justice partners together 

developed interventions (see box) to reduce re-entering 

adults’ and adolescents’ criminal activity, substance 

abuse relapse, and sexual behaviors that carry high risk 

of HIV/AIDS and other sexually transmitted diseases. 

Investigators have now tested interventions in seven randomized controlled trials, with 3- and 9-month followups. 

Several appear promising.

Surveys of Treatment Services for Offenders—A 

team led by the CJ-DATS Research Center at Virginia 

Commonwealth University and the University of 

Maryland conducted a National Criminal Justice 

Treatment Practices Survey to inventory treatments available in correctional facilities, community supervision 

programs, and drug treatment programs with offender 

clientele. The data included information on treatment 

providers, frequency and duration of treatment, and the 

number of offender clients. The results indicate that there 

is a significant shortage of treatment opportunities for this 

population (see box).

Another survey, by investigators at the National 

Development and Research Institutes Rocky Mountain 

2
3

Research Center, focuses on services 

for offenders who have both substance 

abuse and other mental disorders—a 

large and growing percentage of the 

U.S. criminal justice population. This 

survey is using the specially developed 

CJ-DATS Co-occurring Disorders 

Screening Instrument (CODSI) to 

identify patients with dual disorders. 

The findings will provide a foundation for efforts to improve treatment 

services for these offenders.

In a third practice-monitoring project, 

CJ-DATS investigators are developing 

a Web-based system to inventory drug 

court processes and treatment services for the drug court participants. 

The researchers have pilot-tested a 

drug court management information system based on the Center for 

Substance Abuse Treatment’s Web 

Infrastructure for Treatment Services 

(WITS) system.

New Directions

Over the next 5 years, CJ-DATS 

investigators will shift their focus to 

issues of implementation. NIDA program officer Dr. Akiva Liberman says, 

“The new studies will identify efficient and effective ways to implement 

screening and assessment tools, a continuum of HIV care, and behavioral 

or medications interventions. They 

will provide criminal justice organizations with science-based information on how staffing, infrastructure, 

policies, practices, and incentive 

systems may be adjusted to facilitate 

new evidence-based practices.” Dr. 

Liberman will monitor these studies. 

Dr. Redonna K. Chandler, chief of 

NIDA’s Services Research Branch in 

the Division of Epidemiology, Services and Prevention 

Research, says, “Federal, state, and community criminal justice facilities are overwhelmed by the number of 

offenders with drug problems, and many administrators 

and staff want to incorporate addiction treatment into 

their programs. CJ-DATS will offer them evidence-based 

therapies and information to guide decisionmakers as they 

integrate treatment into their services.”

To date, reports of CJ-DATS research have appeared in 

several publications and in five special issues: The Prison 

Journal, March 2007; the Journal of Substance Abuse 

Treatment, April 2007; Criminal Justice and Behavior, 

September 2007; Behavioral Sciences and the Law, July/

August 2008, and the Journal of Psychoactive Drugs, 

December 2008. For more information about ongoing 

research from the CJ-DATS treatment studies, visit 

www.cjdats.org. 

3
Research Findings

Volume #, Number (Month Year)

4

Legal Pressure Increase Treatment Retention

Volume 22, Number 3 (April 2009) 
High-Risk Drug Offenders Do Better With Close Judicial 

Supervision

Low-risk offenders do equally well with and without regularly scheduled court appearances.

By NIDA NOTES Staff

Research Findings

Volume 22, Number 2 (December 2008)

Adjusting the frequency of mandatory drug court monitoring sessions according to offenders’ risk of lapsing into 

criminal activity, including drug abuse, can enhance program success rates while conserving resources, according to 

a recent NIDA-supported study. Researchers found that 

high-risk drug offenders—those with antisocial personality disorder or prior histories of drug abuse treatment—

achieved better outcomes when ordered to attend a judicial 

status hearing every 2 weeks, rather than at the 4- to 6-week 

intervals that drug courts typically impose. In contrast, 

lower risk offenders’ treatment success was not compromised when courts required them to appear only if they 

committed serious or repeated infractions of program rules.

“Our research represents a first step in tailoring adaptive 

supervision interventions to drug-abusing offenders,” says 

Dr. Douglas Marlowe of the Treatment Research Institute 

and the University of Pennsylvania, Philadelphia. Dr. 

Marlowe, Dr. David Festinger, and colleagues conducted 

the study as part of a broader effort to improve the efficacy 

and cost-effectiveness of drug court interventions by identifying which components of the model work best for various 

groups of drug offenders.

Custom Tailoring Court Supervision

Drug courts are intensive, community-based programs that 

substitute judicially supervised treatment and case management for prosecution or incarceration. Defendants who 

complete the drug court program and remain arrest-free for 

6 months after graduation have their charges dropped and 

their arrest records expunged. The judicial status hearing, 

during which a judge rewards achievements and punishes 

infractions with sanctions that progressively increase in 

severity, is among the costliest components of drug 

court programs.

Drs. Marlowe and Festinger designed their study to answer 

two questions: Would high-risk drug offenders benefit from 

hearings held more frequently than usual, and would lowrisk drug offenders still experience treatment gains if their 

hearings were held less often than the norm? The researchers had reason to predict the answers would be “yes” to 

both questions because of observations they had made in a 

previous study. That study’s design and small participant 

population, however, had not allowed definitive findings on 

these issues.

Participants in the new study were recruited from a misdemeanor drug court in Wilmington, Delaware. Among 

the drugs that they reported abusing at the time of their 

assignment to drug court, cannabis was the most common, 

followed by alcohol, stimulants or cocaine, opiates, sedatives, and hallucinogens. Each participant was assigned to a 

clinical case manager who coordinated treatment referrals, 

submitted monthly reports to the judge, and appeared at 

the participant’s judicial status hearings.

Ninety-two of the 279 participants were classified as highrisk because they had an antisocial personality disorder 

or had relapsed after previous treatment for drug abuse. 

Within the high-risk group, 42 were assigned to report to 

drug court biweekly, and 50 reported every 4 to 6 weeks. In 

the low-risk group, 92 were put on the 4- to 6-week schedule, and 95 were told to appear in court only after serious 

rule infringements—most commonly failure to attend 

counseling appointments or provide drug-free 

urine specimens.

Within a year, 75 percent of the high-risk participants who 

attended hearings every 2 weeks graduated from the program, compared with 56 percent of high-risk participants 

assigned to follow the standard schedule. The former 

5
6

group also provided more drug-free urine samples and 

reported less alcohol intoxication (see table), as well as 

less criminal activity.

Among the low-risk participants, outcomes were similar 

regardless of how often hearings took place. For example, 

program graduation rates were 75 percent among the 

offenders who appeared in drug court every 4 to 6 weeks 

and 72 percent among those who appeared in court only 

when a problem arose, averaging less than two hearings 

during the study year. “Reducing the number of court 

hearings for these individuals could permit a program to 

conserve costly resources without sacrificing client outcomes or public safety,” Dr. Marlowe says.

Room for Improvement

“Adjusting the frequency of court hearings to participants’ risk status will make a difference, but there still 

will be considerable room for improvement in drug court 

outcomes,” Dr. Marlowe notes. For high-risk participants who continue to have drug or alcohol problems, 

the program needs further tailoring, he explains. Those 

who are not compliant with the program—for example, 

those who fail to attend counseling sessions or to deliver 

urine specimens—might respond to more frequent judicial supervision or to sanctions such as home curfews. In 

contrast, increasing the scope of treatment services might 

be more effective with high-risk participants who are compliant with program rules but fail to achieve abstinence 

because of the severity of their drug addiction or a related 

difficulty, such as a co-occurring mental disorder, family 

problems, unemployment, or homelessness. Dr. Marlowe 

notes that even low-risk drug offenders need more effective interventions.

“Dr. Marlowe is helping us fill our knowledge gap 

about drug courts by identifying the elements that make 

them effective,” says Dr. Redonna K. Chandler, chief of 

NIDA’s Services Research Branch. “We may eventually 

be able to match criminal justice supervision and treatment services to the needs of individual offenders, making 

drug courts both more effective and 

more costeffective.” Dr. Marlowe says, 

“We hope that drug court programs 

eventually become flexible enough to 

allow participants doing poorly to be 

switched to a more intensive track and 

allow those doing well in an intensive 

program to move to a lower supervision 

regimen.”

Source

• Marlowe, D.B., et al. Adapting judicial supervision to the risk level of 

drug offenders: Discharge and 

6-month outcomes from a prospective 

matching study. Drug and Alcohol 

Dependence 88(Suppl. 2):S4-13, 

2007. 
Reducing Postpartum Drug Use

Research Findings

Volume 22, Number 2 (December 2008)

In a recent clinical trial, a 20- minute computerized intervention reduced new mothers’ 

drug abuse in the first 4 months postpartum. The computer software program, which was 

developed by Dr. Steven J. Ondersma and colleagues at Wayne State University in Detroit 

and Virginia Commonwealth University in Richmond, was administered in an urban 

obstetric hospital soon after each woman gave birth. The program features an animated 

narrator who asks questions, addresses ambivalence, provides feedback, and offers options. 

The intervention also included vouchers for an initial session of drug treatment and 

an easy-to-read brochure, mailed to the women after they took their babies home, 

that discussed infant and maternal health and briefly addressed drug abuse. The researchers 

estimated that the intervention had a “small to moderate” beneficial effect in their study 

population—107 mostly poor women who abused drugs. At a 4-month followup, those 

who received the intervention reported using cocaine, amphetamine, and opiates less 

frequently than before the birth, while the comparison group reported slightly increased abuse of these drugs. No

definitive differences were observed between the two groups regarding marijuana use.

Source

• American Journal of Preventive Medicine 32(3):231-238, 2007. 

Lofexidine May Enhance Naltrexone Efficacy

The anti-hypertensive medication lofexidine is used commonly in the United Kingdom and less often in the United 

States to alleviate symptoms of opiate withdrawal. Now, a pilot study by Dr. Rajita Sinha and colleagues at Yale 

University School of Medicine suggests that lofexidine can enhance success rates among patients taking maintenance 

naltrexone to avoid relapse to opioids. The researchers stabilized 18 opioid-detoxified men and women on naltrexone 

(50 mg) and lofexidine (2.4 mg) daily for 1 month. They then retained all the patients on naltrexone for 4 more weeks, 

but kept 8 on lofexidine and gave 10 others identical-looking pills containing lofexidine doses that—unbeknownst to 

the patients—tapered to zero over several days. Of the 13 patients who completed the study, 80 percent of those who 

continued to receive combination therapy submitted opiate-free urine samples throughout the 4-week period, compared 

with 25 percent of those tapered to placebo. A followup laboratory session that exposed 10 of the patients to stressful and 

opiate-related stimuli showed that lofexidine—but not placebo—reduced the patients’ reaction to stress, stress-induced 

opiate craving, and negative emotions (such as anger), all of which can trigger relapse.

Source

• Psychopharmacology 190(4):569-574, 2007. 

7
New Therapy Reduces Drug Abuse Among Patients With Severe 

Mental Illness

A specially designed group intervention also improves patients’ functioning in the community.

By NIDA NOTES Staff

Research Findings

Volume 21, Number 6 (June 2008)

A new intervention enhances prospects for substance abusers whose mental illness complicates the path to recovery. 

In a recent clinical trial, a 6-month course of Behavioral 

Treatment for Substance Abuse in Severe and Persistent 

Mental Illness (BTSAS) reduced drug abuse, boosted treatment-session attendance, and improved the quality of life 

of outpatients with a wide spectrum of mental disorders.

A Focus On Extra Obstacles

Dr. Alan S. Bellack and colleagues at the University of 

Maryland School of Medicine in Baltimore designed 

BTSAS to counter the factors that make recovery from 

addiction especially difficult for people who have cooccurring severe and persistent mental illness. These factors include frequent failure to meet their own and others’ 

expectations, inconsistent motivation, and social and personal pressure to appear normal.

BTSAS therapy comprises six integrated components:

• motivational interviews (directive counseling that 

explores and resolves ambivalence) to increase the 

desire to stop using drugs; 

• contingency contracts linking drug-free urine samples 

with small financial rewards; 

• realistic, short-term, structured goal-setting sessions; 

• training in social and drug-refusal skills; 

• information on why and how people become addicted 

to drugs and the dangers of substance use for people 

with mental illness; and 

• relapse-prevention training that inculcates behavioral 

strategies for coping with cravings, lapses, and highrisk situations. 

Twice-weekly sessions begin with urine tests. Patients who 

have provided drug-free urine samples are praised by the 

therapists and group members. They also receive financial 

incentives that start at $1.50 for the first drug-free sample 

and increase in $0.50 increments for every consecutive one 

thereafter, up to $3.50. The amount is set back to $1.50 

after a drug-positive sample or an absence.

When participants submit drug-positive samples, the group 

takes a nonaccusatory 

approach 

by focusing 

on problem 

solving to 

help them 

achieve 

future abstinence. Each 

participant 

agrees upon 

a personal 

goal for 

drug abuse reduction or abstinence that he or she believes 

is achievable during the coming week and signs a contract 

stating that he or she will strive for it. The rest of the session consists of drug abuse education plus training in social 

skills and relapse-prevention strategies.

Superior Results

Substance abuse is common among the mentally ill. For 

example, surveys estimate that 48 percent of those with 

schizophrenia, 56 percent with bipolar disorder, and as 

many as 65 percent with severe and persistent mental illness have abused substances.

Dr. Bellack’s research team recruited 175 patients from 

community clinics and a Veterans Affairs medical center 

in Baltimore. All had a dual diagnosis of severe and persistent mental illness and an addiction to cocaine, heroin, 

or marijuana. Among the participants, 38.3 percent met 

the diagnostic criteria for schizophrenia or schizoaffective 

disorders, 54.9 percent for major affective disorders, and 

the remainder for other mental disorders. Cocaine was the 

predominant drug abused by 68.6 percent of participants, 

opiates by 24.6 percent, and marijuana by 6.8 percent.

The researchers assigned half the trial participants to 

BTSAS group therapy and half to a program called 

Supportive Treatment for Addiction Recovery (STAR), 

which is the typical treatment at the University of 

Maryland clinics. Unlike participants in BTSAS, those in 

STAR do not follow a structured format but instead select 

their own topics and work at their own pace. Patient 

8
9

interaction with other patients is 

encouraged but not required as it is 

with BTSAS. Although urine samples 

are collected before each session, 

results are not discussed in the group, 

and no systematic feedback is provided to the patient.

Assignments to the BTSAS and STAR 

groups were balanced for gender, psychiatric diagnosis, type of drug dependency, and number of substance use 

disorders. Treatment groups of four 

to six participants met twice a week for 6 months. BTSAS 

and STAR group sessions were all led by trained therapists and lasted from 60 to 90 minutes. Group meetings 

were videotaped weekly and then reviewed and assessed 

by independent reviewers to verify that the therapists were 

following the programs’ parameters correctly.

The BTSAS group fared better than the STAR group on 

a wide range of treatment-related criteria. For example, 

more people in the BTSAS group stayed in treatment 

throughout the 6-month trial period (57.4 percent versus 

34.7 percent). The BTSAS group produced more drugfree urine samples and had longer periods of abstinence 

(see table). They also had better clinical and general living outcomes than people in the STAR group (see table, 

below) and reported larger improvements in their ability 

to perform the activities of daily living.

“It was apparent from watching videotapes of treatment 

sessions that subjects in BTSAS valued the intervention 

and were learning important skills for reducing drug use,” 

says Dr. Bellack. “We were very gratified that the data 

supported our clinical observations.”

The researchers reported that the extra costs of running 

the BTSAS program were modest. For the 6-month trial, 

monetary rewards averaged roughly $60 per patient; total 

per-patient cost, including therapist time, was $372.

Ongoing Refinements

The trial data indicate that patients who remain in BTSAS 

for at least three sessions are much more likely to finish 

the 6-month program than patients who do not make it 

through the third session. Because a third of individuals 

initially recruited for the study left before the third treatment session, the researchers are currently developing new 

intervention strategies to keep people in the program until 

they have truly given it a chance. The innovation has two 

key components: a structured intervention to help patients 

overcome obstacles to treatment and an intervention to 

enlist family and friends as partners to connect patients 

with treatment.

“The BTSAS program will help clinicians make a difference in the lives of a very difficult-to-treat population,” 

says Dr. Dorynne Czechowicz of NIDA’s Division of 

Clinical Neuroscience and Behavioral Research. “One of 

its key strengths is that it positively affects many aspects 

of patients’ lives. Moreover, as an outpatient treatment, 

it is well-suited to the situation. Most mentally ill people 

who abuse drugs live in the community, not in a sheltered 

facility, and this is where the majority of clinicians must 

treat them.”

Sources

• Bellack, A.S., et al. A randomized clinical trial of a 

new behavioral treatment for drug abuse in people 

with severe and persistent mental illness. Archives of 

General Psychiatry 63(4):426-432, 2006. 

• Kinnaman, J.E., et al. Assessment of motivation to 

change substance use in dually-diagnosed schizophrenia patients. Addictive Behaviors 32(9):1798-1813, 

2007. 
Combination Treatment Extends Marijuana Abstinence

Vouchers provide a strong incentive for abstinence during treatment, and cognitive-behavioral therapy 

helps patients maintain abstinence after treatment ends.

By Debra P. Davis, NIDA NOTES Senior Editor

Research Findings

Volume 21, Number 5 (March 2008)

Treatment that combines vouchers and cognitive-behavioral therapy (CBT) may be more effective in keeping 

marijuana abusers abstinent in the longer term than 

vouchers-only and CBT-only programs. In a study by Dr. 

Alan Budney and colleagues at the University of Vermont, 

vouchers alone generated the longest periods of abstinence during 14 weeks of treatment, while vouchers and 

CBT in combination yielded superior abstinence during a 

12-month posttreatment period.

“This is our second study demonstrating that an abstinence-based voucher program can increase positive outcomes for folks seeking treatment for marijuana dependence,” says Dr. Budney, who is now at the University of 

Arkansas for Medical Sciences. “It provides evidence that 

vouchers used as adjuncts to traditional behavioral therapy 

can improve outcomes.”

The current study extended the earlier one by including 

post-treatment assessments. Vouchers provided a strong 

incentive for abstinence during treatment, as they did in 

the earlier study, but the effect of vouchers alone did not 

hold up as well as the combined treatment once the program ended. The higher posttreatment abstinence rates 

for the combined treatment relative to the vouchers-only 

treatment suggest that the behavioral therapy helped to 

maintain the effect of the vouchers, Dr. Budney says. He 

attributes 

this maintenance 

effect to the 

coping skills 

and motivational 

training 

provided by 

the CBT.

For the 

study, 90 

adults (69 

men, 21 

women) 

seeking 

treatment 

for marijuana dependence at a university-based outpatient clinic 

in Burlington, Vermont, were randomly assigned to treatment with vouchers (30), CBT (30), or both (30). Most 

were smoking marijuana daily and presenting themselves 

for treatment for the first time; their average length of 

marijuana abuse was 14 years. Each time a participant in 

the vouchers-only or combination treatment submitted 

a marijuana negative urine sample, he or she received a 

voucher worth $1.50; a second consecutive negative sample earned $3.00, a third $4.50, and so on. In addition, 

each consecutive pair of negative samples netted a bonus 

voucher worth $10. A full 14-week run of weekly drugfree samples would net vouchers worth $570, which were 

redeemable for retail goods or services.

The CBT included 50-minute weekly sessions involving 

motivational counseling, drug refusal, and coping skills. 

To encourage cooperation with the urine screens and 

help equalize retention and treatment contact across the 

groups, researchers paid the CBT-only participants $5 in 

vouchers each time they showed up for a screen, regardless 

of their test results. Complete adherence to the sessions 

and screens would earn $140 over the 14-week period.

During treatment, vouchers-only patients produced the 

most marijuana-negative urine specimens (55 percent 

versus 43 percent for combined treatment and 32 percent 

for CBT only), weeks of continuous abstinence (mean 6.9 

versus 5.3 for combined treatment and 3.5 for CBT only), 

and continuous abstinences lasting 6 or more weeks (50 

percent versus 40 percent for combined treatment and 17 

percent for CBT only). In addition to duration of abstinence, researchers measured days of self-reported marijuana abuse, changes in marijuana-related problems, and 

psychosocial outcomes. Participants in all three groups 

showed similar improvements in these areas at the end of 

treatment (see chart).

Combined Treatment Benefits

At the end of treatment and at each of four quarterly followups, patients who received the combined treatment 

had the highest abstinence prevalence, averaging 38 percent over the 12 months, compared with 23 percent for 

vouchers only and 20 percent for CBT only. The combined treatment group also had the highest rate of contin10
11

uous abstinence throughout treatment and followup, 37 

percent, compared with 30 percent for CBT and 27 percent for vouchers. On average, patients who received the 

combination treatment used marijuana 13 days out of 30 

during followup, compared with 18 days among patients 

who received the single treatments.

“The findings of this study show that vouchers are effective in producing initial abstinence during treatment,” 

says Ms. Debra Grossman of NIDA’s Division of Clinical 

Neuroscience and Behavioral Research. “The addition 

of cognitivebehavioral therapy did not enhance initial 

abstinence, but helped maintain abstinence and produced 

better long-term outcomes. These findings are consistent 

with other studies.” In two previous studies with cocaine 

abusers, vouchers alone performed as well as vouchers plus 

CBT during treatment. One of the studies indicated that 

CBT augmented the effects of the vouchers during the 

posttreatment period.

Dr. Budney says his team set the value of the vouchers 

arbitrarily, with the aim of keeping costs down; he believes 

bigger payoffs would produce better outcomes. The 

escalating values for consecutive negative urine samples 

progressively strengthened the incentive for participants 

to avoid lapses; each time a participant submitted a positive sample or missed a screening, the reward for the next 

negative sample reverted to the original $1.50 voucher. 

Dr. Budney suggests that future studies might cut costs by 

incorporating behavioral therapy only at key points in the 

treatment, rather than weekly throughout. In the researchers’ experience, such a point often comes in the fourth to 

sixth week of abstinence, when patients may start to lose 

motivation and become vulnerable to relapse.

Fewer than half of the participants in Dr. Budney’s 

study had positive outcomes, indicating that more effective treatments are needed for marijuana dependence. 

“Despite the promising findings, the majority of patients 

are not being sufficiently helped, and thus we need continued research focused on maximizing the outcome,” Ms. 

Grossman notes. “Marijuana is the most commonly used 

illegal drug in the United States, yet among the least studied, and treatment based on abstinence-based vouchers has 

been found to be effective for other drugs of abuse.”

Source

• Budney, A.J., et al. Clinical trial of abstinence-based 

vouchers and cognitive-behavioral therapy for cannabis dependence. Journal of Consulting and Clinical 

Psychology 74(2):307-316, 2006. 
Sertraline Does Not Help Methamphetamine Abusers Quit

Selective serotonin reuptake inhibitors do not relieve the depressive symptoms of methamphetamine 

withdrawal and may produce unpleasant side effects.

By Elizabeth Ashton, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 5 (March 2008)

In a recent NIDA-funded study, the antidepressant sertraline (Zoloft) made quitting methamphetamine harder. 

Prescribed to relieve depression during the methamphetamine withdrawal process, sertraline produced a number 

of unpleasant side effects and may have interfered with 

behavioral interventions as well.

Dr. Steven Shoptaw, Dr. Alice Huber, Dr. Walter Ling, 

and their colleagues at the University of California, Los 

Angeles (UCLA) noted that methamphetamine abusers 

in withdrawal frequently complained of fatigue, lack of 

pleasure, sad mood, and persistent daytime sleepiness. The 

researchers hypothesized that the sertraline might alleviate 

these symptoms and promote abstinence because:

• methamphetamine is toxic to several pathways that 

produce the neurotransmitter serotonin; 

• sertraline belongs to a class of antidepressant medications, the selective serotonin reuptake inhibitors 

(SSRI), that treat major depression by raising 

serotonin levels in the brain. 

Hypothesis Disproved

The team recruited 229 men and women who were 

addicted to methamphetamine. All were between the ages 

of 18 and 65, and all were seeking treatment. The trial 

began with a 2-week preparation process. The researchers 

performed baseline testing and encouraged the participants to stop taking methamphetamine with the help of 

twice-weekly recovery skills groups. At the end of 2 weeks, 

they randomly assigned the participants to one of four 

groups: sertraline with contingency management (CM), 

sertraline alone, placebo with CM, and placebo alone. 

All participants provided urine samples on Mondays, 

Wednesdays, and Fridays and attended a 90-minute psychological support group three times a week based on the 

Matrix Model relapse prevention program. This standardized, manual-driven model is evidence-based and incorporates social learning, behavioral and cognitive therapies, 

and psychological and HIV-risk education.

The researchers evaluated methamphetamine use, time 

spent in the program, methamphetamine craving, and 

depressive symptoms. They found that:

• more participants in the CM program achieved 3 

consecutive weeks of abstinence than participants who 

were not in the CM program (47 vs. 33 percent); all 

participants who received CM benefitted from this 

therapy, but its positive effects were blunted in the 

sertraline-with-CM group. 

• fewer participants on sertraline alone, as compared 

with those on placebo alone (34 percent vs. 47 

percent), achieved the goal of at least 3 consecutive 

drug-free urine samples during the study’s 12-week 

treatment phase; participants on sertraline alone also 

attended fewer relapse prevention sessions and were 

more likely to drop out. 

• craving and depressive symptoms were affected only 

by time since the last methamphetamine dose, and 

neither sertraline nor CM changed either of these 

two measures. 

12
13

In addition, the sertraline group reported significantly 

more sexual, gastrointestinal (including nausea), and 

anticholinergic side effects.

Rethinking Withdrawal Support

The researchers concluded that treatment with sertraline 

did not relieve the depression associated with methamphetamine withdrawal or decrease methamphetamine use, 

and its side effects reduced the amount of time participants spent in treatment. Those who took sertraline also 

seemed to benefit less from behavioral interventions, and 

the researchers speculated that this might be due to the 

dampening effect of the medication since they had excluded all other possible factors in the statistical analysis.

The team recommends that clinicians not give SSRIs to 

people withdrawing from methamphetamine unless an 

underlying primary depressive disorder is definitively diagnosed. The recommendation reflects their own results and 

those of previous smaller studies with fluoxetine (Prozac) 

and paroxetine (Paxil), both of which were also found to 

have no effect on depressive symptoms during methamphetamine withdrawal. Together, these findings suggest 

that the etiology of mood disorder during methamphetamine withdrawal differs from that of primary depression.

The UCLA researchers suggest that clinicians offer people 

addicted to methamphetamine an effective behavioral 

intervention for depressive symptoms during the withdrawal process before prescribing any of the currently 

available pharmacotherapies for depression. If medication 

is needed, only non-SSRI antidepressants, such as bupropion, should be used.

“The SSRI sertraline is not only inefficacious for the treatment of methamphetamine dependence, but also produces 

a number of unprecedented side effects and has no effect 

on the secondary depression experienced during methamphetamine withdrawal,” says Dr. Ivan Montoya, Clinical 

Director of NIDA’s Pharmacotherapies and Medical 

Consequences of Drug Abuse Branch. “In addition, the 

negative effects of this SSRI in methamphetamine users 

are so powerful that they can dampen the strong therapeutic effects of contingency management. If these reactions 

can be traced to their source, they may help us understand 

the extent and duration of the effects of methamphetamine on the brain.”

“We are trying to determine what people withdrawing 

from methamphetamine need to make withdrawal easier,” 

Dr. Shoptaw says. “We’ve figured this out for other drugs, 

such as cocaine and heroin, but finding medications that 

counter the withdrawal symptoms of methamphetamine 

addiction is still a work in progress. We need this information so we can design treatment programs that help 

people get off and stay off this damaging drug.” 

Source

• Shoptaw, S., et al. Randomized, placebo-controlled 

trial of sertraline and contingency management for 

the treatment of methamphetamine dependence. 

Drug and Alcohol Dependence 85(1):12-18, 2006. 

13
Chronic Cocaine Abusers Have Occult Insomnia in Early Abstinence

Patients in early treatment may not recognize their own sleep impairment or its impact on their 

performance.

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 5 (March 2008)

Chronic cocaine abusers may feel they are sleeping better 

and better during early abstinence, but objective measures 

show the opposite happens. A team of NIDA-funded 

addiction and sleep researchers at the Yale and Harvard 

Schools of Medicine found evidence of insomnia, with 

learning and attentional deficits, on days of taking the 

drug and after 2.5 weeks of abstinence. The researchers 

believe cocaine may impair the brain’s ability to gauge its 

own need for sleep, and patients’ ability to benefit from 

early treatment may suffer as a result.

“Problems in memory and attention are linked with 

increased treatment dropout and likely 

affect patients’ ability to ‘take in’ lessons 

from drug abuse counseling,” says Dr. 

Robert Malison of Yale, a co-investigator 

on the study. If the results are confirmed, clinicians and patients may want 

to consider addressing sleep disorders in 

early therapy, perhaps with the use of 

medications or behavioral treatments.

The researchers recruited 10 men and 

two women aged 24 to 49 who, on average, had abused cocaine for 17 years 

and had used $500 worth of the drug 

per week. All the participants declined 

an offer of drug abuse treatment. Urine 

tests indicated that cocaine was the only 

drug any of them had abused during the 

week before the study.

At the outset of the study, participants 

self-administered cocaine from a pump 

under physician oversight, building up 

to a dose of 32 mg/kg of body weight 

over 1.5 hours, then repeating this dose 

essentially at will, but no less than 5 

minutes apart, for another 1.5 hours. 

Subsequently, they self-administered 

the higher dose with the same minimal 

restriction for 2 hours on each of three 

consecutive days, either on days 4-6 or 

18-20. This schedule simulated chronic 

cocaine abusers’ typical bingeing pattern 

of drug abuse and allowed researchers 

to monitor each participant’s sleep and cognitive performance for 17 days after a binge.

Research staff made sure the participants stayed awake 

from 7:45 AM to 9:30 PM, and let them sleep through 

the night. At night, the participants wore Nightcap sleep 

monitors, a bandana-like device that records eye and 

body movements that indicate whether someone is awake, 

asleep and dreaming, or sleeping dreamlessly. On most 

nights participants also wore polysomnographic (PSG) 

devices that continuously assessed brain activity with 

electroencephalography (EEG) and measured eye and 

14
15

muscle movements associated with different sleep stages. 

Combining the information gathered by these measures 

with participants’ responses to daily questionnaires on 

their sleep experience and with cognitive testing, the 

researchers demonstrated that the participants had:

• Sleep deficits—After 14 to 17 days of abstinence, the 

study group exhibited sleep deficits on several measures, relative to healthy, age-matched peers who participated in prior studies. For example, they had less 

total sleep time (336 versus 421-464 minutes) and 

took longer to fall asleep (19 versus 6-16 minutes). 

• Declines in sleep quantity and quality—The time 

participants took to fall asleep and their total time 

asleep transiently improved during the first week of 

abstinence, but then reverted to the patterns recorded 

on days of cocaine taking. On abstinence days 14-17, 

participants took an average of 20 minutes to fall 

asleep (from a low of 11) and slept for 40 minutes less 

than their minimum. Slow-wave sleep—a deep sleep 

that often increases following sleep deprivation—rose 

during the binge and on abstinence days 10-17. 

• Lack of awareness of their sleep problems—In contrast 

to the evidence of objective measures, the study participants reported steadily improving sleep from the 

beginning to the end of their days of abstinence. 

• Impairments in learning and attention—As with sleep 

quality, participants’ performance on tests of alertness 

and motor-skills learning initially improved and then 

deteriorated. On abstinence day 17, they registered 

their lowest scores on alertness and ability to learn a 

new motor skill. 

Increased Risk 

of Relapse

“Unlike most 

people with 

chronic insomnia, 

including alcoholics, cocaine abusers do not perceive sleep problems and may 

not ask clinicians 

for treatment to 

improve sleep,” 

says Dr. Malison. 

The problem 

often goes unaddressed and persists as a result, 

and the accompanying impairments in attention and learning 

may affect how 

well they respond 

to drug abuse 

treatment (see 

“Cocaine Abusers’ 

Cognitive Deficits 

Compromise 

Treatment 

Outcomes”). 

Clinical studies 

have shown that 

poor objective 

sleep during the 

first 2 weeks of 

abstinence predicts relapse to 

alcohol 5 months 

after treatment.

In fact, the insidious nature of 

cocaine-related 

insomnia may 

directly trigger relapse, suggests Dr. Peter Morgan, lead 

investigator of the study. “Addicted people may take 

cocaine to improve sleep-related cognitive functioning 

deficits—unaware that they are abusing, in part, to ‘solve’ 

these problems.”

Dr. Morgan adds, “Cocaine abusers who recognize their 

cognitive problems often report that it takes them 6 

months to a year to turn the corner—a clinical observation that points to the need for longer term studies of 

sleep and treatment outcomes among this population.” In 

addition to studies with larger numbers of participants, 

the investigators say there is a need to investigate possible 

gender differences in cocaine-related sleep problems. Dr. 

Morgan and his team are currently testing two medications, tiagabine and modafinil, to see if they can improve 

cocaine abusers’ sleep and restore cognitive performance.

“Experts believe that not getting enough sleep is an unmet 

public health problem in the general population. These 

findings highlight this important problem in cocaine 

abusers,” says Dr. Harold Gordon of NIDA’s Division of 

Clinical Neuroscience and Behavioral Research.

Source

• Morgan, P.T., et al. Sleep, sleep-dependent procedural 

learning and vigilance in chronic cocaine users: 

Evidence for occult insomnia. Drug and Alcohol 

Dependence 82(3):238-249, 2006. 
Bupropion Reduces Meth’s Subjective Effects and Cue-Induced 

Craving

Research Findings

Volume 21, Number 5 (March 2008)

A small placebo-controlled trial produced evidence that the antidepressant bupropion may be useful for treating methamphetamine addiction. Drs. Thomas Newton and Richard De La Garza at the University of California, Los Angeles, and 

Dr. John Roach and colleagues, at the University of Texas, San Antonio, divided 20 methamphetamine-addicted individuals into two groups for 6 days of treatment: one group received bupropion (150 mg/d) throughout the trial and the 

other, placebo. At baseline and the end of the trial each participant received three infusions; one of an inert vehicle and 

two of methamphetamine (15mg and 30 mg), spaced over 2 hours. Before and at frequent intervals after each infusion, 

participants reported on their subjective reactions. Compared to baseline, those who received bupropion experienced 

reduced highs and slightly decreased cravings at the end of the trial, while those who received placebo experienced 

significantly more craving.

Source

• Neuropsychopharmacology 31(7):1537-1544, 2006. 

16
NIDA’s Newest Division Mines Clinical Applications From Basic 

Research

NIDA’s Division of Clinical Neuroscience and Behavioral Research

By Debra P. Davis, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 4 (October 2007)

NIDA’s Division of Clinical Neuroscience and Behavioral 

Research (DCNBR) identifies, validates, and explores the 

clinical implications of basic science discoveries. Much of 

the Division’s work consists of replicating results obtained 

in laboratory and animal studies in human subjects. A 

DCNBR project typically culminates in one of two outcomes: carrying a new discovery forward for development 

into actual interventions or referring it back to basic scientists for further investigation.

“We are uniquely positioned to uncover the factors in 

humans—neurobiologic, genetic, social-behavioral—that 

help explain the development and effects of drug abuse,” 

says Director Dr. Joseph Frascella. “Being positioned 

between NIDA’s basic research division and other more 

applied programs, our research programs inform basic 

science and promote the development and implementation of new medications and behavioral treatments across 

NIDA.”

For example, building on basic research that linked nicotine acetylcholine receptors to the regulation of attention, 

DCNBR-sponsored researcher David Gilbert and colleagues at Southern Illinois University demonstrated that 

nicotine exposure and smoking cessation both influence 

the ability to pay attention. Now, NIDA’s Division of 

Pharmacotherapies and Medical Consequences of Drug 

Abuse is exploring the clinical impact of these observations. They are testing whether bupropion and nicotine 

patches affect attention during smoking cessation, and 

whether such effects correlate with success in quitting.

In another DCNBR-supported study, Dr. Robert Risinger 

and colleagues at the Medical College of Wisconsin documented a pattern of fluctuating activation of the mesolimbic reward system as six cocaine-abusing men transitioned 

through cycles of cocaine craving, self-administration, and 

highs. The results, obtained with functional magnetic resonance imaging (fMRI), confirmed previous research linking those brain areas to drug self-administration in animals, and extended them by correlating them with drug 

abusers’ subjective feelings and responses. (see “Cocaine 

Craving Activates Brain Reward Structures; Cocaine 

‘High’ Dampens Them,” NIDA NOTES, Vol. 21, No. 2).

Neuroimaging studies comprise onethird of the Division’s 

research portfolio. “Brain imaging has pushed drug abuse 

research in the last 15 to 20 years—allowing us to directly 

observe neural activity of awake and functioning people 

and obtain specific measures on how drugs affect the 

brain,” Dr. Frascella says. Imaging studies indicate that 

the human brain undergoes major changes as a consequence of drug exposure and that the adolescent brain 

may be particularly pliant, “which may help explain why 

adolescence is the period when most new cases of drug 

addiction occur,” Dr. Frascella adds. “Thus, we’ve become 

increasingly committed to using brain imaging to get a 

sharper picture of how the brain changes with development and in response to active and passive exposure to 

drugs of abuse.”

Three Branches of Clinical Research

DCNBR, formed in May 2004, has three Branches:

Clinical Neuroscience: Under Dr. Steven Grant’s 

leadership, the Clinical Neuroscience Branch focuses on 

how drug abuse affects the human central nervous system, 

including brain changes during different stages and states 

of abuse, such as addiction, withdrawal, abstinence, 

craving, and relapse. It also studies:

• The factors that make some individuals more vulnerable and others more resilient to drug abuse and 

addiction; 

• The impact of drugs on learning, memory, judgment, 

and decision-making; 

• Co-occurrence of drug addiction with other mental 

disorders; 

 • Neurobiological changes that result from behavioral 

and pharmacological treatments for drug abuse; and 

• Interventions to ameliorate the negative health 

consequences of drugs, whether self-administered 

or incurred prenatally. 

As an example of a recent Branch achievement, Dr. Grant 

points to a study by Dr. Martin Paulus and colleagues at 

the University of California, San Diego.

17
18

The researchers performed fMRI while 46 men who had 

been abstinent from methamphetamine for about a month 

took a decisionmaking test. The researchers found that 

patterns of activation in certain brain regions predicted 

with high accuracy which men would and would not 

relapse 1 year later (see “Brain Activity Patterns Signal 

Risk of Relapse to Methamphetamine,” NIDA NOTES,

Vol. 20, No. 5). “This use of fMRI, if replicated, could be 

adapted for treatment and preventive interventions,” Dr. 

Frascella says.

Behavioral and Brain Development: Led by Dr. Vincent 

Smeriglio, this Branch examines drug exposure and abuse, 

and their health and social consequences, through the 

course of human development—from the prenatal period 

through childhood, adolescence, and young adulthood. 

Research focuses on:

• The effects of drugs on behavioral and brain 

development; 

• The role of genetic, neurobiological, 

and environmental factors in youths’ 

vulnerability to drug abuse and 

addiction; and 

• The developmental effects of cooccurring exposure to drugs and infectious 

diseases as well as the impact of drug 

abuse on youths with mental illness.

One theme of the Branch’s work is 

research to tailor drug abuse treatments 

to individual needs. As a recent example, 

a Branch-supported study by Dr. Leslie 

Jacobsen and colleagues at Yale University 

School of Medicine found that adolescent smokers experienced greater memory 

impairment during nicotine withdrawal if 

their mothers had smoked while pregnant. 

The study also produced fMRI evidence 

implicating particular brain regions in the 

deficits, which may be useful diagnostically as well as therapeutically.

Behavioral and Integrative Treatment: 

This Branch, under Dr. Lisa Onken’s 

direction, aims to develop new and 

improved treatments for drug abuse and 

addiction, including behavioral, combined 

behavioral-pharmacological, and complementary and alternative treatments. The 

Branch designs new interventions, tests 

them for efficacy, and evaluates strategies to improve treatment engagement, 

adherence, and retention—key factors in 

success. The Branch also supports research 

that prepares treatments for use in community settings, where cost, training, and fit with existing 

services can be constraints.

“Behavioral therapies that work well in a research setting 

cannot necessarily be taken into the community. 

Oftentimes, they are too complicated and expensive, and 

require extensive training for clinicians,” Dr. Frascella 

notes. One way of developing a community-friendly treatment is to identify the active ingredients of effective treatments, explains Dr. Onken. “In this way, we may be able 

to create more streamlined treatments that retain their 

potency. Another novel approach to making a treatment 

more community-friendly is to use computers to help 

counselors deliver treatment. For example, Dr. Kathleen 

Carroll at Yale University is testing the efficacy of computer-assisted cognitive-behavioral therapy in preventing 

cocaine relapse. 
Standard Treatments Help Depressed Smokers Quit

As smoking rates fall in the United States, mentally ill individuals comprise a larger percentage of people 

who continue to light up.

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 3 (April 2007)

Smoking cessation interventions that are effective in the 

general population also help for depressed smokers, suggests a study of outpatients at four mental health clinics. Dr. Sharon Hall and colleagues at the University of 

California, San Francisco; the University of Rhode Island; 

and Kaiser Permanente Northern California found that 

depressed smokers who were treated with a combination 

of motivational counseling, nicotine patches, and behavioral therapy were more likely than their counterparts who 

did not receive the interventions to be smoke-free at 12- 

and 18-month assessments.

“Patients in our study mirrored the general population 

of smokers in their readiness to quit, acceptance of treatment, and cessation outcomes—findings that surprised me 

and my colleagues,” says Dr. Hall, lead investigator of the 

study. Further, patients with severe symptoms of depression both accepted the interventions and benefited from 

them. “Our findings suggest that clinicians should offer 

depressed outpatients nicotine addiction treatment and 

should start with available smoking cessation interventions. They need not be overly concerned about patients’ 

levels of depression,” says Dr. Hall.

The investigators recruited 322 men and women from a 

university-based clinic and three sites of a health maintenance organization who were being treated for depression 

and smoked daily. Most of the volunteers (79 percent) 

were taking psychiatric medication for moderate depression. On average, they had smoked for 24 years, smoked 

15 cigarettes a day, and had tried to quit six times.

At the start of the study, the participants provided information on their depression severity and treatment, smoking behavior (confirmed by expired air carbon monoxide 

measurements), nicotine dependence level, readiness to 

quit smoking, previous quit attempts, and commitment to 

abstinence. They repeated these self-reports 3, 6, 12, and 

18 months later.

The active intervention in the study was Staged Care 

Intervention (SCI). At the outset and months 3, 6, and 

12, participants assigned to SCI answered a computerized questionnaire about smoking, its advantages and 

disadvantages, triggers for smoking-related thoughts and 

behaviors, and ways to change these thoughts and behaviors. The computer provided an individualized feedback 

report that the patients and counselors reviewed together 

in a 15-minute session. The report classified each patient’s 

readiness to quit based on the Stages of Change model, 

compared his or her responses with those of others in the 

program, showed changes from earlier reports, and identified triggers for smoking and strategies to move to the 

next stage. If the patient expressed a desire to quit, he or 

she began an 8-week cessation treatment. Each participant 

in the control group received a self-help guide to smoking 

cessation and a list of programs in the area, but no therapeutic contact or advice about smoking cessation.

Opportunity to Engage

About one-third (34 percent) of SCI participants entered 

cessation treatment. They received nicotine patches (7, 

14, or 21 mg, depending on level of smoking and week of 

study) and six 30-minute counseling sessions. The focus 

of counseling was immediate and complete cessation at 

an agreedupon date. During sessions, patients developed 

a commitment to abstinence, established a quit plan, 

identified reasons for smoking, reviewed the benefits of 

quitting, and received information on nutrition and exercise. Patients who did not attain abstinence with nicotine 

patches were prescribed bupropion if their mental health 

care provider deemed it medically appropriate.

19
20

The researchers included all SCI participants, including those who did not 

enter cessation treatment, in their data 

analysis. At the 12-month assessment, 

20 percent of participants in the SCI 

group and 13 percent in the control 

group had verified 7-day tobacco 

abstinence. The SCI group’s advantage 

persisted at the 18-month assessment 

(25 percent versus 19 percent). More 

SCI (44 percent) than control group 

participants (34 percent) endorsed 

permanent abstinence—an attitude 

the researchers say predicts success in 

changing behavior. The intervention 

was particularly effective for heavy 

smokers: Among participants who 

smoked more than a pack of cigarettes 

a day, those assigned to SCI were 

about twice as likely as controls to 

report a quit attempt during the study.

“The findings of Dr. Hall and her 

colleagues suggest that, even among 

severely depressed smokers who 

are not motivated to quit, the SCI 

increases abstinence rates compared with a standard 

control,” says Ms. Debra Grossman of NIDA’s Division 

of Clinical Neuroscience and Behavioral Research. The 

finding adds to the justification for American Psychiatric 

Association and Agency for Health Care Research and 

Quality recommendations to offer smoking cessation 

therapy to people with mental disorders.

“The high prevalence of smoking in mental health clinics 

presents an opportunity to engage people with depression in smoking cessation,” says Dr. Hall. She adds that 

one advantage to doing so is the supportive environment 

of such settings: if cessation worsens depression, then 

patients can obtain additional help. Dr. Hall notes that 

the treatment benefits seen among the study population 

of mostly employed patients enrolled in a health maintenance organization might not apply to depressed people 

who are disadvantaged or in treatment at publicly funded 

hospitals. Dr. Hall’s team plans to conduct a cost-effectiveness analysis of the intervention to help clinic directors 

decide on resource allocation.

Source

• Hall, S.M., et al. Treatment for cigarette smoking 

among depressed mental health outpatients: a randomized clinical trial. American Journal of Public 

Health 96(10):1808-1814, 2006. 
Depot Naltrexone Appears Safe and Effective for Heroin Addiction

A long-lasting, injectable formula of naltrexone performed well in a pilot clinical trial.

By Sarah Teagle, NIDA NOTES Contributing Writer

Research Findings

Volume 21, Number 3 (April 2007)

In a NIDA-supported pilot study, a new formulation of 

naltrexone that patients receive by injection once every 30 

days appeared safe and helped heroin-addicted outpatients 

persevere in treatment. Investigators observed a dosedependent relationship between the medication, called 

depot naltrexone, and patient retention rates.

Naltrexone helps patients overcome urges to abuse opiates 

by blocking the drugs’ euphoric effects. Some patients do 

well with it, but the oral formulation, the only one available to date, has a drawback: It must be taken daily, and a 

patient whose craving becomes overwhelming can obtain 

opiate euphoria simply by skipping a dose before resuming abuse.

“What’s exciting about this slow-release formula is that 

it provides continuous protection for a month at a time, 

freeing patients from having to decide to take or not take 

the medication every day,” says Dr. Sandra Comer, lead 

investigator of the study. “By increasing treatment retention, depot naltrexone may allow patients greater contact 

with appropriate supportive counseling and ease their 

transition to a life without heroin.”

Dr. Comer and her collaborators recruited 60 heroinaddicted, predominantly male (77 percent) adults, aged 

18 to 59 years, through advertising in local newspapers 

and word of mouth in New York City and Philadelphia. 

To be eligible, patients could not be addicted to any drugs 

other than heroin, caffeine, or nicotine. After initial heroin detoxification, the investigators randomly assigned participants to receive low-dose depot naltrexone, high-dose 

depot naltrexone, or placebo at the beginning of weeks 1 

and 5. All participants received twice-weekly relapse prevention behavioral therapy.

After 8 weeks, 68 percent of the patients receiving 384 mg 

of naltrexone remained in treatment, compared to 60 percent of those receiving 192 mg, and 39 percent of those 

on placebo. The percentage of urine samples negative for 

opioids was highest for the group receiving 384 mg of naltrexone (62 percent) and lowest for the placebo group (25 

percent). After receiving the medication, patients in the 

naltrexone groups reported “needing heroin” significantly 

less than those taking placebo.

The study participants experienced no apparent serious 

side effects. Despite previous reports associating high 

doses of naltrexone with hepatotoxicity, only one patient 

developed elevated liver enzymes, which the researchers 

attributed to a new-onset hepatitis C infection rather than 

the medication. Heroin overdose, another potential concern for patients on naltrexone, was not observed in the 

study; several patients did abuse heroin while on naltrexone, but reported no pleasure from it.

Encouraged by their results, Dr. Comer and her colleagues 

are beginning a 6-month trial with a larger number of 

participants. “We want to make sure the depot formula 

helps over a longer period of time,” she explains. “Having 

more tools is really helpful for providers. Some people do 

better on methadone, others on naltrexone. We’ll have 

more success if we can offer both.”

Dr. Richard Hawks of NIDA’s Division of 

Pharmacotherapies and Medical Consequences of Drug 

Abuse, says pharmaceutical companies are developing even 

longeracting versions of naltrexone—a 6-month sustainedrelease formula. “But a drug alone never works,” he says. 

21
22

“To be effective, the medication must be combined with 

behavioral therapy. Many years of behavioral therapy 

research shows that the longer someone is in treatment, 

the longer the time to relapse. Longer-acting, sustainedrelease medications help maximize this effect.”

Source

• Comer, Sandra D., et al. Injectable, sustained-release 

naltrexone for the treatment of opioid dependence. 

Archives of General Psychiatry 63(2):210-218, 2006. 
Research Findings

Volume 21, Number 3 (April 2007)

23

Interim Methadone Raises Odds of Enrolling in Comprehensive 

Treatment

Patients reduced heroin abuse and criminal activity while awaiting admission to a treatment program.

By Sarah Teagle, NIDA NOTES Contributing Writer

Providing methadone maintenance to heroin addicts while 

they are wait-listed for a treatment program can increase 

the likelihood they will enroll when spaces open up, say 

NIDA-funded researchers. The finding corroborates several previous studies in Europe and the United States. In the 

new study, participants who received methadone maintenace reported reduced use and criminal activity.

Across the Nation, full-to-capacity opioid treatment programs commonly put heroin-addicted men and women 

who present for treatment on waiting lists. By the time a 

treatment slot becomes available, the deferred applicants 

often have lost touch with the program or no longer desire 

treatment. The underlying idea of interim methadone 

maintenance is to capitalize on individuals’ possibly transient motivation by providing help when help is requested, explains Dr. Robert Schwartz, who conducted the 

study with colleagues from the Friends Research Institute, 

the University of Maryland, and The Johns Hopkins 

University.

Benefits Early and Late

The researchers recruited 319 heroin-addicted men and 

women who placed themselves on the wait list of a single 

community-based program for methadone maintenance. 

The men and women typified people on methadone wait 

lists in the Baltimore area, in that most were AfricanAmerican and reported abusing heroin daily as well as 

cocaine during the past month. The investigators randomly assigned each individual to receive free interim 

methadone maintenance for up to 120 days—the maximum time programs can legally provide methadone to an 

unenrolled individual—or to remain on a wait list. Both 

groups received information on how to access the waiting 

lists of the 11 other public methadone programs in the 

area.

The investigators interviewed each participant at the start 

of the study; upon his entry into comprehensive methadone treatment or, if he or she did not go into treatment, 

after 120 days; and 6 months after the second interview. 

Participants reported their alcohol, heroin, and cocaine 

abuse and provided urine samples at all three time points; 

those in the interim treatment group also provided samples at weeks 6 and 7 post-entry.

The results 

showed that 

76 percent of 

study participants receiving 

interim methadone entered 

comprehensive 

care within 4 

months, compared with only 

21 percent in the 

control group. At 

the time of the 

last interview, 

78 percent of 

interim methadone patients had 

entered a fullservice program, 

compared with 

33 percent of 

controls. Of the 

study participants 

who entered 

comprehensive 

treatment programs, 80 percent 

of those who had 

received interim 

methadone and 

64 percent of 

controls were still 

attending at their 

last interviews.

The men and women who received interim treatment 

reported abusing heroin on a mean of 4 of the last 30 days 

prior to the 4-month followup interview, compared with 

26 days for wait-listed patients. At the end of 4 months, 

the interim methadone group had a 57 percent rate of 

heroin-positive urine samples, while the control group had 

a 79 percent positive rate (see chart). The substantial difference in opiate-positive drug tests remained at the last 

interview, with a 48 percent positive rate among interim-
24

treated patients, 

compared to a 72 

percent positive 

rate among controls. Participants 

who received 

interim methadone reported 

spending less 

money on drugs 

and receiving less 

illegal income 

in the past 

month compared 

with controls. 

On average, 

study participants reported 

spending $872 

monthly on illegal drugs at the 

beginning of the 

study. By the 

end, the methadone-maintained 

participants had 

reduced these 

expenditures 

dramatically, to an average of $76, compared with $560 

among the controls—a difference that was also maintained at the 6-month followup. “If we can corroborate 

this self-report data from other sources, the money saved 

from not spending on drugs would more than pay for the 

interim medication,” Dr. Schwartz notes. “It costs about 

$20 to $30 per week per person. That is cheap, especially 

when you consider the cost of criminal activity foregone, 

and the hospitalizations and incarcerations avoided.”

While more of the participants who received methadone 

entered full-service treatment, they took longer to do so 

(a mean of 117 days) compared to those in the control 

group (59 days). However, Dr. Schwartz says, “People in 

the interim group knew they were going to get full service 

at the clinic where they were receiving their interim medication at the end of the study. Those in the control group 

who accessed treatment probably represent a highermotivated subgroup—they actively sought it out using the 

local program information we gave them.”

Dr. Thomas Hilton of NIDA’s Division of Epidemiology, 

Services and Prevention Research says, “Dr. Schwartz 

and his team have demonstrated that interim medication 

is a significant recruitment tool. This might even be an 

appropriate way to start treatment for everyone needing methadone maintenance. It exposes patients to some 

degree of structure, helps them ease into a more intensive, 

full-service program and accommodate their lifestyle to 

the structure required in the full service program.” Interim 

methadone also may be an important tool for retention, 

says Dr. Hilton, because patients may be ready for the 

medication before they’re ready for counseling. After a few 

months on methadone alone, patients may be better able 

to engage with a counselor, making the relationship more 

productive. Six methadone programs in the Baltimore area 

have taken their cue from the study’s findings and now 

offer interim maintenance. “What the interim treatment 

approach does is add patients to existing programs,” Dr. 

Schwartz explains. “It is not hard for the staff to do, it’s 

less expensive, and it’s effective. We hope it becomes more 

widespread.”

Sources

• Schwartz, R.P., et al. A randomized controlled trial of 

interim methadone maintenance. Archives of General 

Psychiatry 63(1):102-109, 2006. 

• Schwartz, R.P., et al. A randomized controlled trial of 

interim methadone maintenance: 10-month followup. 

Drug and Alcohol Dependence 86(1):30-36, 2007. 
25

Incentives Reduce Stimulant Abuse During Methadone 

Maintenance

Methadone maintenance patients who earned chances to win prizes by providing stimulant-negative urine samples 

were twice as likely as those who received usual care to attain abstinence from these drugs in a study conducted at six 

outpatient programs. Dr. Maxine Stitzer and colleagues in the NIDA Clinical Trials Network found that adding an 

abstinence-based incentive to usual care—daily methadone and individual and group counseling at least once a month—

tripled the likelihood of continuous stimulant abstinence for 4 or more weeks during the 12-week study. Prizes for the 

incentive program cost about $120 for each of the 388 participants, on average, or $1.42 a day. Prize-based incentives 

have proven successful in helping stimulant abusers attain abstinence during community-based treatment (see “Low-Cost 

Incentives Improve Outcomes in Stimulant Abuse Treatment,” NIDA NOTES, Vol. 21, No. 1), and the new findings 

demonstrate the intervention’s efficacy for a diverse population of opioid-addicted patients receiving usual care in typical 

treatment settings.

Source

• Archives of General Psychiatry 63(2):201-208, 2006. 

Naltrexone-Nicotine Patch Combination Shows Promise

Supplementing nicotine replacement therapy with naltrexone yielded improvements in outcomes in a double-blind 6-week trial. Among the 295 enrollees who completed the trial, 

quit rates were 72 percent with 100 mg of naltrexone, 51 percent with 25 mg, 48 percent 

with 50 mg, and 48 percent with a naltrexone placebo. Patients who took the 100 mg dose 

reported the greatest reductions in nicotine cravings and withdrawal symptoms. The investigators observed that patients receiving the 25 mg and 50 mg doses gained the least weight, 

and suggested that combination therapy with low-dose naltrexone and the patch be considered for smokers concerned about weight gain. The researchers cautioned that naltrexone 

augmentation for smoking cessation requires further study, as abstinence differences evened 

out by a 3-month followup, and did not recur at 6- and 12-month followups.

Source 

• Archives of Internal Medicine 166(6):667-674, 2006. 

Research Findings

Volume 21, Number 3 (April 2007)
Research Findings

Volume #, Number (Month Year)

26

Cocaine Abusers’ Pretreatment Cue Responses Predict Recovery 

Success

In the future, patients’ brain scans may help clinicians tailor addiction treatment to improve therapeutic 

outcomes.

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 2 (February 2007)

A recent NIDA study strengthens prospects that brain 

imaging may one day help clinicians assign individual 

patients to treatment models that maximize their 

personal chances of a successful outcome. The study, 

conducted by Dr. Thomas Kosten and colleagues at Yale 

University School of Medicine, the University of Arkansas 

for Medical Sciences, and the Massachusetts Institute of 

Technology, correlated cocaine-addicted patients’ regional 

brain responses to drug cues with their outcomes in subsequent treatment. The patients whose brain scans revealed 

rapid and strong activation in sensory, motor, and cognition- and emotion-processing brain areas were more 

likely to drop out of treatment and fail to achieve 

stable abstinence.

“A test that predicts treatment outcomes, especially 

vulnerability to relapse, could help guide individualized 

treatment. For example, a clinician might recommend an 

extended stay in residential treatment or more intense 

behavioral intervention for patients with a propensity 

for relapse,” says Dr. Kosten, now at Baylor College

of Medicine.

Dr. Kosten and colleagues pursued the implications of an 

intriguing finding made in a prior study of cocaine cue 

responses: In some patients, strong, rapid activation of 

brain areas associated with emotion and sensing preceded 

the onset of craving. Although craving itself does not 

generally predict relapse, Dr. Kosten’s team speculated 

that cue-induced brain activation that occurs quickly and 

reflexively, below awareness, might do so. They hypothesized that patients who showed such responses during the 

first 30 seconds of cue exposure would also demonstrate 

poorer treatment outcomes.

To test their hypothesis, the investigators recruited 17 

men and women who were participating in a trial of an 

antidepressant—sertraline—that is being evaluated as a 

possible treatment for cocaine addiction. The participants 

reported abusing cocaine 20 days, on average, during the 

month before the study. All met standard clinical criteria 

for cocaine addiction and had abused the drug for 6 years, 

on average. Most were new to treatment.

After being cocaine-free for 5 days, on average, each participant underwent functional magnetic resonance imaging (fMRI) while watching two 4-minute videotapes. The 

first minute of each tape reported on vegetable prices, and 

the participants’ brain activity while hearing this emotionally neutral information served as a baseline for comparison. During the last 3 minutes, an actor pretended to 

smoke cocaine and experience a “rush.” Immediately after 

viewing the tapes, each participant rated peak cocaine 

craving intensity on a scale from 0 to 10. After the imaging session, participants began taking either sertraline or a 

placebo daily and completed 2 weeks of residential treatment. During the 10-week outpatient phase of the trial, 

they were to continue their medication regimen, receive 

weekly individual cognitive-behavioral therapy, and submit urine samples three times a week.

26
2727

Interplay Within Cingulate Cortex?

Nine of the 17 participants relapsed, defined by the 

investigators as submitting fewer than 15 of a possible 30 

cocaine-free samples during the study and not completing outpatient treatment. Participants taking sertraline 

were just as likely as those taking the placebo to relapse. 

Relapsers and nonrelapsers reported cue-induced cravings of comparable intensity. The two groups differed, 

however, on brain activation during the first 30 seconds 

of the cocaine-cue videotapes. Relapsers showed greater 

cue-induced activation than nonrelapsers in several areas 

of the cortex: the left precentral (movement control), right 

superior temporal (auditory processing), right lingual and 

right inferior occipital (visual processing), and the left posterior cingulate cortices. The cingulate cortex is integral to 

attention, response inhibition, emotional regulation, and 

decisionmaking (see chart).

The relapsers’ greater activation of the posterior cingulate 

cortex (PCC) was the most notable of the findings. Also 

significant was the lack of any difference between the 

outcome groups in activation of the neighboring anterior 

cingulate cortex (ACC). This contrasts with findings from 

previous studies, in which ACC activation and craving 

were associated in patients who had longer abstinence 

(average 14-28 days) and were imaged for periods longer 

than 30 seconds after being shown cues.

“If researchers can determine changes in brain activity that 

predict responses to particular treatments, then clinicians 

could match therapy with individuals’ scan results or even 

monitor progress in therapy.”

Taken together Dr. Kosten says, these 

results suggest that an interplay occurs 

between the PCC and ACC following 

exposure to cocaine cues and changes 

with increasing stability of abstinence. 

In patients highly vulnerable to cues, 

intense PCC activation occurs within 

30 seconds of cue exposure and is 

positively associated with risk for 

relapse. In less vulnerable patients, 

early PCC activation is less intense, 

and these patients are able to activate 

the ACC to counter the association 

with relapse risk.

Dr. Kosten’s findings highlight the 

promise of imaging linked to behavioral assessments as a tool for guiding 

the treatment of addictions and other 

psychiatric disorders. They parallel a 

previous NIDA-funded study in which 

brain activity patterns during a decisionmaking task predicted treatment 

outcomes among patients addicted to methamphetamine 

(see “Brain Activity Patterns Signal Risk of Relapse to 

Methamphetamine,” NIDA NOTES, Vol. 20, No. 5).

“If researchers can determine changes in brain activity 

that predict responses to particular treatments, then clinicians could match therapy with individuals’ scan results or 

even monitor progress in therapy,” says Dr. Kosten. More 

generally, studies that examine biological and behavioral 

predictors of treatment response elucidate the physiology 

underlying addiction—particularly the neural circuitry 

integrating stress, craving, and the propensity to relapse. 

New tools—for example, scanners that highlight brain 

areas that are working together—are expected to reveal 

more about these physiological processes. “With such 

functional connectivity imaging, one could examine how 

the anterior and posterior cingulate ‘talk’ to each other 

during a drug cue or other experience,” says Dr. Rajita 

Sinha, an investigator in the Kosten study.

“Eventually, researchers will integrate the findings of such 

studies into a complete picture that will specify therapeutic pathways or help in the development of targeted medications to reduce relapse probability,” adds Dr. Harold 

Gordon of NIDA’s Division of Clinical Neuroscience and 

Behavioral Research.

Source

• Kosten, T.R., et al. Cue-induced brain activity 

changes and relapse in cocaine-dependent patients. 

Neuropsychopharmacology 31(3):644-650, 2006. 
2828
NIDA’s division of Basic Neuroscience and Behavioral Research

How Drug Abuse Affects the Brain and Alters Behavior Are Key Questions Driving Division’s Work

By Debra P. Davis, NIDA Notes Staff Writer

Research Findings

Volume 21, Number 2 (February 2007)

A compound that appears promising for treating cocaine 

relapse is wending its way along a chain of discovery 

and trial that links NIDA’s various Divisions. Its discovery occurred under a grant from the Division of 

Basic Neuroscience and Behavioral Research (DBNBR), 

NIDA’s locus for studies into the fundamental brain 

mechanisms underlying drug abuse and addiction.

Dr. David Shurtleff, director of the Division, sees his 

unit as the base of a pyramid upon which other NIDA 

Divisions and the scientific community at large build. 

“Much NIDA-supported research hinges on a basic 

understanding of the important biological components of 

drug abuse and addiction and how we can modify them 

to treat this disease,” says Dr. Shurtleff. “Our research in 

DBNBR, which probes the genetic, molecular, neurobiological, and behavioral levels, is fed to all other Divisions 

at NIDA for further studies and for development of medications and new behavioral treatments.”

With an eye toward developing a new medication for 

treating cocaine relapse, DBNBR “handed over” the 

JDTic compound, a potent and selective kappa-opioid 

antagonist that has been shown to significantly reduce 

stress-induced cocaine relapse in rodents, to the Division 

of Pharmacotherapies and Medical Consequences of 

Drug Abuse for further tests in animals and—if warranted—in people. 

Ultimately, the compound may undergo large-scale clinical trials sponsored 

by NIDA’s Clinical Trials Network.

The flow of research is two-way: As 

DBNBR feeds the findings of its 

grantees to other Divisions, it also 

relies on them for information that 

drives the development of its own 

research portfolio. For example, 

says Dr. Shurtleff, “The Division of 

Epidemiology, Services and Prevention 

Research tells DBNBR what the 

trends in drug abuse are and who 

is affected.”

Key Research Components

DBNBR’s research portfolio is divided among four 

Branches: Genetics and Molecular Neurobiology, headed 

by Dr. Jonathan Pollock; Behavioral and Cognitive 

Science, under Dr. Minda Lynch; Chemistry and 

Physiological Systems, under Dr. Rao Rapaka; and 

Functional Neuroscience, run by Dr. Nancy Pilotte. 

Investigations fall into the following categories:

• Genetic, which seeks to pinpoint genetic variations 

that make some individuals more susceptible to

addiction;

• Developmental, which examines, primarily in animal 

models, the effects of drugs on prenatal development 

as well as on the still developing brains of children 

and adolescents;

• Behavioral, which looks at the consequences of 

drug abuse on behavior and cognition, providing 

important information for the design of treatment 

and prevention interventions; and

• Neurobiological, which delves into the processes 

and mechanisms in the brain and nervous system 

underlying addiction.

29
The research projects touch on a broad range of drugs, 

health problems, populations, and scientific disciplines. 

For example, teams of scientists specializing in virology, 

immunology, neuroscience, and other disciplines are trying to determine how and why some individuals with 

HIV/AIDS develop a type of dementia called neuroAIDS 

and how exposure to neurotoxic drugs such as methamphetamine exacerbates this condition. Another study, by 

NIDA-supported scientists using technology developed by 

the California-based pharmacogenetics company Perlegen, 

Inc., is probing how genes affect tobacco addiction. The 

goal is to lay the groundwork for developing antismoking 

medications tailored to individuals who are genetically 

predisposed to nicotine addiction. Other nicotine studies 

focus on the effects of this drug on adolescents. Research 

by Dr. James Belluzzi and others shows that adolescent 

rats are more sensitive than adult rats to nicotine and 

that a combination of nicotine and acetaldehyde, another 

ingredient of cigarettes, is particularly addictive to the 

adolescents (see “Study Points to Acetaldehyde-Nicotine 

Combination in Adolescent Addiction,” NIDA Notes, 

Vol. 20, No. 3). 

A number of studies are examining how drug abuse 

changes the brain’s structure. They include research by 

Dr. Eric Nestler and colleagues looking at short- and 

long-term changes that cocaine engenders in the brain’s 

limbic system and studies by Drs. Terry Robinson and 

Bryan Kolb indicating that repeated exposure to amphetamine and cocaine alters neuronal structures called dendrites, which, in turn, increases sensitivity to the drugs.

“Thanks to advances in neuroscience and genetics, we’re 

finding answers to longstanding questions,” Dr. Shurtleff 

notes. “Now we’re able to view the human brain in action 

and understand how drug abuse affects the molecular 

mechanisms of cell signaling. As a result, we can develop 

new medications to stave off or reverse those effects. 

Information provided by the mapping of the mouse and 

human genomes is also helping us to answer longstanding 

questions about the etiology of drug addiction.” 

30
Medical Care During Addiction Treatment Reduces Hospital Use

Research Findings

Volume 21, Number 2 (February 2007)

On-site delivery of primary care reduces emergency department (ED) visits and 

inpatient hospital stays over the next 12 months among adult patients in methadone 

maintenance or in long-term residential treatment programs, according to a recent 

article by Dr. Peter D. Friedmann and colleagues. Their longitudinal analysis showed 

that offsite referrals reduced hospitalizations, but not ED visits, among those in 

long-term residential programs. Neither on-site care nor offsite referral curbed health 

service use by outpatients in nonmethadone treatment programs. In all three types 

of programs, health care use declined after substance abuse treatment. Overall, ED 

visits decreased from 47 percent to 23 percent, and hospitalizations from 42 percent 

to 13 percent; the greatest reductions were observed among patients with the longest stays in treatment. The National 

Treatment Improvement Evaluation Study included six methadone maintenance programs, 14 long-term residential 

programs, and 24 outpatient nonmethadone programs with over 2,000 patients. The investigators advocate future studies 

of the cost-effectiveness of integrating primary care into addiction treatment.

Source

•	 Medical Care 44(1):8-15, 2006. 

31
Research Findings

Volume #, Number (Month Year)

32

Low-Cost Incentives Improve Outcomes in Stimulant Abuse 

Treatment

In community-based treatment programs, the intervention added $2.42 per patient per day to counseling 

costs.

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 1 (October 2006)

The opportunity to win rewards worth as little as $1 for 

abstinence can help motivate outpatients to stay in behavioral therapy and remain drug-free, according to a NIDA 

Clinical Trials Network (CTN) study. At eight community-based addiction treatment programs across the United 

States, stimulant abusers who could earn a chance to win 

a prize by providing drug-free urine samples were four 

times as likely as peers who were not offered this incentive 

to attain 12 weeks of continuous abstinence. Prizes for the 

incentive intervention cost the programs about $200, or 

$2.42 a day per participant.

Many addiction treatment clinics face the challenge of 

high patient dropout rates. Reinforcing abstinence helps 

keep patients interested in attending treatment for longer 

periods, which can facilitate behavioral changes to keep 

them off drugs for the long haul,” says Dr. Nancy Petry 

of the University of Connecticut School of Medicine, 

coleader of the study. Prior research has found that, no 

matter how it is achieved, duration of abstinence during 

treatment is one of the best predictors of abstinence 1 year 

later. “More patients achieve this therapeutic milestone 

with a boost from incentive programs,” says the study’s 

other coleader, Dr. Maxine Stitzer of The Johns Hopkins 

University School of Medicine.

The CTN investigators randomly assigned 415 treatmentseeking stimulant abusers (see chart) to one of two conditions: usual care or usual care plus abstinence-based 

incentives for 12 weeks. Usual care typically consisted of 

group counseling, although some patients received individual and family therapy. Patients gave urine and breath 

samples twice weekly. Research assistants tested the urine 

samples for stimulants, opiates, and marijuana, and tested 

the breath samples for alcohol.

Each participant in the incentive condition received 

immediate feedback on his or her samples. After submitting stimulant- and alcohol-negative samples, the patient 

could draw from an opaque container with 500 chips, 

each with words of encouragement or an assigned value: 

Half of the chips simply said, “good job;” 209 could be 

traded for $1 prizes, 40 for $20 prizes, and 1 for a $100 

prize. Prizes were conferred immediately and included 

many options, ranging from toiletries, snacks, and bus 

tokens to 

kitchen 

items, telephones, and 

retail store 

certificates 

for televisions, music 

players, and 

DVD players. The 

number 

of draws 

earned 

increased 

by one each 

week in 

which all the 

patient’s samples were stimulant- and alcohol-negative, 

but fell back to one following a positive sample or an 

unexcused absence. When a participant first achieved two 

consecutive weeks of abstinence, he or she received a $20 

prize. Participants who submitted stimulant- and alcoholnegative samples could earn two bonus draws a week 

if their urine samples were also opioid- and marijuananegative.

More patients in the incentive program (49 percent) than 

in usual care (35 percent) completed 12 weeks of counseling. Patients in the incentive group achieved an average duration of sustained abstinence of 4.4 consecutive 

weeks, compared with only 2.6 weeks among counselingonly patients. Nineteen percent of patients receiving the 

incentive intervention attained 12 weeks of continuous 

abstinence compared with 5 percent of those in usual 

care. Intervention patients also attended more counseling 

sessions (19 versus 16) and submitted more stimulantnegative urine samples during treatment than patients in 

usual care (48 versus 36 percent).

Incentives Accentuate The Positive

“Incentive programs, including low-cost ones, add excitement and additional reasons to attend substance abuse 

treatment. Many substance abusers are ambivalent about 

32
3333

treatment, and rewards may help them stay involved in 

counseling,” says Dr. Petry. Extending retention in treatment may prolong abstinence, in part, because it gives 

counselors more time to help patients re-engage in a drugfree lifestyle, says Dr. Stitzer. Helping patients sustain 

abstinence once they leave therapy is a challenge for all 

treatments, including incentive programs.

Some previous clinical trials of voucher-based incentive 

programs showed benefits of the treatment persisting for 

1 to 2 years, but others found no added value over the 

long term compared with usual care. Further research will 

focus on followup with patients to determine the conditions under which incentive interventions, particularly as 

applied by community-based treatment programs, support 

extended abstinence.

Other relatively small, often single-site NIDA-funded 

clinical trials over the past 15 years have demonstrated 

that motivational incentives are an 

effective adjunct to standard therapy 

for opiate-, marijuana-, alcohol-, and 

cocaine-addicted patients. Patients 

in most of those early studies always 

received vouchers exchangeable for 

goods or services, rather than chances 

to win prizes, for positive behaviors; 

costs typically ran to about $1,000 per 

patient over 3 months, with the result 

that few community programs adopted 

the motivational incentive approach. 

Dr. Petry developed her prize-drawing 

system to make incentives affordable for community programs. She 

has tested it successfully in several 

Connecticut treatment programs, and 

now its effectiveness is confirmed by 

the CTN trial. NIDA is collaborating 

with the Substance Abuse and Mental 

Health Services Administration’s 

Addiction Technology Transfer Center 

to promote awareness of the low-cost 

motivational incentive technique (see 

textbox).

The CTN researchers note that some 

community-based treatment providers 

resist the idea of motivational incentives based on a belief that clinicians 

should not reward patients for behaviors “that they are supposed to do 

anyway.” In response, the researchers 

point out that groups and individuals 

often use external incentives to motivate others—from employees’ bonuses 

to children’s allowances for household 

chores. Dr. Stitzer advocates a shift in 

perspective from punishing lapses to celebrating successes. 

She observes that counselors have often changed their 

views when they have seen incentives help revolving-door 

patients stay in therapy. “Incentive programs—the idea of 

catching people being good and rewarding the behavior—

can infuse addiction treatment with a positive outlook and 

reinvigorate patients and counselors,” says Dr. Stitzer.

Source

• Petry, N.M., et al. Effect of prize-based incentives on 

outcomes in stimulant abusers in outpatient psychosocial treatment programs: A National Drug Abuse 

Treatment Clinical Trials Network Study. Archives of 

General Psychiatry 62(10):1148-1156, 2005. 
Research Findings

Volume #, Number (Month Year)

34

Study Finds Withdrawal No Easier With Ultrarapid Opiate Detox

Three serious adverse events among 35 ultrarapid procedures were all related to unreported preexisting 

medical conditions.

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 1 (October 2006)

Heroin-addicted patients who undergo so-called ultrarapid, anesthesia-assisted detoxification suffer withdrawal 

symptoms as severe as those endured by patients in 

detoxification by traditional methods, according to a 

NIDA-funded clinical trial. Researchers Dr. Eric Collins 

and colleagues at the College of Physicians and Surgeons 

of Columbia University concluded that there is no compelling reason to use general anesthesia in the treatment 

of opiate dependence, especially as it presents particular 

safety concerns. The new findings corroborate those of 

three international studies.

The ultrarapid detox technique, developed about 15 years 

ago by clinicians who hoped to mitigate the discomfort of 

withdrawal and speed the initiation of relapse prevention 

therapy, relies on a general anesthetic to sedate the patient 

for several hours while an opiate blocker precipitates withdrawal.The method is not covered by insurance, which 

makes it difficult to determine how many patients have 

received anesthesia-assisted detox.

To compare anesthesia-assisted detox with other 

approaches, Dr. Collins and colleagues enrolled 106 people seeking heroin detox at Columbia University Medical 

Center’s Clinical Research Center. The patients, aged 21 

through 50, had abused heroin every day during the past 

month. All spent 3 days as Center inpatients during detox, 

then were scheduled for twice-weekly outpatient relapse 

prevention psychotherapy and naltrexone maintenance 

(50 mg/day) for 12 weeks.

The investigators randomly assigned the participants to 

one of three detox methods (see chart). The goal of each 

method was to minimize patients’ discomfort during withdrawal. In the ultrarapid approach, physicians put patients 

under anesthesia for 4 to 6 hours while administering 

naltrexone, a medication that precipitates withdrawal by 

blocking opioid molecules from their receptors in the 

brain. In the second method, patients remained awake 

and took a 

single dose of 

buprenorphine, 

a medication that eases 

withdrawal 

symptoms by 

moderating 

and smoothing the rate of 

opioid clearance from the 

brain. In the 

third approach, 

patients also 

remained 

awake and 

received clonidine and other 

nonopioid 

medications 

as needed to 

counter symptoms for all 

3 inpatient 

days. These 

34
3535

medications were available to all groups as needed for the 

duration of the inpatient phase. Throughout detox, the 

researchers closely monitored patients for complications, 

assessed physical indications of withdrawal, and asked the 

participants to rate their subjective experiences.

Once awakened from anesthesia, patients in the ultrarapid 

detox group demonstrated and reported symptoms of discomfort comparable to those experienced by participants 

receiving the buprenorphine- and clonidine-assisted methods (see chart). Three patients receiving the anesthesiaassisted method experienced serious adverse events—pulmonary and psychiatric complications as well as a metabolic complication of diabetes, all of which required hospitalization. The complications were related to preexisting 

medical conditions that the patients had failed to reveal 

when they were screened for admission into the study. No 

adverse events occurred with the other detox methods.

Treatment outcomes among the three groups were similar. 

Following detox, the researchers offered all the patients 

relapse prevention therapy consisting of outpatient counseling and naltrexone, which counteracts the pleasurable 

effects of subsequently administered opioids. More than 

90 percent of the patients who received the anesthesia- and 

buprenorphine-assisted detox completed naltrexone induction; only 21 percent of those receiving clonidine completed induction. By the third week, more than half the 

patients in all three groups had dropped out of the study; 

only 18 percent remained in treatment the full 12 weeks. 

The percentages of patients submitting opiatepositive urine 

samples during outpatient treatment also were comparable, 

roughly 63 percent, across the three detox methods.

“No Advantage”

“Although providers advertise anesthesia-assisted detox as 

a fast and painless method to kick opiate addiction, the 

evidence does not support those statements,” says Dr. 

Collins. “Patients should consider the many risks associated with this approach, including fluid accumulation in the 

lungs, metabolic complications of diabetes, and a worsening of underlying bipolar illness, as well as other potentially serious adverse events,” he says. Those with preexisting 

medical conditions—including some psychiatric disorders, 

elevated blood sugar, insulin-dependent diabetes, prior 

pneumonias, hepatitis, heart disease, and AIDS—are 

particularly at risk for anesthesia-related adverse events. 

“Careful screening is essential with the anesthesia-assisted 

method, because the thought of sleeping through withdrawal is so compelling that some patients may conceal 

their medical histories,” says Dr. Collins.

“We now have several rigorous studies indicating that 

anesthesia-assisted detox— a costly and risky approach—

offers no advantage over other methods,” says Dr. Ivan 

Montoya of NIDA’s Division of Pharmacotherapies and 

Medical Consequences of Drug Abuse. Dr. Montoya 

notes, “The low retention of patients in subsequent outpatient treatment in the present study, which is not unusual 

for the opiate-addicted population, highlights the need to 

engage people in long-term recovery after detoxification.” 

Naltrexone can help motivated patients stay off opiates, 

but many do not stick to the regimen of daily tablets 

because of the medication’s side effects of anxiety and 

restlessness. Long-acting monthly injections of naltrexone, 

which are now available for alcoholism treatment, may 

work better for patients and show promise in NIDAsupported clinical trials.

Dr. Montoya also points out that with the current 

epidemic of prescription painkiller abuse, clinicians need 

more research on costeffective detox methods for these 

opiates (see “2003 Survey Reveals Increase in Prescription 

Drug Abuse, Sharp Drop in Abuse of Hallucinogens,” 

NIDA NOTES, Vol. 19, No. 4). Some clinics are using 

buprenorphine for this purpose, and NIDA-funded 

investigators are studying various methods to improve 

prescription opiate detox and help patients engage in 

longer term treatment.

Source

• Collins, E.D., et al. Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and 

naltrexone induction: A randomized trial. Journal of 

the American Medical Association 294(8):903-913, 

2005. 
Research Findings

Volume #, Number (Month Year)

36

Buprenorphine Plus Behavioral Therapy Is Effective

For Adolescents With Opioid Addiction

A new study looks at extending the role of buprenorphine for treatment of adolescents.

BY Patrick Zickler, NIDA NOTES Contributing Writer

Research Findings

Volume 21, Number 1 (October 2006)

Adolescents addicted to opioids responded better to 

buprenorphine than clonidine in a clinical trial in which 

all patients also received behavioral therapy. In the NIDAsupported comparison trial at the University of Vermont, 

adolescents who received buprenorphine attended more 

scheduled counseling sessions than peers who received 

clonidine and had higher rates of successful induction to 

a relapse prevention regimen of naltrexone. The study, 

led by Dr. Lisa Marsch, is the first published randomized 

controlled study of treatments for adolescents addicted 

to opioids.

“Heroin abuse among American teens has doubled over 

the past decade, and abuse of prescription opioids such as 

OxyContin and Vicodin has increased even more,” says 

Dr. Marsch. “In light of those figures, it’s important to 

have a scientific basis for selecting treatments for opioiddependent teens. We know from previous research and 

clinical experience that buprenorphine and, to a lesser 

extent, clonidine are among the medications that have 

been shown to be effective for treating opioid-addicted 

adults, but we haven’t known how helpful they can be for 

adolescents.”

Dr. Marsch and colleagues enrolled 36 opioid-addicted 

adolescents, aged 13 to 18, in a 28-day outpatient treatment program. Half the participants (9 male, 9 female) 

received buprenorphine in tablet form, the rest (5 male, 

13 female) clonidine via transdermal patch; each patient 

also was given a placebo resembling the other treatment. 

Medication dosages varied depending on each participant’s weight and the amount of drug he or she reported 

abusing before beginning treatment; dosages of buprenorphine were in the low to moderate range of those typically 

given to opioid-addicted adults.

All participants also received behavioral therapy based on 

the Community Reinforcement Approach: three 1-hour 

sessions each week of counseling on methods to minimize 

involvement in situations that might lead to drug-taking, 

training to help recognize and control urges to abuse opioids, and encouragement to recruit family members as 

allies for abstinence. Participants earned vouchers worth 

$2.50 for the first opioid-negative urine sample, plus 

an additional $1.25 for each subsequent one, and a $10 

bonus for each set of three consecutive negative samples. 

Continuous abstinence could earn participants $152.50 in 

vouchers redeemable for rewards such as ski passes, CDs, 

gym passes, and clothing.

Buprenorphine and clonidine both supported high rates 

of abstinence. Among participants who completed treatment, rates were 78 percent and 81 percent, respectively, 

confirmed by urine samples provided at the thrice-weekly 

sessions. However, nearly twice as many buprenorphine 

as clonidine recipients completed the 4-week treatment 

(72 percent compared with 39 percent). “The high rate 

of retention in the buprenorphine group is particularly 

noteworthy,” Dr. Marsch says, “because long-term success in recovery is directly related to the amount of time 

patients spend in treatment.” And, she adds, the willingness of most patients who received buprenorphine to 

continue treatment with naltrexone following completion 

of the 28-day program is similarly encouraging. Sixty-one 

percent of the buprenorphine group, but only 5 percent of 

those who received clonidine accepted naltrexone.

36
3737

“Dr. Marsch’s research is an important first step in systematically studying adolescents who are addicted to 

opioids,” says Dr. Ivan Montoya of NIDA’s Division of 

Pharmacotherapies and Medical Consequences of Drug 

Abuse. “We know that there are differences in the patterns 

of opiate abuse and addiction in young people compared 

with adults. We need dedicated studies like this one to 

understand how teens are affected by opiate drugs and 

how best to treat them.” 

The next step in Dr. Marsch’s research will involve a 

larger sample of young opioid abusers. “We want to 

evaluate buprenorphine’s effectiveness if treatment is 

extended to 2 months rather than 28 days,” she says. 

“We will also examine the most effective doses and dosing 

regimens for various subgroups of young patients.”

Source

• Marsch, L.A., et al. Comparison of pharmacological 

treatments for opioid-dependent adolescents: A randomized controlled trial. Archives of General Psychiatry

62(10):1157-1164, 2005. 
Research Findings

Volume 20, Number 6 (July 2006)

38

Court-Mandated Treatment Works as Well as Voluntary

Regardless of their impetus for participating in drug treatment—internal drive or external pressure—men 

had similar outcomes in the long term.

By Lori Whitten, NIDA NOTES Staff Writer

A group of men who completed court-ordered treatment for alcohol and drug 

problems reported lower 

intrinsic motivation at the 

beginning of treatment, but, 

5 years later, reported the 

same rates of abstinence, 

employment, and rearrest 

as peers who sought help 

on their own. The findings from a NIDA- and 

Department of Veterans 

Affairs (VA) Health Services 

Research and Development 

Service-supported analysis of 

data on treatment outcomes 

affirm the results of shorter 

term studies that have 

shown similar therapeutic 

outcomes for voluntary and 

legally mandated patients. The new study also included 

an important, but largely unstudied, comparison group: 

people who had been in court, but were not mandated to 

enter treatment.

“Once in a therapeutic environment, mandated patients 

seem to reflect on their situation and accept the need for 

treatment,” says Dr. John Kelly, lead investigator of the 

study, conducted at the VA Palo Alto Healthcare System 

and Stanford University School of Medicine. “Our findings suggest that people can learn from the ‘teachable 

moment’ offered by a judicial mandate, even though the 

initial motivation for treatment is external. Judicial mandates may provide an opportunity for offenders to gain 

access to and benefit from needed treatment.”

Drs. Kelly, Rudolf Moos, and John Finney analyzed 

data, gathered by Drs. Moos and Finney and Dr. Paige 

Ouimette, on 2,095 men who were treated for alcohol 

and drug problems in 15 VA programs and followed for 

5 years. About half the men (54 percent) were addicted 

to drugs; 80 percent were dependent on alcohol. Most 

(82 percent) had no criminal justice system involvement 

and entered treatment voluntarily (No-JSI); 7 percent 

were on probation or parole and were required to participate in treatment by order of a court or criminal justice 

official (JSI-M); 11 percent had been before a court, but 

not mandated to treatment (JSI). About half (49 percent) 

of the participants were African-American; 45 percent 

were White; and the remaining 6 percent were Hispanic, 

Native American, or Asian. Most (74 percent) were unemployed when they started treatment.

The men completed 21 or 28 days of residential treatment, which took one of three therapeutic approaches: 

group psychotherapy and individual activities based on the 

12-step approach, cognitive-behavioral therapy, or a mix 

of both. When they completed treatment, the men were 

urged to participate in outpatient programs and self-help 

activities.

At the beginning of treatment, each man completed a 

questionnaire that assessed characteristics considered 

important to recovery: motivation, self-efficacy, coping 

skills, 12-step participation, psychiatric symptoms, history 

of negative consequences of alcohol and drug problems, 

number of previous treatment episodes, and whether they 

considered themselves to be addicted. They also reported 

any prior year arrests and any judicial mandate for treatment. At the end of the treatment program, participants 

repeated the assessment and reported their perceptions 
39

of the therapeutic experience. Most also received a selfadministered assessment in the mail at the 1- and 5-year 

follow up points, with the rest contacted by telephone or 

in person. Research assistants telephoned patients when 

necessary to complete or clarify information.

In the initial assessment, men in the JSI-M group reported 

experiencing fewer negative consequences of alcohol and 

drug consumption, fewer symptoms of depression and 

anxiety, and less desire to abstain than No-JSI or JSI participants. Fewer mandated (45 percent) than voluntary 

patients (58 percent) met the standard clinical criteria for 

drug addiction. Voluntary patients more frequently recognized their addictions, connected them to other problems, 

and reported a readiness to change.

Rearrest Rates Fall, Remain Low

At the end of treatment, all three groups of patients 

demonstrated enhanced coping skills and expressed more 

confidence that they could resist alcohol or drugs in 

high-risk situations. Symptoms of psychological distress 

improved for participants in all groups. At the 1-year followup, larger proportions of JSI-M participants reported 

abstinence, successful moderation in their use of alcohol, 

and freedom from drug-related consequences (for example, 

missing work or fighting with a family member because of 

drugs) than JSI and No-JSI participants (see chart). Arrest 

rates for the two JSI groups fell dramatically after treatment. Mandated patients showed arrest rates similar to 

those of their No-JSI peers (about 20 percent) and lower 

than those of their JSI peers (32 percent) at the 1-year followup. Five years after treatment, most outcomes among 

the three groups did not differ (see chart).

The investigators believe that, in addition to the other 

positive effects of treatment, mandated patients may 

acquire motivation to change. “The high level of camaraderie in VA residential treatment, where these individuals 

interacted with self-motivated peers, may have contributed 

to a shift in attitude,” says Dr. Kelly.

The implications of Dr. Kelly’s findings go beyond the 

criminal justice population, says Dr. Beverly Pringle, formerly of NIDA’s Division of Epidemiology, Services and 

Prevention Research. “The idea that patients must want to 

change seems to permeate current practice, but the drug 

abuse treatment field may need to reexamine its definition of motivation,” she says. Clinical measures of motivation mostly indicate intrinsic drive to change, but extrinsic 

motivators as well as rewards can increase treatment entry 

and improve long-term outcomes.

Source

• Kelly, J.F.; Finney, J.W.; and Moos, R. Substance use 

disorder patients who are mandated to treatment: 

Characteristics, treatment process, and 1- and 5-year 

outcomes. Journal of Substance Abuse Treatment 

28(3):213-223, 2005. 
Checkup System Catches Relapse Early and Facilitates Return to 

Treatment

Researchers in Chicago apply an old medical maxim: “Chronic diseases require chronic cures.”

By Lori Whitten, NIDA Notes Staff Writer

Research Findings

Volume 20, Number 6 (July 2006)

Supplementing regular recovery checkups with motivational interviewing and active linking to treatment can 

get relapsing patients back into treatment sooner and help 

them stay longer, report NIDA-funded researchers. In 

the 2 years following treatment, patients who received the 

additional interventions were three times as likely to reenter treatment as others who received assessments only.

Lead investigator Dr. Christy Scott and coinvestigator 

Dr. Michael Dennis developed the effective intervention, which they call the Recovery Management Checkup 

(RMC) system, to expedite the recovery of people who 

had attended treatment and were now living in the community and experiencing substance abuse problems. They 

say the findings suggest that their approach to treating 

substance abuse as a chronic condition may help patients 

shake off the shame of relapse. “By the time patients had 

participated in checkups for 2 years, many who were 

initially reluctant to reenter treatment would call a peer 

to link them with help after a slip,” says Dr. Scott, of 

Lighthouse Institute in Chicago, a Division of Chestnut 

Health Systems, Inc.

Intervention Matches Relapse Patterns

In developing the RMC system, the researchers built 

on previous studies in which they had identified patterns 

of chronic substance abuse, relapse, and recovery. They 

found that, during the first 3 years after treatment, people 

frequently transitioned between recovery, substance abuse, 

and treatment—a cyclic pattern suggesting that periodic 

checkups, with intervention when necessary, might help 

shorten relapse episodes. They also researched approaches 

used to manage other chronic health conditions and 

found that monitoring for relapse and reducing the 

time from relapse to treatment reentry improved longterm outcomes. 

To implement the RMC system, Drs. Scott and Dennis 

hired and trained a cadre of research assistants and linkage 

managers, many of whom were local recovering individuals. Chestnut staff and clinical colleagues at Haymarket 

Center, the largest addiction treatment provider in 

Illinois, interviewed 448 men and women who had met 

the standard criteria for a substance abuse diagnosis at 

some time in their lives, had abused alcohol or other drugs 

in the past 90 days, were not in protective custody, and 

intended to live in Chicago for the next year. Cocaine, 

alcohol, opiates, and marijuana were the most commonly 

abused drugs. Immediately following the interview, 

patients received a referral to Haymarket Center for 

treatment—60 percent as residents and 40 percent as outpatients—for 27 days, on average; 11 percent remained in 

treatment for 90 days or more. Upon leaving treatment, 

each patient scheduled eight quarterly followup appointments. Before the first checkup, researchers randomly 

assigned the patients to either the RMC intervention or 

an assessment-only control group.

At each checkup appointment, patients met with a research 

assistant. The assistant administered a 45-minute version 

of the Global Appraisal of Individual Needs assessment 

and ascertained information about the patient’s living 

40
situation and substance involvement. If the patient had 

not abused any substance during the past 90 days, the 

assistant encouraged continued abstinence and scheduled 

the next appointment. Patients who reported slips were 

merely advised to reenter therapy if they were in the control group, but met with a linkage manager if they were in 

the intervention group and living in the community.

The linkage manager conducted motivational interviews, 

usually lasting less than 30 minutes, in which he or she 

provided feedback on patients’ substance abuse and related problems, discussed ways to work through barriers to 

treatment reentry, and considered motivations to return to 

therapy. If a patient was willing to reenter treatment (even 

with low motivation), the linkage manager scheduled an 

appointment, telephoned with a reminder, and arranged 

transportation. The linkage manager provided assistance 

for 2 weeks, but afterward, responsibility for continuing 

therapy fell to the patient. Between RMC appointments, 

the patient received cards and calls from the research 

office; these served as a reminder of the next visit and 

carried a message of support from the research team.

Checkups Boost Check-Ins

The researchers were able to interview patients at both the 

beginning and end of a quarter in 87.5 percent of cases. 

They categorized each patient’s current status as in the 

community abusing substances, in treatment, in recovery (no substance abuse, problems, or treatment while 

living in the community), or incarcerated. Between the 

beginning and end of each quarter, about one-third of 

the patients, on average, transitioned from one status to 

another. Most (82 percent) transitioned at least once 

during the study, with 62 percent moving between points 

several times (see chart on previous page).

Among patients who relapsed, 67 percent of RMC 

patients reentered treatment within 90 days after the 

checkup, compared with 51 percent of assessment-only 

patients. RMC patients returned to treatment sooner (27 

versus 45 days) and stayed in treatment longer (7.75 versus 4.68 days), on average, than the control group. Length 

of treatment predicted transition to recovery at the next 

quarterly assessment—for every 10.5 days in treatment, 

a patient was 1.2 times more likely to be abstinent at the 

next quarterly checkup.

“The checkups help a patient evaluate his or her behavior and recovery-related issues—much as a person with 

diabetes would report on blood sugar levels and diet and 

exercise patterns,” says Dr. Thomas Hilton of NIDA’s 

Division of Epidemiology, Services and Prevention 

Research. “By employing individuals in recovery as linkage 

managers, the program also offered an opportunity for the 

patient to return to treatment or at least receive support 

from someone who has been there.”

Drs. Scott and Dennis plan to tailor the checkups for 

specific populations—for example, women involved in 

the criminal justice system. 

Source

• Scott, C.K.; Dennis, M.L.; and Foss, M.A. Utilizing 

recovery management checkups to shorten the cycle 

of relapse, treatment reentry, and recovery. Drug and 

Alcohol Dependence 78(3):325–338, 2005. 

41
Medications Development Division Nurtures the Creation of New 

Addiction Treatments

By Lori Whitten, NIDA Notes Staff Writer

Research Findings

Volume 20, Number 6 (July 2006)

In the Anti-Drug Abuse Act of 1988, Congress mandated 

NIDA to promote the development of medications “to 

treat the symptoms and disease of drug abuse.” Research 

by NIDA-supported scientists and others had by then 

made clear that drug abuse is a neurological disorder treatable by pharmacotherapy, but only three anti-addiction 

medications were available (disulfiram, methadone, and 

naltrexone), all developed in the 1960s and early 1970s. 

Congress recognized the need for Federal leadership and, 

because of NIDA’s resources and expertise, entrusted the 

Institute with facilitating the development of pharmacotherapies to treat addiction.

With an initial appropriation of $8 million, NIDA 

launched a Medications Development Program that 

same year and formally established the Medications 

Development Division in 1990. From its beginning, the 

Division has supported and coordinated academic and private sector scientists engaged in every stage of medications 

development—from the creation of new compounds in 

the laboratory to the testing of products in clinical trials. 

The Division’s efforts have been instrumental in bringing 

buprenorphine and buprenorphine-naloxone—safe and 

effective treatments for opiate addiction, the latter suitable 

for office-based therapy—to the Nation’s clinics and 

pharmacy shelves. Among other current priorities, the 

Division supports work to establish the safety and efficacy 

of the smoking-cessation aids nicotine replacement and 

bupropion for people with psychiatric conditions, pregnant women, and adolescents.

Under the leadership of Division Director Dr. Frank 

Vocci, Dr. Nora Chiang, Chief of the Chemistry and 

Pharmaceutics Branch, manages laboratory research 

grants designed to develop new compounds with therapeutic potential; Dr. Jane Acri, Director of the Addiction 

Treatment Discovery Program, leads a multidisciplinary 

team that screens compounds and advances those 

with therapeutic potential into testing for safety and 

efficacy; and Dr. Ahmed Elkashef, Chief of the Clinical/

Medical Branch, coordinates the evaluation 

of data from clinical trials.

The Division pursues a dual strategy that balances the 

need to advance scientific discovery and the need to find 

safe and effective treatments as rapidly as possible. On 

one track, NIDA intramural and funded scientists seek 

new medications. Researchers in the Cocaine Treatment 

42
Discovery Program have identified and evaluated more 

than 3,000 compounds whose molecular characteristics 

or performance in animal studies suggested they might 

reduce cocaine craving and prevent relapse. This process has, for example, identified a new compound called 

JDTic, which has anti-stress and antidepressant characteristics and prevents relapse in animals, and is developing 

the agent for potential clinical testing. Under the second 

approach, NIDA has established a network of clinical 

investigators to screen marketed medications with neurochemical effects that suggest a potential for reducing 

drug abuse (see chart, page 4 of NIDA NOTES, Vol. 20, 

No. 6). Among 65 medications examined so far, eight 

potential treatments for cocaine abuse—including topiramate, disulfiram, and modafinil—have advanced to the 

confirmatory stage of clinical trials in cocaine-dependent 

patients.

Throughout the 1990s, as well, the Division advanced 

research on vaccines that prevent drugs from reaching 

the brain. A vaccine to prevent cocaine addiction and 

another for nicotine abuse are now being tested for safety 

and efficacy.

Because medication development is an enormously complex and costly enterprise, the Division collaborates with 

other Government agencies, particularly the U.S. Food 

and Drug Administration (FDA), and the pharmaceutical industry. The relationship with FDA has been vital to 

overcoming scientific and regulatory barriers to evaluating new medications for opiate addiction and shepherding buprenorphine through the necessary approvals. The 

Division’s relationships with industry frequently have been 

formalized as Cooperative Research and Development 

Agreements (CRADAs). In this type of arrangement, 

NIDA provides expertise, equipment, and facilities to 

test a corporate-owned compound as a potential pharmacotherapy; if the results are as hoped and a marketable 

medication results, the company maintains the commercial rights and NIDA retains a license to perform further 

research. Under a current CRADA, NIDA is working 

with Teva (formerly IVAX Corporation) to determine 

whether talampanel, a compound in clinical testing for 

treatment of epilepsy, may help cocaine abusers overcome 

their addiction.

Dr. Vocci says, “Our first 15 years have taught us the 

importance of developing treatments that patients will 

accept and readily use, and that medications are most 

effective in combination with psychotherapy or counseling. We now apply these lessons to all efforts.” Looking 

ahead, Dr. Vocci lists Division goals for the next 5 years:

• Validate the effectiveness of promising medications 

for cocaine addiction; 

• Advance compounds that have shown promise in 

animal research to clinical testing in people who are 

addicted to methamphetamine and marijuana;

• Advance a new smoking cessation aid into clinical 

trials (possibly selegiline, which has shown promise 

in preliminary studies); 

• Determine optimal immunization schedules for nicotine and cocaine vaccines and obtain FDA approval;

• Identify medications to curb cognitive problems 

that limit patients’ ability to benefit from behavioral 

therapies;

• Continue preliminary clinical studies of interactions 

between HIV infection, antiviral therapies, and antiaddiction pharmacotherapies and identify interventions that slow the progress of the infection in drug 

abusers; and

• Collaborate with other branches of NIH and industry 

partners to test a vaccine for hepatitis C among drugabusing populations.

“Bringing a new medication to market is a lengthy and 

expensive endeavor, but physicians and patients need a 

choice of many treatment options. The progress in antiaddiction pharmacotherapies shows the strength of the 

dual strategy of medications development, which will 

continue to provide us with the best hope for novel 

approaches to treating addiction,” says Dr. Vocci. 

43
44

Community-Based Treatment Benefits Methamphetamine Abusers 

A large California study finds favorable effects for inpatients and outpatients; women’s gains are larger.

By Lori Whitten, NIDA Notes Staff Writer

Research Findings

Volume 20, Number 5 (April 2006)

Methamphetamine abusers can achieve long-term abstinence with the help of standard community-based drug 

abuse treatment. Nine months after beginning therapy, 

87 percent of patients treated for heavy or long-term 

methamphetamine abuse in California outpatient and residential programs were abstinent from all drugs, according 

to a NIDA-supported analysis. “In the public dialogue, 

and even among professionals in the field, one sometimes 

hears that meth abuse is ‘not treatable.’ But that view is 

not borne out by recent clinical trials or our study, which 

shows that community-based treatment reduces drug 

abuse and other problems,” says lead investigator Dr. 

Yih-Ing Hser.

Dr. Hser and colleagues at the University of California, 

Los Angeles analyzed data from the California Treatment 

Outcome Project (CalTOP), an ongoing study that has 

followed the progress of adult substance abusers treated 

at 43 outpatient and residential programs throughout the 

State since April 2000. The researchers focused on 1,073 

patients who reported that methamphetamine abuse was 

their primary drug problem (572) or that they had abused 

the stimulant regularly for at least 1 year before beginning treatment (501). Most were in their 30s or younger, 

White or Latino, unemployed, and on public assistance; 

most had an arrest history. They had abused methamphetamine for about 9 years, on average, and nearly onequarter (22 percent) reported injecting drugs at least once. 

Although 64 percent had children aged 18 or younger, 

one-third of parents did not live with their children in the 

month before beginning treatment. One parent in five 

reported that a child protection court had ordered that his 

or her children live with someone else, and 6.3 percent 

had their parental rights terminated by 

the State.

The patients 

received the 

addiction 

treatment 

services 

routinely 

provided 

by each 

program. 

These usually included 

group therapy, with an 

average of 

69 drug-related 

and 51 alcoholrelated sessions 

during the first 

3 months of 

treatment. On average, the patients also received 22 sessions on dealing with mental health symptoms and 13 

addressing psychosocial problems, including family, parenting, and employment.

More than 60 percent of the patients completed 3 months 

of treatment. Among all the patients in the study—those 

who finished 3 months and those who did not—the average reported frequency of methamphetamine abuse fell 

from 2.7 to 0.5 days per month from the start of treatment 

to 9 months later. The portion who were abstinent from 

all drugs rose from 55 percent to 87 percent in the same 

interval, and 68 percent were abstinent and also not incarcerated. Patients improved in all areas—drug and alcohol 

abuse; mental health symptoms; and employment, family, 

and legal problems—except one: men’s medical problems. 

Dr. Thomas Hilton of NIDA’s Division of Epidemiology, 

Services and Prevention Research says these findings 

should reassure professionals working in the addiction, 

social services, and criminal justice fields that current 

therapies work for these troubled patients. “Dr. Hser’s 

findings suggest that treatments available in the community help meth abusers reduce drug abuse and start to get 

80

70

60

50

40

30

20

10

0

n n

Percent reporting problem in past month

Any Drug Criminal Depression

Abuse Activity

45

13

63

51

42

30

Abusers Achieve Gains 

With Treatment

Nine months after methamphetamine abusers 

began addiction treatment, they had reduced 

past-month drug abuse and criminal activity, 

and fewer reported depression.

“Because methamphetamine abusers respond to treatment, getting 

them into therapy is a top priority. For 

women, there is added urgency to 

help them avoid exposing the children 

they may bear to the consequences of 

prenatal drug exposure.”

Before

Treatment

9-Month

Follow up
45

their lives back on track, echoing prior 

research,” he says.

Women’s Experiences

Dr. Hser’s findings confirm gender 

differences seen in other studies: 

Women began treatment with more 

severe psychosocial problems than 

men (see chart, right) and benefited 

more. Although treatment retention 

levels were similar for the two sexes, 

the women made greater gains in the 

areas of family relationships and medical problems, while achieving similar 

improvements in all other areas at the 

9-month followup. The women’s better outcomes may have resulted in part 

from more intensive services (see chart 

below); as well, Dr. Hser says that 

many women in the study had a powerful motivator—family. “Many were 

trying to maintain or regain custody 

of their children by demonstrating 

improvement during treatment. Others 

had ‘hit bottom,’ saw how drug abuse 

was hurting their families, and decided 

to make a change,” she says.

“Because methamphetamine abusers 

respond to treatment, getting them 

into therapy is a top priority. For 

women, there is added urgency to help 

them avoid exposing the children they 

may bear to the consequences of prenatal drug exposure,” says Dr. Hser.

Dr. Hser and her 

colleagues continue to 

analyze CalTOP 

data, aiming to 

determine the 

longer-term 

impact of therapy 

and identify 

ways programs 

can improve 

outcomes. 

“Enhancing 

psychiatric, 

parenting, and 

employment services would better 

match patients’ 

needs, and my 

team plans to study the relationship between help for 

these problems and longer-term outcomes,” says Dr. Hser. 

They also plan to investigate whether women-only treatment is more effective for pregnant methamphetamine 

abusers than mixed-gender programs.

“The field needs more research following meth abusers over 

time to get a picture of the long-term outcomes of treatment, relapse episodes, and whether these patients require 

additional support to sustain gains made during therapy,” 

says Dr. Hilton. “Because the availability of community 

health and social services varies across States, we cannot 

generalize the findings from one State, such as California. 

We need data from across the country,” he adds. 

Source

• Hser, Y.-I.; Evans, E.; and Huang, Y.-C. Treatment 

outcomes among women and men methamphetamine 

abusers in California. Journal of Substance Abuse 

Treatment 28(1):77-85, 2005. 

Men, Women Experience Different Problems 

Family and Social Circumstances

Women, % 

(n=567)

Men, % 

(n=506)

Total, % 

(N=1,073)

Children living with someone else by court order 29.3 9.9 20.1

Parental rights terminated 10.1 2.2 6.3

Family abused substances 21.7 10.5 16.4

Physically abused (past month) 5.5 1.8 3.7

Sexually abused (past month) 2.5 0.6 1.6

Employed 23.8 43.9 33.3

On public assistance 63.1 37.0 50.8

Criminal Justice System Involvement

On parole 4.4 12.7 8.3

On probation 32.3 37.6 34.8

Ever arrested 76.7 88.3 82.2

Arrest in past year 36.7 45.1 40.6

Criminal activity (past month) 55.2 71.7 63.0

Psychiatric Symptoms (Past Month)

Serious depression 38.8 29.8 34.6

Difficulties with understanding,

concentrating, remembering 36.2 26.5 31.6

Suicidal thoughts 11.3 6.3 9.0

Prescribed psychiatric medicine 21.3 15.4 18.6

Women beginning treatment for methamphetamine abuse reported more psychosocial 

problems, while men reported more crime and criminal justice involvement.

For some problems, women received more 

services than men during the first 3 months 

of treatment.
Research Findings

46

Treatment During Work Release Fosters Offenders’ Successful 

Community Reentry 

Long-term studies are helping to determine the most effective drug treatment protocols for 

prisoners in transition.

By Lori Whitten, NIDA Notes Staff Writer

Volume 20, Number 5 (April 2006)

Addiction treatment for prisoners during the pivotal time 

when they are returning to the community has a strikingly persistent benefit and may create a ‘turning point’ 

that helps them stay off drugs and out of trouble, NIDA 

researchers have concluded after tracking the progress of 

more than a thousand released offenders. The investigators 

found that prisoners who participated in drug abuse treatment during a work-release program were three times as 

likely as untreated peers to remain drug-free up to 5 years. 

Treatment during work release delayed relapse and resulted in more drug-free time during the followup period. 

Attendance at continuing weekly group sessions following 

completion of work-release treatment further enhanced 

outcomes up to 3 years.

Dr. Clifford Butzin, a co-investigator of the study led by 

Dr. James Inciardi, at the University of Delaware compared the effectiveness of therapy given in different stages 

of incarceration, release, and reintegration into the wider 

community. Their project was part of the State’s efforts 

to offer criminal justice-related treatment programs in 

three stages—during prison, work release, and parole. 

In 1990, Delaware established a work-release treatment 

program to ease the prison-to-community transition with 

funds from a NIDA treatment demonstration grant. The 

program utilizes the same therapeutic community model 

that is the format for Delaware’s in-prison treatment. In 

the mid-1990s, the State added a continuing care component designed to help offenders who have completed work 

release adapt to living in the community with criminal 

justice supervision. 

The research team analyzed the outcomes of 1,122 druginvolved offenders who participated in work release 

between 1991 and 1998 and in any followup. The participants’ (80 percent male, 72 percent African-American) 

risk profiles included characteristics typically associated 

with relapse to drug abuse and crime: extensive criminal 

histories, low rates of marriage, and substantial unemployment before prison (see chart, next page). The investigators assigned each participant to either standard workrelease (WR-S) or the work-release therapeutic community 

(WR-TC). Because WR-TC slots were limited, priority 

for them was given to participants who had graduated 

from the in-prison therapeutic community or whose sentence required treatment as a condition for release.

The participants assigned to the WR-S program served 

the last 6 months of their sentences working for pay in 

the community and spent their nonworking hours in a 

secured residence, but received no formal intervention 

focused on drugs. Participants in the WR-TC intervention 

served the last 6 months of their sentences in a secured 

TC—a “family setting”—in which peers in recovery help 

participants develop a sense of accountability for their 

behavior and change negative patterns that lead to drug 

Greater Participation In Treatment Increased 

Drug-Free Time for Most of Followup Period

During the 5 years after prison release, Delaware offenders receiving treatment in a work-release therapeutic community (WR-TC) 

demonstrated more drug-free time than those in the standard 

work-release program (WR-S). For the first two followup periods, 

percentage of drug-free time increased with greater participation in 

treatment. Beginning 3 years after treatment, the four groups were 

not significantly different from each other; however, participants in 

WR-TC demonstrated more drug-free time than those in WR-S.
47

abuse. They concentrated on treatment goals, performed 

assigned duties in the residence, and attended group and 

individual counseling sessions during the first 3 months 

of the program. They also participated in mock interviews 

and seminars on job seeking, started looking for work and 

housing, opened bank accounts, and developed household 

budgets. During the subsequent 3 months, they worked in 

the community and continued therapy during nonworking 

hours. WR-S participants received no additional services.

Benefits of Work-Release Treatment

After completing work release and returning to the community, WR-TC participants continued treatment for at 

least 6 months. They attended weekly group sessions at the 

TC, visited a counselor once a month, and were encouraged 

to spend at least 1 day a month at the facility.

The investigators interviewed participants at work-release 

initiation and completion and at 18-, 42-, and 60-month 

followup points, confirming abstinence reports with urinalysis. The results showed that WR-TC participants who 

relapsed took twice as long to do so as WR-S participants 

(28.8 months versus 13.2 months, on average). After leaving prison, WR-TC participants had higher abstinence rates 

than WR-S participants (32 percent versus 10 percent). 

Employment rates were also higher with WR-TC (55 percent) than without (45 percent). 

To further analyze the relationships between the levels 

of treatment and outcomes, the investigators subdivided 

the two groups into four: those in WR-S; those who participated in WR-TC but failed to complete it; those who 

completed WR-TC but did not participate in aftercare; 

and treatment graduates with aftercare. At each followup, 

each increase in level of care was associated with a higher 

percentage of time spent drug-free, for most of the followup 

period (see chart, previous page).

Participants in the WR-TC program typically had abused 

drugs once a day before incarceration, whereas those in 

WR-S had abused drugs several times a week. Because of 

their severe drug problems, more WR-TC participants (32 

percent) than WR-S participants (5 percent) had received 

in-prison treatment. However, the researchers determined 

that treatment during work release was much more effective than in-prison treatment, contributing the bulk of the 

advantage attained by the WR-TC group. Treatment during work release halved the likelihood of relapsing, whereas 

other factors—including treatment before or during prison—did not have a significant impact. “Although addiction 

treatment episodes have a cumulative effect, several studies 

have shown that the benefits of treatment during prison 

seem to fade over time compared with therapy during the 

prison-to-community transition,” says Dr. Butzin.

Among 690 participants who completed all followup 

interviews, treatment during work release also reduced 

arrest rates over 

the 5-year period. Rearrest was 

common in all 

groups, however, 

with 77 percent 

of WR-S participants, 58 percent 

of WR-TC treatment graduates 

who did not 

receive aftercare, 

and 52 percent 

of those who also 

received aftercare facing new 

charges at some 

point.

Supportive 

Environment 

is Key

“It makes sense 

that a therapeutic community—

a stable residence 

with a drug-free culture and supportive peers—helps 

people who are looking for a job and a place to live after 

prison. Continuing care for prisoners with drug problems 

during the transition back to the community is essential 

for sustained recovery and other public health benefits, 

including reduced spread of HIV/AIDS and hepatitis 

C,” says Dr. Thomas Hilton of NIDA’s Division of 

Epidemiology, Services and Prevention Research.

Although the prison-to-community transition is critical and may set the pattern for post-release behaviors, 

research is needed on the best ways to coordinate social 

and health interventions with criminal justice supervision. 

Recognizing the importance of science-based knowledge 

on the effective components of treatment for this population, NIDA established the Criminal Justice–Drug Abuse 

Treatment Studies (CJ–DATS) research network with 

Federal partners in justice and public health. CJ–DATS 

investigators around the United States, including the 

team in Delaware, are testing interventions and studying 

approaches for coordinating services for offenders reentering the community.

Source

•	 Butzin, C.A., et al. Treatment during transition from 

prison to community and subsequent illicit drug use. 

Journal of Substance Abuse Treatment 28(4):351-358, 

2005.

Characteristic Percentage

Ever married 29

Unemployed prior 

to incarceration 58

Treatment prior 

to incarceration 72

Incarcerated for 

drug-related crime* 33

Characteristic Average Number

Arrests prior to 

incarceration 9

Prior incarcerations 4

* Does not include crimes committed to obtain 

money for drugs.

Work-Release Participant 

Characteristics

Most participants in the Delaware workrelease program demonstrated a long history 

of criminal activity, chronic drug abuse, 

and characteristics associated with high rates 

of relapse and recidivism.
Research Findings

48

A Brief Encounter With Peer Educator Can Motivate Abstinence

By Lori Whitten, NIDA NOTES Staff Writer

Volume 20, Number 3 (October 2005)

A single meeting with a peer addiction educator 

during a routine medical visit has helped outof-treatment cocaine and opiate abusers attain 

abstinence, report NIDA-funded researchers 

who conducted a study at three Boston clinics. 

The peer educators were bilingual individuals 

in long-term recovery recruited from the same 

ethnically mixed community as the out-oftreatment drug abusers. The meeting consisted 

of a structured motivational interview that culminated in a plan for recovery and referrals.

“Talking with a person like yourself—someone 

who knows your language and culture and 

views you as an equal, who has successfully 

recovered from addiction—shows that change is 

possible and seems to motivate people to get off 

drugs. It’s not a substitute for treatment, but it 

is a good first step,” says Dr. Edward Bernstein 

of Boston University School of Medicine, one 

of the lead investigators of the study. 

Dr. Bernstein and his coinvestigator Dr. Judith 

Bernstein hired and trained individuals who 

had been in recovery for at least 3 years to 

serve as peer educators and research assistants. 

This staff then screened 23,669 outpatients 

who were seeking routine medical care at Boston Medical 

Center walk-in clinics between May 1998 and November 

2000. Altogether 1,175 patients (about 5 percent of those 

screened) met the criteria for study participation—they 

reported abusing cocaine, opiates, or both drugs during the 

past 30 days; scored 3 or higher on the Drug Abuse Severity 

Test; and were not in addiction treatment or protective 

custody—and agreed to participate. A research assistant 

met with each participant to administer further assessments, 

including an abbreviated Addiction Severity Index (ASI), 

and an educator then randomly assigned each patient to 

either an intervention or a control group. Similar proportions of patients in the two groups had abused cocaine 

(about half), opiates (about 10 percent), or both drugs 

(33 to 40 percent) during the month before the study 

(see “Demographic Characteristics of 1,175 Study 

Participants,” on next page).

An educator conducted a motivational interview with each 

patient in the intervention group. This lasted from 10 to 

45 minutes, engaging the patient in a discussion of drug 

abuse, its consequences, the gap between his or her actual 

and desired quality of life, and readiness to seek help. The 

educator concentrated on a few of the patient’s problems 

as identified by the ASI, negotiated a plan for behavioral 

change, and provided a handout listing treatment resources 

in the community. The educator was able to convey personal knowledge about the community programs and mention particular people for patients to contact, having visited 

the organizations as part of his or her training. Ten days 

after the motivational interview, the educators telephoned 

patients to review the action plan, ask what happened, and 

provide additional referrals, if necessary. These calls reached 

less than a third of patients (31 percent).

Participants assigned to the control group received written 

advice—“based on your screening responses, you would 

benefit from help with drug abuse”—along with the handout listing treatment resources. They were not given a 

motivational interview, and those who expressed interest in 

the treatment programs were merely encouraged to call a 

number from the handout. No followup call was attempted 

with these patients.

16.9

30.6

Intervention

% Patients Abstinent 6 Months 

After Intervention

0

5

10

15

20

25

30

35

40

45

50% Cocaine Opiates Both Cocaine and Opiates

Treatment Sources List Only Motivational Interview

12.8

22.3

40.2

17.4

Motivational Interview During Routine 

Medical Visit Reduces Drug Abuse

Six months after meeting with a peer addiction educator during a routine medical 

care visit, patients who participated in a motivational interview had higher rates 

of abstinence than patients who received a treatment sources list only.
49

Results at Six Months

All participants, both the intervention group and controls, 

were given appointments to return to the clinic for followup 6 months after their original assessments. The team’s 

research assistants tracked down no-shows by using the 

clinic’s appointment system and visiting shelters and sites 

frequented by drug abusers. Altogether, they reached 962 

(82 percent) of the 1,175 participants. Ultimately, 184 of 

these patients were excluded from the data analysis, either 

because hair samples taken at study entry did not confirm 

their initial reports of drug abuse, or because they did not 

give samples at followup.

Among the remaining 778 (66 percent of the original 

sample), 22.3 percent of those who had participated in the 

motivational interview had been abstinent from cocaine for 

at least 30 days at the time of the followup interview, compared with 16.9 percent of those who had received just the 

referral list. The motivational intervention was associated 

with superior abstinence rates among the subgroups of 

participants who abused opiates (40.2 percent versus 30.6 

percent) and both cocaine and opiates (17.4 percent versus 12.8 percent). These differences occurred even though 

patients in the motivational interview group had more 

severe medical and drug-related problems and reported 

more psychiatric conditions at the beginning of the study. 

About 40 percent of patients in each group reported that 

they had participated in formal treatment with a health care 

professional during the 6 months between the initial assessment and followup. This similarity in rates of treatment 

suggests that the brief motivational encounter with the 

peer educator was beneficial in itself, and not because it 

prompted participants to seek therapy. Ninety percent 

of the patients who said they received professional help 

underwent detoxification but did not enter ongoing addiction therapy to prevent relapse, a finding the researchers attribute in part to lack of access. “During the study, 

our patients had very limited access to public methadone 

treatment, which many had requested,” says Dr. Edward 

Bernstein.

About half the patients in each group who achieved abstinence cited the peer educator as a source of help. The 

investigators believe patients viewed these individuals as 

role models for abstinence, which may prompt some to 

reduce drug abuse even without a motivational interview. 

“Doctors and patients are not equal, especially when there 

are language, class, and culture differences. Add drug abuse 

to the mix, and you usually get ‘shaming and should-ing,’ 

which makes patients feel inferior and close down,” says 

Dr. Judith Bernstein. Because of their combination of training and life experiences, peers seemed to inspire optimism 

about the prospect for recovery, even in patients who felt 

that others had given up on them. Other sources of support 

included family, mentioned by 50 percent of patients who 

achieved abstinence, and self-help groups (68 percent).

Peer Educators Welcomed

Clinic staff at the Boston Medical Center welcomed the 

study’s structured effort to deal with drug abuse, which is 

a serious problem in the community. They appreciated the 

fact that the program fit unobtrusively into routine care. 

“Most doctors don’t feel they have the time or training to 

deal with substance abuse and are happy to suggest that 

patients see the peer counselor,” says Dr. Edward Bernstein. 

An emergency room physician, Dr. Bernstein plans next to 

implement and evaluate a peer counseling intervention at 

five emergency centers.

“It’s promising to see reduced drug abuse among these vulnerable patients, many of whom were homeless and unemployed,” says Dr. Dorynne Czechowicz of NIDA’s Division 

of Clinical Neuroscience, Development and Behavioral 

Treatment. Previous studies have demonstrated that alcohol-addicted patients benefit from screening and brief 

motivational interviews in primary-care settings, but few 

investigations have involved drug abusers. “More research 

is needed, but these findings suggest that peer educators 

can play an important role in busy clinical environments 

and enhance outreach to abusers of cocaine, opiates, and 

perhaps other drugs,” she says. 

Source

• Bernstein, J., et al. Brief motivational intervention at a 

clinic visit reduces cocaine and heroin use. Drug and 

Alcohol Dependence 77(1):49–59, 2005. The research team worked with outpatients seeking routine 

medical care at Boston Medical Center walk-in clinics.

Characteristic %

Female 29

Race

 African-American 62

 Hispanic 23

 White 14

Born in the United States 82

Homeless 46

Reported psychiatric problems 24

Education less than high school 38

Employed 17

Had health insurance coverage 66

Never participated in substance abuse treatment 54

Demographic Characteristics of 

1,175 Study Participants
Research Findings

50

Telephone-Based Continuing Care Sustains Abstinence

By Lori Whitten, NIDA NOTES Staff Writer

Volume 20, Number 3 (October 2005)

Telephone-based continuing care, 

in which an addiction counselor 

supports patient recovery with 

15-minute calls once a week, can 

be as good as or better than face-toface care at helping most patients 

maintain abstinence after intensive 

outpatient treatment (IOP). In a 

recent NIDA-funded study, the benefits of a telephone support protocol 

were evident nearly 2 years after the 

last call for all but the 20 percent 

of patients with severe addiction 

problems that did not resolve during 

IOP.

“Telephone-based continuing care 

does not require transportation or 

interfere much with work or childcare responsibilities, and this flexibility may help patients stay engaged 

in recovery and maintain the gains 

achieved during initial inpatient 

or outpatient treatment,” says Dr. 

James McKay, lead researcher of the 

study. 

Dr. McKay and colleagues at the 

University of Pennsylvania, the 

Treatment Research Institute 

in Philadelphia, and Brandeis 

University worked with two 

Philadelphia-area outpatient addiction programs. Patients seeking 

treatment in these programs received 

about 9 hours of outpatient group 

therapy each week for 1 month, on 

average. The therapy concentrated 

on overcoming denial of substance 

abuse, learning about the addiction 

process and cues to relapse, and 

beginning self-help participation. 

Dr. McKay and colleagues recruited 

patients who “graduated” from 

therapy—that is, continued in the 

IOP and achieved abstinence in the 

Telephone Counseling Helps Outpatient Treatment 

Graduates Stay Abstinent

All patients participated in 12 weeks of continuing care after completing a month of intensive 

outpatient treatment, and reported outcomes every 3 months during the 2-year followup.

Two years after graduating 

from intensive outpatient 

treatment, more patients 

who participated in telephone-based continuing 

care (TELE) had maintained 

abstinence during the 

previous 3 months than 

those receiving standard 

group counseling (STND). 

The percentage of abstinent patients did not differ 

between TELE and relapse 

prevention (RP) continuing 

care.

Throughout the study, 

patients with four or more 

characteristics reflecting 

severe addiction were better able to maintain abstinence if they participated 

in STND compared with 

TELE. 

The percentage of 

cocaine-positive urine 

samples did not increase 

as quickly during the 

followup for TELE patients 

as it did for those who 

participated in RP, with 

a similar trend for TELE 

compared with STND.

Months After Graduation 

% Patients Abstinent 

0 

10 

20 

30 

40 

50 

60 

70 

80 

TELE 

RP 

STND 

3 6 9 12 15 18 21 24 

Number of High-Risk Characteristics 

% Patients Abstinent 

0 

10 

20 

30 

40 

50 

60 

70 

80 

90 

100 

TELE

RP

STND 

0 1 2 3 4 5 6 7 

Months After Graduation 

% Patients Showing CocainePositive Urine Tests 

0 

5 

10 

15 

20 

25 

30 

35 

40 

45 

TELE 

RP 

STND 

3 6 9 12 18 24 
51

last week—to receive 12 weeks of continuing care and followup for 2 years. 

The patients, 359 men and women aged 18 to 65, were 

typical, in terms of demographics and problem severity, 

of individuals seeking treatment at publicly funded outpatient addiction programs. Half met the Diagnostic and 

Statistical Manual of Mental Disorders, 4th Edition (DSMIV) criteria for co-occurring cocaine and alcohol dependence, 87 were dependent on cocaine only, and 91 were 

alcoholic. Thirty percent had met the criteria for a diagnosis of major depression at some time in their lives. When 

they began treatment, they reported 8 years of cocaine 

and 18 years of alcohol abuse, on average, and multiple 

attempts to quit.

Regular Contact With a Therapist Is Crucial

The investigators randomly assigned each patient to one 

of three continuing care therapies: a face-to-face therapy, 

either standard group (STND) or relapse prevention 

(RP); or telephone-based (TELE) counseling. In STND 

care, the most common approach to continuing care for 

addiction, 122 patients attended twice-weekly counseling 

sessions that emphasized overcoming denial and engaging in mutual- and self-help activities. In RP therapy, 

135 patients attended an individual session of cognitivebehavioral therapy and then group sessions once a week. 

In this approach, patients identify situations that prompt 

substance abuse and work to improve coping responses 

using structured activities and homework exercises. 

In TELE care, 102 patients met with counselors in person 

the week before beginning the telephone phase to discuss 

the therapy and receive a workbook with exercises that 

structured subsequent calls. At a scheduled time each 

week, they telephoned counselors and talked for 15 to 

20 minutes about progress during the previous week, any 

episodes of substance abuse, participation in self-help and 

other pro-recovery activities, plans for achieving the next 

week’s goals, and any concerns. Counselors contacted 

patients who did not call and discussed in a supportive 

way their reasons for not doing so. To ease the transition 

from outpatient to continuing care, therapists offered the 

TELE patients group counseling once a week for a month. 

Patients struggling with relapse at that point could continue with group sessions; more than a third (35 percent) 

exercised this option.

The researchers followed up with patients every 3 months 

throughout the study and contacted 86 percent 2 years 

after graduation from IOP. At this point, about two-thirds 

of TELE patients reported abstinence during the previous 

3 months, compared with about half of those who had 

participated in STND. An analysis of urine samples from 

the cocaine-addicted patients showed an overall increase 

in the percentage of cocaine-positive samples during the 

followup period, but the increase was more rapid among 

RP participants than TELE participants. The TELE group 

had higher abstinence rates than STND throughout followup. Patients who participated in TELE maintained 

the gains of IOP even though they received about half as 

much therapeutic contact (428 minutes) as those receiving 

STND or RP (845 and 861 minutes, respectively). 

“Continuing care benefits people in recovery in several 

ways, but regular contact with a therapist is crucial for 

patients with a chronic condition, and especially helps 

patients who have relapsed get back into treatment,” says 

Dr. Dorynne Czechowicz of NIDA’s Division of Clinical 

Neuroscience, Development, and Behavioral Treatment. 

Although larger studies with more diverse patients are 

needed, Dr. McKay and his colleagues laid important 

groundwork, she says.

Face-to-Face Care for Severe Problems

Some patients need more contact with a counselor than 

telephone-based continuing care affords to maintain 

recovery. To identify these patients, Dr. McKay and his 

colleagues examined the link between outcomes and seven 

patient characteristics: co-occurring addiction to alcohol 

and cocaine at the beginning of IOP; any alcohol use, any 

abuse of cocaine, minimal attendance at self-help meetings, below-average social support during IOP; and a lack 

of commitment to complete abstinence, and low selfefficacy for recovery at the end of IOP. 

Patients who demonstrated three or fewer of the characteristics—about 80 percent of the study population—did 

at least as well with TELE continuing care as with the 

other two approaches. But the remaining patients, those 

who met the criteria for co-occurring addiction at the 

beginning of treatment and did not achieve the main goals 

of IOP—abstinence from cocaine and alcohol during 

treatment, commitment to abstinence, and participation 

in self-help programs—were at high risk for relapse and 

showed better outcomes with STND continuing care, relative to TELE, during most of the followup. The findings 

suggest that TELE may be inappropriate for patients with 

more severe addiction problems until they demonstrate 

stable abstinence from drugs and alcohol, says Dr. McKay.

Flexible Continuing Care 

“Some practitioners are developing flexible arrangements 

to engage and retain more patients in continuing care,” 

says Dr. McKay. Flexibility in the practical sense—the 

ability to call one’s counselor from any location—extends 

participation in continuing care, not only to busy people, 
52

but also to those living in rural areas or who have lost 

driver’s licenses.

Telephone-based care is one way that a treatment intervention can respond to each patient’s progress during 

recovery; it gives counselors the flexibility to intensify 

care if the patient is struggling to maintain abstinence. 

“Clinicians managing other chronic disorders—for example, hypertension and cancer—are using progress during 

initial treatment to determine subsequent care. It’s not 

a new therapeutic approach, but it is novel to addiction 

treatment,” Dr. McKay says.

Sources

• McKay, J.R.; Lynch, K.G.; Shepard, D.S.; and 

Pettinati, H.M. The effectiveness of telephone-based 

continuing care for alcohol and cocaine dependence. 

Archives of General Psychiatry 62(2):199-207, 2005. 

• McKay, J.R., et al. Do patient characteristics and initial progress in treatment moderate the effectiveness 

of telephone-based continuing care for substance use 

disorders? Addiction 100(2):216-226, 2005. 
53

Successful Drug Abuse Treatment in Adolescents Should Address 

Co-Occurring Mental Health Problems

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 19, Number 6 (May 2005)

Adolescent substance abuse patients with co-occurring 

emotional and behavioral problems are more likely than 

peers without coexisting psychiatric conditions to relapse 

in the year following treatment, a NIDA-funded study has 

found. “We must improve identification of co-occurring 

psychiatric disorders among substance-abusing teens and 

move away from a ‘one size fits all’ approach to therapy, 

or treatment gains will remain limited for these vulnerable 

youth and their families,” says Dr. Cynthia Rowe at the 

University of Miami School of Medicine in Florida, who 

led the study.

Following 182 adolescents for a year after substance abuse 

treatment, Dr. Rowe and her colleagues found that those 

with co-occurring externalizing disorders—a combination 

of aggressive and delinquent behaviors including persistent 

lying, stealing, fighting, and destroying property—recovered more slowly than those without psychiatric disorders. 

Youths with externalizing and internalizing disorders—

acting out mixed with anxiety and depression—obtained 

the least favorable treatment outcomes. Dr. Rowe says 

this combination of symptoms often relates to multiple 

problems in life and indicates psychiatric severity—the 

best predictor of substance abuse treatment outcomes in 

adults. “Our results mirror those seen in adults: People 

with more severe psychiatric problems show a significantly 

diminished response to substance abuse treatments of 

known effectiveness,” says Dr. Rowe.

All the youths had been referred to substance abuse treatment, almost 85 percent by the juvenile justice or child 

service systems; they ranged in age from 12 to 17 at the 

beginning of the study. Participants received manualized 

treatment—cognitive behavioral therapy (CBT) or multidimensional family therapy (MDFT)—in weekly officebased sessions for an average of 10 weeks. At the outset 

of the study, the participants’ reports of substance abuse 

frequency in the past month averaged 12.7 days; by the 

end of the treatment, this figure dropped by 2.5 days. Six 

months after treatment, past-month substance abuse had 

fallen another 2.5 days; at the 12-month followup, abuse 

incidence had dropped an additional 2.5 days. The rates 

and patterns of change, however, varied depending on 

coexisting psychiatric disorders.

Substance abusers with no co-occurring disorders (12 percent of the study population) showed the best long-term 

outcomes. Although initially unresponsive to treatment, 

they markedly and 

rapidly reduced substance abuse between 

the 6- and 12-month 

followups—changing at a rate approximately 1.5 times 

that of peers with 

co-occurring externalizing disorders 

(35 percent of the 

study population), 

who also were initially unresponsive to 

treatment and also 

recovered. Youth 

demonstrating mixed 

externalizing and 

internalizing symptoms (48 percent of the study population) showed the 

opposite pattern. Initially improving in response to therapy, they had relapsed to pretreatment levels of substance 

abuse a year later. The responses did not differ in patients 

participating in CBT and MDFT.

Dr. Melissa Racioppo of NIDA’s Division of Clinical 

Neurosciences, Development and Behavioral Treatments 

says CBT and MDFT are very effective treatments for 

most adolescent substance abusers (see “Family-Based 

Treatment Programs Can Reduce Adolescent Drug 

Abuse,” NIDA NOTES Vol. 17, No. 4, p. 7). Poorer 

treatment outcomes among people with co-occurring 

psychiatric disorders suggest that therapists may need to 

tailor substance abuse treatment for the patient’s particular psychiatric condition, although the necessary level of 

specificity is not clear. “To adapt treatments for people 

with co-occurring psychiatric disorders, researchers must 

link particular therapeutic processes with outcomes,” she 

adds—something Dr. Rowe and her colleagues plan to do 

in future studies.

“Looking within the therapeutic process may help us 

discover what must happen to realize recovery from substance abuse. Effective components of therapy may vary 

for adolescents with different co-occurring mental health 

problems, and identifying such mechanisms of change 

may help us develop better interventions,” says Dr. Rowe. 
54

Girls Had More Severe Problems

Most (82 percent) of the study’s par-

ticipants were boys; however, girls were 

overrepresented in the group with the 

least favorable treatment outcomes. 

More girls (83 percent) than boys (44 

percent) displayed externalizing and 

internalizing disorders. Dr. Rowe says 

the pattern is familiar to clinicians 

across the country—there are typically 

more girls among the substance abuse 

patients with pronounced problems 

and disorders. “By the time a girl with 

substance abuse problems is referred to 

treatment, she is usually in considerable 

distress and experiencing severe psychi-

atric symptoms and relationship prob-

lems. Family, school, and legal prob-

lems will continue unabated without 

better identification, referral, and treat-

ment of these vulnerable girls,” says Dr. 

Rowe. Dr. Racioppo emphasizes the 

need for more research on differences in 

how boys and girls develop and mani-

fest behavior problems. Troubled youth 

often have experienced family conflict 

and instability in relationships, but boys 

and girls may react differently. Studies 

indicate that females tend to turn their 

stress inward, developing anxiety and 

depression, which are often unnoticed 

by adults. Dr.Racioppo says girls tend 

to act out in ways that don’t necessarily 

grab the attention of adults—through 

sexual behavior, for example—whereas 

boys externalize in ways that are more 

obvious, such as fighting. “To improve 

identification and treatment outcomes 

of adolescents with co-occurring psychi-

atric disorders, we need to study gen-

der differences in the root causes and 

expression of behavioral and 

emotional problems,” she says.

Source: • Rowe, C.L.; Liddle, H.L.; 

Greenbaum, P.E.; and Henderson, 

C.E. Impact of psychiatric comor-

bidity on treatment of adolescent 

drug abusers. Journal of Substance 

Abuse Treatment 26(2):129-140, 

2003. 
55

Economists Offer Program for Costing Out Drug Abuse Treatment

By Marion Torchia, NIDA NOTES Contributing Writer 

Research Findings

Volume 19, Number 5 (January 2005)

NIDA-supported economists are offering drug treatment program administrators a comprehensive program to 

estimate their costs. The Drug Abuse 

Treatment Cost Analysis Program 

(DATCAP) features materials and a 

method to capture and put dollar values 

on the full range of treatment resources. 

Along with analyzing their own economic operations, administrators eventually will be able to use a nationwide 

DATCAP database to compare their 

costs with those of similar programs, 

become more efficient, and achieve better treatment outcomes. Dr. Michael T. 

French of the University of Miami in 

Coral Gables, Florida, one of the system’s designers, says that ultimately, the 

database should provide answers to the 

questions asked by cost-conscious public agencies and insurers: How much 

do today’s drug treatment programs 

cost? What are the most cost-effective 

treatment approaches? Which programs 

return the greatest net benefits?

DATCAP Features

Administrators can download DATCAP 

survey forms and user manuals free 

of charge from www.DATCAP.com.

DATCAP’s developers note, however, 

that most programs will require the 

services of an economist trained in cost 

analysis and program evaluation to 

obtain the most useful results.

DATCAP captures both accounting 

costs (the costs usually entered on an 

institution’s financial statements, such 

as outlays for labor and supplies) and 

economic costs (all the resources a treatment center uses to serve its patients). 

Economic costs include resources that 

are partially subsidized or made available at no charge, such as volunteer labor. 

DATCAP’s inclusive cost perspective permits comparison 

of treatment programs that have very different financial 

structures.

Mean Patient Flow and Costs of

Substance Abuse Treatment Programs

Program Type

(Number Surveyed)

Average

Length of

Stay, weeks

(SD)

Average 

Daily 

Census

(SD)

Total 

Annual

Economic

Cost (SD)

Weekly 

Economic

Cost Per

Client1 (SD)

Economic 

Cost Per 

Treatment 

Episode2 (SD)

Methadone 

clinics (11) 99 (53) 388 (186) $1,684,254

($674,444) $91 ($33) $7,358($3,849)

Standard 

outpatient (14) 17 (9) 212 (188) $1,080,690

($757,227) $121 ($85) $1,944($1,960)

Intensive 

outpatient (6) 7 (8) 13 (9) $328,007 

($411,364) $462 ($243) $4,445($6,302)

Adolescent 

outpatient (13) 13 (6) 8 (2) $48,170

($50,518) $194 ($91) $2,678($2,787)

Drug court (9) 46 (20) 205 (184) $539,660

($136,713) $82 ($43) $3,463($2,187)

Outpatient Programs

Information gathered between 1993 and 2002 from 53 outpatient programs.

Residential Programs

Information gathered during the same period from 32 residential programs.

Program Type

(Number Surveyed)

Average 

Length of 

Stay, weeks

(SD)

Average 

Daily 

Census

(SD)

Total 

Annual 

Economic 

Cost (SD)

Weekly 

Economic 

Cost Per 

Client1 (SD)

Economic 

Cost Per 

Treatment 

Episode2 (SD)

Adult residential 

(18) 13 (14) 34 (21) $1,104,189

($643,053) $700 ($343) $9,426($11,023)

Adolescent 

residential (1) 8 22 $1,307,064 $1,138 $9,347

Therapeutic 

community (5) 33 (22) 152 (265) $3,330,137

($4,821,587) $587 ($194) $18,802($12,409)

In-prison 

therapeutic 

community (8) 

28 (12) 265 (288) $1,083,017

($1,587,030) $55 ($11) $1,534($947)

Notes: All amounts, including dollar amounts, are means. All costs are reported in 2001 dollars.

1

 Total annual economic cost divided by the average daily census, divided by 52.14 weeks.

2

 Weekly economic cost per client multiplied by the average length of stay. 

Source: Roebuck, M.C.; French, M.T.; and McLellan, A.T. (2003). 
56

The program is adaptable to any treatment setting. By 

focusing on the cost of specific treatment methods rather 

than on entire programs, it can capture costs in settings 

that also offer other services. The same questionnaire is 

provided for inpatient and outpatient services.

“Program DATCAP” gathers detailed information about a 

program’s resources, revenues, and expenses, and about its 

clients and the services they receive. “Brief DATCAP” is

a less labor-intensive alternative to the full instrument. 

“Client DATCAP” surveys clients directly and assigns 

a dollar value to costs they incur as a result of getting 

treatment, such as travel and child care. Although the 

DATCAP project is still in its early stages, administrators 

who use it can identify costs they were unaware of and 

find opportunities to strengthen their operations.

The Nationwide Database

Dr. French hopes that as program administrators around 

the country begin to use DATCAP to track their own 

costs, they will see the advantage of reporting their findings to a central repository. “Only when everyone’s costs 

are pooled will it be possible for a program to compare 

itself with other programs,” he says.

To encourage wider participation in the ongoing research 

on DATCAP, its creators have published some early 

survey results. Among these, they found that among 85 

programs surveyed between 1993 and 2002, methadone 

maintenance programs had lower labor costs (55 percent 

of total costs compared with 68 percent for standard outpatient programs) and relatively higher costs for supplies 

and materials. Not surprisingly, standard outpatient programs were much less expensive than intensive programs: 

The 14 standard programs reported a mean weekly economic cost per client of $121; for the intensive programs, 

the weekly cost was nearly four times that amount—or 

$462 per client. However, the intensive programs generally offered a shorter course of treatment, so their mean 

total cost for a client’s treatment episode was only slightly 

more than twice the cost of the standard outpatient programs ($4,445 versus $1,944).

The new database has limitations, the authors caution. 

The programs were not selected randomly and are not 

geographically representative. Also, the costs of a small 

number of atypical programs sometimes skewed the 

results. Nevertheless, says Dr. French, the results of the

85 surveys constitute a rich new source of information. 

“The database will get better as new programs are added, 

and eventually the cost estimates will be updated continually on the DATCAP Web site,” he says.

Next Step: Link Cost to Outcome

Although program managers find it useful to compare 

their costs with those of their peers, policymakers are 

much more interested in the relationship between costs 

and the intended program outcomes. Cost-effectiveness 

analysis and cost-benefit analysis of drug abuse treatment 

have demonstrated encouraging results. One California 

study found that $1 invested in substance abuse treatment 

saves taxpayers $7 in future costs, including those related 

to crime and care for medical problems resulting from 

drug use. “Evaluating Recovery Services: The California 

Drug and Alcohol Treatment Assessment (CALDATA),” 

California Department of Alcohol and Drug Programs, 

April 1994.

In a recent study using DATCAP, Dr. Jody Sindelar and 

her colleagues at Yale University in New Haven, Connecticut, found that Philadelphia treatment programs that 

offered “enhanced care” produced better outcomes with 

regard to drug abuse compared with those that offered 

only standard care. However, standard care programs had 

better results with respect to other treatment outcomes.

Says Dr. Sindelar, “Looking at treatment programs with 

too narrow a focus may produce misleading results. 

Reduced drug use is certainly the most direct outcome of 

treatment, but it is not necessarily the only one, or even 

the most important one to society. We need to find ways 

to give appropriate weight to all the outcomes we believe 

are important. But we believe that combining DATCAP 

and ASI [Addiction Severity Index] is a good first step.”

Techniques of Economic 

Analysis of Drug Treatment

•	 Cost-Effectiveness Analysis: A technique for

evaluation of clinical outcomes. It asks whether 

one treatment produces a better outcome at the 

same cost as another, comparable outcomes at 

less cost, or if an enhanced outcome is “worth” 

the additional cost. 

•	 Cost-Benefit Analysis: Decisionmakers use costbenefit analyses in determining how to allocate 

their budgets. The “cost” part of the analysis 

estimates the dollars necessary to achieve each 

alternative policy goal—for example, reducing 

drug abuse by 10 percent or raising school test 

scores by 10 percent. The “benefit” part estimates the dollar value of all the positive effects 

of success—for example, reduced medical costs 

because of fewer health problems associated 

with drug abuse, or a better educated, more 

skillful workforce attracting new industry to the 

area. All other concerns being equal, the goal 

that produces the most benefits for the lowest 

cost gets budget priority.
57

Dr. William S. Cartwright, an economist with NIDA’s 

Division of Epidemiology, Services and Prevention 

Research, believes DATCAP is the beginning of something 

important. “We know more about where the hidden costs 

are, and we are able to link costs to outcomes. I hope this 

information will enable us to make better use of scarce 

resources, toward our shared goal of reducing drug abuse 

and the problems it causes.”

Sources

• French, M.T.; Salomé, H.J.; Sindelar, J.L.; and 

McLellan, A.T. Benefit-cost analysis of addiction 

treatment: Methodological guidelines and application 

using the DATCAP and ASI. Health Services Research 

37(2):433–455, 2002.

• Roebuck, M.C.; French, M.T.; and McLellan, A.T. 

DATStats: Results from 85 studies using the Drug 

Abuse Treatment Cost Analysis Program (DATCAP). 

Journal of Drug Abuse Treatment 25(1):51–57, 2003.

• Sindelar, J.L.; Jofre-Benet, M.; French, M.T.; and 

McLellan, A.T. Cost-effectiveness analysis of addiction 

treatment: Paradoxes of multiple outcomes.

Drug and Alcohol Dependence 73(1):41–50, 2004. 
58

Adults With Co-Occurring Depression and Substance Abuse

Benefit From Treatment of Depression

Research Findings

Volume 19, Number 4 (December 2004)

New evidence is overturning the long-held view that 

patients with co-occurring mental health and substance 

use disorders must achieve abstinence from drugs before 

treatment for depression can begin. There were sound reasons for adhering to this view, including clinician concern 

about drug interactions and recognition that depressive 

symptoms brought on by substance abuse are difficult to 

separate from clinical depression itself. As the field continues to refine screening tools that distinguish the disorders, 

however, new treatment approaches are being developed 

and assessed.

In a study that reinforces the need to revisit traditional 

management of these conditions, NIDA-funded researchers Drs. Edward Nunes and Frances Levin of Columbia 

University in New York City reviewed 33 years of published literature on the treatment of depression

in the context of ongoing substance abuse. They found 

that antidepressant treatment is not sufficient for these 

patients, and they emphasize the need to integrate the 

treatment of depression and substance abuse. The investigators examined 44 placebo-controlled clinical trials published from 1970 to December 2003; 14 followed a rigorous methodology and were included in the study. Drs. 

Nunes and Levin used meta-analysis—a technique that 

synthesizes data from similar studies and determines how 

much particular factors affect outcomes—to examine the 

effects of antidepressant medication in approximately 850 

patients with co-occurring substance abuse. They found 

that treating the depression of patients with co-occurring 

substance abuse conveys moderate benefit. Patients who 

responded to the antidepressant treatment also showed 

a reduction in substance abuse. However, cessation rates 

were generally low, even among studies demonstrating 

positive effects of antidepressants. Drs. Nunes and Levin 

suggest that clinicians first treat the depression with an 

evidence-based psychosocial intervention, followed by 

antidepressant medication if the depression does not 

improve.

“The study provides quantitative evidence on the benefit 

of treating depression in those with co-occurring substance abuse and supports integrated treatment of both 

disorders. Cognitive behavioral therapy is a good first 

approach for treating these patients, but the findings show 

the efficacy of antidepressant medications for patients with 

coexisting depression and substance abuse,” says Dr. Ivan 

Montoya of NIDA’s Division of Pharmacotherapies and 

Medical Consequences of Drug Abuse. Some clinicians 

worry that treating a patient’s depression distracts attention from treating their co-occurring substance abuse.

But Dr. Montoya says, “Patients may attach less stigma

to seeking treatment for depression than substance abuse. 

Clinicians are increasingly finding that they have an opportunity to treat substance abuse in patients who present 

with depression; now, they have quantitative evidence

to support the decision of concurrent treatment.”

Source

• Nunes, E.V., and Levin, F.R. Treatment of depression in patients with alcohol or other drug dependence: A meta-analysis. JAMA 291(15):1887-1896, 

2004. 
59

CTN Update: Teamwork Develops Treatment Concept Into

Study Protocol

By Barbara Shine, NIDA NOTES Contributing Writer 

Research Findings

Volume 19, Number 4 (December 2004)

In NIDA’s Clinical Trials Network 

(CTN), researchers and practitioners 

collaborate in the design as well as the 

execution of drug abuse treatment studies. 

Continuous collaboration with treatment 

providers, a distinguishing feature of the 

network, ensures a research focus on practical questions that arise in typical patient 

populations and community treatment 

settings.

A new study begins when a researcher or treatment provider identifies a clinical need and formulates a solution or 

intervention to meet it. Research ideas are accepted only 

if they coincide with public health priorities and meet 

two standards—feasibility and sustainability. A feasible 

research concept is one that can be tested in established, 

community-based treatment programs with varied patient 

populations. To meet the sustainability standard, the 

proposed intervention should be possible to continue in 

community treatment programs equipped with a realistic 

complement of resources after study completion. The concept proposal also must stand on a foundation of previous 

supporting research. Once it meets these criteria and gains 

approval within CTN and by NIDA, the proposal is ready 

to move on to protocol development and final NIDA 

approval and funding.

An example of the pragmatic approach to research

design is the recently completed CTN-sponsored study 

“Motivational Incentives for Enhanced Drug Abuse 

Recovery.” This work is based on the general idea that 

rewards—including supportive words, praise, money, or 

desirable objects—for a particular behavior promote like 

behavior in the future. Two protocols emerged: one for 

implementation in methadone maintenance clinics and 

another for study in clinics using treatments other than 

methadone maintenance.

“There were two key points to negotiate in designing 

these trials,” says Dr. Maxine Stitzer of Johns Hopkins 

University School of Medicine in Baltimore, the principal 

investigator for both motivational incentive protocols. 

“The first was selection of the drug target. Previous incentive studies had targeted only one drug, but we targeted 

both cocaine and methamphetamine to address regional 

differences in stimulant abuse. We added alcohol as a primary target and opiates and marijuana as secondary drug 

targets to emphasize the importance of giving up all drugs, 

not just the particular one that brought the patients into 

treatment. Patients could draw chances 

to win prizes when their breath and 

urine samples were negative for target 

drugs.”

“The second big issue was how much 

the prizes should be worth,” says Dr. 

Stitzer. “Early studies in research centers 

cost upwards of a thousand dollars per 

patient for prizes; community treatment 

providers made it clear they needed an 

effective motivational approach that would not exhaust 

their much smaller budgets. People in our study drew 

chances to win a range of prizes—from bus tokens, to 

$20 grocery vouchers, to compact disc players—that were 

more realistic for community treatment centers.”

Members of the protocol development group benefited 

from meeting with Dr. Nancy Petry, an investigator who 

conducted similar studies at the University of Connecticut 

in Farmington, and with several of her clinical staff and 

patients. “We really gained valuable insights and heard 

firsthand how the patients’ motivations changed over 

the course of their treatment, from working for prizes to 

working for their own good,” says Dr. Stitzer.

Once NIDA approved the motivational incentives protocol, investigators implemented the study in 14 treatment 

programs with a total of about 800 patients. Preliminary 

analysis of the data suggests that the addition of reward 

systems to standard therapy will improve outcomes for 

drug abuse patients. Once Dr. Stitzer and her team analyze and publish the results, clinicians will know whether 

motivational incentives are truly an effective adjunct to 

current therapies.

For More Information

To learn more about CTN protocols, including studies 

that are now recruiting patients, visit the NIDA Clinical 

Trials Network Web site, www.drugabuse.gov/CTN. Both 

English and Spanish brochures for patients and physicians 

are available for download, and the site lists contact information for all regional research and training centers and 

clinical trials.

Dr. Petry’s research is highlighted in “Fishbowls and 

Candybars: Using Low-Cost Incentives To Increase Treatment Retention” (NIDA Science & Practice Perspectives,

Vol. 2, No. 1, p. 55), which is also available on NIDA’s 

Web site, www.drugabuse.gov.
60

Research Findings

Testing New Treatments in the Nation’s Clinics

Volume 19, Number 1 (April 2004)

In NIDA’s first 

30 years, its 

research programs produced 

many promising 

new medications 

and behavioral 

treatments. Yet, 

as in other 

areas of medicine, new and 

improved treatments for drug 

abuse have often 

taken too long to make their way into wide clinical use. 

In 1999, NIDA acted to bridge the critical gap between 

research and practice by launching the largest initiative in 

its history—the National Drug Abuse Treatment Clinical 

Trials Network (CTN).

The CTN embraces an ambitious plan to accelerate the 

transfer of new science-based behavioral and pharmacological approaches into treatment: to create a national 

research-practice infrastructure to test and modify promising treatments in community treatment programs, rather 

than specialized research settings, and rapidly transfer 

those proven effective into clinical practice. The network 

also seeks to develop new treatments that reflect the practical knowledge of the clinic, thus accelerating their acceptance and application in practice. 

Beginning with 5 regional research and training centers, 

each linked to as many as 10 community treatment programs, the CTN brought researchers into community 

clinics to work alongside practitioners in testing researchbased treatments. In little more than a year, NIDA and 

the pioneering group of university researchers, treatment 

programs, and practitioners built the organizational and 

procedural foundation for the CTN, selected promising 

pharmacological and behavioral approaches, developed 

standardized clinical protocols, and began testing them

in trials with a variety of patients at multiple sites. 

The CTN now encompasses 17 regional research and training centers and 115 community treatment programs across 

the Nation. Minorities, pregnant women, adolescents, and 

drug abuse patients suffering from post-traumatic stress 

disorder or depression are among the pool of nearly 9,000 

drug abuse treatment patients in 27 States who have or 

will soon participate in 22 clinical protocols—some under 

way, some still being refined—for a variety of new treatment approaches. Medication trials range from assessing 

the effectiveness of buprenorphine in detoxifying opiatedependent patients to determining whether a combination 

buprenorphine/naloxone tablet can help treat heroinaddicted adolescents. Behavioral treatment trials take 

many approaches: tests using motivational enhancement 

techniques or tangible incentives for staying drug-free to 

enhance standard counseling approaches, several HIV

risk-reduction interventions, and an intervention to

help patients in drug abuse treatment stop smoking.

Taking Prevention Programs Into Our Communities

Although a relatively new science, drug abuse prevention 

has already yielded a bounty of programs capable of steering many young people away from drug use. As with drug 

abuse treatments, however, many of these research-proven 

programs stayed on the shelf, while simpler, less effective 

approaches were used. Even when such approaches were 

selected, they often were not delivered to maximum effect.

Taking a cue from the CTN, NIDA began to partner prevention researchers and practitioners to establish researchbased programs in the Nation’s communities. A major 

component of NIDA’s recently launched broad-based 

National Prevention Research Initiative instituted four 

Community-based prevention programs teach children strategies to 

avoid drug initiation and other harmful behaviors.
61

large-scale field trials of proven drug abuse prevention 

approaches. These trials find scientists and practitioners 

collaborating to deliver a research-tested intervention to 

diverse groups of children and adolescents in urban, suburban, and rural sites. Each trial examines factors with 

potential impact on a program’s effectiveness, such as how 

different training methods affect its delivery or how accurately community service programs deliver an intervention 

to different groups in various settings. 

Results of these joint research-practice studies will reveal 

practical barriers to widespread dissemination and implementation of research-tested programs. Equally important, 

they will point to how programs can be adapted to meet 

the needs of local communities while still reducing drug 

use. Ultimately, blending science-based knowledge with 

community realities will produce more practical prevention programs that will be used by more communities to 

divert children and adolescents from initiating drug use.

Advancing the Frontiers of Addiction

Research and Practice

The first three decades of 

NIDA leadership ushered 

drug abuse science toward 

full maturity. The result: 

profound and practical 

insights into the complex 

biological, behavioral, 

cognitive, and environmental interactions that 

influence every aspect of 

drug abuse and addiction. 

Practitioners now have 

many effective tools for 

preventing and treating 

drug abuse and addiction 

and their costly public 

health and social consequences. Yet, much work remains. Too many children and 

adolescents continue to experiment with drugs, putting 

themselves at risk for addiction. Research

to speed the development and application of prevention 

strategies stands at the forefront of NIDA’s priorities.

Additional NIDA research initiatives continue to address 

the critical need for treatments for drug abusers who suffer 

from mental illnesses or abuse multiple substances, including nicotine and alcohol. And more broadly effective 

prevention and treatment approaches will enable NIDA 

to fulfill its public health mission of reducing the severe 

health consequences of addiction, including increased risk 

of contracting and transmitting infectious diseases.

NIDA is applying revolutionary new techniques in 

molecular biology, brain imaging, and cognitive neuroscience to these outstanding issues in drug abuse etiology, 

prevention, and treatment. For example, neuroscientists 

in the Institute’s proteomics program are using 3-dimensional imaging technology to map how distinct proteins 

in different regions of the human brain function, interact, 

and change from initial drug use through the transition 

to addiction. Such research promises new understanding 

of the molecular mechanisms of drug addiction and the 

underlying processes of normal and diseased brain function. While offering important new targets for the next 

generation of therapeutic approaches, this research may 

someday allow clinicians to match an intervention to a 

patient’s physiological or genetic traits.

The role that interactions between genetic factors and the 

environment play in vulnerability to addiction is another 

area of promise recently opened up through advances in 

scientific technologies. For while genes and the proteins 

they produce may increase or reduce the risk of addiction, 

they do not function in isolation. Using brain-imaging 

techniques, researchers recently found that social environment can modify monkeys’ neurobiology, thereby reducing their likelihood of 

self-administering drugs. 

In the study, housing 

conditions and social 

interactions altered the 

genetic expression of 

proteins in the brain that 

enable animals, including 

humans, to experience 

pleasure and the effects of 

drugs. 

The complexity of drug 

abuse questions that have 

come to the fore requires 

investigation from multiple perspectives. To 

achieve this goal, NIDA 

has launched broad 

research initiatives 

involving Federal, State, 

and local government 

agencies; scientists from 

many different fields; public and private health service 

providers; prevention and treatment professionals; and 

private pharmaceutical companies. One key feature of 

these collaborations is their emphasis on the resources and 

practical needs of communities at all research stages—

from basic discovery through intervention development to 

actual trial and integration in community prevention and 

research programs. Examples of collaborative initiatives 

include the following.

Environmental factors, such as 

a positive home life, may boost 

brain chemicals that offer resistance to drugs’ reinforcing effects.
62

Collaborating to Combat Tobacco Use and Nicotine Addiction

In July 1998, NIDA, with the National Cancer Institute (NCI), the 

Centers for Disease Control and Prevention, and The Robert 

Wood Johnson Foundation (RWJF), sponsored “Addicted to 

Nicotine,” a national research conference on tobacco use and 

nicotine addiction. This event shed new light on the complexity of research challenges posed by nicotine addiction. Informal 

conversations among researchers and policymakers highlighted 

the need for an innovative research approach to meet these 

challenges. Within a year, this dialogue yielded a proposal: 

develop Transdisciplinary Tobacco Use Research Centers 

(TTURCs) to foster collaborations among scientists across 

many disciplines and allow them to investigate tobacco use and 

nicotine’s effects at levels ranging from molecular genetics to 

peer interactions. By October 1999, NIDA and NCI announced 

the first TTURC awards and committed about $70 million to the 

effort over 5 years. RWJF committed an additional $14 million.

Today, investigators at seven TTURCs across the country are 

carrying out the research agenda that gave birth to the centers. 

Their collaborations have produced scores of published studies 

that advance our understanding of nicotine’s addictive effects 

and the scope of influence smoking has on the Nation’s health. 

Consider the following research accomplishments and initiatives:

Brown University—described intergenerational effects, including maternal smoking during pregnancy, that 

influence smoking initiation and increase the risk for nicotine addiction among adolescents. 

University of California, Irvine—elucidated the neurobiological impact of nicotine, particularly on the developing brain.

University of Pennsylvania/Georgetown University—shed new light on how inherited variations in enzymes 

increase or decrease the likelihood of becoming addicted to nicotine or contribute to the effectiveness of smoking cessation treatments.

University of Southern California—expanded understanding of the role of cultural, ethnic, and peer influences 

on smoking behavior.

Yale University—identified sex differences that contribute to differential success of treatment for men and 

women and is developing treatments to help smokers who have had the most difficulty quitting

University of Minnesota—began developing and evaluating new smoking cessation treatments, including 

vaccines to prevent nicotine from reaching the brain.

University of Wisconsin—is pursuing strategies to expand access to and increase use of smoking cessation 

programs and identify measures that reduce the risk of relapse.

The transdermal patch, based on early NIDA 

research, has proven helpful to many smokers

trying to overcome nicotine dependence.

Transdisciplinary Research Centers. Teams of researchers pool their expertise to search for new knowledge about 

the interplay of individual, cognitive, social, and environmental circumstances in fostering drug abuse and its many 

harmful consequences. NIDA currently supports transdisciplinary centers in prevention and tobacco use research. 

In the tobacco use centers, NIDA, with the National 

Cancer Institute and the Robert Wood Johnson Foundation, supports investigation of all aspects of tobacco use, 

from factors that influence initiation through those that 

aid cessation. The goal is to discover new ways to prevent 

and treat nicotine addiction, particularly in adolescents.
63

Collaborating With 

Other Federal Agencies.

NIDA is participating in research initiatives with other NIH 

Institutes, including 

those that research allergy 

and infectious diseases, 

neurological disease and 

stroke, mental health, 

alcoholism and alcohol 

abuse, cancer, and child 

health and development. 

Studies funded under 

these initiatives will help 

the biomedical research and practice community better 

understand the links between addiction and comorbid 

mental and physical disorders. This research will accelerate 

discovery of prevention and treatment interventions for 

such disorders as hepatitis, HIV, mood and conduct disorders, and other problems often associated with drug abuse 

as cause, consequence, or both.

Working With Private Industry and Practice. Research 

partnerships with private pharmaceutical companies are 

fostering new approaches to treat drug abuse and addiction, including vaccines currently in clinical trials. Agreements negotiated with pharmaceutical companies are 

enabling NIDA’s Medications Development Program to 

explore the potential of patented compounds in treating cocaine, methamphetamine, and nicotine addiction. 

NIDA also is working to raise private medical practitioners’ awareness that they can play a critical role in improving their patients’ health by being alert to the signs and 

symptoms of substance abuse and aware of treatment 

options for addiction and related medical and psychiatric 

problems. 

Strengthening ResearchPractice Partnerships.

To broaden the researchpractice partnership that 

the CTN has initiated, 

NIDA has organized 

regional blending conferences to extend the reach 

of treatment research into 

the Nation’s community 

treatment programs. The 

conferences allow clinicians and researchers to 

examine how to apply 

cutting-edge findings 

about drug use and addiction in clinical settings. 

NIDA also supports the 

Substance Abuse and 

Mental Health Services 

Administration (SAMHSA) in developing, deploying, and 

evaluating evidence-based treatment approaches for drug 

abuse in community-based clinics. These efforts bring 

research and practice closer together, inform development 

of more effective and use-ful interventions, accelerate 

adoption of research-tested approaches, and improve the 

quality of drug abuse prevention and treatment.

Improving Criminal Justice Drug Abuse Treatment 

Services. The majority of the 600,000 inmates who return 

to their communities from prison each year have untreated 

substance abuse problems that can quickly lead to relapse to 

drug abuse and criminal behavior. Thus, NIDA has taken 

the lead in building a multi-agency consortium to develop 

integrated approaches to the treatment of incarcerated individuals with drug abuse and addictive disorders and test 

them at multiple sites throughout the Nation. Joining the 

Institute in this much-needed National Criminal Justice 

Drug Abuse Treatment Study to improve drug abuse treatment services for offenders are SAMHSA, the Centers for 

Disease Control and Prevention, and the Department of 

Justice. 

Fostering research-clinician partnerships is a focus of Science & 

Practice Perspectives, NIDA’s 

peer-reviewed journal.
64

Research Findings

Developing Effective Addiction Treatments

Volume 19, Number 1 (April 2004)

Pursuing New Medications

In recent years, people from all walks of life have sought 

treatment for addiction to powerful narcotic pain-relieving 

medications, such as OxyContin and Vicodin, that they 

have abused outside of a medical regimen. These medications share many properties with heroin, which currently 

ensnares more than a million people nationwide in the 

web of addiction. Those who become addicted to legal 

painkillers or street opiates now have a new medication to 

help them reclaim their lives. Approved by FDA in 2002, 

buprenorphine joins two other approved opiate treatment 

medications—methadone, used in long-term treatment, 

and the NIDA-developed opiate blocker naltrexone, used 

to help patients remain 

drug-free after they have 

stopped using opiates. 

Buprenorphine is the 

first medication for opiate addiction treatment 

that can be prescribed 

by private physicians in 

offices and clinics. Use 

of this medication in 

mainstream medicine 

should help reduce the 

stigma still associated with 

drug abuse treatment, 

while encouraging more 

patients to seek treatment 

for addiction to heroin 

and other opiates. NIDA also is pursuing medications for 

cocaine and methamphetamine abuse and addiction, for 

which no medications are yet available. To fill this void, 

the Institute is applying the same scientific medications 

development methodologies that put effective opiate treatment medications into the hands of clinicians and their 

patients. 

On one research track, clinical researchers are screening 

medications previously approved to treat other disorders. 

In these small-scale trials, several agents have appeared to 

weaken the addictive cycle of drug-craving, drug-seeking, 

and drug-taking. Among them are amantadine (currently 

used for Parkinson’s disease), disulfiram (Antabuse), 

baclofen (an antispasticity agent), tiagabine and topiramate (antiepileptics), and modafinil (used in narcolepsy). 

Disulfiram and naltrexone, both effective in treating alcoholism, may fill a critical need for medications that can 

help cocaine-abusing individuals who also abuse alcohol. 

Propranolol, a medication used to lower blood pressure, 

may help substance abuse patients stay the course during 

the critical early days of treatment, by alleviating their 

unpleasant withdrawal symptoms. Researchers are now 

conducting larger, longer studies to confirm these encouraging results. Because the medications work by a variety 

of different mechanisms, some of which may complement 

each other, researchers also will examine whether they 

may be more effective in combination than alone. Some 

may also work optimally 

with specific behavioral 

therapies.

On another track, 

researchers in NIDA’s 

cocaine and methamphetamine treatment discovery 

programs are working 

to identify new chemical compounds whose 

pharmacological actions 

modulate the effects of 

psychostimulants on 

the brain and behavior. 

They already have shown 

that one compound 

that blocks a brain cannabinoid receptor can prevent animals from reinitiating 

cocaine use after exposure to drug-related cues and stressful events. Other compounds that curb the drug-induced 

flooding of the brain’s reward pathways with dopamine 

may be able to treat addiction to all abused drugs. Still 

other compounds counter psychostimulants’ ability to 

activate receptor molecules, nerve networks, and neurochemical mechanisms to create pleasure and craving.

Another NIDA initiative is focusing on new medications 

for treating nicotine addiction. Launched in the 1970s, 

NIDA’s basic research in this area provided the scientific basis for nicotine replacement therapies, such as the 

transdermal patch, that today help many patients overcome nicotine dependence. The Institute is now pursuing 

several approaches to medications that could intercept 
65

and neutralize nicotine, 

cocaine, and methamphetamine in the bloodstream 

before they can act in the 

brain. In one approach, 

vaccines containing the 

abused substance are linked 

with a larger carrier molecule and stimulate the body 

to produce antibodies to 

the drug. Another approach 

enhances the rate at which 

the body’s enzymes break 

down the drug molecules 

into inactive byproducts. 

Identifying Effective 

Behavioral Therapies

Therapies that help drug 

abuse patients overcome 

erroneous thought patterns and behaviors 

that reinforce their abuse and addiction are critical in 

treating drug abuse and preventing its harmful consequences. Cognitive-behavioral therapies can stand alone 

as front-line interventions that help many patients stop 

using drugs and remain 

drug-free. And they can 

increase the effectiveness 

of treatment medications 

by boosting patients’ 

motivation to remain 

in treatment, take their 

medication as scheduled, 

and learn strategies to 

avoid relapse and lead 

drug-free lives. NIDAsupported research has 

demonstrated that combining medications, as available, with behavioral treatments is the best way to enhance success for most patients. 

Over the last decade, NIDA’s Behavioral Therapies 

Development Program established a three-stage process

to develop and introduce new behavioral approaches into 

clinical practice, similar to that required by the Food and 

Drug Administration to establish the safety and efficacy 

of medications. Building on research that suggests avenues 

for developing new therapies or refining existing ones, 

pilot studies explore the potential of each new or refined 

treatment. Those showing promise are then tested in 

research settings in small- and large-scale clinical trials. 

Finally, clinical trials can be done in community settings 

for those therapies that demonstrate therapeutic efficacy.

NIDA behavioral therapy researchers have designed several 

cognitive-behavioral therapies to help methamphetamine 

abusers. One innovative therapy gives patients a voucher 

each time they submit a drug-free urine sample. Vouchers 

may be exchanged for goods or services that provide pleasurable, legal alternatives to drug use or, as in methadone 

treatment programs, for special privileges, like reducing 

the number of required visits to a treatment clinic. Studies 

show that providing vouchers for drug-free urine tests 

can help patients stop cocaine and methamphetamine use 

and remain abstinent for extended periods. Variations of 

voucher-based therapies that use lower cost vouchers or 

involve family and other community resources in treatment can be matched to the resources of treatment programs and needs of cocaine-addicted individuals. 

In the last 10 years, behavioral treatments have demonstrated their potency in improving the health of diverse 

individuals with many types of drug abuse and other mental disorders. Proven 

treatments include 

individual cognitivebehavioral therapy, 

family therapies for 

Hispanic and AfricanAmerican adolescent 

substance abusers, 

combination behavioral and medication 

therapies for adult 

smokers, and couples 

therapy for opiateaddicted men and 

women in methadone treatment programs. The benefits 

of many of these treatments endure long after treatment 

has ended. And with individual cognitive-behavioral therapy, the benefits appear to increase over time. 

Family therapies tailored to the 

ethnicity or race of substance-abusing 

teens have proven successful.

NIDA uses art cards, displayed 

in restaurants and other public 

places, to warn smokers that 

nicotine, like other drugs, can 

be addictive.
66

Research Findings

Animal Studies Suggest D3 Receptors Offer New Target for 

Treatment Medications

By Jill Schlabig Williams, NIDA NOTES Contributing Writer 

Volume 18, Number 4 (November 2003)

Collaboration between a NIDA scientist and a researcher 

from St. John’s University in Jamaica, New York, has identified a chemical compound that prevents animal responses 

to cocaine that correspond to human drug liking, seeking, 

and relapse. While the compound is not suitable as a medication, the researchers believe its mechanism of action—

restricting neurotransmitter access to the dopamine D3

receptor—may provide a basis for pharmacological treatments for addiction to cocaine and other drugs.

The chemical messenger dopamine plays a critical role 

in networks of brain cells that trigger the rewarding feelings that result when we engage in pleasurable activities, 

such as eating. Drugs of abuse activate hot buttons, called 

receptors, on these brain cells, flooding the brain’s reward 

pathways with dopamine and producing intense pleasure. 

With continued drug abuse, overstimulation of these 

pathways changes the brain, leading to the intense craving 

and uncontrollable pursuit of drugs that mark addiction.

To derail this process, research has focused on the use 

of agonists, compounds structurally similar to dopamine 

that bind to and stimulate dopamine receptors and seem 

to inhibit drug-seeking behavior, and antagonists, which 

bind to and block these receptors. Until now, researchers have tried developing a treatment medication that 

can counter the addictive effects of abused drugs at two 

different dopamine receptors, called D1 and D2, with 

little success. Potential treatment agonists that activated 

these receptors produced such strong stimulation that it 

seemed likely they themselves would be abused. And the 

antagonists used to block the pleasurable effects of abused 

drugs at these receptors produced aversive, unpleasant 

effects. However, recent NIDA-funded research on use of 

an antagonist designed to target a less-studied dopamine 

receptor called D3 offers new promise. Researchers Dr. 

Charles Ashby, Jr., of St. John’s University, and Dr. Eliot 

Gardner, of NIDA’s Intramural Research Program, note 

that D3 appears to play a major role in addiction and may 

be the elusive target for medications that could help control addictive behavior.

Scientists have identified five subtypes of dopamine receptors, each with distinct properties and each found in

varying densities in different areas of the brain. To date, 

most research has focused on the roles of the D1 and D2

receptors, which occur in higher densities and more places 

in the brain than do D3 receptors. Nevertheless, several 

characteristics of the D3 receptor suggested that medications that interact with it may have promise as treatments 

for cocaine addiction. D3 receptors are mainly concentrated in the brain’s reward pathway. In addition, dopamine is attracted more strongly to the D3 receptors than 

to other receptors. Yet researchers found that D3 agonists 

caused rats to resume drug-seeking behavior more quickly 

after a period of abstinence. This reaction suggested that 

a compound capable of selectively blocking this receptor—an antagonist—could be important in developing a 

medication to reduce or block craving.

The D3 antagonist compound used in the Ashby-Gardner 

studies, called SB-277011-A, is highly selective, with an 

80- to 100-fold preference for D3 over D2 receptors and 

66 other receptors, enzymes, and ion channels. When the 

compound was first developed in 1997, Drs. Ashby and 

Change in Reward Threshold (%)

-20 -15 -10 -5 0

3 mg/kg SB compound & 2 mg/kg cocaine

2 mg/kg cocaine

Placebo -0.5

-0.5

-19.0

Cocaine exposure lowered by 19 percent rats’ reward threshold, the 

amount of current needed to motivate an animal to push a lever to 

activate electrical stimulation of its brain reward system. When rats 

were given the D3 antagonist before being given cocaine, however, 

their reward threshold remained the same as when they were given 

placebo.

D3 Receptor Antagonist Blocks 

Cocaine Reward in Rats
67

Gardner saw its potential. “Until then, study of the D3

receptor was hampered because the available compounds 

antagonized D2 as well as D3 receptors to some extent, 

making it difficult to sort out which was responsible for 

the observed effects. As a result, research on the D3 receptor and compounds that affect it had yielded inconsistent 

and contradictory results,” explains Dr. Ashby. “We knew 

this compound and its unambiguous selectivity for D3

receptors would allow us to test the role of these receptors, 

while offering promise as a treatment for addiction.”

Drs. Ashby and Gardner performed three types of animal 

experiments. “Each experiment used the D3 antagonist to 

focus on a unique aspect of addiction, and all three yielded promising results,” says Dr. Ashby. “Antagonizing the 

D3 receptor appears to weaken cocaine’s rewarding effects, 

reduce cocaine-induced conditioned place preference, and 

block reinstatement of drug-seeking behavior. And the 

compound we were testing was not found to be rewarding 

or aversive.”

Cocaine’s Rewarding Effects

In the first set of studies, researchers used brain stimulation reward experiments to measure the direct rewarding 

properties of cocaine. This type of experiment is thought 

to produce the closest equivalent in animals to the cocaineinduced subjective high experienced by humans. The 

researchers implanted brain stimulation electrodes in rats 

and trained the animals to press a lever to self-administer 

electrical stimulation that produced feelings of pleasure

or euphoria. Baseline reward thresholds, the amount of

current below which the animal no longer finds the stimulation rewarding enough to press the lever, were determined for each animal. Drugs of abuse, which activate the 

same neurons in the brain’s reward system as the electrical 

current, increase the amount of pleasure obtained from a 

given amount of current and therefore decrease the reward 

threshold. The difference between baseline reward threshold and the reward threshold after administration of a drug 

gives a measure of the rewarding potency of the drug being 

tested.

After establishing the rats’ baseline reward thresholds, 

researchers injected the animals with placebo, 2 mg/kg 

cocaine, or 3 mg/kg SB compound followed by 2 mg/kg 

cocaine; researchers then retested the rats. As expected,

the reward threshold of animals injected with placebo 

remained unchanged; those injected with cocaine had an 

average 19-percent decrease in their reward thresholds. 

Rats pretreated with the D3 antagonist and then given 

cocaine had no change in their reward thresholds, indicating that the antagonist completely abolished the enhancing effect of cocaine on brain reward.

Cocaine-Seeking Behavior

The second set of experiments used conditioned place preference, aiming to measure cocaine-seeking behavior evoked 

by environmental cues associated with cocaine. The experiments involved providing rats one of five pretreatments—

placebo or varying doses of the SB compound—and then 

confining them to one chamber of a two-room cage. The 

rats were subsequently given cocaine and confined to the 

other chamber. Each chamber had distinct visual and tactile furnishings. Rats were then allowed to freely explore 

Average Minutes in Chamber

0

5

10

15

10.0 mg/kg SB & Cocaine

3.0 mg/kg SB & Cocaine

1.0 mg/kg SB & Cocaine

0.3 mg/kg SB & Cocaine

Placebo & Cocaine

4.9 5.7

7.7 7.0 7.7

Placebo-Associated Chamber

0

5

10

15

10.0 mg/kg SB & Cocaine

3.0 mg/kg SB & Cocaine

1.0 mg/kg SB & Cocaine

0.3 mg/kg SB & Cocaine

Placebo & Cocaine

10.1 9.3

7.3

6.0

7.3

Cocaine-Associated Chamber

 Rats were given placebo and confined to one chamber of a two-chamber cage, then given cocaine and confined to the other chamber. They 

were then allowed to roam throughout the cage for 15 minutes, with researchers measuring the time spent in each chamber. This exercise was 

repeated with four other groups of rats, which were given either 0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg D3 antagonist (SB compound) 

and then cocaine. Rats treated with the SB compound before receiving cocaine spent significantly less time in the cocaine-associated chamber 

than rats pretreated with placebo.

D3 Receptor Antagonist Blocks Rats’ Incentive to Seek Cocaine
68

the entire cage for 15 minutes, while researchers measured 

their time in each chamber.

Rats given placebo and then cocaine spent roughly two 

thirds of their time in the chamber they associated with 

cocaine. However, rats pretreated with the D3 antagonist 

(SB compound) spent, on average, less time in the cocaineassociated chamber, with the minutes spent in that chamber decreasing as the D3 antagonist dose increased from 

0.3 mg/kg to 1 mg/kg, 3 mg/kg, and up to 10 mg/kg. Rats 

pretreated with the highest dose of the D3 antagonist spent 

about 40 percent fewer minutes in the cocaine-associated 

chamber than did rats in the placebo-cocaine group. The 

results indicate that the D3 antagonist blocked the rats’ 

motivation to seek out cocaine, eliminating their acquisition and expression of cocaine-induced conditioned

preference.

Reinstatement of Drug Seeking

The final set of experiments focused on cocaine self-administration and reinstatement. The researchers implanted an 

intravenous catheter in the rat’s external jugular vein and 

trained the animal to self-administer cocaine by pressing 

a lever. The daily 3-hour sessions continued until the rat 

was self-administering consistent amounts of the drug every 

day. The researchers then phased out the lever-pressing 

behavior by substituting saline for the cocaine; since

pressing the lever no longer resulted in cocaine, the rats 

lost interest and pushed the lever much less often. At this 

point, the researchers gave rats that had been pretreated 

with placebo or the SB compound a priming dose of 

cocaine (1 mg/kg) normally sufficient to 

trigger reinstatement of the drug-seeking, 

lever-pressing behavior. The rats returned 

to the lever, and the researchers counted 

how many times they pressed it.

On the day before they were given the 

priming dose of cocaine, rats pressed the 

active lever an average of 7.7 times. After 

receiving the priming dose, the rats pretreated with placebo pressed the lever an 

average of 38.8 times, while rats pretreated 

with 3, 6, or 12 mg/kg of the D3 antagonist 

pressed the lever an average of 39.0, 18.6, 

and 14.2 times, respectively. Pretreatment 

with the D3 antagonist thus produced

a dose-related weakening of cocaineriggered resumption of the drug-seeking 

behavior.

Future of D3 Antagonist Research

The researchers are optimistic about the 

future of this line of research. “The SB 

compound has jumped through many 

hoops already,” says Dr. Ashby. “It’s 

been shown in our studies and other studies to block 

cue-induced, drug-induced, and stress-induced relapse 

to cocaine-seeking behavior, and acquisition and expression of heroin-induced conditioned place preference. It 

is neither rewarding nor aversive and has been found to 

work on cocaine, heroin, and nicotine. We’ve seen no 

significant adverse effects of the compound in animals. 

We think antagonizing the D3 receptor represents a breakthrough for addiction treatment.”

“In more than 35 years in the field, this D3 antagonist 

research is the most promising thing I have ever seen,”

Dr. Gardner says. “No one else has assembled such a 

variety of animal evidence showing that acute administration of a compound so profoundly modifies the addictive 

properties of cocaine as this selective D3 antagonist.”

Both Drs. Ashby and Gardner are quick to note, however, 

that much work lies ahead. “We don’t know if these results 

will hold up in long-term studies,” says Dr. Gardner. “We 

think the reason this compound is successful in animal 

studies is because of its D3 antagonist action. To verify 

this, we still need to develop other, chemically different 

D3 antagonists and redo all the tests. If we obtain the same 

results with these other D3 antagonists, then we’ll be more 

comfortable that we are on the right track and that D3

receptor antagonism is truly responsible for our findings.”

More animal experiments are planned to focus on other 

drugs of abuse and other animal paradigms, such as progressive ratio studies that measure a drug’s motivational 

potency. Studies with chronic administration and with 

other mammalian species also will be needed, as will 

Number of Lever Presses

Event/Treatment

0 5 10 15 20 25 30 35 40

CPD Plus 12 mg/kg

SB Compound

CPD Plus 6 mg/kg

SB Compound

CPD Plus 3 mg/kg

SB Compound

CPD Plus

Placebo

Day Before

CPD* 7.7

38.8

39.0

18.6

14.2

*CPD stands for cocaine priming dose.

After receiving a priming dose of cocaine, rats pretreated with placebo resumed cocaineseeking behavior, pressing a lever to self-administer cocaine. However, rats pretreated 

with the D3 antagonist (SB compound) pressed the lever fewer times as the SB compound dose increased.

D3 Receptor Antagonist Inhibits

Reinstatement of Cocaine Seeking
69

toxicology studies. The human pharmacokinetics of the 

compounds also will have to be improved; for instance, 

the current compound has a very short half-life, lasting 

only about 30 minutes in primates.

“Almost without fail, people I’ve spoken with who are 

addicted to drugs express a strong desire for clinically effective anticraving, antirelapse medication,” says Dr. Gardner. 

“We hope this research takes us in that direction.”

Source

• Vorel, S.R.; Ashby, C.R., Jr.; Paul, M.; Liu, X.; 

Hayes, R.; Hagan, J.J.; Middlemiss, D.N.; Stemp, G.; 

Gardner, E.L. Dopamine D3 receptor antagonism 

inhibits cocaine-seeking and cocaine-enhanced brain 

reward in rats. Journal of Neuroscience 22(21):9595-

9603, 2002. 
70

Research Findings

Network Therapy Expands Treatment Capabilities

Of Small Practice Providers

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 18, Number 2 (August 2003)

NIDA-supported researchers have found that clinicians 

without access to the resources of a comprehensive substance abuse program can treat cocaine abuse with “network therapy,” a treatment approach that combines individual therapy and the involvement of patients’ friends 

or family members. The patient completion rate—a key 

measure of the likelihood that patients will remain drug 

free—is comparable to that of other outpatient treatment 

approaches, the researchers say.

Network therapy was developed through NIDA’s 

Behavioral Therapies Development Program by Dr. Marc 

Galanter and his colleagues at the New York University 

School of Medicine in New York City. The treatment 

combines cognitive-behavioral therapy, which enables 

patients to identify and develop strategies to avoid or 

cope with circumstances that lead to their drug use, with 

network sessions that include the patient and one or more 

“network members”—family members or peers who are 

not substance abusers.

“Network therapy expands the practitioner’s capability to 

treat cocaine abuse by enlisting family and peer support to 

provide the reinforcement necessary for the patient’s success,” says Dr. Galanter. “Physicians in small practices do 

not have the benefits offered by a large clinical environment, such as social workers, multidisciplinary psychiatric 

staff, or the opportunity to schedule nightly group meetings. This approach helps overcome those limitations.”

The researchers trained 28 psychiatry residents to provide 

network therapy. Training involved classroom seminars 

and video presentations based on a 122-page manual. The 

residents then treated 47 patients who had applied for 

cocaine abuse treatment and had no other substance abuse 

or psychiatric disorder.

The patients (mean age 35 years, 85 percent male, 62 percent white) paid $20 per session over a 24-week sequence 

of twice-weekly individual therapy sessions. Network sessions were held weekly for the first month and monthly 

thereafter. Twelve patients dropped out of the program 

after the first week. Of the 35 who remained beyond the 

first week, nearly half (17) completed the full 24-week 

course of treatment, a completion rate comparable to 

those in other outpatient treatment programs.

Treatment success for each participant was based on two 

measures: the proportion of drug-free weekly urine tests 

and the participant’s drug-free status for the last three 

tests. Overall, 73 percent of tests throughout treatment 

were drug free; 20 participants (43 percent of the entire 

group) were drug free the last 3 weeks of treatment. 

Success was most likely among patients who involved

network members and remained in treatment longest.

“The network sessions involved training network members 

to provide a supportive environment for abstinence to 

help patients adhere to behavioral strategies, such as avoiding situations that might trigger drug use,” Dr. Galanter 

explains. “Interestingly, it was the number of network sessions—not the number of individual sessions—that most 

closely correlated with a good outcome. This suggests 

the central role of involvement with network members in 

shaping outcome.”

Dr. Dorynne Czechowicz of NIDA’s Division of Treatment Research and Development says that the involvement of young doctors in the delivery of network therapy 

represents a significant additional accomplishment of

this research. “The recent approval of buprenorphine for 

office-based treatment of opiate addiction represents a

first step in the movement of drug abuse treatment out

 Dr. Marc Galanter, of New York University School of Medicine, 

reviews a training tape to be shown to clinicians learning network 

therapy. Developed through NIDA’s Behavioral Therapies Development Program, network therapy combines individual cognitivebehavioral therapy with sessions that include the patient and

members of his or her network—family members or peers.
71

of specialized facilities and into the more routine world of 

health care,” she says. “Training young doctors to deliver 

therapy is a crucial step in getting general practitioners 

involved in drug abuse treatment, and treatments such

as network therapy can help accelerate that movement.”

Dr. Galanter is now conducting a study of the effectiveness of network therapy in combination with the administration of buprenorphine in treating heroin addiction. 

“There is a need for training in psychosocial approaches to 

drug abuse treatment that are applicable to a practitioner’s 

office, both as a stand-alone option and in combination 

with pharmacotherapy.” Dr. Galanter says. “Our findings 

in the use of network therapy in treating cocaine addiction are promising. Results so far suggest that network 

therapy may also be a valuable, easily delivered approach 

to support buprenorphine treatment in an office setting.”

Source

• Galanter, M.D.; Dermatis, H.; Keller, D.; and 

Trujillo, M. Network therapy for cocaine abuse:

Use of family and peer supports. American Journal

on Addictions 11(2):161-166, 2002. 
72

Research Findings

A Double Dose of Research for Patients Addicted to

Both Drugs and Alcohol

By NIDA Director Nora D. Volkow, M.D. 

Volume 18, Number 1 (June 2003)

 Addiction researchers and treatment 

professionals have long known that drug 

addiction and alcoholism are strongly 

linked. In the last decade, research has 

broadened our understanding of many 

shared neurobiological and behavioral 

mechanisms that underpin the two disorders. Yet, while two in five substance abuse 

treatment patients abuse both drugs and 

alcohol, the treatment they are likely to 

receive will target only one disorder. A lack 

of science-based information on concurrent treatment of drug and alcohol abuse 

limits the ability of treatment professionals 

to provide the comprehensive treatment 

these patients need.

Recent research suggests that some medications developed 

to treat drug or alcohol abuse may be useful for treating 

both problems. This information, along with our increased 

understanding of the underlying factors that drive drug 

and alcohol abuse, provides a strong rationale for a coordinated research effort to meet the critical need for treatments for people suffering from both disorders. Toward 

that end, NIDA and the National Institute on Alcohol 

Abuse and Alcoholism (NIAAA) have issued a joint program announcement (PAS-03-029) to spur both drug 

and alcohol abuse researchers to investigate all aspects of 

pharmacological treatment for dually addicted patients.

Coordinated research on dually addicted patients will 

address the needs of the overwhelming number of 

Americans who abuse both alcohol and illicit drugs.

More than 2.4 million of the 5.6 million people 

who abused illicit drugs in 2001 also abused alcohol, 

according to the National Household 

Survey on Drug Abuse. In fact, the more 

heavily someone abused alcohol, the 

more likely he or she was to use illicit 

drugs, the survey found. In 2001, nearly 

two of every three American teenagers, 

ages 12 to 17, who engaged in frequent 

drinking binges also abused drugs. In 

comparison, only 1 in 20 young people 

who didn’t drink at all used drugs.

The substantial portion of drug- and 

alcohol-abusing patients in community 

treatment programs provides additional 

evidence of the need for science-based 

information on treating dual addiction. Patients who abuse both drugs and 

alcohol accounted for more than 42 percent of admissions to substance abuse treatment facilities reported by 

State agencies in 2000, the last year for which these data 

are published. Alcohol abuse is even more likely among 

patients who abuse certain drugs, such as cocaine, methamphetamine, and marijuana. For example, more than 

half of cocaine-abusing patients who entered treatment in 

2000 also abused alcohol.

To develop effective treatments for patients who abuse 

both drugs and alcohol, we need to understand why so 

many people do so. Part of the answer probably has to

Recent research suggests that some 

medications developed to treat 

either drug or alcohol abuse may

be useful in treating co-occurring 

substance abuse.

We aim to generate a broad 

spectrum of useful clinical information about appropriate sequencing 

or combining of medications and 

behavioral therapies, possible drug 

interactions that could affect optimal 

dosages, and unique requirements 

of specific groups of dually 

addicted patients...
73

do with genes—underlying genetic variations that may 

play a role in common brain mechanisms that fuel both 

disorders. NIDA-supported brain imaging studies conducted at Brookhaven National Laboratory in Upton, 

New York, have documented similarities in the structure 

and function of the brains of alcoholics and chronic 

cocaine abusers that appear to be implicated in the abuse 

of both substances. Individuals with either disorder have 

low levels of dopamine D2 receptors in the brain’s reward 

pathways that may impair their capacity to derive pleasure 

from normally rewarding activities. This deficit may make 

them more vulnerable to the rewarding effects of alcohol 

and cocaine.

Dually addicted individuals also may combine alcohol and 

illicit drugs because of interactions between abused substances in the body. Because both drugs and alcohol activate brain areas involved in reward, combining substances 

may increase these effects. Other alcohol-drug interactions 

may counter unpleasant effects that often accompany

or follow substance abuse. Clinical reports suggest that 

cocaethylene, a combined cocaine-alcohol metabolite that 

is formed in the body following concurrent alcohol and 

cocaine use, appears to reduce the anxiety that can accompany cocaine use. Recent research in rats confirms that 

cocaethylene plasma levels remain high as cocaine levels 

fall, producing a delayed, relatively long-lasting rewarding 

effect that may counter the aversive effect induced when 

cocaine plasma levels recede.

While the perceived benefits of combining alcohol and 

drugs may play a big part in the high percentages of people 

who do so, the addictive effects and harmful consequences 

of both substances increase when they are used together. 

Dually addicted patients are more likely to drop out of 

treatment and have poorer results than patients who abuse 

only one substance. However, since most studies on treating drug and alcohol abuse have examined these disorders 

separately, drug and alcohol treatment counselors now 

have little science-based information on which to base their 

treatment of these patients.

The joint NIDA-NIAAA program announcement addresses this critical need for effective approaches to treating 

dually addicted patients. Our research partnership seeks 

studies that will evaluate the efficacy of established drug 

and alcohol treatment medications and novel pharmacological agents in patients with concurrent addictions. 

We aim to generate a broad spectrum of useful clinical 

information about appropriate sequencing or combining 

of medications and behavioral therapies in dually addicted 

patients, possible drug interactions that could affect optimal dosages, and unique requirements of specific groups

of patients, such as minorities, the elderly, and adolescents.

Drug and alcohol abuse wreak incalculable damage on 

individuals, families, and communities. When they

occur together, these disorders double the challenge to 

researchers and treatment providers. Now, NIDA and 

NIAAA have launched a concerted scientific response

to address these challenges. Ultimately, this expanded 

research will fuel the development of new treatments that 

will enable substance abuse treatment programs to more 

effectively meet the needs of the many patients who abuse 

both alcohol and illicit drugs. 

The joint NIDA-NIAAA program 

announcement addresses the critical need for effective approaches to 

treating dually addicted patients.
74

Research Findings

Treating Adolescent Substance Abuse by Addressing

Family Interactions

Volume 18, Number 1 (June 2003)

Brief Strategic Family Therapy (BSFT) 

is described in the latest addition to the 

Therapy Manuals for Drug Addiction series. 

The short-term intervention is used to treat 

adolescent drug use that occurs along with 

other problem behaviors. This therapy 

focuses on an adolescent’s drug use within 

the context of family dynamics.

The BSFT manual introduces counselors 

to concepts they need to understand the 

family as a vital context within which 

adolescent drug abuse occurs. It also 

describes strategies for creating a therapeutic relationship with families, assessing and 

diagnosing maladaptive patterns of family 

interactions, and changing family interaction patterns from maladaptive to adaptive.

BSFT can be adapted to a range of family situations and 

used in a variety of service settings—such as mental health 

clinics, drug abuse treatment programs, and other social 

service settings. It also can be delivered in various ways, 

such as on an outpatient basis or in combination with residential or day treatment. Treatment lasts 8 to 24 sessions, 

depending on the severity of the problem.

In addition to targeting an adolescent’s conduct problems 

at home and at school, BSFT addresses oppositional, 

aggressive, violent, or risky sexual behavior; association 

with antisocial peers; and delinquency. Family dynamics 

are a key focus of this therapy.

Over 25 years of extensive evaluation has found BSFT 

to be effective in treating adolescent drug abuse, conduct 

problems, association with antisocial peers, and impaired 

family functioning. It has been shown to be particularly 

successful with cultural groups that emphasize family and 

interpersonal relationships. BSFT has not been tested with 

adult addicts and is not considered a treatment for adult 

addiction.

The upcoming manual and the series of which it is a part 

exemplify NIDA’s commitment to applying basic research 

findings to treatment needs. In addition to describing scientifically based therapies for addiction, the five manuals 

provide guidance on content for counseling sessions and 

effective counseling techniques. Audiences 

include drug abuse treatment practitioners, mental health professionals, and 

others involved in treating drug abuse 

and addiction.

Therapy Manuals Offer a Range of 

Treatment Strategies

The four earlier therapy manuals can

be downloaded from NIDA’s Web site, 

www.drugabuse.gov, or ordered through 

the National Clearinghouse for Alcohol 

and Drug Information, http://ncadi.samhsa.

gov/. The Brief Strategic Family Therapy

manual also will soon be available from 

these sources.

• A Cognitive-Behavioral Approach: Treating Cocaine 

Addiction (Manual 1) describes cognitive-behavioral 

coping skills treatment, a short-term, focused approach 

to helping cocaine-dependent individuals abstain from 

cocaine and other drugs. 

• A Community Reinforcement Plus Vouchers Approach: 

Treating Cocaine Addiction (Manual 2) integrates a 

community reinforcement approach with an incentive 

program that uses vouchers. Patients earn points to 

redeem for retail items by remaining in treatment and 

abstaining from cocaine. 

• An Individual Counseling Approach to Treat Cocaine 

Addiction: The Collaborative Cocaine Treatment Study 

Model (Manual 3) presents a guide for the individual 

treatment of cocaine addiction that emphasizes an 

individual’s physical, emotional, spiritual, and interpersonal needs in supporting recovery. 

• Drug Counseling for Cocaine Addiction: The Collaborative Cocaine Treatment Study Model (Manual 4) 

describes the Group Drug Counseling (GDC) model 

developed for the Collaborative Cocaine Treatment 

Study (CCTS), a multisite clinical trial. The study 

found the combination of GDC and individual drug 

counseling to be more effective than GDC alone or 

the combination of GDC and psychotherapy. 
Many factors influence adolescent drug abuse. Peer 

relationships; family, school, and neighborhood environments; and social or cultural norms can each act as 

protective factors or can put adolescents at increased risk. 

NIDA-supported researchers are developing and evaluating a variety of treatments designed to address the range 

of influences that play a role in adolescent drug abuse.

In a study that compared three treatment approaches, 

researchers have found that Multidimensional Family 

Therapy (MDFT), which involves individual therapy and 

family therapy, produced better treatment outcomes than 

did Adolescent Group Therapy (AGT) or Multifamily 

Educational Intervention (MEI), a treatment delivered

in sessions involving more than one family.

Dr. Howard Liddle at the 

University of Miami School 

of Medicine and colleagues 

at the University of Pennsylvania in Philadelphia, the 

University of Washington

in Seattle, and Families

First, a treatment center in 

Stockton, California, evaluated the treatment programs 

in a study involving 152 

adolescents who had been 

referred to treatment through 

the juvenile justice system. 

The participants (average age 

15.9 years, 80 percent male) 

came from single-parent 

families (48 percent), twoparent families (31 percent), 

and stepfamilies (21 percent) 

and had been using drugs for 

an average of 2.5 years; 51 

percent were polydrug users, 

49 percent marijuana and 

alcohol users.

Participants were randomly 

assigned to one of the treatment programs, which were 

administered in community 

clinics in weekly sessions over 

a period of 5 to 6 months. 

Before treatment began, the researchers evaluated each 

participant’s drug use, school performance, problem 

behavior (acting-out behavior measured by a widely used 

assessment scale), and family functioning (measured by 

the Global Health Pathology Scale). The same characteristics were measured at the end of treatment and at 

followup evaluations 6 months and 12 months after treatment ended.

Overall, the adolescents showed reductions in drug use 

after all three treatment programs, but the improvements 

were greatest for participants who received MDFT. At the 

end of treatment, 42 percent of MDFT, 25 percent of 

AGT, and 22 percent of MEI participants had decreased 

their drug use. Drug use declined further in the 12 months 

75

Research Findings

Family-Based Treatment Programs Can Reduce Adolescent 

Drug Abuse

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 17, Number 4 (November 2002)

Multidimensional Family Therapy Reduces Youth Drug Use,

Improves School Performance and Family Interaction

a Average of all patients.

b

MDFT = Multidimensional Family Therapy; AGT = Adolescent Group Therapy; MEI = Multifamily Educational Intervention.

Drug Use, Past 30 days a

1 (no use) to 15 (marijuana use

daily and other drugs used more

than twice per week)

MDFTb 9.89 4.79 4.25

AGT 8.83 7.33 5.08

MEI 10.03 7.26 7.26

Academic Performancea

Grade point average from 1 (D) to 4 (A)

MDFT 1.77 2.56 2.62

AGT 1.85 2.44 2.26

MEI 1.98 2.05 1.92

Family Functiona

1 (optimal) to 10 (severely dysfunctional)

MDFT 6.15 5.18 4.70

AGT 6.00 5.67 5.83

MEI 4.31 4.77 5.35

Multidimensional Family Therapy, which involves individual therapy and family therapy, produced 

better treatment outcomes for teenagers than did Adolescent Group Therapy or Multifamily Educational 

Intervention, a treatment delivered in sessions involving more than one family.

Start of 

Treatment

End of 

Treatment

12-Month 

Followup
76

following treatment, with MDFT associated with the 

greatest reduction. Participants in MDFT also showed 

greater improvement in family functioning and academic 

performance than did adolescents who received AGT or 

MEI treatment.

“There was an overall pattern of improvement for each 

of the treatments, but family-based therapy stands out in 

its success in this study,” Dr. Liddle says. “Those receiving MDFT showed the most improvement in drug use 

and academic performance, followed by participants who 

received AGT, then those receiving MEI.”

Improvement in family function was most notable in 

MDFT participants, Dr. Liddle says. “The MDFT families moved from assessments of ‘behaviorally incompetent’ 

to the ‘competent’ range, while AGT families showed no 

change, and MEI families deteriorated on the family functioning scales.” 

Participants in MDFT were less likely than those in other 

programs to drop out of treatment—70 percent of those 

assigned to MDFT completed treatment, compared with 

66 percent of participants in MEI and 52 percent in AGT.

Each program provided improvement in one or more 

outcomes measured in the study, but involvement of 

family members was associated with the best overall progress. “Given the pattern of results, it seems reasonable to 

conclude that a simultaneous focus on the family and 

the individual adolescent is an important ingredient for 

successful treatment of adolescent drug abuse,” Dr. 

Liddle says.

Source

• Liddle, H.A., et al. Multidimensional family therapy 

for adolescent drug abuse: Results of a randomized 

clinical trial. American Journal of Drug and Alcohol 

Abuse 27(4):651-687, 2001. 
77

Research Findings

New Insights Into Relapse

By NIDA Acting Director Glen R. Hanson, Ph.D., D.D.S.

Volume 17, Number 3 (October 2002)

Drug addiction is a chronic relapsing disorder. As when patients in treatment for 

hypertension or asthma temporarily lose 

control, relapse to drug abuse does not 

mean treatment does not work, or the 

patient is not making an effort, or he or she 

will never have a productive life with longterm freedom from disease. Nevertheless, 

relapse is perhaps the most frustrating and 

demoralizing feature of drug addiction, for 

those who have it and those who would 

help them.

Clinical observation and research tell us 

that three types of stimulus can trigger 

intense drug craving, leading 

to renewed abuse:

• Priming: “Just one” 

exposure to the formerly 

abused substance—be it 

a cigarette, a drink, or 

an illegal drug—can precipitate rapid resumption of abuse at previously established levels 

or greater.

• Environmental cues

(people, places, or 

things associated with past drug use): One vivid 

illustration of the power of such cues is a negative 

one: A small percentage of American

service personnel became addicted to heroin while 

overseas during the Vietnam War. When they were 

removed from that environment, the great majority, 

after detoxification, reported no further problems 

with opiates.

• Stress: Both acute and chronic stress can contribute 

to the establishment, maintenance, and resumption

of drug abuse. Patients and treatment providers alike 

point to stress as the most common cause of relapse. 

The impact of stress recently was highlighted when 

researchers documented increased rates of smoking 

and alcohol consumption by New Yorkers after the 

September 11, 2001 attacks. 

Our knowledge of relapse is incorporated 

in science-based drug treatments. In 

cognitive-behavioral therapy, for example, 

patients learn to confront the consequences of their drug use, recognize the environmental cues and potentially stressful situations that trigger strong drug cravings, and 

develop strategies to steer clear or respond 

without relapsing. Recent research has 

shown that patients who benefit from 

cognitive-behavioral therapy may even 

show further improvement after treatment 

has ended and with passing time.

Science-based medical treatments buffer 

patients against the craving that leads to relapse. 

Methadone and other opioid agonist agents block the 

euphoric effects of opioids 

and stabilize brain processes 

whose disruption is linked 

to craving. Naltrexone, an 

opioid antagonist, blocks 

opioid-induced euphoria 

and counters opioid craving with an aversive effect. 

Disulfiram (Antabuse) is 

used to treat alcohol abuse, and it is currently being tested 

to determine whether it also can offset cocaine craving. 

Antianxiety agents are prescribed to moderate stress.

New research findings appear to shed light on one of the 

deepest mysteries involving drug relapse: We know that 

former abusers of addictive drugs remain vulnerable to 

powerful drug cravings for months or years after establishing abstinence. What accounts for the extraordinary persistence of drug cravings?

Scientists have known for some time that addictive drugs 

hyperactivate key brain circuits that provide pleasure and 

are closely linked to motivation and memory. Research 

also has shown that drugs change brain cells in these circuits in numerous ways, some of which might be linked to 

craving. However, these changes generally last only as long 

as a drug is actually present, or a little longer. To explain 

New research findings appear to 

shed light on one of the deepest 

mysteries involving drug relapse: 

What accounts for the extraordinary 

persistence of drug cravings?
78

how craving can recur after long abstinence, researchers 

need to show that the drugs change the cells in ways that 

change back slowly or not at all.

The natural place to look for long-lasting drug-induced 

alterations is in the same circuits that produce short-term 

effects. Key cells in these circuits are located in an area 

called the midbrain; they manufacture a chemical called 

dopamine and release it in a nearby area called the nucleus 

accumbens, where it produces powerful mood effects.

During the past 3 years, research teams at Yale and Texas 

Southwestern Universities demonstrated that repeated 

exposure to cocaine produces alterations in gene activity

in the nucleus accumbens that can persist for weeks. Last 

year, researchers at the University of Michigan showed 

that cocaine self-administration changes the actual shape 

of these neurons—a change that is long-lasting or even 

permanent. Moreover, its specific nature—a proliferation 

of signal receptors—might be expected to contribute to 

craving by heightening the cells’ general reactivity.

Further research will tell whether these changes are critically important to long-term vulnerability to drug craving, 

or whether they play a relatively minor role. The studies 

were conducted with laboratory animals and cocaine, and 

we need to find out whether they also apply in humans 

and with other drugs. Although uncertainties remain, 

these new results provide powerful confirmation of the 

neurobiological and chronic nature of drug addiction, evidenced at still more fundamental levels of brain cell operation. The studies also demonstrate the power of new neuroscience tools to elucidate the underlying causes of drug 

abuse. Ultimately, we need approaches this powerful to 

gain the understanding necessary to solve the mysteries

of craving and generate treatments that help all patients 

move beyond the reach of relapse. 
79

Research Findings

In Drug Abuse, Gender Matters

By NIDA Acting Director Glen R. Hanson, Ph.D., D.D.S. 

Volume 17, Number 2 (May 2002)

Recent decades have seen a marked increase 

in awareness of the importance of gender 

in medical treatment and research. In the 

complex field of drug abuse research, scientists have helped us understand that there 

are genetic, physiological, psychosocial, and 

environmental dimensions to drug abuse 

and addiction. Male and female differences 

in any of these dimensions can give rise to 

gender differences in the causes, effects, and 

consequences of drug abuse. Researchers 

and clinicians have developed a repertoire 

of effective treatment and prevention principles that can now be enhanced through 

their adaptation for the differing needs of men and women 

and boys and girls.

NIDA’s National Drug Abuse 

Treatment Clinical Trials 

Network adheres to the overall 

National Institutes of Health 

requirement for analysis of 

data by gender and supports 

gender-specific protocol development. NIDA recently issued 

a Program Announcement 

for support of dissertation 

research in five areas, one of 

which is women and gender. A new Program Announcement on Women and 

Gender Differences will be issued soon to fund research 

specifically in the areas of epidemiology, prevention, and 

treatment. These efforts will build on NIDA-sponsored 

research that has established that important gender effects 

exist in biological and behavioral responses to drugs, risk 

for drug abuse, and treatment response.

Response to drugs: The neurobiological basis of drug 

abuse and addiction is essentially the same, regardless of 

the drug taken or the person taking it. Still, males and 

females may differ in their biological and behavioral 

responses to drugs. Laboratory studies have revealed 

sex-related differences in the ways that male and female 

animals metabolize drugs, the amount of drug they will 

self-administer, how soon after their first exposure they 

begin to administer drugs, and their vulnerability to relapse 

after abstinence. Preliminary results from 

studies of human drug abusers appear 

to be consistent with the findings from 

animal studies of gender differences in 

the patterns and the biological impact of 

drug use. For example, women typically 

progress from first use of cocaine, heroin, 

or marijuana to dependence more quickly 

than men. Additionally, cocaine-induced 

cognitive impairments and risk for stroke 

have been found to be more severe in men 

than in women.

Risk for drug abuse: While risk factors related to drug abuse vulnerability 

in males and females largely 

overlap, a variety of differences exist. Depression is 

much more common among 

women than men in the 

general public. This gender difference is much less 

pronounced among drug 

abusers. Possible explanations are that depression is a 

more potent risk factor for 

drug abuse among men than 

among women, or that drug 

abuse itself is more likely to 

cause depression among men 

than among women. Other risk factors that appear to be 

stronger for one gender than the other include conduct 

disorders, which correlate more with drug abuse by adolescent females, and aggression, which correlates with drug 

abuse by adolescent males.

Along with these differences, studies of gender and risk 

have revealed an unexpected and important similarity 

between males and females. Most experts long assumed 

that females were less attracted to or more wary of drug 

abuse than were males. That seemed a straightforward 

conclusion based on the fact that the percentage of 

women who abuse drugs is lower than the percentage of 

men who abuse drugs. However, the conclusion turns out 

to be not true. A recent study found that the lower rate of 

drug abuse for females is largely a matter of opportunity. 

Researchers and clinicians have 

developed a repertoire of effective 

treatment and prevention principles 

that can now be enhanced through 

their adaptation for the differing 

needs of men and women 

and boys and girls.
80

(See “Gender Differences in Prevalence of Drug Abuse,” 

NIDA NOTES, Vol. 15, No 4). During the youthful ages 

when most drug abuse initiation occurs, more boys than 

girls receive offers of drugs. When drug offers are made, 

both genders are equally likely to accept. Once having 

accepted, males and females generally are equally likely to 

become dependent. This underscores the importance of 

drug refusal skills in prevention efforts with both genders.

Response to treatment: Success in drug treatment is 

directly associated with the length of time spent in treatment: The more time in treatment, the better the outcome. Science-based drug treatments are equally effective 

for men and women, but women often spend less time 

than men in treatment. In part, this could reflect differences in social and economic circumstances. Women 

entering treatment are more likely than men to be custodial parents and to have fewer economic resources; they 

are less likely than men to have graduated from high 

school, to be employed, or to have sufficient supportive social networks. Studies also indicate that males and 

females tend to relapse to drug use for different reasons. 

For example, among men relapse is more likely to be

associated with anxiety and positive feelings, while among 

women depression and negative feelings appear to be more 

common triggers. All these differences suggest that it may 

be possible to enhance the effectiveness of treatment by 

tailoring it for the patient’s gender.

The area of nicotine addiction is one in which our understanding of gender effects is relatively advanced, although 

still far from complete. Research has shown that different 

aspects of smoking more strongly influence addiction to 

nicotine in men and women. For men, the compulsion to 

smoke is driven more strongly by nicotine’s pharmacological effects on the brain, while women’s addiction owes 

more to the visual, tactile, taste, and olfactory sensations 

involved in smoking. Because of these differences, men 

tend to get more relief overall from nicotine replacement 

therapy, and women who use nicotine replacement do 

better with nicotine inhalers than the nicotine patch. 

Recent NIDA research also suggests that women can 

increase their chances for quitting by timing their attempt 

to coincide with the first half of their menstrual cycles, 

since nicotine craving and withdrawal symptoms are generally more severe during the second half of their cycles.

Although the focus on gender is relatively new in drug 

abuse science, we already know that gender’s impact is far 

reaching and complex. A comprehensive and detailed picture of gender-related effects can lead to improvements in 

treatment and prevention efforts that bring us closer to 

the goal of individualized interventions that best meet the 

distinct needs of each patient. When it comes to reducing 

the tremendous burden of drug abuse and addiction, 

gender most certainly matters. 

Although the focus on gender is relatively new in drug abuse science, we 

already know that gender’s impact is 

far reaching and complex. 
81

Research Findings

Adolescent Treatment Programs Reduce Drug Abuse,

Produce Other Improvements

By Kimberly R. Martin, NIDA NOTES Contributing Writer 

Volume 17, Number 1 (April 2002)

In the first large-scale study designed 

to evaluate drug abuse treatment 

outcomes among adolescents in agespecific treatment programs, NIDAsupported researchers have found that 

longer stays in these treatment programs can effectively decrease drug and 

alcohol use and criminal activity as well 

as improve school performance and 

psychological adjustment.

The study, part of NIDA’s ongoing 

Drug Abuse Treatment Outcome 

Studies for Adolescents (DATOS-A), 

analyzed data from 23 communitybased adolescent treatment programs 

that addressed peer relationships, educational concerns, and family issues 

such as parent-child relationships and 

parental substance abuse. Successful 

elements of adult treatment programs, 

such as participation in group therapy 

and participation in a 12-step program, 

were also included in treatment plans.

“The results of this study are particularly impressive in light of the fact that 

the adolescents had multiple problems,” says Dr. Christine Grella of the 

University of California, Los Angeles 

(UCLA), Drug Abuse Research Center, 

one of the study’s investigators. “Although this is also typical of many adults in treatment, timely resolution of these 

problems is even more critical for adolescents. These young 

people are in the process of developing values, making 

lifestyle decisions, and preparing to assume adult roles

and responsibilities, such as family and work; whereas 

when many adults enter treatment, they have completed 

this process.”

Treatment Programs Varied

Dr. Yih-Ing Hser, also of UCLA, led the research team 

that evaluated the treatment outcomes for 1,167 adolescents, age 11 to 18, who were admitted to one of the treatment programs between 1993 and 1995. The treatment 

centers, located in Pittsburgh, Pennsylvania; Minneapolis, 

Minnesota; Chicago, Illinois; and Portland, Oregon, 

included eight residential programs, nine outpatient drugfree programs, and six short-term inpatient programs.

The 418 adolescents in the residential treatment programs 

received education, individual and group counseling, and 

interventions to develop social responsibility. The 292 adolescents in the outpatient drug-free programs received education, skills training, and individual and group counseling. 

The 467 adolescents in short-term inpatient programs 

received counseling and a 12-step program. Family therapy 

was strongly emphasized, and adolescents in these programs 

were referred to continued outpatient treatment. The average length of treatment for adolescents in the residential, 

outpatient drug-free, and short-term inpatient programs 

was 5 months, 1.6 months, and 18 days, respectively.

The adolescents were interviewed when they began treat-

 Behaviors of Adolescents Before and 

One Year After Treatment

An evaluation of more than 1,100 adolescents who received substance abuse treatment in 

residential, short-term inpatient, or drug-free outpatient programs found improvement in 

rates of drug use and social behavior. Some 53 percent of those treated met or exceeded the 

minimum recommended stay in treatment.
82

ment and again 1 year after discharge by professional 

interviewers who were not employed by the treatment 

centers. Problem severity was determined at the initial 

interview according to a number of criteria. Dependence 

on drugs or alcohol was determined from standardized 

diagnostic measures. To validate self-reports of drug use, 

one-quarter of the participants were selected randomly to 

submit urine samples during the posttreatment interview.

Before treatment, 25 percent of the participants used three 

or more drugs, 36 percent were dependent on alcohol,

64 percent were dependent on marijuana, and 10 percent 

were dependent on cocaine. In addition to substance 

abuse problems, 63 percent were diagnosed with a mental 

disorder and 67 percent were criminally active.

Outcomes Overall

Research has indicated that 

in general the rate of drug 

and alcohol use tends to 

increase during adolescence. 

In the present study, however, improvements were 

observed in many of the 

areas evaluated, although 

some of the participants did not complete their treatment 

program. Comparing the year before treatment to the year 

after treatment, the adolescents showed significant declines 

in the use of marijuana and alcohol, which are considered 

to be the major drugs of abuse for this age group. Weekly 

or more frequent marijuana use dropped from 80 percent 

to 44 percent, and abstinence from any use of other illicit 

drugs increased from 52 percent to 58 percent. Heavy 

drinking decreased from 34 percent to 20 percent, and 

criminal activity decreased from 76 percent to 53 percent. 

Adolescents also reported fewer thoughts of suicide, lower 

hostility, and higher self-esteem. In the year following 

treatment, more adolescents attended school and reported 

average or better-than-average grades. Some exceptions 

to the general pattern of improvement were that overall, 

cocaine and hallucinogen use did not improve during the 

year after treatment.

Treatment Length and Outcomes

Previous research indicates that a minimum of 90 days of 

treatment for residential and outpatient drug-free programs 

and 21 days for short-term inpatient programs is predictive of positive outcomes for adults in treatment. Better 

treatment outcomes were reported among adolescents who 

met or exceeded these minimum lengths of treatment than 

for those who did not. Among the treatment participants, 

58 percent of those in residential programs, 27 percent in 

outpatient drug-free programs, and 64 percent in shortterm inpatient programs met or exceeded the minimum 

stay. In the year following treatment, those who met or 

exceeded the minimum treatment were 1.52 times more 

likely to abstain from drug and alcohol use and 1.2 times 

more likely to not be involved in criminal activity. In addition, these adolescents were 

1.34 times more likely to 

have average or better-thanaverage grades.

This study confirms 

that community-based 

drug treatment programs 

designed for adolescents 

can reduce substance 

abuse and have a positive impact on many other aspects 

of their life, says Dr. Tom Hilton of NIDA’s Division of 

Epidemiology, Services and Prevention Research. These 

results justify new research to identify the key elements 

common to effective treatment programs for adolescents, 

he noted.

Source

• Hser, Y-I.; Grella, C.E.; Hubbard, R.L.; et al. An 

evaluation of drug treatment for adolescents in four 

U.S. cities. Archives of General Psychiatry 58(7):689-

695, 2001. 

In the year following treatment, 

more adolescents attended school 

and reported average or 

better-than-average grades.
83

Research Findings

NIDA Clinical Trials Network Begins First Multisite Tests of New 

Science-Based Drug Abuse Treatments

By Robert Mathias, NIDA NOTES Staff Writer 

Volume 15, Number 6 (January 2001)

NIDA’s National Drug Abuse Treatment Clinical Trials 

Network (CTN) is up and running. Seven research-based 

drug abuse treatment protocols are being tested under realworld treatment conditions by the network’s 6 pioneering 

regional research centers in collaboration with more than 

35 community treatment programs (CTPs). Approximately 

3,000 drug abuse patients are expected 

to participate in this first wave of clinical trials of promising 

new pharmacological and behavioral drug abuse 

treatments.

“The CTN is definitely not business as usual,” says Dr. 

Betty Tai, who directs NIDA’s CTN Office. In these studies, researchers and practitioners are breaking new ground 

by working together to see whether and how treatments 

that are effective under carefully controlled conditions can 

be adapted and applied effectively with diverse patient 

populations in a variety of treatment settings, she says. “We 

expect that protocols that work under these real-world conditions will quickly become the standard of care for physicians, treatment programs, and their patients,” she says.

Goals of the Protocols

The CTN’s Steering Committee selected the first treatment concepts for testing using three main criteria-solid 

scientific evidence of efficacy, ease of implementation, and 

potential to improve public health, Dr. Tai says. Three 

broad pharmacological and behavioral treatment research 

concepts were approved from which CTN protocol development teams produced seven treatment protocols for 

implementation.

Two pharmacological protocols are studying whether 

buprenorphine/naloxone (BUP/NX) would be more effective in detoxifying opiate-dependent patients than clonidine, a medication that has been used to detoxify opiate 

addicts. A related protocol is studying the relative effectiveness of different BUP/NX dosing regimens in detoxifying opiate-dependent treatment patients. BUP/NX is a 

new medication that is nearing FDA approval for treating 

opiate addiction. Detoxification, the medically supervised 

withdrawal from an addicting drug on which a patient is 

physically dependent, represents the first step in treating 

opiate addiction. Following detoxification, patients are 

treated with a variety of behavioral and pharmacological 

approaches in many different treatment settings.

The primary objective of the BUP/NX studies is to 

evaluate the medication’s usefulness in detoxifying opiate addicts in both inpatient and outpatient community 

treatment settings and to determine the most effective 

dosing regimens. The lead investigator for these studies, 

Dr. Walter Ling from the University of California, Los 

Angeles, directs the CTN’s Pacific Region Node. A total 

of 1,080 patients from 14 CTPs in California, Oregon, 

New York, Pennsylvania, Connecticut, Virginia, and 

Maryland are expected to participate in these 3 studies.

Two cognitive treatment protocols are adding motivational enhancement therapy (MET) to standard drug 

abuse treatment. MET is a brief, nonconfrontational 

treatment in which a clinician seeks to increase patients’ 

commitment to reducing their drug abuse by heightening their awareness of the harmful personal consequences 

of that use. In one protocol, a therapist delivers MET in 

three individual therapy sessions during the first 3 weeks 

of treatment. In the second protocol, called motivational 

interviewing, therapists use MET techniques only in 

Dr. Betty Tai, Clinical Trials Branch, NIDA; Dr. Robert 

Forman, University of Pennsylvania, Delaware Valley Node; and 

Paul Nagy, Duke Addictions Program, North Carolina Node, discuss drug abuse treatment at the CTN meeting in October. 

“We expect that protocols that work 

under these conditions will quickly 

become the standard of care.” 
84

the intake interview given to patients when they 

enter treatment.

Both MET protocols are trying to determine if patients 

who are treated with motivational enhancement techniques stay in treatment longer and reduce their drug use 

more than patients who receive standard treatment alone. 

The principal investigator for these studies is Dr. Kathleen 

Carroll of Yale University in New Haven, Connecticut, 

who directs the CTN’s Southern New England Node. 

It is anticipated that 1,100 patients from 11 CTPs in 

California, Connecticut, Virginia, Pennsylvania, Oregon, 

and New York will participate in these 2 studies.

The last two protocols are assessing the benefit of adding a behavioral treatment called motivational incentive 

(MI) therapy to standard treatment. One protocol is being 

tested with patients in methadone clinics and the other 

in drug-free clinics. MI therapy offers patients tangible 

rewards for remaining drug free. Patients are given the 

chance to draw for prizes whenever tests indicate they 

have not used cocaine, amphetamines, methamphetamine, 

or alcohol. Abstinent patients can win prizes that range 

from small items such as candy bars and sodas all the 

way up to larger items, such as clothing, radios, and TVs. 

Patients have a better chance of winning smaller prizes 

than larger ones, but the longer they remain abstinent the 

more chances they get to win.

The primary objective of the MI protocols is to determine 

if offering tangible incentives for remaining drug free 

can keep patients in treatment longer and reduce their 

drug abuse more than standard treatment alone does. 

Dr. Maxine Stitzer of The Johns Hopkins University 

School of Medicine in Baltimore, Maryland, and the 

CTN’s Mid-Atlantic Node is the lead investigator for 

these studies. A total of 800 patients from 5 methadone 

treatment programs and 6 drug-free clinics in California, 

Connecticut, Maryland, New York, and Pennsylvania are 

expected to participate in these 2 studies.

From Protocol to Practice

“We wanted this first wave of protocols to be easy to 

implement and transfer into community practice,” Dr. 

Tai says. One of the ways the protocols are accomplishing this is by simply adding the therapy being tested to the 

standard treatment normally used in participating CTPs. 

Patients in the study are assigned randomly to either the 

enhanced treatment or standard treatment alone. If a 

study establishes that patients do better with the enhanced 

treatment than the standard treatment alone, CTPs can 

simply use the protocol to add the new treatment to standard treatment as needed, Dr. Tai says.

CTN participants modified research-based treatments to 

enable them to be sustained in practice, says Dr. Tai. For 

example, the protocols to implement the MI therapy in 

the CTPs set the total value of rewards that patients can 

accumulate for staying drug free considerably lower than 

the total used in research settings. Researchers initially felt 

that higher rewards might be needed to provide sufficient 

incentive for drug abuse patients to remain abstinent. 

However, practitioners were concerned that such awards 

would prove too costly for their programs. After much 

negotiation, the CTN’s Steering Committee, which is 

made up of both researchers and CTP representatives, 

agreed on a middle ground that kept the maximum value 

of incentives within a range that CTPs felt they could 

afford. The bottom line was that CTPs would not have 

been able to support more costly incentives, no matter 

how well they worked.

“The CTN has made a very good start towards allowing 

research and clinical practice to impact one another,” says 

Albert L. Hasson, administrative director of the Matrix 

Institute on Addiction, an outpatient drug-free clinic in 

the Los Angeles area that is participating in the CTN. 

“The researchers have ideas about how the research should 

be done based on what has worked in controlled settings. 

In turn, the CTPs have ideas about how the research 

should be adapted and integrated into existing treatment 

settings to best suit the needs of the programs and the 

patients they serve.

“Participating in a project of this magnitude has been 

invaluable for us,” says Mr. Hasson, who also serves on the 

CTN’s Steering Committee. “To have input into the direction the research will take has enabled our organization to 

become part of something that could very well shape the 

future of drug treatment for years to come.” 

CTN researchers, treatment providers, and NIDA staff met in Los Angeles in October to discuss new treatment protocols and related issues. 

From left: NIDA Director Dr. Alan I. Leshner; Dr. Ivan Montoya, Clinical Trials Branch, NIDA; Dr. Dennis McCarty, Oregon Health 

Sciences University, Northwest Node; Kevin McEneaney, Therapeutic Communities of America, Inc.; Allan Bray, Self Help Addiction 

Rehabilitation, Inc., Great Lakes Node; and Dr. Kathleen Carroll, Yale University, Southern New England Node.
Research Findings

85

Gender Differences in Drug Abuse Risks and Treatment

Volume 15, Number 4 (September 2000)

Over the past few years NIDA has made a major research 

commitment to identifying and understanding differences in the ways that women and men-or girls and 

boys-are first exposed to drugs, in their risks of abuse 

and addiction, and in the effectiveness of drug treatment. 

Understanding these differences, and incorporating that 

understanding into drug abuse prevention and treatment, 

can reduce the dangers and improve outcomes. NIDAsupported research has shown that gender differences play 

a role from the very earliest opportunity to use drugs, that 

women and men tend to abuse different drugs, that the 

effects of drugs are different for women and men, and 

that some approaches to treatment are more successful for 

women than for men.

Are Women Less Likely Than Men to Abuse Drugs?

Men are more likely than women to have opportunities to 

use drugs, but men and women given an opportunity to 

use drugs for the first time are equally likely to do so and 

to progress from initial use to addiction. However, women 

and men appear to differ in their vulnerability to some 

drugs. Both are equally likely to become addicted to or 

dependent on cocaine, heroin, hallucinogens, tobacco, and 

inhalants. Women are more likely than men to become 

addicted to or dependent on sedatives and drugs designed 

to treat anxiety or sleeplessness, and less likely than men 

to abuse alcohol and marijuana. There are also differences between men and women who seek treatment for 

drug abuse. Women in treatment programs are less likely 

than men to have graduated from high school and to be 

employed and are more likely than men to have other 

health problems, to have sought previous drug treatment, 

to have attempted suicide, and to have suffered sexual 

abuse or other physical abuse.

Are There Gender Differences In the Biological Effects 

of Drugs?

Animal research and human studies have revealed that 

males and females may differ in their biological responses 

to drugs. In studies of animals given the opportunity to 

self-administer intravenous doses of cocaine or heroin, 

females began self-administration sooner than males and 

administered larger amounts of the drugs. Women may 

be more sensitive than men to the cardiovascular effects 

of cocaine. In human studies, women and men given 

equal doses of cocaine experienced the same cardiovascular response despite the fact that blood concentrations 

of cocaine did not rise as high in women as in men. In 

studies involving long-term cocaine users, women and 

men showed similar impairment in tests of concentration, 

memory, and academic achievement following sustained 

abstinence, even though women in the study had substantially greater exposure to cocaine. Women cocaine users 

also were less likely than men to exhibit abnormalities 

of blood flow in the brain’s frontal lobes. These findings 

suggest a sex-related mechanism that may protect women 

from some of the damage cocaine inflicts on the brain.

Does Gender Play a Role in Nicotine Addiction?

Women and men are equally likely to become addicted 

to nicotine, yet women typically smoke cigarettes with 

lower nicotine content than those smoked by men, smoke 

fewer cigarettes per day, and inhale less deeply than men. 

Overall, however, women are less successful than men in 

quitting smoking and have higher relapse rates after they 

do quit. Treatment involving nicotine replacement 

therapy—nicotine gum or patch—works better for men 

than for women.

What Are Women’s Risks for HIV/AIDS?

Research suggests that there are sex-related differences 

in some fundamental aspects of the HIV/AIDS disease 

process. For example, an HIV-infected woman with half 

the amount of virus circulating in the bloodstream as an 

infected man will progress to a diagnosis of AIDS in about 

the same time. And, according to the Centers for Disease 

Control and Prevention, among cases that progress to a 

diagnosis of AIDS, drug abuse accounts for a greater percentage of cases among women than among men. Nearly 

half (47 percent) of all women diagnosed with AIDS are 

injecting drug users (IDUs), whereas among men, IDUs 

account for 32 percent of AIDS cases. An additional 19 

percent of women, compared with 2 percent of men, with 

AIDS report having sex with users who inject drugs. In 

all, drug abuse is nearly twice as likely to be directly or 

indirectly associated with AIDS in women (66 percent) as 

in men (34 percent).

For More Information

NIDA’s gender-related research is discussed in Drug 

Addiction Research and the Health of Women, available 

on NIDA’s web site: www.drugabuse.gov.
Research Findings

86

Treating the Brain In Drug Abuse

By NIDA Director Dr. Alan I. Leshner 

Volume 15, Number 4 (September, 2000)

Remarkable research and technological 

advances in the past two decades have 

proved that brain disruption and damage play central roles in the consequences 

of drug abuse and addiction. Knowing 

the nature of a problem, of course, opens 

the way for systematic attempts to fix it. 

Thus, today, finding ways to restore normal 

brain function after it has been changed 

by drugs is a main goal of NIDA research. 

(See “NIDA Pursues Many Approaches to 

Reversing Methamphetamine’s Neurotoxic 

Effects,” NIDA NOTES, Vol. 15, No. 4). 

This goal involves two challenges:

• To reverse the brain changes 

that underlie addiction, and 

• To roll back the loss of cognitive and motor functions that 

occurs when drugs damage 

and kill brain cells. 

To approach the first challenge, 

NIDA gives top priority to mapping the sequence of neurobiological changes that takes 

place during the transition from voluntary to compulsive 

drug taking. Researchers have already identified some 

of the changes involved in two of the key phenomena 

associated with addiction: drug tolerance and drug craving. With respect to drug tolerance—the abuser’s need 

for increasing amounts of drug to achieve the desired 

effect—we now know that drugs significantly increase the 

availability of dopamine, a neurotransmitter that activates 

the brain’s pleasure circuits. When cells are exposed to 

repeated surges of dopamine due to chronic drug abuse, 

they may eventually become less responsive to dopamine 

signals. In recent months, researchers presented evidence 

pointing to a specific change in the dopamine receptor 

molecule that may be instrumental in this loss of responsiveness.

As for drug craving—the intense hunger that drives addicts 

to seek drugs despite the strong likelihood of adverse 

consequences-researchers have shown that it is related to 

widespread alterations in brain activity, but especially to 

changes in the nucleus accumbens area of the forebrain. 

An important type of craving experienced by addicts, 

called cue-induced craving, occurs in the presence of 

people, places, or things that they have previously associated with their drug taking. Brain 

imaging studies have shown that cue-induced 

craving is accompanied by heightened activity in the forebrain, the anterior cingulate, 

and the prefrontal cortex—key brain areas 

for mood and memory. A next step in understanding craving will be to learn what brain 

processes tie drug abusers’ memories 

so strongly to the desire to take drugs.

Researchers have also made a solid start 

toward meeting the second challenge posed 

by drugs’ effects on the brain: the restoration 

of cognitive and motor capabilities 

lost because of drug abuse. 

Studies have identified specific 

brain changes that are likely 

causes of the persistent losses 

that are caused by many drugs 

of abuse. For example, they have 

shown that:

• Inhalants can produce a variety 

of deleterious effects—including reduced vision and 

hearing, impaired movement, and lowered cognitive 

ability, sometimes to the point of dementia-by stripping the protective myelin sheath from brain fibers; 

• Cocaine causes repeated microscopic strokes in the 

brain, leading to dead spots in the brain’s nerve 

circuitry; 

• Methylenedioxymethamphetamine (MDMA) damages serotonin-producing neurons, which play a direct 

role in regulating aggression, mood, sexual activity, 

sleep, and sensitivity to pain; 

• Methamphetamine amplifies apoptosis—the normal 

process by which the brain culls defective cells—to 

the point where it also eliminates healthy cells. 

In extreme cases, drugs can cause such severe destruction 

that users become severely disabled. For example, some 

methamphetamine abusers have developed a syndrome 

marked by uncontrollable tremors similar to those seen in 

Parkinson’s disease. The method of heroin self-administration by inhalation known as “chasing the dragon” has 

rendered some young people nearly comatose with large 

brain lesions.

Finding ways to restore normal 

brain function after it has been 

changed by drugs is a main 

goal of NIDA research. 
87

To counteract the drug-related 

brain disruptions that produce 

addiction and cognitive and motor 

problems, researchers are seeking to mobilize two important 

brain capacities. First, under the 

right circumstances, the brain can 

self-repair some types of damage. 

Second, the brain is plastic—that 

is, when cell losses disrupt the 

neural circuits that the brain has been using for a specific 

function, it can learn to use other circuits to perform 

that function. Plasticity is extremely powerful, as shown 

by numerous patients’ recoveries from extensive cerebral 

injuries.

Treatments that alleviate some drug-related brain damage are already here. In fact, in recent months, researchers 

have demonstrated that methadone therapy ameliorates a 

particular biochemical abnormality in the brains of opiate 

abusers. The longer patients stayed in therapy, the more 

this aspect of their brain biochemistry approached normal. NIDA is currently supporting several similar projects 

that use new brain imaging techniques to evaluate the full 

impact of current medication and behavioral treatments 

on brain neurology and biochemistry. Ultimately, such 

imaging is likely to become an important tool for assessing 

patients’ treatment needs, their progress in treatment, and 

the effectiveness of treatment approaches.

Ultimately, researchers envision a 

two-stage process for helping restore 

drug abusers’ impaired abilities. 

Interventions will be used first to stop 

ongoing brain damage and repair 

damaged brain cells, and then to 

retrain the brain. The rationale for 

this approach is that repairing the 

brain first will restore lost mental 

resources and capacities that patients 

then can apply in further treatment. Both behavioral and 

medication treatments may prove to be effective for both 

stages of treatment. The first stage may benefit from medications already in use to treat neurological conditions that 

produce brain abnormalities similar to those associated 

with abuse of some drugs. For example, deprenyl (used 

in Parkinson’s disease) and acetylcysteine (being tested in 

Lou Gehrig’s disease) have the potential to help people 

with drug-related neurological damage.

The new knowledge produced by drug abuse research not 

only brings present goals closer, it also makes possible new 

and farther-reaching goals. Today we are applying our 

understanding of brain processes to the development of 

treatments that directly target the brain mechanisms of 

addiction and to the alleviation or reversal of drug-related 

brain disruption. What we learn in that effort will 

undoubtedly lead to even more powerful insights and 

strategies for reducing drug abuse and addiction and their 

health and social consequences. 

Interventions will be used 

first to stop ongoing brain 

damage and repair damaged brain cells, and then to 

retrain the brain. 
Research Findings

88

Drug Abuse Treatment Programs Make Gains in Methadone 

Treatment and HIV Prevention

By Steven Stocker, NIDA NOTES Contributing Writer 

Volume 15, Number 3 (August 2000)

Drug abuse treatment programs have substantially 

improved their methadone treatment practices and 

increased their HIV prevention efforts since the late 

1980s, according to recent NIDA-funded research. These 

improvements appear to be partly 

the result of NIDA’s efforts to 

improve drug abuse treatment 

and HIV/AIDS outreach.

Clinical studies conducted in the 

late 1980s and early 1990s indicated that methadone treatment 

is more likely to reduce heroin 

use if the dose level is at least 

60 milligrams per day (mg/day), 

if patients are given a voice in 

determining their dose levels, 

and if no restriction is placed on 

treatment duration. Subsequent 

research, however, indicated that the majority of the 

Nation’s methadone treatment facilities were dispensing 

methadone doses less than 60 mg/day, were not giving 

patients a voice in dosage decisions, and were encouraging 

patients to stop taking methadone in 6 months or less.

In response to this situation, NIDA and other Federal 

agencies took steps to improve methadone treatment. 

NIDA funded an Institute of Medicine report that recommended changes in heroin addiction treatment practices 

and their regulation. NIDA also funded the development 

of a quality assurance program that evaluates methadone 

treatment facilities in terms of patient outcomes. In addition, the Center for Substance Abuse Treatment (CSAT) 

developed a set of methadone treatment guidelines and 

distributed them to State substance abuse agencies and 

treatment providers around the country.

To determine whether these efforts were in fact improving methadone treatment practices, in 1995 Dr. Thomas 

D’Aunno of the University of Chicago and his colleagues 

at the University of Michigan in Ann Arbor collected data 

from 116 methadone treatment facilities located throughout the country and compared them with data collected 

on these same facilities in 1988 and 1990. Results showed 

improvement during the 7-year period, particularly 

regarding methadone dosage. The average dose was 

45 mg/day in 1988 and 46 mg/day in 1990. By 1995, 

however, the average dose had increased to 59 mg/day. 

Also, more programs were allowing patients to participate 

in dosage decisions, and more programs were waiting at 

least a year before encouraging 

patients to stop taking methadone.

“Although these results show that 

methadone treatment facilities 

have made substantial improvements, we still need to make more 

progress,” says Dr. D’Aunno. 

“We found an average dose of 59 

mg/day in our sample of treatment facilities, but recent research 

indicates that doses between 80 

and 100 mg/day may be the most 

effective in reducing heroin use.” 

(See “High-Dose Methadone 

Improves Treatment Outcomes,” NIDA NOTES, Vol. 14, 

No. 5).

The study found differences in treatment practices in 

different areas of the country and for different population groups. Dr. D’Aunno suggests that efforts targeted 

at particular groups of programs may be a further step to 

improve treatment.

Dr. Bennett Fletcher of NIDA’s Division of 

Epidemiology, Services, and Prevention Research agrees 

that efforts to improve methadone treatment practices 

should continue but adds that misunderstandings some 

patients have about methadone may also contribute to 

the problem. For example, he says, some patients attribute adverse effects to methadone that it actually does 

not cause. “These patients may develop medical or dental problems while taking heroin, but they don’t notice 

them either because of heroin’s analgesic effect or because 

they are distracted by withdrawal symptoms during 

abstinence,” he says. “Once they’re in methadone treatment and physiologically stabilized, the medical or dental 

problems are unmasked. It is easy to blame methadone 

for these problems, when in fact they were pre-existing.” 

These misunderstandings may cause some patients to 

request lower methadone doses or to stop methadone prematurely, says Dr. Fletcher.

The treatment facilities most 

likely to conduct HIV prevention 

activities were those that had 

more patients at high risk of HIV 

infection, more resources, and 

lower patient-to-staff ratios.
89

The Bandwagon Effect

Dr. D’Aunno, along with colleagues at the University of 

Iowa in Iowa City and the Centers for Disease Control 

and Prevention in Atlanta, also evaluated treatment facilities’ HIV prevention efforts, including HIV testing, counseling, and outreach. For this project, they used data collected from the sample of methadone treatment facilities 

plus other substance abuse treatment facilities for a total 

of 618 facilities.

As with the methadone treatment practices, the investigators found that the facilities had made substantial 

improvements in their HIV prevention efforts over the 

period from 1988 to 1995. In both 1988 and 1990, only 

39 percent of the facilities provided HIV testing and 

counseling, but by 1995, 61 percent were providing these 

services. Also, 51 percent of the facilities in 1988 and 

65 percent in 1990 were engaging in HIV outreach, 

but by 1995 this had increased to 75 percent.

The investigators found that the treatment facilities most 

likely to conduct HIV prevention activities were those 

that had more patients at high risk of HIV infection, 

more resources, and lower patient-to-staff ratios. Also, 

these facilities generally were publicly rather than privately 

funded and had clinical supervisors who supported HIV 

prevention practices.

Perhaps the most important factor in promoting HIV 

prevention practices, however, seemed to be pressure 

from people in the drug abuse treatment field. “When the 

HIV epidemic first started, many treatment facilities were 

uncertain how to react,” says Dr. D’Aunno. “As some 

facilities began conducting HIV testing, counseling, and 

outreach, pressure began to mount for other facilities to 

do the same. This eventually created a bandwagon effect.”

NIDA helped get the bandwagon going by supporting 

research programs in which scientists worked together 

with practitioners to develop effective HIV/AIDS outreach techniques, according to Dr. D’Aunno. “These 

programs set a good example for treatment providers,” 

he says. “The providers saw local researchers and other 

providers working together on HIV prevention, and they 

decided to follow their lead.”

Sources

• D’Aunno, T.; Folz-Murphy, N.; and Lin, X. Changes 

in methadone treatment practices: Results from a 

panel study, 1988-1995. American Journal of Drug 

and Alcohol Abuse 25(4):681-699, 1999. 

• D’Aunno, T.; Vaughn, T.E.; and McElroy, P. An 

institutional analysis of HIV prevention efforts by the 

Nation’s outpatient drug abuse treatment units. 

Journal of Health and Social Behavior 40(2):175-192, 

1999. 
Research Findings

90

Adding More Counseling Sessions and 12-Step Programs Can 

Boost Drug Abuse Treatment Effectiveness 

By Robert Mathias, NIDA NOTES Staff Writer 

Volume 14, Number 5 (December, 1999)

Drug abuse treatment programs can significantly increase 

the likelihood that patients will stay in treatment and 

remain abstinent by offering them more group and individual counseling opportunities and encouraging them 

to participate in complementary 12-step programs, such 

as Narcotics Anonymous, according to NIDA-supported 

research.

A series of studies by Dr. Robert Fiorentine of the 

University of California, Los Angeles (UCLA) and his 

colleagues from the UCLA Drug Abuse Research Center 

has been looking at how individual treatment components 

affect patient outcomes. One study found that patients 

who attended more group and individual counseling sessions had significantly lower levels of drug use during and 

after treatment than those who participated less frequently. Even among patients who completed the treatment 

program, those who participated more frequently in 

counseling had lower rates of relapse than those who 

participated less. 

Increasing Counseling Opportunities

Dr. Fiorentine then examined whether treatment programs could improve their effectiveness by providing 

more opportunities for patients to participate in counseling. This study assessed the treatment outcomes of 330 

patients in 26 Los Angeles outpatient programs. Seventeen 

programs had added treatment services and increased 

counseling opportunities by hiring additional counselors.

This study found that patients in the enhanced programs 

attended about four more group counseling sessions 

and one more individual counseling session each month 

than did patients in comparison programs. Patients in 

enhanced programs also used drugs 40 percent less than 

did patients in comparison programs in the 6 months 

following an initial in-treatment assessment; in the 

last month, they used drugs 60 percent less. When the 

researchers examined whether patient characteristics or 

other treatment services provided by enhanced programs 

may have affected these results, they found that the frequency of patients’ participation in individual and group 

counseling accounted for virtually all of the differences in 

post-treatment drug use.

This study suggests that even minimal increases in counseling opportunities may produce impressive gains in 

treatment outcomes, the researchers note. By hiring only 

one or two additional counselors, enhanced programs 

could reduce their counselors’ caseloads and offer more 

group and individual counseling sessions, Dr. Fiorentine 

says. “It was only a few more sessions per week but, since 

patient attendance in these sessions often depends on session availability, it made a difference,” he says.

Adding 12-Step Programs

Because many patients in Los Angeles area treatment 

programs attend 12-step programs either on their own 

or as part of their treatment regimen, Dr. Fiorentine and 

his colleagues also examined the relationship between 

Even minimal increases in counseling 

opportunities may produce impressive 

gains in treatment outcomes.
91

participation in such programs and the effectiveness of 

drug abuse treatment. One study found that patients who 

attended at least one 12-step meeting per week after 

completing drug abuse treatment had much lower levels 

of drug use than those who participated less frequently 

or not at all. In this study, the researchers interviewed 

262 patients in 26 Los Angeles area drug abuse treatment 

programs during treatment and 6 and 24 months later. 

Almost half of these patients had attended a 12-step 

meeting in the 6 months preceding the last interview.

During this 6-month period, only about 22 percent of 

weekly 12-step participants had used an illicit drug. By 

contrast, 44 percent of those who attended 12-step programs less than once a week or not at all during that period 

had used an illicit drug. Additional analyses indicated that 

the more favorable outcomes of frequent 12-step participants could not be attributed to differences in motivation 

or to other posttreatment activities, such as attending 

other aftercare programs. Weekly 12-step participants did 

score slightly higher than nonparticipants on a scale of 

self-reported measures of recovery motivation. However, 

statistical analyses indicated the differences in motivation 

accounted for little if any of the more favorable outcomes 

for frequent 12-step participants. The important difference 

between the two groups was not recovery motivation but 

at least weekly 12-step participation, the researchers say.

This study’s findings suggest that 12-step programs can 

serve as a useful and inexpensive aftercare resource that 

can help many patients to maintain abstinence from drugs 

and alcohol after they complete drug abuse treatment, say 

the researchers.

Findings from another study by Dr. Fiorentine indicate 

that participation in 12-step programs before and during 

drug abuse treatment also may benefit patients’ treatment 

engagement and recovery. In this study, more than twothirds of 419 patients who entered outpatient treatment 

programs in Los Angeles during a 2-month period were 

attending 12-step meetings in the 3 months before they 

entered treatment. About 45 percent were attending meetings at least once a week.

Patients who attended 12-step meetings regularly before 

entering drug abuse treatment stayed in treatment longer 

and were more likely to complete the treatment program and participate in posttreatment 12-step programs, 

the study found. Moreover, an assessment conducted 

8 months after the initial intake interview showed that 

patients who attended 12-step meetings at least once a 

week while they were participating in conventional drug 

abuse treatment had significantly higher rates of abstinence than patients who participated in only one or the 

other of those programs.

These findings suggest an “additive effect” on the recovery 

process from concurrent participation in drug abuse treatment and 12-step programs, Dr. Fiorentine says. “You get 

a better outcome with both than if you do either alone,” 

he concludes.

Sources

• Fiorentine, R. After drug treatment: Are 12-step programs effective in maintaining abstinence? American 

Journal of Drug and Alcohol Abuse 25(1):93-116, 

1999.

• Fiorentine, R. and Anglin, M.D. Does increasing the 

opportunity for counseling increase the effectiveness 

of outpatient drug treatment? American Journal of 

Drug and Alcohol Abuse 25(3):369-382, 1997.

• Fiorentine, R. and Anglin, M.D. More is better: 

Counseling participation and the effectiveness of 

outpatient drug treatment. Journal of Substance Abuse 

Treatment 13:341-348, 1996.

• Fiorentine, R. and Hillhouse, M. Drug treatment and 

twelve-step program participation: The additive 

effects of integrated recovery activities. Journal of 

Substance Abuse Treatment 18(1):65-74, 2000. 
Research Findings

92

The State of the Art in Drug Addiction Treatment

By NIDA Director Dr. Alan I. Leshner 

Volume 14, Number 5 (December 1999)

NIDA’s recent publication, Principles of Drug 

Addiction Treatment: A Research-based Guide, 

distills the lessons of 25 years of scientific 

investigation. Principles is written for health 

care providers, to stimulate their awareness 

of the variety of effective approaches to drug 

treatment. It is also for patients and potential patients and their families, to help them 

understand the nature of addiction and to 

tell them about scientifically based treatments 

and what to expect if they enter treatment. 

And it serves planners and policymakers as 

well, enabling them to make informed 

decisions concerning treatment 

programs.

In short, this book is for you. That 

is why NIDA mailed a copy in 

October to every NIDA NOTES

reader in the United States. If you 

have not yet read yours, I urge you 

to do so. If you did not receive a 

copy or want additional copies to 

pass on to friends or colleagues, you 

can obtain copies from the National 

Institute on Drug Abuse’s DRUG 

PUBS Research Dissemination 

Center, Educational Materials Online Catalog’s Web 

site drugpubs.drugabuse.gov.

Based on a yearlong review of treatment research, 

Principles describes where we stand today in our quest 

for the most effective, replicable treatments for drug 

abuse. The book contains many important messages, 

but one is central.

Treatment is effective. Scientifically based drug addiction 

treatments typically reduce drug abuse by 40 percent to 

60 percent. These rates are not ideal, of course, but they 

are comparable to compliance rates seen with treatments 

for other chronic diseases such as asthma, hypertension, 

and diabetes. Moreover, treatment markedly reduces 

undesirable consequences of drug abuse and addiction—

such as unemployment, criminal activity, and HIV/AIDS 

and other infectious diseases—whether or not patients 

achieve complete abstinence. Research has shown that 

every $1 invested in treatment saves $4 to $7 in costs 

related to drug abuse.

That treatment is effective will not be 

news to treatment providers or to the tens 

of thousands of individuals and families who have benefited from treatment. 

Unfortunately, many members of the public 

still mistakenly doubt that treatment can 

help someone overcome addiction, perhaps 

because, as Principles explains, recovery 

from addiction can be a long-term process 

and frequently requires multiple episodes of 

treatment. To these people, the message 

of Principles is: We have the tools, let’s do 

the job.

By describing the current state 

of the art, Principles also clarifies 

the many challenging research 

pathways that remain to be traversed on the way to our goal of 

fully effective treatment for every 

patient. To cite just a few of the 

more pressing objectives, we 

need to:

• Understand the complete behavioral and biological mechanisms 

of addiction; 

• Obtain a full picture of the transition from drug use to drug addiction and the stages 

of recovery in order to fashion optimal treatments for 

patients at every point along that trajectory; 

• Understand better how gender affects vulnerability to 

drug addiction and the response to treatment in order 

to more appropriately tailor treatments for men and 

women; 

• Develop additional medications for treating opiate 

addiction and effective medications for addiction to 

stimulants such as cocaine and methamphetamine; 

• Continue to test the effectiveness of treatments in 

real-life community-based settings. 

NIDA is adjusting its organizational structure and has 

instituted key procedures to expedite the next stage of 

our treatment research journey. As I write, the Institute is 

completing the creation of a new Division of Treatment 

Research and Development (DTRD). The new Division 

Based on a year-long review of 

treatment research, Principles 

describes where we stand 

today in our quest for the most 

effective, replicable treatments 

for drug abuse. 
93

will facilitate research on combined medication and 

behavioral treatments, which appears to be an essential 

strategy for improving many patients’ chances of successful treatment outcomes. 

With the support of its Medications Development 

Division, one of DTRD’s predecessors, NIDA has developed cooperative links with the pharmaceutical industry 

that enable NIDA-supported researchers to obtain proprietary chemical compounds for testing as possible medications for drug abuse. As a first fruit of these partnerships, 

a new cocaine “vaccine” is currently being tested in a 

large-scale clinical trial. Based on NIDA-supported basic 

studies, this new medication appears to reduce the desire 

to use cocaine by blocking the drug’s euphoric effects. 

NIDA also is exploring ways for new medications to reach 

more of those in need. The demonstrated effectiveness of 

buprenorphine and naloxone in treating opiate addiction, 

for example, suggests that these drugs may be safely dispensed by physicians in controlled settings. 

With respect to behavioral therapies, NIDA has established a three-stage process for developing, evaluating, and 

introducing new approaches into mainstream clinical use. 

The potential of each proposed new behavioral treatment 

is first explored in a small pilot study. If the preliminary 

data are promising, the treatment is tested in a full-scale 

clinical trial. If the trial demonstrates efficacy, clinicians 

take the treatment out of the research setting and adapt it 

as necessary for mainstream use. This new model establishes the first clear benchmarks for testing, comparing, 

and implementing behavioral treatments. To date, two 

new treatments have passed the preliminary stage of testing and moved on to the clinical trials stage. 

As regular readers of NIDA NOTES are aware, the largest 

initiative in NIDA’s history is focused on treatment. This 

is the National Drug Abuse Treatment Clinical Trials 

Network (CTN), in which research centers ally with 

nearby community treatment programs to set research 

goals and participate in large-scale multisite clinical trials. 

NIDA recently announced the establishment of the first 

five CTN locations. Ultimately, the CTN will provide 

a nationwide coordinating infrastructure with sufficient 

patient numbers and diversity to enable scientists to optimize treatment effectiveness by matching treatments with 

appropriate patient groups. 

There is a pattern in scientific research in which knowledge and techniques are slowly, painstakingly developed 

until they reach a critical mass that makes possible a more 

rapid and direct approach to problem solving. This first 

edition of Principles reflects the power of this pattern of 

progress to produce epochal advances in public health and 

welfare. With well-defined questions and powerful new 

technologies and research techniques coming on line every 

year, we do not expect to wait very long before publishing 

the second edition of Principles. 
Research Findings

94

Thirteen Principles of Effective Drug Addiction Treatment

Volume 14, Number 5 (December 1999)

1. No single treatment is appropriate for all individuals. Matching treatment settings, interventions, 

and services to each patient’s problems and needs 

is critical. 

2. Treatment needs to be readily available.

Treatment applicants can be lost if treatment is not 

immediately available or readily accessible. 

3. Effective treatment attends to multiple needs

of the individual, not just his or her drug use. 

Treatment must address the individual’s drug use 

and associated medical, psychological, social, vocational, and legal problems. 

4. Treatment needs to be flexible and to provide 

ongoing assessments of patient needs, which may 

change during the course of treatment. 

5. Remaining in treatment for an adequate period 

of time is critical for treatment effectiveness. The 

time depends on an individual’s needs. For most 

patients, the threshold of significant improvement is 

reached at about 3 months in treatment. Additional 

treatment can produce further progress. Programs 

should include strategies to prevent patients from 

leaving treatment prematurely. 

6. Individual and/or group counseling and other 

behavioral therapies are critical components 

of effective treatment for addiction. In therapy, 

patients address motivation, build skills to resist 

drug use, replace drug-using activities with constructive and rewarding nondrug-using activities, 

and improve problem-solving abilities. Behavioral 

therapy also facilitates interpersonal relationships. 

7. Medications are an important element of treatment for many patients, especially when combined 

with counseling and other behavioral therapies. 

Methadone and levo-alpha-acetylmethadol (LAAM) 

help persons addicted to opiates stabilize their lives 

and reduce their drug use. Naltrexone is effective 

for some opiate addicts and some patients with cooccurring alcohol dependence. Nicotine patches or 

gum, or an oral medication, such as bupropion, can 

help persons addicted to nicotine. 

8. Addicted or drug-abusing individuals with 

coexisting mental disorders should have both 

disorders treated in an integrated way. Because 

these disorders often occur in the same individual, 

patients presenting for one condition should be 

assessed and treated for the other. 

9. Medical detoxification is only the first stage of 

addiction treatment and by itself does little to 

change long-term drug use. Medical detoxification 

manages the acute physical symptoms of withdrawal. For some individuals it is a precursor to effective 

drug addiction treatment. 

10.Treatment does not need to be voluntary to be 

effective. Sanctions or enticements in the family, 

employment setting, or criminal justice system can 

significantly increase treatment entry, retention, and 

success. 

11.Possible drug use during treatment must be 

monitored continuously. Monitoring a patient’s 

drug and alcohol use during treatment, such as 

through urinalysis, can help the patient withstand 

urges to use drugs. Such monitoring also can provide early evidence of drug use so that treatment 

can be adjusted. 

12.Treatment programs should provide assessment 

for HIV/AIDS, hepatitis B and C, tuberculosis 

and other infectious diseases, and counseling to 

help patients modify or change behaviors that place 

them or others at risk of infection. Counseling can 

help patients avoid high-risk behavior and help 

people who are already infected manage their illness. 

13.Recovery from drug addiction can be a long-term 

process and frequently requires multiple episodes of 

treatment. As with other chronic illnesses, relapses 

to drug use can occur during or after successful 

treatment episodes. Participation in self-help support programs during and following treatment often 

helps maintain abstinence. 

Principles of Drug Addiction Treatment: A Research-based 

Guide can be obtained by visiting the NIDA DRUG 

PUBS Research Dissemination Center’s Web site at 

drugpubs.drugabuse.gov.

More than two decades of scientific research have yielded a set of fundamental principles that characterize effective 

drug abuse treatment. These 13 principles, which are detailed in NIDA’s new research-based guide, Principles of Drug 

Addiction Treatment: A Research-based Guide, are:
Research Findings

95

Medications Reduce Incidence of Substance Abuse Among 

ADHD Patients 

By Steven Stocker, NIDA NOTES Contributing Writer 

Volume 14, Number 4 (November 1999)

Attention-deficit hyperactivity disorder (ADHD) causes 

difficulties in paying attention, keeping still, and suppressing impulsive behaviors. It can lead to problems 

in school and on the job and create tensions with family members and other people. In addition, research has 

shown that children with ADHD have an elevated risk of 

becoming abusers of drugs and alcohol. Studies that have 

tracked children to adulthood have found higher rates of 

transition to abuse among those with ADHD compared 

to those without the disorder. Conversely, studies with 

adult substance abusers, particularly cocaine abusers, have 

found that when they were children a high percentage had 

ADHD that was undiagnosed and therefore untreated.

NIDA-supported researchers have been trying to learn 

why ADHD increases the risk of drug and alcohol abuse. 

Two possible explanations have been suggested. First, the 

disorder itself may be responsible. Alternatively, the medications used to treat the disorder may be to blame.

ADHD is usually treated with behavioral therapy and 

prescription stimulants, especially Ritalin® (methylphenidate), Dexedrine®, or Adderall®. Such therapy frequently 

reduces symptoms, but some clinicians have feared that 

giving prescription stimulants to children may get them in 

the habit of taking stimulants, and, as a result, they may 

be more likely to take illicit stimulants, such as cocaine 

and methamphetamine. Another possibility is that the use 

of prescription stimulants for treating ADHD may sensitize the brain to the rewarding properties of stimulants, 

and, as a result, patients who use illicit stimulants may be 

more likely to become addicted to them.

Some children treated for ADHD with stimulant medications experience adverse effects, such as tics or loss of 

appetite. These children may be treated instead with tricyclic antidepressants (TCAs), a class of medications that 

includes imipramine, desipramine, and nortriptyline. Just 

as with mild stimulants, some clinicians are concerned 

that giving these mood-altering medications to children 

may get them in the habit of taking drugs to feel better 

and so they may be more at risk of using illicit drugs.

If ADHD treatment medications increase the risk of 

drug abuse, then using them might do more harm than 

good over the course of the child’s lifetime. However, 

two new NIDA-supported studies suggest that treatment 

medications may be part of the solution to drug abuse in 

ADHD, rather than the problem.

One study found that children who were medicated for 

their ADHD were less likely to become substance abusers during 4 years of followup than were children with 

ADHD who were not medicated. The other study found 

that administering an ADHD medication to adult cocaine 

abusers with the disorder reduced their cocaine use.

Boys Treated for ADHD Abuse Drugs Less Than 

Untreated Boys

Researchers at Massachusetts General Hospital and the 

Harvard Medical School, both in Boston, compared the 

incidence of substance abuse and dependence in 56 boys 

with ADHD who were being treated with either stimulants or TCAs at the beginning of the study, 19 boys with 

ADHD who were not receiving any medications, and 137 

boys without ADHD. All boys were Caucasian and were 

Children with ADHD often have trouble concentrating and keeping still, which can lead to problems in school. 
96

followed for 4 years and then evaluated for abuse of or 

dependence on marijuana, alcohol, hallucinogens, stimulants, or cocaine. At the time of evaluation, the boys were 

at least 15 years old.

Treating ADHD with medications appeared to reduce the 

tendency to abuse drugs and alcohol. While 75 percent of 

the unmedicated ADHD boys had started abusing these 

substances in the previous 4 years, this was true of only 25 

percent of the medicated ADHD boys and 18 percent of 

the boys without ADHD. The researchers calculated that 

treating ADHD with medications reduced the risk of substance abuse or dependence by 84 percent.

Dr. Joseph Biederman, the principal investigator of the 

study, calls this very important information for the field of 

pediatrics. “These are the first data to refute the argument 

that ADHD medications increase the risk that children 

will become addicts,” he says. “There have been studies 

consistent with these findings for many years, but now 

we have solid statistical evidence that these medications 

decrease, rather than increase, vulnerability to addiction, 

at least in adolescent Caucasian boys.”

Why treatment with medications should reduce the incidence of substance use disorders in boys with ADHD 

is not known, says Dr. Biederman, just as what causes 

ADHD and how medications reduce ADHD symptoms 

are also unknown. “I can only speculate that by reducing 

ADHD symptoms, the medications allow the children to 

interact better with their families and friends and to perform better in school,” he says. “As a result, they are less 

likely to be ridiculed and rejected by other children and 

to fail in school. Because of this, they are less likely to be 

depressed and to take drugs in an attempt to treat their 

depression.” He says that another reason may be that the 

medications reduce the tendency of ADHD children to 

be impulsive, which often leads them to engage in risky 

activities, such as taking drugs.

Other researchers have reported that some adult cocaine 

abusers with childhood histories of ADHD state that 

when they first started using cocaine, the drug initially 

improved their ADHD symptoms. Their concentration 

improved, they were less impulsive, and they felt calmer. 

This would suggest that young people with ADHD who 

abuse cocaine and other stimulants may be doing so to 

self-medicate their ADHD symptoms rather than to treat 

depression resulting from rejection and failure.

“In some cases, young people with ADHD are not properly diagnosed and treated, and, as a result, they have 

terrible problems,” says Dr. Arthur Horton of NIDA’s 

Division of Treatment Research and Development 

(DTRD). “Their lives are not going well, so they try different things to make themselves feel better. They don’t 

know that Ritalin® will alleviate their symptoms. If they 

happen to try cocaine, they might find that it initially 

makes them more focused and able to deal with life, so 

they keep taking it, and that’s how they get hooked.”

DTRD Director Dr. Frank Vocci points out that more 

research needs to be done before definite conclusions can 

be drawn about the relationship between ADHD therapy 

and substance abuse. “As it stands, this study clearly supports the idea that medications protect individuals with 

ADHD from becoming substance abusers during childhood and adolescence,” he says. “However, whether or not 

they become substance abusers when they reach adulthood 

is still an open question.”

Dr. Biederman says that his group is continuing to collect data on his sample as they age. Another followup 

study is currently under way on the young men, who are 

now between 16 and 27 years old. This study should help 

answer the question of whether ADHD medication therapy can protect against substance abuse in late adolescence 

and early adulthood. The researchers are also following 

a group of girls with ADHD and a comparison group of 

girls without ADHD. A key question to be answered will 

be whether gender differences exist in the effects of stimulants, including the effects on substance abuse.

Treatment That Includes Methylphenidate Helps 

Adult Cocaine Abusers With ADHD

In addition to helping protect children with ADHD from 

becoming substance abusers, methylphenidate may also 

help adult cocaine abusers with ADHD reduce their drug 

use. In a pilot study, Dr. Frances Levin and researchers at 

Columbia University in New York City gave methylphenidate for up to 12 weeks to 12 adult cocaine abusers with 

ADHD. Patients also received individual weekly relapse 

prevention therapy, which involved identifying situations 

in which they were likely to return to cocaine use and 

developing strategies to avoid cocaine use in these situations. Of the 12 patients who entered the study, 7 could 

be reached for a 3-month assessment. Patients reported a 

reduction in ADHD symptoms, cocaine use, and craving; 

urine tests confirmed that their cocaine use had in fact 

decreased significantly.

At present, Dr. Levin cannot say whether methylphenidate, the behavioral therapy, or a combination of both was 

responsible for the positive results. To answer this question and to determine whether these preliminary results 

can be reproduced among other cocaine abusers with 

ADHD, she is conducting a large clinical trial in which 

neither the patients nor their therapists know whether the 

patients are receiving methylphenidate or placebo.
97

Sources

• Biederman, J., et al. Pharmacotherapy of attentiondeficit/hyperactivity disorder reduces risk for 

substance use disorder. Pediatrics 104(2):e20, 1999 

(www.pediatrics.org).

• Gawin, F.; Riordan, C.; and Kleber, H. 

Methylphenidate treatment of cocaine abusers without attention deficit disorder: A negative report. 

American Journal of Drug and Alcohol Abuse 11(3-

4):193-197, 1985.

• Levin, F.R., Evans, S.M.; McDowell, D.M.; and 

Kleber, H.D. Methylphenidate treatment for cocaine 

abusers with adult attention-deficit/hyperactivity 

disorder: A pilot study. Journal of Clinical Psychiatry

59(6):300-305, 1998.

• Levin, F.R., and Kleber, H.D. Attention-deficit/

hyperactivity disorder and substance abuse: 

Relationships and implications for treatment. 

Harvard Review of Psychiatry 2:246-258, 1995. 
Research Findings

98

Drug Abuse and Mental Disorders: Comorbidity Is Reality

By NIDA Director Dr. Alan I. Leshner 

Volume 14, Number 4 (November 1999)

A quarter century of basic and clinical research 

has provided us with a substantial number of 

scientifically developed and tested pharmacological and behavioral techniques for treating 

drug abuse and addiction. A main thrust of 

NIDA’s current research is to discover which 

combinations of treatments and services work 

best for individual patients with particular constellations of problems. The goal is to customize treatment for every patient, including those 

with coexisting problems such as multiple drug 

abuse, drug abuse-related infectious diseases, 

histories of sexual abuse, or homelessness.

Drug abusers who have concurrent, or comorbid, mental health 

problems are at the top of the list 

of those who will benefit from 

this research, for two reasons. 

First, they are numerous. Recent 

epidemiologic studies have shown 

that between 30 percent and 60 

percent of drug abusers have concurrent mental health diagnoses 

including personality disorders, 

major depression, schizophrenia, 

and bipolar disorder. Second, drug 

abusers with mental illness comorbidity are more likely to engage in 

behaviors that increase risk for HIV/AIDS. For example, 

two studies of injecting drug abusers have found that 

antisocial personality disorder (APD) is associated with a 

higher frequency of needle sharing.

In order to direct treatment and services research to where 

it is most needed, NIDA supports epidemiologic studies 

of mental health comorbidities. The results to date suggest 

that the most common are personality disorders including APD and borderline personality disorder; anxiety 

disorders including post-traumatic stress disorder (PTSD); 

and depression. Some evidence suggests that men who 

use drugs are more likely to have APD, while women and 

minorities are more likely to have depression or PTSD. 

While people with schizophrenia do not constitute a large 

portion of the drug-abusing population, an extraordinarily 

high percentage of people with this disease abuse drugs.

A concurrent mental disorder can complicate drug abuse treatment in a multitude 

of ways. For example, research suggests 

that clinically depressed individuals have 

an exceptionally hard time resisting environmental cues to relapse—that is, urges 

to resume drug taking that commonly 

occur when abstinent addicts encounter 

people, places, or things associated with 

their previous drug use. In some cases, 

treatment for mental disorders must be 

adjusted because of concurrent drug 

abuse. For example, opiate users with 

anxiety disorders are 

considered poor candidates for standard therapy 

with anti-anxiety drugs of 

the benzodiazepine class 

because these drugs can 

cause a second addiction.

NIDA-supported researchers have identified effective 

ways to tailor treatment for 

some patients with dual 

diagnoses. In one study, 

opiate addicts with APD 

responded better when 

standard contingency management therapy was modified. In the standard type of 

this therapy, patients receive small rewards for abstinence 

that become progressively greater the longer abstinence 

is maintained. In the modified version, treatment professionals gave more frequent rewards for desirable behaviors, such as attending scheduled counseling sessions and 

testing clean for drugs.(See “Specialized Approach Shows 

Promise for Treating Antisocial Drug Abuse Patients,” 

NIDA NOTES, Vol. 11 No. 4). In another study, drug 

craving was reduced among teenage cocaine abusers with 

bipolar disorder who receive lithium, and in depressed 

heroin abusers who were treated with imipramine. (See 

“Treating Mood Disorders in Drug Abuse Patients,” 

NIDA NOTES, Vol. 13 No. 6). In this issue of NIDA 

NOTES, we report on promising results with methylphenidate and antidepressants in children with attention-deficit/ hyperactivity disorder (ADHD) and with 

Recent epidemiologic studies have 

shown that between 30 percent and 

60 percent of drug abusers have 

concurrent mental health diagnoses including personality disorders, 

major depression, schizophrenia, 

and bipolar disorder. 
99

methylphenidate in adult cocaine abusers with ADHD. 

(See “Medications Reduce Incidence of Substance Abuse 

Among ADHD Patients,” NIDA 

NOTES, Vol. 14, No. 4).

Just as the co-occurrence of drug 

abuse and mental health problems presents special problems 

for treatment, so does it also 

for research. The problems arise 

in part because drug abuse and 

other mental health disorders can 

intertwine in several ways. For 

example, successful treatment of 

cocaine addiction often also dispels concurrent depression, while nicotine addicts’ 

depression commonly persists after successful smoking 

cessation treatment. Such variations make it difficult 

to generalize treatment research findings across large 

patient groups.

As a result, progress has been made in relatively small 

increments. Another problem facing researchers is that a 

study population that is ostensibly uniform because all 

individuals have the same drug abuse and mental health 

disorders may actually be nonuniform. The reason is 

that the relationship between the two disorders may vary 

in different patients. For example, some people with a 

mental disorder may initiate drug use as an inappropriate form of self-medication, some people who take drugs 

may develop mental disorders as a consequence of their 

drug use, and a third group may simply have the two disorders at the same time. If an intervention is evaluated in 

a study population where some patients have drug abuse 

as a primary disorder and others as a secondary disorder, 

the treatment may appear to be ineffective even though it 

works well for one of these subgroups.

A structural difficulty that complicates research on drug 

abuse and mental illness comorbidity is that few drug 

abuse treatment programs treat enough patients with a 

particular mental health disorder to easily generate the 

preliminary data necessary to justify a full-scale study of 

a treatment for the disorder. To 

overcome this difficulty and accelerate the pace of discovery, NIDA’s 

Behavioral Therapy Development 

Program places special emphasis on 

pilot studies in drug abuse and mental illness comorbidity. The program 

represents a kind of research “venture capital,” making possible the 

rapid initial testing of many ideas, 

the best of which will then proceed 

rapidly to further, more definitive testing. Starting next year, NIDA’s Clinical Trials 

Network will accelerate this wider testing by facilitating 

the recruitment of large numbers of patients with the 

drug abuse and comorbidity characteristics that treatments 

are designed to address. (See “Clinical Trials Network 

Will Speed Testing and Delivery of New Drug Abuse 

Therapies,” V14-1, April 1999.)

Drug abuse and mental health professionals both confront 

the difficulty of providing effective care to patients whose 

problems overlap two health care specialties that share 

much, but are also in many ways very distinct. In response 

to this situation, NIDA and the National Institute of 

Mental Health have been actively collaborating on epidemiologic and treatment research on comorbidity. For 

example, the two Institutes are examining the problem of 

treating the relatively small population of patients who 

abuse drugs and also have severe mental disorders, such as 

schizophrenia or bipolar disorder. These patients require 

integrated specialty treatments.

In drug abuse as in other areas of health care, isolated 

disorders are simplest to study and treat, but comorbidity 

is reality for many individuals. NIDA research has laid 

the foundation for successful investigations of these 

complex realities. 

Drug abusers who have concurrent, or comorbid, mental 

health problems are at the top 

of the list of those who will 

benefit from this research. 
Research Findings

100

Clinical Trials Network Will Speed Testing and Delivery Of New 

Drug Abuse Therapies

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 14, Number 1 (April 1999)

Over the past quarter century, NIDA research programs 

have produced dramatic advances in understanding drug 

abuse and addiction and led to the development of an 

array of new treatments and therapies to help patients 

with drug abuse problems. But, in order to fulfill their 

promise, the advances achieved in drug abuse research 

centers must reach patients in the community-based settings where most treatment is provided. To enhance the 

delivery of scientifically based treatments to drug abuse 

patients, NIDA is establishing the National Drug Abuse 

Treatment Clinical Trials Network. 

The Clinical Trials Network (CTN) will provide a structured partnership in which NIDA, treatment researchers, 

and community-based service providers will cooperatively develop, validate, refine, and deliver new treatment 

options to patients in community-level clinical practice. 

“The Clinical Trials Network is a revolutionary advance 

in the study and treatment of drug abuse and addiction. 

It is the most important initiative the Institute has ever 

undertaken,” says NIDA Director Dr. Alan I. Leshner. 

The CTN framework will consist of Regional Research 

and Training Centers (RRTCs) linked in partnership with 

5 to 10 or more community-based treatment programs 

(CTPs). These RRTC/CTP partnerships will constitute 

CTN Research Nodes. “Each Node will include CTPs 

that represent a variety of patient populations and will be 

linked through the Network with other Nodes throughout 

the country,” says Dr. Stephen Zukin, director of NIDA’s 

Division of Clinical and Services Research. “This means 

the Clinical Trials Network will provide a broad and powerful infrastructure for rapid multisite testing of promising science-based therapies. Patients in community-based 

treatment settings across the country will benefit, and 

benefit sooner, from well-developed science-based care.” 

The CTN will be national in scope but anchored on community-level programs. The size and diversity of patient 

populations participating in CTN studies will provide a 

resource for concurrent testing of promising therapies and 

will make it possible to conduct comprehensive investigations of factors such as environmental and genetic determinants of vulnerability to drug dependence and abuse. 

CTN investigators and treatment providers and others in 

the broader research community will have access to the 

research database generated by the CTN. 

The CTN will help meet one of the principal needs identified in Bridging the Gap Between Research and Practice, 

the Institute of Medicine’s 1998 report on communitybased drug and alcohol treatment. The report recommended the development of an infrastructure to facilitate 

research within a network of community-based treatment 

programs. NIDA announced its intention to establish the 

CTN in December 1998, and has issued a Request for 

Applications soliciting cooperative agreement applications 

from established clinical investigators to participate in the 

Clinical Trials Network. 

NIDA has committed first-year funding of $10 million 

for the CTN. The Institute plans to make as many as four 

awards, for project periods up to 5 years, during the first 

year. When fully developed, the Network will include 

from 15 to 30 Nodes incorporating well over 100 community treatment facilities. 

The CTN partnership is designed to meet a range of 

objectives that include: 

• supporting studies of behavioral, pharmacological, 

and combined behavioral and pharmacological treatment interventions of proven efficacy in rigorous, 

multisite clinical trials to determine effectiveness 

across a broad range of treatment settings and patient 

populations; 

• furthering the development of effective treatments by 

integrating behavioral, pharmacological, and treatment research; 

• investigating the impact of advances in treatment 

research on community-level treatment practices; 

• ensuring that treatment research in drug abuse and 

addiction meets the needs of the wider community, 

including minorities, women, children, and underserved populations; 
101

• fostering the collaboration of community treatment 

practitioners and researchers to provide opportunities for exchange of ideas, information, and values 

between the treatment and academic communities; 

and 

• determining the impact of the transport of novel, 

effective treatments in the community on the incidence and prevalence of various other illnesses and 

conditions, including HIV and hepatitis. 

For More Information

Additional information about the Clinical Trials Network 

can be found at www.nida.nih.gov/funding/clintrials.html.
Research Findings

Volume #, Number (Month Year)

102

Antistress Medications May Help Drug Abuse Patients 

Avoid Relapse 

Volume 14, Number 1 (April 1999)

A class of medications currently being developed by several pharmaceutical companies may help drug abuse patients 

avoid relapse after experiencing stress. Called CRF antagonists, the compounds block the action of corticotropinreleasing factor (CRF), a naturally occurring chemical in 

the brain. Scientists think that CRF may play a key role in 

producing arousal, anxiety, and other emotional responses 

to stress. 

Dr. Yavin Shaham, formerly of the University of Toronto 

and now in NIDA’s Intramural Research Program in 

Baltimore; NIDA grantee Dr. Jane Stewart of Concordia 

University in Montreal; and their colleagues at Concordia 

University and the Addiction Research Foundation in 

Toronto have conducted a series of studies to determine 

whether CRF antagonists can prevent stress-induced 

relapse to drug-seeking in rats. In these studies, rats were 

trained to press a lever to receive a dose of cocaine or 

heroin. After the rats learned this behavior, the supply of 

drugs was terminated so that pressing the lever no longer 

resulted in a dose of drug. As a result, the rats reduced 

their lever pressing to practically nothing. However, when 

the rats were given mild intermittent footshocks for 10 to 

15 minutes, they started to press the lever again as soon as 

it became available, even though they did not receive any 

drug. This indicates that stress can reinstate drug seeking 

in rats, just as it is reported to do in human addicts, says 

Dr. Stewart. 

The researchers found that giving the rats a CRF antagonist prior to giving them footshocks could greatly reduce 

the rate at which the rats would press the lever again. 

However, the compound had no effect when the rats were 

pressing a lever to receive a drop of sugar solution that 

they could drink. “This suggests that the CRF antagonist 

blocks stress-induced relapse to drug seeking specifically 

and does not produce its effects by interfering with the 

animal’s ability to press the lever,” says Dr. Stewart. 

Results such as these have interested staff in NIDA’s 

Medications Development Division (MDD) in the potential of CRF antagonists for treating drug abuse relapse. 

“What’s so interesting about CRF antagonists is that evidence suggests that they may be useful in treating relapse 

to a variety of drugs, including cocaine, heroin, and nicotine,” says Dr. Jane Acri of MDD. “This is particularly 

important considering that people who abuse drugs often 

abuse a number of different drugs.” 

Source 

• Shaham, Y.; Erb, S.; Leung, S.; Buczek, Y.; and 

Stewart, J. CP-154,526, a selective, non-peptide 

antagonist of the corticotropin-releasing factor 

receptor attenuates stress-induced relapse to drug 

seeking in cocaine- and heroin-trained rats. 

Psychopharmacology 137:184-190, 1998. 
Research Findings

103

Treating Mood Disorders in Drug Abuse Patients Yields 

Improvement in Both Conditions

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 13, Number 6 (March 1999)

For many drug abuse 

patients, mood disorders 

are a constant companion. Among cocaine 

abusers, for example, 

depressive disorders are 

the most commonly 

diagnosed coexisting, 

or comorbid, conditions. The relationship 

between mood disorders 

and drug abuse in these 

patients is often complex and interconnected: 

Drug abuse patients may 

develop depression as 

a result of the physical 

and psychological suffering associated with their 

drug use, and patients 

suffering from mood 

disorders may become drug dependent in attempts to selfmedicate. For patients suffering from both drug abuse and 

mood disorders, the conditions once seemed impossible 

to untangle, but recent NIDA research suggests that treatment for the mood disorder alone also can have a positive 

effect on drug abuse treatment. 

One NIDA-supported study found that drug use declined 

among teenage drug dependence patients being treated 

with a medication for bipolar disorder, which is characterized by alternating periods of depression and mania. In a 

related study, chronic opiate-dependent adults reported 

less drug abuse when they were treated with the antidepressant imipramine for comorbid depression. 

Reducing Substance Dependence in Bipolar Teens 

Lithium has proven effective in treating adult bipolar 

disorder patients and research with adult patients suggests 

that lithium also may be an effective treatment for comorbid substance dependence. However, no double-blind, 

placebo-controlled studies have tested the therapy in 

adolescents. Now, at Washington University in St. Louis, 

Dr. Barbara Geller and her colleagues have found that, 

in adolescent patients, lithium treatment for the manic 

phase of bipolar disorder also reduces drug and alcohol 

dependence. 

The researchers’ 

double-blind, placebocontrolled study 

involved 25 teenage 

patients who had been 

diagnosed with bipolar 

disorder and secondary 

substance abuse disorder involving marijuana, alcohol, inhalants, or multiple drugs. 

“Most of these kids 

have had bipolar disorder since the age of 9,” 

Dr. Geller says. “They 

have been severely ill 

for a long time, and 

most are from families 

with a history of bipolar disorder.” 

More than half of the patients also came from families 

with a history of substance abuse, sometimes reaching 

back several generations. All had begun using drugs in 

the year prior to being enrolled in the study. “Secondary 

substance dependence disorders are the most common and 

most severe comorbidity in bipolar patients,” Dr. Geller 

says. “We wanted to get to them within the first year, 

when they were newly addicted.” 

All participants in the study received packets of capsules to 

be taken twice each day during the 6-week study. For half 

the teenagers, the capsules contained lithium dosages that 

have proven effective in treating adult bipolar patients. 

The other patients received placebo only. All participants, 

who were treated as outpatients, also received weekly therapy sessions. Blood levels of lithium were checked twice 

each week—once randomly—to make sure the participants were taking the pills. Urine samples were collected 

twice weekly—once randomly—to monitor drug use. 

The percentage of drug-positive urine samples for participants receiving placebo remained essentially unchanged, 

at roughly 40 percent, throughout the study. But for 

the group receiving lithium, drug-positive urine samples 

dropped from 40 percent to approximately 10 percent. 

Percent of Urine Samples Positive for Drugs: 

Patients Taking Lithium vs. Patients 

Taking a Placebo

Random weekly urine analysis showed significantly lower drug use 

among patients who received lithium compared with patients who 

received a placebo. 
104

“We tested randomly six times during the study and the 

urine samples confirmed the patients’ self-reports. There 

was a significant decrease in drug use,” Dr. Geller says. 

In addition, patients in the lithium group showed significantly greater improvement in symptoms of bipolar disorder—such as their ability to function in family, school, 

and social settings—than did those receiving a placebo. 

“Lithium treatment of bipolar disorder in adolescents with 

secondary substance dependence disorders was an efficacious treatment for both disorders,” Dr. Geller concludes.

Reducing Craving in Methadone Patients 

Dr. Edward Nunes and his colleagues at the New York 

State Psychiatric Institute and Columbia University 

College of Physicians and Surgeons in New York City 

found that antidepressants used to treat comorbid depressive disorders in adult methadone treatment patients not 

only can improve their mood but also reduce their craving 

for drugs. 

“We were able to identify and treat primary or secondary depression in chronically drug-dependent adults,” Dr. 

Nunes says. “In some respects, treating depression as a 

separable disorder represents a sea change in the way we 

look at comorbidity in these patients.” 

In Dr. Nunes’ study, patients receiving imipramine to 

treat depression showed substantial drops in depressive 

symptoms, and many patients whose depressive symptoms improved also reported decreased craving and use of 

drugs, including opiates, cocaine, and marijuana. 

“There is evidence that treating the depression helps some 

patients take advantage of therapy and could be successful 

as one part of treatment,” Dr. Nunes says. 

The 12-week study involved 137 patients recruited from 

2 community-based methadone maintenance programs. 

Patients also were diagnosed with primary depression 

that predated their drug use or secondary depression that 

emerged or persisted through a period of abstinence or had 

lasted for at least 3 months during a current period of drug 

use. Patients were randomly assigned to either imipramine 

or placebo. Eighty-four patients completed at least 6 weeks 

of the trial. Fifty-seven percent of patients receiving imipramine were rated as having substantial improvement in 

both mood and drug use compared with only 7 percent 

among the patients receiving placebo. Fourteen percent of 

patients receiving imipramine achieved abstinence, confirmed by urinalysis, for 4 weeks compared with 2 percent 

of patients who received placebo. 

“Imipramine had a very robust and positive effect on 

mood. This improved mood was associated with less 

intense and less frequent drug craving and, to a lesser 

extent, with reduced drug use,” Dr. Nunes says. 

Sources 

• Geller, B., et al. Double-blind and placebo-controlled 

study of lithium for adolescent bipolar disorders 

with secondary substance dependency. Journal of the 

American Academy of Child and Adolescent Psychiatry

37(2):171-178, 1998. 

• Nunes, E.V., et al. Imipramine treatment of opiatedependent patients with depressive disorders. Archives 

of General Psychiatry 55:153-160, 1998. 
Research Findings

105

Matching a drug abuse treatment patient with the right 

type of treatment program is a much-discussed but elusive 

goal for drug abuse treatment providers. In the real world, 

a patient simply may not have the option of switching to 

another treatment program that might be a better match 

for his or her needs. For example, a patient’s choices may 

be limited by the insurers, employers, or Government programs that pay for the treatment. 

Even within these limitations, however, treatment needs 

can be evaluated and special services can be targeted 

to meet patients’ specific needs with effective outcome 

results, NIDA-funded research shows. 

Dr. Thomas McLellan and his colleagues at the University 

of Pennsylvania in Philadelphia first sought to develop 

and evaluate a clinically practical matching procedure 

for assigning patients to treatment programs that were 

deemed most appropriate to the patients’ needs. But the 

investigators could find no evidence of better outcomes 

for any particular type of patient, regardless of whether 

the assigned program was inpatient or outpatient. The 

researchers also found that insurance coverage requirements made it difficult to place patients in selected treatment programs even when the patients were willing to go 

to that program. 

So the researchers redirected their goal from “matching 

patients with programs” to “matching patients’ problems with targeted therapy services” furnished within the 

treatment program that was covered. They compared 

outcomes of patients in matched-services programs to outcomes of patients receiving standard, unmatched services, 

in four private treatment programs in Philadelphia - two 

inpatient and two outpatient programs. The 94 adult 

patients in the study all were employed and were dependent on drugs, alcohol, or both. All treatment costs were 

covered by employer-provided insurance. 

On entering treatment, patients were interviewed using 

the Addiction Severity Index (ASI), a standard hour-long 

interview designed to measure severity of problems in 

Matching Drug Abuse Treatment Services to Patient Needs Boosts 

Outcome Effectiveness

By Neil Swan, NIDA NOTES Staff Writer 

Volume 13, Number 5 (February 1999)

Variables reflect the 30 days prior to treatment admission and 6-month followup.

On Entering 

Treatment

6 Months After 

Discharge

On Entering 

Treatment

6 Months After 

Discharge

Changes in the Addiction Severity Index Variables

Days of Alcohol Use 12 2 15 1

Days of Alcohol Intoxication 11 2 13 1

Days of Opiate Use 3 1 1 1

Days of Cocaine Use 4 1 5 1

Days of Medical Problems 4 5 3 3

Days Worked 16 14 14 17

Employment Income $1,318 $1,072 $1,042 $1,435

Days of Family Problems 4 4 3 1

Days of Psychological Problems 10 7 11 4

Problems

Standard Treatment Patients Match Services Patients

 Targeted Problems

 Problems Not Targeted
106

the following areas: medical symptoms, employment and 

self-support, drug use, alcohol use, legal status, family and 

social relationships, and psychiatric symptoms. 

Randomly selected matched-services patients received 

focused services in the areas of employment, family relations, or psychiatric problems, depending on their needs. 

These problem areas were targeted because studies had 

shown them to be most important in predicting poor 

treatment outcome. The treatment providers gave these 

matched patients a minimum of three individual therapy 

sessions from a psychiatrist, psychologist, or social worker, 

for each identified problem. For example, matched 

patients with a psychiatric problem received at least three 

targeted individual therapy sessions from a psychiatrist or 

psychologist. Standard patients were also interviewed with 

the ASI. The information was provided to the treatment 

programs, and the programs were asked to treat them “in 

the usual manner.” 

Both matched- and standard-treatment patients were 

monitored with weekly phone calls and were evaluated 

again with the ASI interview 6 months after discharge. 

The results showed that matched-treatment patients 

stayed in treatment longer, were more likely to complete 

treatment, and had better 6-month outcomes than the 

standard-care patients treated in the same programs. The 

standard-care group showed significant improvements 

between admission and 6-month followup in drug use, 

alcohol use, family relations, and psychiatric problems, 

but failed to show improvements in medical status and 

showed significantly worsened status in employment. 

The matched group showed statistically significant 

improvement in all ASI problem areas. 

The researchers caution against generalizing their findings 

to other groups. The study patients were referred by an 

employee assistance program and thus probably differed 

from other insured groups in the amount of pressure they 

were under to enter treatment, as well as in aspects of 

their backgrounds, the researchers note. 

The matching strategy was clinically and administratively 

practical and attractive to patients, the researchers say. 

The results indicate that, despite obstacles to matching 

patients to programs, strategies can be designed to target 

services effectively within programs. 

“In the real world of addiction treatment, providers can 

find ways to best utilize treatment resources,” says Dr. 

McLellan. “Each patient’s unique treatment needs can 

be identified easily and reliably at the time of treatment 

admission, and the appropriate services can then be targeted to that patient as part of the overall treatment. It’s 

not very different from what most treatment clinicians 

describe as individually tailored treatment.” 

Source 

• McLellan, A.T.; Grissom, G.R.; Zanis, D.; Randall, 

M.; Brill, P.; O’Brien, C.P. Problem-service “matching” in addiction treatment: A prospective study in 4 

programs. Archives of General Psychiatry 54:730-735, 

1997. 
Research Findings

107

Men and Women in Drug Abuse Treatment Relapse at Different 

Rates and for Different Reasons

By Steven Stocker, NIDA NOTES Contributing Writer 

Volume 13, Number 4 (February 1998)

Recent NIDA-funded studies have found that women in 

drug abuse treatment relapse less frequently than men do, 

at least partly because women are more likely to engage 

in group counseling. Other NIDA-supported researchers 

have found that cocaine-addicted women and men differ 

in the factors that cause them to relapse, indicating that 

males and females might benefit from different relapse 

prevention strategies. 

Likelihood of Relapse 

In a study conducted at the University of California, Los 

Angeles, Dr. Robert Fiorentine and his colleagues have 

found that women drug abusers are less likely than men 

drug abusers to relapse after entering treatment because 

women participate more frequently in group counseling 

and that this more intensive level of treatment 

engagement helps them to remain drug-free. 

The researchers followed 182 women and 148 men in 26 

public outpatient drug abuse treatment programs in Los 

Angeles County. The programs provided group, 

individual, and family counseling; educational activities; 

and referrals to other health and social services. The treatment lasted 6 months. 

About half the patients regularly used just one drug—

primarily crack cocaine, marijuana, or powder cocaine, 

and about half used more than one drug. Regular use was 

defined as three or more times per week. The patients 

were interviewed while in treatment and approximately 6 

months after the first interview. 

The scientists found that the women in their sample were 

less likely than the men to relapse: only 22 percent of the 

women compared to 32 percent of the men relapsed to drug 

use in the 6 months between interviews. The researchers 

considered several theories to account for this finding. 

One possibility was that the women used drugs less than 

the men, so abstaining from drug use was easier for them. 

However, the study findings showed otherwise. In the 

year preceding treatment, more women had used crack 

cocaine than men, and about the same percentages of 

women and men had used powder cocaine, marijuana, 

and other drugs. In addition, women used all drugs as 

frequently as men, except for crack and heroin, which 

women used more frequently. Finally, about the same percentage of women and men used two or more drugs. 

Another possibility the researchers considered was that the 

women received more social support than the men from a 

variety of sources, such as families, friends, and coworkers. 

The investigators found that, although the women were 

more likely than the men to maintain a social network, they 

were no more likely than men to receive emotional support 

for their problems and encouragement to stop using drugs. 

What did appear to explain the difference in relapse 

was the fact that the women were more likely to engage 

in treatment, particularly group counseling, says Dr. 

Fiorentine. In his study, the women engaged in an average 

of 10.9 sessions of group counseling per month compared 

to 7.9 sessions a month for the men. Research has shown 

that more intense participation in treatment is associated 

with lower rates of relapse. 

The women did not seem to be attending group counseling sessions more often than men because the sessions 

were somehow oriented more toward women. The sessions dealt with the problems of both genders more or 

less equally and were usually attended by both men and 

women, Dr. Fiorentine says. 

The reason that women attended group counseling sessions more than men may stem from women’s greater 

willingness to seek professional help for their health problems, speculates Dr. Fiorentine. “Women appear to be 

more willing to seek help for their problems, including 

their substance abuse problems,” he says. “Men, on the 

other hand, are more likely to say, ‘I’m OK. I don’t need 

help. I can take care of this. It’s just a little problem.’” He 

recommends that treatment providers discuss with male 

drug abusers the possibility that their reluctance to seek 

help may be hampering their recovery. 

Even though the women attended more group counseling 

sessions than men, they did not attend more individual 

counseling or family counseling sessions than men did. 

If women are more likely to use services in general, why 

did they not engage more often in these other types of 

therapies? The explanation seems to be that these other 

therapies are not offered as frequently as group counseling 

in Los Angeles County, primarily because of the county’s 

budget constraints, Dr. Fiorentine suggests. “Individual 

counseling, for example, is expensive and there are only 

so many counselors to go around, so treatment programs 

ration individual counseling,” he says. 
“Both women and men already may be attending the 

maximum number of individual counseling sessions they 

can attend. If patients could attend as many of these sessions as they desired, you might see more women than 

men in these sessions, just as you see more women than 

men in group counseling sessions.” 

In a related study, Dr. Roger Weiss and his colleagues at 

McLean Hospital in Belmont, Massachusetts, also found 

less likelihood of relapse for women than for men among 

patients who were hospitalized for cocaine addiction. 

When 74 patients were interviewed 6 months after the 

hospitalization, 51 percent of the women had remained 

abstinent compared to 25 percent of the men. 

Like Dr. Fiorentine, Dr. Weiss theorizes that the women 

in his sample were more motivated for therapy than the 

men were. “Studies have identified barriers to entering 

drug abuse treatment programs that exist for women but 

not for men,” says Dr. Weiss. “These include childcare 

difficulties and the predominance of male patients and 

staff. There is also more social stigma for women in being 

labeled an addict. Women who come to these treatment 

facilities must be willing to overcome these barriers, which 

could lead to a higher percentage of women who are motivated to change.” 

Reasons for Relapse 

In addition to identifying gender differences in the likelihood that drug abusers relapse, scientists also have identified gender differences in drug abusers’ experiences before 

and during relapse. Dr. James McKay and his colleagues 

at the University of Pennsylvania in Philadelphia found 

that women in treatment for cocaine addiction were more 

likely than men to report negative emotions and interpersonal problems before they relapsed. The men, on the 

other hand, were more likely to report positive experiences prior to relapsing and were more likely to engage 

in self-justification and rationalizing afterward. They 

reported, for example, that they felt entitled to use cocaine 

or that they believed they could control their cocaine use. 

The women also were much more likely to be impulsive in their return to cocaine use. Fifty-six percent of 

the women, compared with only 17 percent of the men, 

reported that they relapsed immediately after the thought 

of using cocaine occurred to them. 

These gender differences in relapse factors suggest that 

different relapse prevention strategies might be emphasized for women and men, says Dr. McKay. For example, 

women might benefit more from techniques that enable 

them to deal more effectively with unpleasant emotions 

and interpersonal problems. “One strategy is to take 

action quickly as your mood starts to deteriorate rather 

than waiting until you are in a really bad mood and then 

trying to do something about it,” he says. “If it’s a small 

problem, planning an enjoyable activity might be all that 

is needed. If, however, it’s a serious depression, medication or psychotherapy might be necessary.” 

In contrast, men might benefit more from strategies that 

counter their tendency to let down their guard when 

feeling good, Dr. McKay says. “These strategies are 

derived from concepts taught in 12-step programs, such 

as not getting too cocky or confident when your mood 

improves,” he says. “Patients are told to be on the lookout for warning signs that might be present when they’re 

feeling good, such as thinking to themselves, ‘I’m feeling 

great today. I don’t need to go to that meeting. I can go 

hang out with this friend of mine. I know he uses, but I’m 

feeling good today, and I’m not vulnerable to using.’” 

More Research 

Gender differences in drug abuse are of intense interest to 

NIDA, says Carol Cowell of NIDA’s Division of Clinical 

and Services Research. “Researchers are finding gender 

differences across the broad spectrum of drug abuse 

research —from basic research to studies such as these on 

treatment and services—and we would like to encourage 

more study of these differences,” she says. She occasionally 

suggests that NIDA-funded researchers analyze their data 

in terms of gender differences. “This sometimes results in 

a study that increases our knowledge of the role of gender 

in treatment outcomes,” she says. 

“Performing gender analyses is simply a matter of doing 

good science,” says Dr. Cora Lee Wetherington, NIDA’s 

women’s health coordinator. When gender differences exist 

but investigators fail to test for them, flawed conclusions 

may be drawn, either for males or females or both, she says. 

Sources 

• Fiorentine, R.; Anglin, M.D.; Gil-Rivas, V.; and 

Taylor, E. Drug treatment: Explaining the gender 

paradox. Substance Use and Misuse 32(6):653-678, 

1997. 

• Fiorentine, R.; Nakashima, J.; and Anglin, M.D. 

Client engagement in drug treatment. Journal of 

Substance Abuse Treatment 17(3):199-206, 1999. 

• McKay, J.R.; Rutherford, M.J.; Cacciola, J.S.; 

Kabasakalian-McKay, R.; and Alterman, A.I. Gender 

differences in the relapse experiences of cocaine 

patients. The Journal of Nervous and Mental Disease

184(10):616-622, 1996. 

• Weiss, R.D.; Martinez-Raga, J.; Griffin, M.L.; 

Greenfield, S.F.; and Hufford, C. Gender differences 

in cocaine dependent patients: A 6 month follow-up 

study. Drug and Alcohol Dependence 44(1):35-40, 

1997. 

108
Research Findings

109

Drug Addiction Treatment Conference Emphasizes 

Combining Therapies

By Steven Stocker, NIDA NOTES Contributing Writer 

Volume 13, Number 3 (July 1998)

Drug addiction can often be treated best through a combination of behavioral and pharmacological treatments 

and social service interventions, according to speakers 

at NIDA’s National Conference on Drug Addiction 

Treatment. The conference, held in Washington, D.C., 

in April, attracted more than 800 drug abuse treatment 

researchers and service providers, leaders of professional 

organizations, criminal justice and law enforcement personnel, representatives from State drug abuse agencies, 

and public policymakers. The conference was presented as 

part of NIDA’s Treatment Initiative, which is designed to 

improve the quality of the Nation’s drug abuse treatment. 

(See “NIDA Launches Drug Abuse Treatment Initiative,” 

NIDA NOTES, Vol. 12, No. 4). 

Research is showing that drug addiction therapy that 

combines different approaches is often more effective than 

therapy that uses only one approach, said NIDA Director 

Dr. Alan I. Leshner. “When all is said and done, the ultimate cure for drug addiction will probably involve a combination of biological and behavioral treatments and social 

services,” he said. 

This approach of treating drug addiction by combining 

biological and behavioral therapies stems in part from 

studies showing that addiction is both a biological and a 

behavioral disorder, Dr. Leshner said. “What science has 

taught us is that drug addiction is a result of an interaction between an individual’s biological vulnerability plus 

his or her experiences plus environmental factors plus, of 

course, drugs. The final result is a changed brain,” he said. 

Viewing drug addiction as exclusively biological or behavioral is too limiting, he cautioned. “Let us not pit biology 

against behavior. These are not opposing viewpoints.” 

Combining medications with behavioral treatments can 

have an additive effect on therapy because the different 

treatments work on different aspects of addiction, said 

Dr. Bruce Rounsaville of Yale University in New Haven, 

Connecticut. Medications, such as methadone or medications that treat psychiatric disorders, can increase the 

chances that patients will stay in treatment. Psychotherapy 

can then help motivate patients to abstain from drugs and 

help them develop healthier lifestyles, said Dr. Rounsaville. 

Several speakers examined behavioral therapies that are 

proving effective in treating drug addiction. 

Dr. Kathleen Carroll of Yale University School of 

Medicine described cognitive-behavioral therapy (CBT), a 

comparatively brief intervention that helps cocaine-dependent individuals become abstinent from cocaine and other 

substances. In CBT, patients learn to recognize and avoid 

the situations in which they are most likely to use cocaine. 

They also learn how to cope with their urges to use 

cocaine and to deal with their psychological, occupational, 

and other problems. “Drug use requires skills involving 

getting the money to buy drugs, getting the drugs, and 

other activities,” said Dr. Carroll. “In CBT, the patient 

learns that he or she has the capacity to learn skills that 

are healthier and more productive,” she said. 

Another effective behavioral approach involves rewarding 

patients for staying abstinent, according to Dr. Maxine 

Stitzer of Johns Hopkins University in Baltimore. For 

example, patients can be given vouchers as a reward for 

drug-free urines. The vouchers can be exchanged for 

healthful goods or services valued by the patients. 

In family therapy for drug addiction, the therapist suggests ways that family members can help their addicted 

relatives stop abusing drugs, said Dr. José Szapocznik of 

the University of Miami School of Medicine in Miami, 

Florida. In one situation, for example, a mother ordinarily may allow her adult drug-abusing daughter to stay 

with her for several days in between drug binges, despite 

her misgivings about the daughter’s drug abuse. In family 

therapy, the therapist might encourage the mother to set 

limits for her daughter, such as allowing her to stay only if 

she agrees to remain abstinent. In addition to helping an 

addict, family therapy also has the potential for reaching 

other members of the family who may themselves have 

problems with drug abuse, said Dr. Szapocznik. 

At the conference, 

Dr. Mary Jeanne Kreek 

of Rockefeller University 

describes the health benefits of methadone treatment combined with 

behavioral treatments. 
110

Dr. Herbert Kleber of Columbia University in New York 

City reported on detoxification techniques that help opiate addicts cope with withdrawal symptoms when they 

stop using opiates. Newer techniques include the use 

of a combination of the opiate treatment medications 

buprenorphine, clonidine, and naltrexone and the use of 

anesthesia or heavy sedation. Detoxification is only the 

first step in treating opiate addicts, Dr. Kleber stressed. 

“You should measure success not only by the level of comfort during withdrawal but also by how many patients go 

on for further therapy,” he said. 

Other speakers discussed the challenges of providing drug 

abuse treatment for special populations. For example, 

individuals with both severe mental disorders, such 

as schizophrenia, and drug abuse disorders should be 

treated for both conditions concurrently, said Dr. Robert 

Drake of Dartmouth Medical School in Hanover, New 

Hampshire. This is best accomplished by multidisciplinary 

case management teams that might include a psychiatrist, 

a mental health case manager, a substance abuse specialist, 

and a vocational specialist who can address the patient’s 

needs in an integrated fashion. 

This approach yields a number of benefits, including 

fewer relapses and hospitalizations and a higher functional 

status, said Dr. Drake. 

Many drug-abusing adolescents also have a mental disorder, such as conduct disorder or depression, said Dr. 

Paula Riggs of the University of Colorado Health Sciences 

Center in Denver. These disorders contribute to the severity of the drug abuse disorder and should be treated concurrently, she said. 

Drug abuse treatment can have health benefits in addition to reducing drug use, according to several speakers. 

Dr. David Metzger of the University of Pennsylvania in 

Philadelphia described numerous studies demonstrating that drug abuse treatment reduces the rates of HIV 

infection, by reducing both syringe sharing and risky 

sexual behaviors. Dr. Mary Jeanne Kreek of Rockefeller 

University in New York City presented data showing that, 

among injection drug users in New York City, methadone 

treatment, when combined with appropriate behavioral 

treatment, is reducing rates of both HIV infection and 

hepatitis B and, to a lesser extent, hepatitis C. Methadone 

treatment can also improve the health of addicts by normalizing immune function and the levels of stress and 

sex hormones, all of which are altered by drug abuse, Dr. 

Kreek said. 

Thirteen million people in the United States currently 

abuse drugs, and 4 million are compulsive drug abusers, 

said General Barry McCaffrey, director of the Office of 

National Drug Control Policy, in the keynote address. 

The goal is to reduce the percentage of the U.S. population that is abusing drugs to under 3 percent by 2007, he 

announced. 

At NIDA’s treatment conference, Dr. Kathleen Carroll of 

Yale University describes how 

cognitive behavioral therapy 

can help patients learn to 

avoid situations in which 

they are likely to use cocaine. 
Research Findings

111

Study Sheds New Light on the State of Drug Abuse 

Treatment Nationwide

By Michael D. Mueller and June R. Wyman, NIDA NOTES Staff Writers 

Volume 12, Number 5 (September/October 1997)

The four most common 

forms of drug abuse treatment are all effective in 

reducing drug use. That is 

the major finding from a 

NIDA-sponsored nationwide study of drug abuse 

treatment outcomes. The 

Drug Abuse Treatment 

Outcome Study (DATOS) 

tracked 10,010 drug abusers in nearly 100 treatment 

programs in 11 cities who 

entered treatment between 

1991 and 1993. 

“DATOS is the largest 

study of drug abuse treatment outcomes since the 

early 1980s and the most 

important in the last 10 

years in terms of telling us 

how treatment programs are 

doing,” says Dr. Bennett 

Fletcher, chief of NIDA’s 

Services Research Branch. 

DATOS investigators measured treatment outcomes using 

a random sample of approximately 3,000 patients. The 

researchers compared patients weekly and daily drug use 

for the 12 months before they entered treatment with 

their weekly and daily drug use 12 months after they 

stopped treatment. Patients in outpatient methadone 

treatment who were still in treatment were interviewed 

approximately 24 months after admission. Other outcomes that the researchers measured included: 

• whether patients reported fewer illegal acts, including 

assault, robbery, burglary, larceny, forgery, and fencing stolen property; 

• whether patients were working full time, defined as at 

least 35 hours per week; and 

• whether patients reported fewer attempts or thoughts 

of suicide, which was used as a marker for depression. 

The researchers chose that marker because several previous studies had established its validity as an indicator of depression. 

The four types of programs with the number 

of programs that DATOS 

studied in parentheses 

were outpatient methadone (29), outpatient 

drug-free (32), longterm residential (21), 

and short-term inpatient 

(14). (For descriptions 

of the program types, 

see the textbox on next 

page.) Three of the four 

types were also studied 

in DATOS’s two predecessors: the Drug Abuse 

Reporting Program 

(DARP), which included 

admissions to treatment 

from 1969 to 1973, and 

the Treatment Outcome 

Prospective Study 

(TOPS), which covered 

admissions from 1979 

to 1981. The short-term inpatient treatment programs, 

originally developed to treat alcohol abuse but admitting 

increasing numbers of cocaine abusers during the 1990s, 

were studied in DATOS but not in the two earlier projects. 

Highlights From the Study 

For the four treatment types, DATOS investigators found 

reductions almost without exception in the use of all 

drugs including cocaine, heroin, and marijuana after treatment. (See “Percentages of Patients Reporting Weekly 

or More Frequent Substance Use Before and After 

Treatment” on next page.) Likewise, after treatment a 

smaller percentage of patients reported committing illegal 

acts, working less than full time, and thinking about or 

attempting suicide. (See “Percentage of Patients Reporting 

These Behaviors Before and After Treatment ” on last 

page of article.) The data also revealed that: 

• Except in outpatient methadone programs, cocaine 

was the primary drug of abuse, with alcohol running 

a close second. Cocaine abuse was common even in 

Percentage of Patients Reporting Weekly or More 

Frequent Cocaine Use Before and After Treatment 

* Outpatient methadone patients still in treatment were interviewed 

approximately 24 months after admission. 

In all four types of treatment programs that the Drug Abuse Treatment 

Outcome Study examined, the percentage of patients reporting frequent 

use of cocaine dropped dramatically after treatment. 
112

outpatient methadone treatment programs for heroin 

addicts. About 42 percent of patients who entered 

methadone treatment programs also abused cocaine. 

• Heroin use had decreased since the 1979 to 1981 

period that TOPS studied. Large declines in the abuse 

of depressants such as barbiturates and tranquilizers 

had also occurred since TOPS. 

• Short-term inpatient treatment programs yielded significant declines in drug use, even though patients 

stayed in these programs no more than 30 days. “This 

is one of our most surprising findings,” Dr. Fletcher 

says. “This treatment mode had a high percentage 

of patients reporting daily or weekly use of cocaine 

in the year before treatment and a sharp decline in 

weekly and daily use after treatment.” The percentage 

of patients reporting illegal acts and thoughts of suicide also declined significantly after treatment in these 

programs. The researchers are exploring whether continuing involvement in outpatient services and mutual 

help groups may have contributed to these positive 

outcomes. 

• In every city studied in DATOS, support services such 

as medical, legal, financial, psychological, employment, and family services had declined dramatically 

since TOPS, while the need for those services had 

increased. (See “DATOS Documents Dramatic 

Decline in Drug Abuse Treatment Services,” NIDA 

NOTES, Vol. 12, No. 5).

• Patients surveyed by DATOS reported that it took 

them about 7 years after they first used their primary 

drug to enter treatment. (See “Treatment Histories: 

The Long View of Addiction,” NIDA NOTES, Vol. 

12, No. 5).

New Demographics 

Demographic characteristics of patients studied in 

DATOS had changed since the earlier study. For example, DATOS patients were older and had more years of 

schooling than TOPS patients, and a greater percentage of 

them were women. 

In DATOS, 39 percent of patients admitted to outpatient methadone programs were women compared to 

approximately 31 percent in TOPS. Women made up 

approximately 33 percent of the patients admitted to 

long-term residential programs, as opposed to 22 percent for TOPS. Outpatient drug-free programs saw little 

change from TOPS to DATOS, with women accounting 

for approximately 33 percent of patients in these programs 

in both studies. In DATOS, about 37 percent of patients 

admitted to short-term inpatient programs, which were 

not included in TOPS, were women. The researchers are 

conducting additional analyses to further explore the characteristics and outcomes for women in DATOS. 

Substance Abuse and Psychological Disorders 

DATOS researchers looked at co-occurring psychological disorders and dependencies in 7,402 patients in the 

DATOS programs who were diagnosed as substance 

dependent. They found that 32.1 percent of those patients 

were dependent on cocaine alone. Of that 32.1 percent, 

The Drug Abuse Treatment Outcome 

Study found reductions in the use of 

all drugs including cocaine, heroin, 

and marijuana after treatment. 

Four Common Types of Drug Abuse Treatment

Investigators with the Drug Abuse Treatment Outcome 

Study (DATOS) studied patients in the four most common 

kinds of treatment programs: 

•	 Outpatient methadone programs administer the 

medication methadone to reduce cravings for heroin 

and block its effects. Counseling, vocational skills 

development, and case management to help patients 

access support services are used to gradually stabilize 

the patients functioning. Some patients stay on methadone for long periods, while others move from methadone to abstinence. 

•	 Long-term residential programs offer around-theclock, drug-free treatment in a residential community 

of counselors and fellow recovering addicts. Patients 

generally stay in these programs several months or 

up to a year or more. Some of these programs are 

referred to as therapeutic communities. 

•	 Outpatient drug-free programs use a wide range of 

approaches including problem-solving groups, specialized therapies such as insight-oriented psychotherapy, 

cognitive-behavioral therapy, and 12-step programs. 

As with long-term residential treatment programs, 

patients may stay in these programs for months or 

longer. 

•	 Short-term inpatient programs keep patients up to 

30 days. Most of these programs focus on medical 

stabilization, abstinence, and lifestyle changes. Staff 

members are primarily medical professionals and 

trained counselors. Once primarily for alcohol abuse 

treatment, these programs expanded into drug abuse 

treatment in the 1980s. 
113

59.1 percent were male. Another 26.3 percent of the 

patients were dependent on both cocaine and alcohol, 

and, of those, 69.8 percent were male. In addition, 10.6 

percent of the patients were dependent on heroin alone, 

and 64.2 percent of those were male. 

The prevalence of co-occurring psychological disorders 

among the group was high, especially for antisocial personality disorder (APD) and major depression. APD was 

characterized as a pattern of disregard for the rights of 

others, irresponsibility, and lack of remorse. Major depression was characterized as either a depressed mood or a loss 

of interest or pleasure for 2 weeks or more. 

The prevalence of those two disorders differed widely 

among men and women. Approximately 40 percent of the 

group was diagnosed with APD, and males were twice as 

likely as females to be diagnosed with the disorder. While 

12 percent of the group had experienced a major depression, female patients were twice as likely as male patients 

to have done so. 

Keeping Patients in Treatment 

When the researchers looked at retention rates, they found 

big differences within each of the four treatment types and 

among individual programs. “We found a lot of diversity 

in how well they’re doing at keeping patients in treatment, and we wanted to know why,” says Dr. Dwayne 

Simpson of Texas Christian University in Fort Worth. 

The investigators found that programs with low retention 

rates tended to have patients with the most problems, 

particularly antisocial personality disorder, cocaine addiction, or alcohol dependence. In addition, heroin abusers 

who also abused crack cocaine but not powder cocaine 

had significantly lower retention rates than other heroin 

abusers did. “These programs are dealing with some tough 

people. Programs with the highest concentration of these 

problem patients naturally tend to have low retention,” 

Dr. Simpson says. 

What makes patients stay in treatment? The researchers 

found that the major predictors were: 

• high motivation; 

• legal pressure to stay in treatment; 

• no prior trouble with the law; 

• getting psychological counseling while in treatment; 

and 

• lack of other psychological problems, especially 

antisocial personality disorder. 

Lessons From DATOS 

What were the overall conclusions? “Clearly there were 

significant changes from before to after treatment in each 

of the four modalities,” says Dr. Fletcher. That finding 

When the researchers looked 

at retention rates, they found big 

differences within each of the four 

treatment types and among 

individual programs. 

Percentage of Patients Reporting Weekly or More 

Frequent Substance Use Before and After Treatment 

* Weekly or more frequent use with 5 or more drinks at a sitting.

** Outpatient methadone patients still in treatment were interviewed

approximately 24 months after admission. 

Patients in programs surveyed for DATOS showed a marked reduction 

in drug use after treatment regardless of the type of treatment program 

in which they participated. DATOS analyses focused on marijuana use 

instead of heroin use among patients in short-term inpatient programs 

and outpatient drug-free programs because the number of patients using 

heroin in those programs was too small to allow statistical comparisons.
114

raises some interesting questions, he adds. “For example, 

retention has been our most powerful and consistent predictor of treatment outcomes - yet even people in shortterm inpatient treatment for 30 days or less improved significantly.” Although DATOS replicated the finding from 

DARP and TOPS that time in treatment is important, the 

relationship to retention of other factors such as motivation, psychiatric comorbidity, and treatment process needs 

to be studied more, he says. 

One would also expect worse outcomes from DATOS 

compared to TOPS because of the steady decline in 

availability of support services, says Dr. Fletcher. A possible explanation for the better DATOS outcomes is that 

although support services have decreased, core treatment 

services have improved. “Core services - basic treatment 

techniques such as drug abuse counseling, mutual-help 

groups, and patient participation in devising treatment 

plansmay have improved over the past 10 years. What 

we’re seeing may be a result of this improvement, even 

though availability and use of noncore support services 

have declined,” Dr. Fletcher says. 

The study’s encouraging results verify the effectiveness of 

drug abuse treatment no matter what its form, says NIDA 

Director Dr. Alan I. Leshner. “The service system has 

changed dramatically over the last two decades. This study 

gives us a unique opportunity to understand the effect of 

those changes and to have an impact on the way treatment is delivered,” Dr. Leshner says. 

Sources 

• Etheridge, R.M.; Hubbard, R.L.; Anderson, J.; 

Craddock, S.G.; and Flynn, P.M. Treatment structure and program services in DATOS. Psychology of 

Addictive Behavior 11(4):244-260, 1997. 

• Flynn P.M.; Craddock, S.G.; Luckey, J.W.; Hubbard, 

R.L.; and Dunteman, G.H. Comorbidity of antisocial 

personality and mood disorders among psychoactive 

substance-dependent treatment clients. Journal of 

Personality Disorders 10(1):56-67, 1996. 

• Hubbard, R.L.; Craddock, S.G.; Flynn, P.M.; 

Anderson, J.; and Etheridge, R.M. Overview of 

one-year follow-up outcomes in DATOS. Psychology 

of Addictive Behavior 11(4):291-298, 1998. 

• Simpson, D.D.; Joe, G.W.; Broome, K.M.; Hiller, 

M.L.; Knight, K.; and Rowan-Szal, G.A. Program 

diversity and treatment retention rates in DATOS. 

Psychology of Addictive Behavior 11(40:279-293, 

1997. 

Percentage of Patients Reporting These Behaviors 

Before and After Treatment 

* Outpatient methadone patients still in treatment were interviewed 

approximately 24 months after admission. 

The DATOS data showed reductions after treatment in illegal acts, 

which included assault, robbery, burglary, larceny, forgery, and fencing; less than full-time employment; and suicidal thoughts and suicide 

attempts, indicators of depression. 
Research Findings

115

Peer Community Helps Homeless Drug Abusers With Mental 

Illnesses Reduce Drug Use

By Neil Swan, NIDA NOTES Staff Writer

Volume 12, Number 4 (July/August 1997)

“I made good friends here. I call 

them family . . . . Even the staff, 

they are my family. They gave me 

suggestions, ideas, looking to my 

future. They helped me. . . . I had 

2 years of college, but I didn’t get 

anything out of it. I was using 

[crack]. . . . I see myself with a 

future now. . . . Now I want to 

work for my money. I plan to get 

my children back, and I am seeking housing for me and my children.” 

- Sarah, a graduate of a program in New York City for 

homeless, mentally ill substance abusers 

Researchers at the Center for Therapeutic Community 

Research (CTCR) in New York City, one of NIDA’s 

major multidisciplinary research centers, are studying a 

treatment program they devised to meet the complex psychiatric and substance abuse needs of homeless substance 

abusers who are also mentally ill. They have designed a 

“modified therapeutic community (TC)” that provides 

24-hour-a-day supervised residential treatment for 12 

months or more followed by less intense aftercare in 

which patients live alone or together in apartments and 

hold down jobs. 

Patients are recruited into the program by counselors at 

New York City homeless shelters and psychiatric facilities. 

Staff members, some of them former homeless substance 

abusers themselves, help make the program attractive to 

the homeless. The NIDA-funded treatment research was 

conducted by the Center at the National Development 

and Research Institutes. Led by CTCR director Dr. 

George De Leon, the research has shown that the modified TC program can be effective in treating this elusive 

population that has “fallen through the cracks” in traditional treatment approaches. Patients substantially reduce 

drug use and criminal behavior following treatment 

and also find and keep jobs more frequently than 

before treatment. 

The original TC approach was developed to treat serious 

substance abusers in a residential program by changing 

their behavior and thinking. Support of the treatment 

program members—peers 

and counselors—is a key 

ingredient of TCs, which 

have been enhanced over 

the years with additional 

services for vocational, 

medical, family, and other 

needs. Today’s TC has more 

participation from mental 

health, medical, and education professionals who 

serve along with TC paraprofessionals who are trained 

recovered addicts. 

The TC approach, according to Dr. De Leon and his 

colleagues, views substance abuse as a disorder of the 

whole person. Thus the approach provides a combination 

of social and psychological therapy that fosters change 

in patients’ behavior, attitudes, feelings, and values. 

Individuals are motivated to change through their interaction with others, including their peers from the streets. 

The New York City research is built on a concept of 

“community as method,” which uses the treatment community itself and its activities, relationships, and expectations to enable patients to learn about and change themselves. 

Dr. Stanley Sacks, CTCR’s deputy director, explains that 

the resident community, which usually consists of 12 

to 20 patients, provides a structured daily regimen with 

morning and evening community meetings, seminars, 

classes, conflict-resolution therapy sessions, and a peer 

work structure in which community members maintain 

the facility and prepare their meals. The residents’ progress toward reentry into society by moving first through a 

transitional program in which they share apartments with 

other patients. Mutual support and community ties are 

continued while patients advance toward entering the job 

market. Some are employed in clerical or maintenance 

positions; others eventually become peer counselors in 

similar recovery programs. After 6 to 12 months of transitional apartment living—18 to 24 months after entering 

the residential program—patients advance to independent 

living while maintaining kinship ties with peers and 

holding jobs. 

This program for homeless, mentally 

ill substance abusers can be effective 

in treating an elusive population that 

has “fallen through the cracks” in 

traditional treatment approaches.
116

The CTCR study profiled 342 homeless patients as they 

entered the modified TC program. Interviews by CTCR 

researchers showed that the fundamental needs of the 

patients were extensive, combining psychiatric, substance 

abuse, medical, and social problems that were acute and 

intricately intertwined. The patients interviewed were 

three-quarters male and 70 percent African-American, 

with a median age of 35. The researchers found that 99 

percent reported illegal drug use some time in their lives; 

24 percent reported injecting drugs. Half reported crack 

or cocaine as their primary drug of abuse; 22 percent 

cited alcohol and 16 percent identified marijuana as their 

secondary substance of abuse. Some 84 percent of the 

patients had not had a job in the past year. Four in 10 

said they had had difficulty throughout their lives in making and keeping friends. Virtually all, 99 percent, of the 

patients reported past criminal activity, and 81 percent 

said they had broken the law in the past year. Threequarters of the patients said they had been tested for infection with HIV, the AIDS virus, and 10 percent reported 

positive HIV test results. 

Using a standardized diagnostic test, the researchers also 

found that 60 percent of their patients had one or more 

serious mental illnesses—38 percent were diagnosed with 

major depression, 34 percent with schizophrenia, and 13 

percent with mania. When other mental disorders such as 

posttraumatic stress disorder and phobia were included, 

82 percent of the patients had diagnoses of serious mental 

illness. 

The modified TC targets treatment to meet these multidimensional needs. Compared to standard TC programs, 

treatment interventions are more individualized, more 

flexible, and less intense, explains Dr. Sacks. However, the 

program remains grounded in peer interactions and the 

“community as method” concept to foster change, he says. 

Even in the face of the homeless patients’ severe and accumulated problems, the modifications to the TC model are 

proving effective, initial treatment outcome data indicate. 

Patients in modified TCs had more successful outcomes at 

followup, an average of 750 days after entering treatment, 

than did other New York patients with similar diagnoses who were enrolled in more conventional treatment 

programs. Those in modified TC treatment reported 

less illegal drug use and less criminal activity and showed 

greater improvement on tests to evaluate depression compared with the conventional treatment patients. In addition, those in modified TC showed important gains in 

employment levels compared with their pretreatment 

levels (see “Changes in Outcomes After Treatment,” 

at bottom of page).

Aftercare is critical for these patients as they progress 

toward independent living, says Dr. De Leon. Mental 

The fundamental needs of the patients 

were extensive, combining psychiatric, 

substance abuse, medical, and social 

problems that were acute and 

intricately intertwined.

Changes in Outcomes After Treatment

(Measured an Average of 750 Days After Patients 

Entered Treatment)

Homeless mentally ill patients in a modified therapeutic community in 

New York City who were treated for both substance abuse and psychiatric 

problems had more successful outcomes after treatment than did patients 

with similar disorders in other treatment programs.
117

health and medical needs are the most pressing, he adds. 

Patients who enter treatment with a long history of severe 

drug abuse—10 years or more— and psychiatric problems 

require more time than do others in the program, he says. 

But it may be possible to shorten the time in the residential setting with improved aftercare services, he adds. 

Currently, NIDA is supporting a CTCR study to examine the cost-effectiveness of the modified TC program. 

This study is evaluating program costs against benefits 

to society measured in taxpayer savings through reduced 

crime and social services expenditures and increased tax 

revenues as patients become productive wage-earners. 

Also with NIDA funding, CTCR is evaluating a modified 

TC for mentally ill substance abusers in the San Carlos 

Correctional Facility in Pueblo, Colorado. 

Sources 

• De Leon, G. Modified therapeutic communities for 

dual disorder. In: J. Solomon, S. Zimberg, and E. 

Shollar (Eds.), Dual Diagnosis: Evaluation, Treatment, 

and Training New York, Plenum Press, 1993. 

• De Leon, G. Therapeutic communities for addictions: 

A theoretical framework. The International Journal of 

the Addictions 30(12):1603-45, 1995. 

• Sacks, S.; De Leon, G. Modified therapeutic community for homeless MICAs [mentally ill chemical abusers]: profiles, process and outcomes. Paper presented 

at the American Psychological Association annual 

meeting, Chicago, 1997. 
Research Findings

118

Access to Housing and Job Training Helps Recovering Homeless 

People Stay Drug Free

By Neil Swan, NIDA NOTES Staff Writer

Volume 12, Number 4 (July/August 1997)

“I came to the city, and my first day here I spent all my 

money—$800—on drugs. For the first time in my life I 

was homeless, and it set into me that I was addicted. . . . 

I entered treatment, and I think that without drug screening early on, I would never have stayed clean. Housing was 

important, too. In a shelter or on the streets, being around 

using people makes it almost impossible to recover. . . . I’m 

clean today, two years down the road. I work in construction; 

I made $40,000 last year. I’m making restitution for 

my child support. I fly my son down for visits during 

the summers.” 

—Mr. C., who successfully completed a treatment program 

in Birmingham, Alabama with access to housing and 

work therapy 

Therapy targeting homeless crack and alcohol abusers 

reduces substance abuse more if it offers patients housing 

and jobs, NIDA-funded research has shown. A key component is a requirement that participants stay drug free to 

remain in the housing and enter work therapy, according 

to the study’s researchers at the University of Alabama at 

Birmingham.

This therapeutic approach, in which rules and consequences are applied to help people change their behavior, 

is called contingency management. In the Birmingham 

program, access to housing and employment is contingent 

on following the rules, which homeless participants soon 

learn: stay clean of drugs and alcohol, and you can live in 

a furnished apartment and enter work therapy. Test positive for drugs or alcohol and you go back into a shelter 

and lose your job until you are drug free.

The approach works. The Birmingham researchers have 

demonstrated that participants in the contingency management program remained abstinent from drugs substantially longer than patients who did not receive contingency-based housing and work therapy. “The contingencies 

for reinforcements of housing and a job are powerful 

motivators,” says Dr. Jesse B. Milby, principal investigator 

for the project.

Program participants were either homeless or at risk of 

becoming so. Three-quarters of the patients were male, 

and 83 percent were African American. Average age was 

38 years; average time spent in school was 12.5 years. 

Some 79 percent met criteria for one or more mental 

disorders—56 percent for 

mood disorders, 39 percent 

for anxiety disorders, 6 percent for adjustment disorders, 4 percent for psychotic 

or organic mental disorders, 

and 4 percent for other 

mental disorders. The drug 

that participants said they 

used most frequently was 

cocaine followed by alcohol 

then marijuana.

In the study, participants 

were placed for 2 months 

either in existing local 

substance abuse treatment 

programs or an intensive 

day treatment program 

that included contingency 

management. The conventional treatment program 

consisted of weekly, 12-step-oriented group meetings and 

individual counseling sessions.

The intensive day treatment required program attendance 

for 5 1/2 hours every weekday, including group and individual counseling sessions and participant involvement in 

goal-setting exercises. Intensive day treatment patients also 

received transportation, lunch, and individual counseling. 

Patients who completed day treatment were then eligible 

for the contingency management component—housing 

and 4 months of work therapy refurbishing abandoned or 

dilapidated houses as long as they stayed drug-free. The 

renovated dwellings became housing for participants who 

met contingency requirements. So far, patient-workers 

have renovated six houses and have worked on four small 

apartment buildings now used as drug-free housing.

In the work program, patients learned job skills like 

carpentry and painting. They worked for “Bad Boy 

Builders,” operated by a Birmingham contractor, and 

received minimum wages, which they used to pay modest 

rent for their own housing in dwellings that were previously refurbished by other program enrollees. The conPatients in the Birmingham, 

Alabama treatment program 

who participate in the work 

therapy program develop a 

sense of pride and kinship while 

learning job skills such as 

carpentry and painting.
119

tractor provided tools, materials, 

insurance, and on-the-job training. Job references were provided for successful patients seeking 

to move on to other jobs.

Patients moved into the housing after four successive “clean” 

urine tests. Those who tested 

positive for drug use were immediately evicted from their apartments and taken to a local shelter to stay during the eviction. 

Following two successive clean 

drug tests, these participants 

were readmitted to their apartments. Most wanted to move back, and most qualified 

with clean tests, Dr. Milby says. After completion of the 

4-month work therapy, treatment graduates were permitted to remain in the program-provided housing. Some 

program graduates continue to live in this housing, 

paying rent.

In the work therapy phase, the program seeks to establish 

a sense of pride, kinship, and unity among patients. One 

way the program builds this sense of community is by 

membership in Club Birmingham. The club holds social 

activities and distributes identification cards and tee shirts 

with the club logo.

“We want to provide models of social and recreational 

activities that are not related to substance abuse,” says Dr. 

Milby. “When they have been homeless and using cocaine 

and alcohol for a long time, they forget that there are 

other ways to have fun. We give them a chance to enjoy 

themselves in drug-free settings like cookouts and fishing 

parties.”

Investigators found that participants in treatment with 

contingencies were more likely than those in conventional 

treatment to test clean of drugs, move into stable housing, 

and be employed regularly following treatment. Those 

receiving the 4 months of contingency management had 

18 percent fewer positive cocaine tests than did conventional care patients after 6 months. That study demonstrated that a multicomponent treatment that addresses 

homelessness, employment problems, and substance abuse 

may be the key to successful therapy, Dr. Milby says. 

However, he notes that participants in the day treatment 

group spent four times longer in counseling sessions, 

which is an important variable in addition to contingencies. “We questioned whether the intensive day treatment 

with contingencies was necessary or whether intensive day 

treatment alone was sufficient for best results.”

A second study was designed to answer this question. 

In this study, currently under way, all participants are 

exposed to the intensive day treatment, but only half of 

the participants receive the abstinence-contingent housing and work 

therapy. A vocational counselor assists 

participants in developing job goals. 

Also, participants are allowed to enter 

program-provided housing as soon as 

they are drug-free for four successive 

tests. As a result, most participants 

move into the housing during day 

treatment. Once they complete day 

treatment, they move into work therapy and begin paying for housing. To 

help avoid relapse, aftercare therapy 

follows day treatment.

In this second study, several refinements have been made to the treatment regimen. Each 

week, patients define specific goals on issues such as addiction, housing, jobs, legal problems, psychiatric concerns, 

and family relations. “Patients review their own performance in meeting goals, and they are rated aloud by their 

peers and counselors,” says Dr. Cecelia Lee McNamara, 

project coordinator. “They build self-esteem with a record 

of accomplishments on their goal sheets.”

Following the 4 months of work therapy, clients in day 

treatment with the contingency management component were drug free an average of twice as many weeks as 

participants who received only day treatment. The two 

groups showed equally improved outcomes for days of 

homelessness and days of employment.

From the second study, it appears that the abstinence contingency works most powerfully on substance abuse, says 

Dr. Milby. This study also shows that contingency management with day treatment may also reduce the risk of 

transmission of HIV, the virus that causes AIDS, according to Dr. Joseph Schumacher, another investigator.

Because of the increased costs of providing contingency 

management, Dr. Milby and his team next plan to study 

the cost-effectiveness of the enhanced day treatment when 

used in combination with contingency management.

Sources

• Milby, J.B.; Schumacher, J.E.; Raczynaski, J.M.; 

Caldwell, E.; Engle, M.; Michael, M.; and Carr, J. 

Sufficient conditions for effective treatment of substance abusing homeless persons. Drug and Alcohol 

Dependence 43:39-47, 1996.

• Schumacher, J.E.; Milby, J.B.; Caldwell, E.; 

Raczynski, J.; Engle, M.; Michael, M.; and Carr, C. 

Treatment outcome as a function of treatment attendance with homeless persons abusing cocaine. Journal 

of Addictive Diseases 14(4):3-85, 1995. 

Patients in the study who 

tested positive for drug use 

were immediately evicted 

from the program housing and 

taken to a local shelter to stay 

during the eviction. Following 

two successive clean drug 

tests, they were readmitted.
Revised September 2009

Reprinted August 2008

Revised September 2007

Revised September 2006

Printed September 2002
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