www.drugabuse.gov Volume 23, Number 3 U.S. Department of Health and Human Services | National Institutes of Health

Cocaine Vaccine Helps Some ALSO IN THIS ISSUE

Reduce Abuse Research Findings 8 Study Supports Methadone Maintenance A clinical trial encourages continued development of strategy based in Therapeutic on immune system response. Communities 11 Marijuana Linked With Testicular Cancer BY LORI WHITTEN, drug will not produce the euphoria or other psy- 13 Multidimensional Family NIDA Notes Staff Writer choactive effects that reinforce drug taking and Therapy for Adolescent Drug Abuse Offers Broad, . Lasting Benefits vaccine to prevent abuse For the first placebo-controlled test of the Director’s Perspective proved mildly effective in its first vaccine’s ability to reduce cocaine use among 2 Incentives Promote placebo-controlled test. Although people who are addicted to the drug, Dr. Kosten Abstinence their individual responses varied, and colleagues recruited 115 men and women Research in Brief Avaccine recipients reduced their cocaine use who were seeking treatment at an outpatient 3 • Substance Abuse Among Women With Children more quickly than placebo recipients. A sub- clinic after having abused cocaine for about • Deep Stimulation group of vaccinated patients generated lev- 15 years. The study participants were taking Reduces Rats’ Cocaine Seeking • Intervention els of antibodies that were sufficient to block cocaine, on average, three times daily, 3 days Improves Abstinence, Employment Among cocaine’s effects, and during the period of peak per week. All were also addicted to and Welfare Recipients antibody production, they submitted more had initiated methadone maintenance therapy NIDA at Work drug-free urine samples than participants in 2 weeks prior to their first dose of the cocaine 4 Workgroup Keeps NIDA on the placebo group or those who did not respond the Cutting Edge of Brain strongly to the vaccine. With further refinement Anti-cocaine antibodies Science to increase response, a vaccine might someday latch onto cocaine molecules Bulletin Board 16 • NIDA Appoints New be available as a therapy for cocaine abuse, says in the bloodstream and Director of the Intramural lead investigator Dr. Thomas Kosten of Baylor Research Program keep them from entering • Addiction Science College of Medicine in Houston. Awards Announced the brain. • Program Enhances Physician Knowledge on TESTING THE CONCEPT vaccine or placebo. The researchers chose this Substance Abuse • NIDA Grantee Wins Prize for The cocaine vaccine consists of a small population because the patients came to the Genetics Web Sites • Three amount of the drug chemically bonded to a clinic daily to receive their doses of metha- Scientists Join Advisory Council protein, derived from cholera toxin, that stimu- done, thereby increasing the likelihood that Update lates the immune system to produce antibodies they would be available for injections, as well as 18 • Parental Supervision (see illustration, page 6). Anti-cocaine antibod- urine and blood tests, and would remain in the and Genetics Interact To Influence ies latch onto cocaine molecules in the blood- study for its full 24-week duration. Addiction • Modafinil Normalizes Sleep During stream, forming drug-antibody complexes that Dr. Kosten and colleagues randomly Early Cocaine Abstinence are too large to pass through the fine-grained assigned 58 patients to receive the cocaine vac- Tearoff tissue filter that enwraps and protects the brain. cine in five intramuscular injections spaced 19 NSDUH: Drug Abuse Levels If the vaccinated person develops enough anti- over 12 weeks, a regimen that previous research Rising bodies to capture and hold onto most of the had suggested should cumulatively produce What the Numbers Say cocaine molecules circulating in the blood, the enough antibodies to neutralize the amount of 20 Prisons Lack Detox Services [ Continued on page 6 ]

NIDA Notes | Volume 23, Number 3 1 ■ DIRECTOR’S PERSPECTIVE By NORA D. VOLKOW, M.D., NIDA Director NIDA Notes

EDITOR David Anderson Public Health Advisor, Office of Science Policy and Communications, National Institute on Drug Abuse

DEPUTY EDITOR Julie Ann Miller, Ph.D. Incentives Promote RTI International MANAGING EDITOR Andrew Keegan Abstinence RTI International SENIOR SCIENCE WRITER Lori Whitten, Ph.D. RTI International taying the course and achieving abstinence in substance abuse treatment are ASSOCIATE EDITOR two strong indicators that a patient is on the way to stable recovery. Patients Debra P. Davis who attend more therapy sessions gain more assets for long-term recovery, such RTI International as drug-avoidance skills and awareness of the benefits of healthy recreational DESIGN/LAYOUT Maggie Bray activitiesS and drug-free social networks. During drug-free intervals, patients accumulate RTI International experience in living without . EDITORIAL BOARD Motivational incentives—tangible rewards for verifiable abstinence—are power- David Anderson, Chair; Public Health Advisor, Office of Science Policy ful tools for promoting both goals. In typical motivational incentive programs, patients and Communications receive vouchers for cash or goods each time they show up for a therapy session, pass a Nicolette Borek, Ph.D., Research Breathalyzer test, or submit a drug-free urine sample. Studies have shown that substance Psychologist, Division of Clinical Neuroscience and Behavioral Research abuse patients are better able to maintain desirable behaviors when they are rewarded Scott Chen, Ph.D. , M.B.A., Scientific Review daily or weekly rather than when they are asked to focus solely on the ultimate goal of Officer, Office of Extramural Affairs long-term recovery. This accords with other research showing that addiction changes the J.C. Comolli, Public Health Advisor, Division of Pharmacotherapies and Medical brain in ways that make individuals more responsive to short-term rewards and less able Consequences of Drug Abuse to forgo them in the interest of longer term benefits. Jennifer Elcano, M.A., Science Writer, Incentives extend abstinence during treatment for addiction to cocaine, methamphet- Office of Science Policy and Communications amine, opioids, and nicotine, and they help cocaine abusers remain in treatment longer. Lynda Erinoff, Ph.D., Associate Director, AIDS Research Program, Division Although the effectiveness of incentives tends to weaken after they are discontinued, of Epidemiology, Services and Prevention some studies have found that benefits persist for 1 to 2 years. Research Petra Jacobs, M.D., Associate Director Motivational incentives can promote and reinforce multiple healthy behaviors. For for Program Development, Center for Clinical example, such interventions have improved drug abusers’ adherence to HIV antiviral Trials Network medication regimens and helped patients maintain regular exercise, job-hunting, and Jacqueline Lloyd, Ph.D., Health Science Administrator, Division of Epidemiology, other activities that support a drug-free lifestyle. Investigators are currently examining Services and Prevention Research how to tailor incentive programs for adolescents and pregnant women. Marsha F. Lopez, Ph.D. , Health Science Motivational incentives need not strain budgets. NIDA-supported researchers have Administrator, Division of Epidemiology, Services and Prevention Research developed a program in which the rewards cost about $200 per patient. Each drug-free Ivan Montoya, M.D., M.P.H., Medical sample earns the right to draw from a container of chips. Most of the chips say “good job” Officer, Division of Pharmacotherapies and or can be traded for $1 prizes, such as personal care products and bus tokens, but a few Medical Consequences of Drug Abuse Mary Pfeiffer, Ph.D., Editor and Writer, can be exchanged for prizes of greater value, such as music and video players. In a study Intramural Research Program conducted in the community-based facilities of the Clinical Trials Network, adding this Kenzie Preston, Ph.D., Chief, Clinical program to usual care quadrupled the likelihood of stimulant abusers attaining 12 weeks Pharmacology and Therapeutics Research Branch of continuous abstinence. This is important because the longer patients are continuously Paul Schnur, Ph.D., Deputy Director, abstinent, the greater their chances of maintaining future abstinence. NIDA hopes that Division of Basic Neuroscience and Behavioral these findings will encourage more clinics to adopt motivational incentives. n Research Anna Staton, M.P.A., Public Health Analyst, Office of Science Policy and Communications Cora Lee Wetherington, Ph.D., Psychologist, Division of Basic Neuroscience and Behavioral Research This publication was produced and printed by RTI International, under Contract No. HHSN271200900042C from the National Institute on Drug Abuse. 2 NIDA Notes | Volume 23, Number 3 ■ RESEARCH IN BRIEF Highlights of recently published NIDA-supported studies

less healthy, and more likely response that mimics human stern and colleagues at Colum- to be unmarried or divorced, relapse to drug abuse. In the bia University. In a study of unemployed, receiving public Boston experiment, rats that 302 applicants for Temporary assistance, victims of interper- received 2 hours of deep brain Assistance for Needy Families sonal violence, and affected by stimulation to the shell area in New Jersey, the research- serious mental illness. of the nucleus accumbens ers assigned roughly half to Parental substance abuse (NAc) immediately following an ICM intervention that increases a child’s risk for the priming injection pressed included weekly visits from neglect, abuse, and health the lever about half as much as a case manager, help in over- Substance Abuse and behavioral problems, control animals. coming treatment barriers, Evaluated Among including poor socialization, Dr. Pierce says his team’s assistance in identifying and Women With Children attention deficit hyperactiv- findings suggest that deep meeting other patient service In two nationally representa- ity disorder, depression, and brain stimulation of the needs, and voucher incentives tive surveys, about 2 percent substance use disorders. Dr. NAc shell holds promise as for remaining in treatment. of mothers with at-home Simmons and colleagues urge a therapy for severe cocaine The rest of the trial partici- children under the age of 18 increased attention to detect- addiction. Deep brain stimula- pants received the care welfare reported symptoms meeting ing and responding to parental tion of a different brain region agencies typically provide to the clinical criteria for abuse of drug abuse in primary care, has benefited patients with substance-abusing clients, or dependence on illicit drugs pediatric, and emergency set- Parkinson’s disease, and the which consists of screening or prescription drugs that are tings and support for research technique is also being tested and referral for treatment. being misused. to better understand the as a potential therapy for When interviewed after Dr. Leigh Ann Simmons, impact of parental drug abuse severe depression that does 24 months, 47 percent of the currently of Duke University, and related factors on chil- not improve with medication. women receiving ICM had and former colleagues at the dren’s development. > Journal of Neuroscience been abstinent from drugs for University of Kentucky found > Annals of Epidemiology 28(35):8735–8739, 2008. the past 30 days, compared that 1.1 percent of the 19,300 19(3):187–193, 2009. with 24 percent of those in the mothers in this category who usual care group. At that same responded to the 2002 and Deep Brain time, 22 percent of the women 2003 National Survey on Stimulation Reduces in the ICM group—but only 9 Drug Use and Health had a Rats’ Cocaine Seeking percent of those in the usual substance use disorder involv- A stream of electrical pulses care group—were employed ing prescription painkillers, delivered to the brain’s reward full-time. For comparison, the tranquilizers, sedatives, or center curbs the power of a full-time employment rate was stimulants; 0.9 percent involv- cocaine injection to spur rats 34 percent among 150 female ing marijuana; 0.4 percent, to drug seeking. welfare recipients who did not cocaine; 0.1 percent, ; Dr. R. Christopher Pierce abuse drugs. and 0.2 percent, multiple of Boston University School Intervention The researchers are now drugs. The overall rates of drug of Medicine and colleagues Improves Abstinence, conducting a cost-benefit abuse were not higher among trained rats to press a lever to Employment Among analysis of ICM. If their prom- these women compared with self-administer the drug, then Welfare Recipients ising results are replicated in other women who participated weaned the rats off that behav- Intensive case management future evaluations, welfare in the survey. Compared with ior by withholding the drug. (ICM) can help substance- agencies may have an effective non-drug-using mothers, how- Normally, after rats exposed abusing women who receive tool to help some of their most ever, mothers who used drugs to this protocol receive a welfare benefits stay off drugs vulnerable clients. were, on average, younger, priming injection of cocaine, and make strides in employ- > American Journal of Public Health less educated, more stressed, they resume lever pressing, a ment, report Dr. Jon Morgen- 99(2):328–333, 2009.

NIDA Notes | Volume 23, Number 3 3 n NIDA AT WORK :

Neuroscience Consortium Behavioral Research—coordinate the group’s overall activities. Other mem- bers initiate and lead activities accord- ing to their interests and expertise. Workgroup Keeps NIDA Consortium members seek out and share the latest, most promising find- on the Cutting Edge of ings with each other and the rest of the Institute staff. Part of each monthly Brain Science Consortium meeting is devoted to what the group calls Hot Trends in NeuroSci-

BY LORI WHITTEN, announce new tools and insights that ence. One member reports on a research NIDA Notes Staff Writer have potential to reduce drug abuse and paper relevant to his or her area. The addiction and ameliorate their health group discusses the study, focusing on he past 4 decades have wit- and social consequences. It is the mis- how the results might influence NIDA’s nessed explosive growth in sion of the Institute’s Neuroscience research. Consortium members then knowledge about the brain’s Consortium to monitor developments share the information with other NIDA inner workings. For exam- in brain science and ensure that NIDA’s colleagues whose initiatives might ben- Tple, neuroscientists have identified an research programs are infused with the efit from it. expanding list of neurochemicals and most current and most powerful knowl- The Consortium also conducts receptor proteins that form the back- edge and tools. NIDA’s Cutting Edge Seminar series bone of cell-to-cell communication, for all staff, other NIH researchers, and developed animal models that mimic SHARING NEUROSCIENCE the public. These seminars enlist speak- neurological conditions, and parsed KNOWLEDGE ers from outside NIDA—some from how gene activation and suppression by Neuroscience is progressing so rap- other NIH institutes, others from uni- environmental factors influence learn- idly that scientists find it challenging versities—for a half-day event focus- to stay abreast ing on a specific topic. A 2009 Cutting of advances in Edge Seminar, for example, presented their own areas, the techniques, findings, and potential NATIONAL INSTITUTE ON DRUG ABUSE PRESENTS let alone across of resting state functional connectiv- the entire field. ity. This promising new neuroimaging Created in 1994, approach analyzes the network dynam- NIDA’s Neuro- ics of the whole brain when a subject is science Consor- awake but not responding to any par- tium helps NIDA ticular external stimulus. The technique staff keep pace measures synchronous activity across with cutting- brain regions. Researchers are investi- edge brain sci- gating how resting brain dynamics differ ence related to between normal individuals and people addiction. The with brain disorders, such as attention ing and memory. NIDA-funded scien- approximately 50 Consortium members deficit hyperactivity disorder and tists have contributed to and drawn represent every division of NIDA and bulimia. The technique also exam - upon these advances as they have estab- virtually all offices, centers, and pro- ines brain dynamics as people shift lished that drug addiction is a brain grams. Co-chairs of the Neuroscience from the resting state to a task- disease—the conceptual foundation of Consortium—NIDA’s Science Educa- oriented one. NIDA-funded scientists effective drug abuse treatment and pre- tion Coordinator Dr. Cathrine Sasek, are examining whether normal brain vention. Office of Science Policy and Communi- activity during the shifts is disrupted in Today the rate of discovery in brain cations, and Program Officer Dr. Mary people addicted to drugs. science is swifter than ever. Each Kautz, Clinical Neuroscience Branch, The Consortium also organizes week, neuroscience labs and journals Division of Clinical Neuroscience and activities to attract a greater number

4 NIDA Notes | Volume 23, Number 3 of talented scientists to the challenges FROM PLANT TO PAINKILLER The Use of Resiniferatoxin to Reduce Chronic Pain by of addiction research. As part of this Selectively Ablating Spinal C-Fiber, a Cutting Edge Seminar sponsored by the Neuroscience effort, the Consortium coordinates a Consortium, called NIDA program officers’ attention to research on resiniferatoxin (RTX; below, NIDA-sponsored Frontiers in Addiction left). That chemical had been extracted from a cactus-like plant, Euphorbia resinifera (below, right) and seems to provide powerful pain relief. NIDA subsequently facilitated FDA approval for clinical Mini-Convention at the annual meeting trials to be conducted by Dr. Andrew Mannes of the NIH Clinical Center. Because RTX does not of the Society for Neuroscience (SfN), act on brain receptors, it may offer a long-term treatment for some types of chronic pain without many of the side effects and addiction potential that are associated with analgesics. the world’s largest forum for research on brain science and health. The day-long mini-convention on trends in addiction research typically draws more than 500 scientists, including many who are new to addiction science. A highlight is always an address by the winner of the Jacob P. Waletzky Memorial Award, selected by SfN to recognize a junior scientist conducting innovative research into the neurobiology of drug addiction.

INFLUENCING NIDA PROGRAMS NIDA Notes, Volume 22, Number 1, page to learn from each other to keep up,” Consortium activities have had a 1). NIDA staff who coordinate efforts to says Dr. Kautz. “As a program official, major impact on NIDA research pro- develop safe and effective treatments I find Consortium events thought- grams and initiatives. For instance, in for pain attended the seminar and subse- provoking and a great opportunity to a November 2002 Cutting Edge Semi- quently formed a team to seek approval find out about advances in neuroscience. nar, Dr. Andrew Mannes of the National from the Food and Drug Administration These help NIDA staff to generate creative Institute of Dental and Craniofacial (FDA) for clinical trials of RTX. In 2008, approaches to the science of addiction.” Research presented his results from ani- the FDA granted such approval for the Looking to the future, the Consortium mal research on the pain-fighting effects testing of RTX in patients with pain from plans to continue to highlight exciting of resiniferatoxin (RTX)—a naturally advanced cancer. Initial findings indicate findings about the brain. “Our goal is to occurring nonopioid pain reliever with that RTX has strong analgesic power with encourage NIDA scientists to delve into a different biological target than most no appreciable side effects. new areas of scientific inquiry that have analgesics (“Basic Science Discoveries “The pace of new findings in neuro- great potential to transform addiction Yield Novel Approaches to Analgesia,” science is staggering, and it is necessary research,” says Dr. Sasek. n

NIDAMED: Resources for Patient Care

NIDAMED is a NIDA initiative designed to provide the medical community with drug abuse resources to enhance patient care. At the heart of NIDAMED are research-based drug use screening tools and resources. Designed with the demands of modern clini- cal practice in mind, these products help clinicians to efficiently screen at-risk patients and conduct the followup steps necessary to provide excellent medical care. Visit www.drugabuse.gov/NIDAMED for more information.

NIDA Notes | Volume 23, Number 3 5 n COCAINE VACCINE The vaccinated [ Continued from page 1 ] VACCINE DESIGNED TO KEEP COCAINE OUT OF THE patients varied BRAIN Under normal conditions, cocaine molecules (shown as gold greatly in their anti- circles) easily cross from the blood into the brain (top diagram). A drug typically in the body during cocaine body responses, and series of vaccines, however, stimulates patients’ immune systems to produce cocaine antibodies (red Ys) that attach to molecules of the abuse. The remaining 57 patients received only 38 percent of drug and prevent them from reaching the brain (bottom diagram). placebo injections on an identical sched- the 55 who complet- ule. All patients also attended weekly ed the entire series Unprotected drug abuse counseling sessions focused of injections pro- Brain on relapse prevention. The participants duced anti-cocaine submitted urine samples for cocaine assay antibodies in the three times each week and gave blood quantity (at least 43 samples for antibody level monitoring at mg/mL of blood) that the end of the second week and then at the researchers cal- 4-week intervals. culate will reliably block drug-induced ANTIBODY LEVEL CRUCIAL euphoria. During Blood Some of the patients noted that the the 8 weeks of the Cocaine vaccine achieved its desired effect of sup- greatest antibody pressing cocaine’s psychoactive effects. response, this group These individuals said that they felt little provided cocaine- Protected by Antibodies difference even after taking large amounts free urine samples Brain of the drug—in some cases up to 10 times 45 percent of the their normal intake—confirmed by levels time, as compared of a cocaine metabolite in their urine. In with 35 percent for most of these cases, loss of cocaine’s psy- the placebo group choactive effects occurred after three to and the group with four injections of the vaccine. a lesser response The patients who received the vaccine to the vaccine. Of and those given placebo both reduced the patients who Blood their cocaine use, but the former did so produced euphoria- Cocaine more rapidly. During the period of highest blocking antibody antibody response to the vaccine—from levels, 53 percent the week following the fourth booster at least doubled injection through the month following the the frequency with final one—30 percent of the vaccinated which their urine estimates that, with the current vaccine, patients, but only 15 percent of the place- samples demonstrated no new cocaine about 70 percent of cocaine abusers would bo patients, achieved a 50 percent reduc- use, compared with 23 percent of those develop high enough levels of antibody to tion in cocaine-positive urine samples who received the vaccine but produced block cocaine’s euphoric effects by more compared with levels at the beginning of lower levels of the antibodies. than 90 percent, an effect considered suffi- the study. In prior research, this measure “If a patient makes enough antibod- cient to prevent relapse in individuals moti- of success corresponded with improve- ies, this treatment works well,” says Dr. vated to quit. However, people not moti- ments in daily functioning among people Kosten. Among cocaine abusers who vated to quit but who receive the antibody addicted to cocaine, Dr. Kosten says. No receive the full course of injections, those treatment, perhaps in response to family further injections were given after the who are motivated to quit are expected pressure or other reasons, would require an 12th week of the study, and the difference to achieve abstinence with a lower level antibody level high enough to completely in cocaine use between the vaccine and of antibody than those who are not prevent euphoric effects from whatever placebo groups disappeared by week 16. motivated to quit, he adds. Dr. Kosten amount of cocaine they typically take.

6 NIDA Notes | Volume 23, Number 3 There were no serious adverse events scheduled for daily clinic visits for meth- rier has been used in a human meningitis related to the vaccine, and no patients adone. To bolster participants’ motiva- vaccine for over 10 years. The newly con- dropped out of the study because of the tion, the researchers are supplementing figured vaccine has reduced cocaine self- treatment. “The active protein compo- relapse-prevention behavioral therapy administration in animals but has yet to be nents of this vaccine (cholera toxin B) and with the opportunity to earn rewards for tried in people. the adjuvant of aluminum are used widely; keeping clinic appointments. Dr. Kosten envisions a 2-year course of millions of people have received them,” In other ongoing research with differ- vaccine-aided therapy for cocaine addic- says Dr. Kosten. “Because the amount ent collaborators, Dr. Kosten is modifying tion that will include behavioral therapy of cocaine in this vaccine is very small, it poses no threat to safety.” There were no serious adverse events related to the IMPROVING THE VACCINE vaccine, and no patients dropped out of the study Dr. Kosten’s team is currently plan- because of the treatment. ning to enroll 300 participants in a large NIDA-supported multisite trial to confirm the results of this proof-of-concept study the vaccine in hopes of producing a stron- and a series of vaccine injections followed and determine whether the vaccine can ger, more sustained antibody response. by bimonthly or quarterly boosters. benefit the general population of cocaine The researchers have replaced the cholera Dr. Jamie Biswas of NIDA’s Division abusers. The team expects the challenge toxin with a carrier molecule developed by of Pharmacotherapies and Medical Con- of retaining patients for the entire course Merck Pharmaceuticals from the Neisseria sequences of Drug Abuse agrees with this of vaccinations and assessments to be meningitidis bacteria coat protein, which proposed length of treatment: “Patients greater than in the just-completed trial, has boosted the amount of antibodies need a couple of years of blocking the however, as none will be opiate abusers produced by other vaccines. This car- cocaine high to get used to being off the drug, and they may benefit from appropri- ate behavioral therapies as well. ANTIBODIES HELP CUT COCAINE ABUSE As the study progressed from week 1 to week “NIDA is interested in vaccines as 16, all patients reduced cocaine abuse—but vaccine recipients did so more quickly and to a greater extent. During the vaccination period, those who produced high levels of cocaine-blocking immu- a therapeutic strategy for mopping up an noglobulin G (IgG) antibodies (greater than or equal to 43 μg/mL) submitted a greater percentage of abused drug before it reaches the brain, cocaine-free urine samples than participants who had a lesser response to the vaccine or those in the placebo group. as an alternative to addiction medica- tions that influence the nervous system directly,” Dr. Biswas adds. In addition to 60 the cocaine vaccine, NIDA’s immunother- apy program supports the development 50 and testing of vaccines for smoking ces- sation and to counter overdoses of phen- 40 cyclidine (PCP), , and (see “Antibody Fragment 30 Removes Methamphetamine From the Brain,” NIDA Notes, Volume 22, Number 5,

Urine Samples 20 page 6). n Active cocaine vaccine wth high lgG levels (>43 µg/mL)

Percentgae of Cocaine-Free 10 Active cocaine vaccine wth low lgG levels (<43 µg/mL) SOURCE Placebo Martell, B.A., et al. Cocaine vaccine for the treatment 0 of cocaine dependence in methadone-maintained 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 patients: A randomized double-blind placebo- controlled efficacy trial. Archives of General Psychiatry Time Since First Treatment (in weeks) 66(10):1116–1123, 2009.

NIDA Notes | Volume 23, Number 3 7 ■ RESEARCH FINDINGS Study Supports Methadone Maintenance in Therapeutic Communities

Methadone-treated and other patients fare equally well.

BY LAURA BONETTA, undermine other members’ unity of pur- peutic community that has been accom- NIDA Notes Contributing Writer pose, threatening their progress. Practical modating methadone patients for over 2 and logistical difficulties add to the chal- decades. All the participants were opioid- ethadone maintenance lenge of merging the two treatments. dependent and met eligibility criteria for and therapeutic commu- In a recent NIDA-funded study, Dr. methadone maintenance therapy, and nities are two effective James Sorensen and colleagues at the roughly half were receiving methadone. treatment approaches University of California, San Francis- The methadone patients were similar to Mthat are seldom combined. Few metha- co, showed that these issues, although the others in terms of co-occurring stimu- done patients apply to therapeutic com- significant, need not be prohibitive. lant abuse, psychiatric history, criminal

METHADONE PATIENTS FARE AS WELL AS DRUG-FREE PATIENTS IN A THERAPEUTIC COMMUNITY SETTING At half-yearly assessments, the proportions of methadone and comparison-group patients testing positive for illicit opioid or stimulant use were statistically equivalent. In both groups, the number of individuals using opioids or stimulants increased as more people left the treatment program. All study participants were tracked for 2 years whether or not they left treatment; participants who switched into methadone treatment during the study are included among the comparison group in this graph.

Methadone Group Comparison Group Opioids Stimulants

60 60

40 40

20 20

Percent Testing Positive 0 0 Entry 6 months 12 months 18 months 24 months Entry 6 months 12 months 18 months 24 months

munities, and few therapeutic com - Opioid-dependent patients who were justice involvement, and expected length munities will accept them. Methadone taking methadone upon admission to a of stay in the therapeutic community. patients may anticipate that therapeutic therapeutic community fared as well as At the beginning of the study and then communities will be inhospitable because the rest of the community over 2 years at 6, 12, 18, and 24 months, the research- many therapeutic communities tradi- of followup. ers tested participants for use of illicit tionally have held that recovery requires opioids, alcohol, and stimulants (cocaine abstinence from all psychoactive drugs, EQUIVALENT RESULTS and amphetamine) and questioned them including medications. Therapeutic com- The researchers recruited 145 men and about drug injection and risky sexual munities may be concerned that admit- 86 women at the time of their admission behaviors. They used the program’s client ting methadone-reliant individuals could to Walden House, a San Francisco thera- database and staff logs to determine par-

8 NIDA Notes | Volume 23, Number 3 Many Patients Still Receive Lower Than Recommended Methadone Doses

Methadone is a synthetic agent that relieves symptoms of In 1988, 1990, and then at 5-year intervals through 2005, withdrawal from heroin and other opioids by occupying the the researchers surveyed nationally representative samples same brain receptor as those drugs. This therapy has been of 146 to 172 outpatient treatment facilities. Although the shown to have many benefits, including reductions in illicit proportion of patients receiving doses below the recom- drug use, needle-associated diseases, and crime. The treat- mended minimum decreased during this 17-year span, 34 ment can also help a person work and participate in other percent of patients in 2005 still received methadone doses normal social interactions. of less than 60 mg/day, while 17 percent received doses below 40 mg/day. The study also found that methadone In the United States, there are about 1,400 methadone maintenance programs serving over 254,000 patients, programs strongly advocating an abstinence recovery goal according to a 2006 report by the Substance Abuse and were the most likely to provide doses of methadone below Mental Health Services Administration. Research has estab- 60 mg/day. lished that most patients require a methadone dose of 60–120 mg/day, depending on their individual responses, to achieve optimum therapeutic effects. Yet, a study by SOURCE Drs. Harold Pollack and Thomas D’Aunno at the University Pollack, H.A., and D’Aunno, T. Dosage patterns in methadone treatment: of Chicago found that many methadone patients receive Results from a national survey, 1988-2005. Health Services Research 43 (6): lesser doses. 2143–2163, 2008.

ticipants’ retention in treatment. Previ- range of patients, such as those with psy- patients to understand the medication’s ous studies had indicated that the longer chiatric disorders. Some of these individu- effects and counter negative attitudes patients stay in treatment, the greater als receive medications to treat their con- toward it, says Dr. Sorensen. “There has their likelihood of recovery. ditions, “but methadone still remains an to be training about what it is like to be on By all measured outcomes, the metha- issue,” says Dr. Sorensen. methadone and how to work with individ- done patients were statistically indistin- A 2005 national survey of 380 thera- uals who are taking it. A program needs guishable from patients who were not peutic communities by the Institute for to provide staff with strategies that they receiving that medication. In particular, Behavioral Research at the University can use in working with issues specific both groups of patients stayed in treat- of Georgia found that only 7 percent of to patients who take methadone, such as ment for similar periods of time and had therapeutic communities integrated being drowsy and falling asleep at meet- similar success rates in avoiding illicit opi- methadone treatment into their pro- ings.” He notes that similar problems arise oids and stimulants (see graph, page 8). grams. A more recent survey by the Sub- with other psychiatric medications. “The methadone patients’ outcomes stance Abuse and Mental Health Ser- There also are practical hurdles, such were entirely equivalent to those of vices Administration determined that as difficulty in supplying the medication. other patients,” says Dr. Sorensen. “That among residential treatment settings, In the United States, methadone is typi- removes one reason for not admitting including halfway houses and therapeu- cally provided in highly regulated clinics them to therapeutic communities.” tic communities, only 3.6 percent used that patients initially have to visit each methadone in their opioid-treatment day to receive their dose; only after several NECESSARY ADJUSTMENTS programs. months of adherence to the clinic’s regu- During the past decade, some thera- Therapeutic communities wishing to lations are patients allowed to take home peutic communities have modified their integrate methadone patients into their a supply of methadone. Unsupervised programs to be accessible to a broader programs must teach staff and their other trips to a methadone clinic may expose

NIDA Notes | Volume 23, Number 3 9 therapeutic community patients to risks the 2-year mark of the study, a signifi- Partly because of Dr. Sorensen’s work, such as encounters with drug dealers or cant number—about 30 percent—of the there is now a growing openness toward old acquaintances who are still abusing individuals who started their residencies the integration of different medical treat- drugs. Thus, a residential facility accept- in the drug-free group had initiated ment approaches within therapeutic ing methadone patients needs to provide methadone maintenance therapy. communities, including addiction phar- transportation to and from the clinics, Methadone maintenance patients, in macotherapies. “Dr. Sorensen’s research as well as a secure place for storing and contrast, tended to continue with their is helping therapeutic communities administering the medication. original therapy. evolve so that they can reach a broader All these provisions require additional “It is not a trivial matter to incorpo- spectrum of patient recovery needs,” Dr. staff and resources, and thus add costs. Yet rate methadone treatment in a residential n for therapeutic communities that make treatment setting, but we encourage ther- Hilton adds. the investment, the payoff is the capacity apeutic communities to do so,” says Dr. SOURCES to provide more patients with the benefits Sorensen. “In that way, they can expand Chen, T., et al. Residential treatment modifications: of the therapeutic community model: a the care they are providing to reach more Adjunctive services to accommodate clients on meth- safe place to interact with peers who share patients.” adone. American Journal of Drug and Alcohol Abuse experiences, an emphasis on self-reliance, “Dr. Sorensen has shown that thera- 35(2):91–94, 2009. a program of motivational reinforcement, peutic communities can support the Hettema, J.E., and Sorensen, J.L. Access to care for and a dedication to recovery. recovery of patients regardless of whether methadone maintenance patients in the United States. International Journal of Mental Health and Dr. Sorensen and colleagues note that their therapeutic goals are abstinence Addiction 7(3):468–474, 2009. therapeutic communities that adjust to or long-term maintenance,” says Dr. Sorensen, J.L., et al. Methadone patients in the thera- accommodate methadone patients give Thomas F. Hilton of NIDA’s Health Ser- peutic community: A test of equivalency. Drug and residents a useful treatment option. At vices Research Program. Alcohol Dependence 100(1–2):100–106, 2009.

CORRECTION: An earlier version of this article attributed the 2005 survey of therapeutic communities to the Institute for Behavioral Research at Texas Christian University instead of at the University of Georgia.

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10 NIDA Notes | Volume 23, Number 3 ■ RESEARCH FINDINGS

Marijuana Linked With Testicular Cancer

Use is associated with more aggressive form of the disease.

BY LORI WHITTEN, hypothesize a connection between the recruited all of the study participants NIDA Notes Staff Writer drug and the cancer. Research has shown from three counties in Washington State that marijuana smoking reduces sperm and controlled statistically for smoking, en who use marijuana production and male fertility, and other drinking, and other testicular cancer risk may increase their risk work has linked diminished fertility to factors. for developing testicular increased risk of testicular cancer. Can- Approximately 70 percent of each cancer. A recent study of nabinoid receptors—the cell-membrane group reported smoking marijuana at Mseveral hundred Washington State men proteins that bind to a component of mar- least once. The researchers found that the with testicular cancer showed an associa- tion between current marijuana use and the more aggressive of the two types of STRUCTURAL CONNECTION? Cannabinoid receptors (at arrows) of two types, cannabinoid 1 the disease. Moreover, the association was receptors (left) and cannabinoid 2 receptors (right), occur in mice testes cells (shown). Human testes cells also have these receptors. These proteins may underlie a proposed link between marijuana strongest among men with a long history smoking and testicular cancer. of regular marijuana use. To firmly link marijuana use and the cancer, however, scientists will need to replicate the findings among large groups of men across many geographical regions and identify the underlying bio- 80(2):235–242, 2009. logical mechanisms, says NIDA-funded researcher Dr. S. K. Dey of the Cincinnati Children’s Hospital Medical Center, who collaborated on the study with Drs. Janet Biology of Reproduction Daling and Stephen M. Schwartz and col- leagues at the Fred Hutchinson Cancer Research Center and the University of ijuana as well as to the naturally occur- odds of having testicular cancer were 70 Washington. ring compounds known as endocannabi- percent higher among men who reported During the past 50 years, the number noids—occur on the cell membranes of current marijuana use compared with of new cases of testicular cancer reported sperm, the testes (see photograph), the nonusers. In addition, the research - annually in the United States has nearly uterus, and embryos, as well as on brain ers observed 80 percent higher odds of doubled. So has the percentage of the . Marijuana smoking causes testicular cancer among men who started general population who report having widespread effects in the endocrine and to use marijuana before age 18 compared smoked marijuana at least once. Dr. Dey reproductive systems and might alter the with nonusers. They also found that the suspected that the two trends might growth of somatic and germ cells in the odds for testicular cancer among men be related, although exposure to vari- testes, resulting in testicular cancer. who used marijuana at least weekly were ous environmental factors may also be The research team interviewed 369 twice that of nonusers. involved. men who were diagnosed with testicular Of the two categories of testicular Along with the simultaneous rise in cancer between 1999 and 2006 and 979 cancer, nonseminomas and seminomas, rates, there are biological reasons to men who never had the disease. They the former was strongly associated with

NIDA Notes | Volume 23, Number 3 11 a history of marijuana smoking, but the during puberty—such as chemicals that ter system that underlies its psychoactive, latter had little or no association, Dr. Dey affect estrogen and androgen produc- endocrine, and reproductive effects. says. Nonseminomas occur in younger tion—are risk factors for both. “If these interesting findings are rep- men, grow more rapidly, and have lower “My colleagues and I hope our study licated in a large, nationally representa- survival rates. While a man diagnosed sparks similar epidemiological investiga- tive group of participants, then future with seminomas is 98 percent as likely as tions of the relationship between testicu- research should delve into the molecular someone without the disease to still be lar cancer and marijuana abuse around mechanism underlying the association,” alive 10 years later, the figure for someone the world,” says Dr. Dey. “These results says Dr. Vishnudutt Purohit of NIDA’s diagnosed with a nonseminoma ranges may also spur animal research, which is Division of Basic Neuroscience and from 46 percent to 92 percent, depending essential for interpreting our findings.” on the tumor subtype. (For more infor- Animal research, he says, will be Behavioral Research. He notes that the mation on these cancers, see http://seer. required to determine whether mari- study by Drs. Dey, Daling, and Schwartz cancer.gov/publications/survival/ juana’s psychoactive ingredient, delta-9- is part of NIDA-supported research to surv_testis.pdf.) tetrahydrocannabinol (THC), or its other determine how drugs of abuse affect the The association between marijuana components increase the risk of testicu- cardiovascular, pulmonary, reproductive, smoking and nonseminomas, but not lar cancer. Studies with animals may also and immune systems of the body. n seminomas, is difficult to explain, says search for molecular pathways connect- SOURCE Dr. Dey. The rates for both types of cancer ing marijuana and testicular cancer. Such Daling, J.R., et al. Association of marijuana use and have been rising, and subnormal fertil- studies would probably focus on mari- the incidence of testicular germ cell tumors. Cancer ity and certain environmental exposures juana’s activation of the neurotransmit- 115(6):1215–1223, 2009.

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12 NIDA Notes | Volume 23, Number 3 ■ RESEARCH FINDINGS Multidimensional Family Therapy for Adolescent Drug Abuse Offers Broad, Lasting Benefits

An approach that integrates individual, family, and community interventions outperformed other treatments.

BY CARL SHERMAN, Sessions NIDA Notes Contributing Writer held exclusively THE STAYING POWER OF MULTIDIMENSIONAL FAMILY THERAPY Differences between Multidimensional Family Therapy (MDFT) with individual and cognitive-behavioral therapy (CBT) in reducing teens’ social and behav- therapy that engages sub- teens aim to ioral consequences of drug abuse, as measured by the Personal Experience stance abusing teens and establish mean- Inventory, were most pronounced a year after the end of treatment. their parents individually ingful thera- while building the relation- peutic goals, 30 MDFT Aship between them has lasting benefits foster motiva- CBT that extend beyond reduced drug use, tion, and help 25 according to two NIDA-sponsored, the adolescents randomized trials. A year after treat- develop con- 20 ment, teenage participants treated with crete strategies Multidimensional Family Therapy to solve prob- 15 (MDFT) had fewer drug-related problems lems and find and had improved more on general mea- alternatives to 10 sures of behavior and mental health than drug taking and teens treated with cognitive-behavioral delinquency. 5 therapy (CBT). Sessions Average Score on Problem Assessment with parents 0 TEENS AND PARENTS, ALONE AND include such Before End of 6-month 12-month Treatment Treatment Followup Followup TOGETHER topics as fam- In MDFT, adolescent drug abuse is ily management, viewed as a complex phenomenon in the parent-adolescent relationship, and fits-all approach,” says Dr. Liddle. MDFT which personal issues, interpersonal parenting skills, including monitoring and has been used for young (11 to 15 years relationships, overall family functioning, setting limits. These sessions also provide old) and older adolescents and juvenile and social forces must all be addressed to opportunities to provide emotional sup- offenders. It has been applied in clients’ effect enduring change. Some MDFT ses- . “We connect with parents in a way homes, community-based clinics, resi- sions involve both generations, some only that recognizes their stress and the anger, dential treatment centers, and correc- the adolescent, and some just the parent hopelessness, and even despair they may tional facilities. or parents. In joint sessions, the therapist feel about their child,” notes Dr. Howard guides parents and teens through discus- Liddle of the University of Miami, who led ADVANTAGES EMERGE OVER TIME sions of family problems and introduces the two studies. “Then we help parents The setting for the first of the two methods that build family strengths, reconnect emotionally to their child. This studies was a community-based drug improve communication, and reduce renewed caring is instrumental in chang- abuse clinic. Two hundred and twenty- conflict. Counselors also help families ing parenting practices. four youths—predominantly African- negotiate school, work, justice systems, “MDFT is a flexible and individualized American males, averaging 15 years of age, and community service agencies. treatment system rather than a one-size- from low-income, single-parent homes—

NIDA Notes | Volume 23, Number 3 13 participated. Cannabis was the most com- In the months after treatment, youths alternate therapy did not work at all with monly abused drug; 75 percent of partici- who had received MDFT fared better than families. Both treatments lasted 12–16 pants were diagnosed as cannabis depen- those in the CBT group. Using a statisti- weeks and addressed substance abuse dent, 20 percent alcohol dependent, and cal technique called latent growth curve together with associated problems, such 13 percent dependent on other substances. modeling, which compares rates of change as low self-esteem and school and social The researchers randomly assigned half to over time, the researchers concluded that difficulties. receive MDFT and half, CBT. by 6 months after the start of treatment, As in the earlier study, both treat - The CBT intervention, like MDFT, the benefits of MDFT had begun to out- ments were effective at discharge, but aimed to equip patients with skills not pace those of CBT. One year after starting once again MDFT recipients experienced only to reduce drug abuse but also to treatment: longer lasting gains. At a followup assess- cope with problems in many areas of life. n Youths assigned to MDFT had lower ment 12 months after the adolescents However, unlike MDFT, it focused on scores on the Personal Experience started treatment, only 7 percent of the individual, rather than family, develop- Inventory, which assesses impairment MDFT sample reported substance use in ment. Parents attended only the first two due to personal, social, educational, the previous 30 days, compared with 45 sessions, during which they helped their and legal problems tied to drug abuse. percent of youths who had received the children assess their problems and priori- n MDFT recipients were using drugs CBT-based group therapy. Remarkably, tize goals. To ensure high-quality delivery other than cannabis less frequently the MDFT recipients’ prevalence of drug of both interventions, counselors trained than before treatment, while such drug use at this juncture also compared favor- extensively with manuals, and research use by CBT recipients increased over ably with the rate of 8.5 percent reported assistants rated videotapes of the therapy pre-treatment levels. by a nationally representative sample sessions. n 47 percent of youth treated with of eighth graders in the Monitoring the “CBT is an evidence-based treatment MDFT had used alcohol or drugs no Future study. that everybody knows about and likes, for more than once in the prior month, In addition, during the followup year, good reason,” Dr. Liddle says. He notes compared with 28 percent in the CBT MDFT recipients: that the empirical evidence supporting group. n improved their academic performance, CBT for adults is strong and that similar while the grades of youths who had had evidence is emerging for adolescent popu- MDFT ALSO BENEFITS YOUNGER the CBT-based group therapy wors- lations as well. “Clinicians find it intuitive, TEENS ened; logical, and if they have proper training, The second study tested MDFT ver- n had fewer arrests and placements on easy to do,” he explains. sus CBT-based peer-group therapy in a probation; At the conclusion of therapy in Dr. younger group of adolescent substance n suffered fewer psychiatric symptoms, Liddle’s trial, CBT and MDFT seemed abusers—a population that is at particu- such as those related to depression and similarly effective. Youths in the CBT larly high risk of worsening developmental anxiety; group reported that they had used can- problems, severe and chronic substance n reduced self-reported delinquency and nabis 10 times, on average, in the month use disorders, depression, school failure, associations with delinquent peers, before they started treatment; those and unemployment in adulthood. Eighty- while youths receiving the group CBT in the MDFT group reported 12 days of three teens, average age 13.5 years old, par- increased delinquent peer involvement. such usage. By the last month of treat- ticipated. Most had been referred to a sub- “Consistent with results from our ment, both groups’ use of cannabis had stance abuse treatment program by either other trials, outcomes of MDFT appeared dropped, to 7.5 days and 6 days, respec- their schools or the juvenile justice system to improve even after therapists completed tively. A similar pattern held for use of after using alcohol or a drug during the 30 their work with teens and families,” Dr. any drugs or alcohol. At intake, 94 per- days prior to an initial assessment or dem- Liddle says. cent of the CBT group and 92 percent of onstrating imminent risk for substance The young teens demonstrated another the MDFT youths reported using drugs use—for example, by getting caught with MDFT benefit: Participants were more or alcohol more than once in the previous drugs in their possession. likely to remain in treatment—an impor- month; these percentages had dropped As in the study with older youths, tant challenge in substance use interven- to 77 and 73 percent, respectively, at MDFT therapists counseled families as tions. In the MDFT group, 97 percent of discharge. well as teens, but those conducting the the participants completed treatment,

14 NIDA Notes | Volume 23, Number 3 Therapy Powers HIV/STD Risk Reduction

In addition to reducing drug use, Multidimensional Family sively, according to Dr. Liddle, the rate of new infections Therapy (MDFT) may also ameliorate a serious associated declined over this period in the MDFT group. The research- problem: behaviors that increase risk of human immuno- ers plan to track the teens for 42 months. deficiency virus (HIV) infection and other sexually trans- Dr. Liddle speculates that to the extent the intervention mitted diseases (STD). Interim data from a trial sponsored proves effective, it will reflect the power of family involve- by NIDA’s Criminal Justice-Drug Abuse Treatment Studies ment. “Attending to and reducing high-risk sexual behavior (CJ-DATS) program support that suggestion. Participants is framed in the same way we approach adolescent drug were recently released juvenile offenders who were abus- taking,” he says. ing drugs, a population in which risky sexual behaviors, such as unprotected sex, are especially widespread. Dr. Akiva Liberman, formerly of NIDA’s Division of Epidemiology, Services and Prevention, describes MDFT as “very relevant In the trial, 154 adolescents were randomly assigned to and appropriate for adolescents involved in juvenile justice. receive MDFT or usual services. While in detention, ado- These youths face an array of problems—individual, social, lescents in both treatment groups had received a standard and family. MDFT seems to be a natural fit.” educational, one-session Centers for Disease Control HIV/ STD risk-reduction program. After release and 1 to 2 SOURCES months of therapy, adolescents in the MDFT group and Liddle, H.A., et al. Implementation Outcomes of Multidimensional Family their parents participated in three 2-hour multifamily group Therapy-Detention to Community (DTC)—A Reintegration Program for Drug- sessions designed to raise awareness of HIV/STD risks and Using Juvenile Detainees. International Journal of Offender Therapy and Comparative Criminology. Published online before print April 28, 2010, doi: encourage behavior changes to reduce them. 10.1177/0306624X10366960.

Marvel, F., et al. Multidimensional family therapy HIV/STD risk-reduction Data collected 6 and 9 months after release from detention intervention: An integrative family-based model for drug-involved juvenile were “generally promising,” Dr. Liddle says. Most impres- offenders. Family Process 48(1)69–84, 2009. compared with 72 percent of those who Division of Neuroscience and Behavioral implement it in the community,” she says. had CBT-based group therapy. Dr. Liddle Research. “Not only does it work, but it Dr. Liddle notes his team and others notes that these engagement rates are far joins the category of behavioral interven- have begun work along these lines. n superior to the average rate of only 27 per- tions whose effects seem to endure after SOURCES cent among those who completed 90 days treatment ends.” Liddle, H.A. Treating adolescent substance abuse of standard outpatient treatment in the Sustainability of treatment effects, as using Multidimensional Family Therapy. In J. Weisz NIDA-sponsored Drug Abuse Treatment indicated by 12-month outcomes, was “the and A. Kazdin (eds.). Evidence-based Psychotherapies for Outcome Study (DATOS), a national most important finding” of the studies, Children and Adolescents (2nd ed.), New York: Guilford Press, pp. 416–432, 2010. study of adolescent drug problems. she says. “This is important particularly Henderson, C.E., et al. Parenting practices as media- In both of Dr. Liddle’s studies, MDFT for younger adolescents, who would be on tors of treatment effects in an early-intervention was administered by therapists from a very negative developmental trajectory trial of Multidimensional Family Therapy. American community-based drug-treatment agen- without effective treatment.” Journal of Drug and Alcohol Abuse, 35: 220–226, 2009. cies. “This suggests that the approach may Dr. Onken would like to see further Liddle, H.A., et al. Multidimensional Family Therapy be readily generalized to a serve a broad research to identify which aspects of for young adolescent substance abuse: Twelve-month outcomes of a randomized controlled trial. Journal of population,” says Dr. Liddle. MDFT make it effective. “This is a very Consulting and Clinical Psychology 77(1):12–25, 2009. “MDFT treatment outcomes are complex treatment, and the more we can Liddle, H.A., et al. Treating adolescent drug abuse: A among the best there are for adolescents,” figure out the essential ingredients—what randomized trial comparing Multidimensional Family says Dr. Lisa Onken, chief of the Behav- is critically important and what is of lesser Therapy and cognitive behavior therapy. Addiction ioral and Integrative Branch of NIDA’s importance—the better we will be able to 103(10):1660–1670, 2008.

NIDA Notes | Volume 23, Number 3 15 n BULLETIN BOARD

NIDA Appoints New Director of Ameya Ashish Deshmukh, a 16-year-old student at Upper the Intramural Research Program Arlington (Ohio) High School, won first place for his project, titled “Rational Drug Design Methods for the Identification of Antonello Bonci, M.D., one of the world’s a Novel Negative Allosteric Modulator of a4b2 Nicotinic Recep- leading researchers in neuropsycho- tors.” To identify molecules that bind to nicotine receptors and pharmacology, has joined NIDA as scien- thus demonstrate potential for treating nicotine addiction, he tific director of the Intramural Research used computerized molecular models to compare candidate Program (IRP) in Baltimore. compounds identified by previous research and tested the Dr. Bonci is known for the elegance and finalists on human cells. multidisciplinary breadth of his studies on Second place went to Kevin Michael Knight, a 17-year-old the long-term effects of drug exposure on student at Collegiate High School at Northwest Florida State the brain. Dr. Bonci and colleagues were College in Niceville, Florida. The results of his project, “Improv- the first to demonstrate that drugs of abuse, such as cocaine, ing ADHD Treatment: A Comparison of Stimulant Medication modify the strength of the connections between neurons. This Treatment for Children with ADHD, Computerized Cognitive finding cast drug addiction in a new light—as a process of mal- Training of Attention and Working Memory, and the Combina- adaptive learning. tion of the Two,” suggest that some cognitive games could be “We think Dr. Bonci will bring tremendous strength to useful, as an adjunct to medication, in treating attention deficit our already robust intramural research portfolio,” says NIDA hyperactivity disorder. Director Dr. Nora D. Volkow. “His impressive background as a Joseph Hunter Yagoda, a 17-year-old student at the William superb neuroscientist with strong clinical training brings NIDA A. Shine Great Neck (N.Y.) High School, won third place for an exceptional investigator committed to translational science “Risky Business: What Cognitive Factors Influence Risk Taking and will bring us closer to new and better medicines for the in the Academic Setting?” treatment of addiction.” He investigated the cal- Prior to joining NIDA, Dr. Bonci was in the Department of culations that go into a Neurology at the University of California, San Francisco, where teenager’s decision to cut he held the Howard J. Weinberg Endowed Chair in Addiction classes. Research. In 2009, he received the Daniel H. Efron Award for Friends of NIDA, a outstanding basic and translational research at the American coalition of individuals College of Neuropsychopharmacology. He also received the and groups that support 2004 Jacob P. Waletzky Memorial Award, given to young scien- NIDA’s mission, awarded tists for innovative research in drug addiction and . scholarships to the win- Addiction Science Award winners, Kevin “I am thrilled to be a part of one of the world’s most impor- ners: $2,500 for first place, Knight (2nd place), Ameya Deshmukh tant scientific organizations looking at the challenging problem $1,500 for second place, (1st place), Joseph Yagoda (3rd place). of drug abuse and addiction,” says Dr. Bonci. “I especially look and $1,000 for third place. forward to working with Dr. Volkow and her colleagues in the extramural program, as well as the many top-level investigators at the IRP who have been responsible for many advances Program Enhances Physician in addiction science.” Knowledge on Substance Abuse Dr. Bonci replaces Dr. Barry Hoffer, who had served as the IRP scientific director since 1996. Although substance abuse can have significant health conse- quences, most medical schools do not provide future primary care physicians with adequate training on addiction. To address Addiction Science Award this situation, NIDA funded the development of the Chief Winners Announced Resident Immersion Training (CRIT) program in addiction med- icine, which started in 2002. NIDA presented Addiction Science Awards to three high school An evaluation of the CRIT program at the Boston Univer- students during the 2010 Intel International Science and sity School of Medicine was recently conducted by Program Engineering Fair (ISEF), held last May in San Jose, California. Directors Drs. Jeffrey H. Samet and Daniel P. Alford and

16 NIDA Notes | Volume 23, Number 3 n BULLETIN BOARD

colleagues. They evaluated 64 chief residents who had partici- to supplement their curricula. Among these tools are “print and pated in the CRIT program from 2003 to 2005. The research- go” lesson plans covering a broad range of topics, such as clon- ers found that CRIT improved knowledge, confidence, and ing, gene therapy, personalized medicine, and stem cells. preparedness to diagnose, manage, and teach about substance Web designer Mr. Kevin Pompei collaborated with Dr. Stark abuse. in designing the sites. Dr. Stark is director of the Genetic Science CRIT program developers chose chief residents because Learning Center at the University of Utah. these young physicians help teach medical students and resi- dents and often go on to other leadership roles. During the 4-day program, participants received science-based resources Three Scientists Join and teaching tools on substance abuse and met with individu- Advisory Council als in recovery. They learned teaching techniques and, working with faculty mentors, developed plans to share newly learned Three scientists have knowledge and skills about substance abuse with other staff at joined NIDA’s National their home institutions. Advisory Council on When retested immediately after the program, participants Drug Abuse. The new achieved an average score of 78 on a multiple-choice exam cov- members, presented at ering addiction neurobiology, screening, referral options, phar- the council’s February macotherapy, and relapse, compared with 67 at the start of the meeting, are: n training. The program also had a longer-term impact: 6 months Caryn E. Lerman, NEW COUNCIL MEMBERS (From left) Drs. after the training, 97 percent of participants reported being Ph.D., a professor Caryn E. Lerman, Jon-Kar Zubieta, and (far either more or much more likely to incorporate information on in the Department right) Steven M. Wolinsky with NIDA Director Dr. Nora D. Volkow. substance abuse into teaching than before the training. All the of Psychiatry and participants had developed a teaching project related to sub- the Annenberg stance abuse, and 86 percent reported that these had an impact Public Policy Center and scientific director of the Abramson on their residency program curriculum. For more information Cancer Center at the University of Pennsylvania. Dr. Lerman on the CRIT program, see http://www.bumc.bu.edu/crit. has extensive expertise in research on nicotine dependence,

SOURCE including behavioral pharmacology, pharmacogenetics, Alford, D.P., et al. Promoting substance use education among generalist physicians: medications development, and, more recently, neuroimag- An evaluation of the Chief Resident Immersion Training (CRIT) program. Journal ing. She was recently elected president of the Society for of General Internal Medicine 24(1):40–47, 2009. Research on Nicotine and . n Steven M. Wolinsky, M.D., a professor of medicine and chief of the Division of Infectious Diseases at Northwestern NIDA Grantee Wins Prize for University’s Feinberg School of Medicine. Dr. Wolinsky’s Genetics Web Sites research focuses on the evolutionary mechanisms underlying host-pathogen interactions and their role in the emergence, Dr. Louisa Stark, a NIDA science education grantee, has won the spread, and containment of infectious diseases, such as HIV/ Science Prize for Online Resources in Education for developing AIDS. He also considers how viral genetic variation, driven by two interactive Web sites on genetics, one of which includes a host genetics and immunity, affects HIV infection dynamics module on addiction. and epidemic behavior. The first site, http://learn.genetics.utah.edu, explains genetics n Jon-Kar Zubieta, Ph.D., M.D., a research professor in the in terms that students in grades 5 through 12 can easily under- Molecular and Behavioral Neuroscience Institute, a profes- stand. It covers 15 topics ranging from DNA to epigenetics. The sor in the departments of psychiatry and radiology, and site’s module “The New Science of Addiction: Genetics and the director of the Neuroimaging Core at the University of Mich- Brain” (http://learn.genetics.utah.edu/content/addiction) has igan. Dr. Zubieta’s research focuses on the neurobiological been used in addiction treatment in several countries. mechanisms underlying the regulation of stress responses. The second site, http://teach.genetics.utah.edu, complements He has extensive experience in the use of imaging technolo- the Learn Genetics materials. It helps educators bring genetics gies for the quantification of metabolism, blood flow, and alive in the classroom by providing them with tools and resources neuroreceptor sites in human subjects. n

NIDA Notes | Volume 23, Number 3 17 ■ UPDATE Followup on previous NIDA Notes reports

Parental Supervision and Modafinil Normalizes Genetics Interact To Influence Sleep During Early Cocaine Nicotine Addiction Abstinence

Modafinil, a medication used to treat narcolepsy and related dis- GENE VARIANT AND LOW PARENTAL MONITORING COMBINE TO ELEVATE SMOKING RISK Increased risk of orders, dramatically improves sleep among recently abstinent nicotine addiction conferred by one genotype of CHRNA5 dramatically cocaine abusers. Better sleep may boost patients’ attention, increases among people who experienced low parental supervision as memory, and mood—helping them benefit from behavioral ther- young teens. apy for addiction. Ten inpatients in a behavioral therapy program who received Genotype #1 Genotype #2 Genotype #3 10 a daily morning dose of modafinil for the 16 days of the study 8 fell asleep more quickly, spent more time in deep sleep, and slept 6 longer than 10 inpatients in a placebo group, reports a team of 4 2 NIDA-funded

Addiction (multiplier) 0 addiction and SLEEP OF ABSTINENT COCAINE Highest Lowest Highest Lowest Highest Lowest Increase in Risk for Smoking Level Level Level Level Level Level sleep research- ABUSERS NORMALIZES WITH (n=673) (n=179) (n=664) (n=218) (n=190) (n=58) ers at the Yale MODAFINIL Cocaine abusers treated with Parental Monitoring modafinil for 16 days demonstrated improvements and Harvard in several characteristics of sleep, including total schools of sleep time. A gene variant that increases the risk for nicotine addiction medicine. All exerts less influence when parents monitor young adolescents’ the inpatients Total Sleep Time whereabouts and activities, report Dr. Laura Jean Bierut and col- were absti-  leagues at Washington University in St. Louis and other institu- nent through-  tions. They studied 2,027 adults who had smoked at least 100 out the study,   cigarettes in their lifetime, of whom 1,032 were dependent on and the sleep Minutes nicotine. The researchers determined which participants car- of patients in  ried a specific variant of the gene called CHRNA5, which encodes the placebo  Placebo Modafinil Non-Addicted the a5 subunits of nicotinic acetylcholine receptors. The variant group dete- Comparison elevated the risk for smoking addiction eightfold among peo- riorated during Group ple who recalled lax parental supervision during their middle- the weeks of school years, but it only doubled the risk among people who abstinence. After 1 and 2 weeks of abstinence, patients treated reported intense parental supervision. Among participants with modafinil reported less daytime sleepiness and demonstrat- with two other genotypes of CHRNA5, low parental monitoring ed less fatigue on tests than those who received placebo. On only roughly doubled risk for nicotine addiction. most measures, the sleep of the modafinil-treated cocaine abusers In previous research, Dr. Bierut and colleagues had linked by the end of the study was more similar to that of 12 non- an increased risk for nicotine addiction to at least two distinct addicted volunteers than to that of the cocaine abusers receiving variants near the a5 subunit of the nicotinic receptor (see “Stud- the placebo, reports the team, headed by Yale’s Dr. Peter Morgan. ies Link Family of Genes to Nicotine Addiction,” NIDA Notes, The new results, the first to show modafinil’s sleep-enhancing Volume 22, Number 6, page 1). The team’s new research sug- effects among abstinent drug abusers, extend the team’s previ- gests that strong parental supervision may mitigate the influence ous finding that during early abstinence, cocaine abusers dem- of some addiction-associated genes by limiting young teens’ onstrate disrupted sleep without being aware of it (“Chronic opportunities to try cigarettes and to smoke regularly. Without Cocaine Abusers Have Occult Insomnia in Early Abstinence,” these critical steps in the development of nicotine addiction, the NIDA Notes, Volume 21, Number 5, page 12). If the beneficial genetic vulnerability never comes into play. effects of modafinil are verified, clinicians may incorporate the medication into addiction treatment. Addiction 104(10): 1731–1740, 2009. American Journal of Psychiatry 167(3):331–340, 2010.

18 NIDA Notes | Volume 23, Number 3 n TEAROFF Information to clip, save, and share

Drug Abuse at Highest the decline in marijuana use over the past decade had begun to reverse. In the past few years, a growing percentage of youth who Level in Nearly a responded to the two surveys said they did not believe that regu- Decade lar use of the drug was very harmful. PRESCRIPTIONS, METH, AND ECSTASY ON THE RISE llicit drug use in the United States has risen to its highest Abuse of prescription drugs and the less frequently used meth- level in 8 years, according to the 2009 National Survey on amphetamine and ecstasy also saw increases. Nonmedical use of I Drug Use and Health (NSDUH). Last year, 8.7 percent of prescription drugs rose 12 percent, from 2.5 percent in 2008 to 2.8 Americans aged 12 and older—an estimated 21.8 million people— percent in 2009. Abuse of methamphetamine rose from 0.1 per- said they used illicit drugs in the month prior to the survey, which cent to 0.2 percent, and ecstasy from 0.2 percent to 0.3 percent. represents a 9 percent increase over the 2008 rate.

The rise was driven largely by an increase in the use of mari- RISE IN MARIJUANA USE DRIVES UPSWING Marijuana is juana, which rose to 6.6 percent in 2009 after holding steady the most commonly used illicit drug, with 16.7 million people aged 12 and older reporting past-month use in 2009. A 6.6 percent increase in at around 6 percent since 2002. The increase was particularly usage—the highest in 8 years—drove up overall illicit drug use. high among youth aged 12 to 17 and young adults aged 18 to 25. Marijuana is the most commonly used illicit drug; about three- Any Illicit Drug Use Marijuana Prescription Drugs quarters of those who report illicit drug use cite marijuana abuse. Cocaine Hallucinogens “These results are a wake-up call to the Nation,” said 9 Ms. Pamela S. Hyde, administrator of the Substance Abuse and 8

Mental Health Services Administration (SAMHSA), at a press 7 conference held September 16 to announce the findings. “Our 6 strategies of the past appear to have stalled with ‘Generation Next.’ Parents and caregivers, teachers, coaches, and faith and 5 community leaders must find credible new ways to communicate 4 with our youth about the dangers of substance abuse.” 3 Mr. Gil Kerlikowske, director of the White House Office of Percentage Using in Past Month 2 National Drug Control Policy, speculated at the press conference 1 that daily coverage in the media of efforts to change state laws 0 to allow the sale of “medical marijuana” and policy debates over 2002 2003 2004 2005 2006 2007 2008 2009 legalization of the drug could be contributing to the notion that marijuana is benign. The 2009 survey also found that: Changes in state policies and the widening availability of med- n Drug abuse among those aged 50 to 59 doubled to 6.2 percent ical marijuana are consistent with the shift in attitudes evident in from 2.7 percent in 2002. This trend reflects the entry into the survey, says Dr. Wilson Compton, director of NIDA’s Division this age bracket of increasing numbers of baby boomers, who of Epidemiology, Services and Prevention Research. “However, have a higher rate of illicit drug use than older cohorts. we can’t tell which comes first,” he says. “Do the changes in per- n Only about 11 percent of those who need treatment for drug ceived risk lead to changes in laws and regulations, or do these or alcohol abuse received therapy in a specialty facility. Previ- policy changes lead to a shift in attitudes?” ous years had shown a similar disparity. Dr. Compton says the rise in drug abuse also corresponds The annual NSDUH survey is sponsored by SAMHSA. The with a decrease in prevention messages targeting youth, as well 2009 results are based on responses from 68,700 civilians nation- as a weakening perception among young people that drugs are wide who do not live in institutions. The report is available online harmful. “We need to redouble our prevention efforts in families, at www.oas.samhsa.gov/NSDUH/2k9NSDUH/2k9Results.htm. n schools, and communities,” he says. SOURCE The increase in marijuana use was foreshadowed in survey Substance Abuse and Mental Health Services Administration, 2010. Results from the results released late last year. Both the 2008 NSDUH survey and 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings the 2009 NIDA-sponsored Monitoring the Future survey, which (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4586). Rockville, MD. covers students in the 8th, 10th and 12th grades, indicated that

NIDA Notes | Volume 23, Number 3 19 ■ WHAT THE NUMBERS SAY

Detoxification Services and Pharmacotherapies Lacking in Nation’s Jails and Prisons Although many people in jails and prisons have a history of substance abuse, the majority of  correctional facilities offer neither detoxification services to help inmates through  No Detoxification Services or Pharmacotherapies Provided nor pharmacotherapies, such as methadone, Pharmacotherapies Provided naltrexone, or buprenorphine, to aid them in But Not Detoxification Services maintaining abstinence. The findings were derived Detoxification Services Provided  from responses to a nationally representative But Not Pharmacotherapies sample of 198 correctional institutions that partic- Detoxification Services and ipated in the National Criminal Justice Treatment Pharmacotherapies Provided Practices survey, which was developed by NIDA’s  Criminal Justice–Drug Abuse Treatment Studies research network.

Source: Oser, C.B., et al. Organizational-level correlates of the provision of detoxification services and medication-based treatments for substance abuse in correctional institutions. Drug and Alcohol Dependence 103S:S73–S81, 2009.

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