www.drugabuse.gov Volume 22, Number 6 U.S. Department of Health and Human Services | National Institutes of Health

Studies Link Family of Genes ALSO IN THIS ISSUE to Nicotine Addiction Research Findings 4 Recovery Checkup Genes for protein constituents of nicotinic acetylcholine receptors System Helps Substance Abusers Who Have influence early smoking responses and the likelihood of nicotine Mental Disorders dependence. 6 Study Gives Green Light to Antiretroviral Medications for HIV-Infected Injection BY LORI WHITTEN, Scientists have long known that nicotine Drug Users NIDA Notes Staff Writer produces many of its effects by attaching to 7 Rare Glutamate Receptor receptors for acetylcholine, a neurochemical Proliferates After Cocaine ne person reaches for a cigarette that influences memory, arousal, attention, and Withdrawal soon after waking, smokes a pack mood. These nicotinic acetylcholine (nACh) Director’s Perspective a day, and cannot seem to quit. receptors comprise five subunits arranged 2 NIDA’s 35th Anniversary: Another smokes a few cigarettes around a central pore, like sections of an orange. Science Focused on nowO and then but never feels driven by the Each of the genes identified by the new studies Solutions need for nicotine. A third person smoked for a provides the blueprint for one of a dozen pro- Research in Brief while in youth and then stopped. According to teins, labeled α2-10 and β2-4, that serve as sub- several recent NIDA-funded studies, such con- units in nACh receptors. Variations in the DNA 3 • Rats Reared Alone Show ADHD Signs • Anticipation trasting smoking patterns and responses may that encodes these genes may alter the struc- of Methadone Enhances arise because individuals inherit different ture or amount of the proteins produced, which Brain Reactivity to Heroin Cues • Recovery May Be forms of half a dozen genes that dictate in turn can modify what happens when nicotine Harder for Adolescents • the features of the brain receptor to which molecules attach to the receptors. Test Substance Attenuates Signs of Cocaine nicotine binds. [ Continued on page 10 ] Withdrawal in Rats

NICOTINIC RECEPTORS VARY IN COMPONENT PROTEINS AND ACTIVITY Nicotine initiates its Bulletin Board effects by binding to nicotinic acetylcholine (nACh) receptors, each consisting of five proteins arranged in a circle around a central pore. The receptors occur in subtypes, which differ in their constituent proteins and physiological 15 • Program to Train and pharmacological characteristics. Asterisks indicate where nicotine and acetylcholine bind to each receptor Physicians Who Treat Drug subtype. Addiction • Substance Abuse and Sexual Risk Show Town-Gown Divide • Recognition for NIDA β2 β3 α7 Notes

Index β2 α4 β2 α6 α7 α7 16 Volume 22 Tearoff

α4 β2 α6 β2 α7 α7 19 Report Discusses Co-Occurrence of Drug Abuse and Other Mental α4 β2: The most α6 β2 β3: A subtype α7: A subtype Disorders common and best- localized to a few containing just one studied subtype brain areas kind of subunit 20 What the Numbers Say

NIDA Notes | Volume 22, Number 6 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. NIDA’s 35th Anniversary: MasiMax Resources, Inc. MANAGING EDITOR Andrew Keegan Science Focused on Solutions MasiMax Resources, Inc. SENIOR WRITER Lori Whitten, Ph.D. MasiMax Resources, Inc. ongress created the National Institute on Drug Abuse in 1974 to bring the ASSOCIATE EDITOR power of science to bear against a burgeoning epidemic of drug abuse and Debra P. Davis addiction. The wisdom of that decision is evident in today’s roster of proven MasiMax Resources, Inc. effective interventions to prevent and treat addiction and in the increased DESIGN/LAYOUT Maggie Bray Cpublic understanding that addiction is a chronic brain disease rather than a moral failure. MasiMax Resources, Inc. Since its inception, NIDA has funded and guided a comprehensive program of basic EDITORIAL BOARD and clinical research involving many of the Nation’s premier scientists and clinicians. Our David Anderson, Chair; Public goal is to apply the fruits of scientific discovery to real-world problems. Our mission also Health Advisor, Office of Science Policy and Communications includes informing the Nation about the nature and dangers of drug abuse and addiction. Nicolette Borek, Ph.D., Research Among their major accomplishments, NIDA-supported researchers have Psychologist, Division of Clinical Neuroscience and Behavioral Research ■ Established and maintained national data collection systems to monitor patterns of J.C. Comolli, Public Health Advisor, drug abuse and identify population groups at risk. Division of Pharmacotherapies and Medical ■ Showed that all abused and addictive substances share certain neural and molecular Consequences of Drug Abuse effects. These findings and others on the particular effects of specific drugs led to the Jennifer Elcano, M.A., Science Writer, Office of Science Policy and Communications development of medications to treat opioid and nicotine addiction. Lynda Erinoff, Ph.D., Associate ■ Identified principles of successful drug abuse prevention. Director, AIDS Research Program, Division ■ Advanced effective drug abuse treatments based on biological, developmental, social, of Epidemiology, Services and Prevention Research and environmental factors. Jacqueline Lloyd, Ph.D., Health Science ■ Demonstrated that drug abuse treatment can reduce the spread of HIV and support Administrator, Division of Epidemiology, effective treatment of HIV disease. Services and Prevention Research Marsha F. Lopez, Ph.D. , Health Science ■ Applied genetics, epigenetics, and neuroimaging techniques to the study of drug abuse, Administrator, Division of Epidemiology, opening up extraordinary opportunities for the development of new and increasingly Services and Prevention Research individualized approaches to prevention and treatment. Gerald McLaughlin, Ph.D. , Chief, Grants Review Branch, Office of Extramural Affairs Mary Ellen Michel, Ph.D., Deputy Drug abuse evolves constantly as new drugs and new patterns of abuse emerge, each Director, Center for the Clinical Trials Network with new consequences for public health. In its 35 years, NIDA has responded to epidem- Ivan Montoya, M.D., M.P.H., Medical Officer, Division of Pharmacotherapies and ics of cocaine, methamphetamine, and steroid abuse, as well as drugs’ contributions to Medical Consequences of Drug Abuse the spread of HIV and hepatitis C. Today, NIDA-funded researchers are seeking answers Mary Pfeiffer, Ph.D., Editor and Writer, to the emergence of marijuana of unprecedented potency, rising prescription drug abuse, Intramural Research Program and the impact of combat stress on veterans’ risk of drug involvement. In the future, as Kenzie Preston, Ph.D., Chief, Clinical Pharmacology and Therapeutics Research now and in the past, NIDA will engage each new challenge with comprehensive scientific Branch strategies and the most advanced scientific tools and technologies to alleviate the impact Joni Rutter, Ph.D., Program Director, of drugs on the health and prosperity of affected individuals, their families and communi- Genetics and Molecular Neurobiology Research Branch, Division of Basic Neuroscience and ties, and the Nation. ■ Behavioral 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 MasiMax Resources, Inc., under Contract No. N01DA-4-1117 from the National Institute on Drug Abuse. 2 NIDA Notes | Volume 22, Number 6 ■ RESEARCH IN BRIEF Highlights of recently published NIDA-supported studies

Anticipation of Test Substance Methadone Enhances Attenuates Signs of Brain Reactivity to Cocaine Withdrawal Heroin Cues in Rats Images of heroin prepa- An experimental compound ration and injection can that selectively stimulates incite craving and excite Recovery May delta opioid receptors reduc- brain areas associated with Be Harder for es anxiety- and depression- Rats Reared Alone reward-seeking even in Adolescents, Animal like behaviors that follow Show ADHD Signs stabilized, long-term, Study Suggests cessation of chronic cocaine Laboratory animals raised in methadone-maintained Adolescents’ heightened sensi- exposure in rats. Dr. Ellen isolation may provide use- patients, according to Drs. tivity to drug reward puts them Unterwald of Temple Uni- ful subjects for studies of Daniel Langleben, Anna Rose at enhanced risk for progressing versity School of Medicine attention-deficit hyperactivity Childress, Charles O’Brien, from drug experimentation to and The Rockefeller Univer- disorder (ADHD) and other and colleagues at the Penn- addiction and may also increase sity tested the compound, conditions characterized by VA Addiction Treatment their challenges in recovery. In SNC80, after she, Dr. Shane impulsive choice. Dr. Jenni- Research Center at the a recent experiment, research- Perrine, and colleagues dis- fer Perry of the Minneapolis University of Pennsylvania ers taught rats to associate a covered that delta opioid Medical Research Foundation School of Medicine and specific site with cocaine infu- receptors in the rat brain and Dr. Michael Bardo of the McLean Hospital, Harvard sions. After dispensing of the do not respond effectively University of Kentucky found University. The research drug was halted, adolescent rats after chronic cocaine expo- that rats make more impul- team used functional mag- continued to return to the site sure. Other researchers had sive choices after being raised netic resonance imaging for 9 days; adult rats, in com- linked decreased delta opioid alone in bare laboratory cages to monitor activity in the parison, stopped frequenting receptor responsiveness than when raised in group extended limbic system of 25 the site after 5 days. The find- with rodent behavior resem- housing equipped with novel patients in long-term metha- ing confirms that adolescents bling human anxiety and objects. Treating rats from the done maintenance while experience cocaine’s reward- depression. two contrasting environments showing them heroin-relat- ing effects more intensely and Two FDA-approved with medications for ADHD ed images before and after suggests that they develop medications, propranolol produced results parallel to their daily methadone dose. cocaine–environment and amantadine, have also those seen in people with and Subjective heroin craving associations that are harder to shown potential to ease without ADHD: Injections and limbic reactivity to her- break, say Drs. Heather Bren- these cocaine withdrawal of the ADHD medications oin cues were greater before, house and Susan Andersen symptoms in clinical trials. d-amphetamine or methylphe- as compared with after, the of McLean Hospital, Harvard Propranolol appears to blunt nidate moderated the excess daily methadone medica- Medical School, in Boston. anxiety by blocking the recep- impulsivity of the animals tion, but methadone plasma The adolescent animals in tor for adrenaline, a hormone reared alone. In contrast, levels were uncorrelated the experiment also renewed released during stressful situ- among animals reared in the with the brain response. The their predilection for the ations. Amantadine seems enriched environment, the findings suggest that indi- cocaine-associated site more to boost mood by increas- drugs did not decrease impul- viduals in methadone main- readily than the adults when ing levels of dopamine and sive choice, and d-amphet- tenance treatment remain given a priming mini-dose of norepinephrine in the brain. amine actually increased that responsive to cues that may the drug. One potential impli- Treatment of the anxiety and trait. The researchers plan to motivate heroin seeking and cation, the researchers say, is depression that frequently use rats raised in isolation to relapse, particularly under that adolescent drug abusers accompany withdrawal from explore the neurobiology that conditions of high drug may need longer treatment cocaine is important because links impulsivity and vulner- expectancy, such as prior to interventions than adults do to it reduces the rate of relapse ability to addiction. their daily medication dose. achieve stable recovery. to cocaine addiction.

> Behavioural Brain Research > American Journal of Psychiatry > Behavioral Neuroscience > Neuropharmacology 54(2):355– 193(1):48–54, 2008. 165(3):390–394, 2008. 122(2):460–465, 2008. 364, 2008.

NIDA Notes | Volume 22, Number 6 3 ■ RESEARCH FINDINGS Recovery Checkup System Helps Substance Abusers Who Have Mental Disorders

Benefits include quicker return to treatment when recovery falters and longer retention.

BY LORI WHITTEN, measures than did substance abusers appropriate community resources, includ- NIDA Notes Staff Writer without other mental health problems. ing admission to a treatment program, Recovery management checkups and continues to work with them until posttreatment intervention (RMC) aim to identify and alleviate cli- they have been engaged in treatment for at to support recovery may ent problems before they derail recov- least 2 weeks. The conceptual framework be especially beneficial for ery and to facilitate rapid readmission to of RMC is to treat addiction as a chronic substance abusers with co- treatment when recovery falters. Quar- disease, with long-term management to Aoccurring mental disorders. In a recent terly appointments form the core of minimize the number of acute episodes of subgroup analysis of data from previous RMC. During these sessions, interviewers substance abuse and with prompt treat- trials, Dr. Michael Dennis and Dr. Christy assess clients using the structured Global ment when episodes occur to prevent Scott of Chestnut Health Systems in Appraisal of Individual Needs tool and them from becoming more severe and Chicago and Dr. Brian Rush of the Cen- refer those with significant problems to a consequential. tre for Addiction and Mental Health in linkage manager, who administers a brief The new analysis included 865 people Toronto, Canada, found that clients with intervention using motivational inter- who were recruited as they entered sub- co-occurring disorders responded to the viewing techniques. The linkage man- stance abuse treatment at the Haymar- intervention with improvements on more ager connects clients who are willing to ket Center in Chicago. Over 66 percent of the participants met past-year criteria for one or more co-occurring mental dis- RECOVERY MANAGEMENT CHECKUP SYSTEM BENEFITS SUBSTANCE ABUSERS orders, including 27 percent with only WITH MENTAL DISORDERS More patients who participated in quarterly Recovery Management Checkups returned to treatment upon relapse than those who received assessments internalizing disorders (e.g., mood, anxi- only. The enhanced-checkup intervention benefited substance abusers whether or not they had ety, and trauma disorders) and 39 percent mental disorders. with both internalizing and externalizing disorders (e.g., attention, hyperactiv- Recovery Management Checkups Outcome Monitoring Only 100 ity, impulse, conduct, and gambling disor- ders). Among the three groups, the like- 90 lihood of having a history of substance 80 abuse treatment, of mental health treat- 70 ment, and of a wide range of other prob- 60 lems, such as homelessness and victimiza- 50 tion, was lowest in the participants with 40 substance use disorder only and highest 30 in those with substance abuse and both 20 internalizing and externalizing mental 10 disorders. In the latter group, 76 percent Percentage Readmitted to Treatment 0 of the participants reported having been Substance Use Substance Use Substance Use, and homeless at some time, and 91 percent Disorder Only and Internalizing* Internalizing*and Disorders Externalizing** Disorders reported having been victimized. * Mood, Anxiety, and Trauma Disorders. The study protocol assigned the par- ** Attention, Hyperactivity, Impulse, Conduct, and Gambling Disorders. ticipants to receive intensive outpatient

4 NIDA Notes | Volume 22, Number 6 therapy, short- or long-term residential The sizes of these differences were similar step in that direction,” adds Dr. Rush. The therapy, or detoxification, as deemed across all the comorbidity subgroups. researchers plan to verify their results by appropriate based on their initial presen- On some additional outcomes, only following part of the cohort for an addi- tation. The study protocol scheduled all RMC recipients with mental disorders tional 2 years. The Chestnut team also participants for quarterly visits to a clinic, showed a benefit. For example, RMC plans to test RMC with women leaving beginning 90 days after their pretreat- recipients with an internalizing disorder the criminal justice system in Chicago, ment interview and assessment and con- spent at least 40 more days in treatment and Dr. Rush has proposed developing an tinuing for 2 years. Patients randomized than controls with those problems. Among RMC system in Canada. to RMC received support from the linkage patients with both an internalizing and an “The RMC intervention offers a recovery- manager if they needed treatment, while externalizing disorder, those who received oriented approach,” says Dr. Thomas patients randomized to control were only RMC were abstinent on 51 more days than Hilton of NIDA’s Division of Epidemiol- assessed, although they could re-enter controls during the study and demon- ogy, Services and Prevention Research. “It treatment on their own. strated an unmet need for treatment at not only monitors substance abuse after Among all three comorbidity sub- nearly one-third fewer of their visits. treatment but also assesses the character- groups—those with only substance abuse, istics, or recovery capital, that facilitate those with substance abuse and at least CONCRETE LONG-TERM SUPPORT a healthy, productive, drug-free lifestyle one internalizing disorder, and those with For most substance abusers—and espe- in the long term. Knowing each patient’s substance abuse and internalizing and cially those with co-occurring mental health recovery capital is critical because recov- externalizing disorders—more than 80 problems—addiction is a chronic, relaps- ery occurs outside the direct care system percent were assessed as needing to return ing condition. “Our recovery management and rests heavily on the shoulders of the to treatment at least once over the 2-year checkup system addresses that reality, and individual. It makes good clinical sense to study. Consistent with the goals of RMC, it’s good to see that the intervention helps build up the patient’s capacity for recovery more participants who received the inter- an important subgroup of patients—those if it is low, and the RMC offers a concrete vention returned to treatment, and they with co-occurring mental disorders—as intervention that provides support.” ■ returned sooner. Overall, 59 percent of the well as others,” Dr. Dennis says. RMC group returned to treatment, as com- “Decisionmakers need data to con- SOURCE pared with 45 percent of the other group, vince them that RMC can work with Rush, B.R. et al. The interaction of co-occurring men- tal disorders and recovery management checkups on and their average time before treatment patients who have the most severe prob- substance abuse treatment participation and recov- was 306 days, as compared with 630 days. lems, and our findings are a good first ery. Evaluation Review 32(1): 7–38, 2008.

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NIDA Notes | Volume 22, Number 6 5 ■ RESEARCH FINDINGS Study Gives Green Light to Antiretroviral Medications for HIV-Infected Injection Drug Users

HIV mortality rates were similar regardless of whether patients used illicit injection drugs.

BY LORI WHITTEN, MONITORING PATIENT MORTALITY respectively, did not differ meaningfully NIDA Notes Staff Writer In their study, Dr. Evan Wood of the at any point. These rates yielded an esti- British Columbia Center for Excellence in mate that the drug injectors’ risk of dying imited access, financial con- HIV/AIDS and colleagues enrolled every- was 1.09 times that of the other patients— straints, and stigma—rather one who started HAART therapy in British a difference well within the range that is than lifestyle—may be the main Columbia, Canada, between August 1996 potentially attributable to chance. The obstacles keeping HIV-infected and June 2006. Of these 3,116 men and relative risk estimate narrowed further, to Linjection drug users from obtaining the women, 915 used injection drugs. At the 1.06, when the researchers excluded from benefit of highly active antiretroviral ther- time they initiated anti-HIV therapy, both their analysis 87 deaths—caused by acci- apy (HAART). In a prospective study in a the injection drug users and the other dental poisonings, suicides, and trauma setting of universally guaranteed health patients averaged about 40 years of age (see graph)—that were clearly unrelated care, including free medications for the and, as citizens of Canada, had access to to the HIV disease process. Although the indigent, mortality rates from HIV in free medical care and HAART. two groups’ mortality rates appeared to infected people who used illicit injection Dr. Wood and colleagues followed the be diverging at the end of the followup drugs and those who did not use injec- participants until June 30, 2007—a span period, the data demonstrated a clear tion drugs were nearly identical over the 5 of 5.3 years on average for the patients clinical benefit of making HAART avail- years following HAART initiation. who used injection drugs and 4.3 years for able to patients who use injection drugs. In 2006, 205,000 injection drug users the other patients. During the first year on “Potent antiretroviral therapies were living with HIV in the United States, HAART, 41 percent of the patients using equally benefited people with and with- according to the Centers for Disease Con- injection drugs took 95 percent or more out injection drug use, despite the lower trol and Prevention. Although HAART is of their medications on schedule, as com- medication adherence among people who not a cure, it improves the prognosis for pared with 63 percent of the other patients. had used injection drugs,” says Dr. Wood. people infected with the virus. However, Nevertheless, the two groups’ cumulative “HAART not only benefits the health of past studies have shown that physicians mortality rates, 27 percent and 22 percent, [ Continued on page 9 ] tend not to recommend HAART when a patient has a history of INJECTION DRUG USERS BENEFIT FROM HAART In British Columbia, where everyone has full injection drug use. Some doc- access to HIV care and medications, injection drug users’ all-cause and HIV-related survival rates did not differ tors assume that injection drug from those of other patients throughout 7 years following initiation of highly active antiretroviral therapy (HAART). users will be unable to adhere to All-Cause Mortality Non-Accidental Mortality HAART’s stringent medication 30 30 regimens or that liver disease, 25 25 which is common among injec- 20 20 tion drug users, might impede the medications’ therapeutic 15 15 efficacy. The new results counter 10 10 Injection Drug Injection Drug those concerns and indicate that Users (IDU) Users (IDU) 5 5 access to HAART can improve the Non-IDU Non-IDU health of HIV-infected patients Cumulative Mortality (percentage) 0 Cumulative Mortality (percentage) 0 who have a history of injection 0 12 24 36 48 60 72 84 0 12 24 36 48 60 72 84 Time (months) Time (months) drug use.

6 NIDA Notes | Volume 22, Number 6 ■ RESEARCH FINDINGS Rare Glutamate Receptor Proliferates After Cocaine Withdrawal

Molecular change in rat brains parallels increase in drug-seeking behavior.

BY MOLLY MCELROY, the NAc, an area that shapes motivation NOSE POKES AND RECEPTORS NIDA Notes Contributing Writer by linking experience to feelings of reward Scientists have long recognized that and satisfaction. Most AMPA receptors cocaine craving intensifies, or incubates, roliferation of a rare neuro- include subunits called GluR1 and GluR2, for several weeks following withdrawal receptor may underlie the but those newly generated following from the drug. Cocaine abusers’ reports of intensification of craving that cocaine withdrawal lack GluR2. craving and their risk of relapse both peak cocaine abusers experience “Switches in the subunit composition after several weeks of abstinence. duringP their first weeks of abstinence. of AMPA receptors have been uncovered Prior NIDA-funded research has shown NIDA-funded researchers found that, in in other neural modifications, but our that drug craving involves a complex neu- rats, the quantity of these receptors in the study describes the most long-lasting ronal circuit that includes cortical and nucleus accumbens (NAc) increased from change that has yet been found in any limbic regions, as well as NAc. However, the first to the 45th drug-free day and cor- brain region,” says Dr. Marina Wolf of there is evidence that glutamate inputs related with an increase in the animals’ the Chicago Medical School at Rosalind into the NAc are part of a final common drug-seeking. Franklin University of Medicine and Sci- pathway for drug seeking. What’s more, The implicated receptors are a subtype ence. According to Dr. Wolf, her team’s AMPA-type glutamate receptors are of the α-amino-3-hydroxy-5-methyl-4- results are particularly exciting because they increasingly recognized as key players in isoxazolepropionic acid (AMPA) recep- show how long-lasting modifications can the rewiring of brain circuits in response tor. AMPA receptors regulate cellular be produced in the adult brain and because to many kinds of experience. Dr. Wolf’s responses to the neurotransmitter gluta- the brain alteration is directly linked to a team therefore focused on testing the role mate throughout the brain, including in disease-related behavioral change. of NAc AMPA receptors in the incubation of cocaine craving.

NEW RECEPTORS APPEAR DURING WITHDRAWAL FROM COCAINE The team’s first step was to induce AMPA receptors respond to glutamate signals within the brain and play a role in cocaine seek- craving incubation in rats. Animals were ing. These receptors have four subunits that typically include one called GluR2 (left). However, trained to poke their noses into a hole during withdrawal from cocaine, new AMPA receptors that lack GluR2 (right) appear in the mem- branes of nerve cells in the brain’s nucleus accumbens. The new receptors are more permeable in a test chamber to elicit an intrave- to calcium and have a higher ion flow when activated than the more common AMPA receptors. nous infusion of cocaine. Each infusion was paired with a light or light-plus- tone cue, enabling the rats to learn to + Na Na+ Ca2+ associate these cues with cocaine avail- ability. Rats had access to cocaine for 6 hours a day, enabling a high level Glu Glu Glu Glu of drug intake. After 10 days of this regi- R1 R2 R1 R1 men, the researchers initiated cocaine withdrawal by halting the rats’ access to the drug. At intervals during the rats’ withdrawal from the drug, the researchers returned them to the test chamber. The rats resumed poking their noses in the hole, but the poking now brought no cocaine.

NIDA Notes | Volume 22, Number 6 7 n RESEARCH FINDINGS

The researchers counted the number of AMPA RECEPTORS PRODUCED DURING COCAINE WITHDRAWAL LACK GLUR2 nose pokes as a measure of the animals’ SUBUNITS Between day 1 and day 45 of cocaine withdrawal, the number of GluR1 receptor desire for the drug and the willingness subunits increased dramatically, while the number of GluR2 subunits stayed about the same. to expend effort to obtain it. The rats poked more than twice as much on with- 300 drawal day 45 than on withdrawal day 1, GluR1 GluR2 demonstrating that their urge to obtain Withdrawal cocaine had increased—incubated— 200 Day 1 during the interval. Biochemical assays of the rats’ brain Withdrawal tissue showed that the number of GluR1 Day 45 receptor subunits in the NAc doubled 100 between withdrawal day 1 and day 45.

There was no concomitant increase in Receptor Subunit Presence* GluR2 subunits, however, indicating that the NAc cells had generated a new 0 Saline Cocaine Saline Cocaine complement of GluR2-lacking recep- tors during this interval. No other brain Test Group area exhibited AMPA changes, nor were * Expressed as percentage of level measured for the saline control on day 1 of withdrawal. there changes in another common type of glutamate receptor, the NMDA receptor. as other consequences for intracellular “This compensatory change backfires The researchers next established signaling. when the animal encounters a cocaine- a causative role for the newly formed “Calcium entry through the GluR2- related cue and glutamate is released into GluR2-lacking AMPA glutamate recep- lacking AMPA receptor channel may con- the NAc,” says Dr. Wolf. “This occurs tors in the rats’ drug-seeking behavior. tribute to cocaine-induced brain changes because the responsiveness of the NAc They injected a chemical (1-naphthyl by activating signaling pathways that are neurons to glutamate has been increased acetyl spermine, or NASPM) that prevents not in play when other types of AMPA due to synaptic incorporation of GluR2- glutamate from binding to GluR2-lacking receptors are stimulated in normal rats,” lacking AMPA receptors. We propose AMPA glutamate receptors into the NAc Dr. Wolf suggests. For example, calcium that this enhanced responsiveness of NAc of cocaine-exposed rats and showed influx into brain cells via glutamate recep- neurons underlies increased cue-induced that, in this situation, incubation is tors has been shown to promote lasting cocaine craving.” inhibited. Derived from a spider toxin, sensitization of the cell to future gluta- the chemical reduced cocaine-seeking mate signals in a process, called long-term CLINICAL APPLICATIONS behavior on withdrawal day 45 by more potentiation, that encodes information In recovering addicts, exposure to than half. and experience during learning. Such sen- environmental cues previously associated sitization in the NAc, with its role in moti- with drug use, such as cocaine parapher- MECHANISMS OF INCUBATION vation and reward, would be compatible nalia, is an important trigger for cocaine The new findings may be explained with incubation of cocaine craving and craving leading to relapse. Dr. Wolf’s in terms of previous research that has seeking. work on cue-induced cocaine craving in shown that what happens when glutamate Why should cocaine withdrawal pre- rats suggests that GluR2-lacking AMPA binds to an AMPA receptor depends, in cipitate AMPA receptor proliferation in glutamate receptors might be a useful part, on whether the receptor contains the NAc? Dr. Wolf and colleagues note target for medications designed to reduce GluR2. All AMPA receptors contain an that during cocaine withdrawal, areas of the frequency of relapse. While blocking ion channel that allows sodium entry, the brain that release glutamate into the glutamate receptors may lead to serious which excites neurons by depolarizing NAc are hypoactive. Possibly, the NAc side effects, selective blockade of GluR2- them. AMPA receptors that lack GluR2 ramps up its AMPA receptor complement lacking AMPA receptors might be less admit calcium as well as sodium. This to compensate for the resulting reduction problematic because these receptors are leads to a stronger depolarization as well in incoming neurotransmitter. a minority population in the normal brain,

8 NIDA Notes | Volume 22, Number 6 according to Dr. Wolf. brain disorders, including neuronal cell ■ A N T I R E T R O V I R A L MEDICATIONS NASPM cannot be used in people death and epilepsy. [ Continued from page 6 ] because it works only when injected “The expression of GluR2 in neurons directly into the brain. Scientists is altered not only by drugs of abuse but individuals, but it may also reduce the may, however, develop similar block- also, in certain vulnerable neurons, after transmission of HIV to others.” The team ers in the future that could be taken seizures, ischemia, or administration of plans to examine whether, by lowering as pills or by injection. Such a medi- ­ some other drugs. For example, in some viral load, HAART can decrease the num- cation might be used to dampen cue- neurons, ischemia triggers down-regula- ber of new transmissions from both injec- induced cocaine craving during the first tion of GluR2 and enhances AMPA recep- tion drug users and people who do not few months of withdrawal, when absti- tor-mediated calcium and zinc influx inject drugs. nent cocaine addicts are particularly that may mediate the death of these “Approximately one-third of HIV prone to cue-induced relapse, Dr. Wolf neurons. Therefore, NASPM-like medi- infections outside sub-Saharan Africa are says. cations may obtain several therapeutic attributable to injection drug use, accord- Dr. Jerry Frankenheim of NIDA’s applications,” Dr. Frankenheim says. ing to the Joint United Nations Pro- Functional Neuroscience Research “Dr. Wolf’s work represents part of gramme on HIV/AIDS,” says Dr. Jacques Branch agrees that a drug that acts like an exemplary, synergistic collaboration Normand, director of NIDA’s AIDS NASPM could potentially be a useful with members of NIDA’s Intramural Research Program. “Because HAART has treatment for blocking cue-induced Research Program, including Dr. Yavin produced dramatic improvements in HIV cocaine seeking. “NIDA’s medications Shaham, who in 2001 first reported incu- patients’ survival and may reduce trans- development group is also looking into bation of cocaine craving in an animal mission of the virus, increasing HAART NASPM as a lead towards a therapy to model,” says Dr. Frankenheim. ■ delivery to injection drug users should be prevent relapse,” he says. a global public health priority.” ■ He adds that NASPM-like compounds SOURCE may be useful for other cue-induced Conrad, K.L. et al. Formation of accumbens GluR2- SOURCE Wood, E. et al. Highly active antiretroviral therapy drug cravings as well as in treating lacking AMPA receptors mediates incubation of cocaine craving. Nature 454(7200): 118–121, 2008. and survival in HIV-infected injection drug users. JAMA 300(5):550–554, 2008.

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NIDA Notes | Volume 22, Number 6 9 ■ R E C E P T O R L I N K T O morphisms (SNPs) that produce alternate individuals’ initial smoking responses, NICOTINE ADDICTION [ Continued from page 1 ] forms, or alleles, of the gene in some indi- particularly feelings of dizziness, relax- viduals. ation, or “pleasurable buzz.” The fol- Initially, research examining the influ- For four of the β3 SNPs, the allele that lowup also pointed to similar effects of ence of nACh receptor proteins on nico- the youths possessed correlated with their one SNP in the gene for the α6 protein. tine addiction focused on the α4 and β2 initial responses to smoking, which could More recently, the Colorado research- subunits. These are the most abundant have included nausea, dizziness, positive ers, in collaboration with Dr. Laura Jean and widely distributed nACh subunit feelings such as mellowness or increased Bierut’s team at Washington University in proteins in the brain. Animal and human energy, or negative feelings such as St. Louis, found an association between β3 imaging studies have shown that nACh depression or anxiety. SNPs and early response to nicotine in a receptors consisting of two α4 and three The researchers looked again at two third sample. β2 subunits are critical for the rewarding of these β3 SNPs in a followup study of a Dr Ehringer and colleagues found that effects of nicotine. separate sample of approximately 2,500 the same α6 and β3 SNPs that correlated The new studies highlight genes that subjects, including some sibling pairs. with initial responses to smoking also code for less common nACh receptor This complementary analysis also found correlated with nicotine dependence in proteins (see table, p. 11). Researchers evidence that these four β3 SNPs shape adults. have implicated the genes—located on chromosome 15—for the α3, α5, and β4 proteins in early initiation of smoking, the transition to dependence, and two Laboratory Studies smoking-related diseases: lung cancer Link Receptor Subtypes and peripheral arterial disease. Investi- gators have also found that whether or to Nicotine Withdrawal not a person experiences extreme dizzi- ness upon first trying cigarettes, as well Researchers are also conducting experiments with genetically engineered as his or her risk of addiction, depends animals to investigate the roles of nACh proteins on smoking responses. in part on the genes—on chromosome NIDA-funded researchers Dr. M. Imad Damaj and colleagues at Virginia 8—for the and proteins. Taken α6 β3 Commonwealth University recently showed that mice whose genes for together, the results suggest that genes various nACh subunit proteins had been deleted exhibited altered profiles for several nACh receptor proteins of nicotine withdrawal. For example, removing the gene for the β2 protein drive different aspects of the multistep reduced expressions of anxiety and aversion without affecting other signs of process of nicotine addiction. withdrawal; animals lacking the gene for the α7 protein, in contrast, demon- strated less hypersensitivity to pain; and deletion of the α5 protein resulted FIRST RESPONSES TO SMOKING in fewer paw tremors and backing movements, which are considered to be A study led by Dr. Marissa A. Ehringer physical signs of nicotine withdrawal. Overall, the findings suggest that the at the University of Colorado exam- β2 nicotinic acetylcholine receptor protein contributes to the negative emo- ined responses of more than 1,000 17- tions triggered by nicotine withdrawal, while the α5 and α7 proteins underpin to 21-year-olds who had been asked to specific bodily signs of the withdrawal process. More recent research by recall their initial responses to smok- Dr. Damaj and colleagues suggests that the α6 protein influences nicotine ing. All the youths had smoked almost reward and negative emotions triggered by nicotine withdrawal but not every day for at least one month at acute nicotine-induced physical signs of the withdrawal process. some time, but not all had continued smoking or had become addicted to SOURCES nicotine. The researchers compared the Jackson, K.J. et al. The role of α-containing nicotinic acetylcholine receptors in nicotine reward and with- youths’ reports with analysis of their drawal. The Journal of Pharmacology and Experimental Therapeutics 331(2):547–54, 2009. DNA, focusing on the gene for the β3 Jackson, K.J. et al. Differential role of nicotinic acetylcholine receptor subunits in physical and affective nico- protein and specifically on seven small tine withdrawal signs. The Journal of Pharmacology and Experimental Therapeutics 325(1):302–312, 2008. variations called single nucleotide poly-

10 NIDA Notes | Volume 22, Number 6 Dr. Ehringer hypothesizes that the “Our results suggest that, once an individual intensity of early smoking experiences begins smoking, this [ ] allele predisposes may be as important as their character— α3 him or her to smoke heavily and find it either pleasant or unpleasant—in deter- mining whether someone continues to difficult to stop.” use nicotine after initial experimentation. —Dr. Kári Stefánsson For example, dizziness is not a sensation that people generally enjoy, yet reporting of these SNPs, one allele was associated the gene for the α5 protein, according to intense dizziness after the first few ciga- with having first smoked and consumed Dr. Robert B. Weiss and colleagues at the rettes is associated with nicotine depen- alcohol sooner and the other with having University of Utah School of Medicine. dence in adulthood. done so later. Dr. Ehringer and colleagues Searching for links between the genes

In another project, the Colorado team hypothesize that genes in this region for the α3, α5, and β4 proteins and the tested for associations between the genes confer vulnerability to problematic risk- severity of nicotine dependence, these on a region of chromosome 15 that code taking, a character trait that affects the age researchers collected smoking histories, for three nACh receptor proteins—α3, at which people begin smoking. diagnostic assessments, and DNA from α5, and β4—and individuals’ experiences A genetic influence on the age of smok- over 2,800 European-American long- with smoking and alcohol. Their ini- ing initiation, such as Dr. Ehringer has term smokers. The researchers found sev- tial study with youths and a larger, more identified, may have public health conse- eral SNPs in the α5 gene whose alternate focused study with adults both linked quences: Studies have indicated that the alleles corresponded to different levels three SNPs—one in the α5 gene, one in the younger people are when they first light of risk for severe nicotine dependence. β4 gene, and one located between these up, the more likely they are to become But the correspondence held only among genes—to the age at which individuals had addicted. This may be particularly true for people who started smoking daily before begun using both substances. For each individuals who inherit certain alleles of age 16. Dr. Weiss suggests that people with

DEVELOPMENT OF AN ADDICTION Recent studies link genes for subunits of the nicotinic acetylcholine receptor to early smoking, initial responses to tobacco smoke, and vulnerability to addiction.

Aspect of Subunit Type of Participants Researchers Smoking Gene(s) Study

Dizziness from first cigarette β3 Gene association* 1,075 adolescent smokers and Marissa A. Ehringer et al. nonsmokers Pleasure from initial cigarette Gene association* 435 adult smokers Laura Jean Bierut, Ovide Pomerleau, α5 Richard Sherva, et al. Age of smoking initiation Gene association* 1,075 adolescent smokers and M. A. Ehringer et al. α5, β4 nonsmokers Increased risk of dependence Candidate-gene** 2,827 long-term smokers Robert B. Weiss et al. α5 among early smokers

Transition to dependence β3 Genome-wide association*** 1,929 smokers, Collaborative Genetic L.J. Bierut, Scott Saccone, et al. Study of Nicotine Dependence Transition to dependence Candidate-gene** 1,929 smokers, Collaborative Genetic L.J. Bierut, S. Saccone, et al. α3, α5, β3 Study of Nicotine Dependence Transition to dependence Genome-wide association*** Approximately 15,000 adults Wade Berrettini et al. α5 Transition to dependence Genome-wide association*** Approximately 14,000 smokers, Kári Stefánsson et al. α3 16,000 nonsmokers Lung cancer and peripheral Genome-wide association*** Approximately 14,000 smokers, K. Stefánsson et al. α3 arterial disease 16,000 nonsmokers * Links genes with smoking by comparing the genetic markers of participants with and without the condition. ** Compares genes, selected on the basis of a demonstrated or hypothesized link, from individuals with and without the condition. *** Considers genetic markers across the entire genome to compare participants with and without the condition.

NIDA Notes | Volume 22, Number 6 11 the higher risk alleles of these SNPs may response the first time they smoked. had each smoked at least 100 cigarettes in especially benefit from early smoking pre- their lifetime; about half were moderately vention interventions. FROM THE FIRST CIGARETTE to severely dependent on nicotine, while A recent study linked another aspect TO ADDICTION the others had not developed depen- of risk with one of the α5 SNPs associated Drs. Bierut, Scott Saccone, and col- dence on the drug, according to the Fag- with nicotine dependence in the Weiss leagues found that the genes for the α5 and erstrom Test for Nicotine Dependence. study. Drs. Bierut, Ovide Pomerleau, and β3 nACh receptor proteins affect an indi- The researchers looked for correlations colleagues found that regular smokers vidual’s risk of progressing from casual between these divergent smoking histo- who had the higher-risk allele were more smoking to addiction. The 1,900 individu- ries and 4,000 SNPs within 348 genes that likely to recollect having had a pleasurable als who contributed DNA to their study previous research had linked to nicotine

Genes Newly Linked to Nicotine Dependence

Smoking addiction commences when nicotine binds to nicotinic The St. Louis researchers also corroborated a suspected asso- acetylcholine receptors, but the process ultimately involves ciation between nicotine dependence and the gene NRXN1. This proteins that participate in a wide variety of neuronal func- gene provides the blueprint for one of a family of proteins, called tions. A recent study by Dr. Laura Jean Bierut and colleagues at the neurexins, that influence neurotransmitter release and other Washington University in St. Louis suggests that several genes aspectsf o cell-to-cell communication. Prior research by other that code for basic brain functions may influence an individual’s teams had linked genes in this family to other addictions (see vulnerability to nicotine’s addictive effects. “New Technique Links 89 Genes to Drug Dependence,” NIDA Notes, Volume 22, Number 1). More recently, a NIDA-funded The genome-wide association study compared the genetic pro- team y led b Dr. Ming Li at the University of Virginia linked vari- filesf o a group of smokers with moderate to severe nicotine antsf o the NRXN1 ogene t nicotine dependence in 2,000 people dependence to those of another group whose members had from 600 families. consumed at least 100 cigarettes but had not become nico- tine–dependent. Out of thousands of small genetic variations “Thiss i a good start toward identifying new genes related to examined, several were linked to genes associated with nicotine nicotine dependence, and the next step is to validate these find- dependence. One was within a gene, called VPS13A, that helps ingsn i a independent data set and then determine what these determine which proteins should be broken down and eliminated genes may contribute to nicotine dependence,” says Dr. Bierut. by the waste disposal organelles inside cells. A second small “The findings of our genome-wide association study, for exam- variation associated with nicotine dependence was within a ple, point to novel biological pathways for nicotine addiction gene called CTNNNA3, which other researchers have linked with and prompt us to think of its neurobiology in a different way.” levelsf o plasma amyloid beta protein in Alzheimer’s disease.

SOURCES Two genes associated with calcium channels, which control the Nussbaum, J. et al. Significant association of the neurexin-1 gene (NRXN1) responsef o cells to stimulation, were also highlighted: with nicotine dependence in European- and African-American smokers. • CLCA, which encodes the protein that forms the calcium Human Molecular Genetics 17(11):1569–1577, 2008. channeln i lungs and which other research has linked to Bierut, L.J. et al. Novel genes identified in a high-density genome wide chronic obstructive pulmonary disease. association study for nicotine dependence. Human Molecular Genetics 16(1):24–35, 2007. • TRPC7, which earlier work had associated with main- tenancef o calcium channels and with nicotine-induced behaviorn i roundworms.

12 NIDA Notes | Volume 22, Number 6 dependence. The strongest associations company based in Reykjavik, Iceland, also Two studies by researchers at the were with five SNPs: two in the gene for implicated an α 3 gene SNP that influences University of Texas in Houston and the the α3 nACh receptor subunit, two in the nicotine dependence but not smoking ini- International Agency for Research on β3 subunit gene, and one in the α5 subunit tiation. Both of these studies employed Cancer in Lyon, France, also found that gene. One of the α5 alleles carried double the risk of its alternative allele. The trial participants who were not “Once scientists determine how dependent on nicotine were unusually resistant to the drug’s addictive effects, these genetic variants affect nicotinic Dr. Bierut says. These are smokers who receptor function and behavioral can quit at any time. Identifying the ways responses to nicotine, they can develop that the trial participants’ genetic makeup pharmacotherapy interventions.” protected them, even past the 100-cigarette —Dr. David Shurtleff threshold, could provide powerful clues to prevention and treatment. “Our findings point to a role for the genome-wide association (GWA) scan the α 3 variant increases risk for lung can- α3 and α5 proteins, as well as β4, in nico- methodology, which analyzes hundreds cer. These researchers, however, disagree tine dependence,” says Dr. Bierut. “The of thousands of SNPs simultaneously. with Dr. Stefánsson’s explanation for the α5 proteins are expressed in the brain’s Although GWA scans sometimes produce link; they argue that the variant increases reward areas, which makes our findings spurious associations, the convergence of cancer risk via mechanisms independent particularly intriguing.” these results with those of the St. Louis of nicotine addiction. Dr. Saccone says, “We are very excited group provides strong evidence for the to discover that genes encoding nicotinic positive findings. FROM GENE DISCOVERY TO acetylcholine receptor proteins confer TREATMENT risk for nicotine dependence because they SMOKING-RELATED DISEASES The SNPs identified in these studies have strong biological relevance to the The Icelandic study included nearly may themselves affect nACh responses to addiction. My colleagues and I are using 14,000 smokers, a sample large enough nicotine by altering the form of their prod- samples of DNA from different groups of to detect relationships between genes uct proteins or their patterns of expres- people to confirm these findings; the next and long-term smoking outcomes of lung sion in different regions of the nervous step is to determine exactly how alleles of cancer and peripheral arterial disease. system. Alternatively, further investiga- these genes cause someone to keep smok- Among these Caucasian European men tions may reveal that some of the SNPs ing.” Both St. Louis studies also found a and women, the same α3 allele that pro- are genetic bystanders that correlate link between the gene for the β3 protein— motes dependence also accounted for 18 with smoking behaviors only because which was highlighted in the results of the percent of lung cancer cases and 10 per- they are inherited along with nearby, as Colorado studies—and nicotine depen- cent of peripheral arterial disease cases. yet unidentified DNA variants. Scientists dence, bolstering confidence in this gene’s “Our results suggest that, once an indi- plan to sort through these possibilities, involvement in the addiction. vidual begins smoking, this allele predis- pinpointing which alleles affect receptor Other researchers have corroborated poses him or her to smoke heavily and responses to nicotine singly and which and extended the St. Louis team’s find- find it difficult to stop,” says Dr. Stefáns- work in concert with others and determin- ings. For example, Dr. Wade Berrettini son. It may also influence other aspects ing how those altered responses promote and colleagues at the University of Penn- of smoking, he adds, such as vulnerability or protect against nicotine addiction. A sylvania found that SNPs in the gene for to harmful effects of smoking or depth of similar agenda applies to research on sev- the α5 protein influence the risk of smok- inhalation. “These traits would affect the eral genes that code for proteins that are ing a pack of cigarettes a day as compared risk for lung cancer and peripheral arterial unrelated to the nACh receptor but have with smoking fewer than 5 cigarettes a disease, erasing the line that people have recently been linked to addiction (see box, day. A study led by Dr. Kári Stefánsson of traditionally drawn between environmen- page 12). deCODE Genetics, a biopharmaceutical tal and genetic contributions,” he says. “Once scientists determine how these

NIDA Notes | Volume 22, Number 6 13 genetic variants affect nicotinic receptor Dr. Stefánsson. “It is only smoking that Sherva, R. et al. Association of a single nucleotide function and behavioral responses to nic- converts the risk into addiction and dis- polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and otine, they can develop pharmacotherapy ease,” he notes. “The ultimate preventive with “pleasurable buzz” during early experimentation interventions,” says Dr. David Shurtleff measure for these conditions is to never with smoking. Addiction 103(9):1544–1552, 2008. of NIDA’s Division of Basic Neuroscience start smoking.” ■ Thorgeirsson, T.E. et al. A variant associated with and Behavioral Research. “Of the nicotinic nicotine dependence, lung cancer and peripheral arte- rial disease. Nature 452(7187):638–642, 2008. receptors identified as novel targets in SOURCES Weiss, R.B. et al. A candidate gene approach identi- these studies, the α protein stands out. It Ehringer, M.A. et al. Association of CHRN genes with 5 fies the CHRNA5-A3-B4 region as a risk factor for “dizziness” to tobacco. American Journal of Medical seems to influence severe nicotine addic- age-dependent nicotine addiction. PLoS Genetics Genetics. Part B Neuropsychiatric Genetics [Epub ahead tion,” he says. 4(7):e1000125, 2008. of print, September 16, 2009]. NIDA geneticist Dr. Joni Rutter agrees Zeiger, J.S. et al. The neuronal nicotinic receptor Berrettini, W. et al. Alpha-5/alpha-3 nicotinic recep- subunit genes (CHRNA6 and CHRNB3) are associ- that the α5 receptor, in particular, is an tor subunit alleles increase risk for heavy smoking. ated with subjective responses to tobacco. Human interesting target. “This protein is not as Molecular Psychiatry 13(4):368–373, 2008. Molecular Genetics 17(5):724–734, 2008. abundant in the brain as other nicotinic Hoft, N.R. et al. Genetic association of the Bierut, L.J. et al. Novel genes identified in a high- CHRNA6 and CHRNB3 genes with tobacco depen- receptor subtypes, so medications that density genome wide association study for nicotine dence in a nationally representative sample. target it might have few side effects and dependence. Human Molecular Genetics 16(1):24–35, Neuropsychopharmacology 34(3):698–706, 2008. higher efficacies,” she adds. 2007. Schlaepfer, I.R. et al. The CHRNA5/A3/B4 gene cluster Saccone, S.F. et al. Cholinergic nicotinic receptor For people who have a genetic pre- variability as an important determinant of early alco- genes implicated in a nicotine dependence association disposition to various aspects of smok- hol and tobacco initiation in young adults. Biological study targeting 348 candidate genes with 3713 SNPs. Psychiatry 63(11):1039–1046, 2008. ing addiction, the solution is simple, says Human Molecular Genetics 16(1):36–49, 2007.

NIDA Establishes New Center for Distributing Its Publications

Teachers, drug abuse counselors, parents, and others who want to order copies of NIDA’s publications have three quick-and-easy options:

n Call 1-877-NIDA-NIH. n Send an e-mail to [email protected] specifying the name or catalog number of the publication and the mailing address to which it should be sent. n Place an order at www.drugabuse.gov/pubcat. Visitors to the site can also peruse NIDA’s online catalog and read and download publications.

NIDA previously distributed its educational materials via the Substance Abuse and Mental Health Services Administration National Clearinghouse for Alcohol and Drug Information. That clearinghouse is now forwarding requests for NIDA publications to the new distribution center.

14 NIDA Notes | Volume 22, Number 6 n■ BULLETIN BOARD

Program Aims to Expand Physician percent of their noncollege peers. In contrast, drug and nicotine Training to Treat Drug Addiction dependencies were more common among nonstudents (7 percent versus 5 percent; 21 percent versus 15 percent). The researchers Physicians in all areas of medical practice—not just those based their estimates on data from the National Epidemiologic already specializing in addiction—can receive certification to Survey on Alcohol and Related Conditions (NESARC), the largest treat drug addiction under a new program the American Board nationally representative survey of substance abuse and mental of Addiction Medicine (ABAM) is establishing. health disorders to include college-age students and their noncol- “We want addiction prevention, screening, intervention, and lege peers. Their analysis linked the difference in alcohol abuse treatment to become routine aspects of medical care, available rates to sociodemographic factors that differentially affected virtually any place health care is provided,” says ABAM President the two groups and to recent stressful life events. Fewer than 10 Dr. Kevin Kunz. percent of the survey participants with drug or alcohol problems ABAM was founded in 2007 to set standards for educating reported having utilized treatment resources, and only half as physicians in addiction medicine, to certify primary care practi- many college as noncollege individuals reported doing so. The tioners and a wide range of medical specialists to treat addiction, researchers say that their findings, reported in the Archives of and to require and track continuing education in addiction treat- General Psychiatry, highlight the need for more alcohol abuse ment. A major focus of the program is the creation of accredited screening and intervention, especially on college campuses. addiction residency programs in medical schools and hospitals In a survey of 834 youths, college freshmen reported lower across the Nation. rates of risky sexual behavior 6 months after high school gradua- Dr. Kunz says he believes that within 3 to 7 years, “a 1- to 2-year tion than same-age youth who were not attending college. About residency will be mandatory for those seeking certification in 23 percent of the college students reported inconsistent condom addiction medicine.” He says ABAM is establishing a framework use during the past month, compared with 35 percent of their for model residencies that meet the criteria of the Accreditation noncollege peers; 15 percent said they had engaged in casual Council for Graduate Medical Education, the group that accredits sex during the same period (versus 29 percent), and 5 percent postgraduate medical training programs in the United States. reported high-risk sex (versus 16 percent). Jennifer A. Bailey of ABAM will also seek recognition for the field of addiction medi- the University of Washington in Seattle and colleagues report in cine by the American Board of Medical Specialties. the Journal of Adolescent Health that the college students had lower For a limited time, physicians who meet certain criteria can rates “largely because they were more likely to do well in school become ABAM-certified without completing all the training and less likely to use drugs and to engage in sexual risk behaviors requirements that will eventually be established. These include during high school.” Prevention efforts in high school “should some 4,500 physicians who have been certified by examination by result in reductions in the prevalence of risky sexual behaviors in the American Society of Addiction Medicine. They can apply for the transition to adulthood,” they conclude.

“grandfathering” until December 31, 2009. Thereafter, physicians SOURCES who are certified in a nonaddiction specialty and meet certain Archives of General Psychiatry 65(12):1429–1437, 2008. Journal of Adolescent Health other criteria can receive ABAM certification by taking an exam, 42(6):573–579, 2008. scheduled for December 11, 2010. Further information on ABAM and the exam are available at Recognition for NIDA Notes www.ABAM.net. Science Writing NIDA Notes received first place in Science Writing in the 2009 Substance Abuse and Sexual Risk Blue Pencil & Gold Screen Awards Competition of the National Show Town-Gown Divide Association of Government Communicators (NAGC). The award, which recognized the article, “Basic Science Discover- Two recent studies found differences in ies Yield Novel Approaches to Analgesia” (NIDA Notes, Vol. 22, behavior between young adults attending No. 1, p. 1), named Senior Science Writer Lori Whitten, Manag- college and their peers. Dr. Carlos Blanco ing Editor Andrew Keegan, Deputy Editor Julie Ann Miller, and of Columbia University in New York and Editor David Anderson. NAGC is a network of professionals who colleagues report that in 2001–2002, one fifth of the Nation’s col- disseminate information on behalf of Federal, State, and local lege students had met the clinical criteria for a diagnosis of alco- governments. The association’s annual awards “salute superior hol abuse disorder within the past 12 months, compared with 17 communications efforts of government agencies.” ■

NIDA Notes | Volume 22, Number 6 15 n VOLUME XXII22 INDEX I NDEX

Issue number appears in parentheses, auditory cortex: (3)13 chromatin remodeling: (4)18 (ADHD): (4)5; (5)20; (6)3, 19 followedy b page number(s). basal ganglia: (3)15 cigarettes: (4)19, 20 behavioral: (4)4 caudate-putamen: (2)6, 13 addiction: (3)11; (4)1, 11; (6)1 bipolar: (1)8; (2)4; (4)9 A cingulate cortex: (2)11; (3)9 craving: (2)1; (4)3; (5)3 conduct: (4)5; (5)20; (6)19 abstinence: (4)3, 11 damage: (3)11 denicotinized: (2)12; (5)3 co-occurring: (2)16; (4)10; (6)4 acetylcholine: See brain development: (1)3 effects: (5)18 depression: (4)14; (5)20 addiction: function: (1)9 sensory aspects: (5)3 mental/psychiatric: (2)16; (4)9, 14; (5)2; (6)19 studies: (3)17; (4)2 hippocampus: (1)9; (2)13 See also nicotine, smoking, and tobacco oppositional defiant: (4)5 treatments: (4)2 hypothalamus: (2)13 club drugs: See MDMA (ecstasy) posttraumatic stress: (4)14; (5)2 See also drug abuse and addiction imaging: (2)1; (3)9, 18; (6)3 cocaine: schizophrenia: (2)4; (4)14; (6)19 Addiction Science Awards: (1)15 insula: (2)13; (3)11 lateral geniculate nuclei: (1)3 abuse and addiction: (2)3, 7, 15; (3)1, 7, disulfiram: (4)3 Adinoff, Bryon: (3)7 15; (4)3, 17; (5)10, 17, 19; (6)3, 7 limbic system: (6)3 dopamine: (2)4; (4)11; (5)3 adolescents: (1)15; (2)15; (3)3, 18, 19; chronic: (2)6; (5)10, 11, 17 (4)12, 19; (5)4, 19, 20; (6)3, 19 neural damage: (3)9 receptor: (2)4; (5)10, 11 craving: (6)7 See also children, teenagers, and neural pruning: (1)3 availability: (3)15 effects: (2)6; (3)1, 7; (4)9; (5)10 school-age children neural signaling: (3)1 complexes: (4)15 overdose: (2)3 African-Americans: (5)3 nucleus accumbens (NAc): (2)4, 6, 8, surges: (4)15 genetic risks: (4)1 13; (6)7 relapse: (2)5; (6)3 See also brain aggression: (5)5 orbitofrontal cortex: (3)1, 7 seeking: (2)4, 7 drug abuse and addiction: (3)19; (6)2 AIDS: See HIV/AIDS prefrontal cortex: (5)12 treatment: (2)4; (6)12 consequences: (2)14 Aigner, Thomas: (1)9; (3)14 receptors: withdrawal: (6)3, 7 dual addiction: See co-occurrence/ alcohol: cannabinoid: (1)13 college students: (6)15 comorbidity abuse and addiction: (1)15; (3)19; (4)3; delta opioid: (6)3 community-based treatment: education: (5)17; (6)15 See treatment (6)15 glutamate: (6)7 effects: (5)17; (6)2 Community Reinforcement Approach treatment: (5)5 AMPA ( -amino-3- environmental factors: (5)4 a with Vouchers: (5)14 use: (4)19; (5)19 hydroxy-5-methyl-4- gender differences: (3)7, 19; (5)19 comorbidity: See co-occurrence Alegría, Margarita: (4)18 isoxazolepropionic genes: (1)6; (4)1; (6)1 Compton, Wilson: (5)4, 19 Alzheimer’s disease: (1)3, 8 acid): (6)7 genetic factors: (5)4 mu opioid: (2)8 Computer-Based Training for Cognitive- amantadine: (6)3 Behavioral Therapy: (5)14 information: (4)17 amphetamine: (6)3 nicotinic acetylcholine: (2)1, 11; initiation: (5)19 (3)3, 13, 14; (4)11; (6)1, 10 Condon, Timothy: (3)17 analgesics: See pain relief master’s degree: (3)17 vanilloid: (1)13 Conway, Kevin: (5)4 Andersen, Susan: (6)3 physician training: (2)14 See also dopamine and serotonin co-occurrence/comorbidity: animal studies: (1)2, 10; (6)14 postpartum: (2)3 retinogeniculate segregation: (1)3, 4 screening: (3)5 See also mice, monkeys, and rats prevention: (4)17; (5)4 striatum: (2)6; (4)15; (5)3, 11 substance abuse and mental disorders: antibody fragment: (5)6 (2)4, 9, 16; (3)3; (5)2; (4)10; (5)20; (6)4, publishing: (6)15 temporal cortex: (2)13 anxiety: See disorders 19 racial differences: (4)1 ventral tegmental area (4)10 aripiprazole: (2)4 See also disorders and substance research:(5)4; (6)2 Brain Awareness Week: (5)17 astrocytes: (1)1, 3 abuse screening and assessment: (3)4 Brenhouse, Heather: (6)3 See also glial cells Coping Power Program: (4)5 treatment: See treatment Brody, Arthur: (2)1; (4)10; (5)3 attention deficit hyperactivity disorder Cosgrove, Kelly: (4)11 trends: (5)4 buprenorphine: (5)3, 15 (ADHD): See disorders craving: (5)1 vulnerability: (4)9; (5)4 patch: (5)3 Avant-Garde Award: (4)17 cue-induced: (6)9 age differences: (3)3 bupropion: (2)1; (5)8 criminal justice: gender differences: (3)3 B community re-entry: (3)4 drug court: (2)9, 10; (3)5 baby boomers: (2)15 C interventions: (3)5 drug cues: (4)3 Bailey, Jennifer: (6)15 Cadet, Jean Lud: (5)3 drug abuse treatment: (3)4 drug offender: (2)9 Bardo, Michael: (6)3 calcium signaling: (4)15 Cristea, Ileana: (4)18 community re-entry: (3)4 Barres, Ben: (1)3 cannabis: (5)19 Crowley, Thomas: (3)17 drug refusal skills: (5)14 Bechara, Antoine: (3)11 See also marijuana Cutting-Edge Basic Research Awards: drug-seeking behavior: (5)11; (6)7 (1)2 behavior(s): capsaicin: (1)13 drug-seeking: (5)11; (6)7 Carroll, Kathleen: (5)14 E Castellanos, F. Xavier: (3)17 sexual: (6)15 D ecstasy: See MDMA Caucasian European: Dalley, Jada Nicole: (5)18 Berrettini, Wade: (6)11, 13 Ehringer, Marissa: (6)10, 11 smoking addiction genes: (6)13 Damaj, M. Imad: (6)10 Beveridge, Thomas: (2)6 electrodes: (1)11 cell adhesion: (1)7 Daughters, Stacey: (3)3 Bickel, Warren: (5)1 elementary school: (4)5 Centers of Excellence for Physician deep brain stimulation: (5)17 Bierut, Laura Jean: (6)10, 11, 12 endorphins: (2)8 Information: (2)14 Deisseroth, Karl: (1)9, 10 Bigelow, George: (5)3 European-Americans: Chamberlain, Patricia: (4)12 De La Rosa, Mario: (4)18 Biswas, Jamie: (5)7 genetic risks: (4)1 Chandler, Redonna: (2)10; (3)5; (5)5 delinquency: (4)12 Blacks: See African-Americans smoking addiction genes: (6)11 channelrhodopsin 2: (1)10 Dennis, Michael: (6)4 Blanco, Carlos: (6)15 Everett, Anita: (3)17 Chat Day: (4)17 deoxyribonucleic acid (DNA): (1)7, 8, 10 Bland, Sondra: (1)13 exercise: (4)20 Blue Pencil & Gold Screen Awards Childers, Steven: (3)17 Department of Defense: (5)2 Competition of the National children: Department of Veterans Affairs: (5)2 Association of Government drug abuse risk factors: (6)19 depression: See disorders F factors in drug abuse: Communicators: (6)15 intervention for: (4)5 disorders: genetic: (4)1 brain: See also adolescents, school-age alcohol use: (6)15 Feltenstein, Matthew: (2)4 activity: (2)6; (3)7 children, and teenagers anxiety: (4)14; (5)20; (6)19 Festinger, David: (2)9 amygdala: (2)13; (3)1 Childress, Anna Rose: (4)3; (6)3 attention deficit hyperactivity

16 NIDA Notes | Volume 22, Number 6 Fletcher, Bennett: (3)4 impulsivity: (6)3 memory: withdrawal: (5)3; (6)10 fluorescence microscopy: (1)9 injection drug users: formation: (1)6 See also cigarettes, smoking, and Frankenheim, Jerry: (6)9 HIV-infected: (6)6 methadone treatment: (2)7; (5)3 (6)3 tobacco Frontiers in Addiction Research mini- Intel International Science and methamphetamine: NicVAX: (2)2 conference: (5)17 Engineering Fair: (5)18 abuse and addiction: (2)15; (3)9 (4)3, NIDA’s Criminal Justice–Drug Abuse fruit flies: (1)15 International Programme in Addiction 19; (5)3, 6 Treatment Studies Project: (3)4 functional magnetic resonance imaging Studies: (3)17 effects: (4)3, 17; (5)3, 18 NIDA’s Division of Epidemiology, Services and Prevention Research:(5)4 (fMRI): (2)11; (4)3; (6)3 intervention: See prevention and overdose: (5)6 treatment NIDA’s Frontiers in Addiction Research See also brain imaging Metherate, Raju: (3)13, 14 miniconference: (5)17 Furr-Holden, Debra: (4)18 methylphenidate: (6)3 NIDA’s Intramural Research Program: J mice: (1)3, 10, 11, 14; (4)9; (6)10, 14 (1)6; (3)3; (6)9 G Jacob P. Waletzky Memorial Award for microendoscope: (1)9 Innovative Research in Drug Addiction Normand, Jacques: (6)9 gamma-aminobutyric acid (GABA): (3)18 and Alcoholism: (5)17 microglia: (5)3 novelty-seeking: (4)9 gender differences: (3)7 Jenkins, Richard: (5)16 microneedles: (5)13 genes/genetics: (1)6; (3)2; (4)1; (6)1 John, Simon: (1)5 middle school: (4)5, 19 O African-American: (1)6; (4)1 Johnson, Kirk W.: (1)1 military personnel: (5)2 O’Brien, Charles: (4)3; (6)3 European-American: (1)6; (4)1 Johnston, Lloyd: (4)19 Miner, Lucinda: (1)15; (5)18 offenders: See criminal justice quit-smoking: (5)8 judicial supervision: (2)9 minimum drinking age: (5)4 Ondersma, Steven: (2)3 smoking addiction: (4)1; (6)1 juvenile justice: (4)12 Mocz, Lucia: (5)18 opiate(s)/opioid(s): (1)1 genetic engineering: (4)9; (6)10 Monitoring the Future survey: (3)19; abuse and addiction: (2)7; (5)15 genetic markers: (4)7 (4)19, 20; (5)4 detoxification: (2)3; (5)3 genome-wide association studies: (1)6; K monkeys: (2)6; (3)3, 15 Kampman, Kyle: (4)3 relapse: (2)3 (6)12, 13 Montaner, Julio: (4)17 Kawai, Hideki: (3)14 side effects: (1)12, 14; (4)17 George, Susan: (4)15 Montoya, Ivan: (5)9 Kerr, David: (4)13 tolerance: (1)1, 12 girls: (4)12 morphine: Kinlock, Timothy: (5)3 withdrawal: (1)1; (2)3; (5)3 glial cells: (1)1 abuse and addiction: (1)12 Kreek, Mary Jeanne: (2)8 opsin: (1)11 glutamate: See brain effects: (1)13 optical remote: (1)10 Gordon, Harold: (3)7 tolerance: (1)12 optical technologies: (1)9 Grant, Steven: (3)10, 12 L withdrawal: (1)12 orexin: (1)11 Groopman, Jerome: (4)17 Langleben, Daniel: (6)3 mothers: (2)3 Owens, S. Michael: (5)7 Guinn, Ethan Garrett: (1)15 Lazar, Ronit: (3)14 mu-delta agonist-antagonist (MDAN): oxycodone (OxyContin): (4)19; (5)4 Gust, Steven: (4)6 Leri, Francesco: (2)7 (1)14 Leve, Leslie: (4)12 Mukhin, Alexey: (3)3 H Levin, Edward: (3)3 Multidimensional Treatment Foster P Care: (4)12 pain: HAART: See HIV/AIDS Levitin, Teresa: (3)17 chronic: (1)12 health care: Li, Ming: (4)1; (6)12 medication: (1)13; (5)4 disparities: (4)18 Liberman, Akiva: (3)5 N neuropathic: (1)1 Hemby, Scott: (2)3 Lin, Geraline: (1)11 N-acetyl aspartate: (3)9 relief: (1)1 hepatitis C: Lochman, John: (4)5 Nader, Michael: (3)15 Park, Moo: (5)16 screening: (4)18 lofexidine: (2)3 naltrexone: (2)3, 8; (4)3; (5)13 Parkinson’s disease: (1)11 treatment: (4)18 London, Edythe: (4)3 via skin patch: (5)13 Paulus, Martin: (3)10 heroin: See also opiate(s)/opioid(s) Loos, Mary: (3)17 narcolepsy: (1)11 PCP (phencyclidine): (4)17 cues: (6)3 Lopez, Marsha: (2)15; (5)4 National Advisory Council on Drug Abuse: (3)17; (5)18 Perkins, Kenneth: (4)3 detoxification: (5)3 LSD: (4)19 National Center on Minority Health and Perrine, Shane: (6)3 high school: (3)19; (4)19, 20; (6)20 Lynch, Minda: (4)10 Health Disparities: (4)18 Perry, Jennifer: (6)3 Hillery, Paul: (1)15 National Epidemiologic Survey on Peterson, Eric: (5)7 Hilton, Thomas: (6)5 M Alcohol and Related Conditions: (2)16; Pettinati, Helen: (4)3 Hispanic/Latino Americans: (4)18 magnetic resonance imaging (4)10; (6)15 (MRI): Pierce, R. Christopher: (5)17 HIV/AIDS: National Institutes of Health Summit See also brain imaging and functional Pijlman, Femke: (3)17 antiretroviral treatment/HAART: (6)6 on the Science of Eliminating Health magnetic resonance imaging Disparities: (4)18 Pilotte, Nancy: (2)8, 13 infection: (6)6 magnetic resonance spectroscopy: (3)9 National Survey on Drug Use and Pollock, Jonathan: (1)5 research: (4)17 See also brain imaging Health: (2)15 Pomerleau, Ovide: (6)12 risk factors: (5)15 marijuana: (1)13 Natronomonas pharaonis halorhodopsin: Porrino, Linda: (2)6 screening: (4)18; (5)5 (1)10 abuse: (2)15; (3)19; (4)19, 20 Portoghese, Philip S.: (1)1 transmission: (5)5 Nemeth, Ro: (2)12; (4)14 effects: (4)17 Positive Choice: (5)15 treatment: (2)3; (4)18 Nestler, Eric: (5)18 Marlowe, Douglas: (2)9 positron emission tomography (PET): Hubel, David: (1)5 Marsch, Lisa: (5)14 neurodegeneration: (5)3 (2)11; (3)15; (5)3 Hurwitz, Barry: (2)3 Martin, Daniel Jeffrey: (5)18 neuropathy: See also brain imaging Hutchinson, Mark: (1)13 Masson, Carmen: (4)18 diabetic: (1)12 posttraumatic stress disorder: See dis- hypocretin: See orexin. Matthys, Walter: (4)5 nicotine: orders McClung, Colleen: (4)9 addiction: (2)16; (3)3; (4)1; (6)1 Prado, Guillermo: (4)18 I McNamara Spitznas, Cecilia: (5)16 genes: (4)1; (6)1, 12 Prausnitz, Mark: (5)13 ibudilast (AV411): (1)1, 12 MDMA (ecstasy): (4)19 effects: (5)3 prenatal exposure: (4)4 illicit drug use: (2)15; (3)19 medication: nasal spray: (5)8 nicotine: (2)16; (3)13 imaging: See brain imaging relapse-prevention: (5)17 patch/replacement therapy: (5)8 prescription drug(s): immune complement cascade: (1)3 transdermal delivery: (5)13 prenatal exposure: (2)16; (3)13 abuse: (2)15; (4)19; (5)4, 15 immune system: (1)3 vaccine: (2)2 See also opiate(s)/opioid(s)

NIDA Notes | Volume 22, Number 6 17 prevention: See also adolescents, college, high Stevens, Beth: (1)3 U drug abuse: (4)4, 12; (5)4 school, middle school, Monitoring the stimulants: (4)19 Uhl, George: (1)6; (5)8 Future survey, and teenagers pregnancy: (4)13 stimulus funds: (3)2 Unterwald, Ellen: (6)3 science: Price, LeShawndra: (4)18 Stinchcomb, Audra: (5)13 U.S. Food and Drug Administration: drug abuse: (6)2 prisoners: See criminal justice Stroop test: (3)10 (1)11 Scott, Christy: (6)4 propranolol: (6)3 substance abuse: sedatives: (1)16 Publishing Addiction Science: A Guide for adolescent: (4)19; (6)20 V See, Ronald: (2)4 the Perplexed, 2nd Edition: (6)15 co-occurring with mental disorders: vaccines: Seeman, Philip: (5)11 (2)9, 10; (3)3; (5)20; (6)4, 19 antiaddiction: (2)2 selenium: (2)3 R See also co-occurrence/ cocaine: (2)2 serotonin: (3)18 comorbidity and disorders radiotracer: (3)3 nicotine: (2)2 receptor: (2)4 genes: (1)6; (4)1; (6)1 See also tracer veterans: (5)2 sexual behavior: (6)15 prevention: (4)5, 12 Ramachandran, Kapil Vishveshwar: (1)15 Vicodin: (5)4 sexually transmitted disease(s): treatment: (5)1; (6)4 Rapaka, Rao: (1)13 Video Doctor: (5)15 See HIV/AIDS and hepatitis C synapse: (1)3, 5 rats: (1)10, 13; (2)4, 7; (3)1, 13; (5)10, 11; video game: Shaham, Yavin: (6)9 Szeto, Hazel: (3)17 (6)3, 7 addiction: (1)15 Shurtleff, David: (4)16; (6)13 Raye, Shelby Marie: (1)15 Volkow, Nora: (1)2, 15; (2)2, 14; (3)2, 17; receptor: single-chain variable fragment 6H4: (5)6 T (4)2, 17; (5)2, 18, 19; (6)2, 19 dual/dimeric: (1)14 single nucleotide polymorphisms TA-CD: (2)2 Volman, Susan: (3)8; (5)12 (SNPs): (1)7, 8; (5)8 toll-like: (1)13 teenagers: (2)15; (3)19; (4)19, 20 vulnerability to drug abuse/addiction: See also brain single-photon emission computed See also adolescents and Monitoring See drug abuse and addiction tomography (SPECT): (4)11 recidivism: the Future survey Sinha, Rajita: (2)3 risk: (3)4 therapy: See treatment Sirocco, Karen: (3)18 W Recovery Management Checkup: (6)4 Thomas, David: (1)13, 14 Walker, R. Dale: (5)18 smoking: Reider, Eve: (4)6, 14; (5)5 tobacco: war impact: addiction: (3)11; (4)1; (5)2; (6)1 relapse: use: (5)2, 19 Afghanistan: (5)2 adolescent: (4)19, 20 cue-induced: (2)4 See also cigarettes, nicotine, and Iraq: (5)2 and co-occurring mental disorders: smoking risk: (3)4 Watkins, Linda: (1)1 (2)16; (6)19 tracer: (5)11 vulnerability: (4)3 weight-control behaviors: (6)20 cessation: (3)11; (4)11; (5)8 See also radiotracer research: Weiss, Robert: (6)11 craving: (2)1; (3)11 training: innovative: (1)2 Wells, Karen: (4)5 effects: (4)3; (5)3; (6)10 counselor: (4)5 neuroscience: (6)2 Wermeling, Daniel: (5)13 eradication: (3)2 Translationally Oriented Approaches, resiniferatoxin: (1)13 initiation: Devices and Strategies: (1)2 Wetherington, Cora Lee: (2)5; (3)18 reward: early: (6)10 treatment: See also listings for specific Wiesel, Torsten: (1)5 sensitivity: (4)9 responses: (6)10 drugs withdrawal symptoms: (1)11 Rice, Kenner: (1)13 prenatal exposure: (2)16; (3)13 access: (5)1 Wolf, Marina: (6)7 Robertson, Elizabeth: (5)5 relapse: (4)11 availability: (3)4 Wolff, Kim: (3)17 Robinson, Terry: (5)10, 11 sensory aspects: (2)12; (5)3 combination: (2)3; (4)3 women: Rush, Brian: (6)4 treatment: (4)1; (5)8 community-based: (5)3 pregnant: (2)16 Rutter, Joni: (1)7; (4)8; (6)14 vulnerability: (4)1; (6)1 computer-based: (2)3; (5)1 See also gender differences withdrawal: (4)11 co-occurring substance abuse and Wood, Evan: (6)6 S See also cigarettes, marijuana, mental disorders: (3)3; (5)20 World Health Organization World Saccone, Scott: (6)11, 12 nicotine, and tobacco court-mandated: (3)3, 20 Mental Health Survey Initiative: (5)19 Salman, Sehar Anjum: (5)18 Society for Neuroscience meeting: (1)12 criminal justice: (3)4 Salo, Ruth: (3)9 Sorensen, James: (5)18 interactive multimedia: (5)1 Y schizophrenia: See disorders Sorensen, Roger: (5)17 prison-based: (5)3 young adults: (2)15 Schnitzer, Mark: (1)2, 9 Staley, Julie: (4)11 research: (5)2 Schoenbaum, Geoffrey: (3)1 Stefánsson, Kári: (6)11, 13 retention: (3)3, 20; (6)4 Z school-age children: (5)4, 17 Stein, Elliot: (3)8 two-odor go/no-go discrimination task: Zhang, Feng: (1)10 (3)1

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18 NIDA Notes | Volume 22, Number 6 ■ TEAROFF Information to clip, save, and share

Report Discusses Co-Occurrence of Drug Abuse and Other Mental Disorders

any individuals who abuse drugs also have other mental disorders. NIDA’s latest Research Report M describes the co-occurrence, or comorbidity, of substance use disorders and other psychiatric disorders such as attention–deficit hyperactivity disorder (ADHD), schizophrenia, and depression. Drug addiction is a brain disease “characterized by compulsive, at times uncontrollable drug craving, seeking, and use despite dev- astating consequences—behaviors that stem from drug-induced changes in brain structure and function. These changes occur in some of the same brain areas that are disrupted in various other is the use of tobacco products by patients with schizophre- mental disorders,” writes Dr. Nora D. Volkow in the introduction nia. The nicotine in tobacco may diminish symptoms of the to the report, Comorbidity: Addiction and Other Mental Illnesses. disease, improve cognition, or decrease the side effects of “Even though we cannot always prove a connection or causality, we medications. do know that certain mental disorders are established risk factors for ■ Drug abuse and other mental disorders are both caused by subsequent drug abuse—and vice versa.” common factors, such as underlying brain deficits and early Surveys show high rates of substance use disorders among people exposure to stress or trauma. For example, brain circuits that with mental illness. People diagnosed with a mood or anxiety disor- use dopamine are typically affected by addictive substances der are about twice as likely as others to abuse drugs, and people with and may also be involved in depression, schizophrenia, and schizophrenia have higher rates of tobacco and alcohol use disorders other psychiatric disorders. than the general population. For example, 41 percent of mentally All three scenarios are likely to contribute, in varying degrees, to ill respondents to the 1991–1992 National Comorbidity Survey said the establishment and expression of specific comorbidity pairings. they were current smokers, almost double the rate of those with no mental illness. Other studies indicate that as many as 90 percent of DEVELOPMENTAL FACTORS people with schizophrenia smoke. There is evidence suggesting that early drug use may be a risk People who abuse drugs also have high rates of mental illness. By factor for the later occurrence of mental illness. The link may hinge some estimates, about 60 percent of people with drug use disorders upon genetic vulnerability, psychosocial experiences, or a person’s have been diagnosed with another mental disorder. A recent clinic- environment. Having a mental disorder in childhood or adolescence based study of 865 substance abusers found that 66 percent had at also increases the risk of drug abuse. least one co-occurring mental disorder (see “Recovery Checkup Sys- Numerous studies have documented an increased risk for drug tem Helps Substance Abusers Who Have Mental Disorders,” page 4). use disorders in youth with untreated ADHD; some of these stud- The high prevalence of comorbid substance use and other mental ies suggest that only a subset of these young people—those with disorders does not necessarily indicate that one condition causes co-occurring conduct disorders—are vulnerable. Treatment with the other. According to the report, there are at least three possible stimulants reduces ADHD symptoms and may also reduce the asso- explanations for such co-occurring diagnoses: ciated risk of drug abuse. ■ Drug abuse may be a risk factor for one or more symptoms The report stresses the importance of careful and accurate diag- of another mental illness. The increased risk of psychosis in nosis and treatment of each disorder. It gives examples of medica- some marijuana abusers has been offered as evidence sup- tions and behavioral therapies that have been successful and others porting this possibility. that show promise in treating co-occurring disorders. ■ Some individuals with mental disorders use drugs as a form The full report is available online at www.drugabuse.gov/ of self-medication. A common example of this hypothesis researchreports/comorbidity. ■

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