Herbert D. Kleber, M.D., Director
Richard W. Foltin, Ph.D., Associate Director for Research, Research Scientist VI
Frances R. Levin, M.D., Associate Director of Education, Psychiatrist II
Susan Carden, Ph.D., Associate Director of Administration
Efrat Ahronovich, Ph.D., Research Scientist III
Evaristo Akerele, M.D., Psychiatrist II
Adam Bisaga, M.D., Psychiatrist II
Kenneth Carpenter, Ph.D., Research Scientist III
Reynolds C. Clodfelter, Jr., Psy.D., Research Scientist II
Eric Collins, M.D., Psychiatrist II
Sandra Comer, Ph.D., Research Scientist V
Allison Dorlen-Pastor, Ph.D., Research Scientist II
Suzette M. Evans, Ph.D., Research Scientist V
Margaret Haney, Ph.D., Research Scientist V
Carl Hart, Ph.D., Research Scientist III
Aparna Kalbag, Ph.D., Research Scientist II
David McDowell, M.D., Psychiatrist II
Edward Nunes, M.D., Psychiatrist II
Jami Rothenberg, Ph.D., Research Scientist IV
Wilfrid Raby, M.D., Ph.D., Medical Specialist II
Eric Rubin, M.D., Ph.D., Psychiatrist II
Elizabeth Schreiber, Ph.D., Research Scientist II
Maria Sullivan, M.D., Ph.D., Psychiatrist II
Suzanne Vosberg, Ph.D., Research Scientist III
Jeffrey Wilson, M.D., Medical Specialist II

Research in the Division focuses on the antecedents and consequences of substance use and abuse, with particular emphasis on the development and testing of novel approaches to the treatment of substance abuse. The Division is unique in its ability to examine substance abuse issues at three levels: in non-human primates, in controlled laboratory research with human volunteers and, clinically, in treating substance abusing patients.

Overall, the Division has over 25 M.D. or Ph.D. faculty, seven faculty with K awards and a total of 30 grants. A number of these were under the direction of our co-founder and co-director, Dr. Marian Fischman, who died in October, 2001.

Medications Development Research Centers
Two NIDA funded medication Development Centers are now active in the Division. The first of these, under the direction of Dr. Kleber (Co-P.I., Evans), consists of two Cores (a Central Administrative Core and a Training/Education and Biostatistics Core) and four separate projects.

Project 1 (P.I., Comer) has developed a laboratory model of heroin abuse to evaluate new medications for opiate addiction as well as improving outcome and acceptability of existing medications such as methadone and naltrexone. Drs. Comer and Collins showed that a depot formulation of naltrexone can provide narcotic blockage for four weeks, and as well evaluated the partial opioid agonist buprenorphine and the combination product containing buprenorphine and naloxone.

Project 2 (P.I., Laruelle), in collaboration with the Division of Brain Imaging, measures mesolimbic dopamine D1/D2 receptors in response to cocaine administration as a possible marker for cocaine medication.

Project 3 (P.I., Raby) continues to explore pharmacological treatments for depressed cocaine abusers. An ongoing double-blind, placebo-controlled trial assessing the efficacy of venlafaxine is near completion.

Project 4 (P.I., Haney), with the collaboration of Drs. Hart, Comer, Vosberg, and Foltin studies possible treatment medications for marijuana withdrawal and craving. Dr. Haney has completed a residential laboratory study in marijuana smokers demonstrating that the antidepressant, nefazodone, improved symptoms of anxiety during marijuana withdrawal, whereas sustained-release bupropion significantly worsened symptoms of marijuana withdrawal.

The Central Administrative Core, headed by Dr. Susan Carden, in addition to providing centralized coordination, statistical help, and resources, supports pilot studies on promising medications and funding for other small pilot studies, several of which focus on dually-diagnosed patients.

Our second Center grant, Novel Pharmacotherapies for Cocaine Dependence (P.I., Levin, Co-P.I., Nunes) supports an Administrative Core, pilot studies, and two Projects.

Inpatient Laboratory Research with Human Participants

Residential Laboratory In their ongoing characterization of drug use by the workforce, Drs. Foltin, Haney, Hart, and Vosberg (P.I., Hart) examine the effects of stimulants and sedatives in shift workers. Psychomotor performance and subjective-effects ratings were differentially altered during the night-shift: performance and alertness were decreased while ratings such as “sleepy” were increased. Zolpidem improved subjective ratings of sleep, but not nighttime performance or mood. Methamphetamine did not improve sleep ratings, but did improve nighttime performance and mood. Studies assessing treatments for marijuana withdrawal (Project 4: P.I. Haney) are also conducted in the residential laboratory.

Cocaine Laboratory Three NIDA-funded grants support this research: “I.V. Cocaine Abuse Treatment: A Laboratory Analysis”(Foltin, PI); "Novel Cocaine Pharmacotherapies: Clinic and Lab Studies,” (Haney, PI); and “Laboratory Analysis of Cocaine Abstinence" (Foltin, PI). Drs Foltin, Haney, Hart, Vozburg, Collins, Rubin and Evans are all conducting studies with the goal of better understanding cocaine abuse and its treatment. Several potential medications were evaluated this past year in our laboratory model, including venlafaxine, gabapentin, and baclofen. We are currently testing new models for evaluating the choice to take cocaine under laboratory circumstances and continuing our studies on the effects of menstrual cycle phase on the response to cocaine in females. Dr. Hart and colleagues continue to evaluate the role of indirect dopamine modulation on cocaine related behaviors. Our study on I.V. Cocaine Abuse Treatment: A Laboratory Analysis was recently refunded for an additional 5 years. In the coming year, we plan, with the help of Drs Levin and Nunes, to further expand our studies to focus on cocaine's effects in individuals with comorbid psychiatric disorders.

Imaging Studies
The Division is collaborating on a variety of imaging studies of cocaine dependence. Dr. Rubin continues his positron emission tomography (PET) study of regional cerebral metabolism in cocaine-dependent individuals who have developed major depression to understand better the mechanisms for affective disorders among cocaine users. Dr. Foltin is collaborating with the Functional Brain Mapping Division (Drs. M. Laruelle and D. Martinez) to correlate drug-related behavioral measures with dopamine receptor imaging. We are also collaborating with the Department of Radiology (Drs. T. Brown and D. Shungu) to develop magnetic resonance spectroscopy procedures to image cocaine’s effects on the brain.

Alcohol Inpatient Studies
The Division is expanding its medications development theme to include alcohol. Drs. Evans and Bisaga are using laboratory procedures to examine the interaction of NMDA antagonists and gabaergic drugs with alcohol. An acute interaction study with memantine in combination with alcohol found memantine decreased craving for alcohol. Ongoing studies include an acute interaction study of gabapentin in combination with alcohol, as well as studies evaluating the effects of memantine or gabapentin maintenance on alcohol self-administration, drug discrimination, and cue reactivity.

Outpatient Laboratory Research with Human Participants
Alcohol and Anxiolytics Dr. Evans continues to focus on several behavioral and electrophysiological markers that may be associated with increased risk for drug or alcohol abuse in women. In collaboration with Dr. Gerard Bruder in the Department of Biopsychology, she is adding electrophysiological measures and assessing changes across the menstrual cycle in her study of vulnerability to abuse these substances in females with and without a family history of alcoholism. She is also investigating women with depressive symptoms, women who are social drinkers, and women with multiple risk factors (e.g., depressive symptoms and a paternal history of alcoholism).

Opiates Drs. Comer, Evans and Bisaga are completing a study that evaluated sex differences in response to pain stimuli at five different phases of the menstrual cycle. Overall, normally cycling women showed increased tolerance to pain in the luteal phase of the menstrual cycle. They are currently conducting a study assessing sex differences to the analgesic effects of morphine.

Marijuana Drs. Haney and Foltin have a number of ongoing studies comparing the effects of smoked marijuana and oral THC across a range of behaviors: food intake, subjective effects and neurocognitive performance in individuals with and without HIV-related weight loss. These studies attempt to define the potential medical use of smoked marijuana, compared to oral THC, in a clinically relevant population.

Research with Non-human Primates
Under the direction of Dr. Foltin, the Division's preclinical studies in non-human primates continue. Drs Foltin, Evans and Comer are conducting studies aimed at understanding the behavioral and biological processes that underlay drug seeking (craving) and drug taking. Separate studies and grants focus on behavior related to food intake, heroin smoking and the effects of cocaine across the menstrual cycle.

Clinical Treatment Studies
Substance Treatment and Research Service (STARS) STARS has continued to expand at our 168th Street Site and our new satellite site in Long Island. Jami Rothenberg, Ph.D. was appointed to Clinical Director of STARS. New researchers at STARS include Elizabeth Schreiber, Ph.D., Reynolds C. Clodfelter, Jr., Psy.D., and Wilfrid Raby, M.D. Ph.D., Associate Director for Medical Affairs. David McDowell continues to serve as the Medical Director, and Dr. Akerele, the Assistant Medical Director.

Since our protocols usually have an intensive psychosocial treatment component, STARS treats a wide spectrum of individuals with substance problems who are willing to participate in research. Current protocols and treatment studies taking place at STARS involve problems with cocaine, marijuana, opiates, alcohol, nicotine, and cognitive studies. Dr. Rothenberg has developed a training site at STARS where clinical psychology graduate students may rotate as part of their predoctoral internship experience at the NYSPI. STARS has allowed for the centralization of all outpatient clinical substance abuse research and has increased both the visibility and productivity of treatment research for substance abuse disorders. Spearheaded by Drs. Raby and Aharonovich, STARS has taken a major step in broadening their recruitment base by opening a second recruitment and treatment site at the Long Island Jewish Hospital in Long Island.

Cocaine Studies Cocaine studies include gabapentin trials conducted by Drs Bisaga and Nunes, venlafaxine trials for depression by Drs. Raby, McDowell, and Nunes, both of which are funded by the Medications Development Center Grant. In addition, Drs. Levin and Evans are investigating the efficacy of methylphenidate in individuals with cocaine dependence and ADHD.

Marijuana Studies Drs. McDowell and Levin are conducting a clinical trial comparing nefazodone and bupropion to placebo for the treatment of marijuana dependence. This study builds on our previous work, showing that abrupt cessation of marijuana leads to withdrawal symptoms similar to those of depression and nicotine withdrawal. Drs. Levin and Clodfelter are conducting a randomized pilot trial funded by the Center comparing dronabinol to placebo for marijuana dependence.

Opiate Studies Drs. Sullivan, Rothenberg, Kleber, and Nunes continue to assess the effectiveness of naltrexone in combination with behavioral therapy for opiate dependence. Drs. Comer and Sullivan are also conducting a depot naltrexone tolerability and treatment study for opiate dependence. As an extension of her work in developing and implementing novel treatments for opiate dependence, Dr. Sullivan plans to assess the efficacy of double-blind nefazodone in combination with open-label naltrexone for depressed opiate-dependent individuals. Drs. Collins and Kleber are evaluating several detoxification strategies (including ultra-rapid anesthesia detoxification) for opiate dependence. Drs. Akerele and Kleber recently completed a study comparing lofexidine (an adrenergic agonist) to placebo for opiate detoxification and the medication was highly effective for opiate detoxification.

Alcohol Studies Drs. Evans and Levin have recently initiated a double-blind trial assessing the utility of memantine compared to placebo for alcohol-dependent individuals. Using a new treatment developed at STARS, Drs. Rothenberg and Carpenter are collecting pilot data to study naltrexone in combination with behavioral therapy in alcohol dependence as well.

Clinical Research and Community Programs Dr. Levin continues her ADHD and cocaine abuse research at Bridge Plaza Treatment/ NARCO Freedom, Inc. and the Addiction Research and Treatment Corporation comparing the efficacy of methylphenidate SR, bupropion SR, and placebo in methadone maintenance patients with adult ADHD. In conjunction with this study, Drs. Levin, Evans, Kalbag, and Rothenberg are examining high-risk HIV behavior in methadone- maintained patients with or without ADHD, and comparing 2-risk reduction interventions in this population.

Clinical Trials Network The Long Island Regional Node (P.I.,Nunes) in NIDA’s Clinical Trials Network is currently participating in two clinical trials using Buprenorphine/Naloxone for opiate detoxification at Phoenix House and a Long Island Jewish/Hillside Hospital Community Treatment Program. The Node is also implementing a smoking cessation trial at Bridge Plaza/Narco Freedom, Inc. and at St. Luke’s Roosevelt Hospital Center/Smithers-Trinity Addiction Treatment and Research Center. Bridge Plaza/Narco Freedom Inc. will also be participating in a Motivation Enhancement Therapy for Spanish speaking substance users.

Education and Training
Dr. Levin organizes the training for the Division research fellowship in substance abuse and serves as the Addiction Psychiatry Fellowship Director. She was appointed as the new Q. J. Kennedy Associate Professor of Clinical Psychiatry Chair in recognition of her ongoing educational work and commitment to improving substance abuse training for the Medical Center. Drs. Kleber, Levin, and Collins continue to provide substance abuse curriculum for medical students and Drs. Levin and McDowell coordinate a course for second and third year psychiatric residents. In addition, Drs. Kleber and Levin have a program to teach house staff at Columbia-Presbyterian Medical Center key aspects of the diagnosis and treatment of substance abuse. Dr. Levin continues to serve as the substance abuse course director for the Clinical Practice Course for the first and second year medical students and coordinates the substance abuse section of the pharmacology course for the second year medical students.

The NIDA-funded Research Fellowship in Substance Abuse Disorders The purpose of this fellowship is to train candidates for careers in clinical research in substance abuse and dependence. Dr. Levin has been successful in obtaining ACGME certification for the Division's NIDA-funded Research Fellowship in Substance Abuse Disorders.

This year we had five Fellows: Vladamir Ginzburg, M.D., Jennifer Nasser, Ph.D., Reynolds C. Clodfelter, Jr., Psy.D., Eric Gunderson, M.D., and Andrew Bennett, M.D.. In July of 2002, two other Fellows plan to join our group: Mikhail Nickita, M.D. and Lesley Green, Ph.D. On completing his fellowship, Dr. Clodfelter took a position at STARS as a Research Scientist. One of our past Research Fellows, Dr. Wilson (child psychiatrist) was hired on staff as a Medical Specialist. Research conducted by Fellows this year also includes Dr. Bennett’s work on Dr. Haney’s Divalproex study for cannabis withdrawal and Dr. Gunderson’s work on evaluating substance abuse training for medical housestaff.