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The Alkaloids: Chemistry and Biology

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The Alkaloids: Chemistry and Biology CONTRIBUTORS Numbers in parentheses indicate the pages on which the authors’ contributions begin. B. EMMANUEL AKINSHOLA (135), Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, eakinshola@ howard.edu NORMA E. ALEXANDER (293), NDA International, 46 Oxford Place, Staten Island, NY 10301, [email protected] SYED F. ALI (79, 135), Division of Neurotoxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, [email protected] KENNETH R. ALPER (1, 249), Departments of Psychiatry and Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, [email protected] MICHAEL H. BAUMANN (79), Clinical Psychopharmacology Section, Intra- mural Research Program, NIDA, National Institutes of Health, Baltimore, MD 21224, [email protected] DANA BEAL (249), Cures-not-Wars, 9 Bleecker Street, New York, NY 10012, [email protected] ZBIGNIEW K. BINIENDA (193), Division of Neurotoxicology, National Cen- ter for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, [email protected] WAYNE D. BOWEN (173), Laboratory of Medicinal Chemistry, NIDDK, NIH, Building 8 B1-23, 8 Center Drive, MSC 0820, Bethesda, MD 20892, [email protected] FRANK R. ERVIN (155), Department of Psychiatry and Human Genetics, McGill University, Montreal, Quebec H3A 2T5, Canada, md18@musica. mcgill.ca JAMES W. FERNANDEZ (235), Department of Anthropology, University of Chicago, 1126 E. 59th Street, Chicago, IL 60637, jwfi@midway. uchicago.edu xi xii CONTRIBUTORS RENATE L. FERNANDEZ (235), Department of Anthropology, University of Chicago, 1126 E. 59th Street, Chicago, IL 60637, rlf2@midway. uchicago.edu GEERTE FRENKEN (283), INTASH, P.O. Box 426113, San Francisco, CA 94142, [email protected] STANLEY D. GLICK (39), Center for Neuropharmacology and Neuro- science, Albany Medical College, Mail Code 136, Albany, NY 12208, [email protected] AUDREY HASHIM (115), Nathan S. Kline Institute for Psychiatric Re- search, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962, [email protected] W. LEE HEARN (155), Metro-Dade County Medical Examiner Department, Number One Bob Hope Road, Miami, FL 33136-1133, [email protected] dade.fl.us SCOTT HELSLEY (63), Department of Anesthesiology, Duke University Medical Center, Box 3094 Med. Ctr., Durham, NC 27710, scotthelsley@ hotmail.com JEFFREY D. KAMLET (155), Addiction Treatment Program, Mt. Sinai Med- ical Center, 300 Arthur Godfrey Road, Suite 200, Miami, FL 33140, [email protected] CHARLES D. KAPLAN (249), Department of Psychiatry and Neuropsychol- ogy, Maastricht University, P. O. Box 616, Maastricht 6200MD, The Neth- erlands, [email protected] HERBERT KLEBER (xv), Columbia University College of Physicians and Surgeons, 1051 Riverside Drive, New York, NY 10032, [email protected] CRAIG A. KOVERA (155), Departments of Neurology and Pharmacology, University of Miami School of Medicine, Miami, FL 33124, ckovera@ brandinst.com ABEL LAJTHA (115), Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962, lajtha@nki. rfmh.org HOWARD S. LOTSOF (293), NDA International, 46 Oxford Place, Staten Island, NY 10301, [email protected] ISABELLE M. MAISONNEUVE (39), Center for Neuropharmacology and Neuroscience, Albany Medical College, Mail Code 136, Albany, NY 12208, [email protected] CONTRIBUTORS xiii DEBORAH C. MASH (79, 155), Departments of Neurology and Pharmacol- ogy, University of Miami School of Medicine, Miami, FL 33124, dmash@ miami.edu EMANUEL S. ONAIVI (135), Departments of Psychiatry and Pharmacology, Vanderbilt University School of Medicine, 5428 Country Drive, Nashville, TN 37211, [email protected] JOHN PABLO (79, 155), Departments of Neurology and Pharmacology, University of Miami School of Medicine, Miami, FL 33124, jpp71@ hotmail.com LINDA A. PARKER (211), Department of Psychology, Wilfrid Laurier Uni- versity, Waterloo, Ontario N2L 3C5, Canada, [email protected] PIOTR POPIK (227), Institute of Pharmacology, Polish Academy of Sci- ences, 12 Smetna Street, Krakow 31-343, Poland, [email protected] RICHARD A. RABIN (63), Department of Pharmacology and Toxicology, SUNY Buffalo, 132 Farber Hall, South Campus, Buffalo, NY 14214, [email protected] RICHARD B. ROTHMAN (79), Clinical Psychopharmacology Section, Intra- mural Research Program, NIDA, National Institutes of Health, Baltimore, MD 21224, [email protected] ANDREW C. SCALLET (193), Division of Neurotoxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, [email protected] LARRY C. SCHMUED (193), Division of Neurotoxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, [email protected] HENRY SERSHEN (115), Nathan S. Kline Institute for Psychiatric Re- search, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962, [email protected] SHEPHARD SIEGEL (211), Department of Psychology, McMaster Univer- sity, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada, [email protected] PHIL SKOLNICK (55), Lilly Research Laboratories, Lilly Corporate Center, Drop Code 0510, Indianapolis, IN 46285, skolnick [email protected] KAREN K. SZUMLINSKI (39), Center for Neuropharmacology and Neuro- science, Albany Medical College, Mail Code 136, Albany, NY 12208, [email protected] xiv CONTRIBUTORS RACHEL TYNDALE (155), Center for Addiction and Mental Health, Univer- sity of Toronto, Toronto, Ontario M5S 1A1, Canada, [email protected] J. C. WINTER (63), Department of Pharmacology and Toxicology, SUNY Buffalo, 118a Farber Hall, South Campus, Buffalo, NY 14214, jcwinter@ acsu.fjbuffalo.edu MALGORZATA WROBEL´ (227), Institute of Pharmacology, Polish Acad- emy of Sciences, 12 Smetna Street, Krakow 31-343, Poland, widla@if- pan.krakow.pl FOREWORD The use of, abuse of, and dependence on a variety of licit and illicit sub- stances constitute the major public health problem facing the United States and many other countries. Drug abuse is the leading cause of new HIV infections, a major cause of cancer deaths as well as automobile and boat accidents, the largest contributor to our burgeoning prison population, and the largest cause of crime, violence, domestic and child abuse, and commu- nity destruction. In the United States there are more than 50 million nicotine addicts, at least 15 million alcoholics and problem drinkers, more than 3 million marijuana addicts, 2 to 3 million cocaine addicts, and more than a million heroin addicts. The number of ‘‘hardcore’’ addicts to illicit drugs is well over 6 million. It is not surprising, given these numbers and social costs, that theories of ways to improve the situation abound. From total prohibition to total legalization and numerous steps in between, arguments rage over the best approach. For experienced observers of the situation, not blinded by partisan beliefs and rhetoric, it appears clear that there is no one answer. Mencken’s observation about simple solutions, ‘‘there is always a well- known solution to every human problem—neat, plausible, and wrong,’’ is as true now as in 1920 when he made it. Pure ‘‘supply reduction’’ models founder on the rocks of ‘‘need’’ and ‘‘greed’’—the desire for the euphoric effects of these agents, and the willingness of individuals to take risks to provide them because of the large profits. Likewise, the pure ‘‘demand reduc- tion’’ model shows its inadequacy by the lack of interest of many addicts in stopping and the failures of our current prevention and treatment programs to either prevent or treat sufficiently. We need both a balanced model and better prevention and treatment methods. The current view of addiction is a marriage of brain and behavior. Sophis- ticated imaging procedures and basic science research into the neurobiology of reward have identified key elements in the reinforcing effects of various psychoactive substances. Motivational circuits underlie the desirability of abused drugs. Brain changes after prolonged use help keep the habit going, as well as increase the likelihood of relapse after hard-won abstinence. In one sense, the reward circuitry has been ‘‘hijacked’’ by the rapid intense effects of chemicals at the expense of the more usual rewarding behaviors. Success- ful treatment thus often requires both medications—to help addicts cope with the brain’s changes and urges—and relapse prevention techniques and xv xvi FOREWORD learning—to help addicts regain the ability to get rewards from nonchemical means. The failure of many treatment attempts is a testimony to the difficulty of the task. Because of this difficulty, there is a constant search for new methods— better, faster, easier. The search for a ‘‘quick fix’’ is not limited to addicts— researchers, treatment providers, family members, friends, and policy makers share it at times as well. The fact that it hasn’t yet been found doesn’t mean it can’t be found, so efforts continue. The story of ibogaine for addiction is part of that search. One hundred years ago, as well as recently, treatment of withdrawal was often seen as synonymous with treatment of addiction. Numerous drugs and techniques—some innocuous, some lethal, most in between—were tried to improve withdrawal. None were successful for the larger task of healing addiction, although some have worked reasonably well in treating with- drawal. We still cannot successfully treat a substantial number of addicted individuals. The difficulty may lie both in the persistence of brain changes and in the difficulty of making
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