Drugs of Abuse, Immunity, and Immunodeficiency

316 Pages·1991·11.37 MB·English

by  John W. Hadden (auth.)

DRUGS OF ABUSE,
IMMUNITY, AND
IMMUNODEFICIENCY
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of SCience
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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DRUGS OF ABUSE,
IMMUNITY, AND
IMMUNODEFICIENCY
Edited by
Herman Friedman,
Steven Specter,
and
Thomas W. Klein
The University of South Florida
Tampa, Florida
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Drugs of abuse, immunity, and immunodeficiency I edited by Herman Friedman,
Steven Specter, and Thomas W. Klein.
p. cm. - (Advances in experimental medicine and biology; v. 288)
Based on the International Conference on Drugs of Abuse, Immunity, and Im
munodeficiency held in Clearwater Beach, Fla., Dec. 13-15, 1989; sponsored by the
University of South Florida College of Medicine with the support of the National In
stitute of Drug Abuse.
Includes bibliographical references and index.
ISBN-13: 978-1-4684-5927-2
I. Narcotics - Immunology - Congresses. 2. Psychoneuroimmunology - Con
gresses. 3. Immunological deficiency syndromes-Congresses. 4. Marihuana
Immunology - Congresses. 5. Cocaine - Immunology - Congresses. 6. Alcohol
Immunology-Congresses.!' Friedman, Herman, 1931- . II. University of South
Florida. College of Medicine. III. National Institute of Drug Abuse. IV. International
Conference on Drugs of Abuse, Immunity and Immunodeficiency (1989: Clearwater
Beach, Fla.) V. Series.
[DNLM: I. Alcohol, Ethyl-pharmacology-congresses. 2. Antibody Formation
drug effects - congresses. 3. Cannabis - congresses. 4. Cocaine - pharmacology
congresses. 5. Immune System-drug effects-congresses. 6. Narcotics-pharma
cology-congresses. WI AD559 v. 288 I QW504 D7945 1989]
RM316.D79 1991
616.97/071-dc20
DNLM/DLC 91-3888
for Library of Congress CIP
Proceedings of a symposium on Drugs of Abuse, Immunity, and
Immunodeficiency, held December 13-15, 1989, in Clearwater Beach, Florida
ISBN-13: 978-1-4684-5927-2 e-ISBN-13: 978-1-4684-5925-8
DOl: 10.1007/978-1-4684-5925-8
© 1991 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1991
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All righ ts reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
This volume is based on the program of the International Conference on Drugs
of Abuse, Immunity and Immunodeficiency held in Clearwater Beach, Florida. It
was sponsored by the University of South Florida College of Medicine with the
support of the National Institute on Drug Abuse.
During the past few decades, drugs of abuse, including marijuana, cocaine,
opiates and alcohol, have been studied by biomedical scientists in terms of the
systemic effects of the drugs as well as alterations in neurophysiology and the
psychology. More recently, the scope of such investigations has been broadened to
include alterations within the immune system, and the influence of altered immunity
on physiological and psychological consequences of drug abuse. In this regard,
participants in the Clearwater Beach conference provided new information concern
ing both basic and clinical aspects of drugs of abuse and immunity, especially
immunodeficiency. Advances have been made in recent years in understanding the
nature and mechanisms regulating the immune response and the mechanisms by
which drugs may influence immune responses. In particular, the emergence of
psychoneuroimmunology as a new discipline has heightened interest in immune
responses influenced by psychoactive drugs. This has resulted in interdisciplinary
investigations involving clinical and basic scientists including microbiologists, immu
nologists, physiologists, psychiatrists, oncologists and others.
The recreational use of the above mentioned drugs by large numbers of
individuals has aroused serious concern about the consequences of this activity. It is
well known that marijuana is a widely used substance in this as well as other
countries. Currently cocaine, especially crack, use is considered to be epidemic. The
"war on drugs" by the U.S. government is directly aimed at the use of marijuana,
cocaine and opiates, as well as other elicit drugs. Alcoholism is also a major
problem in this country, as it is in many other countries. It is estimated there are at
least 10,000,000 alcoholics in the U.S. alone. A significant proportion of those who
are hospitalized for infectious diseases are alcoholics and recently there have been
reports of an association between marijuana use and cancer. These observations
have encouraged laboratory studies aimed at determining the nature and mechanism
whereby these drugs may affect immune functions. There has been a very strong
concern that if drugs of abuse are indeed immunosuppressive, individuals who use
such drugs would be prone to infectious diseases and would have increased mortality
due to such infections. This has not been observed for acute infections but there are
some observations which suggest that chronic diseases may be more frequent in drug
abusers. Beginning in the 1970's systematic studies were begun to determine
v
whether drugs such as marijuana or its components can influence immune responses
in a negative manner. Since then, the number of these types of studies has increased
along with increased funding for drug effects on immunity.
With the onset of the acquired immunodeficiency syndrome (AIDS) epidemic
in the United States and other countries, attempts have been made to search for
possible "cofactors" which interact with the human immunodeficiency virus. Approxi
mately one fifth of all AIDS patients in this country are i.v. drug abusers and it has
been shown that the AIDS virus is spread by contaminated needles or equipment
used by such drug users. In addition, the drugs used are now known to be immuno
suppressive in many instances. Other AIDS patients are not i.v. drug abusers but
often utilize other drugs, such as marijuana and cocaine. There is a possibility that
such drugs may act as co-factors in AIDS progression. Thus, there has been a
concerted effort to examine in detail the mechanism(s) whereby such drugs may
compromise the immune system in general.
This volume begins with a chapter reviewing the subject of immunopharmaco
logy and immunotoxicologyy in order to provide a background of these areas for the
reader. The volume is then divided into groups of chapters dealing with marijuana,
cocaine, opiates, alcohol and miscellaneous drugs. These groups are then subdivided
generally into human and animal studies. For example, the section on marijuana
begins with chapters describing an immune abnormality in marijuana smokers (see
Nahas and Osserman) and a chapter reporting the association of marijuana smoking
with cancer (see Donald). The marijuana section continues with studies involving
the effects of THe on cultured human leukocytes and contains reports on the
modulation by the drug on natural killer cell function, neutrophil function, and
secretion of cytokines by human leukocytes. These human studies are followed by a
series of chapters involving the use of animal models in marijuana research. This
section begins with the chapter by Zimmerman, wherein the positive and negative
enantiomers of THe are examined for their immunomodulating potential in a mouse
model of antibody production. This chapter is followed by an interesting one by
Lyman, wherein THe treatment is shown to actually suppress the development of
experimental allergic encephalomyelitis in rats. Next, several chapters appear
involving the influence of various cannabinoids on macrophage function and on
lymphocyte responses to nonspecific mitogens and specific antigens of bacterial and
viral origin.
The next section of this volume contains the emerging area of immunomodula
tion by cocaine. The first chapter in this section reports on distrubances of human
peripheral blood T cell phenotypes in cocaine and heroin addicts (see Donahoe et
al.,), and this is followed by a report demonstrating that cocaine can directly modu
late the function of human and mouse lymphocytes in culture. The section dealing
with opiates and the immune response begins with a chapter reviewing the area of
immune alteration associated with heroin abuse and methadone maintenance (see
Novick et al). Several chapters follow, wherein human leukocytes are removed and
the influence of various opiates on cell function is examined in vitro. Peterson et aI.,
report among other things that human peripheral mononuclear cells treated with
morphine in vitro replicate the HIV virus to a greater extent than non-treated
leukocytes. Succeeding chapters, employing cultured human leukocytes, suggest that
morphine can modulate cytokine production (see Jessop and Teplits) and surface
receptors (see Falek et al.) of these cells. The rest of the section on opiates involves
animal studies wherein the influence of opiates and opiate analogs on lymphocyte
VI
proliferation is examined, the interaction of endorphins with lymphocytes is explored
and the influence of morphine on a murine infectious disease model is examined.
The effects of alcohol on the immune response of experimental animals is
discussed in the chapters of the next section. lerrells reviews many of the studies
involving either the administration of alcohol to rodents or the addition of alcohol to
cultured rodent cells and the consequent effects of these drug additions on immune
cell function. Ewald et aI., report on the immune alteration observed in the off
spring of mice previously exposed to alcohol in utero. Other chapters in this section
deal with the influence of alcohol on the intricate functioning of leukocytes impor
tant in host defense mechanisms existing in both the lung (see Nelson et al) and the
liver (see Spitzer et al). The final section deals with various putitive immunomodul
ating compounds ranging from the isobutyl nitrates to the herpesviruses.
The immune system of humans is continuously exposed to a variety of environ
mental antigens and toxic substances. Drugs of abuse are one of many such groups
of these toxic agents. The studies reported in this volume clearly show that drugs of
abuse readily impact upon and modulate the function of the immune system.
Although many of the drug induced alterations in immune function have been
defined, little is understood concerning the molecular and cellular basis for these
changes. Furthermore, the acute and chronic public health implication are not fully
appreciated. This volume should be of interest to immunologists, pharmacologists,
toxicologists, and public health workers who care for and rehabilitate drug abusers.
It is our hope that the publication of this volume will inspire a continuing interest in
drug abuse and immunomodulation, and will result in a better definition of the true
public health imp ace of drugs of abuse and immunity.
The editors take this opportunity to express gratitude to Ms. Sally Baker, Ms.
Judy Flynn, and Ms. Ilona Friedman for outstanding secretarial assistance in the
preparation of this volume. Also, we would like to thank NIDA members, Dr.
Charles Sharp and Ms. Iris O'Brien, for helpful advice and suggestions in construct
ing the meeting program.
H. Friedman
T. W. Klein
S. Specter
Tampa, FL
November 1990
VII
CONTENTS
Immunopharmacology and Immunotoxicology .......................... .
JOHN W. HADDEN
Neuroimmunopharmacologic Effects of Drugs of Abuse ................... 13
NICHOLAS R. S. HALL, MAUREEN P. O'GRADY, and
ROBERT A. MENZIES
Altered Serum Immunoglobulin Concentration in Chronic Marijuana
Smokers ....................................................... 25
GABRIEL G. NAHAS and ELLIOTT F. OSSERMAN
Advanced Malignancy in the Young Marijuana Smoker ................... 33
PAUL J. DONALD
Effects of Marijuana on Human Natural Killer Cell Activity ................ 47
STEVEN SPECTER and GERALD LANCZ
Adverse Effect of a9-Tetrahydrocannabinol on Human Neutrophil
Function ...................................................... 57
JULIE Y. DJEU, MIN WANG, and HERMAN FRIEDMAN
Influence of Marijuana Components (THC and CBD) on Human Mono-
nuclear Cells Cytokine Secretion In Vitro .............................. 63
BERNARD WATZL, PHIL SCUDERI, and
RONALD R. WATSON
Effect of Stereospecific Cannabinoids on the Immune System . . . . . . . . . . . . . .. 71
A. M. ZIMMERMAN, N. TITISHOV, R. MECHOULAM, and
S. ZIMMERMAN
IX
Drugs of Abuse and Experimental Autoimmune Diseases .................. 81
WILLIAM D. LYMAN
Effects of Marijuana on Macrophage Function .......................... 93
G. A CABRAL and R. VASQUEZ
Cannabinoid Induced Changes in Eicosanoid Synthesis by Mouse Perito-
neal Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
SUMNER BURSTEIN
Suppression of T Lymphocyte Subpopulations by THC .................... 113
SUSAN PROSS, CATHERINE NEWTON, THOMAS KLEIN,
RAY WIDEN, JUDY SMITH, and HERMAN FRIEDMAN
Drugs of Abuse and Infections ...................................... 119
S. G. BRADLEY
Effect of Delta-9-Tetrahydrocannabinol on Mitogenic and Antigenic
Stimulation of Lymphoid Cells from Inbred Hamsters Infected with
Treponema Pallidum subsp. Pallidum ................................. 127
LOIS J. PARADISE, ANGELA PRUITT, and
ANDREW W. O'B. BURGESS
Combined Immunosuppressive Activities of Delta-9-Tetrahydrocannabinol
and Murine Retrovirus ............................................ 135
STEVEN SPECTER, GERALD LANCZ, GINA WESTRICH, and
HERMAN FRIEDMAN
Effects of Cocaine and Other Drugs of Abuse on Immune Function .......... 143
ROBERT M. DONAHOE, ARTHUR FALEK,
JOHN J. MADDEN, JANET K. A NICHOLSON,
PETER BOKOS, KARL GALLEGOS, and RICHARD VEIT
Cocaine Effects on Cultured Lymphocytes ............................. 151
THOMAS W. KLEIN, CATHERINE NEWTON, and
HERMAN FRIEDMAN
In Vivo and In Vitro Studies of Opiates and Cellular Immunity in Narcotic
Addicts ....................................................... 159
DAVID M. NOVICK, MIRIAM OCHSHORN, and
MARY JEANNE KREEK
x
Opiates, Human Peripheral Blood Mononuclear Cells, and HIV ............. 171
PHILLIP K. PETERSON, BURT M. SHARP, GENYA GEKKER,
BROOKS JACKSON, and HENRY H. BALFOUR, JR.
In Vitro Effect of High Doses of Morphine on Con A Induced Lympho-
kine Production ................................................. 179
JOHN J. JESSOP and MICHAEL S. TAPLITS
Opiates as Immunosuppressive and Genotoxic Agents ..................... 189
ARTHUR FALEK, ROBERT M. DONAHOE,
JOHN J. MADDEN, and DAVID A SHAFER
The Effect of Morphine and DAGO on the Proliferative Response of
Murine Splenocytes .............................................. 203
TOBY K. EISENSTEIN, DENNIS D. TAUB,
MARTIN W. ADLER, and THOMAS J. ROGERS
Endorphin Peptides Enhance in Rat Lymphocytes the Mitogen-induced
T Cell Proliferation Which Has Been Suppressed by Prostaglandins .......... 211
LUCINDA M. HEMMICK and JEAN M. BIDLACK
Biochemical Characterization of Naloxone-Resistant Receptors for
p-Endorphin on a Human Mononuclear Cell Line (U937) and Murine
Splenocytes .................................................... 215
BURT M. SHARP, NAHID A SHAHABI,
PHILLIP K. PETERSON, and KRISTIN M. LINNER
Effects of Morphine Addiction on the Pathogenesis of Murine
Toxoplasmosis .................................................. 223
CHUN C. CHAO, BURT M. SHARP, CLAIRE POMEROY,
GREGORY A FIliCE, and PHILLIP K. PETERSON
Immunodeficiency Associated with Ethanol Abuse ....................... 229
THOMAS R. JERRELLS
Effect of Prenatal Alcohol Exposure on Lymphocyte Populations in Mice ...... 237
SANDRA J. EWALD, CHING HUANG, AND LAURA BRAY
The Effects of Ethanol, Tumor Necrosis Factor, and Granulocyte Colony-
Stimulating Factor on Lung Antibacterial Defenses ....................... 245
STEVE NELSON, GREGORY BAGBY, JEFF ANDRESEN,
CHESTER NAKAMURA, JUDD SHELLITO, and
WARREN SUMMER
XI