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Chemical Dependency Research Working Group |
Literature produced by the Chemical Dependency Research Working Group (CDRWG, formerly the Cocaine/Crack Research Working Group, C/CRWG) is published by the New York State Office of Alcoholism and Substance Abuse Services (OASAS). Resources for literature production and mailing were provided by the Aaron Diamond Foundation, Inc. through a grant to Medical and Health Research Association of New York City, Inc. (MHRA).
For further information about the activities of the Chemical Dependency Research Working Group contact Dr. Herman Joseph at (646) 728-4523.
Opinions contained in this compendium are those of the author(s) and are not necessarily endorsed by the Aaron Diamond Foundation, Medical and Health Research Association of New York City, Inc. (MHRA), or the New York State Office of Alcoholism and Substance Abuse Services (OASAS).
The effective treatment of cocaine and crack abuse is a major concern for drug and alcohol treatment programs and the staff of the New York State Office of Alcoholism and Substance Abuse Services (OASAS). The urgency of this problem led to the formation of the Chemical Dependency Research Working Group (CDRWG) within our agency. The overall objective of the CDRWG is to encourage interdisciplinary research that will help develop more effective treatment options for cocaine and crack abuse among consumers in drug and alcohol treatment facilities throughout New York State.
During its four year history, 25 symposia have brought together scientists, researchers and clinicians to present and exchange ideas. Symposia topics have included promising approaches to the understanding and treatment of cocaine and crack abuse, the transmission of HIV infection, problems related to pregnancy in substance abusing women, the development of drug exposed neonates and advances in neuroscience.
An important objective of the CDRWG is to disseminate the ideas that are presented in the symposia through newsletters and publications. The current publication presents eleven original papers that were delivered at two symposia held in September of 1993 and February of 1994. These symposia were cosponsored by the Chemical Dependency Institute of Beth Israel Medical Center and funded through a grant from the Aaron Diamond Foundation to the Medical and Health Research Association of New York City, Inc. (MHRA). As a result of our symposia, clinicians and research scientists from Mount Sinai Medical Center, Beth Israel Medical Center and National Development and Research Institute, Inc. (NDRI) have applied for an interinstitutional grant from the National Institute on Drug Abuse (NIDA) to implement a treatment program for cocaine using methadone patients.
The CDRWG is an innovative project that was developed by the OASAS research and evaluation staff as a service to the clinical and research community in New York. It is now considered a highly respected platform for presenting research and clinical issues related to substance abuse and treatment. The current publication is an example of the high professional standards maintained by CDRWG.
Cocaine is a natural substance extracted from the coca leaves of the Erythroxylon coca plant and grown in the Andes of South America. Initially coca leaves were chewed by the Indians of the Andes. In this form cocaine is not as potent as the purified extract. Once purified and the chemical structure identified in the nineteenth century, cocaine was found to be a powerful anesthetic, especially for numbing the mucous membranes of the nose, throat and eyes. Thus, cocaine found a legitimate use in medicine, but its mood altering effects did not escape notice. The use of cocaine as a 'tonic' spread in Europe and America and as late as 1900 was still a component of Coca Cola. The Harrison Act of 1914 placed cocaine under legal restriction and erroneously classified cocaine as a narcotic. Cocaine has two basic chemical forms, the hydrochloride salt and the free base. The hydrochloride salt dissolves easily in water for injection, or can be inhaled nasally. Free base cocaine and crack, a solidified form of free base cocaine, are smoked. Crack became popular because inexperienced users did not have to learn how to make free base, or inject cocaine. Irrespective of form, cocaine becomes addicting if used frequently and in increasing amounts. The withdrawal symptoms of cocaine addiction include a cocaine induced depression and a recurring specific craving for the drug.
Both crack and injectable cocaine are associated with the transmission of HIV infection. Crack is also associated with a rise in syphilis and congenital syphilis among neonates. Sexual promiscuity (money for drugs) and lesions around the mouth caused by the heat of crack pipes and the use of broken crack pipes (chipped or shattered glass) are the vectors of transmission for STDs and HIV. The use of shared needles during cocaine binges is also an effective means of transmitting HIV and other infectious diseases.
The monograph is divided into four sections. The first article by Dr. Elliot Gardner, Brain Mechanisms of Cocaine/Crack Use, is an overview of the basic neuroscience concepts in the compulsive use of cocaine/crack. For the second section, Dr. Blanche Frank and John Galea present substance abuse trends in New York City with a special emphasis on cocaine use trends and heroin because of its increasing purity and availability.
The third section contains three articles that pertain to laboratory research. The first article by Dr. Richard Rosenthal is an overview of the psychopharmacological chemotherapies available for treating cocaine addiction. Dr. Richard Foltin describes a laboratory model to evaluate the effects of cocaine in humans. The final paper by Dr. Donald Landry describes the use of artificial enzymes to break down the cocaine molecule and render it inactive after it enters the bloodstream.
The papers in the fourth and final section present material pertaining to clinical studies and the treatment of cocaine addiction. Drs. Magura, Foote, Rosenblum, Handlesman and Lovejoy present a cognitive-behavioral model for the treatment of cocaine/crack that was implemented in the methadone program of the Mount Sinai Medical Center. Dr. James David describes some of the serious mental disorders associated with cocaine/crack use presented at a psychiatric emergency service. In the third article, Dr. Edward Nunes discusses the interrelationship between cocaine/crack use and depression and the problems associated with treating the dual diagnosed patient. Employing principles of conditioning, Dr. Ann Childress focuses on craving and craving-related cues in the treatment of cocaine addiction. Although McLellan and colleagues (1993) have reported that "there is no compelling evidence for the efficacy of acupuncture in the treatment of either opiate or cocaine addiction," the final paper investigates this procedure for treating a select group. Dr. Merrill Herman reports that some cocaine dependent patients enrolled in a methadone program have responded positively to acupuncture.
This monograph is devoted to presentations made at two symposia concerning laboratory and clinical research issues about the compulsive use of cocaine/crack. The symposia were cosponsored by the Chemical Dependency Research Working Group of the New York State Office of Alcohol and Substance Abuse Services and the Chemical Dependency Institute of Beth Israel Medical Center. The symposia and the monograph were underwritten by a grant from the Aaron Diamond Foundation to the Medical and Health Research Association of New York City, Inc. (MHRA). The two symposia, entitled Cocaine Addiction: Laboratory and Clinical Research (September 7, 1993) and Cocaine Addiction: Trends in the Use of Cocaine/Crack and Clinical Issues (February 25, 1994) were presented in the Podell Auditorium of the Beth Israel Medical Center. The problems associated with cocaine addiction necessitate an interdisciplinary approach. The intent of this monograph, therefore, was to bring together the numerous interdisciplinary issues involved in cocaine addiction and to present the recent findings from diverse fields in a precise and understandable format.
The CDRWG would like to acknowledge the editorial assistance of Dr. Dorothy Jessup of MHRA.
McLellan, A.T.; Grossman, D.S.; Blaine, J.D.; Haverkos, H.W. Acupuncture treatment for drug abuse: A technical review. Journal of Substance Abuse Treatment 1993 10:569-571.
Elliot Gardner, Ph.D. is Director of the Neurobiology Department of Albert Einstein College of Medicine, Bronx, NY.
There are many causes of chemical dependency, including economic, sociological and psychological determinants. However, it is incontrovertible that there are biological elements involved in chemical dependency which are not sufficiently appreciated by those involved in policy making at local, state and federal levels. Until all aspects of chemical dependency are understood by policy makers, legislators, and society, drug dependency will continue to remain a problem.
The number of substances listed in Chemical Abstracts is more than 15 million. This indicates that more than 15 million substances are known to the human species. Not all of these substances are readily available; only about 55 thousand can be obtained. But the psychoactive substances that are recreationally used by human beings are a very small number indeed. They are ethanol, cocaine, amphetamines, benzodiazepines, barbiturates, opiates, methyl xanines, cannabis, some solvents and some other exotic compounds that are not in ready commerce and only used locally.
The question that arises is: "What do these compounds have in common?" When one first considers this question these substances do not appear to have anything in common. For example, when considering structure, the molecular composition of opium doesn't resemble alcohol, and cannabis is not comparable to cocaine and so on. Also, it is clear that by traditional pharmacological classifications there are no demonstrable commonalities - some are stimulants, some depressants, some analgesics and so forth.
However, of those compounds that humans use recreationally, common properties are seen that are very important. 1) By and large, laboratory animals voluntarily self administer the same compounds that human beings use recreationally. It must be emphasized that laboratory animals will not self administer other compounds. So there is something about the nature of these chemicals that is very appealing, rewarding or reinforcing - something about these substances that makes them attractive to laboratory rats, dogs, monkeys and human beings alike. 2) These chemicals acutely enhance or facilitate the functioning of reward circuits or pleasure centers of the brain. There are a few inexplicable exceptions which may be due to the fact that they have not been properly studied.
The pleasure circuitry in the brain was discovered in 1954 by Olds and Milner at McGill University and therefore has been known to exist for some time. Over the last three and a half, almost four decades, the pleasure/reward circuitry has been studied around the world and in hundreds of laboratories. Therefore quite a bit is known about the pleasure circuitry in the brain including the neuroanatomy, neurophysiology, neurochemistry and neurobehavioral functioning of these circuits. Various techniques and methodologies allow researchers to tap directly into the brain reward circuitry of laboratory animals. While it is dangerous to make assumptions about the sophisticated and complex human brain from laboratory animals, researchers have begun to understand how the pleasure and reward circuitry works in the human brain. By using laboratory animals we can begin to understand how addicting drugs interact with these pleasure and reward circuits in the brain.
An important endogenous substance involved in the reward circuitry is Dopamine (DA), a catecholamine. DA has been known to be a neurotransmitter for several decades. It carries a chemical message from one nerve cell, or neuron, to another. Today DA is known to be one of many hundreds, and perhaps even thousands, of substances that the mammalian brain uses to carry messages from neuron to neuron. Neurons are nerve cells that are specialized to carry chemical-electrical messages, sometimes for long distances, in the brain. The cell body of a neuron contains a nucleus and other machinery common to other cells in the body that help maintain the integrity of the cell. Projecting from the cell body is the axon which carries electrical impulses, transports the substance the cell produces to the end of the axon called the terminal and stores it in vesicles. Located around the cell body and even sometimes along the axon are spiny projections containing receptors called dendrites which are specialized to receive chemical messages. When a substance binds to a receptor on the dendrite an impulse is sent to the cell body and then down the long axon to the terminal where the substance is released across the synapse to the next nerve cell. When neurons are placed end to end they are called nerve tracts. DA is an important substance in the human brain and there are many DA tracts that use this transmitter to carry their chemical-electrical impulse from one neuron to the next nerve cell.
One DA nerve tract is very important to the pleasure/reward circuitry in the brain. This tract originates in a part of the brain called the ventral mesencephalon (VTA) where the cell bodies are located, the axons of these cells project through the medial forebrain bundle to innervate the ventral striatum, septal area, olfactory tubercle, parts of the temporal lobe-including amygdala and periamygdalus cortices-and particularly the nucleus accumbens in the forebrain. This DA wiring, originating in the ventral tegmental area and synapsing in the nucleus accumbens, is believed to be crucial for the pleasure/reward circuit.
There are various techniques to study the pleasure/reward circuitry. One is to implant an electrode or implant a micro-injection device into the brain of a laboratory animal. Laboratory animals will perform tasks for which the reward is mild electrical stimulation in the brain. The delivery of the rewarding electrical stimulation is totally under the animals' control and in fact the test chamber can be filled with food, water and play things and yet the animals will ignore all these things-preferring the stimulation. Laboratory animals will even suffer adverse consequences such as painful electric foot shock to obtain the brief pleasurable stimulation. For example, the animal is placed in a "Start Chamber" which is safe while at the far end of the chamber is the lever and in between the two is an electric grid. Things that the animal likes can be placed in the Start Chamber, so the animals have everything they need right there and can be very content. Nothing is forcing the animal to leave the Safe Chamber. When the animal is placed into the Start Chamber for the first time it will look across to the lever and see it. As the animal moves toward the lever and steps onto the electric grid it receives a very painful foot shock. The animal then goes through an approach-avoidance conflict-is the lever worth the pain? Invariably the animal will choose to receive the very painful foot shock just to get the pleasurable stimulation. This is like a human addict who is addicted to drugs-particularly cocaine-who endures painful consequences to obtain drugs.
On the basis of many years of study, it has been determined that the relevant reward circuitry consists of a descending myelinated, or fast conducting nerve tract which probably starts in the mangocellular region in the vicinity of the ventral pallidum. The tract descends via the medial forebrain bundle, synapses in the ventral tegmental area on DA neurons, which then project through the medial forebrain bundle to synapse in the nucleus accumbens on enkephalin neurons which take the tract one step further and synapse in the ventral palladium. All drugs of abuse - depressants, stimulants and opioids - act on this circuitry to produce the rush and euphoria ("the high") that the user seeks.
The probability that animals will self administer a drug can be increased with two methods, but there are probably more. The first method is to sensitize the animal to a drug by administering a series of injections of the drug. Another method is to selectively breed animals, which are then genetically predisposed to like drugs. In fact, such animals are little polydrug abusers - they like heroin, alcohol, cocaine, and other drugs. There are other animals or strains that are drug resistant, such as Fischer 344 rats who do not like alcohol and will not drink it. They also place condition (1) poorly for cocaine and heroin. Thus, laboratory animals can be genetically bred to like such drugs and voluntarily self administer them. Conversely, laboratory animals can be genetically selected for their resistance to drugs.
Since animals can be genetically bred to like drugs or to not like drugs the question arises, "Are the brain circuities in these animals somehow different?" The answer is yes. Differences are found in the wiring and the circuitry of the nucleus accumbens where DA neurons synapse onto enkephalinergic neurons. Drug preferring animals have a marked increase of tyrosine hydroxylase in the ventral tegmental area. Tyrosine hydroxylase is the precursor for DA that the cell body needs to produce it. A decrease in the neurofilamentary transport system that transports DA within the cell body is also found in drug preferring animals. There are also differences in the release of DA, and increases in the DA2 receptor (2). Also, drug preferring animals have a marked enhancement of various aspects of the effector system, including adenylate cyclase and cyclic AMP and 3rd messenger kinases. In addition to these changes, additional changes in the genetic coding of the cells have been found which are long term and persistent.
It is crucial to understand how these changes in the reward and pleasure circuitry impart the behavior that is typical of drug dependency. From such understanding will come knowledge that will ultimately allow us to alter the circuitry to normalize it. With this essential understanding of drug dependency we can begin to design therapeutic interventions that will interact with the underlying neurobiological substrates that will change the drug preferring laboratory animal or human being into a normal laboratory animal or human being. Of course, this is not to say that environmental and social determinates are not involved. But, in addition to these economic and social factors, there are profound biological determinants of drug abuse and dependency. Until we can begin to change the neurobiology we will not have a definitive treatment for cocaine addiction.
Footnotes
Blanche Frank, Ph.D. is the Director of the Bureau of Applied Studies of the New York State Office of Alcoholism and Substance Abuse Services, New York, NY.
John Galea, M.A. is Director of the Street Studies Unit of the New York State Office of Alcoholism and Substance Abuse Services, New York, NY and a Professor at St. John's University, Queens, NY.
Cocaine, heroin and marijuana continue to be the illicit substances of major concern in New York City. Cocaine activity remains at near-peak levels, with crack continuing to drive the trend. Heroin activity is continuing to show upward trends, with potency at very high levels. Marijuana remains the most widely used illicit substance, but more exotic varieties are attracting what appears to be an expanding market.
More specifically, cocaine activity--especially relating to crack--dominates the New York City drug scene. The Street Studies Unit of the New York State Office of Alcoholism and Substance Abuse Services (OASAS) monitors drug activity on the streets of the city, and reports that crack selling continues to be widespread. Quantities are available in $2, $3, and $5 vials. Youth, under the age of 21 years, remain very much part of the crack trade. In fact, the New York City Police Department reports that youth account for about 26 percent of the arrests for crack felonies.
Hospital emergencies involving cocaine continue to increase in the New York metropolitan area with a 17 percent increase in emergencies in the year ending June 1993. The rate of cocaine emergencies in the New York metropolitan area population is the second highest in the nation after the Baltimore metropolitan area.
In addition to the City's cocaine-related problems, heroin-related problems are increasing quite dramatically with an upsurge in deaths and hospital emergencies. Between 1991 and 1992 heroin-involved deaths increased 17 percent (from 582 deaths to 679 deaths). Between the year ending June 1993 and the previous year, heroin-involved hospital emergencies increased 33 percent (from 7,215 emergencies to 9,593 emergencies).
What is most alarming is the purity of "street" heroin, which is currently averaging about 72 percent. In the past, purities rarely reached about 15 percent. Now more than half of admissions to New York City's treatment programs with heroin as the primary drug of abuse are reporting inhalation or "sniffing" as their mode of use rather than injection which had been the primary method of administration in the past. In fact, the mode of heroin use among treatment admissions shows increases in inhalation from 25 percent of admissions in 1988 to 51 percent in 1993; concomitantly, injecting had declined from 71 percent to 47 percent. At first glance, the decline in injection as a mode of use is a good sign given the risk for AIDS. The long-term view, however, does not bode well. If "street" purities decline or if the addiction becomes severe, there is a strong likelihood that injecting heroin is the course that many heroin users will ultimately take. In any case, this population is at risk for many public health problems.
Marijuana problems have also become more numerous in New York City. Emergency room episodes involving marijuana, arrests involving marijuana, and treatment admissions with marijuana as the primary drug of abuse have increased steadily over the past few years. The Street Studies Unit reports the availability of exotic varieties of marijuana that may cost as much as $800 an ounce. Also, many young people have developed a pattern of use involving the smoking of "blunts" (marijuana rolled in a cigar) and the drinking of "40's" (40 oz of malt liquor or beer). The characteristics of treatment admissions with marijuana as the primary drug of abuse reflects the pattern: more than 60 percent are 20 years of age or younger and two-thirds report alcohol as their secondary substance of abuse.
Although other drugs are also showing a resurgence, such as PCP and LSD, these three illicit drugs--cocaine, heroin and marijuana--account for more than 90 percent of admissions to New York City's treatment programs.
| Year | Quarter | Deaths Involving Cocaine(2) | Cocaine Emergency Room Mentions (N.Y. MSA)(3) | Treatment Admissions With Cocaine as Primary Drug of Abuse(4) | Cocaine Arrests(5) | Births to Women Using Cocaine(6) |
|---|---|---|---|---|---|---|
| 1986 | 1 | --- | --- | 1,705 | ||
| 2 | --- | --- | 1,910 | |||
| 3 | --- | --- | 2,426 | |||
| 4 | --- | --- | 2,099 | |||
| Total | --- | --- | 8,140 | 28,594 | 1,364 | |
| 1987 | 1 | --- | --- | 2,425 | ||
| 2 | --- | --- | 2,573 | |||
| 3 | --- | --- | 2,790 | |||
| 4 | --- | --- | 2,550 | |||
| Total | --- | --- | 10,338 | 37,624 | 1,923 | |
| 1988 | 1 | 2,809 | ||||
| 2 | 2,824 | |||||
| 3 | 2,727 | |||||
| 4 | 2,486 | |||||
| Total | 1,318 | 16,917 | 10,846 | 49,014 | 2,781 | |
| 1989 | 1 | 3,602 | 2,951 | |||
| 2 | 3,826 | 2,528 | ||||
| 3 | 4,171 | 2,930 | ||||
| 4 | 3,326 | 2,877 | ||||
| Total | 1,141 | 14,925 | 11,286 | 53,915 | 3,168 | |
| 1990 | 1 | 3,109 | 2,959 | |||
| 2 | 3,069 | 2,925 | ||||
| 3 | 3,169 | 2,557 | ||||
| 4 | 3,286 | 2,667 | ||||
| Total | 857 | 12,633 | 11,108 | 46,348 | 2,438 | |
| 1991 | 1 | 4,015 | 3,009 | |||
| 2 | 3,754 | 2,968 | ||||
| 3 | 4,043 | 3,352 | ||||
| 4 | 4,288 | 3,302 | ||||
| Total | 804 | 16,100 | 12,631 | 37,769 | 2,239 | |
| 1992 | 1 | 4,643 | 3,593 | |||
| 2 | 4,537 | 3,226 | ||||
| 3 | 5,656 | 3,245 | ||||
| 4 | 5,577 | 3,008 | ||||
| Total | 730 | 20,413 | 13,072 | 33,708 | 1,786 | |
| 1993 | 1 | (10,400) | 3,145 | |||
| 2 | preliminary | 3,081 | ||||
| 3 | estimate | 3,298 | ||||
| 4 | 2,833 | |||||
| Total | 12,357 | 31,296 |
| Year | Quarter | Deaths Involving Heroin(2) | Heroin Morphine Emergency Room Mentions (N.Y. MSA)(3) | Treatment Admissions With Heroin as Primary Drug of Abuse(4) | Heroin Arrests(5) | Average Purity of "Street" Heroin(6)(%) |
|---|---|---|---|---|---|---|
| 1986 | 1 | --- | --- | 3,123 | --- | |
| 2 | --- | --- | 2,796 | --- | ||
| 3 | --- | --- | 2,670 | --- | ||
| 4 | --- | --- | 2,643 | --- | ||
| Total | --- | --- | 11,223 | 17,289 | --- | |
| 1987 | 1 | --- | --- | 2,841 | --- | |
| 2 | --- | --- | 2,908 | --- | ||
| 3 | --- | --- | 3,062 | --- | ||
| 4 | --- | --- | 3,118 | --- | ||
| Total | --- | --- | 11,929 | 22,168 | --- | |
| 1988 | 1 | 3,073 | ||||
| 2 | 3,158 | |||||
| 3 | 2,715 | |||||
| 4 | 3,300 | |||||
| Total | 833 | 5,394 | 12,246 | 25,152 | 34.3 | |
| 1989 | 1 | 1,123 | 2,832 | |||
| 2 | 1,254 | 2,471 | ||||
| 3 | 1,533 | 2,590 | ||||
| 4 | 1,507 | 2,767 | ||||
| Total | 762 | 5,437 | 10,660 | 28,083 | 37.2 | |
| 1990 | 1 | 1,005 | 3,357 | |||
| 2 | 925 | 3,113 | ||||
| 3 | 976 | 2,956 | ||||
| 4 | 904 | 2,493 | ||||
| Total | 557 | 3,810 | 11,919 | 24,421 | 37.0 | |
| 1991 | 1 | 1,405 | 2,811 | |||
| 2 | 1,278 | 2,834 | ||||
| 3 | 1,693 | 2,941 | ||||
| 4 | 1,642 | 3,126 | ||||
| Total | 582 | 6,018 | 11,712 | 23,622 | 55.2 | |
| 1992 | 1 | 1,969 | 3,180 | |||
| 2 | 1,910 | 3,202 | 47.4 | |||
| 3 | 2,226 | 3,242 | 72.3 | |||
| 4 | 2,277 | 2,945 | 64.7 | |||
| Total | 679 | 8,382 | 12,569 | 23,509 | 62.3 | |
| 1993 | 1 | --- | (5,090) | 3,264 | 64.0 | |
| 2 | --- | preliminary | 3,214 | 66.1 | ||
| 3 | --- | estimate | 3,229 | 72.4 | ||
| 4 | --- | 3,229 | ||||
| Total | 12,936 | 24,595 |
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Last Update: March 15, 2001 |
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