Cocaine is a naturally occurring substance derived from the leaves of erythroxylon plants indigenous to South America. Pharmacologically, cocaine has two prominent actions: 1) it is a potent anesthetic; and 2) it is a powerful stimulant. Cocaine has been used in South America for more than 3,000 years and in the United States since the 19th century in a variety of forms: coca leaves, coca paste, powder cocaine, and cocaine base (e.g., freebase and crack cocaine). The final form of cocaine dictates how the drug can be administered and, as a consequence, the intensity and duration of its physiological and psychotropic effects. For example, to be effective powder cocaine can be injected, insufflated (snorted), or ingested, while crack cocaine can only be smoked. Therefore, while powder cocaine users can administer the drug in a variety of ways, crack cocaine users are limited to smoking the drug.
This chapter provides a basic overview of cocaine: what it is, where it comes from, how it is used, its effects on the body, and its addictive potential. Section B of this chapter provides background on the origins of cocaine, its use, and abuse. Section C examines the different forms of cocaine - leaf, paste, powder, and base - the ways cocaine is administered, and the differing methods by which cocaine is absorbed and distributed within the body. Section D discusses the physiological and psychotropic effects of cocaine use, outlining both the impact of various routes of administration (ingestion, injection, insufflation, inhalation) on the intensity and duration of these effects and the side effects and toxicity associated with cocaine abuse. This section also discusses the physiological and psychological aspects of cocaine dependence.
B. ORIGINS OF COCAINE USE AND ABUSE
Coca leaves have been used by South American Indians for more than 3,000 years. The use of coca leaves was associated historically with the religious ceremonies of the Incas and reserved specifically for nobility. Today, the leaves are chewed regularly in Peru and Bolivia for their therapeutic value. J. Murray, "An Overview of Cocaine Use and Abuse," 59 Psychological Reports 243-264 (1986); D.F. Allen and J.F. Jekel, Crack: The Broken Promise (1991). Chewing coca leaves provides a long-lasting, low-grade euphoria that reduces appetite, increases physical stamina, and counters symptoms associated with "mountain sickness" and oxygen deprivation. C. Van Dyke, P.I. Jatlow, P.G. Barash, and R. Byck, "Oral Cocaine: Plasma Concentrations and Central Effects," 200 Science 211-213 (1978).
Cocaine was first extracted from coca leaves around 1860 and used as an anesthetic that proved to be a boon for ophthalmology. Id.; M. Ellenhorn and D. Barceloux, Medical Toxicology: Diagnosis and Treatment of Human Poisoning (1988). In addition to anesthetizing the eye and preventing muscle reflex, cocaine constricts the arterioles which, in turn, reduces the amount of bleeding in an otherwise blood-rich area. Cocaine also widens the air sacs in the lungs, constricts the capillaries in the nasal passages, and makes breathing significantly easier. P. Jatlow, "Drugs of Abuse Profile: Cocaine," 33 Clinical Chemistry 66-71 (1987). During the 19th century, cocaine was promoted as a remedy for such respiratory ailments as asthma, whooping cough, and tuberculosis. Additionally, it was publicized, most notably by Sigmund Freud, as an aphrodisiac and an antidote for morphine addiction and alcoholism. Murray, supra note 1.
By 1890, cocaine had become the primary ingredient in many elixirs and other "restoratives" that claimed to provide relief from depression and a multitude of ailments. It was an ingredient in cigars, cigarettes, chewing gum, and several "tonics," most notably Coca-Cola (today's Coca-Cola does not contain cocaine). Id.; Jatlow, supra note 4; Van Dyke et al., supra note 2; G. Das, "Cocaine Use in North America," 33 Journal of Clinical Pharmacology 296-310 (1993). Cocaine use during the 19th century, however, was far from benign. In 1891, for example, 200 cases of death from cocaine intoxication were reported. Allen and Jekel, supra note 1. According to one estimate, the U.S. population in 1906 - numbering only half of today's population - consumed as much cocaine as did the U.S. population in 1976. Id.
During the beginning of the 20th century, the general perception was that cocaine use increased the risk of crime. By 1914, 46 states, in an effort to control crime, had enacted legislation regulating the use and distribution of cocaine. D. Musto, The American Disease: Origins of Narcotic Control (1973). That same year Congress passed the Harrison Narcotics Act, banning non-medical use of the drug and requiring strict accounting of medical dispensing to patients. Id.
Cocaine became scarce following passage of the Harrison Act. As its availability diminished, the popularity of amphetamines - legal drugs with similar physiological and psychotropic effects - increased. By the 1950s, cocaine was no longer considered a law enforcement problem. Murray, supra note 1; R. Siegel, "New Patterns of Cocaine Use: Changing Doses and Routes," 61 National Institute on Drug Abuse Research Monograph Series 204-222 (1985). During the 1960s, however, cocaine reemerged as a drug of abuse. Id. In 1970, Congress classified cocaine as a Schedule II controlled substance. While Schedule II controlled substances have legitimate medicinal uses - cocaine is used as a local anesthetic - they are recognized as having a high potential for abuse and dependency. 21 U.S.C. 812.
C. FORMS OF COCAINE AND METHODS OF USE
Cocaine derives from plants indigenous to the Andes Mountains of South America. Of the 17 species of erythroxylon plants that produce cocaine, only two (erythroxylon coca and erythroxylon novogranatense) yield sufficient levels of the cocaine alkaloid to justify mass cultivation for processing into cocaine. These two species, cultivated primarily in Peru, Bolivia, and Colombia, supply the world's cocaine. Murray, supra note 1; U.S. Department of Justice, Drug Enforcement Administration, Drugs of Abuse (1989).
1. Forms of Cocaine
Coca leaves can be processed into a variety of usable forms using an array of different and oftentimes toxic chemicals. Because all forms are derivatives of the coca plant, the active ingredient - the cocaine alkaloid - is common to all. Figure 1 illustrates the processing and routes of
administration of the five basic forms of the drug: coca leaves, coca paste, powder cocaine, freebase cocaine, and crack cocaine. The distinction between base and non-base forms of cocaine is important in determining the route of administration. Because, in comparison to base forms of cocaine (e.g., crack cocaine), non-base forms (i.e., powder cocaine) vaporize at significantly higher temperatures that tend to decompose the cocaine molecule; non-base forms of cocaine generally are not smoked.
a. Coca Leaves
Due to differing environmental factors, the cocaine content of the coca leaf ranges between 0.1 percent and 0.8 percent. Coca plants grown at higher altitudes contain a higher percentage of the cocaine alkaloid than those grown at lower altitudes and are consequently more potent. Murray, supra note 1; U.S. Drug Enforcement Administration, supra note 14. Coca leaves typically are chewed but can be rolled into cigarettes or cigars and smoked or infused in liquid and consumed like tea. Id.
b. Coca Paste
Coca paste is a chunky, off-white to light-brown, putty-like substance that exists primarily as an intermediate product in the processing of coca leaves into powder cocaine. Coca paste is derived from coca leaves by mixing the leaves with an alkaline material (e.g., sodium bicarbonate), an organic solvent (e.g., kerosene), and water. The mixture is agitated and the cocaine alkaloid and the organic solvent naturally separate from the water and the leaves. The water and the leaves are removed from the mixture and discarded. Using an acid, the cocaine alkaloid and the kerosene are separated and the kerosene is drawn off the mixture. Additional sodium bicarbonate is added and a solid substance separates from the solution. This solid substance, the coca paste, is removed and allowed to dry. U.S. Department of Justice, Drug Enforcement Administration, Cocaine: Cultivation and Cocaine Processing: An Overview (1991).
Chemically, coca paste is a base form of cocaine (similar to freebase cocaine and crack cocaine) and typically contains residual toxins from the conversion process. Because coca paste is a base, it is hydrophobic - not readily absorbed into water - and, thus, cannot be injected, insufflated, or ingested. While most coca paste is converted into powder cocaine, the paste itself is smoked in South American countries that produce cocaine. R. Jones, "The Pharmacology of Cocaine Smoking in Humans," 99 National Institute on Drug Abuse Research Monograph Series 30-41 (1990). During the early 1980s, several cities in the United States also experienced sporadic episodes of coca paste smoking. U.S. Department of Justice, Drug Enforcement Administration, Crack Cocaine: An Overview. (1989). However, coca paste is typically not imported into the United States. Id.
c. Powder Cocaine
Powder cocaine is a white, powdery substance produced by reacting coca paste with hydrochloric acid. It is the most commonly used form of cocaine. As illustrated in Figure 1, cocaine powder is derived by dissolving the coca paste in hydrochloric acid and water. To this mixture a potassium salt (potassium permanganate) is added. The potassium salt causes undesired substances to separate from the mixture. These substances are then discarded. Ammonia is added to the remaining solution, and a solid substance - the powder cocaine - separates from the solution. The powder cocaine is removed and allowed to dry. U.S. Department of Justice, Drug Enforcement Administration, supra note 18. Prior to distribution, powder cocaine typically is "cut," or diluted, by adding a variety of one or more adulterants: sugars, local anesthetics (e.g., benzocaine), other drugs, or other inert substances. U.S. Department of Justice, Drug Enforcement Administration, Illegal Drug Price and Purity Report (1992). Consequently, the purity level of powder cocaine may vary considerably.
While the active ingredient in powder cocaine - the cocaine alkaloid - does not differ from the active ingredient in coca paste or other forms of cocaine, the salt substrate causes the drug to be hydrophilic - readily dissolved, or absorbed, into water - and, thus, easily injected, insufflated, or ingested. However, unlike base forms of cocaine (such as freebase and crack cocaine), powder cocaine cannot be inhaled (smoked). M. Perez-Reyes, S. Di Guiseppi, G. Ondrusek, A.R. Jeffcoat, and C.E. Cook, "Free-base Cocaine Smoking," 32 Clinical Pharmacology and Therapeutics 459-465 (1982); P. Wilkinson, C. Van Dyck, P.I. Jatlow, P. Barash, R. Byck, "Intranasal and Oral Cocaine Kinetics," 27 Clinical Pharmacology and Therapeutics 386-394 (1980).
Technically, cocaine is not smoked. The concept of smoking implies that the substance is burned and the smoke from the burning substance is inhaled. "Smoked" cocaine, however, is actually vaporized, much like water is vaporized when it boils, and the cocaine-laden vapor is inhaled into the lungs. For the purposes of this discussion, the terms "vaporized" and "smoked" will be used interchangeably to mean inhalation into the lungs. The cocaine alkaloid molecule, when in the powder cocaine form, begins to decompose at a temperature close to which the drug vaporizes (198C, 388F). S. Budavari, M. O'Neil, A. Smith, and P. Heckelman (Eds.) The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (1989); D.R. Wesson and P. Washburn, "Current Patterns of Drug Abuse that Involve Smoking," 99 National Institute on Drug Abuse Research Monograph Series 5-11 (1990).
Once the cocaine alkaloid decomposes, it is inactive pharmacologically and no longer produces any physiological or psychotropic effects. C. Cook and A. Jeffcoat, "Pyrolytic Degradation of Heroin, Phencyclidine and Cocaine: Identification of Products and Some Observations on their Metabolism," 99 National Institute on Drug Abuse Research Monograph Series 97-120 (1990).
d. Cocaine Base
Cocaine base is produced from powder cocaine. In this form, the cocaine alkaloid has been "freed" from the salt substrate and is once again in a base form similar to that of coca paste. Cocaine base vaporizes at a significantly lower temperature (98C, 208F) than powder cocaine (198C, 388F). This lower vaporization point results in less of the drug being decomposed when heated. Budavari, et al., supra note 25; Wesson and Washburn, supra note 25. However, as a base, the drug is not water-soluble. Therefore, if injected, nasally insufflated, or ingested, it will not be absorbed readily into the body. Powder cocaine can be converted into two forms of cocaine base, freebase cocaine or crack cocaine.
i. Freebase Cocaine
Freebase cocaine is derived from powder cocaine that has been dissolved in water and a strong alkaloid solution, typically ammonia. Ether or another organic solvent is added, and a solid substance separates from the solution. This solid substance is the cocaine base. U.S. Department of Justice, Drug Enforcement Administration, supra note 18. Prior to adoption of the federal drug paraphernalia laws in 1986, kits containing the necessary materials and ingredients (except for the cocaine) to "freebase" could be purchased in drug paraphernalia shops. Id.; 21 U.S.C. 863.
The use of freebase cocaine was documented first in the mid-1970s. Because freebase cocaine is significantly purer than coca paste or powder cocaine, many users believed that it was a healthier form of the drug. Even though an estimated ten to 20 percent of the cocaine-abusing population was using freebase cocaine during the 1970s, many resisted the freebasing process because of its complexity and potential danger. Ether, a highly volatile and flammable solvent, will ignite or explode if the freebase cocaine is smoked before the ether has evaporated entirely. This danger received extensive media coverage in 1980 when comedian Richard Pryor suffered third-degree burns over his torso and face while freebasing cocaine. T. Morganthau, "Crack and Crime," Newsweek, June 16, 1986, at 16-22.
ii. Crack Cocaine
Crack cocaine, another form of cocaine base, also is derived from powder cocaine. Unlike the processing of freebase cocaine, converting powder cocaine into crack cocaine does not involve any flammable solvents. The powder cocaine is simply dissolved in a solution of sodium bicarbonate and water. The solution is boiled and a solid substance separates from the boiling mixture. This solid substance, crack cocaine, is removed and allowed to dry. U.S. Department of Justice, Drug Enforcement Administration, supra note 18. The crack cocaine is broken or cut into "rocks," each typically weighing from one-tenth to one-half a gram. One gram of pure powder cocaine will convert to approximately 0.89 grams of crack cocaine. The Drug Enforcement Administration estimates that crack rocks are between 75 and 90 percent pure cocaine. U.S. Department of Justice, Drug Enforcement Administration, supra note 23. See also, Budavari, et al., supra, note 25 at 2451. Although crack cocaine theoretically should be as pure as freebase cocaine, in practice it is less pure because crack cocaine processors tend to be less careful when making crack cocaine. In addition, crack cocaine processors often cut the end product with adulterants to increase the weight and bulk of the crack rocks (See also, Chapter 4).
2. Administration of Cocaine
While cocaine in any form - paste, powder, freebase, or crack - produces the same type of physiological and psychotropic effects, the onset, intensity, and duration of its effects are related directly to the method of use. The form of cocaine generally defines the routes by which it can be administered. Powder cocaine can be injected, insufflated, or ingested; cocaine base, however, can only be smoked. R. Foltin and M. Fischman, "Smoked and Intravenous Cocaine in Humans: Acute Tolerance, Cardiovascular and Subjective Effects," 257 Journal of Pharmacology and Experimental Therapeutics 247-261 (1991); R. Jones, "The Pharmacology of Cocaine," 50 National Institute on Drug Abuse Research Monograph Series 34-53 (1984); J. Javaid, M. Fischman, C. Schuster, H. Dekirmejian, and J. Davis, "Cocaine Plasma Concentrations: Relation to Physiological and Subjective Effects in Humans," 202 Science 227-229 (1978). This section describes the principles underlying drug absorption by and distribution within the body. It compares the four primary routes of cocaine administration - ingestion, nasal insufflation (snorting), injection, and inhalation (smoking) - and the impact of each route on drug absorption and distribution.
a. Absorption and Distribution Within the Body
The route of administration directly affects the rate at which the drug will be absorbed into the bloodstream and transported to the central nervous system and brain where it produces physiological and psychotropic effects. Absorption of a drug into the bloodstream is regulated by two primary factors: the amount of blood flowing to the site of ultimate consumption (e.g., the stomach or small intestine); and the surface area over which the drug is absorbed. Following nasal insufflation (snorting), for example, the surface area is limited to the nasal mucosa in the nasal cavity. In contrast, following cocaine inhalation (smoking), the drug is absorbed by the air sacs of the lungs which have a surface area the size of a football field.
The impact of a drug is additionally governed by the proportion of the drug distributed to various parts of the body. Of ultimate importance is the proportion of the drug reaching the central nervous system, particularly the brain - the primary site of action for drugs of abuse. For example, when a drug is injected intravenously, 100 percent of the drug is distributed to the body. Other routes of administration result in smaller proportions of the administered dose being available for distribution to the central nervous system. This phenomenon is attributable both to the smaller fraction of the drug being absorbed into the bloodstream and to natural safeguards in the body (e.g., metabolism) that cleanse the blood of toxic substances. Figure 2 depicts the pathway of a drug from administration to the central nervous system and brain.
b. Onset of Physiological and Psychotropic Effects
The faster a drug reaches the bloodstream, the faster it is distributed throughout the body and the faster the user feels the desired physiological and psychotropic effects. Id.; Wesson and Washburn, supra note 25. The level of effect and the length of time until maximum effect differ according to the method of administration. Foltin and Fischman, supra note 33. Figures 3 and 4 summarize these differences. Figure 3 depicts, by method of consumption, the average change in physiological and psychotropic responses after cocaine is administered. Figure 4 depicts the average time interval required to reach maximum physiological and psychotropic response after cocaine is administered. The figures show that, upon administration of the drug, the average level of effect and the time until onset of the physiological and psychotropic responses differ significantly based on route of administration. The figures indicate that the psychological effect of the drug - the perceived intoxication - is very strongly associated with the route of administration. Intoxication begins soon after drug use and is perceived as more intense when use is through injection or smoking.
The psychotropic feelings, described as "stimulated" or "high," are correlated to the rate of increased concentration of cocaine in the blood, particularly blood flowing to the brain. The faster
cocaine reaches the brain, the greater the intensity of the psychotropic effects. N. Benowitz, "Clinical Pharmacology of Inhaled Drugs of Abuse: Implications in Understanding Nicotine Dependence," 99 National Institute on Drug Abuse Research Monograph Series 12 (1990); M. Benuck, A. Lajtha, and M. Reith, "Pharmacokinetics of Systemically Administered Cocaine and Locomotor Stimulation in Mice," 257 Journal of Pharmacology and Experimental Therapeutics 307 (1991); J. Boni, W. Barr, and B. Martin, "Cocaine Inhalation in the Rat: Pharmacokinetics and Cardiovascular Response," 257 Journal of Pharmacology and Experimental Therapeutics 307 (1991); Van Dyke, et al., supra note 2. However, these intense psychotropic responses also dissipate more quickly. Consequently, routes of cocaine administration with the more immediate and intense psychotropic responses (specifically, injection of powder cocaine or smoking cocaine vapors) maintain the intensity for shorter periods of time than slower routes of administration. J. Ambre, S. Belknap, J. Nelson, T. Rho, S. Shin, and A. Atkinson, "Acute Tolerance to Cocaine in Humans," 44 Clinical Pharmacology and Therapeutics 1 (1988).
c. Routes of Administration
Users who ingest cocaine typically chew the coca leaves in their mouths much like chewing tobacco. Coca leaves typically are mixed with an alkaline substance (such as lime) and chewed into a wad that is retained in the mouth between gum and cheek and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastro-intestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. Murray, supra note 1. Ingesting coca leaves generally is an inefficient means of administering cocaine. Because cocaine is hydrolyzed (rendered inactive) in the acidic stomach, it is not readily absorbed. Only when mixed with a highly alkaline substance (such as lime) can it be absorbed into the bloodstream through the stomach. Wilkinson et al., supra note 24; Van Dyke et al., supra note 2. Absorption of orally administered cocaine is limited by two additional factors. First, the drug is partly metabolized in the liver. Second, capillaries in the mouth and esophagus constrict after contact with the drug, reducing the surface area over which the drug can be absorbed. Id.
Orally administered cocaine takes approximately 30 minutes to enter the bloodstream. Typically, only 30 percent of an oral dose is absorbed, although absorption has been shown to reach 60 percent in controlled settings. Id.; Jones, supra note 33. Given the slow rate of absorption, maximum physiological and psychotropic effects are attained approximately 60 minutes after cocaine is administered by ingestion. While the onset of these effects is slow, the effects are sustained for approximately 60 minutes after their peak is attained. Id.
ii. Nasal Insufflation (Snorting)
Users who insufflate cocaine "snort" the drug into their nasal passages. The powder cocaine typically is apportioned into "lines," each representing between ten and 35 mg. of cocaine. The powder is drawn into each nostril through a thin straw and absorbed into the bloodstream through the capillaries of the mucous membranes of the nasal cavity. J. Javaid, M. Musa, M. Fischman, C. Schuster, and J. Davis, "Kinetics of Cocaine in Humans after Intravenous and Intranasal Administration," 4 Biopharmacuetics and Drug Disposition 9-18 (1983); A. Jeffcoat, M. Perez-Reyes, J. Hill, B. Sadler, and C. Cook, "Cocaine Disposition in Humans after Intravenous Injection, Nasal Insufflation, or Smoking," 17 Drug Metabolism and Disposition 153-159 (1989). Like ingestion, nasal insufflation is not the most efficient route of cocaine administration. Cocaine constricts the capillaries in the nasal membranes, thus reducing the surface area and making absorption slow and incomplete. Absorption following snorting cocaine is dose-dependent, with larger doses more completely absorbed than smaller doses. Id. One study found that only 28 percent of a 64 mg. intranasal dose of cocaine was absorbed compared to almost 69 percent of a 96 mg. dose. Id.
Cocaine snorted through the nasal passages appears in the blood three to five minutes after administration, significantly faster than the 30 minutes required for it to reach the bloodstream through ingestion. Id. However, both ingestion and insufflation result in approximately the same proportion of the drug being absorbed: 30 to 60 percent. G. Barnett, R. Hawks and R. Resnick, "Cocaine Pharmacokinetics in Humans," 3 Journal of Ethnopharmacology 353 (1981); Jones, supra note 19; Wilkinson et al., supra note 24; Van Dyke et al., supra note 2. Compared to ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes. Jones, supra note 19. Similar to ingestion of cocaine, physiological and psychotropic effects
from nasally insufflated cocaine are sustained for approximately 60 minutes after the peak effects are attained. Van Dyke, et al., supra note 2.
Cocaine injectors dissolve powder cocaine in water and inject the mixture into a vein, typically in the arm, using a hypodermic syringe. While injection is an effective method of delivering a drug dose, it is potentially problematic. Because the drug is injected directly into the bloodstream, natural safeguards (e.g., metabolism) are bypassed. Given the unknown purity of street doses, intravenous drug users are less able to monitor and correct dosages, and therefore are subject to unexpected drug reactions or overdoses. R. Julien, A Primer of Drug Action (1988). Further, safe intravenous administration requires sterile conditions - conditions typically not associated with illicit drug use. Consequently, illicit drug users who inject drugs are generally at a greater risk of health problems than illicit drug users who use drugs in other fashions. Id. (See Chapter Three, Cocaine Use and Public Health Issues, for a detailed discussion of the health problems associated with intravenous drug use.)
Intravenously administered cocaine is absorbed completely into the bloodstream, requiring only one minute to reach the brain. Benowitz, supra note 36. The time interval to attainment of maximum physiological and psychotropic effects is much shorter than the interval following either ingestion or intranasal administration. Maximum physiological effects occur in ten minutes; maximum psychotropic effects in four minutes. These effects are sustained for approximately 30 minutes. Jones, supra note 19.
iv. Inhalation (Smoking)
Cocaine base (including coca paste, freebase cocaine, and crack cocaine) typically is smoked in pipes constructed of glass bowls fitted with one or more fine mesh screens that support the drug. The user heats the side of the bowl (usually with a lighter), and the heat causes the cocaine base to vaporize. The user inhales the cocaine-laden fumes through the pipe. Alternatively, crack cocaine can be sprinkled in cigarettes and smoked. U.S. Department of Justice, Drug Enforcement Administration, supra note 20.
Smoking cocaine combines the efficiency of intravenous administration with the relative ease of consumption of ingestion and insufflation. Wesson and Washburn, supra note 25; R. Foltin and M. Fischman, "Self-Administration of Cocaine in Humans: Choices Between Smoking and Intravenous Cocaine," 261 Journal of Pharmacology and Experimental Therapeutics 841-849 (1992). Facilitated by the large surface area of the lungs' air sacs, cocaine administered by inhalation is absorbed almost immediately into the bloodstream, taking only 19 seconds to reach the brain. Benowitz, supra note 36. However, only 30 to 60 percent of the available dose is absorbed due to incomplete inhalation of the cocaine-laden fumes and variations in the heating temperature. Boni et al., supra note 36; Foltin and Fischman, supra note 33; Jeffcoat et al., supra note 43; D. Paly, P. Jatlow, C. Van Dyke, F. Jeri, and R. Byck, "Plasma Cocaine Concentrations during Coca Paste Smoking," 30 Life Sciences 731-738 (1982). Cocaine smokers achieve maximum physiological effects approximately two minutes after inhalation. Id. Maximum psychotropic effects are attained approximately one minute after inhalation. Benowitz, supra note 36. Similar to intravenous administration, the physiological and psychotropic effects of inhaled cocaine are sustained for approximately 30 minutes after the peak effects are attained. Boni et al., supra note 36; Foltin and Fischman, supra note 33; Jeffcoat, et al., supra note 43; Paly et al., supra note 57; Perez-Reyes, et al., supra note 24.
D. EFFECTS OF COCAINE
Cocaine is the most potent central nervous system stimulant of natural origin. U.S. Department of Justice, Drug Enforcement Administration, supra note 14. While different forms of cocaine do not result in different types of physiological or psychotropic effects, the route of administration does impact, as discussed above, the immediacy, intensity, and duration of cocaine's effects. The sections below discuss cocaine's physiological and psychotropic effects.
1. Physiological Effects of Cocaine
Cocaine, like other central nervous system stimulants such as amphetamine, caffeine, and nicotine, produces alertness and heightens energy. F. Gawin and E. Ellinwood, "Cocaine and Other Stimulants: Actions, Abuse and Treatment," 318 New England Journal of Medicine 1173 (1988). Cocaine acts on the central nervous system by inhibiting the re-uptake of the neurotransmitter norepinephrine. The augmentation of norepinephrine results in increased motor activity, with slight tremors and convulsions in the user's extremities. Jatlow, supra note 4; Julien, supra note 50; Jones, supra note 33; U. Raczkowski, Y. Herandez, H. Erzouki, and T. Abrahams, "Cocaine Acts in the Central Nervous System to Inhibit Sympathetic Neural Activity," 258 Journal of Pharmacology and Experimental Therapeutics 511 (1991). In the cardiovascular system, the augmentation of norepinephrine results in increased heart rate, elevated blood pressure, and other symptoms similar to hypertension. Id. The rate of increase in these physiological responses varies by route of cocaine administration, with the most efficient absorption routes (inhalation and injection) producing the most rapid increases. Id.
Cocaine's vasoconstrictive properties reduce the size of the blood vessels, causing the air sacs in the lungs to dilate and the capillaries in the nasal passages to constrict. Id. Because cocaine permits less body heat to be lost, cocaine users generally experience an increase in body temperature. In cases involving cocaine overdoses, body temperatures as high as 114F have been reported. Id.
2. Psychotropic Effects of Cocaine
Cocaine also inhibits the re-uptake of dopamine, a neurotransmitter that controls the pleasure centers in the central nervous system, causing a sense of euphoria, decreased anxiety and social inhibitions, and heightened sexuality. R.A. Wise, "Neural Mechanisms of the Reinforcing Action of Cocaine," 50 National Institute on Drug Abuse Research Monograph Series 15-33 (1984).
Increased dosages of cocaine and use of the most rapid drug administration routes produce euphoric experiences that create vivid, long-term psychological memories that form the basis for subsequent craving of the drug. Gawin and Ellinwood, supra note 62. Psychoses and hallucinations have been reported with increased doses of cocaine, including foraging and "skin picking" (a slang term for a condition in which addicts mistakenly believe that bugs are crawling on their skin). In addition to producing euphoria and psychoses, cocaine use causes the user to crave other drugs, including alcohol. Polydrug use is particularly significant because concurrent use of cocaine and other drugs is associated with increased toxicity. Id. (See Chapter Three, Cocaine Use and Public Health Issues, for a discussion of the toxicity associated with cocaine and polydrug use.)
3. Drug Dependence
Drug dependence can be both physiological and psychological. Psychoactive substance dependence has been described as a cluster of cognitive, behavioral, and physiologic symptoms that indicate that the person has impaired control of psychoactive substance use and continued use of the substance despite adverse consequences . . . [including but] not limited to the physiologic symptoms of withdrawal and tolerance. . . [Withdrawal symptoms] vary greatly across classes of substances. Marked and generally easily measured physiologic signs of withdrawal are common with alcohol, opiates, sedatives, hypnotics, and anxiolytics. Such signs are less obvious with amphetamines, cocaine, nicotine, and cannabis, but intense subjective symptoms can occur upon withdrawal from heavy use of these substances. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders: DSM-III-R (1987).
The nature and severity of dependence has been shown to be primarily influenced by the individual's drug tolerance and the immediacy and duration of the drug's effect.
a. Physiological Dependence
Unlike some drugs, cocaine is not physiologically addicting. K. Blum, Handbook of Abusable Drugs (1984); L. Keltner and D. Folks Psychotropic Drugs. (1993). Physiological dependence occurs when prolonged use of the drug causes systemic changes in the central nervous system (e.g., lower pulse rate, decreased body temperature, or depressed respiration). When drug use is withdrawn, the body responds with an effect that is opposite the drug's action in an effort to maintain the new equilibrium established through use of the drug. For example, if the drug causes the body temperature to decrease by three degrees, the person's body temperature will increase by three degrees when the drug is withdrawn. Physical changes resulting from cessation of prolonged drug use (such as significant increases in body temperature) cause the user discomfort, including physical events such as nausea, convulsions, or seizures or psychological effects such as hallucinations or paranoia. Withdrawal symptoms can be stopped or mitigated by re-administering the drug. Over time, the homeostatic response to the dependence restores equilibrium in the body's varied systems. Examples of drugs that cause physiological dependence include:
opiates (e.g., heroin, morphine, codeine, and methadone),
barbiturates (e.g., phenobarbital, secobarbital),
anxiolytics (e.g., diazepam, meprobromate),
nicotine (e.g., tobacco products),
caffeine (e.g., coffee and tea), and
For drugs that cause physiological dependence, the nature of withdrawal symptoms varies with the type of drug. For example, opiate withdrawal is characterized by restlessness, sweating, extreme anxiety, fever, chills, and extreme diarrhea; alcohol withdrawal is characterized by hyperexcitability, hallucinations, psychomotor agitation, confusion, and delirium tremens - a syndrome characterized by a variety of discomforts. Julien, supra note 50.
While cocaine is not physiologically addicting, users may experience anxiety and depression when cocaine is not available for use. These sensations, while possibly affecting physical systems in the body, have not been demonstrated to be related to bodily function; rather, these sensations have been classified as psychological manifestations resulting from psychological dependence. F.H. Gawin, "Cocaine Abuse and Addiction," 29 Journal of Family Practice 193-197 (1989).
b. Psychological Dependence
Psychological dependence is a compulsion for repeated use of a drug for its euphoric effects despite any adverse effects that may occur. Julien, supra note 50; American Psychiatric Association, supra note 71. Cocaine exhibits powerful reinforcing properties that cause users compulsively to misuse the drug resulting in psychological addiction. Murray, supra note 1; J. Spotts and F. Shortz, "Drug-Induced Ego States: I. Cocaine Phenomenology and Implications," 19 International Journal of the Addictions 119 (1984). The psychological craving for cocaine is the most important contributor to its abuse potential. Gawin, supra note 75.
Cocaine users discover that higher doses intensify the euphoria. Therefore, unless the user has imposed a limit on the quantity of drug used during a fixed period, or an external limit on supply exists, some users will gradually increase the frequency of use and quantity of the dose. The pursuit of euphoria becomes so great that users may often ignore all signs of physical and psychological risk, either to the individual or to others. With continued use, elation and self-confidence associated with the euphoria diminish, and depression and irritability set in. Often, in an attempt to ward off depression and/or the "crash" from the high, cocaine users further intensify their pattern of use, resulting in cocaine binges lasting for several hours or even days. Gawin and Ellinwood, supra note 62.
The psychological components of dependence are the same across all categories of psychoactive drugs. American Psychiatric Association, supra note 71. For example, persons dependent on psychoactive drugs may exhibit a compulsion to use a drug over a longer period than originally intended. The criteria described in Table 1 were established by the American Psychiatric Association to diagnose drug dependency and the severity of the dependence. These criteria paint a picture of an individual whose drug-using behavior is out of control: the individual uses larger amounts of the drug while enjoying the drug experience less. Because the user is unable to reduce or discontinue use and behavior associated with procuring, preparing, or being intoxicated, drug use consumes increasing amounts of the individual's life. Once the individual seeks treatment for dependence, the distinction between physiological and psychological dependence becomes irrelevant: physiological dependence becomes merely one factor in the diagnosis of psychoactive substance dependence. Id.
c. Mechanisms of Dependence
The level and severity of cocaine dependence is affected by two factors: route of administration and drug tolerance.
i. Route of Administration
As stated earlier, cocaine, regardless of how it is administered (injection, inhalation, nasal insufflation, or ingestion), produces the same type of psychotropic effects but with different levels of immediacy, intensity, and duration. Because of its relationship with immediacy, intensity, and duration, the route of administration plays an important role in determining the likelihood that use will lead to dependence and abuse. Foltin and Fischman, supra note 33; Foltin and Fischman, supra note 55; Perez-Reyes, et al., supra note 24. First, the intensity of the psychotropic effects is greater for those methods of administration that deliver the drug most rapidly to the brain. Consequently, routes of administration that result in the most rapid increases in blood concentration will provide the maximum levels of psychotropic effects. Foltin and Fischman, supra note 33; Gawin and Ellinwood, supra note 62; Javaid. et al., supra note 33; Jeffcoat, et al., supra note 43; Wesson and Washburn, supra note 25.
Second, the duration of the effect is inversely related to its intensity: methods of administration that bring about the most intense effects also will have the shortest durations. Ambre, et al., supra note 37. Consequently, routes of cocaine administration that result in more rapid increases in the blood's drug concentration - such as injection and inhalation - are more likely to lead to drug dependence. For the injection and inhalation administration methods, cocaine's effects are quick in onset, short-acting, and carry a greater likelihood that the user will administer the drug more frequently (e.g., daily or more often). Inhalation also carries a greater likelihood that users will administer the drug in binges. For the insufflation or ingestion administration methods, the cocaine effects are slow in onset, longer acting, and less likely to involve administering the drug frequently (e.g., daily or more often) or in binging episodes.
ii. Drug Tolerance
Drug tolerance is the process by which the effectiveness of a drug diminishes over time such that increasing doses are necessary to achieve effects comparable to prior doses. Acute tolerance is defined as a change in responsiveness to a drug's effects in the short-term, even within the course of a single dose. Id. Cocaine's physiological and psychotropic effects dissipate quickly, but the drug continues to be present in the bloodstream after the effects are no longer being experienced. Therefore, acute tolerance to the physiological and psychotropic effects of cocaine develops rapidly. M. Chow, J. Ambre, T. Atkinson, D. Banshen, and M. Fischman, "Kinetics of Cocaine Distribution, Elimination, and Chronotropic Effects," 38 Clinical Pharmacology and Therapeutics 318-324 (1985). When tolerance occurs, users need increasing amounts of the drug to achieve comparable levels of physical and psychological euphoria. Consistent with the development of drug tolerance, experienced users are often able to administer doses that would otherwise be fatal to a first-time user. M. Fischman, "The Behavioral Pharmacology of Cocaine in Humans," 50 National Institute on Drug Abuse Research Monograph Series 71-91 (1984).
Table 2 summarizes the discussion in this chapter, comparing the various characteristics of powder cocaine and cocaine base.
United States Sentencing Commission