Medical Effects 

Acute effects  

The general acute effects of stimulants have been well documented. Among a range of physiological responses, stimulants are known to raise both systolic and diastolic blood pressure, increase heart rate, increase respiration rate, increase body temperature, cause pupillary dilation, heighten alertness, and increase motor activity (CSAT, 1997). 

Acute effects from excessive doses include dangerously rapid and erratic heartbeat, cerebral hemorrhaging, seizures/convulsions, respiratory failure, stroke, heart failure, brain damage, coma, and death (CSAT, 1997).  Stimulants are also known to cause sensitization (i.e., the opposite of tolerance), for which multiple drug exposures eventually produce some new adverse reaction.

For example, in animals, seizures do not typically occur after single low-to-moderate doses. But with repeated exposure, an animal can become sensitized to the stimulant and may have a seizure after a single, previously harmless, dose. 

Chronic effects  

Although the effects of chronic stimulant abuse in humans has not been well documented, some of the chronic effects include organ toxicity, compromised health (e.g., underfed, malnourished, poor hygiene), dental problems, and dermatitis. (For a complete discussion of the medical aspects of stimulant use, see Chapter 5.) 

Psychological Effects  

The immediate psychological effects of stimulant administration include a heightened sense of well-being, euphoria, excitement, heightened alertness, and increases in motor activity. Stimulants also reduce food intake, reduce sleep time, and may increase socialization activities. Stimulants may also enhance performance of certain types of psychomotor tasks. 

High doses may result in restlessness and agitation, and excessive doses may produce stereotypic behaviors (repetitive and automatic acts). Chronic psychological effects of stimulant use include various psychiatric disorders such as psychosis, paranoia, and suicidal tendencies. 

There may also be neurological impairments and cognitive deficits. Tolerance eventually develops to many of the behavioral effects of stimulants, so that increasing doses are required to achieve the same effect.  The administration of stimulants--particularly if smoked or injected intravenously--can have immediate and often very intense effects on the user.

However, the "rush" and subsequent feelings of euphoria may just as quickly fade. The intense effects can be followed by a dysphoric "crash." To stave the crash, the user will administer another dose of the stimulant, which again produces a rush and subsequent crash.  This cycle will go on again and again.

This pattern of frequently repeated dosing known as bingeing may continue for up to 3 sleepless days. During this period, the user may not eat and may lapse into a severe depression, followed by worsening paranoia, belligerence, and aggression--a period known as tweaking. 

Bingeing eventually ends when the user depletes his supply of stimulants or simply collapses from sheer exhaustion. The stimulant user may then sleep for several days, only to awaken and begin the cycle again. 

There is a great amount of anecdotal evidence on the relationship of stimulant use and various sexual behaviors. Stimulants may be used during sexual activities to intensify sexual acts, heighten pleasure, lengthen the duration of intercourse, and lessen inhibitions.

The abuse of stimulants is also known to lead to uncharacteristically aberrant or deviant sexual behaviors, the use of prostitutes, and HIV high-risk behaviors (Rawson et al., 1998b). 

Effects of Route of Administration  

Cocaine and MA can be smoked, snorted, injected, or ingested orally. These various routes of administration differ in dosage and in the rapidity and intensity of effect, which may affect the course of abuse and dependence. Some evidence
 suggests that the onset of dependence varies according to the route of administration (DEA, 1995). The route of administration affects the amount (i.e., the dosage) of stimulant delivered to the brain, the speed at which it is delivered, and the resulting intensity of the stimulant's effects. 

The intensity of the psychological effects of stimulants, as with most psychoactive drugs, depends on the dose and rate of entry to the brain. For example, when snorted, stimulants generally reach the brain within 3 to 5 minutes, and the resulting rush or "high" may not be perceived as immediate; intravenous administration produces a rush in about 15 to 30 seconds; whereas smoking produces an almost immediate effect (ONDCP, 1998a). 

Because of the rapidity of delivery and higher dosages, the smoking of stimulants produces a high that is said to be far more intense than those produced through other routes of administration.  Route of administration has been shown to affect the resulting level of stimulant in the body. In a comparison of oral ingestion versus smoking, Cook measured plasma levels of MA after oral administration and after smoking (see Figure 2-5)(Cook, 1991).

For the oral dose of 0.25 mg/kg, plasma levels began to rise 30 minutes after ingestion and reached peak levels (approximately 38 ng/mL) at about 3 hours after ingestion. Plateau levels were maintained until about hour 4 and then
 slowly declined over the next 4 hours. After smoking (dose of about 21 mg/subject), MA plasma levels approximated 80 percent of peak levels within minutes, peaked (approximately 42 ng/mL) at about 2 hours after administration, maintained a peak plateau for another 2 hours, and then slowly declined over the next 4 hours.

By comparison, plasma levels of smoked cocaine and smoked MA both peaked rapidly (Cook, 1991). Plasma levels of smoked cocaine (dose of 21 to 22 mg/subject) peaked at approximately 240 ng/mL at about 5 to 10 minutes after administration. Cocaine plasma levels then declined rapidly, dropping to 50 percent of maximum level (half-life) within 1 hour. Smoked MA (dose of 21 to 22 mg/subject) neared peak levels (approximately 50 ng/mL) within minutes and continued to climb until about 2 hours after administration before slowly tapering off.

However, half-life levels were not reached until 11 to 12 hours after administration (see Figure 2-6). The long plateau effect and the much longer half-life of MA versus cocaine suggests considerable dangers in repeated smoking of MA because remarkably higher plasma concentrations could be expected to occur if the dose is repeated, even at fairly long intervals (Cook, 1991).

Because stimulants exert their effects in a dose-dependent manner, the route of administration has serious neurological, medical, psychiatric, and neurocognitive implications for the stimulant user and the treatment provider. The intense highs produced by smoking crack cocaine or ice MA can lead to equally intense "lows" during withdrawal (e.g., dysphoria, depression, irritability, anxiety, paranoia, dramatic mood swings).

The subsequent cravings can also be extremely intense. Prolonged high doses of stimulants (e.g., during bingeing) may cause greater and longer lasting neurological damage, which in turn may lead to greater and longer lasting cognitive deficits. The onset of stimulants' chronic effects varies across individuals, and although there are few data to predict how long it will take for any user to begin suffering from the chronic effects of stimulant abuse and dependence, onset is probably related to the size of the doses, the frequency of dosing, and the route of administration.

However, in general, the higher the doses and the more frequently the doses are administered, the more quickly the chronic effects will appear. From a treatment provider's perspective, a stimulant user's preferred route of administration affects the extent and depth of chronic effects and, therefore, has implications for choosing the most appropriate treatment approach. (See Chapter 4 for a full discussion on the practical applications of treatment strategies.

For a discussion on route-of-administration effects on toxicity and adverse reactions, see Chapter 5.) 

Cocaine Acute Effects  

Cocaine has two main pharmacological actions. It is both a local anesthetic and a central nervous system (CNS) stimulant--the only drug known to possess both of these properties. Cocaine exerts its local anesthetic actions by blocking the conduction of sensory impulses within nerve cells. This effect is most pronounced when cocaine is applied to the skin or to mucous membranes. Cocaine hydrochloride has approved medical use as a local anesthetic in surgery of the nose, throat, and larynx. 

As a CNS stimulant, cocaine affects a number of neurotransmitter systems, but it is through its interaction with the dopamine and the limbic reward system that cocaine produces some of its most important effects, including its positive reinforcing effects.

The major influence of cocaine on the dopamine system is its ability to block the synaptic reuptake of dopamine. As shown in Figure 2-7, cocaine does not directly "stimulate" the dopamine system; rather, it causes the system to be stimulated by preventing dopamine from being removed from the intracellular space.

Cocaine blockade of the dopamine reuptake transporter extends the availability of dopamine in the synaptic space where it continues to occupy the dopamine receptor and causes the postsynaptic neurons to fire for a longer than normal period. This extended firing of the postsynaptic neurons resulting from prolonged dopamine receptor activity is initially experienced subjectively by the cocaine user as a positive sensation involving increased energy, arousal, and stimulation.

A recent study has demonstrated a relationship between the intensity of cocaine's subjective effects and the degree to which the dopamine reuptake transporter is blocked (Volkow et al., 1997a). The effects experienced by users of cocaine during the initial period of their use are generally mood-altering in a positive manner (Washton, 1989).

For most individuals, the subjective experience of the acute effects includes a generalized state of euphoria in combination with feelings of increased energy, confidence, mental alertness, and sexual arousal.  Under the proper environmental circumstances, individuals also report that cocaine heightens their ability to concentrate, increases sexual excitement, increases their sociability, and decreases any preexisting shyness, tension, fatigue, depression, or boredom.

Many people feel more talkative, more intensely involved in their interactions with others, and more playful and spontaneous when high on cocaine. As they come down from their cocaine high, some users experience temporary unpleasant reactions and aftereffects, which may include restlessness, anxiety, agitation, irritability, and insomnia.

During this "rebound" period, suspiciousness, confusion, hyperarousal, and other elements of paranoid thinking may also appear.  With continued escalating use of cocaine, the user becomes progressively tolerant to the positive effects while the negative effects steadily intensify (Washton, 1989). Users report that the highs are not so high anymore and the rebound aftereffects increasingly lead to a dysphoric, depressed state.

These new "lows" may reinitiate the desire for more cocaine in a futile attempt at mood normalization. The search for the previously experienced high will eventually leave the user in the depths of depression and despair.  When snorted, smoked, or injected intravenously, cocaine quickly produces an intense high. But because it is rapidly metabolized in the body, this high is short-lived.

Efforts to replicate the initial high prompt users to take it often and repeatedly. Because of its mechanism of action, cocaine may produce strong craving and strong conditioning of cues associated with its use. The results of a recent brain imaging study revealed that cocaine's fast uptake in the brain has a major role in its rewarding effects and that its fast clearance from the brain sets the stage for frequent abuse, craving, and the binge pattern in cocaine addiction (Volkow et al., 1996).

These researchers postulated that dopaminergic activation of the limbic reward system is involved in the rewarding effects of cocaine (and perhaps most, if not all, substances of abuse) and that continued activation of this system may lead to long-term changes in the associated neural circuits that perpetuate the compulsive administration of this drug (see below). 

Cocaine use also has acute adverse physiological effects involving the respiratory, cardiovascular, and central nervous systems. Systemic toxicity to cocaine is characterized by profound sympathetic stimulation of the respiratory,
 cardiovascular, and central nervous systems, producing a combination of medical and psychological effects sometimes known as the "cocaine reaction." (For additional details on the medical aspects of cocaine abuse, see Chapter 5.) 

Chronic Effects  

For many cocaine users, the initial experimental use begins to give way to more frequent or regular use. With continued, intensified use, the "casual" user will progress to the abuse stage, requiring larger and larger doses to achieve the desired effects. The abuser may become obsessed with the rituals of cocaine administration and may find that many common items or situations trigger cravings for the drug.

For some, abuse will lead to full-fledged addiction. There will be overwhelming urges and cravings for cocaine, and there may be an inability to self-limit or control use. The cocaine addict will deny that she has a drug use problem and will continue use of cocaine despite the negative consequences. At this
 stage, the adverse consequences of cocaine addiction have probably affected all aspects of the user's life.

The addict has succumbed to what Dr. Sidney Cohen called cocaine's "pharmacological imperative" (Washton, 1989). Figure 2-8 lists the characteristics of the stages of cocaine addiction.  The timetable for the onset of the chronic effects of cocaine use varies across individuals and may depend on the size of the doses, the frequency of dosing, and the route of administration. There are no data to base a prediction on how long it will take for any individual to begin to suffer from the chronic effects of cocaine use.

However, similar to the effects of MA, the higher the doses and the more frequently the doses are administered, in general, the more quickly the chronic effects of cocaine will appear. In addition, intranasal administration (snorting) is associated with slower onset of chronic effects than if cocaine is smoked (freebase or crack) or injected intravenously.

Clearly, there are tremendous individual differences in this timetable, with some individuals reporting an ability to use for extended periods with few signs of negative consequences and others reporting a very dramatic onset of severe detrimental effects as soon as a few weeks or months after initiation of cocaine use.  Physically, the cocaine addict may appear thin or even emaciated. Personal hygiene and self-care may be neglected, and medical and dental needs may go unmet.

Because cocaine suppresses appetite, the user fails to eat properly and may
 suffer from vitamin deficiencies. Severe addicts may ignore food, clothing, shelter, and sexual needs.  Psychologically, cocaine's chronic effects are exactly the opposite of the desired initial effects. Continued cocaine use increases paranoia and confusion and causes an inability to concentrate and an inability to perform sexually. The same substance that acutely produced a mild sensation of arousal and decreased fatigue, on a chronic basis results in chest pain, insomnia, anorexia, episodic depression, and extreme fatigue. 

From a treatment perspective, the curious thing is that the user often accurately perceives and attributes the pleasurable, acute effects to the use of cocaine.

However, he frequently is unable or unwilling to recognize the relationship of the negative, chronic effects to the use of cocaine. Although it may be dramatically apparent to family and friends that the effects of cocaine are highly detrimental and destructive to the user, the user may insist that the use of cocaine is very helpful and beneficial.

The extensive health-compromising effects of cocaine abuse are apparent when examining the behavioral and psychological profile of clients as they enter substance treatment. Generally, these clients exhibit a pronounced disruption in healthy behaviors and an elevation in dysphoric emotions including anxiety, depression, and paranoia (Castro et al., 1992). 

Chronic abuse of cocaine may cause neuropsychological impairments (O'Malley et al., 1992) as well as neuropsychiatric syndromes (Herning et al., 1997). Cocaine-induced cognitive deficits can last up to 3 months after heavy use before baseline functioning is restored. In their review, Weinrieb and O'Brien found a strong association between the chronic use of cocaine and deficiencies in short-term auditory recall, memory, concentration--especially for nonverbal abstracting and problem solving--and slowed reaction time (Weinrieb and O'Brien, 1993). 

The physical, psychological, and cognitive effects of chronic cocaine use reflect the underlying physiological effects; at the heart of these effects is cocaine's impact on the neurotransmitter dopamine.