Cocaine is a powerfully addictive stimulant drug. For thousands of years, people in South America have chewed and ingested coca leaves (Erythroxylon coca), the source of cocaine, for their stimulant effects.
Today, cocaine is schedule II drug, which means that it has high potential for abuse but can be administered by a doctor for legitimate medical uses, such as local anesthesia for some eye, ear, and throat surgeries. Dealer often dilute (or “cut”) it with non-psychoactive substances such as cornstarch, talcum powder, flour, or baking soda to increase their profits. They may also adulterate cocaine with other drugs like procaine (a chemically related local anesthetic) or amphetamine (another psychoactive stimulant). Some users users combine with heroin.
People abuse two chemical forms of cocaine: the water- soluble hydrochloride salt and the water-insoluble cocaine base (or freebase). Users inject or snort the hydrochloride salt, which is a powder. The base form of cocaine is created y processing by processing the drugs with ammonia or sodium bicarbonate (baking soda) and water, then heating it to remove the hydrochloride to produce a smokable substance.
A century elapsed between the time that Karl Koller announced his discovery that cocaine was an effective local anesthetic agent and the year (1985) when ‘crack’ smokers began appearing at medical clinics in the Bahamas. The intervening year had seen important advances in coca cultivation, in cocaine refining, and even in the routes by which cocaine is self- administered. Each technical advance translate into higher blood cocaine concentrations- either because the route of administration is more efficient or simply because there is so much more cocaine available to administer. Either way, chronic exposure to high cocaine concentrations makes the occurrence of adverse events more likely.
Coca has been used by the Amara Indians of Peru for more than 1000 years, but in this group of drug-takers coca-related heart attacks and strokes were, and still are, uncommon. There is a limit to the number of leaves that even the most determined user can chew. The physical constraints of leaf chewing restrict the amount of cocaine that can be introduced into the bloodstream, and that acts as a safeguard against toxicity. It would take an enormous amount of coca leaf, and a great deal of chewing, to extract enough cocaine from coca leaves to produce a toxic reaction.
For similar reasons, the practice of drinking coca wines, which were first sold in Europe during the late 1860s, was equally benign. The most famous of these was Vin Mariani. Its formula was proprietary, but the French government guidelines for the manufacture of coca- containing wines were public record, and any pharmacist could make them: 60g of ground coca leaves were soaked for ten hours in one liter of red and wine. The only requirement for the wine was that it contained 10- 15% alcohol. Given an average cocaine content of one by fourth to one by two percent for Bolivian leaf (the only kind of leaf available in France at the time), one liter of wine would have contained as little as 1550mg, and certainly no more than 300mg of cocaine. Two glasses of Martini’s wine would have contained less than 500mg cocaine, equivalent to one ‘line’ of snorted cocaine.
Even with today’s sophisticated measuring techniques, the 50mg of cocaine consumed in a glass of coca wine would have been barely enough to cause measurable effects in humans. The low cocaine content of the commercial wines and tonics explains why there were no reports of toxicity in the 1870s, even though the wines of Martini in particular, and his many competitors in general, were wildly popular.
The benign phase of cocaine consumption abruptly came to an end in 1884, when Freud published hid famous paper praising cocaine as a miracle drug. A few months later, Koller discovered that cocaine was local anesthetic. By the end of 1884, les than two after Koller’s paper had been read at the Heidelberg Ophthalmology Congress and less than five months after the publication of Freud’s paper, cocaine production at Merck’s factory in Darmstadt increased dramatically. Merck’s factory in Darmstadt increased dramatically. Merck was at the time Europe’s main cocaine producer, but in 1883 its total output was less than three- quarter of pound (1.65kg). Output increased to 3179 pounds in 1884, and to 158352 pounds in 1886. This increase in production was, of course, driven by increased demand. But it was also facilitated by an important technical advance – the introduction of semi-refined cocaine.
Coca leaves travel poorly, loosing much of their cocaine content in transit. In 1885 a chemist working for Parke Davis, the largest American cocaine producer and Merck’s fiercest competitor (Parke Davis even paid Sigmund Freud to endorse their brand of cocaine over Merck’s) revolutionized the drug industry by devising a way to produce semi- refined cocaine on site. Shipping and storage were simplified, prices fell, and the supply of semi-refined cocaine increased substantially.
When ample supplies of relatively inexpensive cocaine became available, patent drug-makers began adding very large amounts of purified cocaine to their products. Vi Marini may have contained only 6mg cocaine per ounce, but competitors’ products contained hundreds of milligrams per ounce. Not surprisingly, episodes of toxicity, and even deaths, soon became a regular feature of BMJ and The Lancet. Matters were worsened by the advent of commercially manufactured hypodermic syringes at almost the same time.
Cocaine’s addictive potential is at least partly related to blood concentration. Within certain limits, an increase in the amount of cocaine administered increases the amount entering the bloodstream and ultimately the amount finding its way to the brain. the rate of rise in concentration achieved in the brain, which is why smokable ‘crack’ cocaine has had such devastating results. Smoking a given amount of ‘crack’ cocaine results in a much higher blood concentration than snorting the same amount, and the peak level is reached much more quickly.
The explosion in cocaine use that occurred in America during the late 1980s is widely attributed to economic factors; crack was said to be much cheaper than powdered cocaine. There is no evidence to support this notion. Data from US Drug Enforcement Agency suggest that prices for the two dosage forms are essentially the same. A more plausible explanation would take into account the observation that ‘crack’ smoking offers higher brain concentrations more quickly.
Figures released by US Government in 1996 show that the true the price of cocaine has declined by nearly 75% during the past fifteen years; the sum required to buy enough street drug to yield 1g pure cocaine fell from $587 to $137. The explanation is glut of cocaine experts seem blissfully unaware that the coca plant will grow nearly anywhere. South America is at present the main source; but during the 1800s, exports of coca from Java substantially exceeded those coming from South America. If blight eliminated South America coca production tomorrow, new suppliers in South Est Asia could, and would, quickly make up any shortfall.
Users primarily administer cocaine orally, intranasally, intravenously, or by inhalation. When people snort the drug (intranasal use), they inhale cocaine powder through the nostrils, where it is absorbed into the bloodstream through the nasal tissues. Users also may rub the drug onto their gums (oral use). Dissolving cocaine in water and injecting it (intravenous use) releases the drug directly into the bloodstream and heightens the intensity of its effects. When people smoke cocaine (inhalation), they inhale its vapor or smoke into the lungs, where absorption into the bloodstream is almost as rapid as by injection. This fast euphoric effect is one of the reasons that crack became enormously popular in the mid-1980s.
Cocaine use ranges from occasional to repeated or compulsive use, with a variety of patterns between these extremes. Any route of administration can potentially lead to absorption of toxic amounts of cocaine, causing heart attacks, strokes, or seizures—all of which can result in sudden death.
The brain’s mesolimbic dopamine system, its reward pathway, is stimulated by all types of reinforcing
stimuli, such as food, sex, and many drugs of abuse, including cocaine. This pathway originates in a
region of the midbrain called the ventral tegmental area and extends to the nucleus accumbens, one of the brain’s key reward areas. Besides reward, this circuit also regulates emotions and motivation.
In the normal communication process, dopamine is released by a neuron into the synapse (the small gap between two neurons), where it binds to specialized proteins called dopamine receptors on the neighboring neuron. By this process, dopamine acts as a chemical messenger, carrying a signal from neuron to neuron. Another specialized protein called a transporter removes dopamine from the synapse to be recycled for further use.
Drugs of abuse can interfere with this normal communication process. For example, cocaine acts by binding to the dopamine transporter, blocking the removal of dopamine from the synapse. Dopamine then accumulates in the synapse to produce an amplified signal to the receiving neurons. This is what causes the euphoria commonly experienced immediately after taking the drug.
In the normal neural communication process, dopamine is released by a neuron into the synapse, where it can bind to dopamine receptors on neighboring neurons. Normally, dopamine is then recycled back into the transmitting neuron by a specialized protein called the dopamine transporter. If cocaine is present, it attaches to the dopamine transporter and blocks the normal recycling process, resulting in a buildup of dopamine in the synapse, which contributes to the pleasurable effects of cocaine.
Use of cocaine, like other drugs of abuse, induces long-term changes in the brain. Animal studies show that cocaine exposure can cause significant neuroadaptations in neurons that release the excitatory neurotransmitter glutamate. Animals chronically exposed to cocaine demonstrate profound changes in glutamate neurotransmission—including how much is released and the level of receptor proteins—in the reward pathway, particularly the nucleus accumbens. The glutamate system may be an opportune target for anti-addiction medication development, with the goal of reversing the cocaine-induced neuroadaptations that contribute to the drive to use the drug.
Although addiction researchers have focused on adaptations in the brain’s reward system, drugs also affect the brain pathways that respond to stress. Stress can contribute to cocaine relapse, and cocaine use disorders frequently co-occur with stress-related disorders. The stress circuits of the brain are distinct from the reward pathway, but research indicates that there are important ways that they overlap. The ventral tegmental area seems to act as a critical integration site in the brain that relays information about both stress and drug cues to other areas of the brain, including ones that drive cocaine seeking. Animals that have received cocaine repeatedly are more likely to seek the drug in response to stress, and the more of the drug they have taken, the more stress affects this behavior. Research suggests that cocaine elevates stress hormones, inducing neuroadaptations that further increase sensitivity to the drug and cues associated with it.
Chronic cocaine exposure affects many other areas of the brain too. For example, animal research indicates that cocaine diminishes functioning in the orbitofrontal cortex (OFC), which appears to underlie the poor decision-making, inability to adapt to negative consequences of drug use, and lack of self-insight shown by people addicted to cocaine. A study using optogenetic technology, which uses light to activate specific, genetically-modified neurons, found that stimulating the OFC restores adaptive learning in animals. This intriguing result suggests that strengthening OFC activity may be a good therapeutic approach to improve insight and awareness of the consequences of drug use among people addicted to cocaine.
Cocaine’s effects appear almost immediately after a single dose and disappear within a few minutes to an hour. Small amounts of cocaine usually make the user feel euphoric, energetic, talkative, mentally alert, and hypersensitive to sight, sound, and touch. The drug can also temporarily decrease the need for food and sleep. Some users find that cocaine helps them perform simple physical and intellectual tasks more quickly, although others experience the opposite effect.
The duration of cocaine’s euphoric effects depend upon the route of administration. The faster the drug is absorbed, the more intense the resulting high, but also the shorter its duration. Snorting cocaine produces a relatively slow onset of the high, but it may last from 15 to 30 minutes. In contrast, the high from smoking is more immediate but may last only 5 to 10 minutes.
Short-term physiological effects of cocaine use include constricted blood vessels; dilated pupils; and increased body temperature, heart rate, and blood pressure. Large amounts of cocaine may intensify the user’s high but can also lead to bizarre, erratic, and violent behavior. Some cocaine users report feelings of restlessness, irritability, anxiety, panic, and paranoia. Users may also experience tremors, vertigo, and muscle twitches.
Severe medical complications can occur with cocaine use. Some of the most frequent are cardiovascular effects, including disturbances in heart rhythm and heart attacks; neurological effects, including headaches, seizures, strokes, and coma; and gastrointestinal complications, including abdominal pain and nausea. In rare instances, sudden death can occur on the first use of cocaine or unexpectedly thereafter. Cocaine-related deaths are often a result of cardiac arrest or seizures. Many cocaine users also use alcohol, and this combination can be particularly dangerous. The two substances react to produce cocaethylene, which may potentiate the toxic effects of cocaine and alcohol on the heart. The combination of cocaine and heroin is also very dangerous. Users combine these drugs because the stimulating effects of cocaine are offset by the sedating effects of heroin; however, this can lead to taking a high dose of heroin without initially realizing it. Because cocaine’s effects wear off sooner, this can lead to a heroin overdose, in which the user’s respiration dangerously slows down or stops, possibly fatally.
With repeated exposure to cocaine, the brain starts to adapt so that the reward pathway becomes less sensitive to natural reinforcers. At the same time, circuits involved in stress become increasingly sensitive, leading to increased displeasure and negative moods when not taking the drug, which are signs of withdrawal. These combined effects make the user more likely to focus on seeking the drug instead of relationships, food, or other natural rewards.
With regular use, tolerance may develop so that higher doses, more frequent use of cocaine, or both are needed to produce the same level of pleasure and relief from withdrawal experienced initially. At the same time, users can also develop sensitization, in which less cocaine is needed to produce anxiety, convulsions, or other toxic effects. Tolerance to cocaine reward and sensitization to cocaine toxicity can increase the risk of overdose in a regular user.
Users take cocaine in binges, in which cocaine is used repeatedly and at increasingly higher doses.
This can lead to increased irritability, restlessness, panic attacks, paranoia, and even a full-blown psychosis, in which the individual loses touch with reality and experiences auditory hallucinations. With increasing doses or higher frequency of use, the risk of adverse psychological or physiological effects increases. Animal research suggests that binging on cocaine during adolescence enhances sensitivity to the rewarding effects of cocaine and MDMA (Ecstasy or Molly). Thus, binge use of cocaine during adolescence may further increase vulnerability to continued use of the drug among some people.
Specific routes of cocaine administration can produce their own adverse effects. Regularly snorting cocaine can lead to loss of sense of smell, nosebleeds, problems with swallowing, hoarseness, and an overall irritation of the nasal septum leading to a chronically inflamed, runny nose. Smoking crack cocaine damages the lungs and can worsen asthma. People who inject cocaine have puncture marks called tracks, most commonly in their forearms, and they are at risk of contracting infectious diseases like HIV and hepatitis C. They also may experience allergic reactions, either to the drug itself or to additives in cocaine, which in severe cases can result in death.
Cocaine damages many other organs in the body. It reduces blood flow in the gastrointestinal tract, which can lead to tears and ulcerations. Many chronic cocaine users lose their appetite and experience significant weight loss and malnourishment. Cocaine has significant and well-recognized toxic effects on the heart and cardiovascular system. Chest pain that feels like a heart attack is common and sends many cocaine users to the emergency room. Cocaine use is linked with increased risk of stroke, as well as inflammation of the heart muscle, deterioration of the ability of the heart to contract, and aortic ruptures.
In addition to the increased risk for stroke and seizures, other neurological problems can occur with long term cocaine use. There have been reports of intracerebral hemorrhage, or bleeding within the brain, and balloon-like bulges in the walls of cerebral blood vessels. Movement disorders, including Parkinson’s disease, may also occur after many years of cocaine use. Generally, studies suggest that a wide range of cognitive functions are impaired with long-term cocaine use—such as sustaining attention, impulse inhibition, memory, making decisions involving rewards or punishments, and performing motor tasks.
Former cocaine users are at high risk for relapse, even following long periods of abstinence. Research indicates that during periods of abstinence, the memory of the cocaine experience or exposure to cues associated with drug use can trigger strong cravings, which can lead to relapse.
In 2013, cocaine accounted for almost 6 percent of all admissions to drug abuse treatment programs. The majority of individuals (68 percent in 2013) who seek treatment for cocaine use smoke crack and are likely to be polydrug users, meaning they use more than one substance. Those who provide treatment for cocaine use should recognize that drug addiction is a complex disease involving changes in the brain as well as a wide range of social, familial, and other environmental factors; therefore, treatment of cocaine addiction must address this broad context as well as any other co-occurring mental disorders that require additional behavioral or pharmacological interventions.
Presently, there are no medications approved by the U.S. Food and Drug Administration to treat cocaine addiction, though researchers are exploring a variety of neurobiological targets. Past research has primarily focused on dopamine, but scientists have also found that cocaine use induces changes in the brain related to other neurotransmitters—including serotonin, gamma-aminobutyric acid (GABA),
norepinephrine, and glutamate. Researchers are currently testing medications that act at the dopamine D3 receptor, a subtype of dopamine receptor that is abundant in the emotion and reward centers of the brain. Other research is testing compounds (e.g., N-acetylcysteine) that restore the balance between excitatory (glutamate) and inhibitory (GABA) neurotransmission, which is disrupted by long-term cocaine use. Research in animals is also looking at medications (e.g., lorcaserin) that act at serotonin receptors.
Several medications marketed for other diseases show promise in reducing cocaine use within controlled clinical trials. Among these, disulfiram, which is used to treat alcoholism, has shown the most promise. Scientists do not yet know exactly how disulfiram reduces cocaine use, though its effects may be related to its ability to inhibit an enzyme that converts dopamine to norepinephrine. However, disulfiram does not work for everyone. Pharmacogenetic studies are revealing variants in the gene that encodes the DBH enzyme and seems to influence disulfiram’s effectiveness in reducing cocaine use. Knowing a patient’s DBH genotype could help predict whether disulfiram would be an effective pharmacotherapy for cocaine dependence in that person.
Finally, researchers have developed and conducted early tests on a cocaine vaccine that could help reduce the risk of relapse. The vaccine stimulates the immune system to create cocaine-specific antibodies that bind to cocaine, preventing it from getting into the brain. In addition to showing the vaccine’s safety, a clinical trial found that patients who attained high antibody levels significantly
reduced cocaine use. However, only 38 percent of the vaccinated subjects attained sufficient antibody levels and for only 2 months.
Researchers are working to improve the cocaine vaccine by enhancing the strength of binding to cocaine and its ability to elicit antibodies. New vaccine technologies, including gene transfer to boost the specificity and level of antibodies produced or enhance the metabolism of cocaine, may also improve the effectiveness of this treatment. A pharmacogenetics study with a small number of patients suggests that individuals with a particular genotype respond well to the cocaine vaccine—an intriguing finding that requires more research.
In addition to treatments for addiction, researchers are developing medical interventions to address the acute emergencies that result from cocaine overdose. One approach being explored is the use of genetically engineered human enzymes involved in the breakdown of cocaine, which would counter the behavioral and toxic effects of a cocaine overdose. Currently, researchers are testing and refining these enzymes in animal research, with the ultimate goal of moving to clinical trials.
Many behavioral treatments for cocaine addiction have proven to be effective in both residential and outpatient settings. Indeed, behavioral therapies are often the only available and effective treatments for many drug problems, including stimulant addictions. However, the integration of behavioral and pharmacological treatments may ultimately prove to be the most effective approach.One form of behavioral therapy that is showing positive results in people with cocaine use disorders is
contingency management (CM), also called motivational incentives. Programs use a voucher or prizebased system that rewards patients who abstain from cocaine and other drugs. On the basis of drugfree urine tests, the patients earn points, or chips, which can be exchanged for items that encourage
healthy living, such as a gym membership, movie tickets, or dinner at a local restaurant. CM may be
particularly useful for helping patients achieve initial abstinence from cocaine and stay in treatment.
This approach has recently been shown to be practical and effective in community treatment
Research indicates that CM benefits diverse populations of cocaine users. For example, studies show
that cocaine-dependent pregnant women and women with young children who participated in a CM
program as an adjunct to other substance use disorder treatment were able to stay abstinent longer
than those who received an equivalent amount of vouchers with no behavioral requirements.
Patients participating in CM treatment for cocaine use who also experienced psychiatric
symptoms—such as depression, emotional distress, and hostility—showed a significant reduction in
these problems, probably related to reductions in cocaine use.
Cognitive-behavioral therapy (CBT) is an effective approach for preventing relapse. This approach
helps patients develop critical skills that support long-term abstinence—including the ability to
recognize the situations in which they are most likely to use cocaine, avoid these situations, and cope
more effectively with a range of problems associated with drug use. This therapy can also be used in
conjunction with other treatments, thereby maximizing the benefits of both.
Recently, researchers developed a computerized form of CBT (CBT4CBT) that patients use in a
private room of a clinic. This interactive multimedia program closely follows the key lessons and
skill-development activities of in-person CBT in a series of modules. Movies present examples and
information that support the development of coping skills; quizzes, games, and homework
assignments reinforce the lessons and provide opportunities to practice skills. Studies have shown that adding CBT4CBT to weekly counseling boosted abstinence and increased treatment success rates up to 6 months after treatment.
Therapeutic communities (TCs)—drug-free residences in which people in recovery from substance
use disorders help each other to understand and change their behaviors—can be an effective
treatment for people who use drugs, including cocaine. TCs may require a 6- to 12-month stay and
can include onsite vocational rehabilitation and other supportive services that focus on successful reintegration of the individual into society. TCs can also provide support in other important
areas—improving legal, employment, and mental health outcomes.
Regardless of the specific type of substance use disorder treatment, it is important that patients
receive services that match all of their treatment needs. For example, an unemployed patient would
benefit from vocational rehabilitation or career counseling along with addiction treatment. Patients with
marital problems may need couples counseling. Once inpatient treatment ends, ongoing support—also
called aftercare—can help people avoid relapse. Research indicates that people who are committed to
abstinence, engage in self-help behaviors, and believe that they have the ability to refrain from using
cocaine (self-efficacy) are more likely to abstain. Aftercare serves to reinforce these traits and address problems that may increase vulnerability to relapse, including depression and declining self efficacy.
Scientists have found promising results from telephone-based counseling as a low-cost method to
deliver aftercare. For example, people who misused stimulants who participated in seven sessions of
telephone counseling showed decreasing drug use during the first 3 months, whereas those who did
not receive calls increased their use. Voucher incentives can boost patients’ willingness to participate in telephone aftercare, doubling the number of sessions received according to one study.
Community-based recovery groups—such as Cocaine Anonymous—that use a 12-step program can
also be helpful in maintaining abstinence. Participants may benefit from the supportive fellowship and
from sharing with those experiencing common problems and issues.